The heart of the matter: cardiac assessment in professional footballers.

AIM: Sudden cardiac death is the leading medical cause of death during exercise.1 Our objective was to retrospectively analyse the routine cardiac assessment of professional footballers to aid physician management and improve player safety. METHODS: Footballers from five professional clubs between March 2012 and October 2014 were included (n=265). All were performed in line with the recommendations of the Football Association Cardiology Committee, incorporating clinical examination, 12-lead ECG, echocardiography and health questionnaire.2 Data was retrospectively collected, inspected and analysed using Excel spreadsheets. Findings were classified as 'normal' or 'not normal', and not normal assessments were further broken down into 'clear-cut pathology' (pathology with widely accepted guidance on management) or 'grey screen'. RESULTS: Footballers were aged 13 to 37 years, with 69% aged over 18 and 31% under. The majority of the review population was White European (66%). Of the review population 11% had 'not normal' assessments, of these assessments 83% were considered grey screens (by Consultant Cardiologist) requiring further investigation or surveillance. Overall clear-cut pathology was identified in 2%. CONCLUSIONS: A high proportion of the players (9%) had grey screens. The majority of these were due to ECG or structural abnormalities, which are clinically challenging to differentiate from physiological adaptation of the athletic heart and potentially fatal conditions. The extent to which these findings put the athlete at risk of a life threatening cardiac event is un-?quantified. Team physician's need to be aware of managing the on-going risk with these patients and ensure suitable ?follow up and assessment on a regular basis to mitigate this.

Assessing the cost-effectiveness of type 1 diabetes interventions: the Sheffield type 1 diabetes policy model.

AIMS: To build a flexible and comprehensive long-term type 1 diabetes mellitus model incorporating the most up-to-date methodologies to allow a number of cost-effectiveness evaluations. METHODS: This paper describes the conceptual modelling, model implementation and model validation of the Sheffield type 1 diabetes policy model (version 1.0), developed through funding by the U.K. National Institute for Health Research as part of the Dose Adjustment for Normal Eating research programme. The model is an individual patient-level simulation model of type 1 diabetes and it includes long-term microvascular (retinopathy, neuropathy and nephropathy) and macrovascular (myocardial infarction, stroke, revascularization and angina) diabetes-related complications and acute adverse events (severe hypoglycaemia and diabetic ketoacidosis). The occurrence of these diabetes-related complications in the model is linked to simulated individual patient-level risk factors, including HbA1c , age, duration of diabetes, lipids and blood pressure. Transition probabilities were modelled based on a combination of existing risk functions, published trials, epidemiological studies and individual-level data from the Dose Adjustment for Normal Eating research programme. RESULTS: The model takes a lifetime perspective, estimating the impact of interventions on costs, clinical outcomes, survival and quality-adjusted life years. Validation of the model suggested that, for almost all diabetes-related complications predicted, event rates were within 10% of the normalized rates reported in the studies used to build the model. CONCLUSIONS: The model is highly flexible and has broad potential application to evaluate the Dose Adjustment for Normal Eating research programme, other structured diabetes education programmes and other interventions for type 1 diabetes.

Can diabetes prevention programmes be translated effectively into real-world settings and still deliver improved outcomes? A synthesis of evidence.

OBJECTIVE: Randomized trials provide evidence that intensive lifestyle interventions leading to dietary and physical activity change can delay or prevent Type 2 diabetes. Translational studies have assessed the impact of interventions based on, but less intensive than, trial protocols delivered in community settings with high-risk populations. The aim of this review was to synthesize evidence from translational studies of any design to assess the impact of interventions delivered outside large randomized trials. METHODS: Medical and scientific databases were searched using specified inclusion and exclusion criteria. Studies were included that used a tested diabetes preventive study protocol with an adult population at risk from Type 2 diabetes. Included papers were quality assessed and data extracted using recommended methods. RESULTS: From an initial 793 papers, 19 papers reporting 17 studies were included. Translational studies from a range of settings utilized a variety of methods. All were based on the US Diabetes Prevention Programme protocol or the Finnish Diabetes Prevention Study, with modifications that increased feasibility and access. The main outcome that was reported in all studies was weight change. Weight loss, which occurred in all but one study, was greater in intervention arms than in control subjects. No consistent differences were found in blood glucose or waist circumference. CONCLUSIONS: Translational studies based on the intensive diabetes prevention programmes showed that there is potential for less intensive interventions both to be feasible and to have an impact on future progression to diabetes in at-risk individuals.

Reference intervals for plasma ß-CTX and P1NP in children: A systematic review and pooled estimates.

OBJECTIVE: Reference intervals for plasma P1NP and ß-CTX in children and adolescents from several studies have recently been published. The aim of this study was to combine the available data into a set of reference intervals for use in clinical laboratories. DESIGN AND METHODS: A systematic literature search for primary studies reporting reference intervals for plasma P1NP and ß-CTX in infants, children and adolescents using the Roche methods was carried out. Reference limits were extracted. For each year of age, mean upper and lower reference limits were calculated, weighted by the number of subjects in each study, and were plotted against age. Proposed reference limits were developed from the weighted mean data with age partitions determined pragmatically. RESULTS: Reference limits for clinical use for females to 25 years and males to 18 years, based on the weighted mean reference data, are presented. Ten studies contributed to the pooled analysis. The proposed reference limits are identical for males and females <9 years age, prior to the pubertal growth spurt. For ß-CTX, the weighted mean reference limits showed relatively constant values during the pre-pubertal years but a marked increase during puberty before a rapid decline towards adult values. Those for P1NP showed high values declining rapidly in the first 2 years of life, followed by a modest increase during early puberty. Limited published information for late adolescent and young adult subjects was noted. CONCLUSIONS: The proposed reference intervals may be useful for clinical laboratories reporting these bone turnover markers measured by the Roche assays.

Learning from the challenges of undertaking an evaluation of a multi-partner housing support initiative delivered within a hospital setting.

Objectives: We present learning from a mixed-methods evaluation of a housing support initiative for hospital inpatients. Study design: A mixed-methods process evaluation. Methods: A social housing provider delivered a housing support service in two hospitals (mental health unit and general hospital). Healthcare providers, the social housing provider and academic researchers designed and undertook a co-produced, mixed-methods process evaluation of the intervention. The evaluation included questionnaires, semi-structured interviews, analysis of routinely collected data and economic analysis. Despite commitment from the partners, the evaluation faced challenges. We reflect on the lessons learnt within our discussion paper. Results: Despite the commitment of the partners, we faced several challenges.We took an iterative approach to the design and processes of the evaluation to respond to arising challenges. Recruitment of service-users was more difficult than anticipated, requiring additional staff resources. Given the small-scale nature of the intervention, and the quality of data recorded in hospital records, the planned economic analysis was not feasible. Positive factors facilitating evaluation included involvement of staff delivering the intervention, as well as managers. Being able to offer payment to partner organisations for staff time also facilitated ongoing engagement. Conclusions: Multi-partner evaluations are useful, however, researchers and partners need to be prepared to take an iterative, resource intensive approach. Both availability and quality of routine data, and the resources required to support data collection, may limit feasibility of specific methods when evaluating small-scale cross-sector initiatives. Thus, this necessitates a flexible approach to design and analysis.

Screening for type 2 diabetes: literature review and economic modelling.

OBJECTIVES: To reconsider the aims of screening for undiagnosed diabetes, and whether screening should be for other abnormalities of glucose metabolism such as impaired glucose tolerance (IGT), or the 'metabolic syndrome'. Also to update the previous review for the National Screening Committee (NSC) on screening for diabetes, including reviewing choice of screening test; to consider what measures would be taken if IGT and impaired fasting glucose (IFG) were identified by screening, and in particular to examine evidence on treatment to prevent progression to diabetes in these groups; to examine the cost-effectiveness of screening; and to consider groups at higher risk at which screening might be targeted. DATA SOURCES: Electronic databases were searched up to the end of June 2005. REVIEW METHODS: Literature searches and review concentrated on evidence published since the last review of screening, both reviews and primary studies. The review of economic studies included only those models that covered screening. The new modelling extended an existing diabetes treatment model by developing a screening module. The NSC has a set of criteria, which it applies to new screening proposals. These criteria cover the condition, the screening test or tests, treatment and the screening programme. Screening for diabetes was considered using these criteria. RESULTS: Detection of lesser degrees of glucose intolerance such as IGT is worthwhile, partly because the risk of cardiovascular disease (CVD) can be reduced by treatment aimed at reducing cholesterol level and blood pressure, and partly because some diabetes can be prevented. Several trials have shown that both lifestyle measures and pharmacological treatment can reduce the proportion of people with IGT who would otherwise develop diabetes. Screening could be two-stage, starting with the selection of people at higher risk. The second-stage choice of test for blood glucose remains a problem, as in the last review for NSC. The best test is the oral glucose tolerance test (OGTT), but it is the most expensive, is inconvenient and has weak reproducibility. Fasting plasma glucose would miss people with IGT. Glycated haemoglobin does not require fasting, and may be the best compromise. It may be that more people would be tested and diagnosed if the more convenient test was used, rather than the OGTT. Five economic studies assessed the costs and short-term outcomes of using different screening tests. None examined the long-term impact of different proportions of false negatives. All considered the costs that would be incurred and the numbers identified by different tests, or different cut-offs. Results differed depending on different assumptions. They did not give a clear guide as to which test would be the best in any UK screening programme, but all recognised that the choice of cut-off would be a compromise between sensitivity and specificity; there is no perfect test. The modelling exercise concluded that screening for diabetes appears to be cost-effective for the 40-70-year age band, more so for the older age bands, but even in the 40-49-year age group, the incremental cost-effectiveness ratio for screening versus no screening is only 10,216 pounds per quality-adjusted life-year. Screening is more cost-effective for people in the hypertensive and obese subgroups and the costs of screening are offset in many groups by lower future treatment costs. The cost-effectiveness of screening is determined as much by, if not more than, assumptions about the degree of control of blood glucose and future treatment protocols than by assumptions relating to the screening programme. The very low cost now of statins is also an important factor. Although the prevalence of diabetes increases with age, the relative risk of CVD falls, reducing the benefits of screening. Screening for diabetes meets most of the NSC criteria, but probably fails on three: criterion 12, on optimisation of existing management of the condition; criterion 13, which requires that there should be evidence from high-quality randomised controlled trials (RCTs) showing that a screening programme would reduce mortality or morbidity; and criterion 18, that there should be adequate staffing and facilities for all aspects of the programme. It is uncertain whether criterion 19, that all other options, including prevention, should have been considered, is met. The issue here is whether all methods of improving lifestyles in order to reduce obesity and increase exercise have been sufficiently tried. The rise in overweight and obesity suggests that health promotion interventions have not so far been effective. CONCLUSIONS: The case for screening for undiagnosed diabetes is probably somewhat stronger than it was at the last review, because of the greater options for reduction of CVD, principally through the use of statins, and because of the rising prevalence of obesity and hence type 2 diabetes. However, there is also a good case for screening for IGT, with the aim of preventing some future diabetes and reducing CVD. Further research is needed into the duration of undiagnosed diabetes, and whether the rise in blood glucose levels is linear throughout or whether there may be a slower initial phase followed by an acceleration around the time of clinical diagnosis. This has implications for the interval after which screening would be repeated. Further research is also needed into the natural history of IGT, and in particular what determines progression to diabetes. An RCT of the type required by NSC criterion 13 is under way but will not report for about 7 years.

Alterations of cell membrane composition during prolonged fasting in lizards.

Male lizards fasted for 35 days showed significant alterations in the lipid composition of membranes isolated from a variety of organs and tissues. Unesterified cholesterol was significantly increased in membranes from kidney, skeletal muscle, small intestine, testis and heart but not in those from lung, brain and liver; cholesterol/phospholipid molar ratio was also significantly increased in membranes from all organs except brain and liver. Membrane total phospholipids were reduced for all tissues except brain and liver, whilst significant reductions in the molar ratio of membrane phosphatidylcholine to sphingomyelin occurred in kidney, muscle, testis, intestine and liver. Similar alterations in lipid composition were found in plasma and significant correlations between plasma and membrane cholesterol/phospholipid and phosphatidylcholine/sphingomyelin molar ratios were found for those organs in which significant lipid changes occurred during fasting. Lizards fasted for 35 days and then refed a natural diet, such that they started to regain weight, had normal membrane lipid compositions. These observations suggest that during prolonged fasting certain tissues of the lizard are unable to maintain a normal membrane lipid composition and that abnormal plasma lipoproteins may be involved in this process.

Characteristics of the binding of human and bovine high-density lipoproteins by bloodstream forms of the African trypanosome, Trypanosoma brucei brucei.

Bloodstream forms of Trypanosoma brucei brucei are unable to synthesize cholesterol but appear to bind and take up plasma low-density lipoproteins (LDL) from their host. Whether cholesterol homeostasis of this unicellular parasite also requires interactions with host high-density lipoprotein (HDL) particles is unknown. Equilibrium binding of radioiodinated apolipoprotein E-depleted human HDL3 (d = 1.125-1.21 g/ml) and bovine HDL (d = 1.063-1.21 g/ml) by T.b.brucei was rapid (less than 30 min) at 4 degrees C and was characterized by a saturable, specific component. There were five times the number of high-affinity binding sites for human HDL3 as for bovine HDL (64,000 vs. 11,500 per trypanosome) and their binding affinity was greater with an equilibrium dissociation constant (Kd) of 157 nM compared to 315 nM for bovine HDL). Binding of rat and rabbit HDL3 was similar to bovine HDL. By contrast, equilibrium binding of human LDL was slower (approximately 6 h) and the number of high-affinity binding sites (Kd = 23 nM) was much lower for this ligand (660 per trypanosome). Total binding of HDL3 was independent of divalent cations and was only slightly inhibited by heparin, but when the trypanosomes were preincubated with trypsin or pronase the binding was markedly reduced. After 30 min at 37 degrees C, binding of bovine HDL and human HDL3 was 10-20% higher than at 4 degrees C; after 45 min trypanolysis occurred with human HDL3 but not with bovine HDL. Chemical modification of HDL3 by treatment with cyclohexanedione, by acetylation or by reductive alkylation had little effect on its ability to compete with [125I]labelled HDL3 for binding by the parasite. Nitrosylation of HDL3 with tetranitromethane increased its binding ability, suggesting that trypanosomes might possess scavenger receptors, and native HDL3 was less effective than nitrosylated HDL3 in displacing bound [125I]labelled nitrosylated HDL3. These findings suggest that, in addition to a receptor for LDL, T.b.brucei has other lipoprotein binding sites which separately recognize HDL from permissive host species such as bovine, trypanolytic HDL such as human HDL3, and more negatively charged HDL particles such as nitrosylated HDL3.

Iron-transferrin binding to isolated guinea pig enterocytes and the regional localisation of intestinal iron transfer during ontogeny.

Neonatal animals are iron replete but in comparison with adults they display increased intestinal iron absorption. In order to examine possible mechanisms for this developmental adaptation we have measured the appearance of iron in peripheral blood following 30 min exposure of duodenal and ileal segments of adult and neonatal guinea pigs in vivo to 59Fe-ascorbate. Parallel experiments have determined the kinetics of 125I-labelled diferric transferrin binding to villus enterocytes isolated from duodenum and ileum. In adult animals the rate of appearance of 59Fe in peripheral blood was 11-fold greater following duodenal, compared to ileal exposure to the radioligand. No such regional difference was detected in the neonate. Isolated cells showed saturable binding of [125I]transferrin which was maximal between 30 and 60 min. The kinetics of specific transferrin binding by adult duodenal and ileal enterocytes were similar and were also not significantly different to respective values in neonatal duodenal and ileal cells. Thus, it is likely that increased iron absorption in the neonate is due in part to enhanced ileal iron transfer. The interaction of transferrin with its receptor, however, is not involved in this developmental change in uptake.

Evidence for active phospholipase A in mouse plasma.

Mouse, rat and human plasma were exposed to minimum concentrations of disulphide or minimum pre-incubation at 55 degrees C in order to inhibit lecithin : cholesterol acyltransferase activity completely. The plasma samples were subsequently incubated at 37 degrees C and changes in individual phospholipid concentrations determined. Significant utilization of phosphatidylcholine and formation of lysophosphatidylcholine occurred only in disulphide-treated mouse plasma and this was accompanied by a decrease in total phospholipid concentration. When disulphide-treated mouse plasma was incubated with [U-14C]phosphatidylcholine radioactivity was additionally recovered in the lysophosphatidylcholine, non-esterified fatty acid and glycero-3-phosphocholine fractions; maximum conversion occurred at close to physiological pH. These observations suggest that phospholipase A and lysophosphatidylcholine hydrolase enzymes are active in mouse plasma but that phospholipase A is either absent or inactive in rat and human plasma.

Plasma concentrations of lysolecithin and other phospholipids in the healthy population and in men suffering from atherosclerotic diseases.

The concentrations of individual phospholipids and of cholesterol have been determined in plasma samples taken from 77 apparently healthy individuals, and from 76 male patients presenting with atherosclerotic diseases. Significant differences in the relative and absolute concentrations of lysolecithin were found between different populations. In healthy individuals the plasma levels of lysolecithin were lower in women than in men and lower in the younger age groups studied. The relative and absolute concentrations of plasma lysolecithin were lower in men suffering from chronic ischaemic heart disease and peripheral arterial disease when compared with age-matched healthy male subjects. The lowest levels of plasma lysolecthin were, however, associated with patients suffering from acute myocardial infarction or acute myocardial ischaemia studied within 48 hr of the onset of chest pain. In a further study, significantly decreased relative concentrations of lysolecithin were found in blood platelets and erythrocytes as well as in plasma of patients suffering from chronic ischaemic heart disease. The results are discussed in terms of a possible thrombo-protective role for plasma lysolecithin in man.

Relationship between testosterone, sex hormone binding globulin and plasma amyloid beta peptide 40 in older men with subjective memory loss or dementia.

In a group of 28 older men with either subjective memory loss or dementia, serum total testosterone and sex hormone binding globulin (SHBG) correlated inversely with plasma levels of amyloid beta peptide 40 (Abeta40, r=-0.5, P=0.01 and r=-0.4, P=0.04, respectively). Calculated free testosterone was also inversely correlated (r=-0.4, P=0.03), and all three relationships remained statistically significant after allowing for age. A similar but non-significant trend was seen with dehydroepiandrosterone sulphate (DHEAS), and neither luteinising hormone (LH) nor estradiol correlated with Abeta40. These data demonstrate that lower androgen levels are associated with increased plasma Abeta40 in older men with memory loss or dementia, suggesting that subclinical androgen deficiency enhances the expression of Alzheimer's disease-related peptides in vivo. An inverse correlation exists between SHBG and Abeta40, warranting further investigation.

Trypanosoma brucei brucei: differences in the trypanocidal activity of human plasma and its relationship to the level of high density lipoproteins.

Although high density lipoprotein (HDL) particles purified from human serum by ultracentrifugation are known to lyse Trypanosoma brucei brucei, it is unclear whether individual differences in the trypanocidal activity of human serum reflect changes in the concentration of HDL per se. In the present study, trypanolytic activity, whether assessed in vitro or in vivo, was greater with plasma from normal healthy individuals than with plasma from patients with various hepatic diseases and associated low levels of HDL. For all subjects taken as a single group there were highly significant positive correlations between the plasma concentration of apolipoprotein (apo) A-I, the major protein constituent of HDL and trypanolysis in vivo (r = 0.93, n = 10, P less than 0.001) or in vitro (r = 0.77, n = 36, P less than 0.001). Removal of plasma apoB-containing (i.e. non-HDL) lipoproteins by precipitation revealed that the trypanocidal activity was also significantly correlated with HDL-cholesterol and HDL-apoA-II, as well as with HDL-apoA-I, but not with HDL-apoE. Depletion of all or part of plasma apoA-I by non-ultracentrifugal methods abolished or decreased the trypanolytic effect of the plasma. The findings from these experiments, which were designed to avoid alteration in the composition of HDL by ultracentrifugal forces, provide additional support for the proposal that the trypanocidal action of human plasma resides with native HDL particles.

Gas-liquid chromatographic determination of galactitol in amniotic fluid for possible use in prenatal diagnosis of galactosaemia.

A gas liquid chromatographic method for the estimation of galactitol in amniotic fluid from pregnancies at risk for galactosaemia is described. The method is based on the almost complete removal of glucose from the amniotic fluid by ion exchange, and the subsequent chromatography of galactitol as its hexaacetate.

Hypotriglyceridemic and hypocholesterolemic effects of anti-diabetic Momordica charantia (karela) fruit extract in streptozotocin-induced diabetic rats.

Momordica charantia (karela) is commonly used as an antidiabetic and antihyperglycemic agent in Asian, Oriental and Latin American countries. This study was undertaken to investigate the effects of long term feeding (10 weeks) of M. charantia fruit extract on blood plasma and tissue lipid profiles in normal and streptozotocin (STZ)-induced Type 1 diabetic rats. The results show that there was a significant (P < 0.05) increase in plasma non-esterified cholesterol, triglycerides and phospholipids in STZ-induced diabetic rats, accompanied by a decrease in high density lipoprotein (HDL)-cholesterol. A moderate increase in plasma (LPO) product, malonedialdehyde (MDA), and about two-fold increase in kidney LPO was also observed in STZ-induced diabetic rats. The treatment of diabetic rats with M. charantia fruit extract over a 10-week period returned these levels close to normal. In addition, karela juice also exhibited an inhibitory effect on membrane LPO under in vitro conditions. These results suggest that M. charantia fruit extract exhibits hypolipidemic as well as hypoglycemic effects in the STZ-induced diabetic rat.

Lecithin: cholesterol acyltransfer, dyslipoproteinaemia and membrane lipids in uraemia.

BACKGROUND: Dyslipoproteinaemia is the most important complication linked to the increased morbidity and mortality of uraemic patients from cardiovascular disease. Many factors contribute to the dyslipoproteinaemia, including increased production of very low density lipoproteins (VLDL), decreased lipolysis and impaired low density lipoprotein (LDL) receptor activity. In this study, the role of decreased lecithin:cholesterol acyltransferase (LCAT) activity in relation to plasma and membrane lipid changes is examined. METHODS: Fasted blood samples were taken from 65 uraemic patients, including roughly equal numbers of haemodialysis, peritoneal dialysis and undialysed subjects, and from 29 apparently healthy individuals. Plasma total and free cholesterol, cholesteryl esters (CE), total and individual phospholipids, high density lipoprotein (HDL)-, LDL- and VLDL-cholesterol were all measured, as were erythrocyte and lymphocyte free cholesterol and phospholipids. RESULTS: More than half of all patients, including those both on haemodialysis and peritoneal dialysis, as well as untreated individuals, had relative plasma concentrations of CE below the normal mean - 2SD. These patients had significantly decreased LDL- (2.62 +/- 1.04 compared to 3.61 +/- 0.97 mmol/L; p < 0.001) and HDL-cholesterol (0.71 +/- 0.30 compared to 0.94 +/- 0.27 mmol/L; p < 0.01) and increased VLDL-cholesterol (0.60 +/- 0.50 compared to 0.47 +/- 0.26 mmol/L; p < 0.05) as well as significant increases in membrane cholesterol and cholesterol/phospholipid molar ratio in erythrocytes (3.30 +/- 0.49 and 0.87 +/- 0.08 compared to 2.95 +/- 0.18 mmol/g wet weight and 0.76 +/- 0.04 mol/mol respectively, both p < 0.001) and cholesterol/phospholipid molar ratio of lymphocytes (0.58 +/- 0.14 compared to 0.45 +/- 0.04 mol/mol; p < 0.001). They were markedly deficient in LCAT activity (56.1 +/- 20.4 compared to 105.5 +/- 17.5 nmol/ml/h; p < 0.001). The LCAT activity in plasma of patients with high CE was higher than for those with low CE, but it was also significantly less than normal and this group showed smaller changes in other lipid parameters. CONCLUSIONS: LCAT deficiency is common in uraemia and is associated with changes not just in plasma lipids, but also in membrane lipids which may be relevant to the progression of the disease.

An analytical ultrastructural study of the iron-rich surface layer in rat-incisor enamel.

Electron-dense particles, approximately 4 nm (40 A) in diameter were present. Evidence is offered that these particles represent iron probably in the form of amorphous hydrous ferric hydroxide. From X-ray probe analytical data, it is suggested that this iron component is accommodated through the process of adsorption rather than by direct substitution of calcium and phosphorus. The iron-rich surface layer was more resistant to acid etching than subsurface enamel. Reported areas of reduced mineral density of enamel at the enamel-dentine junction appear to be preparation artifacts.

Inhibitory effect of high-density lipoproteins from plasma of schistosomiasis mansoni patients on the binding of normal low-density lipoproteins to cultured skin fibroblasts.

Total high-density lipoproteins (HDL) isolated from the plasma of patients suffering from hepatosplenic schistosomiasis mansoni have an abnormal apoprotein composition. The apoprotein E content is increased and one or two abnormal apoproteins with pI 6.0 and 6.5 are present in patient HDL. Whilst normal HDL have a negligible effect on the binding of 125I-labelled normal low density lipoproteins (LDL) by cultured human skin fibroblasts, patient HDL is inhibitory. It is concluded that the abnormal apoprotein composition of schistosomiasis HDL allows it to bind to the LDL receptor on the fibroblast membrane.

Alterations in the levels and lipid composition of plasma lipoproteins (VLDL, LDL and HDL) in Brazilian patients with hepatosplenic schistosomiasis mansoni.

1. The plasma concentrations of low- and high-density lipoproteins (LDL and HDL) were significantly reduced in Brazilian patients with compensated hepatosplenic schistosomiasis mansoni (SM) when compared with healthy individuals, but very low-density lipoprotein (VLDL) levels were unchanged. 2. All three classes of lipoproteins isolated from SM plasma had an increased content of triacylglycerol and unesterified cholesterol and decreased cholesteryl ester and phospholipid. 3. The individual phospholipid composition of patient VLDL, LDL, HDL was also altered; the amount of phosphatidylcholine was increased and that of lysophosphatidylcholine decreased. 4. The saturated and monounsaturated fatty acyl content of cholesteryl esters in patient lipoproteins was also significantly increased, and diunsaturated and polyunsaturated fatty acyl content was decreased. 5. When isolated lipoproteins were examined as negatively stained preparations by electron microscopy, the morphology of SM patient LDL was normal but the HDL fraction was abnormal and showed marked heterogeneity of size with the presence of occasional discoidal particles which resembled "nascent" HDL.