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Biomedical subjects

R M Greenhalgh

Publications and source records attributed to R M Greenhalgh.

At least 73 records · Page 4Linked to original sources
PubMed1995

The influence of fibrinogen concentration on the development of vein graft stenoses.

OBJECTIVE: The aim of this study was to identify factors associated with the development of graft stenoses in the first year after bypass. DESIGN AND SETTING: Between January 1992 and April 1993, 75 consecutive patients undergoing distal vein bypass surgery were entered into a graft surveillance programme at Charing Cross Hospital. The grafts (n = 79) were surveyed by colour flow Doppler ultrasonography at 7 days, 3, 6, 9 and 12 months and the site of stenoses (> 50%) recorded. Position of the distal anastomosis, graft type (in situ or reverse) and clinical history were recorded. At the 3-month surveillance a blood sample was taken for the estimation of smoking markers, lipids and fibrinogen. RESULTS: The site of the distal anastomosis was to the suprageniculate popliteal in nine, infrageniculate popliteal in 32 and tibio/peroneal vessels in 38 cases. In the first month following bypass there were six deaths, giving a 30 day mortality of 7.5%, three patients were lost to follow up, seven grafts occluded, three were replaced by PTFE, four patients underwent amputation and one patient had a redo vein graft. In the remaining grafts 20/63 (32%) developed stenoses within the first year after bypass. The development of a graft stenosis was not associated with sex, diabetic status, site of distal anastomosis, graft type or serum lipids. Multiple regression analysis identified only one factor associated significantly with the development of vein graft stenosis: fibrinogen concentration (p = 0.003). Life table analysis showed that after 1 year only 46% of grafts remained free of stenoses in patients with above median fibrinogen concentrations compared with 84% of grafts in patients with below median fibrinogen concentrations, p = 0.009. CONCLUSIONS: Increased plasma fibrinogen concentration is a potent risk factor for the development of vein graft stenosis. These results prompt consideration of the role of fibrinogen in stimulating smooth muscle cell proliferation in the stenotic lesion.

Aged↗
PubMed1995

Factors associated with healing leg ulceration with high compression.

To investigate factors relevant to the healing of leg ulceration by high compression, patients were interviewed using a standard questionnaire prior to treatment with a four-layer bandage high-compression system in six community ulcer clinics. We explored the relation of size, ulcer duration and medical history to healing. Cumulative healing rates were high using this method, being 69% after 12 weeks and 83% after 24 weeks. Twelve-week healing rates varied slightly between clinics, ranging from 62% to 83%. Univariate analysis of the total group showed that male sex (RR = 0.77, p = 0.023), poor limb joint mobility (RR = 0.39, p < 0.001), poor general mobility (RR = 0.49, p = 0.015), treatment at home (RR = 0.52, p < 0.001), ulcer size > 10 cm2 (RR = 0.37, p < 0.001), history of deep vein thrombosis (RR = 0.67, p = 0.016) and ulcer duration >6 months (RR = 0.35, p < 0.001) were significantly inversely associated with healing, Ulcer size, duration, limb joint mobility and general mobility were significant independent factors in multivariate analysis.

Adult↗
PubMed1995

Venous ulcer healing: effect of socioeconomic factors in London.

OBJECTIVE: To determine which social and clinical factors are associated with healing in patients with venous ulceration. DESIGN: Patients were questioned about social factors at their first visit to a community ulcer clinic. They were treated by high compression bandage system and were interviewed again after 12 weeks. SETTING: Community leg ulcer clinics held in health centres throughout Riverside Health Authority in London. PATIENTS: All patients referred to five community leg ulcer clinics with venous ulceration over a six month period. MAIN OUTCOME MEASURES: These were factors significantly associated with healing within 12 weeks of beginning treatment, measured by odds ratio (OR) given by logistic regression analysis. MAIN RESULTS: Of 168 patients with venous ulceration, 87 (52%) healed after 12 weeks of treatment. Univariate analysis showed that low social class (OR = 3.44, 95% CI 1.17, 10.14), lack of central heating (OR = 2.22, 95% CI 1.18, 4.18), and being single (OR = 2.77, 95% CI 1.15, 6.69) were all significantly associated with delayed healing. After adjustment for the known risk factors of ulcer size, ulcer duration, and general mobility only lack of central heating was still significant (OR = 2.27, 95% CI 1.11, 4.55). The remaining factors failing to achieve statistical significance because of their inter-relationship with the known risk factors. CONCLUSIONS: Clinical features of the ulcer seem to determine the progress of healing in patients with leg ulceration. Although there were associations between socio-economic factors and poor healing, adjustment for clinical risk factors generally led to lower non-significant associations. Only lack of central heating retained its association and may play a part in prolonging healing of venous ulceration.

Aged↗
PubMed1995

Inflammation and matrix metalloproteinases in the enlarging abdominal aortic aneurysm.

The risk of rupture of an abdominal aortic aneurysm increases with aortic diameter. To obtain insight into the pathological processes associated with the vascular remodeling that accompanies aortic dilatation, we compared the histological features and the activity of matrix metalloproteinases (MMPs) in biopsies from 21 small (4.0 to 5.5 cm in diameter) and 45 larger abdominal aortic aneurysms. The histological feature most clearly associated with enlarging aneurysm diameter was a higher density of inflammatory cells in the adventitia, P = .018. This inflammation was nonspecific, principally macrophages and B lymphocytes. Fibrosis of the adventitia provided compensatory thickening of the aortic wall as the aneurysm diameter increased. A combination of zymography and immunoblotting identified gelatinase A (MMP-2) as the principal metallogelatinase in small aneurysms, whereas zymography indicated an increasing activity of gelatinase B (MMP-9) in large aneurysms. Homogenates prepared from both small and large aneurysms had similar total activity against gelatin or type IV collagen. However, the concentration of gelatinase A, determined by immunoassay, was highest for small aneurysms: median concentrations, 385, 244, and 166 ng/mg protein for small aneurysms, large aneurysms, and atherosclerotic aorta, respectively. Immunolocalization studies indicated that gelatinase A was concentrated along fibrous tissue of both the acellular media and the atherosclerotic plaque. The recruitment of inflammatory cells into the adventitia, with subsequent elaboration of metalloproteinases, including gelatinase B, may contribute to the rapid growth and rupture of larger aneurysms.

Amino Acid Sequence↗
PubMed1995

[Mode of genetic inheritance of abdominal aortic aneurysm: still no clear answers].

Clear evidence has not yet come concerning the genetics of abdominal aortic aneurysms (AAA). There are circumstantial proof for a hereditary predisposition. In a retrospective study of sixty patients consecutively underwent a surgical repair for AAA, showed that one third of them knew a first-degree relative with the same disease. Environmental factors, such as smoking, ageing or hypertension, must be taken into account. A multifactorial mode of inheritance is under discussion due to both multiple genes with different expressivity and diverse environmental factors. Linkage-analysis or DNA sequencing of the different gene loci in population studies or sibbling-analysis are the tools in search for candidate genes for inheritance of AAA. Mutations in those genes encoding structural components of the aortic wall, such as collagen-type-III, fibrillin or elastin, are not taken to be the underligned genetic cause. Mutations in genes encoding enzymes for the turnover of the aortic wall components, such as alpha-1-antitrypsin or matrix-metalloproteinase-2, may play an important role.

Aortic Aneurysm, Abdominal↗
PubMed1994

Smoking and growth rate of small abdominal aortic aneurysms.

Smoking is an important risk factor for abdominal aortic aneurysm. Limiting the growth rate of small aneurysms has the potential to prevent them reaching a size at which surgical repair is considered. In 43 patients, with small aneurysms, growth rates were studied by serial ultrasound over 3 years. The median expansion rate of these small aneurysms was 0.13 cm per year. Growth rates were higher in those who continued to smoke (0.16 vs 0.09 cm per year in those who no longer smoked, p = 0.038). Higher growth rates were significantly correlated with the concentration of serum cotinine. Stopping smoking could reduce the growth rate of small abdominal aortic aneurysms.

Aged↗
PubMed1994

Pathogenesis of abdominal aortic aneurysm.

The pathogenesis of abdominal aortic aneurysm involves many factors acting over time. However, destruction of elastin in the aortic wall is a key event that shifts the load produced by blood pressure on to collagen. This is exacerbated in the presence of hypertension. Smoking and age are further important factors, as is the site; elastic lamellae are relatively less common in the abdominal aorta. Once the shielding effect of elastin is lost, further dilatation and rupture of the aorta depend on the physical properties of the collagen present.

Age Factors↗
PubMed1994

The use of duplex scanning to diagnose perioperative carotid occlusions.

Perioperative stroke following carotid endarterectomy is reported to occur in 3-20% of patients and may be associated with spontaneous development of thrombus at the operation site or technical imperfections. In 118 consecutive patients, duplex scanning performed immediately before anaesthesia was used to confirm that all high grade carotid stenoses had not progressed to occlusion since the arteriogram. A new technique at completion, using subcuticular prolene sutures for the skin and a plastic dressing for the wound, permitted immediate postoperative assessment by duplex scanning if necessary. Of the 118 patients, symptoms of neurological instability developed in 4 (3.4%) in the first 6 hours after surgery. At duplex scanning, developing thrombus was demonstrated in three of these patients. Arterial thrombus was removed at reoperation and all three patients recovered with no neurological deficit. The fourth patient had occluded the contralateral carotid artery, developed a major stroke and was not considered for re-exploration. Duplex scanning provides accurate diagnostic information in selecting patients for urgent re-exploration, reducing the 24 h stroke rate to 0.8% in this series.

Aged↗
PubMed1994

Is thickening of the basal lamina in the saphenous vein a hallmark of smoking?

OBJECTIVE: To investigate whether smoking causes ultrastructural changes in the intima of the proximal saphenous vein. DESIGN: Proximal saphenous veins from heavy smokers and non-smokers were examined with scanning and transmission electron microscopy to determine changes in surface ultrastructure, in the intercellular junction, and in the thickness of the basal lamina. Immunogold labelling was used to identify specific components of the endothelial basal lamina. MATERIAL: Vein specimens were obtained from patients undergoing varicose vein surgery (12 patients) or distal bypass surgery (eight patients). MAIN RESULTS: The only ultrastructural change that discriminated between specimens was thickening of the endothelial basal lamina. All specimens with a thickened basal lamina were from heavy smokers. Immunogold labelling studies showed that the thickened basal lamina contained specific accumulations of fibronectin but not heparan sulphate proteoglycans, type IV collagen, or laminin. CONCLUSIONS: Two ultrastructural characteristics are associated with smoking: thickening of the endothelial basal lamina and a specific accumulation of fibronectin in the thickened basal lamina. Such abnormalities in the saphenous veins from smokers may contribute to the poorer performance of these veins as bypass conduits.

Adult↗
PubMed1993

High prevalence of unsuspected abdominal aortic aneurysm in patients with confirmed symptomatic peripheral or cerebral arterial disease.

A group of 561 consecutive patients with proven symptomatic peripheral or cerebral arterial disease attending a vascular clinic was screened for abdominal aortic aneurysm (AAA) using B-mode ultrasonography. An aneurysm was present in 40 of 358 men (11.2 per cent) and 13 of 203 women (6.4 per cent), a total prevalence of 9.4 per cent. Thirty-three aneurysms were 3-4 cm in diameter. The prevalence of AAA was similar in patients referred with lower-limb and with cerebral ischaemia. Physical examination for AAA was performed in 200 patients before ultrasonography. The sensitivity of physical examination in the detection of aneurysm was 43 per cent (57 per cent for AAA > or = 4 cm in diameter, 29 per cent for AAA < 4 cm in diameter). Physical examination was an inadequate method of screening. Initial follow-up showed a mean aneurysm expansion rate of 0.20 cm/year. Patients with arterial disease have a high risk of AAA; routine ultrasonographic screening should be considered.

Aortic Aneurysm, Abdominal↗
PubMed1993

Smoking impairs endothelium-dependent relaxation of saphenous vein.

Samples of proximal saphenous vein were obtained from heavy smokers and non-smokers: 28 were obtained at varicose vein surgery and eight at infrainguinal bypass surgery. The veins were prepared for histological examination and for mounting in an organ bath to measure changes in isometric tension. Vein rings from both smokers and non-smokers responded equally to sodium nitroprusside, a reagent that acts directly on smooth muscle cells, undergoing 90-100 per cent relaxation. The mean(s.e.m.) maximum relaxation in response to bradykinin of rings obtained at varicose vein surgery was 50.0(5.3) per cent in non-smokers compared with only 31.6(2.2) per cent in smokers (P = 0.03). Similarly, in specimens obtained at bypass surgery the mean(s.e.m.) maximum relaxation in smokers was only 25.1(6.3) per cent compared with 48.4(4.1) per cent in smokers (P = 0.04). Relaxation in response to the bradykinin stimulus was abolished in the presence of L-nitroarginine methyl ester, a specific inhibitor of the synthesis of endothelium-derived relaxing factor (EDRF). Preincubation of the vein rings with L-arginine, the precursor of EDRF, did not increase the vasorelaxation in smokers. The mean(s.e.m.) maximum relaxation in response to the calcium ionophore A23187 was 53.5(3.8) per cent in non-smokers compared with only 27.0(4.9) per cent in smokers (P = 0.01). The results indicate that heavy smokers have impaired release of EDRF in response to both bradykinin and calcium ionophore. This impairment may increase vasomotor tone, platelet aggregation and smooth muscle proliferation, thereby resulting in an increased risk of graft occlusion.

Adult↗
PubMed1993

Influence of type III collagen genotype on aortic diameter and disease.

Type III collagen contributes to the tensile strength of the aortic wall, and mutations in the type III collagen gene have been suggested as the basis for the familial tendency to abdominal aortic aneurysm (AAA). Variation in this gene was investigated in 153 patients with AAA, 87 with aortoiliac stenosis and 98 age-matched controls. The rare mutation at amino acid 619 of Gly-->Arg, previously associated with AAA in a single family, was not found in any of the patients with aneurysm. For the Ala-->Thr variation at amino acid 531, the frequency of the threonine allele was 0.25 in patients with AAA and stenosis, compared with 0.35 in controls. The frequency of the rare allele in the region 3' to the gene demonstrated by Ava II digestion (0.27 in the general population) was found to be 0.29 in the AAA group and 0.19 in the stenosis group (P = 0.023). In the AAA group the presence of the Ava II rare allele was associated with a significant increase in aneurysm diameter (P = 0.044). Non-invasive assessment of aortic distensibility was available in 25 patients: those carrying the Ava II rare allele had less distensible aortas than those not carrying this allele (median pressure-strain elastic modulus 42.0 and 23.9 N/cm2 respectively, P = 0.008). Variation in the type III collagen gene may influence the mechanical properties of the ageing aorta and hence its susceptibility to disease and dilatation. In contrast, there is no evidence for a single common founder mutation in type III collagen predisposing to AAA.

Aged↗
PubMed1993

The influence of collagen and albumen presealants on knitted Dacron grafts.

Dacron arterial grafts may be sealed with collagen or albumen to avoid preclotting. The influence on graft thrombogenicity and maturation was studied in 36 patients undergoing elective arterial bypass surgery for aortoiliac disease randomised to (i) collagen impregnated (Meadox Hemashield), (ii) albumen coated (USCI) or (iii) standard knitted Dacron (Meadox Microvel, UCSI Vasculour II) preclotted with the patient's own blood. Five days and 2 months postoperatively, autologous 111indium-labelled platelet deposition was measured as the daily increase in the ratio of graft to blood radioactivity and expressed as the Thrombogenicity Index (TI) (units, 10(-3). Duplex Doppler examination was used to detect thrombus, neointima or perigraft fluid. TI (median and interquartile range) was similar in the grafts at 5 days at 2.12 (-0.026-3.67) for preclotted Dacron, 2.72 (1.69-7.15) for collagen impregnated and 2.7 (2.13-8.56) for albumen coated Dacron, and was not significantly different at 2 months at 2.66 (2.07-5.18) (n = 9), 4.22 (1.3-7.02) (n = 8) and 2.89 (1.03-16.5) (n = 7), respectively. Duplex Doppler demonstrated perigraft fluid at the proximal anastomosis of an occluded albumen coated graft but no further abnormalities were detected. On these data sealing of knitted Dacron with collagen or albumen does not influence early graft thrombogenicity or maturation.

Aged↗