Search PubMed⌕ Search

Biomedical subjects

M A Crook

Publications and source records attributed to M A Crook.

At least 19 recordsLinked to original sources
PubMed2001

Fibrinogen response with simvastatin versus atorvastatin in familial hypercholesterolemia.

The clinical and biochemical determinants of the fibrinogen response to simvastatin or atorvastatin therapy were assessed in 130 patients with severe polygenic or familial hypercholesterolemia treated in a randomized open-trial format design. Hyperfibrinogenemia was associated with atorvastatin, baseline fibrinogen, and initial concentration and change in concentration of apolipoprotein B or low-density lipoprotein cholesterol.

Adult↗
PubMed2001

Influence of sialic acid content of low-density lipoprotein particles on endothelium-dependent vasorelaxation in rabbit aorta.

Low-density lipoprotein (LDL) concentration in plasma is an important predictor for atherosclerosis, and desialylated LDL has been proposed to be particularly atherogenic. Atherosclerosis is also associated with vascular endothelial dysfunction. We therefore wished to test the hypothesis that removal of sialic acid residues from LDL increases its ability to inhibit endothelium-dependent vasorelaxation. We studied vasorelaxant responses to acetylcholine (ACh) in isolated rabbit aortic rings as a model of endothelium-dependent relaxation, in the presence or absence of LDL treated either with saline or with neuraminidase, to cleave sialic acid residues. Vasorelaxant responses to ACh were inhibited by 300 microg protein per ml saline-treated LDL (E(max) 77.5+/-4.5 vs. 89.7+/-2.2% in the absence of LDL, P<0.05). This inhibitory effect was not altered by neuraminidase treatment of LDL. In contrast, 300 microg protein per ml LDL, either saline- or neuraminidase-treated, did not affect vasorelaxant responses to the endothelium-independent dilator sodium nitroprusside. We found no correlation between sialic acid content of saline-treated LDL and its ability to inhibit endothelium-dependent vasorelaxation, in rabbit aortic rings, at a concentration of 300 microg protein per ml. Our results therefore suggest that sialic acid content is not an important determinant of the effect of LDL on vascular endothelium-dependent relaxation.

Acetylcholine↗
PubMed2001

Abnormal liver function tests in a patient fed with total parenteral nutrition and treated with octreotide.

Octreotide is a long-acting analog of somatostatin, a hypothalamic release-inhibiting hormone. It is sometimes used therapeutically to relieve symptoms associated with acromegaly and gastroenteropancreatic endocrine tumors. It has also been used in the treatment of short-bowel syndrome and gastrointestinal and biliary fistulae. We report a patient with biliary leakage due to Marizzi's syndrome treated with total parenteral nutrition and octreotide who developed abnormal liver function tests that improved when the two treatments were stopped. We also review the literature regarding abnormal liver function tests in patients on total parenteral nutrition.

Female↗
PubMed2001

Relationship between plasma sialic acid concentration and microvascular and macrovascular complications in type 1 diabetes: the EURODIAB Complications Study.

OBJECTIVE: To test the hypothesis that an increased plasma concentration of sialic acid, a marker of the acute-phase response, is related to the presence of diabetic micro- and macrovascular complications in type 1 diabetes. RESEARCH DESIGN AND METHODS: We investigated the relationship between plasma sialic acid concentration and nephropathy, retinopathy, neuropathy, and coronary heart disease (CHD) in a cross-sectional survey of 1,369 people with type 1 diabetes. Subjects were participants in the EURODIAB IDDM Complications Study, which involved 31 centers in 16 European countries. RESULTS: There was a significantly increasing trend of plasma sialic acid with severity of retinopathy (P < 0.001 in men) and with degree of urinary albumin excretion (P < 0.001 men, P < 0.01 women). Plasma sialic acid correlated with increasing plasma creatinine concentration (P < 0.009 men, P < 0.0002 women), and men with neuropathy had a higher plasma sialic acid concentration than those without (P < 0.006). There was no significant correlation between plasma sialic acid and CHD in either sex. Elevated plasma sialic acid concentrations were also associated with several risk factors for diabetic vascular disease: diabetes duration, HbA1c, plasma triglyceride and cholesterol concentrations, waist-to-hip ratio, hypertension and smoking (in men), and low physical exercise (in women). In multiple logistic regression analysis, plasma sialic acid was independently related to proliferative retinopathy and urinary albumin excretion rate in men. CONCLUSIONS: We conclude that an elevated plasma sialic concentration is strongly related to the presence of microvascular complications in type 1 diabetes, especially retinopathy and nephropathy. Further study of acute-phase response markers and mediators as indicators or predictors of diabetic microvascular complications is therefore justified.

Adult↗
PubMed2000

High-density lipoprotein cholesterol and triglyceride response with simvastatin versus atorvastatin in familial hypercholesterolemia.

The clinical and biochemical determinants of high-density lipoprotein (HDL) and triglyceride response to simvastatin and atorvastatin were assessed in 150 patients with severe hyperlipidemia treated in a randomized open-trial format design. Triglyceride reduction was only dependent on HDL:apolipoprotein A1, change in apolipoprotein B, and dose response, whereas an increase in HDL was dependent on initial LDL, change in LDL or dose response, and therapy with simvastatin.

Anticholesteremic Agents↗
PubMed2000

No difference in serum sialic acid in type 2 diabetic patients from the United Arab Emirates with and without diabetic retinopathy.

Serum total sialic acid (TSA) has recently been shown to be related to diabetic retinopathy. However, there is some controversy as this may be true in European Type 2 diabetic patients but not South Asians. There are few data looking at serum TSA expression in Arab Type 2 diabetic patients from the United Arab Emirates (UAE) and we wished to test the hypothesis that there may be different serum TSA expression in Arab Type 2 diabetic patients as regard to retinopathy. Sixty-five Type 2 diabetic patients from the UAE were studied (19 male and 46 female, age 57.5+/-9.8 (45-74) years, duration of diabetes 9.4+/-5.7 (0-22) years. The serum TSA in 13 patients with diabetic retinopathy was 757+/-130 mg/l and 782+/-163 mg/l in those without retinopathy (NS). There was no significant correlation between serum TSA and patient age, serum fructosamine, diabetes duration, or blood pressure. As in South Asians serum TSA does not appear to be elevated in Type 2 diabetic patients from the United Arab Emirates with diabetic retinopathy.

Aged↗
PubMed2000

Lipid clearance and total parenteral nutrition: the importance of monitoring plasma lipids.

Lipid provides two major advantages for total parenteral nutrition (TPN). First, it provides essential fatty acids, thus avoiding essential fatty acid deficiency, and secondly, it is a useful energy source, providing 9 kcal/g. However, we describe a patient who had TPN containing Intralipid, where problems of lipid clearance developed. We also review the literature of lipid clearance problems in TPN patients and suggest ways by which such problems can be managed. We suggest that patients taking TPN should have their plasma lipids (triacylglycerols) measured before and during TPN initiation. This is particularly important in patients who are at high risk of impaired fat clearance, such as those who are hyperlipidemic, diabetic, septic, or with impaired renal or hepatic function, or those who are critically ill.

Aged↗
PubMed2000

Circulating concentrations of C-reactive protein and total sialic acid in tobacco smokers remain unchanged following one year of validated smoking cessation.

BACKGROUND: Elevated plasma concentrations of C-reactive protein (CRP) and total sialic acid (TSA) have been associated with increased cardiovascular risk. Additionally, levels of both CRP and TSA have been reported to be significantly elevated in smokers. However, it is not clear if the raised TSA and CRP levels noted in smokers are directly attributable to the smoking experience, or if they may be elevated due to a secondary mechanism(s), such as smoking-induced tissue inflammation. SUBJECTS AND METHODS: We measured the plasma concentration of CRP and TSA in a group of smokers at baseline and following one year of validated smoking cessation (n = 30) and in a control group of tobacco users who continued to smoke over the year (n = 30). RESULTS: The baseline concentration of TSA and CRP was 67.2 mg dL(-1) and 1.91 mg L(-1), respectively (n = 60). No significant dose-dependent relationship was noted between baseline CRP or TSA concentration and either plasma cotinine, expired-air CO or daily cigarette consumption. There was no difference in the mean change in CRP level in the quitters over one year (- 0.2 mg L(-1)) compared to the continuing smokers (+ 0.5 mg L(-1)), P = 0.80, or in the change in concentration of TSA in the quitters (- 2.7 mg dL(-1)) compared to the continuing smokers (+ 0.4 mg dL(-1)), P = 0.26. CONCLUSIONS: As the circulating concentrations of both CRP and TSA remain unchanged following one year of smoking cessation, these results would suggest that the elevated levels noted in smokers are not directly attributable to tobacco use and are more likely to be elevated due to a secondary process that is yet to be established.

Adult↗
PubMed2000

A paradoxical severe decrease in serum HDL-cholesterol after treatment with a fibrate.

There have been a handful of reports in the literature of a paradoxical decrease in serum high density lipoprotein (HDL)-cholesterol in patients on fibrate drugs. The reason for this decline in cardioprotective HDL-cholesterol is not known and may have potential deleterious effects on the patient. This report describes a decrease in serum HDL-cholesterol in a patient on both simvastatin and bezafibrate. This patient also developed abnormal renal function, probably interstitial nephritis. In addition, the literature of fibrate induced serum HDL-cholesterol decline is reviewed and possible mechanisms for this phenomenon discussed.

Bezafibrate↗
PubMed2000

Skin tags and the atherogenic lipid profile.

This report details four patients who had skin tags, mainly on their torso, neck, and axillae, and who also displayed an abnormal lipid profile. All showed an increased serum triglyceride (fasting > 1.70 mmol/litre) and a decreased high density lipoprotein (HDL) cholesterol (< 1.1 mmol/litre in women and 1.0 mmol/litre for men) concentration. The displayed lipid profile is also known as the atherogenic profile and is associated with insulin resistance, type 2 diabetes mellitus, and an increased risk of cardiovascular disease. Two of the patients had impaired glucose tolerance and one had type 2 diabetes mellitus. Three of the individuals had coronary artery disease. Skin tags might be a useful clinical sign that could alert clinicians to screen such individuals for abnormal lipids, type 2 diabetes mellitus, and cardiovascular disease.

Adult↗
PubMed2000

Renin-angiotensin system polymorphisms and coronary events in familial hypercholesterolemia.

The role of renin-angiotensin system polymorphisms as risk factors for coronary heart disease (CHD) is controversial. This study investigated their role in patients with heterozygous familial hypercholesterolemia (FH). Polymorphism frequencies for angiotensin-I-converting enzyme insertion/deletion (ACE I/D), angiotensinogen M235T, and angiotensin-II type I receptor (AG2R) A1166C were determined in 112 patients with FH and 72 patients with polygenic hypercholesterolemia, of whom 26.7% and 41.6%, respectively, had established CHD. None of the polymorphisms were associated with risk of CHD in patients with polygenic hypercholesterolemia in this study. Logistic regression analysis of risk factors for CHD in patients with FH identified male sex (odds ratio [OR]=3.03; 95% CI, 3.07 to 3.72; P=0.05), smoking (OR=2.91; 95% CI, 2.16 to 4.24; P=0.05), diastolic blood pressure (OR=3.70; 95% CI, 3.43 to 3.97; P=0.02), plasma glucose (OR=3.31; 95% CI, 3. 10 to 3.52; P=0.04), and the AG2R A1166C polymorphism as risk factors. The OR for the AG2R A1166C polymorphism was 2.26 (95% CI, 1.26 to 3.72; P=0.06) and increased to 3.10 (95% CI, 1.20 to 7.52; P=0.04) after adjustment for other risk factors. The AG2R A1166C polymorphism may interact with severe hypercholesterolemia and other risk factors to increase risk of CHD in FH patients.

Adult↗
PubMed2000

A comparison of algorithms for initiation of lipid lowering therapy in primary prevention of coronary heart disease.

OBJECTIVE: To compare nine different algorithms for determining the necessity for drug treatment of hyperlipidaemia in patients without cardiovascular disease. DESIGN: Risk-factor data on 400 patients were obtained. Algorithms assessed included the Framingham model, National Cholesterol Education Program, European, British, New Zealand, British Regional Heart Study, Sheffield, Munster Heart Study and Dundee guidelines and a local general rule for treatment of atheroma (General Rule to Enable Atheroma Treatment). SETTING: Three hospital lipid clinics. RESULTS: Patients were 56% male, aged 53.8 +/- 12.3 years, 38% smoked, 55% had a family history of disease (37% familial hypercholesterolaemia, 33% hypertension and 5.2% left ventricular hypertrophy); 31% were moderately obese and 15% were diabetic. The average cholesterol level was 7.9 +/- 2.6 mmol/l. Median Framingham risk was 1.66%/year and this risk was > 2%/year for 37% and > 3%/year for 17.5%. Treatment was required for 86% by National Cholesterol Education Program, 70% by General Rule to Enable Atheroma Treatment and European, 61% by New Zealand, 58% by British, 42% by Dundee, 40% by Munster Heart Study, 25% by British Regional Heart Study and 16% by Sheffield guidelines. Algorithms varied regarding recommendations for treatment of men, women, patients with familial hypercholesterolaemia and diabetes. Confounders included risk levels, definitions and weightings for additional risk factors. CONCLUSIONS: Different algorithms vary widely in their predictions of need for drug treatment of this high-risk population with hyperlipidaemia. Authors of guidelines for cardiovascular disease need to unify risk thresholds and definitions and audit the effects of additional weighting factors so that patients can be treated consistently.

Adult↗
PubMed2000

Differing relationships of methylene tetrahydrofolate reductase genotypes with cardiovascular risk in familial and polygenic hypercholesterolaemia.

BACKGROUND: Plasma homocysteine and the methylene tetrahydrofolate reductase C677T polymorphism have been suggested as being risk factors for cardiovascular disease. OBJECTIVE: To determine whether plasma homocysteine and the methylene tetrahydrofolate reductase C677T polymorphism are risk factors for coronary heart disease in patients with heterozygous familial hypercholesterolaemia as compared with those with polygenic hyperlipidaemia. METHODS: Plasma homocysteine and the methylene tetrahydrofolate reductase polymorphism were assessed with other risk factors in 112 patients with familial hypercholesterolaemia and 72 patients with polygenic hyperlipidaemia, of whom 29 (25.8%) and 30 (41%) respectively had established cardiovascular disease and in 100 healthy normal subjects. RESULTS: Plasma homocysteine was not significantly elevated in patients with and without coronary heart disease with familial hypercholesterolaemia or polygenic hyperlipidaemia compared with controls. The allele frequencies for C677T were significantly different in patients with coronary heart disease and with polygenic hyperlipidaemia (0.35 versus 0.29) (P = 0.02) as opposed to those with coronary heart disease and familial hypercholesterolaemia (0.25 versus 0.30) (P = 0.63). Methylene tetrahydrofolate reductase genotype but not homocysteine had a weak association with coronary heart disease in logistic regression analysis in patients with polygenic hyperlipidaemia (P = 0.05) but neither methylene tetrahydrofolate reductase genotype or plasma homocysteine was a risk factor in patients with familial hypercholesterolaemia. CONCLUSION: Whilst methylene tetrahydrofolate reductase genotype may be a weak risk factor for coronary heart disease in polygenic hyperlipidaemia as opposed to familial hypercholesterolaemia, homocysteine does not seem to be an important risk factor for coronary heart disease in patients in southern UK.

Adult↗