PubMed Health⌕ Search

Biomedical subjects

S Nikol

Publications and source records attributed to S Nikol.

43 records · Page 3Linked to original sources

Clinical experience with expanded polytetrafluoroethylene Gore-Tex surgical membrane for pericardial closure: a study of 110 cases.

Complete closure of the pericardium after cardiac operations has the advantage of avoiding injury of the heart and great vessels during reoperation. Between 1985 and 1987, the pericardium was closed with Gore-Tex Surgical Membrane (SM) in a selected series of 110 patients 1 month to 76 years of age. Fifty-three patients had congenital heart lesions and 57 patients had acquired heart disease. Overall hospital mortality was 3/110 cases. In no instance was there a relationship between occurrence of death and pericardial closure with SM. There was one episode of cardiac tamponade on the seventh postoperative day. One patient developed fever and leukocytosis due to a mediastinal hematoma. During a mean follow-up of 15 months, four patients had to be reoperated upon three, four, eight weeks, and eight months after primary operation. The anterior wall of the heart had no adhesion with the SM and the other parts of pericardium could be dissected easily. Scanning electron microscopic examination of the explanted SM patches showed neither cellular ingrowth nor immunocompetent cellular elements. The Gore-Tex Surgical Membrane has the advantages of easy availability and lack of reaction between its surface and the epicardium and pericardium. We believe its routine use should be encouraged in patients with high probability of reoperation after repair of complex cardiac anomalies, implantation of bioprostheses, coronary revascularization for one- or two-vessel disease, and repair of degenerative disease of the ascending aorta.

Adolescent↗

Closure of the pericardium using expanded polytetrafluoroethylene GORE-TEX-Surgical Membrane: clinical experience.

Complete closure of the pericardium after cardiac operation would have the advantage of avoiding injury of the heart and great vessels should repeat sternotomy prove to be necessary. In such situations, various pericardial closure techniques have been described. Synthetic materials produced severe scarring, while xenografts appeared to be satisfactory, although fibrous reactions and aseptic cystic formations have been reported recently. Between 1985 and 1986 we closed the pericardium with GORE-TEX-Surgical Membrane in a selected series of 72 patients aging 1 month to 76 years, median 24 years. Overall hospital mortality was 3/72 cases. In no instance was there a relationship between death occurrence and pericardial closure through Surgical Membrane. There were 5 cases each of low cardiac output and rethoracotomy because of bleeding. No cardiac tamponade occurred. Two patients had to be reoperated three and four weeks after primary repair. Surgical Membrane was explanted. Electron microscopy examination showed no cellular ingrowth in the low porosity membrane. No immunocompetent cellular compounds were present on either side of the graft. Follow-up interval averaged 13 months. No complication related to pericardial closure has occurred until now. The Surgical Membrane has the advantages of easy availability, of lack of reactions both between its surface and the underlying epicardium and with the rest of the pericardium. We believe its routine use should be encouraged mainly in patients with high probability of reoperation.

Adolescent↗

Inducible expression of p21WAF-1/CIP-1/SDI-1 from a promoter conversion retroviral vector.

Constitutive, high-level expression of the potentially therapeutic WAF-1/CIP-1/SDI-1 gene is incompatible with cell growth. A promoter conversion retroviral vector carrying the WAF-1/CIP-1/SDI-1 gene under the transcriptional control of the glucocorticoid inducible promoter of mouse mammary tumor virus was used to infect human bladder carcinoma or feline kidney cells. Reduced cell growth due to a greater proportion of cells being in the G0/G1 phase of the cell cycle was observed when WAF-1/CIP-1/SDI-1 expression was activated by addition of glucocorticoid hormone. This system demonstrates the potential long-term therapeutic use of WAF-1/CIP-1/SDI-1 delivered by retroviral vectors for inhibiting the growth of rapidly proliferating cells. Moreover, the conditional expression of genes such as WAF-1/CIP-1/SDI-1 from such retroviral vectors may facilitate analysis of their function.

Animals↗

In vivo perivascular implantation of encapsulated packaging cells for prolonged retroviral gene transfer.

Long-term benefits of coronary angioplasty remain limited by the treatment-induced renarrowing of arteries, termed restenosis. One of the mechanisms leading to restenosis is the proliferation of smooth muscle cells. Therefore, proliferating cells of the injured arterial wall, which can be selectively transduced by retroviruses, are potential targets for gene therapy strategies. A direct single-dose therapeutic application of retroviral vectors for inhibition of cell proliferation is normally limited by too low transduction efficiencies. Encapsulated retrovirus-producing cells release viral vectors from microcapsules, and may enhance the transduction efficiency by prolonged infection. Primary and immortal murine and porcine cells and murine retrovirus-producing cells were encapsulated in cellulose sulphate. Cell viability was monitored by analysing cell metabolism. Safety, stability, transfer efficiency and extent of restenosis using capsules were determined in a porcine restenosis model for local gene therapy using morphometry, histology, in situ beta-galactosidase assay and PCR. Encapsulation of cells did not impair cell viability. Capsules containing retrovirus-producing cells expressing the beta-galactosidase reporter gene were implanted into periarterial tissue or a pig model of restenosis. Three weeks following implantation, beta-galactosidase activity was detected in the pericapsular tissue with a transduction efficiency of approximately 1 in 500 cells. Adventitial implantation of vector-producing encapsulated cells for gene therapy may, therefore, facilitate successful targeting of proliferating vascular smooth muscle cells, and allow stable integration of therapeutic genes into surrounding cells. The encapsulation of vector-producing cells could represent a novel and feasible way to optimize local retroviral gene therapy.

3T3 Cells↗

Evaluation of beta-galactosidase activity in tissue in the presence of blood.

The reporter gene for beta-galactosidase is frequently used to determine the efficiency of gene transfer in arteries. However, blood is often present in arterial explants and may compromise the results by the presence of hemoglobin. The light absorption of hemoglobin is similar to the absorption of several colorimetric products of the commonly used beta-galactosidase substrates, including o-nitrophenyl-beta-D-galactopyranoside (ONPG) and chlorophenol red galactopyranoside (CPRG). This may result in false-positive measurements of beta-galactosidase enzyme activity. The aim of this investigation was to determine the most appropriate method for quantification of beta-galactosidase activity in the presence of blood. Colorimetric substrates (ONPG, CPRG) or the chemiluminescent Galacton-Plus substrate were used, and light absorption was measured at different concentrations of erythrocyte extract. Among the beta-galactosidase substrates tested, CPRG was the most appropriate, allowing detection of enzyme activity at concentrations as low as 0.05 mU, independent of blood contamination. Addition of reducer stabilized enzyme activity for at least 5 h. Endogenous beta-galactosidase activity was evaluated and used to correct results. CPRG substrate, in combination with the reducer agent mercaptoethanol, was found to be the optimal reagent for quantifying beta-galactosidase activity in the presence of blood after nonviral in vivo reporter gene transfection, even with a relatively low transfer efficiency.

Animals↗