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Biomedical subjects

R M Greenhalgh

Publications and source records attributed to R M Greenhalgh.

At least 109 records · Page 6Linked to original sources
PubMed1991

Within-individual variation in serum cholesterol levels: association with DNA polymorphisms at the apolipoprotein B and AI-CIII-AIV loci in patients with peripheral arterial disease.

We have examined the association between variation at the apolipoprotein (apo) B gene and apo AI-CIII-AIV gene cluster and within-individual variation in serum cholesterol levels. Annual measurements were available over a period of 5-10 years in a group of 117 male patients with peripheral arterial disease. The overall within-individual coefficient of variation in cholesterol levels over time was 13.9%. For all patients, Restriction Fragment Length Polymorphism (RFLP) genotype at the apo B gene (XbaI and EcoRI) and apo AI-CIII-AIV gene cluster (XmnI, PstI and PvuII-CIII) had previously been determined. At the apo B locus, individuals heterozygous for either the XbaI or EcoRI RFLP showed significantly greater within-individual variability over time compared to individuals of other genotypes. At the apo AI-CIII-AIV gene cluster, individuals homozygous for the common allele of either the PstI or PvuIIA RFLPs showed the greatest within-individual variability over time but there was no difference in this estimate associated with XmnI genotype. Our observations suggest that variation at both the apo B and apo AI-CIII-AIV loci interacts with unidentified environmental factors to determine individual variability in serum cholesterol levels over time.

Apolipoprotein A-I↗
PubMed1990

Brachial artery damage following cardiac catheterisation. When to re-explore.

Cardiac catheterisation is frequently performed in modern medical practice and the brachial artery is frequently used. The brachial and forearm systolic pressures were measured by Doppler ultrasound at rest and after hand exercise for 60 s in 75 patients undergoing catheterisation. These objective measurements, together with a history of forearm claudication during the one minute of exercise and clinical examination of the radial pulse were repeated again at 1 hour, 1 week and 3 months. Changes in the forearm/brachial pressure index (PI) at rest and a fall in forearm pressure after exercise were compared with the pre-catheterisation values. Sixteen per cent of patients suffered claudication of the forearm during the one minute hand exercise immediately after catheterisation. Of those seen at 3 months, 12% had persistent claudication and all had a markedly reduced PI measured following catheterisation. Conversely, at 1 [corrected] hour after catheterisation, the radial pulse was weak or absent in 20% and 33% were abnormal on Doppler studies and not all had symptoms. It emerges that to avoid claudicating forearms at 3 months, re-exploration, one hour after brachial catheterisation is indicated in some cases. We are inclined to base this upon the 16% who had forearm claudication after one minute of exercise and who also had absent or reduced radial [corrected] pulse and abnormal Doppler studies. Conversely to base the need for re-exploration upon a reduction or absence of the radial pulse [corrected] (20%) on Doppler studies (33%) would lead to an unnecessarily high rate of re-exploration just after the procedure.

Arterial Occlusive Diseases↗
PubMed1990

Genetic variation on chromosome 16 is associated with abdominal aortic aneurysm.

1. There is a familial tendency to abdominal aortic aneurysms. We have followed up a previous report of a weak association between the haptoglobin 2-1 phenotype and aortic aneurysm and investigated polymorphisms of the haptoglobin gene and neighbouring cholesterol ester transfer protein gene on the long arm of chromosome 16 in patients with atherosclerotic abdominal aortic aneurysm, patients with stenosing aortic atherosclerosis and healthy control subjects. The protein polymorphism of haptoglobin results from variant alpha-chains, alpha 1 and alpha 2, the phenotype nomenclature describing the two alpha-chains. We have also investigated whether the different haptoglobin phenotypes influence the degradation of aortic connective tissue. 2. The frequency of the haptoglobin alpha 1 allele was increased in patients with aneurysms compared with healthy control subjects (0.51 versus 0.35, P less than 0.05). Patients homozygous for the alpha 2 allele had the highest mean age at aneurysm resection. The frequency of a rare polymorphism at the cholesterol ester transfer protein locus was also increased in aneurysm patients (0.15 versus 0.05 in control subjects, P less than 0.01). These two genetic markers appear to act independently. Haptoglobins containing an alpha 1-chain accelerated two- to four-fold the degradation by elastases of aortic elastin in vitro. 3. Genetic variation in the haptoglobin and cholesterol ester transfer protein genes appears to influence dilatation of the abdominal aorta. Variation at the haptoglobin locus could have a direct effect on the degradation of elastin in atherosclerotic aorta, whereas variation at the cholesterol ester transfer protein locus could affect lipid metabolism and promote atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Influence of smoking and plasma factors on patency of femoropopliteal vein grafts.

OBJECTIVE: To determine the effects of smoking, plasma lipids, lipoproteins, apolipoproteins, and fibrinogen on the patency of saphenous vein femoropopliteal bypass grafts at one year. DESIGN: Prospective study of patients with saphenous vein femoropopliteal bypass grafts entered into a multicentre trial. SETTING: Surgical wards, outpatient clinics, and home visits coordinated by two tertiary referral centres in London and Birmingham. PATIENTS: 157 Patients (mean age 66.6 (SD 8.2) years), 113 with patent grafts and 44 with occluded grafts one year after bypass. MAIN OUTCOME MEASURE: Cumulative percentage patency at one year. RESULTS: Markers for smoking (blood carboxyhaemoglobin concentration (p less than 0.05) and plasma thiocyanate concentration (p less than 0.01) and plasma concentrations of fibrinogen (p less than 0.001) and apolipoproteins AI (p less than 0.04) and (a) (p less than 0.05) were significantly higher in patients with occluded grafts. Serum cholesterol concentrations were significantly higher in patients with grafts that remained patent one year after bypass (p less than 0.005). Analysis of the smoking markers indicated that a quarter of patients (40) were untruthful in their claims to have stopped smoking. Based on smoking markers, patency of grafts in smokers was significantly lower at one year by life table analysis than in non-smokers (63% v 84%, p less than 0.02). Patency was significantly higher by life table analysis in patients with a plasma fibrinogen concentration below the median than in those with a concentration above (90% v 57%, p less than 0.0002). Surprisingly, increased plasma low density lipoprotein cholesterol concentration was significantly associated with improved patency at one year (85%) at values above the median compared with patency (only 68%) at values in the lower half of the range (p less than 0.02). CONCLUSIONS: Plasma fibrinogen concentration was the most important variable predicting graft occlusion, followed by smoking markers. A more forceful approach is needed to stop patients smoking; therapeutic measures to improve patency of vein grafts should focus on decreasing plasma fibrinogen concentration rather than serum cholesterol concentration.

Aged↗
PubMed1989

Can thyroxine halt the progression of peripheral arterial disease?

Fifteen women with claudication and increased serum thyrotrophin (TSH) were treated with L-thyroxine (25-75 micrograms). These women were selected from a group of 80 consecutive women presenting with claudication, rest pain or gangrene. One year after their TSH was normal, their progress, serum lipids and lipoproteins were compared with the 58 women with normal levels of serum TSH; the remainder were already receiving thyroxine. Non-invasive assessment showed that three of the 15 (20%) women treated with thyroxine had progression of arterial disease, two in the legs and one in the legs and coronary arteries; two women showed improvement of ankle/brachial pressure indices. There was no accelerated angina, myocardial infarction, stroke or death in this group. Fifty-six of the 58 patients with normal levels of TSH were alive at follow-up and there was progression of distal disease in 24 (43%), coronary artery disease in 6 (11%), increasing carotid stenosis in four and two complained of transient ischaemic attacks. In this group, disease progression affected 32/56 (57%) of the women and this is significantly greater than in the thyroxine treated group chi 2 (P less than 0.05). Treatment with L-thyroxine caused a significant increase in HDL-cholesterol from 1.29 +/- 0.34 to 1.45 +/- 0.49 mmol/L (P less than 0.05) and a significant decrease in cholesterol from 8.0 +/- 1.3 to 7.2 +/- 1.1 mmol/L (P less than 0.01) and apolipoprotein B from 1.23 +/- 0.20 to 1.04 +/- 0.16 g/l (P less than 0.001). Significant changes in apolipoprotein B were observed after 3 months of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Study of DNA polymorphisms of the apolipoprotein AI-CIII-AIV gene cluster in patients with peripheral arterial disease.

1. We have determined the frequency of DNA polymorphisms of the human apolipoprotein AI-CIII-AIV gene cluster, detected with XmnI, PstI, and PvuII, in a group of patients with peripheral arterial disease. 2. Of the patients, 81 had no evidence of disease in the coronary and carotid arteries, 73 had coronary artery disease but no evidence of carotid artery disease, 25 patients had carotid artery disease but no evidence of coronary artery disease, and 38 had both coronary and carotid artery disease. 3. Levels of triacylglycerol, cholesterol, apolipoprotein B and apolipoprotein AI were not significantly different between the four patient groups. 4. The frequencies of the alleles for the apolipoprotein AI-CIII-AIV polymorphisms, detected with XmnI, PstI and PvuII, did not differ significantly in the patient groups when compared with a sample of clinically well normolipidaemic individuals also from a London population. 5. All five patients with the XmnI genotype we designate X2X2 had high levels of cholesterol, apolipoprotein B and apolipoprotein AI. 6. Patients with the rare VB2 allele of the apolipoprotein CIII-AIV restriction fragment length polymorphism had lower levels of cholesterol, acylglycerol and significantly lower levels of serum apolipoprotein. 7. Our observations suggest that variation in the apolipoprotein AI-CIII-AIV gene cluster may not be contributing significantly to the development of peripheral arterial disease, but variation associated with some of the restriction fragment length polymorphisms may be involved in determining levels of cholesterol- and apolipoprotein-B-containing lipoproteins.

Adult↗
PubMed1989

Cellular, enzymatic, and genetic factors in the pathogenesis of abdominal aortic aneurysms.

Aneurysms of the abdominal aorta occur with atherosclerosis or connective tissue disorders. Changes of three components of aortic media, smooth muscle cells, elastin, and collagen, which could contribute to medial weakening, are discussed. Smooth muscle cells cultured from the aging abdominal aorta (normal, atherosclerotic, or aneurysmal) have limited replicative potential at five to six cell doublings, whereas cells from aneurysmal thoracic aorta undergo more than 20 cell doublings in culture. The elastin content is much reduced in aneurysms and this is associated with an increase in elastase activity of medial homogenates to 17.8 U/ng of deoxyribonucleic acid (DNA) compared with 8.3 and 4.4 U/ng of DNA in atherosclerotic and normal aorta, respectively. An elastinolytic enzyme has been purified from aneurysmal aorta and appears to have different properties from human leukocyte elastase. Ruptured aneurysms are associated with an increased total collagenase activity but the increase could be stimulated by, or result from, an influx of inflammatory cells and does not necessarily have a causal significance. In patients with a family history of aneurysm there appears to be a decreased content of type III collagen in aortic media: 24% +/- 4% compared with 32% +/- 5% in most aneurysms. Familial aneurysms are most common in women, and preliminary results suggest that a polymorphic variant of the type III collagen gene, defined by restriction enzyme digest, may be associated with aneurysmal disease in women. The genetic approach may define causal mechanisms predisposing patients to aneurysmal dilatation.

Aged↗
PubMed1988

DNA polymorphisms of the gene for apolipoprotein B in patients with peripheral arterial disease.

We have determined the frequency of DNA polymorphisms of the gene for human apolipoprotein B, detected with XbaI and EcoRI, in 205 patients with documented peripheral arterial disease. Of the patients, 78 have no evidence of disease in the coronary and carotid arteries, 64 have coexisting coronary artery disease but no evidence of carotid artery disease, 26 patients have coexisting carotid artery disease but no evidence of coronary artery disease, and 37 have coexisting coronary and carotid artery disease. Levels of triglycerides, cholesterol and apolipoprotein B were measured for each patient, and RFLP frequency was determined in all the patients. Lipid, lipoprotein and apolipoprotein levels were not significantly different between the different patient groups. Compared with a sample from the clinically well London population, the frequency of the R2 allele of the polymorphism detected with EcoRI, and the frequency of the X1 allele of the XbaI polymorphism was significantly higher in the patient group. The frequency of these alleles was not significantly different in the different patient groups. In patients with only peripheral arterial disease, individuals with the XbaI genotype X1X1 have the lowest and those with the genotype X2X2 have the highest mean levels of serum cholesterol. However, in all other patient groups this trend was reversed (X1X1 highest and X2X2 lowest). Our observations suggest that variation at the apo B locus is one of the factors involved in predisposing an individual to develop arterial disease but does not determine where in the arterial system the disease develops.

Adult↗
PubMed1988

Platelet kinetics following carotid endarterectomy: the effect of aspirin and patch angioplasty.

Platelet deposition on the subintimal surface of the arterial wall following endarterectomy has been implicated in the development of postoperative thrombosis, intimal hyperplasia and may be important in recurrent stenosis. Autologous radiolabelled platelet deposition has been measured in 51 patients following carotid endarterectomy. The effect of platelet inhibitory drugs and patch angioplasty on early postoperative platelet accumulation at the site of endarterectomy has been investigated. In patients undergoing direct suture of the arteriotomy, platelet deposition measured as the Carotid Uptake Ratio was significantly reduced from 1.44 +/- 0.03 to 1.11 +/- 0.35 in those receiving aspirin and dipyridamole (P less than 0.002). Carotid Uptake Ratio was greater following patch angioplasty at 1.41 +/- 0.07 when compared to 1.14 +/- 0.07 with direct suture of the arteriotomy (P less than 0.002).

Aspirin↗
PubMed1987

Raised serum thyrotrophin in women with peripheral arterial disease.

Women with symptomatic peripheral arterial disease were screened for impaired thyroid function using a sensitive immunoradiometric assay for thyrotrophin (TSH). The arterial disease in the aortotibial segment was documented by an abnormal brachial/ankle pressure index in 80 patients. An age-matched control group of elderly women (n = 30) with a normal pressure index was established. In the control group the mean serum TSH was 1.6 +/- 1.1 milliunits/l, median 1.5 milliunits/l and this established a normal range of 0.2-3.9 milliunits/l. Seven patients (8.8 per cent) were already receiving treatment for myxoedema. In the remaining patients, the overall distribution of serum TSH was skewed to higher levels; the mean was 3.7 milliunits/l, median 2.4 milliunits/l, P less than 0.001 compared with controls and 15 (19 per cent) had a serum TSH greater than 4 milliunits/l, compared with only one (3.3 per cent) of the controls. Therefore 22 patients (28 per cent) had myxoedema or a raised serum TSH. For all subjects with a normal TSH, there was a positive correlation of serum TSH with serum cholesterol, r = 0.68, P less than 0.001. For patients with a raised TSH, there was a continuing, but non-linear, increase of serum cholesterol with TSH. These results suggest that a raised serum TSH may be one of the risk factors for the development of peripheral arterial disease in women, possibly by increasing cholesterol levels.

Aged↗