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Biomedical subjects

M J McQueen

Publications and source records attributed to M J McQueen.

At least 19 recordsLinked to original sources
PubMed2005

The HOPE (Heart Outcomes Prevention Evaluation) Study and its consequences.

The HOPE study was a 19 country, prospective randomized trial in which the ACE-inhibitor Ramipril but not Vitamin E significantly reduced the risk of future cardiovascular events in a high-risk population of men and women, including many with diabetes. The benefits were present in all sub-groups, independent of the presence or absence of diabetes, hypertension, evidence of cardiovascular disease, microalbuminuria, blood pressure lowering, the use of aspirin, lipid-lowering or antihypertensive medication. It provided clear evidence that Ramipril should safely and cost-effectively be used in individuals not known to have low ventricular ejection fraction or heart failure but at high-risk of cardiovascular events. It was also beneficial in patients with renal insufficiency, reducing progression of proteinuria and development of new microalbuminuria. It provided micro- and macrovascular benefits in people with diabetes, reduced the development of new cases of diabetes and showed a positive and graded association between the waist-to-hip ratio and the risk of developing diabetes. Sub-studies completed and on-going into the predictive role of natriuretic peptides, infectious and inflammatory markers, provide insight into possible mechanisms of action of Ramipril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Overview of evidence-based medicine: challenges for evidence-based laboratory medicine.

Evidence-based medicine (EBM) has been driven by the need to cope with information overload, by cost-control, and by a public impatient for the best in diagnostics and treatment. Clinical guidelines, care maps, and outcome measures are quality improvement tools for the appropriateness, efficiency, and effectiveness of health services. Although they are imperfect, their value increases with the quality of the evidence they incorporate. Laboratory professionals must direct more effort to demonstrating the impact of laboratory tests on a greater variety of clinical outcomes. Laboratory and clinical practitioners must be familiar with many of the accessible electronic and paper tools for searching for evidence. Detailed statistical and epidemiologic knowledge is not essential, but critical appraisal skills and a competent understanding of the strengths and weaknesses of systematic review and metaanalysis are necessary. Overemphasis on complexity and failure to recognize time limitations are major barriers to translating EBM into everyday practice. Emphasizing and practicing the role of the laboratory professional as a skilled clinical consultant strongly grounded in evidence as well, in addition to better integration of laboratory and clinical information and improved laboratory reports will overcome most barriers. There is a poverty of good, primary studies of test evaluations. Institution of more consistent standards for the design and reporting of studies on diagnostic accuracy should improve the situation. If nothing else, systematic reviews have demonstrated the need for more good-quality primary research in laboratory medicine.

Chemistry, Clinical↗
PubMed2000

Evidence-based medicine: its application to laboratory medicine.

The current health care environment of cost-cutting highlights the need to reinforce the contribution of laboratory medicine to improvement in health care. This must be a patient-focused activity using continuous quality improvement, a familiar concept in laboratory practice. Involvement in the creation of clinical practice guidelines, care maps, and outcome measures will place laboratory medicine in the circle of continuous quality improvement. The laboratory must provide strong evidence that tests contribute to better overall resource utilization. Laboratory Information Systems can be used to better integrate laboratory data with clinical, diagnostic, pharmaceutic, statistical, and financial information. Improving laboratory utilization requires clear demonstrations of appropriate versus inappropriate laboratory use, and instructions on implementing appropriate use. The education of laboratory professionals should include search strategies, understanding the diagnostic accuracy of medical tests, and the application of systematic reviews and meta-analysis. With the rapid increase in the data base supporting evidence-based laboratory medicine, there is a significant challenge in translating the existing knowledge into practice. There is also a need for a cooperative strategy between the diagnostics industry and the laboratory medicine profession to provide evidence of the added value of laboratory testing. There is a significant role in developing the academic basis of the unique aspects of evidence-based laboratory medicine.

Clinical Laboratory Techniques↗
PubMed2000

The surface effect of dentifrices.

The aim of this study was to evaluate clinically three commercially available dentifrices and to determine any surface effects on tooth or gingival surfaces. Sixty-four participants were included in this study and were allocated randomly to one of four treatment groups by an independent person to ensure the investigators were unaware of the brushing material used. All toothbrushes and dentifrices were distributed by this independent person. The treatment groups were: Group 1--brush with water; Group 2--brush with Colgate (Baking Soda and Peroxide); Group 3--brush with Macleans (Whitening); Group 4--brush with Colgate (Sensation Whitening). All participants were requested to brush both morning and evening in their customary fashion using only the designated toothpaste, or water, for four weeks. All participants were required to use the same toothbrush type. No other oral hygiene products such as mouth rinses or dental floss were used during the trial period. Prior to commencement of the brushing period, all participants received a full clinical examination recording the status of the soft and hard tissues including a gingival index (Löe and Silness) to record gingival condition. A polyvinyl siloxane impression was taken of the six anterior teeth and gingival tissues at the commencement of the trial. After four weeks, a second full clinical examination was made and further silicone impressions were taken of the anterior teeth. All impressions were cast in epoxy resin for investigation with light and electron microscopy. Participants were also asked to answer a questionnaire relating to the toothpaste used. The results of this study indicated that no significant clinical differences were recorded for any dentifrice or water and there was no significant difference in gingival index scores over the four week period. Patient responses to each dentifrice varied according to individual patient preferences and expectations and no consistent findings could be determined. Light and electron microscopy indicated that tooth and gingival surface changes that occurred over the four week period with any of the dentifrices were similar to, and not significantly different from, changes seen with the use of water alone. These results indicate that none of the dentifrices tested was harmful to teeth or soft tissues.

Adolescent↗
PubMed1999

Monthly intra-individual variation in lipids over a 1-year period in 22 normal subjects.

OBJECTIVES: Previous reports on biological variation in lipids differ widely in the time interval between sampling, the number of samples analyzed per patient and the total study period. The present investigation was carried out to determine monthly intra-individual variation in lipids over 1 year and to establish whether there was a consistent change in lipid values over the summer months. The importance of taking this variation into consideration during the assessment of risk of coronary heart disease (CHD) was also examined. DESIGN AND METHODS: Cholesterol, triglycerides, HDL, apo A1, and apo B were measured at monthly intervals for 12 months in 22 healthy, free-living volunteers (11 females, 11 males) by standardized methods. RESULTS: When compared to analytical variation, biological variation was the dominant component of the intra-individual changes observed during the 1-year study period. As expected, triglycerides showed the greatest biological variation; the ratio of biological/analytical variation was 33.1. Much smaller ratios were observed for the other lipids measured in this study with values ranging from 4.2 to 6.8. Different subjects attained their maximum and minimum values in virtually every month of the year. There were significant reductions in cholesterol, HDL, LDL, and apo A1 in the summer months while triglycerides showed a non-significant increase and apo B a non-significant decrease during this period. CONCLUSIONS: All the analytes showed considerable intra-individual variation. It is, therefore, important to measure lipids sequentially over several weeks to arrive at an average value for risk stratification for CHD.

Adult↗
PubMed1998

Blood lipid profiles in children with acute lymphoblastic leukemia.

BACKGROUND: Abnormal blood lipid profiles have been associated with cancer. The objective of this study was to investigate the frequency and clinical significance of altered lipid profiles in children with acute lymphoblastic leukemia (ALL), the most common form of malignant disease in this age group. METHODS: Fasting blood lipid profiles (cholesterol [C], triglycerides [TG], high density lipoprotein [HDL], low density lipoprotein, very low density lipoprotein, apolipoproteins A1 [apo A1] and B, and lipoprotein a [Lp(a)]) were obtained in 24 children with ALL at diagnosis, 16 children during consolidation therapy with L-asparaginase, and 18 children during maintenance therapy without L-asparaginase. For comparison the authors studied lipid profiles in 15 children previously treated for leukemia, 15 healthy control children, and 17 children with other forms of cancer, both localized and widespread. RESULTS: An altered blood lipid profile was observed at the time of diagnosis of ALL. Statistically significant values included elevated TG (1.82+/-1.23 mmol/L), reduced HDL-C (0.54+/-0.24 mmol/L), and reduced ApoA1 (0.77+/-0.18 g/L) levels. A wide range of Lp(a) levels (0-1990 mg/L) were observed. Significantly reduced HDL-C (0.55+/-0.20 mmol/L) and ApoA1 (0.69+/-0.22 g/L) were observed in children with widespread but not localized solid tumors at diagnosis. C and TG correlated with serum albumin levels. Significant therapy-related changes in lipid profiles were observed in children with ALL during combination therapy with L-asparaginase (extremely elevated TG levels [3.34+/-2.82 mmol/L] and a striking reduction in Lp(a) levels) that were not observed during combination therapy without L-asparaginase or in children during treatment for solid tumors. In this small study there was no relation between these abnormalities and either thromboembolic events or pancreatitis. Blood lipid profiles in children with ALL returned to normal on completion of therapy. CONCLUSIONS: The lipid abnormalities observed at diagnosis in children with widespread cancer (ALL or solid tumors) may reflect altered nutritional states or altered lipid metabolism. Reduced concentrations of Lp(a) and elevated TG levels suggest L-asparaginase specific alterations and may provide insight into the toxicity associated with this drug.

Antineoplastic Agents↗
PubMed1998

Ethical and legal issues in the procurement, storage and use of DNA.

At the risk of ignoring the benefits, the problems of genetic testing have been widely discussed. Many clinical laboratories are archival stores for human tissues and very few have formal policies and procedures for the use of this material. There is little evidence of planning or preparation of appropriate protocols for the safekeeping of the collected clinical material. The process of informed consent needs to be re-examined. The standard of what would be expected by a reasonable and prudent person poses challenging questions relating to confidentiality and privacy, control and ownership of the stored tissue and cells, withdrawing from a research study, length of storage of samples, the use of biological materials by other parties, and the use of biological materials for purposes other than those for which they were first obtained. There also needs to be a clear understanding of identifiable, non-identifiable and anonymous samples. Clinical laboratory staff and their professional organisations need to engage in the discussion and development around the ethical, legal and social issues raised by testing human DNA. Clinical research laboratories will be increasingly involved in DNA testing and will be asked for access to stored blood or tissue. It is essential that professional responsibility is understood and is then exercised in the presence of appropriate policies and procedures. There is also a paramount need to involve the public who are already demonstrating evidence of alienation from the world occupied by genetics research.

Confidentiality↗
PubMed1998

Cholesteryl ester transfer protein mutations, protein activity and HDL-cholesterol concentration.

We have examined a group of North American subjects, selected to include individuals with a wide variety of HDL-cholesterol concentrations for: 1) mutations in the genes coding for cholesteryl ester transfer protein and hepatic lipase, 2) apolipoprotein E genotype, 3) total cholesterol and triglycerides, 4) HDL-triglycerides. Cholesteryl ester transfer protein activity was also estimated, using a novel technique that does not require separation of substrate and product. Transfer activity was shown to have a monophasic distribution, with a mean activity of 21 pmol substrate transferred/3 h/microl plasma. The cholesterol ester transfer activity of the group with HDL-cholesterol >1.60 mmol/l was significantly less than those with HDL-cholesterol <1.60 mmol/l. The cholesteryl ester transfer protein G1533A mutation was detected at an overall allele frequency of 2.91%. The mutation was more frequent in the group with HDL-cholesterol <1.60 mmol/l than in those >1.60 mmol/l. It was also more frequent in those with protein activity > 30 pmol/ 3h/microl plasma than in those with activity <30. These data suggest that this mutation in cholesteryl ester transfer protein is associated with increased transfer activity and reduced HDL-cholesterol concentrations. The cholesteryl ester transfer protein activity assay described here is simple and convenient. Subject to further evaluation and correlation with the present labour and time intensive assays, this commercially available assay offers the potential of rapid, simple analysis of large numbers of samples.

Carrier Proteins↗
PubMed1997

Monthly intra-individual variation in lipoprotein(a) in 22 normal subjects over 12 months.

OBJECTIVES: It is generally believe that lipoprotein(a) (Lp(a)) levels remain relatively constant in the same individual, but there is a paucity of data to substantiate this belief. This study was undertaken to determine the extent of intra-individual variation in Lp(a) over a 12-month period. DESIGN AND METHODS: Lp(a) was measured monthly in duplicate over a 12-month period in 11 females and 11 males who were healthy, free-living, normal subjects by the Incstar Immunoprecipitin method using a goat antibody which was monospecific for Lp(a). RESULTS: Some subjects showed considerable month-to-month variations which were not correlated with changes in other lipid parameters or with weight. Others showed fairly constant Lp(a) levels, with a few values which were quite different from the rest. This was not attributable to methodological factors; low and high controls gave mean (mg/L), SD and CV values of 181, 8.6, 4.7 and 431, 14, 3.3, respectively. The difference between the minimum and maximum values in the same individuals ranged from a low of 14 mg/L in one subject to a high of 229 mg/L in another over the one-year period. CONCLUSIONS: Lp(a) showed greater intra-individual variations in normal subjects than is commonly believed. It is therefore recommended that Lp(a) should be measured sequentially over a few weeks to arrive at a mean value for assessing risk of coronary heart disease.

Adult↗
PubMed1997

Mutations in cholesteryl ester transfer protein and hepatic lipase in a North American population.

OBJECTIVE: To examine a North American population sample with increased HDL cholesterol for mutations in the genes coding for cholesteryl ester transfer protein (CETP) and hepatic lipase (HL). DESIGN AND METHODS: Seventy individuals with increased HDL cholesterol at the time of initial presentation to the Lipid Clinic (males > 1.7 mmol/L, females > 1.8 mmol/L) were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) analysis for known mutations in CETP intron 14 and exon 15 and HL exons 6 and 8. RESULTS: CETP intron 14 mutation frequency 0.7%, CETP exon 15 A1503G 0%, HL exon 6 C873T 2.1%, HL exon 8 C1221T 0%. An unusual mutation in CETP exon 15 G1533A was found at a frequency of 3.5%. The sequence of this mutation was determined to be a G to A change at bp 1533 resulting in a predicted amino acid change of arginine to glutamine at position 451. CONCLUSIONS: Known mutations in CETP were much less prevalent in this North American population than in the Japanese populations that have been previously reported. HL mutations, described previously in only 6 families worldwide, appear to be more prevalent than previously recognized. CETP G1533A, reported only once previously is prevalent in this population at a surprisingly high frequency. The functional significance of this mutation is unknown.

Carrier Proteins↗
PubMed1997

Reverse cholesterol transport--a review of the process and its clinical implications.

OBJECTIVES: This review article will summarize the current knowledge surrounding the reverse cholesterol transport system; the process, the effect of mutations in genes coding for proteins which function in the system, and the possible clinical implications of these alterations. RESULTS: High-density lipoprotein-cholesterol (HDL-C) concentration is a marker for the reverse cholesterol transport (RCT) system, whereby cholesterol is returned from peripheral cells to the liver for reuse or excretion in the bile. Increased HDL-C concentrations are generally accepted to be protective against the future development of atherosclerosis and coronary artery disease (CAD), but recent evidence has indicated that the underlying cause of the increased HDL-C may affect whether it is protective or detrimental. The major steps in the RCT pathway are the efflux of free cholesterol from cells and binding by pre-beta HDL, esterification of HDL-bound cholesterol by lecithin cholesterol acyl transferase (LCAT), cholesteryl ester transfer protein (CETP) mediated exchange of cholesteryl ester and triglycerides between HDL and apo B-containing particles, and hepatic lipase (HL) mediated uptake of cholesterol and triglycerides by the liver. Mutations in proteins active in the RCT pathway can shed light on the functions and control of the various steps in the system. LCAT deficiency, leading to greatly reduced HDL and fish eye disease, is not usually associated with increased risk of CAD. Several new mutations in LCAT have recently been reported, however, which do result in CAD. Mutations leading to reduced CETP activity result in less CE being directed into apo-B containing particles and more remaining in the HDL. This has been associated with increased HDL-C concentrations. The generally accepted hypothesis that reduced CETP activity leads to reduced CAD risk has been challenged by a number of recent publications, and has become an area of active investigation. Mutations leading to reduced HL activity are rare occurrences. To date, all have been associated with increased HDL-C concentrations and CAD. CONCLUSION: The development of techniques to identify and characterize the functional significance of mutations in proteins involved in RCT will aid in the understanding of the mechanisms and control of this pathway.

Biological Transport↗