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Biomedical subjects

M McLaren

Publications and source records attributed to M McLaren.

At least 19 recordsLinked to original sources
PubMed2001

Knee osteoarthritis and obesity.

OBJECTIVES: To assess the risk of knee osteoarthritis (OA) attributable to obesity, and the interactions between obesity and other established causes of the disorder. METHODS: We performed a population-based case-control study in three health districts of England (Southampton, Portsmouth and North Staffordshire). A total of 525 men and women aged 45 y and over, consecutively listed for surgical treatment of primary knee OA, were compared with 525 controls matched by age, sex and family practitioner. RESULTS: Relative to a body mass index (BMI) of 24.0-24.9 kg/m(2), the risk of knee OA increased progressively from 0.1 (95% CI 0.0-0.5) for a BMI<20 kg/m(2) to 13.6 (95% CI 5.1-36.2) for a BMI of 36 kg/m(2) or higher. If all overweight and obese people reduced their weight by 5 kg or until their BMI was within the recommended normal range, 24% of surgical cases of knee OA (95% CI 19-27%) might be avoided. As a risk factor for knee OA obesity interacted more than additively with each of Heberden's nodes, earlier knee injury and meniscectomy. In comparison with subjects of normal weight, without Heberden's nodes, and with no history of knee injury, people with a combination of obesity, definite Heberden's nodes and previous knee injury had a relative risk of 78 (95% CI 17-354). CONCLUSIONS: Our findings give strong support to public health initiatives aimed at reducing the burden of knee OA by controlling obesity. People undergoing meniscectomy or with a history of knee injury might be a focus for targeted advice.

Aged↗
PubMed2000

Occupational physical activities and osteoarthritis of the knee.

OBJECTIVE: To assess the risk of knee osteoarthritis (OA) associated with kneeling, squatting, and other occupational activities. METHODS: We compared 518 patients who were listed for surgical treatment of knee OA and an equal number of control subjects from the same communities who were matched for sex and age. Histories of knee injury and occupational activities were ascertained at interview, height and weight were measured, and the hands were examined for Heberden's nodes. Data were analyzed by conditional logistic regression. RESULTS: After adjustment for body mass index (BMI), history of knee injury, and the presence of Heberden's nodes, risk was elevated in subjects who reported prolonged kneeling or squatting (odds ratio [OR] 1.9; 95% confidence interval [95% CI] 1.3-2.8), walking >2 miles/day (OR 1.9; 95% CI 1.4-2.8), and regularly lifting weights of at least 25 kg (OR 1.7; 95% CI 1.2-2.6) in the course of their work. The risks associated with kneeling and squatting were higher in subjects who also reported occupational lifting, and appeared to interact multiplicatively with the risk conferred by obesity. People with a BMI of > or =30 kg/m2 whose work had entailed prolonged kneeling or squatting had an OR of 14.7 (95% CI 7.2-30.2), compared with subjects with a BMI <25 kg/m2 who were not exposed to occupational kneeling or squatting. CONCLUSION: There is now strong evidence for an occupational hazard of knee OA resulting from prolonged kneeling and squatting. One approach to reducing this risk may lie in the avoidance of obesity in people who perform this sort of work.

Aged↗
PubMed2000

The effect of hormone replacement therapy and route of administration on selected cardiovascular risk factors in post-menopausal women.

BACKGROUND: There is increasing use of hormone replacement therapy (HRT) by post-menopausal women. Observational epidemiological studies have shown reductions in cardiovascular risk factors in HRT users in the USA, but no randomized controlled trials of HRT have been carried out in the primary practice setting. Previous studies of cardiovascular risk factors have shown a variety of responses according to type of progestagen and oral or topical administration. None has examined the effect of route using an identical progestagen. OBJECTIVES: Our aim was to establish differences, if any, in alteration in cardiovascular risk factors with HRT in post-menopausal women according to route of administration of HRT, oral, transdermal and implant, using first oestrogen alone then oestrogen plus norethisterone, or testosterone for implant. METHODS: Subjects were recruited by letter of invitation to women aged 50-65 years from lists in general practices local to the Charing Cross Hospital Lipid Clinic in West London. Their menopausal status was confirmed and they were randomized to one of three treatment groups or acted as controls. They attended for three visits; at baseline, HRT was initiated as oestrogen alone, oral or transdermal. At the 3-month visit, HRT with the progestagen, norethisterone, was given cyclically, continuously or transdermally until the final visit at 6 months. A separate group of women from the menopause clinic at Chelsea and Westminster Hospital were studied on oestrogen implant then on implanted oestrogen and testosterone. The outcome measures studied were the separate effects of the four regimes as compared with controls on lipoproteins, glucose, insulin, fibrinogen, factor VII and E-selectin, together with weight, waist:hip ratio and blood pressure. RESULTS: The continuous combined oestrogen-progestagen therapy had similar effects on cardiovascular risk factors as oestrogen with cyclical progestagen. All regimes lowered low-density lipoprotein cholesterol, the oral route being more potent than the parenteral; the effect of transdermal HRT was similar to the implant. Lp(a) was reduced only with the oral route. Reductions in factor VII and E-selectin were observed in both the oral and transdermal routes. There was no increase in body mass index, waist:hip ratio, blood pressure or glucose and insulin levels with any of the HRT regimes used. Systolic blood pressure was reduced with the transdermal route. CONCLUSIONS: This study supports the evidence that oestrogen-progestagen HRT, both oral and transdermal, although attenuating some of the benefit of oestrogen alone on fibrinogen and high-density lipoprotein, significantly reduces cardiovascular risk factors, which should diminish post-menopausal risk of coronary disease.

Cardiovascular Diseases↗
PubMed2000

Elevated levels of soluble E-selectin in diabetic patients with severe symptomatic peripheral arterial occlusive disease requiring angioplasty. A possible role in diabetic vascular disease?

BACKGROUND: To study levels of E-selectin in patients with peripheral arterial occlusive disease who were undergoing percutaneous transluminal angioplasty. METHODS: Experimental design and setting: Cross sectional case control study, conducted in a teaching hospital. SUBJECTS: Seven patients with type-2 (non-insulin dependent) diabetes mellitus undergoing transluminal angioplasty for symptomatic peripheral arterial occlusive disease, had blood tests for sE-selectin measurement, and were compared to a similar groups of age and sex matched non-diabetic patients with arteriopathy who are undergoing the same procedure. Also evaluated were a group of diabetic patients and healthy non-diabetics with no peripheral arterial disease. RESULTS: The levels of sE-selectin in the two diabetic groups were significantly higher than the non-diabetic groups measuring at 77 ng/ml (53-120) and 79 ng/ml (43-98) (median, range) vs 54 ng/ml (24-104) in the non-diabetic with arteriopathy, and 42 ng/ml (35-66) in the normal healthy controls, p<0.04, p<0.003 respectively, Mann Whitney "U" test. CONCLUSIONS: We have demonstrated significantly high values of soluble E-selectin in patients with diabetes mellitus requiring angioplasty for symptomatic peripheral arterial occlusive disease. This suggests that sE-selectin may be involved in the diabetic angiopathic process. It may act as a precursor for smooth muscle proliferation.

Angioplasty, Balloon↗
PubMed2000

Seasonal variation in plasma levels of endothelin-1 and nitric oxide.

BACKGROUND: There is a seasonal variation in the incidence of stroke and coronary heart disease with admissions to hospital being higher in the colder months of the year. The mechanism whereby this winter prevalence of vascular disease occurs is still not fully understood. The aim of our study was to measure plasma levels of vasoactive compounds throughout the year to establish whether or not there were any fluctuations which could play a part in the higher winter incidence. METHODS: We measured plasma levels of the vasoconstrictive endothelin-1 (ET) and the vasorelaxant nitric oxide (NO) throughout the year. Blood samples were collected from 176 normal individuals. Samples were collected between 8.00 and 10.00 hours after an overnight fast of at least 12 hours. RESULTS: Results were divided into two-monthly intervals and analysed using a Kruskal-Wallis one-way analysis of variance and Mann-Whitney U tests (SPSS). We found a significant seasonal variation in both parameters. Mean levels of endothelin were highest in January/February (4.0 pg/ml) and lowest in May/June (2.3 pg/ml), whereas plasma 5 nitric oxide levels were lowest in January/February (5.7 microM) and highest in September/October (9.9 microM); p values were <0.0001 (Jan/Feb vs May/June) and 0.049 (Jan/Feb vs Sept/Oct), respectively. CONCLUSIONS: The high levels of the vasoconstrictor endothelin combined with low levels of vasorelaxant nitric oxide may account in part for the increased incidence of stroke and coronary heart disease seen in these months.

Aged↗
PubMed1999

Endothelial activation and response in patients with hand arm vibration syndrome.

BACKGROUND: Hand-arm vibration syndrome (HAVS) is a form of secondary Raynaud's phenomenon (RP) of occupational origin. In other forms of RP, blood and blood vessel wall interaction is one factor in the pathophysiology. Cytokines and cell adhesion molecules both play an important role in this interaction, and basal vascular tone and vasodilatation are regulated by nitric oxide. METHODS: Blood flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP) and levels of soluble intercellular adhesion molecule-1 (sICAM-1) and the inflammatory cytokine interleukin 8 (IL-8) were measured in eight male patients with vibration white finger disease, which is part of HAVS, and in eight healthy matched male control subjects. RESULTS: sICAM-1 levels were statistically higher (P = 0.02, Mann-Whitney U-test) and IL-8 levels (P < 0.01, Mann-Whitney) were significantly lower in the patient group. The patients with HAVS had significantly reduced vascular responses to SNP (P < 0.05, ANOVA). CONCLUSIONS: In this study, we reveal differences in vascular responses to SNP that suggest there may be an impairment of the smooth muscle response to nitric oxide in patients with HAVS. The increase in sICAM-1 that occurs in patients with HAVS suggests that leucocyte adhesion is increased and that adherent neutrophils may contribute to the microvascular damage seen in this disease. The impeded flow of blood cells through the microcirculation may result in the low levels of circulating IL-8 due to the cytokine binding to erythrocytes. The possible role of NO activity in HAVS warrants further investigation.

Acetylcholine↗
PubMed1999

Interleukin-8 (IL-8) may contribute to the activation of neutrophils in patients with peripheral arterial occlusive disease (PAOD).

OBJECTIVES: to investigate the levels of interleukin-8 (IL-8) in patients with peripheral arterial occlusive disease (PAOD) and healthy control subjects both before and after an acute exercise test. MATERIALS AND METHODS: twenty-six patients with intermittent claudication and 22 matched healthy control subjects each had IL-8 levels measured before and after a standard acute treadmill-exercise test. Subjects walked for 10 min or until stopped by claudication pain. Serum IL-8 levels were measured before exercise was commenced and 1, 5 and 10 min after exercise was stopped. RESULTS: patients with PAOD had statistically significantly higher levels of IL-8 than healthy control subjects, before and after an acute exercise test (p <0.00001, Mann-Whitney). Ratios of the change of IL-8 levels post-exercise showed a statistically significant difference at the post-5-min time point (p =0.005), showing a difference in the change of IL-8 levels at this time point between the patient group and control group. CONCLUSIONS: The increased levels and the failure of the cytokine levels to fall by the same extent after exercise in the patient group may be due to a combination of increased neutrophil activation, reduced blood flow and increased cytokine production during ischaemia-reperfusion, which is not observed in the healthy controls.

Adult↗
PubMed1999

The beneficial effects of omega-3 and omega-6 essential fatty acid supplementation on red blood cell rheology.

Twenty healthy, non-smoking subjects were enrolled into a study to investigate the effects of dietary supplementation with essential fatty acid (EFAs) on red blood cell rheology. Ten subjects were given 3 months dietary supplementation with long chain polyunsaturated EFAs containing omega-3 and omega-6 EFAs while 10 others were given placebo (sunflower oil). Venous sampling was performed at 0 and 12 weeks and red blood cell (RBC) aggregation and deformability measured by a filtration system. The results showed a reduction in RBC aggregation in the group given omega-3 and omega-6 EFAs but not in the placebo group. This may be related to changes in the RBC membrane and surface receptor characteristics. Such EFAs may be useful in Raynaud's phenomenon.

Adult↗
PubMed1999

Elevated plasma vascular endothelial cell growth factor and thrombomodulin in juvenile diabetic patients.

The major cause of morbidity and mortality in patients with type 1 diabetes mellitus is vascular disease and the death rate in this group of patients can be up to six times that of the general population. Elevated levels of blood glucose can cause endothelial cell damage, and markers of endothelial damage such as von Willebrand factor (vWF) and thrombomodulin (TM) have been reported to increase in adult diabetic patients. Growth factors are strongly linked to smooth muscle cell proliferation that contributes significantly to the vascular occlusive process and it has been shown that vascular endothelial cell growth factor (VEGF) stimulates release of vWF from endothelial cells. Vascular endothelial cell growth factor levels have been shown to be increased in vitreous fluid from the eyes of diabetic patients with proliferative retinopathy compared to those without. In this study we have shown that plasma levels of both TM and VEGF were significantly increased in juvenile diabetic patients with no clinical evidence of vascular disease compared to normal age and sex-matched control subjects. Median TM levels were 45.5 ng/mL (I.Q.R. 34 to 56 ng/mL) and 61 ng/mL (I.Q.R. 41 to 72 ng/mL) in the control group and in the diabetic patients respectively (p = .0005) and median levels of VEGF were 19.6 pg/mL (I.Q.R. 15.9 to 28.1 pg/mL) in the control group and 37.1 pg/mL (I.Q.R. 22.1 to 50.3 pg/mL) in the diabetic patients (p = .027 Mann-Whitney U test). This suggests that microvascular disease begins in childhood and can be detected using laboratory tests before any clinical changes are apparent.

Adolescent↗
PubMed1999

Decrease in P-selectin levels in patients with hypercholesterolaemia and peripheral arterial occlusive disease after lipid-lowering treatment.

At sites of thrombosis and vascular injury, interactions occur among platelets, leucocytes and endothelial cells. Patients with peripheral arterial occlusive disease (PAOD) have been shown to have raised total serum cholesterol and serum triglycerides and increased sP-selectin levels when compared with controls. A total of 31 patients with PAOD and hypercholesterolaemia took part in this three-staged study. Soluble P-selectin (sP-selectin) levels were significantly lowered after 12 weeks of fluvastatin treatment (157.0 ng/ml versus 113.77 ng/ml, p = 0.01), whereas 12 weeks of placebo treatment had no statistically significant effect on sP-selectin levels (150.0 ng/ml versus 139.4 ng/ml). An unpaired t-test almost reached statistical significance (p = 0.051) when the levels by which sP-selectin fell after 12 weeks of active or placebo treatment were compared. The placebo group was then put onto long-term, active treatment and sP-selectin levels were significantly lowered by fluvastatin when compared to pre-treatment levels (150.0 ng/ml versus 110.0 ng/ml, p = 0.03). By lowering the levels of P-selectin, fluvastatin may not only attenuate atherosclerotic progression but may also decrease the platelet activation associated with PAOD.

Aged↗
PubMed1999

Elevated levels of sE-selectin in post-menopausal females are decreased by hormone replacement therapy to levels observed in pre-menopausal females.

Observational epidemiological studies have shown that mortality from coronary heart disease is reduced in post-menopausal women by hormone replacement therapy (HRT). The aim of this study was to measure sE-selectin levels in post-menopausal females before and after HRT and to compare these with pre-menopausal females and aged matched males. Post-menopausal females (n = 70) were given HRT or no treatment to act as a control group. sE-selectin levels were significantly lower in the pre-menopausal (n = 36) when compared with the post-menopausal females (n = 70) (p = 0.027), whereas no difference between two age matched male groups was found (n = 40). Oral and transdermal HRT significantly decreased sE-selectin levels (p<0.0001 and p = 0.0005 respectively) with no change in the control group. The reduction in the levels of this marker of endothelial activation after HRT, may reflect a decrease in leucocyte/endothelial interaction which may reduce atherosclerotic risk in post-menopausal females.

Adult↗
PubMed1998

Individual risk factors for hip osteoarthritis: obesity, hip injury, and physical activity.

Hip osteoarthritis is a major cause of pain and disability. The authors explored individual risk factors for hip osteoarthritis in a population-based case-control study. The study was performed in two English health districts (Portsmouth and North Staffordshire) from 1993 to 1995. A total of 611 patients (210 men and 401 women) listed for hip replacement because of osteoarthritis over an 18-month period were compared with an equal number of controls selected from the general population and individually matched for age, sex, and family practitioner. Information about suspected risk factors was obtained by a questionnaire administered at interview and a short physical examination. Obesity (odds ratio (OR) = 1.7, 95% confidence interval (CI) 1.3-2.4; highest vs. lowest third of body mass index), previous hip injury (OR = 4.3, 95% CI 2.2-8.4), and the presence of Heberden's nodes (OR = 1.6, 95% CI 1.2-2.2) were independent risk factors for hip osteoarthritis among men and women. Hip injury was more closely related to unilateral as compared with bilateral disease. There were a negative association between cigarette smoking and osteoarthritis among men and a weak positive association with prolonged regular sporting activity. Obesity and hip injury are important independent risk factors for hip osteoarthritis, which might be amenable to primary prevention. Hip osteoarthritis may also arise as part of the polyarticular involvement found in generalized osteoarthritis.

Aged↗
PubMed1998

Dietary supplementation with omega 3 and omega 6 fatty acids reduces induced white blood cell aggregation in healthy volunteers.

Twenty healthy, non-smoking subjects were enrolled into a study to look at the effects of 3 months' dietary supplementation with long chain polyunsaturated essential fatty acids (EFAs) on white blood cell (WBC) aggregation. Ten subjects received 3 months' supplementation with long chain polyunsaturated omega 3 and omega 6 fatty acids, 10 received 3 months of placebo (sunflower oil). Venous blood was sampled at 0 and 12 weeks; whole blood WBC aggregation in response to formyl-methionyl-leucyl-phenylalanine (FMLP) was measured. The results showed that the 3 months' dietary supplementation with a combination of omega 3 and omega 6 fatty acids significantly reduced WBC aggregation to FMLP in healthy volunteers when compared to placebo. Since WBC aggregation to FMLP is dependent on the activity of WBC surface receptors and independent of eicosanoid production, we suggest EFAs may have other anti-inflammatory actions in addition to their role as modulators of mediator production.

Adult↗
PubMed1998

Hodgkin's lymphoma of the nasopharynx.

The lymphoid tissues of Waldeyer's ring, including the nasopharynx, are very rare sites for Hodgkin's disease and are considered to be relatively resistant to it. This report of a case of Hodgkin's disease of the post-nasal space demonstrates the difficulty of making the diagnosis histologically and the characteristic immunohistochemical features of this disease. Before immunohistochemistry became so widely available, some authors speculated it might be underdiagnosed (Eavey and Goodman, 1982; O'Reilly and Kershaw, 1987). Judging by its continued rarity, this appears not to be the case.

Cell Membrane↗
PubMed1998

A circadian variation exists for soluble levels of intercellular adhesion molecule-1 and E-selectin in healthy volunteers.

1. We have previously shown a circadian variation in leucocyte activation and endothelial function which may explain why some inflammatory and vascular diseases show a circadian variation in disease activity/ occurrence. 2. We have investigated the circadian variation of two soluble cell adhesion molecules, intercellular adhesion molecule-1 and E-selectin, in 10 healthy volunteers. Soluble intercellular adhesion molecule-1 is released from both activated leucocytes and endothelial cells while soluble E-selectin is released only from activated endothelium. 3. Results show a circadian variation exists for both soluble intercellular adhesion molecule-1 and E-selectin (both P < 0.0001, analysis of variance) with a peak activity at 12:00 h for both measures and a minimum activity at 04:00 h for intercellular adhesion molecule-1 and 00:00 h for E-selectin. 4. These results demonstrate the existence of a diurnal variation in cell adhesion molecules, providing evidence in support of a diurnal pattern in endothelial and leucocyte activation. An alteration in this biological rhythm may help to explain the diurnal variation in disease activity in certain inflammatory and vascular disease states. Furthermore, it stresses the importance of sample time point standardization in clinical studies.

Adolescent↗
PubMed1998

Soluble cell adhesion molecules--P-selectin and ICAM-1, and disease activity in patients receiving sulphasalazine for active rheumatoid arthritis.

The aim of this pilot study was to examine soluble cell adhesion molecules before and after sulphasalazine (SSZ) therapy in active RA. Assessment of RA patients (n = 13) was undertaken before and after 3 months of SSZ. sICAM-1, sVCAM-1, sP- and sE-selectin were measured using an ELISA. The mean (+/-SEM) C-reactive protein (CRP) and sP-selectin levels were significantly reduced from 3.9(0.89) to 2.01(0.53) mg/dl and from 332.8 (48.2) to 116.2 (11.1) respectively, after 3 months of SSZ. The sICAM-1 and sP-selectin levels were significantly higher in RA patients at baseline and a reduction occurred of sICAM-1, sVCAM-1 and sE-selectin levels, however this was not significant. The fall in mean (SEM) sICAM-1, from 345.0 (29.8) to 333.5 (30.2), correlated with the change in CRP (r=0.66; p = 0.018), but the fall in sP-selectin did not. SSZ therapy reduced sP-selectin and sICAM-1 levels in active RA, sICAM-1 correlates with disease activity. SSZ may reduce platelet and/or endothelial activity in RA which may be a useful marker of response, however studies of longer duration and more patients are required.

Adult↗