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Biomedical subjects

A Lafont

Publications and source records attributed to A Lafont.

At least 19 recordsLinked to original sources
PubMed1998

Thrombus generation after adenovirus-mediated gene transfer into atherosclerotic arteries.

Thrombosis represents a major issue during arterial local delivery. We evaluated the occurrence of thrombosis after adenovirus (Ad)-mediated gene transfer into normal and atherosclerotic arteries. A replication-deficient Ad vector expressing the beta-galactosidase reporter gene (Ad.RSV betagal; 4 x 10(9) PFU) was injected into normal and atherosclerotic arteries (n = 11 in both groups). The contralateral artery received either an Ad vector carrying no transgene (Ad.MLPnull) (n = 7 in both groups, 4 x 10(9) PFU) or vehicle buffer (n = 4 in normal group, n = 8 in atherosclerotic group). Animals were sacrificed 3 days following gene transfer for thrombus detection and assessment of beta-galactosidase activity. Thrombus was absent in normal arteries and in atherosclerotic arteries injected with vehicle buffer only. In contrast, nonocclusive thrombus was present in atherosclerotic arteries injected with either Ad.RSV betagal (5 of 11) or Ad.MLPnull (3 of 7). Beta-galactosidase activity was predominantly found in the endothelial layer of the transfected arteries. Gene transfer and expression occurred despite the presence of the thrombus (4 of 5), and its efficiency did not significantly differ regardless of the thrombus. We conclude that thrombus frequently occurred in atherosclerotic arteries after Ad-mediated gene transfer. Further studies are warranted to identify the mechanisms of thrombus generation after Ad-mediated gene transfer into atherosclerotic arteries.

Adenoviridae↗
PubMed1998

[Mechanisms and prevention of restenosis after coronary angioplasty].

The success of PTCA is limited by late restenosis, which occurs in 30-50% of all cases, chiefly within the first six months after the intervention. Restenosis is due to the proliferation of smooth muscle cells and especially to overproduction of extracellular matrix in the arterial wall. The coronary intervention is followed by a not fully defined constrictive process of wound healing, so-called remodeling. Various alternative intervention techniques were investigated but did not show any clear advantage concerning restenosis compared to PTCA. Although the rate of restenosis is reduced by stent implantation, which hinders remodeling, the remaining intimal hyperplasia often leads to restenosis. In spite of promising results in animal models, to date no effective human pharmacological therapy has been found to prevent restenosis. To determine whether antioxidants, endovascular radiation or gene therapy show any benefit will require further, larger trials.

Angioplasty, Balloon, Coronary↗
PubMed1998

The smooth muscle cell: sinner or saint in restenosis and the acute coronary syndromes?

Proliferation of arterial smooth muscle cells has held center stage as the culprit in restenosis for almost two decades. Many strategies for combating restenosis target smooth muscle replication. However, none have proven beneficial in clinical trials. Indeed, inhibition of smooth muscle proliferation in human patients might produce the undesired effect of destabilizing vulnerable atherosclerotic plaques because these cells furnish the collagen responsible for the biomechanical strength of the plaque. Actually, in some cases the benefit of angioplasty may depend on stimulating smooth muscle replication and collagen elaboration, converting an "unstable" to a more stable plaque. Moreover, recent clinical and experimental evidence suggests that restenosis depends less on neointimal hyperplasia than on constrictive remodeling (i.e., advential scarring, producing a smaller lumen), a process independent of smooth muscle replication. The recognition that plaques vulnerable to disruption often do not produce flow-limiting stenoses highlights a need for reassessment of the strategies to treat or prevent the acute coronary syndromes. We should strive to treat aggressively risk factors such as hyperlipidemia whose control appears to stabilize plaques. Trials are even underway comparing such risk factor management with coronary artery intervention. If we could identify potentially unstable atheroma before they are evident, clinically, we might even contemplate angioplasty of nonsignificant stenoses to induce smooth muscle cell proliferation and reinforce the plaque's fibrous cap. This proposal may seem preposterous, yet we perform "primary" angioplasty every day in patients with an acute myocardial infarction whose "culprit" lesions underlying the thrombus are often not critical. Our knowledge of the biology of restenosis has lagged behind our practice of coronary intervention. Advances in understanding the biology of the complications of interventional therapy, hand in hand with technical advances, should help us to devise more rational and enduring approaches to benefiting our patients.

Animals↗
PubMed1998

Epidemiology of peptic ulcer disease in cirrhotic patients: role of Helicobacter pylori infection.

OBJECTIVE: The aim of this study was to investigate the clinical and epidemiological factors associated with the appearance of peptic ulcer in patients with cirrhosis and, in particular, the role of Helicobacter pylori infection. METHODS: A total of 201 of 220 consecutive patients included in a prospective study that aimed to evaluate the effect of dietary intervention on cirrhotic complications and survival underwent upper gastrointestinal endoscopy. At entry, an epidemiological and clinical questionnaire was completed and the presence of peptic ulcer disease or esophageal varices at endoscopy was prospectively collected. Sera were obtained and stored at -70 degrees C until analyzed, being tested afterward for Helicobacter pylori antibodies using a commercial ELISA kit. RESULTS: Eleven of 201 patients had borderline anti-Helicobacter pylori IgG titers and were excluded from further analysis. In the remaining 190 patients, point prevalence of peptic ulcer was 10.5% and lifetime prevalence 24.7%. Multivariate analysis selected male sex (OR 2.3; 95%CI 1.09-4.89) and Helicobacter pylori seropositivity (OR: 1.7, 95%CI 1.02-2.81) as the variables independently related to peptic ulcer disease. CONCLUSIONS: Male sex and seropositivity for Helicobacter pylori are the major risk factors for peptic ulcer in cirrhosis.

Female↗
PubMed1997

Vasomotor dysfunction early after exposure of normal rabbit arteries to an adenoviral vector.

We aimed to investigate whether infection of normal rabbit arteries with a recombinant adenovirus vector would result per se in alterations in contractile and endothelial functions. In one group of rabbits, right or left femoral and ear artery segments were injected in vivo with a replication-deficient adenoviral vector expressing a beta-galactosidase (beta-Gal) reporter gene (4 x 10(10) pfu/ml) to demonstrate efficient gene transfer. Contralateral arteries were injected with the same concentration of a recombinant adenoviral vector carrying no transgene (Ad.MLPnull). In another group of animals, Ad.MLPnull was injected into the lumen of femoral and ear artery segments. The contralateral arteries were used as controls with the injection of vehicle alone. Histochemical assessment of gene transfer using beta-Gal activity (group 1) or in vitro contractility and endothelial function (group 2) was performed 3 days after adenoviral infection. Gene transfer was efficient and reproducible in the endothelium and was associated with the presence of inflammatory cells in the media. In Ad.MLPnull-injected arteries, in vitro contractile response of femoral artery rings to either KCl 60 mM or phenylephrine (10 microM) was reduced to 10.5 +/- 2.3% (n = 14; p < 0.001) and 8.8 +/- 2.0% (n = 7; p < 0.001) of the control values, respectively. Furthermore, in arteries injected with Ad.MLPnull, the endothelium-dependent relaxation produced by acetylcholine (10 microM) was virtually abolished. Similarly, the relaxant effects of the alpha 2-adrenoreceptor agonist UK14304 (1 microM) or the Ca2+ ionophore A23187 (1 microM) were also abolished. By contrast, sodium nitroprusside (10 microM) was still able to relax adenovirus-infected arteries. We conclude that infection with a recombinant adenoviral vector can induce early severe vasomotor alterations in both contractile function and endothelium-mediated relaxation of normal rabbit arteries.

Acetylcholine↗
PubMed1997

Seroprevalence and epidemiology of Helicobacter pylori infection in patients with cirrhosis.

BACKGROUND: Helicobacter pylori infection is the major pathogenic factor for peptic ulcer disease. Its epidemiology is not fully known; few data are available in patients with chronic liver disease. AIMS: To investigate the seroprevalence and factors associated with Helicobacter pylori infection in a series of liver cirrhosis patients. METHODS: Two hundred and twenty consecutive patients were prospectively included in a study aimed to evaluate the effect of dietary intervention on cirrhosis complications and survival. At inclusion, an epidemiological and clinical questionnaire was completed. Sera were obtained and stored at -70 degrees C until analyzed. They were tested for Helicobacter pylori antibodies using a commercial ELISA kit. RESULTS: Eleven out of 220 patients had borderline anti-Helicobacter pylori IgG titers. Of the remaining 209 patients, 105 (50.2%) showed positive titers of Helicobacter pylori IgG. Univariate analysis showed that Helicobacter pylori infection was more frequent in older patients, those born outside Catalonia, and in patients with a low educational level. Past ethanol consumption and current smoking correlated negatively with Helicobacter pylori infection. Multivariate analysis selected age (OR 3.1. 95% CI 1.46-6.45), educational level (OR 2.2. 95% CI 1.18-4.2) and alcohol consumption (OR 0.7. 95% CI 0.45-0.99) as the variables independently related to Helicobacter pylori infection. CONCLUSIONS: Helicobacter pylori infection in cirrhosis has the same epidemiological pattern as in the general population. Suggestions that the etiology or the severity of the liver disease could be related to Helicobacter pylori infection were not confirmed by our study.

Adult↗
PubMed1997

[Compensatory enlargement versus chronic constriction. The two features of vascular remodelling after experimental angioplasty].

Considerable efforts have been made to prevent post-angioplasty restenosis targeted mainly against a pathogenesis suggesting a dominant role of hyperplasia. We and others have already shown that constrictive remodelling plays a major role in restenosis. This article evaluates not only the constrictive remodeling theory but also compensatory enlargement associated with prevention of restenosis. The present study on 33 rabbits used the following protocol. Four weeks after inducing an atherosclerotic lesion by air-dessication of a femoral artery segment and a high cholesterol diet, angioplasty was performed. The angiographic minimal luminal diameter significantly increased after angioplasty. Three to four weeks later, initial gain was significantly lost. Restenosis was quantified histologically as well as a remodelling index and a hyperplasia index. No correlations were observed between degree of stenosis and hyperplasia present at the same degree in animals with and without restenosis. On the other hand, there was a strong correlation between restenosis and constrictive remodelling, and with absence of restenosis and compensatory enlargement. Moreover, there was significant a correlation between the degree of hyperplasia and the compensatory remodelling. These data point to the double nature of remodelling: compensatory enlargement observed in animals without restenosis, and constrictive remodelling, the principal mechanism observed in animals with restenosis.

Angioplasty, Balloon↗
PubMed1997

Remodelling: therapeutic opportunities.

Restenosis after angioplasty has been recently attributed to a lack of compensatory enlargement and/or chronic constrictive remodelling, rather than neointimal growth. Also, restenosis occurring after stent has been clearly related to neointimal growth. This clarification has dramatically helped in designing strategies targeted against the appropriate mechanisms. The mechanism of stent-related restenosis has been the most studied and several antiproliferative agents including gene therapy and radioactive stents have been successfully tested. Constrictive remodelling has been identified more recently and its pathophysiological mechanism remains poorly understood. Control of extracellular matrix metabolism might be an important pathway. Moreover, detection of the arteries that will 'enlarge' should avoid any preventive strategy including systematic stenting.

Adaptation, Physiological↗
PubMed1996

Decreased free radical scavengers with reperfusion after coronary angioplasty in patients with acute myocardial infarction.

Early reperfusion after myocardial infarction improves survival rate and is thought to preserve myocardial function, but the reperfusion of ischemic tissue may release oxygen free radicals, which could adversely affect left ventricular function and diminish the beneficial effects of reperfusion. Measurements related to free radical scavenging (plasma and erythrocyte enzyme systems, which are involved in free radical control, alpha-tocopherol, selenium, and manganese superoxide dismutase) may be indirect markers of free radical production. We evaluated 10 patients undergoing coronary angioplasty within 4 hours of myocardial infarction to measure the impact of abrupt reperfusion on free radical scavenger-related indexes. Pulmonary artery samples were taken before, immediately after, and 3 hours after angioplasty. During reperfusion, significant reductions occurred in alpha-tocopherol (1.1 +/- 0.3 mg/dl before, 0.9 +/- 0.2 mg/dl immediately after [p = 0.03], and 0.8 +/- 0.2 mg/dl 3 hours after percutaneous transluminal coronary angioplasty [p = 0.02]), and selenium levels (13.7 +/- 2.4 micrograms/dl before, 12.9 +/- 2.4 micrograms/dl immediately after, and 10.2 +/- 3.0 micrograms/dl 3 hours after angioplasty [p = 0.0006]). Erythrocyte markers (glutathione peroxidase and superoxide dismutase) were not altered by reperfusion, possibly reflecting the relatively long half-life of the erythrocyte. The erythrocyte glutathione peroxidase value before reperfusion in patients (30.8 +/- 5.1 IU/gm of hemoglobin) was lower than in a control group (36.1 +/- 6.5 IU/gm of hemoglobin; p = 0.01). Thus the decrease in plasma alpha-tocopherol and selenium after reperfusion in this group of patients may reflect a general alteration in plasma free radical scavenger levels, suggesting consumption of plasma free radical scavengers with reperfusion after acute myocardial infarction.

Angioplasty, Balloon, Coronary↗
PubMed1996

[Should a main coronary artery be dilated when the controlateral vessel is occluded?].

Angioplasty of the dominant left anterior descending or right coronary arteries when the controlateral artery is occluded may lead to major left ventricular dysfunction or cardiogenic shock. The authors assessed the results of angioplasty of a right coronary (n = 52) or left anterior descending (n = 141) artery stenosis when the controlateral artery was occluded and the left circumflex had no significant stenosis in 193 patients. The immediate and late (33 +/- 18 months) results were compared in 3 groups: the study group, a reference surgical group in which patients with comparable coronary lesions underwent double coronary artery bypass and a reference angioplasty group (n = 194) in which patients were treated by angioplasty of the right coronary and left anterior descending arteries. The left ventricular function of the study group was normal or midly abnormal in 72% of cases and moderately to severely abnormal in 28% of cases. During the hospital period, for the study group, there were 5.7% emergency coronary bypass procedures and 2.6% non-emergency bypass procedures, 1.6% of myocardial infarction and 0.5% deaths. After hospital discharge, the study group had 13.1% of coronary bypass procedures, 3.7% of myocardial infarcts and 4.7% deaths. The death and infarction rates were comparable in the 3 groups. The study group had a higher incidence of coronary bypass surgery in and after the hospital period than the control surgical group (p = 0.0.002). The authors conclude that dilatation of a main coronary artery when the controlateral artery is occluded is as safe as double coronary artery bypass surgery and angioplasty of the two vessels. Incomplete revascularisation in the study group did not affect survival rate without myocardial infarction compared with the angioplasty and surgical reference groups.

Actuarial Analysis↗
PubMed1995

Restenosis after experimental angioplasty. Intimal, medial, and adventitial changes associated with constrictive remodeling.

Predicting and preventing arterial restenosis after angioplasty has failed despite considerable research into mechanisms and techniques. We examined the roles of chronic constriction, neointimal-medial growth, and adventitial changes in restenosis in atherosclerotic rabbits. Angioplasty was performed on femoral artery lesions 4 weeks after lesion induction by air drying and cholesterol-supplemented diet. Angiographic and histological evaluation was conducted 3 to 4 weeks after angioplasty. The angiographic minimum luminal diameter (MLD) increased from 1.31 +/- 0.21 to 1.73 +/- 0.41 mm after angioplasty. Loss in MLD by 3 to 4 weeks was 0.95 +/- 0.64 mm. Initial gain and late loss correlated (P = .008). Late residual stenosis, defined histologically as the difference between the luminal areas of a proximal reference site and lesion site normalized by the luminal area of the reference site, was 52 +/- 32%. Histological indices of chronic constriction, neointimal-medial growth, and adventitial growth were defined on the basis of the areas of these arterial wall layers at the lesion site relative to the reference site. Another parameter defined as the ratio of adventitial area to the area of intima+media at the lesion site allowed evaluation of the relative importance of these layers. Surprisingly, late residual stenosis correlated with chronic constriction (P = .0003) but not with neointimal-medial growth or adventitial growth. The ratio of adventitial area to the area of intima+media at the lesion site also correlated with chronic constriction (P = .01). These findings suggest that factors related to arterial remodeling rather than neointimal-medial growth may dominate the response to angioplasty.

Angiography↗
PubMed1995

[Restenosis: physiopathology, treatments and prevention].

Despite fifteen years of extensive research, we still do not know how to predict or prevent restenosis. Angioplasty induces lesions in the intima, media and sometimes adventitia, resulting in a cicatricial process comprising proliferation and migration of smooth muscle cells towards the intima and secretion of extracellular matrix, leading to the formation of a neointima. Since angioplasty is associated with the simultaneous development of neointimal hyperplasia and restenosis, a cause and a effect relationship has therefore been proposed between neointimal hyperplasia and restenosis. All the restenosis prevention strategies based on inhibition of smooth muscle cell proliferation, which successfully limited restenosis in animal models have failed in man, due to the hazardous extrapolations from experimental models which are very different from the atheromatous lesions observed in man, rather than to the use of animal models in general. It is reasonable to wonder whether we have not selected the wrong target: is smooth muscle cell proliferation really responsible for restenosis? Experimental results supported by histological and ultrasonographic data in man, show that the cicatricial process which induces restenosis consists of constrictive remodelling, which decreases the perimeter of the external elastic lamina and the lumen. The use of stents appears to be the primary strategy designed to limit restenosis and prevent constrictive remodelling in man, even if it stimulates neointimal hyperplasia. Progress in the understanding of the mechanisms of postangioplasty remodelling open new perspectives in the prevention of restenosis.

Angioplasty, Balloon, Coronary↗
PubMed1995

[Granulomatous mastitis].

Six cases of granulomatous mastitis are reported. Based on a review of the relevant literature, the clinical features, etiology, and management of this pathologic entity are discussed. The definition of granulomatous mastitis is given and the characteristics that distinguish this condition from other inflammatory breast diseases are pointed out.

Adolescent↗