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Biomedical subjects

M M Thompson

Publications and source records attributed to M M Thompson.

At least 127 records · Page 7Linked to original sources
PubMed1995

Quality of life following infragenicular bypass and lower limb amputation.

AIMS: To objectively assess the quality of life after femorodistal bypass and compare this to quality of life achieved following primary limb amputation. DESIGN: Retrospective review. SETTING: Leicester Royal Infirmary, U.K., 1988-1993. METHODS: A self-assessment postal questionnaire containing scales measuring emotional disorder, social functioning and mobility was sent to 112 patients who had previously undergone femorodistal bypass (n = 86) or primary limb amputation (n = 26). RESULTS: Further analysis demonstrated that a secondary procedure (PTA or graft revision) to maintain graft patency did not adversely affect quality of life. Additionally, patients undergoing secondary amputation after graft failure had an identical quality of life to those undergoing primary amputation. CONCLUSIONS: These data illustrate that the quality of life after successful femorodistal bypass is higher than after primary or secondary amputation. To attain the maximum quality of life in patients with critical ischaemia, femorodistal bypass should be performed wherever feasible.

Aged↗
PubMed1995

Attachment, replication and thrombogenicity of genetically modified endothelial cells.

UNLABELLED: Endothelial cell seeding of prosthetic surfaces has been proposed as a technique to improve the patency of vascular grafts following arterial reconstruction. The introduction of specific recombinant DNA into seeded endothelial cells may enhance the anti-thrombogenic nature of the endothelial-blood interface with a consequent reduction in graft thrombosis. However, the successful use of genetically modified endothelial cells in the seeding process relies on the cells retaining normal function in terms of cellular replication, attachment and secretion of anti-thrombotic mediators. Successful genetic manipulation of human endothelial cells has been accomplished by viral and chemical methods. AIM: To study the functional characteristics of electrontransfected endothelial cells. METHODS AND RESULTS: Endothelial cells were electro-transfected with the test plasmid pTCF at a transfection efficiency of 10% utilising a single electric pulse with an electric field of 1000 volts/cm and a time constant of 12.8ms. The functional status of transfected endothelial cells was then compared with a control endothelial cell population. There were no significant differences in replication (p = 0.76), attachment (p = 0.43), basal (p = 0.89) or stimulated (p = 0.11) prostacyclin release between transfected cells as compared with control endothelial cells. CONCLUSIONS: Genetically modified cells are functionally normal, and may be used in endothelial cell seeding of prosthetic vascular surfaces.

Blood Vessel Prosthesis↗
PubMed1995

Risk factors leading to arterial occlusion following diagnostic arteriography.

OBJECTIVES: Arteriography may precipitate occlusive complications in stenotic vessels by a toxic effect on the vascular endothelium, leading to intra-arterial thrombosis. The aim of this retrospective study was to determine the incidence of arterial occlusion following arteriography. METHODS: We studied 101 consecutive patients (71 male, 30 female; median age 72 years) undergoing percutaneous transluminal angioplasty (PTA) of stenotic lesions, which had been identified on diagnostic arteriograms performed a median of 109 days (range 6-519) previously. One hundred and thirty-one arterial stenoses suitable for PTA were identified in the patient cohort. RESULTS: Seventeen patients (17%) progressed to occlusion in the period between diagnostic arteriography and PTA. Stenoses in the femoro-popliteal segment (21%) progressed to occlusion more frequently than lesions of the iliac arteries (3%). Independent risk factors were analysed to determine the risk factors predisposing to arterial occlusion following diagnostic arteriography. Both groups were well matched for age and sex. The mode of presentation, the presence of ischaemic heart disease, hypertension, diabetes or current smoking habits did not predict progression of disease to arterial occlusion. However, the rate of occlusion appeared to be influenced by the proportion of patients taking anti-platelet medication (51% in non-occluders as compared to 11% in patients who occluded, 95% CI 0.1 to 10), and to the length of time between arteriography and PTA (median of 92 days in non-occluders as compared to 125 days in patients who occluded, 95% CI 21 to 57). CONCLUSIONS: These data demonstrate that occlusion of pre-existing arterial stenoses following diagnostic arteriography is significantly more frequent in patients not taking anti-platelet medication and when the time interval between arteriography and PTA exceeds 92 days. To minimise thrombotic arterial occlusion both diagnostic and therapeutic procedures should be performed simultaneously, but if a delay is unavoidable, patients should be treated with anti-platelet medication, which reduces the incidence of arterial occlusion.

Aged↗
PubMed1995

Immunomodulation of cultured vascular endothelial cells by serial cell passage.

UNLABELLED: Endothelial cell seeding has been successful in reducing the thrombogenecity of prosthetic vascular grafts in animal models, but results from clinical trials have been largely disappointing. These poor results have been associated with poor graft coverage in immediate seeding trials, and failure of cell culture in staged procedures. These problems could be largely overcome by utilising a bank of allogeneic endothelial cells, providing an ever ready supply. However, one potential pitfall with this technique would be the possibility of a rejection response following transplantation. AIM: To study the effects of prolonged tissue culture, on the ability of endothelial cells to generate an immune response. METHODS AND RESULTS: The immunogenecity of human umbilical vein endothelial cells was measured using the mixed lymphocyte endothelial reaction. It was demonstrated that prolonged tissue culture significantly reduced the immunogenecity of the cells, from a mean of 7261 cpm (S.E. +/- 243, n = 3) for cells of subculture 3, to 5478 cpm (+/- 156, p = 0.04) for cells of subculture 7 (p = 0.04, Wilcoxon paired rank test), but did not significantly impair morphology or antithrombotic function. CONCLUSION: This study provides evidence that prolonged tissue culture provides morphologically and functionally intact, immunomodified endothelial cells which may potentially be used in seeding prosthetic vascular grafts.

Blood Vessel Prosthesis↗
PubMed1995

Optimisation of gene transfer into vascular endothelial cells using electroporation.

OBJECTIVES: We have examined the conditions required to obtain optimum transfection efficiencies for human umbilical vein endothelial cells by transduction with a plasmid conferring neomycin resistance. MATERIALS AND METHODS: Preliminary studies examined the effects of electric discharges using the Biorad Gene Pulser on endothelial cells. Post-electroporation, there was a significant decrease in cell survival with increasing voltages (100-400 volts; p = 0.03), capacitances [125-960 microFarads (microF); p = 0.02], number of electric pulses (1-2; p = 0.03) and decreasing cell concentrations (p = 0.01). The optimal cell concentration was 3 x 10(6) cells/ml. Transfection studies utilised the neomycin resistance expressing plasmid, pTCF; transfectants were selected with the neomycin analogue G-148. RESULTS: Electro-transfection was optimised with increasing voltages (p = 0.02) and capacitances (p = 0.01) using a single pulse. Optimal transfection was obtained using 400 volts with a capacitance of 960 microF using a single pulse; the median transfection efficiency was 10%. Transduced endothelial cells stably expressed the plasmid for 12 days and at least two cell passages. CONCLUSIONS: The results indicate that endothelial cells can be efficiently transduced by electroporation to stably express an introduced gene. This may have important implications in vascular surgery.

Cell Survival↗
PubMed1995

The conflicted individual: personality-based and domain-specific antecedents of ambivalent social attitudes.

Historically, attitude theory and research has assumed that attitudes are largely unconflicted and unidimensional summary statements of feelings and beliefs. More recent work has reexamined this assumption (Thompson, Zanna, & Griffin, in press). The present article details two studies that continue to investigate this notion, examining antecedent variables assumed important in the genesis of attitudinal ambivalence. The first study focuses upon personality-based factors such as individuals' Need for Cognition (NFC) and Personal Fear of Invalidity (PFI) (a heightened concern with error). The pattern of results was consistent with our predictions: High NFC was associated with less ambivalence and high PFI was associated with greater ambivalence. The second study investigated a domain-specific antecedent. It was predicted that higher involvement would reduce the level of ambivalence experienced. Further, involvement was expected to moderate the effect of the personality-based antecedents. Again, results confirmed our hypotheses. High NFC was associated with less ambivalence, especially under conditions of high involvement with the issues. Conversely, high PFI individuals who were highly involved with these issues experienced more ambivalence. These results are discussed in terms of their implications for attitude theory.

Adolescent↗
PubMed1995

Nuclear proteins bind a cis-acting element in the smooth muscle alpha-actin promoter.

Identification of the regulators of smooth muscle cell (SMC) gene expression is critical to understanding SMC differentiation and alterations in SMC phenotype in vascular disease. Previous studies revealed positive transcriptional activity within the chicken smooth muscle (SM) alpha-actin promoter region from -209 to -257. In the present study, transient transfections of wild-type and mutant chicken SM alpha-actin promoter/reporter gene constructs into rat aortic SMC demonstrated that the positive transcriptional activity of this region was abolished with a two base pair mutation in a conserved sequence motif at -225 to -233 (TGTTTATC to TACTTATC). Electrophoretic mobility shift assays revealed that nuclear factors bound promoter fragments containing this sequence and that specific mutations in the TGTTTATC motif abolished nuclear factor binding. Studies thus provide evidence for binding of a nuclear factor to a positive cis-acting element within the SM alpha-actin promoter. Further characterization of this factor may contribute to a better understanding of the molecular mechanisms that regulate differentiation of SMC in vascular disease.

Actins↗
PubMed1995

A retinoic acid-induced clonal cell line derived from multipotential P19 embryonal carcinoma cells expresses smooth muscle characteristics.

Despite intense interest in understanding the differentiation of vascular smooth muscle, very little is known about the cellular and molecular mechanisms that control differentiation of this cell type. Progress in this field has been hampered by the lack of an inducible in vitro system for study of the early steps of smooth muscle differentiation. In this study, we describe a model system in which multipotential mouse P19 embryonal carcinoma cells (P19s) can be induced to express multiple characteristics of differentiated smooth muscle. Treatment of P19s with retinoic acid was associated with profound changes in cell morphology and with the appearance at high frequency of smooth muscle alpha-actin-positive cells that were absent or present at extremely low frequency in parental P19s. A clonal line derived from retinoic acid-treated P19s (9E11G) stably expressed multiple characteristics of differentiated smooth muscle, including smooth muscle-specific isoforms of alpha-actin and myosin heavy chain, as well as functional responses to the contractile agonists phenylephrine, angiotensin II, ATP, bradykinin, histamine, platelet-derived growth factor (PDGF)-AA, and PDGF-BB. Additionally, 9E11G cells expressed transcripts for MHox, a muscle homeobox gene expressed in smooth, cardiac, and skeletal muscles, but not the skeletal muscle-specific regulatory factors, MyoD and myogenin. Results demonstrate that retinoic acid treatment of multipotential P19 cells is associated with formation of cell lines that stably express multiple properties of differentiated smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1995

Intratracheal gene delivery to the mouse airway: characterization of plasmid DNA expression and pharmacokinetics.

Intratracheal administration of plasmid DNA resulted in gene expression in mouse airways in the absence of any enhancing agent. Administration of plasmid DNA encoding the chloramphenicol acetyltransferase gene (CAT) in sterile water lead to CAT transgene expression that peaked between 1 and 3 days and was detected up to 28 days after DNA administration. Transgene expression was independent of mouse gender, age and strain. Levels of expression from DNA in various isotonic solutions did not differ from levels obtained with DNA administered in water, suggesting that transfection is not dependent on damage to airway cells caused by a hypo-osmotic delivery vehicle. Pharmacokinetic studies using radiolabeled plasmid DNA showed that DNA was rapidly degraded, while higher levels of radioactivity were retained for longer duration following administration of cationic liposome-DNA complexes in the airway. Southern blot and PCR analysis confirmed that DNA complexed with DOTMA-DOPE was retained in the airways for a longer period. However, cationic liposomes DOTMA-DOPE (1:1) or DOTAP complexed with DNA, did not enhance expression over DNA alone. These results suggest that 'naked' plasmid DNA should be included as a control in all studies on intratracheal gene delivery using nonviral systems.

Animals↗
PubMed1995

Quantification of orotic acid in dried filter-paper urine samples by stable isotope dilution.

A rapid, sensitive, and specific method for quantification of orotic acid from dried filter-paper urine samples is described. The method involves stable isotope dilution with 1,3-[15N2]orotic acid analysis by gas chromatography-mass spectrometry. The assay is sufficiently sensitive to be used with solvent extraction techniques commonly used for urinary organic acid analysis. Extraction efficiencies of both native and isotopic orotic acid from dried filter paper and from water were 31% and 28%, respectively. The concentration of orotic acid in dried filter-paper urine specimens from 50 healthy controls was 1.1 +/- 0.67 (mean +/- SD) mmol/mol of urinary creatinine. The same 50 urine samples, analyzed directly from a 5-mL aliquot of liquid urine, gave values of 0.93 +/- 0.51. The correlation coefficient between the results obtained by the two different collection methods was 0.87. Age-related reference values in filter-paper samples are also reported. The concentrations, which are normalized to urinary creatinine, decrease with age. This method is applicable to rapid screening for urea cycle disorders and may also be used for carrier testing of ornithine transcarbamylase deficiency.

Adolescent↗
PubMed1994

Treatment and outcome of severe lower-limb ischaemia.

The overall outcome of severe lower-limb ischaemia in terms of limb salvage and mortality is poorly documented. A consecutive series of 232 severely ischaemic legs in 209 patients was therefore studied. An aggressive policy of revascularization has been pursued; this was attempted in 89 per cent of legs, with a primary amputation rate of 8 per cent. The perioperative 30-day limb salvage rate was 79 per cent with a patient mortality rate of 20 per cent. At 12 and 24 months the limb salvage rates were 74 and 71 per cent and patient survival rates 75 and 73 per cent respectively. To identify high-risk groups the effects on limb salvage and mortality of age, sex, presentation, diabetes and ankle systolic pressure of 50 mmHg or less were studied. Using life-table analysis, none of the preoperative risk factors had an effect on limb salvage and mortality. An aggressive policy of revascularization provides excellent results in the treatment of patients with severe leg ischaemia.

Adult↗
PubMed1994

Endovascular repair of abdominal aortic aneurysm: limitations of the single proximal stent technique.

Endovascular repair of abdominal aortic aneurysm (AAA) has been performed using both a single proximal stent technique and a double (proximal and distal) stent method to anchor a graft in the aneurysm lumen. This study examined the effect of the single proximal stent technique on femoral artery blood flow, renal function and the occurrence of back-bleeding into the aneurysm sac in a canine model; eight dogs were used. Femoral artery blood flow and glomerular filtration rate were not affected by graft-stent insertion. Two graft-stent combinations failed to deploy in the correct position and led to graft thrombosis in one case. The six correctly positioned grafts all showed back-bleeding from around the distal end into the aneurysm sac. The single proximal stent technique for endovascular repair of AAA is inadequate and attention should continue to focus on a double (proximal and distal) stent method or a bifurcated system.

Animals↗
PubMed1994

Effect of pulsatile shear stress on endothelial attachment to native vascular surfaces.

An in vitro model of vascular damage was used to investigate the ability of seeded endothelial cells to resist shear stresses generated in a perfusion circuit. At perfusion rates of 100 ml/min the maximum shear stress reached 16.5 dyn/cm2. At this level the rate of cell detachment from the damaged vascular surface was 88 per cent per h for the first 20 min of flow but gradually decreased to 5 per cent per h after 90 min. These findings suggest that endothelial cells may be retained on damaged vascular surfaces in conditions that approximate to arterial flow.

Blood Flow Velocity↗