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Objective Estimate the effect of lifestyle adjustment activities in patients with metabolic syndrome treated by prescribed balneotherapy. Methods Observational pilot cohort study with 12-month follow-up after multidimensional lifestyle training (physical, dietary, educational) during 3-week standard stay in the spa town of Eugenie-les-Bains. Results Of 145 eligible patients, 97 were included; 63 were followed and analysable. At inclusion all had ≥ 3 National cholesterol education program-Adult treatment panel III (NCEP-ATPIII) criteria defining metabolic syndrome, 76.2% were female, mean age was 61.2 years. At the end of follow-up (median:10.4 months, Inter-Quartile Range: [6.7;11.4]), 48 of these 63 patients (76.2%) no longer had metabolic syndrome (95%CI [65.7;86.7]). These 48 patients without metabolic syndrome at the end of follow-up represented 49.5% of the 97 included (95%CI [39.5;59.4]). Conclusions Future studies of lifestyle interventions taking advantage of the spa environment can be expected to find least one third of patients free of metabolic syndrome at the end of 12-month follow-up in the intervention group.

Long-term metabolic changes in vein tissue of the limbs and feet have been reported in the course of chronic venous insufficiency (CVI). Low fibrinolytic potential was first demonstrated using fibrin-embedded vein rings (Todd's biopsy), then in blood via increased euglobulin lysis time. This defect is especially pronounced when blood is taken from foot veins of patients with grades 5 and 6 of CVI or skin lesions. Haemorrheological disorders such as increased blood viscosity and red cell aggregation, related mainly to high fibrinogen levels, have also been shown in patients with CVI. Such disorders, particularly observed in blood from foot veins, play an important role in the interaction between the blood cell components and the vessel wall. More recently, the margination and adhesion of white cells to the endothelium and the subsequent activation of white cells have been assumed. Adhesion molecules such as ICAM-1, VCAM-1 and P-selectin have been identified surrounding skin ulceration. There is also evidence that markers of neutrophil degranulation reach high levels in blood taken from foot veins after exposure to experimental venous hypertension. White cell activation results in elevated plasma levels of L-selectin, increased production of oxygen free radicals, pseudopods, CD11b integrin, platelet-monocyte aggregates and abnormal lymphocyte L-selectin. Increased nitric oxide, presumably due to monocyte activation, as well as increased urine haemosiderin related to skin microvessel leakage have also been reported. VCAM-1 and metalloproteinase MMP9 activity have been stated as sensitive markers in relation to endothelium activation and white cell trapping, which follows hypoxia and/or alterations in wall shear stress, mainly in skin venulae and in the region of valves.

Membrane thrombomodulin (TM) is a very efficient natural anti-thrombin glycoprotein with anticoagulant properties expressed on endothelial cell surface. Circulating plasmatic thrombomodulin (TMp) detected by enzyme immunoassay in plasma is considered as a cell marker of endothelial injury. The TMp levels are increased in many conditions (diabetes mellitus, atheromatous disease...). In cases of collagen vascular diseases, where vascular endothelium damage is suspected, TMp is increased particularly in systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). It is noteworthy that the TMp level is correlated with disease activity. Since TMp is a non specific marker of endothelial damage, it may be of interest as a useful marker for the supervision of these diseases. Further studies are needed on larger series. TMp level change during spontaneous evolution or under treatment will help determine wether TMp is a predictor and prognostic marker of these systemic diseases.

Circulating levels of the adhesion molecule P-selectin (CD62P) are increased in the plasma of patients with atherosclerosis, but its relationship to the anatomical location of symptomatic disease or extent of symptomatic disease is unknown. The influence of the risk factors for atherosclerosis on soluble P-selectin is also unclear. To clarify these questions we analysed plasma samples from 170 patients with symptomatic peripheral vascular disease and 119 asymptomatic controls who were, as a group, age- and sex-matched. Soluble P-selectin (ELISA) was increased in 83 patients with symptomatic disease of the iliac and/or femoral arteries alone (P < 0.05, ANOVA) but not in 37 patients with symptomatic carotid artery disease alone compared with controls. Soluble P-selectin was equally raised in 120 patients with disease at one arterial site and in 50 patients with disease at two or more arterial sites (both P < 0.05) compared with controls. Smoking and atherosclerosis were both independent predictors of raised soluble P-selectin. We conclude that increased soluble P-selectin may have value as a marker of peripheral vascular disease of the iliac and/or femoral arteries in group comparisons only, as the poor discrimination and wide variation of data make comparisons at the individual level difficult.

Cytarabine (Ara-C) is currently used in the treatment of adult acute myeloid leukemia (AML). To predict the results of induction chemotherapy, it could be useful to detect leukemic cells that are resistant to Ara-C in patients with AML. Using a bromodeoxyuridine/DNA (BrdUrd/DNA) staining method in flow cytometry (FCM), we have developed a cell resistance index to Ara-C (RI). The technique has been applied to 121 bone marrow (BM) samples from patients with de novo AML treated by a regimen containing Ara-C and daunorubicin (DNR). Ninety-seven patients achieved a complete remission (CR), and 24 patients did not and were considered drug-resistant (DR). The BM cells collected at diagnosis were cultured for 48 hours and underwent BrdUrd/DNA analysis. Among 25 patients with no or very low proliferative activity (

Hyperhomocysteinaemia is a risk factor for premature atherosclerosis and venous thromboembolic disease. Supplementation with folic acid and vitamin B6 has been shown to decrease plasma homocysteine but data fail to assess an effect on the progression of vascular disease. We measured plasma homocysteine and two markers of endothelial injury (plasma soluble thrombomodulin and von Willebrand factor) at baseline and after 3 months of treatment with folic acid and vitamin B6. After this treatment there was a significant decrease in fasting soluble thrombomodulin (−15 ng/ml, 95%CI 5–22.2). Von Willebrand factor was significantly raised after methionine load at baseline but did not significantly rise after supplementation.

Many clinical studies have evaluated the clinical efficiency of ticlopidine in vascular pathology and in few of these studies the plasma Fg level was determined as a biological parameter and not a primary end point. All these studies are heterogeneous because plasma Fg concentration have been measured using various methods, patients were included at various time after the acute event and were followed over a period of 1 to 24 months of treatment with ticlopidine, patients suffered from various pathology: peripheral arterial disease, cerebrovascular disease, diabetes or polycythemia vera. Despite the heterogeneity of these prospective studies, a general trend indicates a decrease in the plasma Fg levels by 10 to 25% with ticlopidine compared to placebo. This decrease in circulating Fg was associated with clinical improvement, and, when studied, hemorheological modifications (decreases in whole blood and plasma viscosities). The mechanism of ticlopidine action is discussed.

The plasma thrombomodulin (TM) level depends on the integrity of the endothelium and the clearance of the molecule. In several different pathological conditions, plasma TM levels increase with damage to the endothelium. We studied plasma TM levels in patients with various localizations of atheromatous arterial disease who had normal serum creatinine levels. Two groups of patients had a single symptomatic localization, which was either peripheral occlusive arterial disease (POAD) or ischemic heart disease (IHD) and a third group of patients had multiple symptomatic localizations (polyvascular). We compared the plasma TM levels with the plasma levels of other specific markers of endothelial cell activation such as: prostacyclin (PGI2), tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1). Plasma TM levels were significantly increased in all three individual groups and when all patients were considered (total patients), as compared with normal controls. When all patients were considered, there was a significant positive correlation between plasma TM levels and t-PA and between plasma TM levels and PGI2. A significant positive correlation was also found between the plasma TM levels and PAI-1 for patients with POAD. Thus, our findings suggest that an increased influx of TM into the plasma may be caused by endothelial cell damage in patients with atheromatous arterial disease. However in our study, the plasma TM levels obtained were similar for all three types of atheromatous arterial disease. Though plasma thrombomodulin is a marker of endothelial cell injury, it cannot be of a clinical interest until its levels are related to the extend of the atheromatous lesions. Moreover, we show that plasma TM is not independent of the usual endothelial cell activation markers.

Hyperchomocysteinaemia is a vascular risk factor. However few data are available as regards the efficacy of vitamin supplementation on the course of hyperhomocysteinaemia-related vascular disease. Since homocystein induces vascular endothelium cell dysfunction in vitro, we investigated the effect of vitamin supplementation on plasma soluble thrombomodulin (sTM) concentration, a marker of endothelium injury. The diagnosis of hyperhomocysteinaemia was assessed by oral L-methionin load. Homocysteinaemia was measured before and 6 hours after the load. The sTM concentration was measured while fasting before and 3-months after supplementation with 5 mg folic acid and 250 mg vitamin B6. The difference between fasting and post-load homocystein concentration decreased from 43.9+/14.9 mol/I before supplementation to 28.1+/-9.4 mol/I after a 3-monthslong supplementation. Then a 37% decrease was obtained in the post load rise in homocysteinaemia. 14 from the 17 patients (82%) no longer had detectable hyperhomocysteinaemia after the 3-months supplementation. The concentration of sTM decreased from 43.6+/19.8 ng/ml to 30.7+/I I ng/ml (p=0.005). After supplementation for 3 months with folic acid and vitamin B6, a significant decrease was obtained in sTM. This may reflect a decrease in injury of the vascular endothelium, sTM might be a useful marker to assess the efficacy of supplementation regiments on hyperhomocysteinaemia-related vascular disease.

Variations of plasma thrombomodulin levels, which is a putative marker of endothelial damage, were measured in 23 cases of systemic lupus erythematosus (without antiphospholipids and/or lupus anticoagulants) and in 7 dermatopolymyositis. This parameter was significantly increased in dermatopolymyositis suggesting the involvement of ischemia in endothelium injury. No change in plasma thrombomodulin levels was observed in patients with systemic lupus erythematosus.

Plasma thrombomodulin (TMp) is proned as a marker of endothelial cell domage. Significantly elevated levels were found in patients with atherosclerosis. Furthermore a positive correlation was pointed out between TMp and prostacyclin (PG12) and tissue-type plasminogen activator (t-PA) which are markers of endothelial cells activation.

In order to assess the role of the megakaryocytes disturbance in several pathological thrombotic situations, we designed a technic for concentration and seperation of megakaryocyte population from bone marrow.Humann bone marrow megakaryocyte were isolated from sternal punction by two consecutive gradiebts of isosmoler Bovine serum albumine (B.S.A) solution in HANKS without Ca++ and Mg++ (Ph = 7.4) and density from 1.0024 to 1.0087 gm/ml at 1 g. Starting with Suspensions of bone marrow cells containing only 0.04% megakaryocyte, the proportion of megakaryocytes was enriched 50 times.Five populations of Rabbit megakaryocyte were separated by B.S.A. density gradient centrifugation from 1,050 to 1.098 gm/ml at 100 g dating 20 mn. The cytophotometric evaluation of megakaryocyte ploidy degree required a novel separation according to the megakaryocyte size by velocity sedimentation in B.S.A. gradient at 1 g. By these technics, the proportion of megacaryocyte was enriched 60 to 100 times in each homogenous class. Then, qualitative and quantitative study were realized by cytopkotametric evaluation of DNA-Feulgen at 560 nm and residues ariginyls and lysyls in histones at 370 and 592 nm and correlated with ultrastructural features. Thus modifications of megakaryocytopoiesis in atherosclerotic coronary disorder in Man and experimental atherosclerosis in rabbit were recognized.Supported by D.G.R.S.T. Grant 77.7. 1406

During the first post burn period (first and second week) the most severe cases showed evidence of a platelet storage pool deficiency, i.e. : no aggregation with ADP, decreased nucleotide content, reduced number of granules loaded with mepacrine (presence of non granulated platelets) and increase in the percentage of light platelets. During the second post burn period (3rd to 5th week) on the same patients and for the least severe cases, the abnormalities were found heterogeneous, suggesting evidence of a partial release phenomenon, Altough the platelet nucleotide content was reduced, quite a few “empty” platelets were found, there was no significant increase of light platelets.These data indicate, with regard to the platelets, the presence of a partial release phenomenon during extensive peripheral destruction of platelets which can sometimes reach the state of a Storage Pool Dasease.