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Biomedical subjects

D Hayoz

Publications and source records attributed to D Hayoz.

At least 55 records · Page 3Linked to original sources
PubMed1999

Physical activity monitoring based on accelerometry: validation and comparison with video observation.

The objective of this feasibility study is to evaluate the use of the 'Physilog' device, an ambulatory physical-activity recorder based on acceleration measurement, for the monitoring of daily physical activities. Accelerations measured at the level of the chest and the thigh are recorded by Physilog over a period of 1 h in five normal subjects. A specially designed studio-like room allowing the performance of most usual activities of everyday life is used. A video film synchronised with the Physilog is obtained for each subject to check the accuracy of the data derived from Physilog. Based on the analysis on the average and the deviation of the acceleration signal, an algorithm is developed to classify the activities in four categories, i.e. lying, sitting, standing and locomotion. Compared with the video observations, the results from the algorithm show an overall misclassification of 10.7%, which is mainly due to confusion between dynamic activities and the standing posture. In contrast, the misclassification between postures is negligible. It is concluded that Physilog can be used in the clinical setting for the reliable measurement and long-term recording of most usual physical activities.

Activities of Daily Living↗
PubMed1999

Pharmacokinetic and pharmacodynamic effects of YM087, a combined V1/V2 vasopressin receptor antagonist in normal subjects.

OBJECTIVE: The pharmacokinetic and pharmacodynamic properties of YM087, (4'-[(2-methyl-1,4,5,6- tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)-carbonyl]-2-p henylbenzanilide monohydrochloride), a new orally active, dual V1/V2 receptor antagonist were characterised in healthy normotensive subjects. METHODS: Six subjects were randomly allocated to receive, at 1-week intervals, a single oral dose of 60 mg YM087 and a single i.v. dose of 50 mg YM087 in an open-label, crossover study. RESULTS: YM087 had an oral bioavailability of 44% and a short half-life. Upon oral and i.v. administration of YM087, a significant sevenfold increase in urine flow rate and a fall in urinary osmolality (from 600 mosmol/l to less than 100-mosmol/l) were observed with a peak effect 2 h after drug intake suggesting effective vasopressin V2 receptor blockade. Simultaneously, significant increases in plasma osmolality (from 283 +/- 1.3 mosmol/l to 288 +/- 1.0 mosmol/l after i.v. and from 283 +/- 2.1 mosmol/l to 289 +/- 1.7-mosmol/l after oral administration) and vasopressin levels (from 1.5 +/- 0.3 pg/ml to 3.7 +/- 0.6 pg/ml after i.v. and from 0.9 +/- 0.1 pg/ml to 3.9 +/- 0.7 pg/ml after oral administration) were found. When administered i.v., YM087 inhibited the vasopressin-induced skin vasoconstriction, suggesting a blockade of V1 receptors. However, the YM087-induced antagonism of V1 receptors was less pronounced than V2 receptor blockade. CONCLUSION: These data show that YM087 is an effective dual V1/V2 receptor antagonist in man.

Administration, Oral↗
PubMed1999

SH2D1A mutation analysis for diagnosis of XLP in typical and atypical patients.

X-linked lymphoproliferative disease (XLP) is a rare inherited immunodeficiency to Epstein-Barr virus (EBV). The gene responsible for XLP has recently been identified as the four-exon SH2D1A gene encoding a 128-amino-acid protein that contains an SH2-domain. Functional studies indicate the SH2D1A protein acts as a regulator of at least two signal transduction pathways initiated by the cell surface molecules SLAM and 2B4, respectively, and possibly related to the host immune response to EBV infection. We have carried out a systematic mutation study of the SH2D1A gene in our series of 19 typical and 8 atypical XLP patients by polymerase chain reaction (PCR), reverse transcription/PCR, and sequencing, and have reconstructed the haplotypes of the patients. Four out of the 13 mutations detected are previously unreported. The identification of SH2D1A mutations in carriers from all three XLP families screened and the detection of mutations in two out of eight atypical patients indicates the usefulness of a DNA-based diagnosis for XLP disease.

Carrier Proteins↗
PubMed1999

Thrombogenicity of deflated intraaortic balloon: impact of heparin coating.

In a calf model, 3 standard and 3 heparin coated intraaortic balloons (IAB) were inserted and left deflated in the descending aorta during 20 min to simulate balloon rupture. At the end of the experiment, the IAB were examined, and 3 samples of each were collected for scanning electron microscopy (SEM) analysis. None of the heparin coated IAB showed any sign of clot or deposit whereas all 3 standard IAB exhibited clots. SEM revealed no deposit on the heparin coated samples while 8 of the 9 standard samples disclosed deposits (p < 0.001). Morphometrically, 16.1+/-21.4% of the surfaces of the standard samples were covered with deposits whereas all the heparin coated samples were free (p = 0.004). The presence of clots on every standard IAB supports the hypothesis that other than local factors of the insertion site can play a role in the vascular complications of IAB. The absence of clots and deposits on the heparin coated IAB suggests a promising role of such devices in circumventing the tendency of clot formation on deflated balloons while avoiding the drawback of systemic anticoagulation.

Animals↗
PubMed1999

Aortic connexin43 is decreased during hypertension induced by inhibition of nitric oxide synthase.

Connexin43 (Cx43), the predominant gap junction protein in vessels and heart, is involved in the control of cell-to-cell communication and is thought to modulate the contractility of the vascular wall and the electrical coupling of cardiac myocytes. We have investigated the effects of arterial hypertension induced by inhibition of nitric oxide synthase on the expression of Cx43 in aorta and heart as well as on the distensibility of the carotid artery. Administration of 0.4 g/L NG-nitro-L-arginine methyl ester (L-NAME) to rats in their drinking water for 4 weeks increased intra-arterial mean blood pressure, wall thickness of aorta and carotid artery (25%), and heart weight (17%). Analysis of heart mRNA demonstrated increased expression of the fetal skeletal alpha-actin and of atrial natriuretic peptide but not of Cx43. In contrast, Cx43 mRNA and protein were decreased by 50% in the aortas of L-NAME-treated rats that did not show increased carotid distensibility. Because these data contrasted with those obtained in the 2-kidney, 1 clip model of rat hypertension, which is characterized by increased arterial distensibility and Cx43 expression in aorta, we investigated by Western blot analysis the posttranslational modifications of Cx43. We found that Cx43 was more phosphorylated in the aorta of 2-kidney, 1 clip rats than in that of L-NAME or control rats, which indicated a differential regulation of Cx43 in different models of hypertension. The data suggest that the cell-to-cell communication mediated by Cx43 channels may help regulate the elasticity of the vascular wall.

Animals↗
PubMed1999

Effect of magnesium deficiency on blood pressure and mechanical properties of rat carotid artery.

The purpose of this study was to determine the effect of dietary Mg deficiency (80 mg/kg versus control diet: 960 mg/kg) on blood pressure and mechanical properties of the rat common carotid artery. The internal diameter and intra-arterial pressure of carotid artery were measured continuously with an echo-tracking device. At 19 weeks, systolic, diastolic, and mean blood pressures were higher in Mg-deficient rats. Histological examination showed an increase in cross-sectional area, intima-media thickness, and media-to-lumen ratio in carotid artery of Mg-deficient rats. Mg deficiency did not modify the arterial distensibility-blood pressure curve. At mean blood pressure, arterial distensibility was significantly less in 19-week-old rats than in 5-week-old rats of both control and Mg-deficient groups. A significant interaction between age and Mg-deficient diet on arterial distensibility (P<0.04) indicates an accelerated age-dependent decreased arterial distensibility with Mg deficiency. At 19 weeks, the artery was stiffer in hypertensive Mg-deficient rats, as illustrated by a shift to higher levels of the incremental elastic modulus-stress curve. In conclusion, the increased blood pressure and the vascular morphological alterations observed in Mg-deficient rats may contribute to an accelerated alteration of the wall material, which in turn leads to a stiffening of the carotid artery.

Age Factors↗
PubMed1998

Diabetes mellitus and vascular lesions.

Cardiovascular complications represent by far the most severe manifestations of diabetes mellitus. Treatment aimed at stopping progression of vascular lesions may fall short if initiated when the disease becomes clinically evident. Therefore, identification of the earliest vascular disfunctions may offer the best opportunity to interfere with pathogenic mechanisms and avoid progression of diabetic vasculopathy. In this report, we present a few mechanisms that alter hemodynamic and metabolic homeostasis in the course of diabetes mellitus. Endothelial function with special emphasis on nitric oxide and oxidative stress, advanced glycation end products, and the renin angiotensin system are briefly discussed. New pharmacological agents that may favorably influence these parameters are presently undergoing clinical trials. However, tight control of plasma glucose and cardiovascular risk factors represent the cornerstone of the treatment in diabetes to slow progression of vascular disease.

Animals↗
PubMed1998

Endothelin-1 and endothelin-converting enzyme-1 gene regulation by shear stress and flow-induced pressure.

Hemodynamic forces have been shown to modulate the expression of endothelin (ET-1) and endothelin-converting enzyme (ECE-1) in endothelial cells. We have subjected E.A. hy 926 cells in culture to steady fluid shear stress with and without flow-induced pressure. The effect of combining these two mechanical forces on the expression of genes in the ET system was studied and the changes were compared to the mRNA levels in static culture. Analysis of total RNA by Northern blot analysis and RNAse protection showed that steady shear stress induced ET-1 gene expression three- to fourfold in this system. The same condition had little to no effect on altering expression of ECE-1 isoforms. A range of flow-induced pressure (80-160 mm Hg) was not able to further augment ET-1 or ECE-1 gene expression. Overall, with the mechanical environment studied, we have been able to detect a predominant contribution of shear stress to altering the ET-1 gene in our system. Furthermore, this induction was independent of an alteration of ECE-1 gene levels, suggesting that these two genes have a different pattern of regulation by the same stimuli in this cell type.

Aspartic Acid Endopeptidases↗
PubMed1998

Influence of oscillatory and unidirectional flow environments on the expression of endothelin and nitric oxide synthase in cultured endothelial cells.

In vivo, endothelial cells (ECs) are subjected to a complex mechanical environment composed of shear stress, pressure, and circumferential stretch. The aim of this study was to subject bovine aortic ECs to a pulsatile pressure oscillating from 70 to 130 mm Hg (mean of 100 mm Hg) in combination with pulsatile shear stresses from 0.1 to 6 dyne/cm2 (1 dyne/cm2=0.1 N/m2) with or without a cyclic circumferential stretch of 4% for 1, 4, and 24 hours. The effect of highly reversing oscillatory shear stress (range -3 to +3 dyne/cm2, mean of 0.3 dyne/cm2) typical of regions prone to the development of atherosclerotic plaques was also studied at 4 and 24 hours. Endothelin-1 (ET-1) and endothelial constitutive nitric oxide synthase (ecNOS) mRNA expression was time and mechanical force dependent. ET-1 mRNA was maximal at 4 hours and decreased to less than static culture expression at 24 hours, whereas ecNOS mRNA increased over time. Pressure combined with low shear stress upregulated ET-1 and ecNOS mRNA compared with static control. Additional increase in expression for both genes was observed under a combination of higher shear stress and pressure. A cyclic circumferential stretch of 4% did not induce a further increase in ET-1 and ecNOS mRNA at either low or high shear stress. Oscillatory shear stress with pressure induced a higher expression of ET-1 mRNA but lower expression of ecNOS mRNA compared with unidirectional shear stress and pressure. We have shown that the combination of pressure and oscillatory shear stress can downregulate ecNOS levels, as well as upregulate transient expression of ET-1, compared with unidirectional shear stress. These results provide a new insight into the exact role of mechanical forces in endothelial dysfunction in regions prone to the development of atherosclerosis.

Animals↗
PubMed1998

Differences in the mechanical properties of the rat carotid artery in vivo, in situ, and in vitro.

The elastic properties of carotid arteries of spontaneously hypertensive rats (SHR) and normotensive controls (Wistar-Kyoto rats [WKY]) were examined in vivo, in situ, and in vitro. The changes of internal diameter were measured with a high-resolution A-mode echo-tracking device simultaneously with the intra-arterial pressure at the carotid. The internal diameter at mean arterial blood pressure (MBP) was substantially smaller in vitro than in vivo in SHR (-33.8%) and WKY (-48.3%). The arterial distensibility was lower in vitro in all arteries compared with in vivo conditions (SHR, -30.1%; WKY, -60.4%; at MBP) despite a reduced incremental elastic modulus in vitro (SHR, -56.9%; WKY, -45.1%; at MBP). However, the in vitro and in vivo measurements show consistent elastic behavior of the carotid arteries between both strains of rats. Carotid arteries from WKY were also examined in situ. Although no significant reduction in internal diameter could be observed in situ, distensibility was dramatically decreased (-87% at MBP). These results emphasize the importance of considering the original vascular geometry when determining elastic properties of arteries. We conclude that experimental conditions are likely to be a critical determinant for the assessment of the mechanical properties of conduit vessels.

Animals↗
PubMed1998

Nitric oxide synthase expression in endothelial cells exposed to mechanical forces.

Nitric oxide (NO) has been demonstrated to play a central role in vascular biology and pathobiology. The expression of endothelial NO synthase (eNOS) is regulated in part by blood flow-induced mechanical factors. The purpose of this study was to evaluate how the expression of eNOS mRNA correlates with the activation of its promoter in both arterial and venous endothelial cells (ECs) exposed to mechanical forces, ie, shear stress and cyclic circumferential stretch. Bovine aortic ECs (BAECs) and EA hy.926, a cell line derived from human umbilical vein ECs, were grown on the inside of elastic tubes and subjected to combinations of pressure, pulsatile shear stress, and cyclic circumferential stretch for 24 hours. Two patterns of shear stress were used: unidirectional (mean of 6, ranging from 3 to 9 dyne/cm2) and oscillatory (mean of 0.3, ranging from -3 to +3 dyne/cm2). The expression of eNOS mRNA was quantified by Northern blot analysis. Activation of the promoter was assessed by luciferase activity after the cells were transiently transfected before the flow experiments with a plasmid construct containing the fully functional eNOS promoter coupled to a luciferase reporter gene. Expression of eNOS mRNA was increased and promoter activity was enhanced by unidirectional shear stress compared with static control. Oscillatory shear slightly upregulated eNOS mRNA in BAECs, whereas it downregulated eNOS mRNA in EA hy.926. In both BAECs and EA hy.926, there was a good correlation between the increase in eNOS mRNA expression and promoter activation by unidirectional shear stress. In contrast, in both BAECs and EA hy.926 cells exposed to shear stress, cyclic stretch did not change eNOS mRNA expression, but the activation of eNOS promoter was significantly lower. Moreover, when ECs were exposed to oscillatory shear stress, there was a dramatic activation of the eNOS promoter. These results demonstrate that unidirectional shear stress increases eNOS mRNA expression via a transcriptional mechanism. However, oscillatory shear stress and cyclic stretch appear to control eNOS expression through posttranscriptional regulatory events.

Animals↗
PubMed1998

[Endovascular treatment of abdominal aortic aneurysm. Preliminary experiences with the Talent endoprosthesis].

BACKGROUND: The treatment of infra-renal abdominal aortic aneurysms (AAA) with endovascular stent-graft prostheses is receiving increasing attention as an alternative to major abdominal surgery. Numerous systems are under clinical investigations. We report our preliminary clinical results with the new Talent straight and bifurcated endografts. METHOD: We treated 5 patients with 3 straight and 2 bifurcated stent-grafts implanted by surgical femoral arteriotomies and placed under fluoroscopic guidance. Control CT and angiographic examinations were performed during an average follow-up of 5.3 months. RESULTS: In the first patient the procedure had to be converted to an open surgical operation to repo sition the distal end of the prosthesis. We had no mortality, or major systemic complication. Three patients had a postimplantation syndrome. All aneurysms showed a decreased size at 3 months, in spite of 3 small persisting leaks. CONCLUSION: The Talent endograft is safe, and efficacious in the endovascular treatment of AAA. This method requires a good cooperation between the vascular surgeon and the interventional radiologist. Learning curves influence preliminary results.

Aged↗
PubMed1997

[Homocysteine and venous thromboembolism].

Congenital homocysteinuria is a rare inherited metabolic disorder with early onset atherosclerosis and arterial and venous trombosis. Moderate hyperhomocysteinemia is more frequently encountered and is recognized as an independent cardiovascular risk factor. Several case-control studies demonstrate an association between venous thromboembolism and moderate hyperhomocysteinemia. A patient with moderate hyperhomocysteinemia has a 2-3 relative risk of developing an episode of venous thromboembolism. The occurrence of mild hyperhomocysteinemia in heterozygotes for the mutation of Leiden factor V involves a 10-fold increase in the risk of venous thromboembolism. The biochemical mechanism by which homocysteine may promote thrombosis is not fully recognized. Homocysteine inhibits the expression of thrombomodulin, the thrombin cofactor responsible for protein C activation, and inhibits antithrombin-III binding. Treatment with folic acid reduces the plasma level of homocysteinemia, but no study has demonstrated its efficacy in reducing the incidence of venous thromboembolism or atherosclerosis. Hyperhomocysteinemia should be included in the screening of abnormalities of hemostasis and thrombosis in patients with idiopathic thromboembolism, and mild hyperhomocysteinemia may justify a trial of folic acid.

Adolescent↗
PubMed1997

[Use and significance of intravascular ultrasonic imaging].

Intravascular ultrasound (IVUS) imaging of coronary arteries has recently become possible in vivo with the improvements achieved in the miniaturisation of ultrasound transducers. IVUS provides informations complementary to angiography, and is considered as the gold standard for the assessment of lumen size, plaque thickness and plaque distribution. As formerly demonstrated by pathological studies, IVUS also reveals an underestimation of plaque thickness with angiography and an incomplete assessment of the true morphologic distribution of the plaque burden. Among its clinical applications, IVUS can be used to monitor revascularisation procedures, and may provide very accurate measurements of progression or regression of coronary atherosclerosis and of the extent of posttransplant vasculopathy. IVUS was employed successfully to assess and optimize the results of percutaneous transluminal coronary angioplasty. Clinical studies have shown that the risk of restenosis is inversely proportional to the size of the postprocedural lumen. With the guidance of percutaneous transluminal angioplasty by IVUS, balloon size and inflation pressures were increased, and better results were obtained with larger lumen size in comparison to the results of the procedures assessed by angiography alone. These improvements contributed to abandon the anticoagulation after stent implantation in most cases. In spite of the valuable information provided by IVUS, its role in clinical settings should still be defined IVUS prolongs the revascularisation procedure and enhances its costs and risks. Thus, the cost effectiveness of IVUS in its clinical application should be determined by prospective studies.

Angioplasty, Balloon, Coronary↗
PubMed1997

[Chronic occlusive arteriopathy of the lower limbs: therapeutic approach].

Chronic arterial insufficiency of the lower limbs is characterized by intermittent claudication often localized to the calf. These early clinical symptoms are the results of the atherosclerotic process of the vasculature of the lower extremities. The treatment is aimed at reducing or eliminating the ischemic pain and at preventing progression of the atherosclerotic disease. Whether surgical or nonsurgical measures are used, the cornerstone of patient care lies in correction of the risk factors. Smoking cessation and exercise therapy remain the fundamental measures in medical treatment of intermittent claudication. percutaneous transluminal angioplasty is an appropriate therapeutic option under certain criteria, especially for the iliac arteries. In the absence of randomized studies, surgery remains the treatment of choice for peripheral revascularization in presence of limb-threatening ischemia or ischemic ulcers. New procedures and materials are presently under trial to test the safety and efficacy of alternative methods or revascularization that would provide better long-term patency rates and shorter hospitalization periods.

Amputation, Surgical↗
PubMed1997

How to assess vascular remodelling in small and medium-sized muscular arteries in humans.

The study of vascular wall changes in humans has generated great interest with the increasing realization that, independently of the potential contribution to mechanisms involved in blood pressure elevation, these structural alterations (remodelling) or functional changes may contribute to the complications of elevated blood pressure. Moreover, some of these changes may be corrected partially or totally by administration of antihypertensive agents and other drugs. This has fuelled interest in the techniques used to evaluate changes in the vascular wall in humans, which are reviewed critically here with a focus on human studies in hypertension. Remodelling of large and small arteries has different characteristics, and is studies with different techniques. In hypertensive patients, small arteries less than 400 microns in diameter exhibit a reduction in lumen diameter, accompanied sometimes but not always by an increase in media width or in media cross-section. The study of capillaries and small arteries of the skin or the eye can be performed non-invasively, but for the sake of obtaining the information of interest in hypertension, at present invasive techniques are required to investigate small arteries. These consist of a biopsy of subcutaneous tissue, usually from the gluteal region, and the study of vessels after they have been mounted on a 'wire myograph' or on a pressurized system. In contrast to small arteries, large arteries from hypertensive humans present increases in media width without a significant reduction in the lumen diameter (when studied under conditions isobaric relative to those in normotensive subjects). Conduit arteries may be studies non-invasively with the use of ultrasound techniques. The study of large elastic arteries is not addressed here. The use of echo-tracking devices to study muscular medium-sized arteries such as the radial artery is described. The relative advantages and disadvantages of these techniques, the questions which may be asked and the relevance of the information obtained using these approaches are discussed.

Arteries↗