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Biomedical subjects

R Milne

Publications and source records attributed to R Milne.

At least 73 records · Page 4Linked to original sources
PubMed1997

Repeatability of three-day dietary records in the EURODIAB IDDM Complications Study.

OBJECTIVES: Repeatability of a dietary method is important in determining the quality of nutritional data. It should be assessed in the population of interest. This study evaluated the repeatability of nutritional data from standardized three-day dietary records, from the clinic-based, cross-sectional multi-centre EURODIAB IDDM Complications Study. DESIGN AND SUBJECTS: 15% of the total EURODIAB cohort was randomly selected to test the repeatability of nutritional intake data. Two three-day records, completed three weeks apart, were available for 216 diabetic patients (7.5%) representative of the total cohort. All records were analysed centrally, for intakes of protein (animal and vegetable), fat (saturated fat and cholesterol), carbohydrate, fibre, alcohol and energy. Repeatability was measured comparing mean intakes, determining the proportion of patients classified into the same/opposite quartile by the two three-day records and assessing mean differences with standard deviations (s.d.d). RESULTS: There were no significant differences in mean energy and nutrient intakes between the first and second records. Classification of individuals into the opposite quartile occurred only in 0-4% of patients and overall about 50% (range 44-74%) of the subjects were classified into the same quartiles of intakes. Only small mean differences were found for energy intake (-156 (1633) kJ; 95% confidence limits -375, 63 kJ) and nutrients with s.d.ds comparable to intra-individual variations in the general population. The differences in energy intake were randomly distributed over the range of intakes. CONCLUSIONS: The present study demonstrates that standardized three day dietary records show a high degree of repeatability within a short period of time in a sample of European IDDM patients. The good repeatability strengthens the conclusions drawn from the nutritional data in the EURODIAB IDDM Complications Study.

Alcohol Drinking↗
PubMed1997

Cholesteryl ester transfer protein activity enhances plasma cholesteryl ester formation. Studies in CETP transgenic mice and human genetic CETP deficiency.

The plasma cholesteryl ester transfer protein (CETP) promotes the removal of HDL cholesteryl esters and is thought to stimulate reverse cholesterol transport (RCT). However, mechanisms by which CETP may stimulate RCT are poorly understood. Thus, we examined the relationship between plasma CETP expression and plasma cholesteryl ester formation in CETP transgenic (Tg) mice, hamsters, and human subjects with genetic CETP deficiency. Incubation of CETP Tg mouse plasma showed a 20% to 40% increase in plasma cholesterol esterification rate (CER, P < .05) compared with control mice. Injection of a neutralizing CETP monoclonal antibody (MAb) (TP2) into natural flanking region CETP Tg mice resulted in an increase in plasma free cholesterol (FC) concentration, FC/CE ratio, FC/phosphatidylcholine ratio, and hepatic CETP mRNA. In hamsters, CETP inhibition also resulted in an increase in plasma FC/phosphatidylcholine ratio and increased CETP mRNA in adipose tissue. In humans with two common CETP gene mutations (an intron 14 splicing defect and a D442G missense mutation), mean plasma CERs were 39 and 60, respectively, compared with 89 nmol x mL-1 x h-1 in normal subjects. By contrast, lecithin:cholesterol acyltransferase (LCAT) mass was normal in CETP-deficient subjects. MAb neutralization of CETP activity in incubated human plasma did not alter the LCAT reaction, even after supplementation with discoidal HDL and VLDL. Thus, genetic alterations in CETP levels lead to secondary changes in the plasma LCAT reaction, possibly because of remodeling of HDL by CETP acting in concert with other factors in vivo. In human genetic CETP deficiency, a moderate impairment in the plasma LCAT reaction may contribute to a defect in RCT, providing a potential mechanism to explain the recently observed excess of coronary heart disease in these subjects.

Animals↗
PubMed1997

Smoking, alcohol and the risk of Dupuytren's contracture.

We investigated the association of Dupuytren's contracture with smoking and with alcohol by a case-control study in which 222 patients having an operation for this condition were matched for age, operation date and gender with control patients having other orthopaedic operations. Fifty of the cases were also each matched with four community controls. Data were collected by postal questionnaire. Dupuytren's contracture needing operation was strongly associated with current cigarette smoking (adjusted odds ratio 2.8 (95% confidence interval (CI) 1.5 to 5.2)). The mean lifetime cigarette consumption was 16.7 pack-years for the cases compared with 12.0 pack-years for the controls (p = 0.016). Dupuytren's contracture was also associated with an Alcohol Use Disorders Test score greater than 7 (adjusted odds ratio 1.9 (95% CI 1.02 to 3.57)). Mean weekly alcohol consumption was 7.3 units for cases and 5.4 units for controls (p = 0.016). The excess risk associated with alcohol did not appear to be due to a confounding effect of smoking, or vice versa. Smoking increases the risk of developing Dupuytren's contracture and may contribute to its prevalence in alcoholics, who tend to smoke heavily.

Alcohol Drinking↗
PubMed1996

Increased prebeta-high density lipoprotein, apolipoprotein AI, and phospholipid in mice expressing the human phospholipid transfer protein and human apolipoprotein AI transgenes.

Human plasma phospholipid transfer protein (PLTP) circulates bound to high density lipoprotein (HDL) and mediates both net transfer and exchange of phospholipids between different lipoproteins. However, its overall function in lipoprotein metabolism is unknown. To assess the effects of increased plasma levels of PLTP, human PLTP transgenic mice were established using the human PLTP gene driven by its natural promoter. One line of PLTP transgenic mice with moderate expression of PLTP mRNA and protein was obtained. The order of human PLTP mRNA expression in tissues was: liver, kidney, brain, small intestine > lung > spleen > heart, adipose tissue. Western blotting using a human PLTP monoclonal antibody revealed authentic human PLTP (Mr 80 kD) in plasma. Plasma PLTP activity was increased by 29% in PLTP transgenic mice. However, plasma lipoprotein analysis, comparing PLTP transgenic mice to control littermates, revealed no significant changes in the plasma lipoprotein lipids or apolipoproteins. Since previous studies have shown that human cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase only function optimally in human apoAI transgenic mice, the human PLTP transgenic mice were cross-bred with human apoAI transgenic mice. In the human apoAI transgenic background, PLTP expression resulted in increased PLTP activity (47%), HDL phospholipid (26%), cholesteryl ester (24%), free cholesterol (37%), and apoAI (22%). There was a major increase of apoAI in prebeta-HDL (56%) and a small increase in alpha-HDL (14%). The size distribution of HDL particles within alpha- and prebeta-migrating species was not changed. The results suggest that PLTP increases the influx of phospholipid and secondarily cholesterol into HDL, leading to an increase in potentially antiatherogenic prebeta-HDL particles.

Animals↗
PubMed1996

Nutritional intake of 2868 IDDM patients from 30 centres in Europe. EURODIAB IDDM Complications Study Group.

The EURODIAB IDDM Complications Study, a cross-sectional, clinic-based study, was designed to measure the prevalence of diabetic complications in stratified samples of European insulin-dependent diabetic (IDDM) patients. As diet may be related to diabetic complications, nutritional intake was analysed in the study population. The aims of this first nutritional paper are to describe the nutrient intake in 2868 IDDM patients from 30 centres in 16 countries throughout Europe, to investigate the degree of regional differences in nutrient intake and to compare current intakes with recommended levels. Nutritional intake from 1458 male and 1410 female IDDM patients was assessed by a validated 3-day record (two weekdays, Sunday) and centrally analysed. Mean energy intake for all patients was 2390 +/- 707 kcal/day. Mean protein intake was 1.5 +/- 0.5 g/kg body weight. Carbohydrate intake was 43% and fibre intake 18 g/day. Alcohol intake for the total cohort was 2% of energy. Total fat contributed 38% of energy, with 14% from saturated fat. The Italian centres reported lower total and saturated fat intakes compared with other centres. Recommendations from the Diabetes and Nutrition Study Group of the EASD for total fat, saturated fatty acids and carbohydrate were only achieved by 14%, 14% and 15% of patients, respectively. The data of the present study clearly indicate current problems in the nutritional intake of European IDDM patients. These findings contribute to the definition of future targets in the nutritional management of IDDM patients, to be achieved as part of the initiatives taken by the St. Vincent Declaration action programme.

Adolescent↗
PubMed1996

Evidence-based consumer health information: developing teaching in critical appraisal skills.

OBJECTIVE: To help people who give health information to the public develop the skills they need to make sense of evidence about effectiveness. DESIGN: Educational approach, preceded by careful planning with representatives of possible participants. SETTING AND STUDY OF PARTICIPANTS: Staff in consumer health information services and members of maternity self-help groups in the UK in summer 1995. INTERVENTIONS: Pairs of half-day workshops introducing participants to randomised controlled trials and systematic reviews and to their critical appraisal. The workshops were run participatively and had at their centre a critical appraisal session in small groups. MAIN OUTCOME MEASURES: Attendance at workshops, satisfaction and enjoyment of workshops; comments at a follow-on event. RESULTS: Four pairs of workshops were held (three for consumer health information services, one for maternity self-help groups), 54 people attended a pair of workshops and a further 34 attended individual workshops. The workshops were enjoyed and found to be a good use of time. CONCLUSIONS: It is feasible to introduce critical appraisal skills to people whose primary role is to give health information to the public. There is a need for comparative evaluation of different approaches.

Community Participation↗
PubMed1996

Hand searching the Journal of Epidemiology and Community Health as part of th Cochrane Collaboration.

STUDY OBJECTIVE: To identify randomised controlled trials (RCTs) published in the Journal of Epidemiology and Community Health and to explore the contribution of these to the evaluation of public health issues. DESIGN: Hand searching of the journal by both authors with independent assessment of topics of the reports and of their relevance to the Cochrane Collaboration. Agreement was assessed using kappa scores. SETTING: All papers and letters published in the journal from the first issue to the end of 1994. SUBJECTS: Reports that might be RCTs were collected and classified into seven categories: definitely/probably/possibly RCTs or quasi-RCTs; or none of these. MAIN RESULTS: Eighty two definite RCTs were identified and a further 23 were probably/possibly RCTs or quasi-RCTs. Most reports dealt with health education, drug treatments, or "other" health service interventions. Both authors failed to identify a number of trials on hand searching. CONCLUSIONS: The journal has published many trials of importance to the development of evidence-based public health policy. Hand searching may need to be done independently by more than one person.

Information Storage and Retrieval↗
PubMed1996

Case mix measurement in English hospitals: an evaluation of five methods for predicting resource use.

OBJECTIVES: The introduction of an internal market in the British National Health Service (NHS) has highlighted the importance of developing appropriate, valid and timely measures of hospital activity, both for the purposes of specifying and monitoring contracts and for evaluating the success of the NHS reforms in general. This paper compares the validity of five case mix methods (Diagnosis Related Groups (DRGs); Healthcare Resource Groups (HRGs) versions 1 and 2; specialty classification; a simple age categorization) in predicting resource use. METHODS: Two data sets were used to compare different case mix methods. A 3% random sample (n approximately equal to 300,000) of the 1992/3 Hospital Episodes Statistics was used to test their ability to predict variation in length of stay, and a second set of individually costed patient episodes from two hospitals (n approximately equal to 40,000) was used to test their ability to explain cost variation. Analysis of variance models were used to assess the fit of each of the case mix systems to test data and a simple significance test of differences in mean squared error between models was applied. RESULTS: All case mix methods performed poorly on untrimmed data. When lengths of stay greater than 29 days were excluded, version 2 of HRGs explained 31% of total variance in length of stay and 25% of cost variation. DRGs explained less variance but performed better than HRGs version 1. For a typical hospital patient population consisting of a range of specialties, the difference in explanatory power between HRGs V2 and DRGs was statistically significant at the 5% level for sample sizes of approximately 2000 or greater. For individual specialties, the minimum sample size required for the difference between the groupers to be significant ranged from around 300 to over 2000. CONCLUSIONS: The locally developed HRGs version 2 system appears to offer superior performance in terms of resource homogeneity to other currently available approaches. It is also more adaptable and cheaper than imported alternatives and has been formally endorsed by the UK medical Royal Colleges.

Analysis of Variance↗
PubMed1996

Structure-function relationships of human cholesteryl ester transfer protein: analysis using monoclonal antibodies.

Cholesteryl ester transfer protein (CETP), a 476 amino acid glycoprotein, mediates cholesteryl ester (CE), triglyceride, and phospholipid transfer among plasma lipoproteins. A monoclonal antibody (mAb), TP2, specific for an epitope within the last 26 amino acids of CETP has been shown to block all CETP-mediated lipid transfer, apparently by limiting access to lipid-binding sites in the carboxy terminal of CETP. A new panel of 16 anti-human CETP mAbs has now been used to further probe the structure-function relationships of CETP. Of the new mAbs, 9 partially inhibit CETP-mediated CE transfer (24-43%) from HDL to LDL. The corresponding epitopes were mapped within the CETP primary structure by the reactivity of the mAbs with CETP variants having deletions or amino acid substitutions. Of the 9 new, neutralizing mAbs, 6 are specific for epitopes situated between residues 410-450 and two others for epitopes between residues 184-260 and 332-366, respectively. The epitope of one neutralizing mAbs could not be mapped. Therefore, binding of mAbs to epitopes situated in four non-overlapping regions within CETP primary structure that are separated by as many as 280 residues can neutralize CETP-mediated CE transfer. Epitopes of mAbs that do not influence CE transfer activity map to the regions 184-260, 261-331, and 367-409, respectively. When pairs of mAbs were tested for their abilities to mutually compete for binding to immobilized CETP, competition was observed for mAbs specific for epitopes that are distant in CETP primary structure. The cross-competition patterns demonstrate that the carboxy terminal 60% of CETP adopts a compact structure. Together with previous mutagenesis studies, the data suggests that a carboxy terminal neutral lipid binding domain may be in close proximity to a lipoprotein binding region within native CETP.

Animals↗
PubMed1995

Helicobacter pylori and upper gastrointestinal disease: a survey of gastroenterologists in the United Kingdom.

The objective of this study was to conduct a survey of the opinions and practices of gastroenterologists in the United Kingdom concerning the impact of Helicobacter pylori infection on the management of upper gastrointestinal diseases. A postal questionnaire was sent to all medically qualified members of the British Society of Gastroenterology working in the UK. Replies were received from 670 of 1037 eligible BSG members (65%). Of these, 73% thought that H pylori was a cause of duodenal ulcer and 84% thought that eradication of H pylori decreased ulcer recurrence in comparison with acid suppression. While 80% used anti-H pylori therapy for a chronic relapsing duodenal ulcer, only 25% used such therapy for an ulcer at first presentation and 17% never used anti-H pylori therapy for patients with duodenal ulcer. Although 75% of respondents did not agree that H pylori was a cause of non-ulcer dyspepsia, 69% used anti-H pylori therapy to treat a patient with this condition. At the time of the survey, 69% of those who used anti-H pylori therapy adopted some variant of standard triple therapy. Only 7% routinely tested for bacterial sensitivity to antibiotics and only 22% assessed their patients for eradication after treatment. There was a lack of consensus about whether H pylori was a cause of gastric ulcer or gastric cancer with only 47% and 17% respectively believing in these associations. In conclusion, at the time of the survey, the use of anti-H pylori therapy had been accepted by a majority of specialist UK gastroenterologists in the management of upper gastrointestinal disease. There was, however, a substantial degree of uncertainty and divergence about which patients should be treated.

Adult↗
PubMed1995

Differences in hospital casemix, and the relationship between casemix and hospital costs.

BACKGROUND: The aim of the study was to examine the relationship between hospital costs and casemix, and after adjustment for casemix differences, between cost and institutional size, number of specialties, occupancy and teaching status. METHODS: A retrospective analysis of all admissions to nine acute-care NHS hospitals in the Oxford region during the 1991-1992 financial year was undertaken. All episodes were assigned to a diagnosis-related group (DRG) and a cost weight assigned accordingly. Costs per finished consultant episode, before and after adjustment for casemix differences, were analysed at the hospital and specialty level. RESULTS: Casemix differences were significant, and accounted for approximately 77 per cent of the difference in costs between providers. Costs per casemix-adjusted episode were not significantly associated with differences in hospital size, scope, occupancy levels or teaching status, but sample size was insufficient to investigate these relationships adequately. Specialty costs were poorly correlated with specialty casemix. This was probably due to poor apportionment of specialty costs in hospital accounting returns. CONCLUSIONS: Casemix differences need to be taken into account when comparing providers for the purposes of contracting, as unadjusted unit costs may be misleading. Although the methods used may currently be applied to most NHS hospitals, widespread use would be greatly facilitated by the development of indigenous cost weights and better routine hospital data coding and collection.

Bed Occupancy↗
PubMed1995

Molecular characterization of two monoclonal antibodies specific for the LDL receptor-binding site of human apolipoprotein E.

Apolipoprotein E (apoE), a 299 amino acid protein, is a ligand for the low density lipoprotein receptor (LDLr). It has been established that basic amino acids situated between apoE residues 136 and 150 participate in the interaction of apoE with the LDLr. Evidence suggests that apoE is heterogeneous on lipoproteins in its conformation and in its ability to react with cell surface receptors. Our goal was to produce mAbs that could serve as conformational probes of the LDLr binding site of apoE. We used a series of apoE variants that have amino acid substitutions at residues 136, 140, 143, 144, 145, 150, 152, and 158 to identify the epitopes of two anti-human apoE monoclonal antibodies (mAbs), 1D7 and 2E8, that inhibit apoE-mediated binding to the LDLr. We show that most of the variants that have reduced reactivity with the LDL receptor also have reduced reactivity with the mAbs. The epitopes for both mAbs appear to include residues 143 through 150 and thus coincide with the LDLr-binding site of apoE. It is notable that mAb 2E8, but not 1D7, resembles the LDLr in showing a reduced reactivity with apoE (Arg158 --> Cys). While most of the receptor-defective variants involve replacement of apoE residues directly implicated in binding, substitution of Arg158 by Cys is thought to indirectly affect binding of apoE to the LDLr by altering the conformation of the receptor-binding site. To determine whether the similarity in specificities of the mAbs and the LDLr reflect structural similarities, we cloned and characterized the cDNAs encoding the light and heavy chains of both mAbs. Primary sequence analysis revealed that, although these two antibodies react with overlapping epitopes, their respective complementarity determining regions (CDRs) share little homology, especially those of their heavy chains. The two mAbs, therefore, likely recognize different epitopes or topologies within a limited surface of the apoE molecule. Four negatively charged amino acids were present in the second CDR of the 2E8 heavy chain that could be approximately aligned with acidic amino acids within the consensus sequence of the LDLr ligand-binding domain. This could indicate that mAb 2E8 and the LDLr use a common mode of interaction with apoE.

Amino Acid Sequence↗
PubMed1995

Immunoelectron microscopy of low density lipoproteins yields a ribbon and bow model for the conformation of apolipoprotein B on the lipoprotein surface.

In the present study, the relative positions of 11 anti-apolipoprotein B monoclonal antibodies have been mapped onto the surface of human low density lipoproteins by electron microscopy. As the epitopes recognized by these antibodies have been previously located on the primary sequence of apoB, these data provide a map of the configuration of the protein on the surface of the LDL. The first 89% of apoB-100 may be modeled as a thick ribbon that wraps once around the LDL, completing the encirclement by about amino acid residue 4050. The thickness of the ribbon is sufficient to penetrate the monolayer, so that it makes contact with the core. There is a kink in the ribbon beginning almost halfway along its length at approximately apoB-48. The C-terminal 11% of apoB constitutes the "bow," an elongated structure of about 480 residues, beginning at 4050 and stretching back into one hemisphere and then crossing the ribbon into the other hemisphere between residues 3000 to 3500, thus bringing sequences in the C-terminal portion of apoB-100 near to the suggested binding site for the LDL receptor. The C-terminal sequences may act as a negative regulator of LDL receptor binding, in agreement with Parhofer et al, 1992. J. Clin. Invest. 89: 1931-1937, who reported the enhanced clearance from plasma of apoB-89-containing lipoproteins. It is proposed that in VLDL the bow could function to inhibit binding to the receptor; during lipolysis to form LDL, it is suggested that these C-terminal inhibitory sequences forming the bow would move sufficiently to allow interaction with the LDL-receptor.

Antibodies, Monoclonal↗
PubMed1995

The type and quality of randomized controlled trials (RCTs) published in UK public health journals.

BACKGROUND: Randomized controlled trials (RCTs) are increasingly being used to evaluate the effectiveness of health care interventions. Systematic reviews of RCTs form the basis of the Cochrane Collaboration, which aims to synthesize all RCTs concerned with the provision of health care. This paper reports the quantity and methodological quality of RCTs published in five UK public health journals, which were searched as part of a planned register of RCTs in public health. METHODS: Five journals were hand searched: The International Journal of Epidemiology, Health Trends, Journal of Public Health Medicine, Public Health and The Journal of Epidemiology and Community Health. All RCTs were identified and their methodological characteristics reviewed. RESULTS: Ninety-one trials were identified from the five journals. A wide variety of topics were covered, the most common being prevention strategies )46 percent of the trials). Although the actual number of reports of RCTs published increased over time, there was no detectable improvement in the quality of reports. The aspect of bias most well controlled was control of bias at entry (randomization), in 83 (91 per cent) of trials. However, even in these trials details about the process of randomization were poor. CONCLUSION: These trials will form the basis of a register of RCTs in public health. The diversity of topics covered illustrates the broad-based nature of public health. For this reason, many other RCTs relevant to the practice of public health are likely to be found in non-public health journals.

Humans↗
PubMed1994

Apoprotein B structure and receptor recognition of triglyceride-rich low density lipoprotein (LDL) is modified in small LDL but not in triglyceride-rich LDL of normal size.

We compared the effect of lipid composition and particle size of triglyceride-rich low density lipoprotein (LDL) upon apoprotein B conformation and binding to the LDL receptor. Three groups of triglyceride-rich LDL were studied: (a) LDL isolated from chronic hypertriglyceridemic individuals (HTG-LDL); (b) normal LDL made triglyceride-rich by in vitro incubation with triglyceride emulsion and the neutral lipid transfer protein (R-LDL); and (c) LDL from normolipidemic individuals made acutely hypertriglyceridemic by intravenous infusion of 10% Intralipid (IV-LDL). HTG-LDL was small and dense, whereas R-LDL and IV-LDL had normal size. HTG-LDL, but not R-LDL or IV-LDL, exhibited decreased binding to the LDL receptor on human skin fibroblasts in studies at 4 degrees C and reduced degradation at 37 degrees C. Apoprotein B conformation was assessed by circular dichroism and by analyzing the immunoreactivity of different monoclonal antibodies. HTG-LDL but not R-LDL or IV-LDL showed a change in the CD spectra and a consistent decrease in the immunoreactivity of monoclonal antibody 3F5 (2.5-fold) which recognizes an epitope adjacent to the receptor binding domain of apoprotein B. These findings suggest that in triglyceride-rich LDL, the relative content of neutral lipid in the core of LDL in the absence of changes in the size of the particle does not significantly affect apoprotein B conformation or its affinity for the LDL receptor.

Antibodies, Monoclonal↗