Search PubMed⌕ Search

Biomedical subjects

J Segovia

Publications and source records attributed to J Segovia.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Practice guidelines of the Spanish Society of Cardiology. Cardiac and heart-lung transplants].

Cardiac transplantation is the only therapy that is able to substantially modify the natural evolution of patients with severe heart failure, along with angiotensin converting enzyme inhibitors. Nevertheless, because of the limited number of donors, its impact is scarce compared to the magnitude of the problem. Up to the end of 1998, 48,541 orthotopic cardiac transplantations and about 2,510 heart and both lung transplantations have been registered throughout the world. In Spain 2,780 procedures have been performed in the last 15 years. The survival expectations for a transplanted patient is 75% after the first year and 60% the following 5 years. The average duration of the graft is 8 years and 6 months. Cardiac transplantation is indicated for young and middle-age patients with irreversible cardiac process in bad clinical condition, with no other possibility of medical or surgical management and with a limited life expectancy. The major debate when choosing this therapy appears with the critical patients, patients older than 65 years, and some patients with systemic diseases. The great demand of transplantation obliges the teams to enlarge the criteria for donors' acceptance. At the same time, the increase of the knowledge about the transmission of some infections, mainly viral, forces to review those criteria day-to-day. The use of different immunosuppressive strategies pursues the control of rejection. The most commonly used is the so-called triple therapy (cyclosporine-azathioprine and steroids). The use of antilymphocytic antibodies such as cytolytic induction treatment is not unanimously accepted. Some of the new immunosuppressive agents such as myphenolate-mofetil and tacrolimus seem to offer advantages mainly due to their greater potency. Since transplantation is a limited procedure, of which its practise has an effect on the whole health system of a country, a perfect planning and adequacy of the Centers is compulsory, as well as the setting-up of clear rules for the use of donors and priority of transplantation. Finally, the patient must be informed clearly and comprehensively at length of the risks, limitations and expectations of these complex procedures.

Biopsy↗
PubMed1999

Nonviral transfer of genes to pig primary keratinocytes. Induction of angiogenesis by composite grafts of modified keratinocytes overexpressing VEGF driven by a keratin promoter.

Cultured epithelial grafts have proven to be life-saving in the treatment of large skin losses. It has become apparent that one of the main difficulties of this technology is the overall poor take of the grafts as a consequence of severely damaged dermal beds. Skin substitutes providing both cultured keratinocytes, as an epidermal layer, and a dermal analogous offer a more suitable material for skin repair. Ex vivo transfer of stroma regeneration-promoting genes to keratinocytes appears to be an attractive strategy for improving the therapeutic action of these grafts. The use of epidermal-specific promoters as expression drivers of exogenous genes results in both high expression levels and stratum specificity, as shown in transgenic mice studies. Most current gene transfer protocols to primary keratinocytes involve transduction of epidermal cells with retroviral vectors. However, transfer of gene constructs harboring these long DNA fragment promoters cannot be achieved through viral transduction. In this paper, we describe a protocol consisting of lipid-mediated transfection, G418 selection and an enhanced green fluorescence protein (EGFP)-based enrichment step for obtaining high levels of transgene-expressing primary keratinocytes. Using this protocol, the cDNA for vascular endothelial growth factor (VEGF), a potent endothelial cell mitogen driven by the 5.2 kb bovine keratin K5 promoter, was stably transfected into pig primary keratinocytes. Genetically modified keratinocytes, expanded on live fibroblast-containing fibrin gels and transplanted to nude mice as a composite material, elicited a strong angiogenic response in the host stroma as determined by fresh tissue examination and CD31 immunostaining. Since the formation of a well-vascularized wound bed is a crucial step for permanent wound closure, the use of an 'angiogenic' composite material may improve wound bed preparation and coverage with cultured keratinocyte grafts.

Animals↗
PubMed1998

Differentiation-dependent expression of transgenes in engineered astrocyte cell lines.

The utility of transgenes for both basic and applied studies has been augmented by the recent advent of versions that can be regulated by the addition of suitable activators. However, still more convenient would be transgenes whose expression responded appropriately to endogenous signals. The promoter of the glial fibrillary acidic protein (GFAP) gene is a candidate for this role in the central nervous system (CNS) since the GFAP gene is specifically expressed in astrocytes in the CNS and its activity is upregulated in response to almost any CNS injury. As a feasibility study, we isolated a C6 rat glioma cell line stably transfected with a lacZ reporter gene driven by the gfa2 human GFAP promoter fragment. We find that the activity of the transgene indeed responds to an environmental signal, forskolin, that induces astrocyte-like differentiation of C6 cells. We also isolated a C6 line carrying a transgene in which the gfa2 promoter directs expression of a cDNA for tyrosine hydroxylase (TH), the rate-limiting enzyme for catecholamine synthesis. This transgene should be of considerable interest for gene therapy for Parkinson's disease. We show that in this cell line both TH mRNA and protein are upregulated by forskolin. Finally, we note that the growth rate of C6 cells is severely depressed by forskolin, suggesting that predifferentiation of these cells prior to implant may retard their tumor forming capacity, prolonging the time that they can be used in animal models in vivo.

Animals↗
PubMed1998

Three cases of tuberculosis after heart transplantation in Spain.

Three cases are presented of tuberculosis occurring in a series of 410 heart transplant recipients in a Spanish hospital, representing a rate of 0.73%. Twenty-eight cases reported in the literature are also reviewed. In most series reported, tuberculosis occurred in a small percentage of heart transplant recipients, the average rate being 1.25%. Compared to the general population, a higher percentage (28%) of extrapulmonary and disseminated forms of the disease is seen in these patients. Although a cure without recurrence can usually be achieved with a conventional anti-tuberculous antibiotic regimen, the disease is still associated with a significant mortality rate of 11%. Guidelines for the early diagnosis and treatment of these patients are discussed.

Aged↗
PubMed1998

Advantage of stents in the most proximal left anterior descending coronary artery.

OBJECTIVES: Balloon angioplasty of the proximal left anterior descending artery is associated with a high rate of restenosis. We hypothesized that the significant reduction in restenosis rates demonstrated by stent implantation in the coronary arteries in general would be especially prominent in the most proximal left anterior descending coronary artery. METHODS: We reviewed 65 consecutive patients in whom stents were placed in the most proximal left anterior descending artery between March 1990 and July 1995 and compared them with 56 consecutive patients with angioplasty. Minimum luminal diameter was measured angiographically before, after, and 6 months after the intervention. We compared the change in minimum luminal diameter and restenosis rate between the patients with stents and the patients with angioplasty to clarify the response of this important artery to these different procedures. RESULTS: There was 6-month angiographic follow-up of the treated lesion in 99% of the patients. The postprocedure minimum luminal diameter, acute gain, and minimum luminal diameter at follow-up were greater in arteries treated with stents than in those treated with balloons. Of importance, late loss was not significantly different between the two groups after treatment at this site. Thus the restenosis rate after angioplasty was 52% compared with 20% after stent implantation (p < 0.001). CONCLUSIONS: Stent implantation in the most proximal left anterior descending artery is associated with an even greater reduction in restenosis rate than implantations elsewhere in the coronary arteries. This enhanced reduction in restenosis appears to be due to an unusually large amount of late loss after angioplasty at this site.

Angioplasty, Balloon↗
PubMed1998

Astrocyte-specific expression of tyrosine hydroxylase after intracerebral gene transfer induces behavioral recovery in experimental parkinsonism.

Parkinson's disease is a neurodegenerative disorder characterized by the depletion of dopamine in the caudate putamen. Dopamine replacement with levodopa, a precursor of the neurotransmitter, is presently the most common treatment for this disease. However, in an effort to obtain better therapeutic results, tissue or cells that synthesize catecholamines have been grafted into experimental animals and human patients. In this paper, we present a novel technique to express tyrosine hydroxylase (TH) in the host's own astrocytes. This procedure uses a transgene in which the expression of a TH cDNA is under the control of a glial fibrillary acidic protein (GFAP) promoter, which confers astrocyte-specific expression and also increases its activity in response to brain injury. The method was tested in a rat model of Parkinson's disease produced by lesioning the striatum with 6-hydroxydopamine. Following microinjection of the transgene into the denervated striatum as a DNA-liposome complex, expression of the transgene was detected by RT-PCR and TH protein was observed specifically in astrocytes by using double-labeling immunofluorescence for GFAP and TH coupled with laser confocal microscopy. Efficacy was demonstrated by significant behavioral recovery, as assessed by a decrease in the pharmacologically induced turning behavior generated by the unilateral denervation of the rat striatum. These results suggest this is a valuable technique to express molecules of therapeutic interest in the brain.

Animals↗
PubMed1997

Clinical and angiographic implications of coronary stenting in thrombus-containing lesions.

OBJECTIVES: This study sought to determine the results of coronary stenting in thrombus-laden lesions. BACKGROUND: The angiographic evidence of intracoronary thrombus has classically been considered a formal contraindication to stent implantation. However, with increasing use of stenting, the indications for this technique have widened to include treatment of patients who have an acute coronary syndrome or lesions with adverse anatomic features. METHODS: We studied 86 consecutive patients (mean age +/- SD 61 +/- 11 years, 14 women) undergoing coronary stenting of a thrombus-containing lesion; the procedure was performed electively in 39% and after angioplasty failure in 61%. Sixty-four patients (75%) were treated for unstable angina, and 19 (22%) underwent the procedure during an acute myocardial infarction. A specific protocol that included clinical and late angiographic follow-up was used. RESULTS: Angiographic success was obtained in 83 patients (96%). Five patients (6%) died during the hospital stay despite angiographic success; four of these had cardiogenic shock, and one (1%) had subacute stent thrombosis. Non-Q wave myocardial infarction developed in five additional patients (6%), and four of these five had data consistent with distal embolization. Of the 78 patients discharged with angiographic success, 67 (86%) were event-free and clinically improved at last follow-up visit (12 +/- 11 months). During the follow-up period, eight patients required repeat angioplasty, one patient required heart transplantation, and two patients died. Quantitative angiography demonstrated excellent angiographic results after stenting (minimal lumen diameter 0.31 +/- 0.4 vs. 2.77 +/- 0.6 mm). Late angiographic follow-up (5.5 +/- 1 months) was obtained in 50 patients with 54 lesions (93% of eligible), revealing a minimal lumen diameter of 2.0 +/- 1 mm and restenosis (lumen narrowing > 50%) in 18 lesions (33%). CONCLUSIONS: Coronary stenting constitutes an effective therapeutic strategy for patients with thrombus-containing lesions, either after failure of initial angioplasty or electively as the primary procedure. Coronary stenting in this adverse anatomic setting results in a high degree of angiographic success, a low incidence of subacute thrombosis and an acceptable restenosis rate.

Adult↗
PubMed1997

Effects of Palmaz-Schatz stents on angled coronary arteries.

This review of consecutive, single Palmaz-Schatz stent implantations reveals that coronary lesion angulation does not result in suboptimal results or increased restenosis after stenting. The implantation of a rigid stent at an arterial hinge point is associated with an increased restenosis rate.

Coronary Angiography↗
PubMed1997

Intracoronary ultrasound before coronary interventions: a prospective comparison of two different catheters.

Intravascular ultrasound (IVUS) provides unique information about the coronary arterial wall that can be used to guide transcatheter therapy. In this prospective study, two different IVUS systems were compared with respect to feasibility of imaging before intervention and angiographic changes induced by the simple advancement of the catheter across the lesion. Eighty-five patients (mean age 59 +/- 10 yr, 11 female) were studied with IVUS before intervention. In 34 patients, a 4.8 F (1.6-mm) IVUS catheter was used (Group I), whereas in the remaining 51 patients, a 3.5 F (1.2-mm) IVUS catheter was used (Group II). Quantitative angiography was performed before and after the IVUS study to determine potential changes in lumen diameter. Clinical and angiographic characteristics were similar in the two groups. A successful IVUS interrogation of the target lesion was obtained more frequently in Group II (45/51 (88%) vs. 19/34 (56%) patients, P < 0.01). After the IVUS study, a change in minimal lumen diameter was seen in Group I (baseline 0.84 +/- 0.2 vs. final 1.17 +/- 0.2 mm, P < 0.001) and Group II patients (baseline 0.80 +/- 0.3 vs. final 1.03 +/- 0.4 mm, P < 0.01). In the 64 lesions successfully crossed, the absolute gain in lumen diameter was significantly higher in Group I (0.40 +/- 0.2 vs. 0.23 +/- 0.2 mm, P < 0.05). In addition, an inverse correlation was found between baseline minimal lumen diameter and the absolute lumen gain induced by the IVUS study in Group I (r = -0.47, P < 0.05) but not in Group II patients (r = -0.16, NS). Neither angiographic nor echogenic lesion characteristics were associated with the change in lumen diameter. When multivariate analysis was applied, catheter size was the only independent predictor of lumen gain induced by IVUS after adjustment. Thus, the advancement of IVUS catheters across severe coronary lesions induces significant angiographic changes consistent with plaque remodeling and a Dotter effect. The use of smaller catheters not only allows a higher number of lesions to be studied before intervention, but also lessens the mechanical disruption of the plaque, yielding a more accurate and veracious picture of baseline plaque characteristics.

Aged↗
PubMed1997

Aortic dissection occurring during coronary angioplasty: angiographic and transesophageal echocardiographic findings.

A localized acute aortic dissection was produced in 2 patients, complicating coronary angioplasty. In both cases a coronary dissection provided the entry door, with subsequent retrograde progression of the dissection into the aortic root. After sealing the entry door, both patients could be managed conservatively using transesophageal echocardiography to accurately define the location of the intimal flap and to rule out dissection progression.

Aged↗
PubMed1997

Feasibility of intravascular ultrasound studies: predictors of imaging success before coronary interventions.

BACKGROUND: Intravascular ultrasound (IVUS) is currently used to study lesions during transcatheter coronary therapy. However, before dilation some lesions cannot be reached or crossed with the imaging catheter. HYPOTHESIS: This study seeks to elucidate which factors determine the feasibility of IVUS examination before coronary interventions. METHODS: Accordingly, 100 consecutive patients undergoing IVUS examination before coronary angioplasty were prospectively studied. The clinical and angiographic characteristics of 77 patients with a successful IVUS study (Group A) were compared with those of 23 patients in whom IVUS was attempted but the target lesion could not be interrogated (Group B). The echogenic characteristics of the target lesion [before (n = 77) or after intervention (in 18 patients in Group B)] were also studied. RESULTS: Patients in Group B were significantly older (62 +/- 7 vs. 57 +/- 10 years, p < 0.05) and more frequently had stable angina [8 (35%) vs. 9 (11%), p < 0.05]. The distribution of lesions within the coronary tree and angiographic lesion characteristics including length, eccentricity, calcification, bend location, and the American College of Cardiology/American Heart Association classification were similar in both groups. However, proximal tortuosities (> 45 degrees at end diastole) were more frequently found in Group B [20 (87%) vs. 47 (61%), p < 0.05]. In addition, by quantitative angiography, patients in Group B had smaller arteries (reference diameter 2.8 +/- 0.4 vs. 3.1 +/- 0.4 mm, p < 0.05) and more severe lesions (minimal lumen diameter 0.46 +/- 0.24 vs. 0.65 +/- 0.34 mm, p < 0.05). On IVUS, calcified lesions were more frequently visualized in Group B (61 vs. 38%, p < 0.05). On multivariate analysis, catheter size, baseline minimal lumen diameter, angiographic proximal tortuosities, and lesion calcification on imaging were independent predictors of the feasibility of IVUS studies. CONCLUSIONS: Unsuccessful IVUS studies before intervention occur more frequently (1) in vessels with proximal tortuosities or severe lumen narrowing, (2) in lesions that are calcified on IVUS, and (3) when large imaging catheters are used.

Angina Pectoris↗
PubMed1997

Angioscopic evaluation of angiographically complex coronary lesions.

Coronary angioscopy (CA) provides direct visualization of the endoluminal surface of coronary vessels. The usefulness of CA during coronary angioplasty of angiographically complex lesions remains to be established. This study was designed to determine the value of CA to elucidate the underlying substrate of angiographically complex lesions. Forty-seven consecutive patients with angiographically complex lesions were studied with CA before coronary intervention. Mean age of the group was 59 +/- 9 years; six patients were women. Forty (85%) patients had unstable angina. Complex angiographic lesions included coronary occlusions (n = 23) (14 with Thrombolysis in Myocardial Infarction coronary flow grade 0 and nine with flow grade 1), lesions with intraluminal filling defects suggestive of thrombus or ulceration (n = 8), and lesions that were highly eccentric (n = 16). Items analyzed with CA included red thrombus (lining or protruding) and plaque color (yellow, white, or mixed). In all patients, CA visualized the protruding material causing the angiographic appearance. At this site CA detected red thrombus in 34 (72%) patients (14 protruding, 20 lining) and atherosclerotic plaque in 45 (96%) patients. At the site of the angiographically complex lesion, plaque was classified as predominantly yellow in 24 patients, mixed in 12, and white in nine. The incidence of thrombus on CA was higher for occluded vessels (91%) or lesions with intraluminal filling defects or ulceration (87%) than in eccentric lesions (37%) (p < 0.05). However, plaque coloration was not significantly different among these three angiographic subgroups. Initial procedural success (without stent requirement) was lower in lesions showing protruding thrombus on CA (64% vs 91 %, p < 0.05). Thus most angiographically complex lesions contain thrombus. On CA red thrombus was more frequently identified on occluded vessels and lesions with filling defects or ulceration than in eccentric lesions. Yellow or mixed plaques are common in these patients, suggesting lipid-laden plaques as the underlying pathologic substrate of angiographically complex lesions.

Aged↗
PubMed1997

[The role of non-angiographic observations (IVUS, angioscopy, doppler) in coronary stenting].

Coronary stenting is increasingly used during transcatheter coronary therapy. Coronary angiography, mainly since the advent of quantitative angiography, provides an effective tool to obtain excellent clinical results with coronary stenting. However, during this procedure some limitations inherent to the angiographic techniques may become apparent. Accordingly, great enthusiasm has been generated regarding the potential value of alternative diagnostic techniques to guide coronary stenting. Intravascular ultrasound is able to study the arterial wall and provides a unique tool to assess stent expansion, apposition and symmetry. Therefore, this technique is increasingly used to optimize stent deployment. Coronary angioscopy directly visualizes stent expansion and is able to precisely recognize protrusion of redundant fronds of tissue or residual dissections within the stent struts. In addition, this technique is the procedure of choice to identify intracoronary thrombus. Intracoronary Doppler permits the application in the catheterization laboratory of sophisticated methods of functional assessment of lesion severity. Coronary stenting allows a faster and complete normalization of coronary flow reserve than balloon angioplasty. Thus, all these new techniques of intracoronary diagnosis provide unique and useful information, which is complementary to that obtained with angiography, potentially useful during coronary stenting.

Angioscopy↗