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Biomedical subjects

S Nikol

Publications and source records attributed to S Nikol.

At least 37 records · Page 2Linked to original sources
PubMed1997

Excessive arterial thrombus in spherocytosis. A case report.

Spherocytosis is the most common of the hereditary hemolytic anemias, with characteristically shaped erythrocytes. An unusually large amount of arterial thrombus was documented in a dissected artery after angioplasty in a patient with spherocytosis. It is hypothesized that the excessive arterial thrombus may have been linked to the spherocytosis.

Aged↗
PubMed1995

Enhanced migratory activity of vascular smooth muscle cells with high expression of platelet-derived growth factor A and B.

UNLABELLED: Proliferation and migration of vascular smooth muscle cells (SMCs) are major events in atherogenesis. It is known that platelet-derived growth factor (PDGF) stimulates both of these processes in a paracrine fashion, whereas autocrine stimulation has been shown only for proliferation. The aim of this study was to investigate the influence of PDGF expression in SMCs on migratory activity of these cells. SMCs were cultivated from the vascular tissue of 23 patients. Cellular motility was analyzed by a computer-assisted motion analysis system; 54 images per sample, obtained during an observation period of eighteen hours, were analyzed. PDGF-A and PDGF-B mRNA levels were determined by quantitative polymerase chain reaction (PCR) following reverse transcription. To quantitate mRNA content of SMCs, the authors coamplified cDNA copies of mRNA from cells and from a synthetic reference RNA in the same reaction vessel. Cells derived from atherosclerotic lesions produced a 1.6-fold increase of PDGF-A (P < 0.05) and a 5-fold increase of PDGF-B mRNA (P < 0.05) as compared with those from normal vessels. The migratory velocity (range 11.1-49.2 microns/hr) was independent of PDGF-A and PDGF-B mRNA expression. A significant correlation between levels of PDGF-A mRNA and PDGF-B mRNA and the degree of directional changes of SMCs on the covered track (klinokinesis) was found (P < 0.05). CONCLUSION: PDGF-A and PDGF-B mRNA expression is significantly correlated with positive klinokinesis without affecting migratory velocity. This finding reflects enhanced migratory activity of SMCs. Besides its known mitogenic effects, the authors present evidence that PDGF may act as an autocrine motogen* in SMCs.

Adolescent↗
PubMed1995

Regulation of smooth muscle cell proliferation and its possible role in preventing restenosis post-angioplasty.

The introduction of balloon angioplasty in 1978 as an alternative treatment for vascular stenosis has created a new clinical problem: restenosis, the renarrowing that occurs after the procedure in certain patients. Restenosis is an important long-term complication, with an incidence of 30-50% within 6 months post-angioplasty. Three mechanisms contribute to vascular restenosis: recoil, thrombus formation and direct trauma. Growth factors which enhance the expression of other growth-regulating proteins, in particular "second messengers", proto-oncogenes and other cell cycle controlling proteins, are released by local thrombi and the injured arterial segment itself, resulting in an excessive inflammatory and myofibroproliferative response which culminates in restenosis. From investigations in animal models it is known that restenosis takes place in several phases: thrombosis, inflammation, cell proliferation and matrix formation. Various factors seem to interact in each particular phase, either as agonists or antagonists; hence the pathway that results in restenosis is complex. The introduction of directional percutaneous atherectomy has made it possible to examine human arterial tissue obtained in vivo, including restenosis material, from a sufficient number of patients in order to complement animal experiments. Not all of the mechanisms which lead to restenosis are known; nevertheless, after more than 15 years' experience of balloon angioplasty, there is an urgent need to develop therapeutic strategies based on currently available information. Selective elimination or alteration of proliferating cells, enhancement of natural growth inhibitors, blocking of signal transduction or inhibition of the gene expression for distinct growth-stimulating proteins all appear to be potentially promising.

Angioplasty, Balloon↗
PubMed1995

[Drug and instrumental therapeutic approaches for prevention of restenosis].

In recent years, several of the shortcomings of coronary angioplasty have been successfully countered. With more effective measures of treating acute complications, better equipment and more experienced operators, there has been a subsequent expansion of the indications and the type of lesions suitable for angioplasty. In the long-term, however, the restenosis rate remains the limiting factor for the success of the procedure. To date, clinical studies using systemic therapy or alternative instrumental devices have not convincingly demonstrated a benefit in preventing restenosis. New devices have mostly been used to manage complications at angioplasty or to increase the type of lesions that can be tackled transluminally. This article will describe recent findings relating to the pathology of restenosis and then discuss a new therapeutic concept, local drug delivery to suppress restenosis. The aim of this method of drug application is to achieve a high local concentration of agents that inhibit restenosis, while avoiding systemic side-effects. Possible substances which could be utilized in this manner include conventional therapies such as platelet or calcium antagonists, or anti-thrombotic, anti-inflammatory or anti-proliferative treatments, and also novel agents such as gene therapy. The latter strategy might include inhibition of certain stimulatory factors that control restenosis, for example, through antisense oligonucleotides, or alternatively, augmentation of naturally occurring inhibitory factors, perhaps with expression vector plasmids and virus-mediated gene integration. The various ways in which these substances can be locally delivered to the arterial wall, together with results from initial experimental studies will be summarized. It is possible that eventually the combination of effective treatments with local drug delivery (LDD) may at last resolve the restenosis problem in patients.

Angioplasty, Balloon, Coronary↗
PubMed1994

[Pathophysiology and pathobiochemistry of restenosis].

The high rate of restenosis after percutaneous transluminal angioplasty obviously depends on multiple factors. Predictors for the clinical outcome seem to be the selection of lesion morphology, the acute result and the biological vessel response in the first months after treatment. Thrombus formation and recoil have been considered to be pivotal events. Thus, anticoagulation and Ca-antagonists were routinely applied after treatment. Multiple studies with medical intervention have been performed, mostly with anticoagulants. However, no effective reduction of restenosis has been achieved so far. Analysis of autopsy tissue obtained after angioplasty indicated the importance of early vascular wall "response to injury" that might as a consequence lead to restenosis formation. This was confirmed by systematic experimental data. With introduction of directional atherectomy "biopsies" of primary and restenotic tissue were obtained. Thus, a subtile diagnostic spectrum including histological, immunohistochemical, electron microscopical, and molecular tissue analysis could be established. In vitro cultures of obtained tissue were performed routinely. They enable a characterization of proliferative and synthetic cellular features. Moreover, the effects of therapeutic measures can be quantified and used for pre-clinical screening. To date, the above described methods indicate as pivotal event the angioplasty induced transformation of contractile myocytes to a synthesizing type of myocytes. The transformation to synthetic active cells is not device dependent, but seems to be a major feature of restenosis. This process is mostly terminated in a period of 3-6 months. To accelerate this physiologic termination would be one interesting therapeutic option. Alternatively, special local drug delivery devices could be used to administer sufficient antiproliferative drugs at the site that needs to be treated.

Angioplasty, Balloon, Coronary↗
PubMed1994

Regional differences in the distribution of the proteoglycans biglycan and decorin in the extracellular matrix of atherosclerotic and restenotic human coronary arteries.

Proteoglycans are important constituents of blood vessels and accumulate in various forms of vascular disease. Little is known concerning the proteoglycan composition of restenotic lesions formed after angioplasty and whether the proteoglycan composition of these lesions differs from that of primary atherosclerosis. Accordingly, we sought to characterize the distribution of two proteoglycans, biglycan and decorin, in primary atherosclerotic and restenotic lesions of human coronary arteries. Restenosis (n = 37) and primary (n = 11) lesions obtained from 48 patients by directional atherectomy of human coronary arteries were stained with antibodies against biglycan and decorin. To further characterize the extracellular matrix of restenotic tissues, we studied the co-distribution of these proteoglycans with collagen types I, III, and IV. The loose fibroproliferative tissue seen predominantly in restenosis lesions consistently stained positively for biglycan in patterns of deposition ranging from disseminated to homogeneous. The density and intensity of biglycan staining was correlated with the density of collagen type I and III fiber networks, both of which were observed to interweave among the loose fibroproliferative tissue. The compact connective tissue of primary atherosclerotic plaque was characterized by strong biglycan staining which co-localized with intense collagen type I and III staining. Only basement membrane-like structures rich in collagen type IV demonstrated negative biglycan staining. In contrast, loose fibroproliferative tissue exhibited no significant staining for decorin. Strong immunostaining for decorin, however, was found in primary atherosclerotic plaque. There are thus regional differences in the distribution of extracellular matrix proteoglycans of restenotic and primary human atherosclerotic lesions; these observations suggest that differences established for the biological roles of biglycan and decorin in other organ systems may extend as well to pathologically altered human coronary arteries.

Angioplasty, Balloon↗
PubMed1992

Percutaneous arterial gene transfer in a rabbit model. Efficiency in normal and balloon-dilated atherosclerotic arteries.

The possibility of using an exclusively percutaneous strategy to deliver foreign DNA to normal and balloon-dilated atherosclerotic arteries was studied by analysis of transfection efficiency in a rabbit model. A total of 22 external iliac arteries from 22 rabbits (10 normal and 12 atherosclerotic) were transfected with a solution of luciferase expression vector plasmid and liposome, using a dual balloon-catheter system. Analysis of the transfected segments revealed luciferase activity in 10 of the 22 arteries (4/10 normal vs 6/12 balloon-injured atherosclerotic, P = NS); no activity could be detected in the contralateral limb arterial segments used as controls. Luciferase activity levels in successfully transfected segments measured 4.10 +/- 1.19 (m +/- SEM) Turner light units (TLU), with 3.03 +/- 1.16 TLU found in normals vs 4.81 +/- 1.87 TLU in balloon-injured atherosclerotic arteries (P = NS). In situ hybridization of successfully transfected atherosclerotic sections showed expression of the luciferase gene mRNA from rare cells (less than 1/1,000) limited to the neointimal lesion. Thus, expression of new genetic material may be achieved in both normal and balloon-dilated atherosclerotic arteries following an exclusively percutaneous approach. The low efficiency of the current delivery strategy, however, represents a potential limitation that must be improved if this strategy is to be applied as a therapeutic approach to human vascular disease.

Angiography↗
PubMed1992

Expression of transforming growth factor-beta 1 is increased in human vascular restenosis lesions.

Human atheromata obtained in vivo were used to test the hypothesis that transforming growth factor-beta 1 plays a role in the development of vascular restenosis. We analyzed 28 specimens from patients with primary atherosclerotic or restenotic lesions; 26 of these were obtained by directional atherectomy and 2 at the time of coronary bypass surgery. Seven control tissues included operatively excised segments of human internal mammary artery, myocardium, and unused portions of vein graft obtained intraoperatively. From these 35 specimens, 210 sections were examined using in situ hybridization. Measurement of silver grains/nucleus disclosed that expression of transforming growth factor-beta 1 mRNA was highest in restenotic tissues (P < 0.001 vs. primary atherosclerotic tissues) and lowest in nonatherosclerotic (control) tissues. In cultures of human vascular smooth muscle cells grown from explants of internal mammary artery, expression of mRNA for transforming growth factor-beta 1 was significantly greater in subconfluent than in confluent smooth muscle cells (P = 0.05). Transforming growth factor type-beta III receptor was expressed in cell cultures and undetectable in the tissue specimens. Sections taken adjacent to those studied by in situ hybridization were examined by immunohistochemistry using antibodies against transforming growth factor-beta 1 and alpha-actin (as a marker for smooth muscle cells) and disclosed transforming growth factor-beta 1 in smooth muscle cells present in these sections. These findings are consistent with the concept that transforming growth factor-beta 1 plays an important role in modulating repair of vascular injury, including restenosis, after balloon angioplasty.

Actins↗
PubMed1990

New site for pacemaker generators in children.

Bipolar pacemaker implantation was performed in three children, aged 5, 6 and 9 years. The two epimyocardial fishhook pacing electrodes were inserted through different incisions. After resection of the anterior part of the 5th and 6th rib, the generator was placed into a pocket with the posterior wall resulting from the remaining periostium/perichondrium and the anterior wall consisting of the isolated intercostal and pectoral muscle. The leads were brought in extrapleurally and connected to the generator. The operations were conducted without perioperative and late postoperative complications.

Child↗
PubMed1990

Selective annuloplasty of the tricuspid valve. Two-year experience.

Between July 1986 and March 1989, 48 patients whose ages averaged 60 +/- 6 years were subjected to a new technique for tricuspid valve annuloplasty. The preoperative New York Heart Association functional class averaged 3.7. There were 32 mitral-tricuspid procedures, 13 aortic-mitral-tricuspid procedures, and three repeat tricuspid annuloplasties. The hospital mortality rate was 6.3% with three deaths resulting from cardiac or respiratory failure, or both. Follow-up averaged 14 +/- 8 months. One patient (2.2%) died suddenly, 7 months postoperatively. All patients whose follow-up period lasted 6 months or more improved to class I or II. Twenty-six patients were reinvestigated by catheter or echocardiographic methods, or both. The gradient over the tricuspid valve averaged 1.4 +/- 0.6 mm Hg, and a moderate regurgitant murmur (2/3) was detected in four cases. The diameter of the tricuspidal anulus in the apical four-chamber view decreased from 23.7 +/- 3.9 mm/m2 body surface area preoperatively to 15.7 +/- 1.9 mm/m2 body surface area at late follow-up examination. The present technique allows an anatomic and functional reconstruction of the tricuspid valve with a good compromise between stenosis and regurgitation. The overall mortality rate is low and functional improvement is striking.

Adult↗
PubMed1989

Controversial aspects of coronary endarterectomy.

Between 1980 and 1987, 635 patients underwent coronary bypass grafting combined with coronary endarterectomy. A total of 728 vessels were endarterectomized and grafted. There were 15 early deaths (2.3%). The mortality rate was higher (7.8%) for multiple-vessel endarterectomy (p less than 0.05). The ratio of MB fraction of creatine kinase to total creatine kinase was greater than or equal to 0.10 in 48% of the cases. The first consecutive 132 survivors were followed for an average of 16 months (range, 4 months to 5 years). No late deaths occurred. Fifty-nine unselected patients underwent postoperative recatheterization at a mean interval of 18 months. An improvement in heart wall contractility could be detected in 13 patients (16.5%) and deterioration in 14 patients (17.7%). A more detailed analysis of wall contractility showed a higher rate of improvement in the posterior wall than in the anterior wall (p greater than 0.05). Furthermore, the better the contractility before operation, the greater the rate of deterioration after operation (p less than 0.05). Despite an average of 55% of all endarterectomized vessels being occluded or severely restenosed, 90% of the patients were clinically improved. A multiparametric analysis revealed that the revascularization of myocardial areas that required endarterectomy had no significant influence with respect to clinical improvement. Endarterectomy should be limited, whenever possible, to myocardial areas with already impaired contractility. Endarterectomy of multiple branches should be treated with caution because the risk of deterioration is potentiated, with a significantly higher perioperative mortality rate.

Adult↗