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Biomedical subjects

L J Feldman

Publications and source records attributed to L J Feldman.

At least 19 recordsLinked to original sources
PubMed2004

[Gene therapy of restenosis and atherosclerosis: hopes and facts].

Stents are the main technique of coronary revascularization in France and western countries. However, a better understanding of the pathophysiology of in-stent restenosis and the well-recognized roles played by inflammation and cell proliferation led to the development of drug-eluting stents, which have nearly eliminated the risk of restenosis. In this context, the success of gene therapy will depend on our ability to simplify and optimize current protocols of arterial gene transfer. For the time being, arterial gene therapy remains a powerful tool for deciphering the complex pathophysiology of restenosis and will certainly have far-reaching implications in the fields of vascular biology and therapeutics.

Adenoviridae↗
PubMed2004

[Angioplasty of saphenous vein grafts in the acute phase of myocardial infarction. Short and mid-term results].

The impact of the progress of interventional cardiology on the improved prognosis of myocardial infarction due to occlusion of a saphenous vein bypass graft is not well known. The aim of this study was to report the modalities and results at short and medium term of revascularisation by angioplasty of venous grafts in the acute phase of myocardial infarction. Out of a total of 870 consecutive patients treated by angioplasty in the first 6 hours of myocardial infarction with persistent ST elevation between 1990 and 2002, 16 (2%) had acute occlusion of a saphenous vein graft. Twelve of the 16 patients had previous myocardial infarction; perfusion was obtained in 7 patients. The attempt failed in 9 patients because of "no-reflow" (n=5), the extensive nature of the thrombosis (n=2) and technical failure (n=2). Three patients died in hospital, all after failed angioplasty. At 6 months, of the 13 survivors of the hospital period, 2 had been readmitted for a revascularisation procedure. At 2 years, 3 patients had died, 2 were readmitted for recurrent myocardial infarction and 8 patients remained free of a major cardiovascular event. Reperfusion by angioplasty of an occluded saphenous vein graft in the acute phase of myocardial infarction remains imperfect and the prognosis at short and medium term is poor.

Aged↗
PubMed2003

[Measurement of coronary reserve by high-frequency transthoracic Doppler ultrasonography: indications and results].

Coronary flow reserve is the ability of coronary flow to increase above its basal value when the coronary vascular bed is maximally dilated. It is a global parameter of coronary flow, which is early altered in the presence of epicardial coronary artery stenosis or a coronary microcirculation disorder. Until now, clinical use of coronary flow reserve has been hampered by the lack of an easy, reliable and non-invasive method. Recently developed high-frequency transthoracic Doppler echocardiography now allows non-invasive assessment of coronary flow reserve. After an initial learning curve, it is possible to study coronary flow, essentially in the left anterior descending artery. Coronary flow reserve is expressed as the ratio of maximal hyperaemic to basal mean coronary velocity. Maximal hyperaemic flow is obtained with adenosine. Clinical applications of coronary flow reserve are numerous. Coronary flow reserve enables the assessment of hemodynamic relevance of a moderate coronary stenosis. Detection of coronary restenosis is also possible by repeated non-invasive measurement of coronary flow reserve. Moreover, evaluation of the microcirculation is of crucial importance in order to appreciate myocardial reperfusion following successful recanalisation on the infarct-related artery. Transthoracic Doppler echocardiography could allow identification of "no-reflow" by analysis of coronary flow pattern and coronary flow reserve. Furthermore, transthoracic Doppler echocardiography constitutes one of the only available and simple means to evaluate microcirculatory disorders (hypertension, diabetes,...). Finally, the possibility of non-invasive follow-up of arterial bypasses constitutes a major advantage of this technique.

Coronary Stenosis↗
PubMed2003

[Femoral artery hemostasis after coronary angioplasty with moderate dose of heparin].

UNLABELLED: Early retraction of the arterial introducer facilitates patient management after coronary angioplasty. Closure systems permit rapid haemostasis, but are costly and do not avoid all serious vascular complications. Moderate doses of heparin, used often at the moment, could allow immediate retraction of the introducer with rapid and safe haemostasis by manual compression. METHODS: We evaluated prospectively in 350 consecutive patients the safety and efficacy of immediate retraction of the 6F introducer after coronary angioplasty performed by the femoral route with a moderate dose of heparin (70 IU. kg-1). Only procedures during acute infarction or using abciximab electively were excluded. RESULTS: Retraction of the introducer was immediate in 340 patients (97%). The dose of heparin administered was 5300 +/- 800 IU and the compression time was 11 +/- 4 minutes. The activated clotting time at retraction of the introducer was 254 +/- 46 s. Six (1.7%) serious vascular complications (4 significant haematomas and 2 false aneurysms) were noted during the hospital phase. A single patient (0.6%) was transfused and no vascular surgical procedure was necessary. The average duration of stay after angioplasty was 2.6 +/- 2.2 days and 73% of patients left before 48 hours. CONCLUSION: Immediate retraction of the arterial introducer is possible with simple manual compression, after coronary angioplasty performed with a moderate dose of heparin.

Angioplasty↗
PubMed2003

[Changes in reperfusion strategies in the acute phase of myocardial infarction from 1988 to 2001].

The objective of this study was to evaluate the evolution of therapeutic strategies in the course of myocardial infarction. Two successive periods were studied: 1988/96 (700 patients) and 1996/2001 (700 patients). The following parameters were compared: patient characteristics, management methods, and results on the hospital morbidity and mortality. The patient characteristics were little changed, in terms of age and sex, with a drop in the frequency of anterior infarcts during the second period (46 vs 51%, p = 0.0001). The average delay to admission remained stable over both periods, 186 vs 189 min. During the second period, primary angioplasty was favoured (66 versus 44%, p = 0.0001), associated with a wider use of stents (47 against 4%, p = 0.0001) and anti GP IIb/IIIa (24 against 0.5%, p = 0.0001). In the acute phase, TIMI3 reperfusion was obtained in 81% of cases (88/96 period) against 88% during the second period (p = 0.02). The hospital mortality was reduced by 1.2% (8.9 against 7.7%, NS). Without cardiogenic shock, the mortality was comparable between the two groups (5%), whereas it diminished in the small group of patients (5%) in cardiogenic shock, from 76 to 66% (NS). Haemorrhagic complications were reduced, but the rate of symptomatic reocclusion remained stable (2.5%). With multivariate analysis, the independent predictive mortality factors were identical in the two groups: age and cardiogenic shock on admission. Currently, TIMI3 reperfusion is possible in close to 90% of patients in the acute phase of infarction. Our efforts should focus on earlier management, especially for older patients, too often excluded without reason, and for those in cardiogenic shock, which constitutes a therapeutic quest for the future. The theory of angioplasty facilitated by anti GP IIb/IIIa and/or prehospital thrombolysis must be evaluated scientifically with the goal of early and efficient reperfusion for the greatest number of patients.

Aged↗
PubMed2002

Impact of availability and use of coronary interventions on the prescription of aspirin and lipid lowering treatment after acute coronary syndromes.

BACKGROUND: It has been suggested that patients undergoing acute intervention for coronary syndromes may not receive adequate secondary prevention. OBJECTIVE: To analyse the impact of availability and use of coronary interventions on the prescription of secondary prevention after acute coronary syndromes. DESIGN: Analysis of a prospective multicentre register of patients admitted to hospital for acute coronary syndromes. SETTING: A 1999 pan-European survey in 390 hospitals. PATIENTS: 3092 patients admitted to hospital with acute coronary syndromes (including 777 for ST elevation myocardial infarction within 12 hours of onset). MAIN OUTCOME MEASURES: Rates of prescription of aspirin and lipid lowering agents. RESULTS: Performance of coronary angiography and percutaneous coronary interventions (PCI) during the hospital stay were independent predictors of prescription of aspirin at discharge (odds ratio (OR) 1.29 and 1.89, p = 0.053 and p < 0.0001, respectively). Lipid lowering agents were prescribed more often on discharge in patients admitted to hospitals with catheterisation laboratories than without (for infarction with ST elevation, 45% v 40% (NS); for other acute coronary syndromes, 46% v 36%; p < 0.05). Prescription rates were higher among patients undergoing coronary angiography or PCI than in those treated conservatively (for infarction with ST elevation, 49%, 53%, and 39%, p < 0.05; for other acute coronary syndromes, 50%, 54%, and 34%, p < 0.05). Logistic regression analysis showed that PCI was an independent predictor of prescription of lipid lowering agents at discharge (OR 1.48, p < 0.0002). CONCLUSIONS: Contrary to expectations, invasive procedures for acute coronary syndromes are associated with higher rates of prescription of pharmacological secondary prevention.

Adrenergic beta-Antagonists↗
PubMed2001

Differential expression of matrix metalloproteinases after stent implantation and balloon angioplasty in the hypercholesterolemic rabbit.

BACKGROUND: Intimal hyperplasia is the principal mechanism of in-stent restenosis. Matrix metalloproteinases (MMPs) play a key role in intimal growth after balloon angioplasty (BA). Little is known, however, about MMP expression after stent implantation (ST). We investigated whether MMP9 and MMP2 are differentially expressed after ST and BA. METHODS AND RESULTS: Hypercholesterolemic rabbits underwent ST and BA in the right and left iliac arteries, respectively. The expression of MMPs and their inhibitors (TIMPs) was studied at various time points in the injured arteries by use of zymography, reverse transcription-polymerase chain reaction, and immunohistochemistry. MMP2, but not MMP9, was constitutively expressed in uninjured arteries. MMP9 expression was rapidly induced after injury, whereas the increase in MMP2 expression was delayed. At all time points, pro-MMP9 activity and MMP9 mRNA levels were >/=2-fold (ANOVA, P=0.002) and >/=3-fold (P<0.0001) higher after ST than after BA, respectively. Active MMP9 was detected only after ST. Although the increases in MMP2 mRNA levels were of similar magnitudes after ST and BA, pro-MMP2 activity was slightly higher 7 and 30 days after ST, and MMP2 activity was >/=2-fold higher 7 to 60 days after ST (P=0.002). No difference in TIMP expression was observed between stented and balloon-injured arteries. Cellular distributions of MMPs and TIMP1 were similar after ST and BA. Early inflammatory cell recruitment and 30-day intimal growth were more severe after ST. CONCLUSIONS: Stent implantation results in more intense and sustained expression of MMP9 and activation of MMP2 than balloon angioplasty.

Angioplasty, Balloon↗
PubMed2001

Effects of interleukin-10 on monocyte/endothelial cell adhesion and MMP-9/TIMP-1 secretion.

OBJECTIVE: Monocyte adhesion to endothelial cells and subsequent secretion of matrix metalloproteinases (MMPs) by activated macrophages are key events in arteriosclerosis and restenosis. We tested the hypothesis that interleukin-10 (IL-10), a potent anti-inflammatory cytokine, inhibits monocyte-endothelial cell interactions. METHODS: The effect of IL-10 on monocyte/endothelial cell adhesion, as well as on the expression of MMP-9 and the tissue inhibitor of MMP-9, TIMP-1, were first tested in vitro in coculture systems. In addition, we used an ex vivo binding assay to study the inhibitory effect of IL-10 on monocyte adhesion to carotid arteries obtained from either normal, or L-nitro arginine-methyl ester (L-NAME)-treated rats. The effect of IL-10 on the expression of monocyte adhesion molecules (CD18 and CD62-L) was studied by flow cytometry. RESULTS: IL-10 (150 ng/ml) inhibits monocyte adhesion to endothelial cells (by 35%) and to carotid arteries (by 40 and 50%, in normal and L-NAME-treated rats, respectively), via direct modulation of the expression of CD18 and CD62-L. Moreover, IL-10 dose-dependently decreases MMP-9 activity and increases TIMP-1 levels in coculture systems, both at the transcriptional level. CONCLUSIONS: Our results suggest that IL-10 is an important modulator of monocyte-endothelial cell interactions.

Analysis of Variance↗
PubMed2001

Expression of pH-sensitive green fluorescent protein in Arabidopsis thaliana.

This is the first report on using green fluorescent protein (GFP) as a pH reporter in plants. Proton fluxes and pH regulation play important roles in plant cellular activity and therefore, it would be extremely helpful to have a plant gene reporter system for rapid, non-invasive visualization of intracellular pH changes. In order to develop such a system, we constructed three vectors for transient and stable transformation of plant cells with a pH-sensitive derivative of green fluorescent protein. Using these vectors, transgenic Arabidopsis thaliana and tobacco plants were produced. Here the application of pH-sensitive GFP technology in plants is described and, for the first time, the visualization of pH gradients between different developmental compartments in intact whole-root tissues of A. thaliana is reported. The utility of pH-sensitive GFP in revealing rapid, environmentally induced changes in cytoplasmic pH in roots is also demonstrated.

Arabidopsis↗
PubMed2001

[Revision of the "Smoker's Paradox": smoking is not a good prognostic factor immediately after myocardial infarction].

In order to determine the reasons for the low mortality after myocardial infarction in smokers compared with non-smokers (the smoker's paradox), the authors analysed the initial clinical data, the therapeutic interventions and hospital mortality in 790 consecutive patients (555 smokers, 235 non-smokers) admitted to hospital within 6 hours of the first symptoms of acute myocardial infarction and treated by intravenous thrombolytic agents and/or coronary angioplasty. Multivariate analysis with linear regression was used to identify the predictive factors of hospital mortality. The main differences between smokers and non-smokers were age (56 vs 67 years, p < 0.0001), gender (male, 90 vs 60%, p < 0.01), cardiogenic shock on admission (3 vs 8%, p < 0.01). TIMI 3 flow was obtained in the culprit artery in 84% of smokers and 79% of non-smokers (NS). Hospital mortality was 5% in the smoking population and 16% in non-smokers (p < 0.0001). In multivariate analysis, the variables of cardiogenic shock, age, gender and hypertension provided most of the prognostic information and tobacco consumption did not appear to have a protective effect. In patients admitted to hospital with acute myocardial infarction, identical incidences of early reperfusion are obtained in smokers and in non-smokers. However, mortality is higher in the non-smoking group due to more severe clinical characteristics on admission. Tobacco consumption is not a protective factor in the immediate period after acute myocardial infarction.

Aged↗
PubMed2000

Interleukin-10 inhibits intimal hyperplasia after angioplasty or stent implantation in hypercholesterolemic rabbits.

BACKGROUND: Intimal hyperplasia after stent implantation is the main cause of in-stent restenosis. Activated monocytes play a key role in intimal growth. The anti-inflammatory cytokine interleukin-10 (IL-10) is a potent monocyte deactivator, endogenously produced in the atherosclerotic plaque. We tested the hypothesis that exogenous IL-10 may limit postangioplasty intimal hyperplasia after balloon angioplasty or stenting. METHODS AND RESULTS: Hypercholesterolemic rabbits were treated with recombinant human IL-10 (rhuIL-10) for 3 days after balloon angioplasty or 28 days after stent implantation. High IL-10 serum levels and intense deactivation of circulating monocytic cells, assessed by inhibition of IL-1beta release by lipopolysaccharide-stimulated whole blood, were detected for at least 8 hours after rhuIL-10 intravenous injection (ELISA). Morphometric analyses, performed 28 days after injury, indicated that rhuIL-10 reduced intimal growth by approximately 50% after balloon angioplasty or stenting, resulting in more preserved lumen in stented arteries. Moreover, rhuIL-10 reduced macrophage infiltration by 67% and proliferative activity by 81% in the intima and the media. No toxic effect was detected except minor changes in blood cell count. CONCLUSIONS: The anti-inflammatory cytokine rhuIL-10 reduces postinjury intimal hyperplasia. The potent attenuation of in-stent intimal growth by rhuIL-10 and its favorable toxicity profile suggest that rhuIL-10 may be useful in the prevention of in-stent restenosis.

Animals↗
PubMed2000

Three maize root-specific genes are not correctly expressed in regenerated caps in the absence of the quiescent center.

The quiescent center is viewed as an architectural template in the root apical meristem of all angiosperm and gymnosperm root tips. In roots of Arabidopsis thaliana (L.) Heynh., the quiescent center inhibits differentiation of contacting initial cells and maintains the surrounding initial cells as stem cells. Here, the role of the quiescent center in the development of the maize (Zeca mays L.) root cap has been further explored. Three maize root-specific genes were identified. Two of these were exclusively expressed in the root cap and one of them encoded a GDP-mannose-4,6-dehydratase. Most likely these two genes are structural, tissue-specific markers of the cap. The third gene, a putative glycine-rich cell wall protein, was expressed in the cap and in the root epidermis and, conceivably is a positional marker of the cap. Microsurgical and molecular data indicate that the quiescent center and cap initials may regulate the positional and structural expression of these genes in the cap and thereby control root cap development.

Amino Acid Sequence↗
PubMed2000

Reperfusion syndrome: relationship of coronary blood flow reserve to left ventricular function and infarct size.

OBJECTIVES: We tested the hypothesis that the reperfusion syndrome (RS), defined as an additional elevation of the ST segment upon reperfusion, may be a marker of microcirculatory reperfusion injury during acute myocardial infarction (AMI). BACKGROUND: The pathophysiology of the RS is unknown, and its prognostic implications are controversial. METHODS: Twenty-one patients with an anterior AMI treated < or =12 h after onset by primary coronary angioplasty (PTCA) were studied. Coronary velocity reserve (CVR), an index of microcirculatory function, was measured using a Doppler guidewire. Left ventricular (LV) ejection fraction, infarct size (percent defect) and LV end-systolic volume index (LVESVi) were evaluated by radionuclide ventriculography, 201T1 single-photon emission computed tomography and contrast ventriculography, respectively. RESULTS: Baseline ST elevation and pain-to-TIMI 3 time were similar in patients with and without RS. Patients with RS (10/21) had a lower post-PTCA CVR than patients without RS (median [95% confidence interval]: 1.2 [1-1.3] vs. 1.6 [1.5-1.7], p < 0.005). Even though predischarge CVR was similar in the two groups, infarct size at six weeks (26 [21 to 37] vs. 14 [10-17]% 201T1 defect, p = 0.001) and predischarge LVESVi (45% [40 to 52] vs. 30% [29 to 38] mL/m2, p = 0.001) were larger, and LV ejection fraction at six weeks (40% [37 to 46] vs. 55% [50 to 60], p = 0.004) was lower in patients with RS than in patients without RS. CONCLUSIONS: Patients with RS during primary PTCA for an anterior AMI have a transiently lower CVR than patients without RS, but sustained LV dysfunction and larger infarct size, suggesting that RS is a marker of microcirculatory reperfusion injury.

Aged↗
PubMed2000

The French Randomized Optimal Stenting Trial: a prospective evaluation of provisional stenting guided by coronary velocity reserve and quantitative coronary angiography. F.R.O.S.T. Study Group.

OBJECTIVES: We sought to make a prospective comparison of systematic stenting with provisional stenting guided by Doppler measurements of coronary velocity reserve and quantitative coronary angiography. BACKGROUND: Despite the increasing use of stents during percutaneous transluminal coronary angioplasty, it is unclear whether systematic stenting is superior to a strategy of provisional stenting in which stents are placed only in patients with unsatisfactory results or as a bail-out procedure. METHODS: Two hundred fifty-one patients undergoing elective coronary angioplasty were randomly assigned either to provisional stenting (group 1, in which stenting was performed if postangioplasty coronary velocity reserve was <2.2 and/or residual stenosis > or =35% or as bail-out) or to systematic stenting (group 2). The primary end point was the six-month angiographic minimal lumen diameter (MLD). Major adverse cardiac events were secondary end points (death, acute myocardial infarction and target lesion revascularization). RESULTS: Stenting was performed in 48.4% of patients in group 1 and 100% of patients in group 2 (p<0.01). Six months after angioplasty, the MLD did not differ between groups (1.90+/-0.79 mm vs. 1.99+/-0.70 mm, p = 0.39), as was the rate of binary restenosis (27.1% vs. 21.4%, p = 0.37). Among patients with restenosis, 13/32 (40.6%) in group 1 but 100% (25/25) in group 2 had in-stent restenosis (p<0.01). Target lesion revascularization (15.1% vs. 14.4% in groups 1 and 2 respectively, p = 0.89) and major adverse cardiac events (15.1% vs. 16.0%, p = 0.85) were not significantly different. CONCLUSIONS: Systematic stenting does not provide superior angiographic results at six months as compared with provisional stenting.

Aged↗
PubMed2000

Floral induction and determination: where is flowering controlled?

Flowering is controlled by a variety of interrelated mechanisms. In many plants, the environment controls the production of a floral stimulus, which moves from the leaves to the shoot apex. Apices can become committed to the continuous production of flowers after the receipt of sufficient amounts of floral stimulus. However, in some plants, the commitment to continued flower production is evidently caused by a plant's commitment to perpetually produce floral stimulus in the leaves. Ultimately, the induction of flowering leads to the specification of flowers at the shoot apex. In Arabidopsis, floral specification and inflorescence patterning are regulated largely by the interactions between the genes TERMINAL FLOWER, LEAFY and APETALA1/CAULIFLOWER.

Arabidopsis↗
PubMed2000

The consequences of a non-uniform tension across kinetochores: lessons from segregation of chromosomes in the permanent translocation heterozygote Oenothera.

The alternate (zigzag) configuration of the chromosome ring in oenotheras fulfills the requirement of high tension across kinetochores for stability of the configuration and the progression to anaphase. However, also semialternate configurations (two pairs of adjacent kinetochores interspaced among the zigzag) fulfill the requirement of high tension across kinetochores. If only the magnitude of tensile force acting on a kinetochore pair governs the stability of microtubule attachments, the probability of occurrence of the semialternate configurations would be higher than that of fully alternate configurations. Yet the percentage of irregularity in the zigzag configuration is surprisingly low, which means that the semialternate configurations are corrected. The only difference which distinguishes the fully alternate and the semialternate configurations with respect to the tension across kinetochores is that the tension across a kinetochore alternating with its neighbors is rather uniformly distributed over the kinetochore, while there is a gradient of the tension in the kinetochore having a non-alternating neighbor, with low tension on the side of this neighbor. Apparently, a low tension across a part of a kinetochore brings about correction of its attachment to microtubules. This hypothesis fits with the repeat subunit model of the kinetochore; apparently, each subunit can function autonomously in the tension-governed mechanisms, stabilizing its attachment and controlling the metaphase-to-anaphase transition.

Chromosome Segregation↗