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Background: The clinical value and the interrelationship of HDL and the metabolic syndrome were studied using plasma levels of TNF-α, IL 6, IL 10, IL 8, IL 1beta, IL 2R in patients with cardiovascular stenosis. Methods: On the basis of exclusion criteria, we recruited 198 male and female patients aged 45 to 75 years with CVD and 43 patients with MS. Patients were subdivided into %stenosis according to the CASS guidelines. Lipids were measured on an Olympus AU640 analyzer. Ox-LDL was measured by the immunosorbent assay and MDA by HPLC. Cytokines were analysed with DPC Immulite 1000. Statistical tests were performed using SPSS for Windows, 14.0 & Medcalc. Results: Ox-LDL and apoB were significantly higher in the MS(+) patient group (88.7 U/L) compared to the MS(-) group (77.5 U/L). Ox-LDL showed a positive correlation (P=0.001) with LDL-C, apoB and MDA. There was a higher concentration of HDL in the patient group MS(-), which was confirmed by a non-significant (P=0.849) change of apoA(I) from 1.267 g/L in the MS(+) to 1.275 g/L in the MS(-) group. A light significant increase of IL 10 (P=0.05) in MS(+) patients was observed, and the other analysed inflammation markers were mostly unchanged. MS has no direct association with the cytokine production. Conclusions: Ox-LDL and apoB were significantly higher in the MS(+) patient group. In a multiple regression analysis for ox-LDL, apoB (P=0.003) emerged as a strong predictor of the ox-LDL concentration, independent of age, gender, BMI and smoking.

Medical laboratories play a vital role in modern healthcare, and qualified specialists in Clinical Chemistry and Laboratory Medicine are essential for the pro vision of high-quality preanalytical, analytical and consultative services. Laboratory medicine has undergone major transformations during the last decade. Ongoing technological developments have considerably improved the productivity of clinical laboratories. Information on laboratory services is globally available, and clinical laboratories worldwide face international competition and there is a huge pressure to reduce costs. To be prepared for the future, clinical laboratories should enhance efficiency and reduce the cost increases by forming alliances and networks, consolidating, integrating or outsourcing, and more importantly create additional value by providing know ledge services related to in vitro diagnostics. Therefore, business models that increase efficiency such as horizontal and vertical integration are proposed, based on collaborative networks for the delivery of clinical laboratory services. Laboratories should cooperate, consolidate and form strategic alliances to enhance efficiency and reduce costs. There is a growing conflict between the science and the art of clinical practice and on the role of the biomedical sciences in medical practice. We have a dehumanizing effect on medical care. Disease is defined at the level of sick molecules and cells and curative medicine is being replaced by the preventive care of the disease. Undoubtedly all those questions will raise considerable problems and challenges for the medical educators.

The observation that obesity, dyslipidemia, diabetes and hypertension occur simultaneously in many people was first made by Crepaldi in 1967. In the late 1970s this clustering of conditions was termed "metabolic syndrome" by German researchers. Since then the syndrome has been described under a number of guises as "Insulin resistance syndrome", "Syndrome X", "Plurimetabolic syndrome" and the "Metabolic syndrome". The syndrome is a multi-component disease brought on by combination of lifestyle and environmental factors, with some populations exhibiting a genetic susceptibility for its development. Metabolic syndrome increases the risk of cardiovascular disease and type 2 diabetes. The National Cholesterol Education Program - Adult Treatment Panel III (NCEP-ATP III) has recognized the metabolic syndrome as a cluster of abnormalities increasing the risk for both cardiovascular disease (CVD) and type 2 diabetes. The NCEP-ATP III guidelines have also underlined the central role of abdominal obesity in the development of this syndrome. The escalating prevalence of the syndrome has important health implications. Each component of the metabolic syndrome is an established cardiovascular disease risk factor, and the presence of multiple components confer greater risk than the sum of the risks associated with the individual ones. For instance, it has been shown that men with the simultaneous presence of fasting hyperinsulinemia, elevated apolipoprotein B concentration and an increased proportion of small LDL particles were characterized by a 20-fold increase in the risk for developing CVD over the 5-year follow-up period of the study, compared with men without this cluster of non-traditional risk markers. In addition, the risk of CVD associated with the atherogenic metabolic triad remained significant even after adjustment for traditional risk factors such as LDL-cholesterol, triglyceride and HDL-cholesterol levels. Risk assessment includes a list of biological parameters wherein lipids play an important role, especially triglycerides and HDL-particles. The traditional factors associated with the syndrome are obesity, insulin resistance, hyperglycemia, dyslipemia, hypertension and microalbuminuria. [ABSTRACT FROM AUTHOR]

The purpose of this study was to establish a relationship between self-association and phospholipid binding of the human and the baboon apoA-1 protein. The enthalpy changes on binding dimyristoyl lecithin and lysolecithin to etther the human or the baboon native apoA-I protein were measured in a microcalorimeter. An endothermal process, most pronounced for the human apoprotein, was observed at low phospholipid levels. At higher phospholipid to protein ratios the binding was exothermal. Gel filtration experiments on Sephadex G-200 showed that the native apoprotein of both species consists of dimers and tetramers. The baboon native apoA-I protein contained a higher amount of dimers. After preincubation of the apoA-I protein with lysolecithin, the enthalpy changes measured on subsequent binding of dimyristoyl lecithin were shifted towards more exotherrnal values compared to the curve for the native apoprotein. The amplitude of this shift corresponds to that of the endothermal process observed on binding dimyristoyl lecithin to the native apoprotein. This process was attributed to a phospholipid-induced disaggregation of the apoA-I protein. Gel filtration data showed a decreased extent of aggregation in the apoA-I protein preincubated with lysolecithin. This sample consisted exclusively of dimers. Ultracentrifugal flotation of the complexes formed between the apoA-I protein, and respectively dimyristoyl lecithin and spbingomyelin indicated that preincubation with lysolecithin increased the extent of complex formation. These results suggest that the dimeric form of the apoA-I protein possesses the highest affinity for phospholipids. Any dissociation of higher polymers enhances the phospholipid-binding capacity of the human and the baboon apoA-I protein. [ABSTRACT FROM AUTHOR]

Abstract: Background: Inflammation processes are considered important links between classical lipid risk factors and the progression of atherosclerosis. The interrelationship of high density lipoproteins (HDL) and apolipoprotein apoA-1 with acute phase proteins and cytokines was examined in a clinical setting of patients with angina pectoris. Methods: On exclusion criteria (myocardial infarction, heart failure, CHD>2years, anticoagulant therapy), 198 patients were recruited and were subdivided according to angiographically documented stenosis, no stenosis vs. =50% stenosis, in accordance with CASS guidelines. Lipids, apoA-1 and apoB, C-reactive protein (hs-CRP), fibrinogen, serum amyloid A (SAA) and cytokines (IL-6, IL-8, IL-10, IL2R, TNFα) were measured. Results: Low HDL-C (and apoA-I) is associated with advanced coronary stenosis (=50%) and with the number of diseased vessels, independent of age, gender, diabetes, smoking and lipid-lowering therapy. In contrast to hs-CRP and fibrinogen, SAA as well as cytokine levels were not significantly associated with stenosis. SAA (P=0.0003) and diabetes (P=0.0002) were strong predictors of apoA-I concentration independent of age, gender, BMI, smoking, CRP, as well as IL-6 in a multiple regression model. High SAA (P=0.0067) and TG (P=0.0123) were significant predictors of apoA-I/HDL-C ratio. However, SAA was not independently related to HDL-C. Conclusions: SAA is independently and inversely related to apoA-I but not to HDL-C in patients with angina pectoris, reflecting the effect of SAA on the quality of HDL particles. However, HDL-c but not SAA is inversely related to the degree of coronary artery stenosis. [Copyright &y& Elsevier]

Abstract: Background: In routine semen analysis, discrepancies may occur between sperm acrosin activity test results and sperm acrosomal morphology. Methods: Discrepant test results of sperm acrosin activity (spectrophotometric assay) vs. sperm morphology (strict criteria) in the initial diagnostic investigation of 107 infertile couples were evaluated with respect to fertilization rate (% oocytes with 2 pronuclei) further obtained in IVF treatment. Results: Acrosin activity positively correlated with sperm morphology (% normal forms) (r=0.537) and fertilization rate (r=0.526). ROC curves for the prediction of ≥50% fertilization rate were comparable for acrosin activity and sperm morphology, with optimal cutoff values at 25 μIU/106 sperm and 10%, respectively. In multiple regression analysis, sperm acrosin activity (P=0.002) predicted fertilization rate independently of sperm morphology (P<0.001) and sperm vitality (eosin–nigrosin stain) (P=0.03). Acrosin activities ≥25 μIU/106 sperm were observed in 36% of severe teratozoospermic samples (≤4% normal spermatozoa) associated with low fertilization rate. Twenty percent of the morphologically normal ejaculates showed a low acrosin activity (<25 μIU/106 sperm) and low hypoosmotic swelling test (HOST) scores (31.4±7.6%) and were associated with low fertilization rate. Conclusion: The sperm acrosin assay can help to predict sperm fertilizing capacity in IVF independently of sperm morphology. [Copyright &y& Elsevier]

Background: In vitro experimental studies demonstrated that iron promotes free radical-induced low-density lipoprotein (LDL) oxidation. Objective: To test the hypothesis that circulating oxidized LDL (oxLDL) levels might be associated with body iron stores (serum ferritin) and iron-related genetic markers (hemochromatosis gene C282Y mutation, haptoglobin polymorphism). Methods: We investigated 381 (176 males, 205 females, age 45 ± 6 years) healthy Caucasians. Serum oxLDL, assayed by a mAb-4E6-based enzyme-linked immunosorbent assay (ELISA), was expressed as oxLDL/LDL ratio to adjust for serum LDL-cholesterol concentration. Hemochromatosis gene C282Y mutation analysis was performed by a Taqman®-based polymerase chain reaction (PCR) assay. Haptoglobin (Hp) phenotypes (Hp 1-1, Hp 2-1, Hp 2-2) were determined by starch gel electrophoresis. Results: In stepwise multivariate regression analysis, gender (P < 0.0001), current smoking (P < 0.0001), HDL-cholesterol (P = 0.0001), ferritin (P = 0.0051), body mass index (BMI) (P = 0.0063), and Hp phenotype (P = 0.0331) independently predicted oxLDL/LDL ratio in the total group. In men, smoking (P < 0.0001), ferritin (P = 0.0052), Hp phenotype (P = 0.0063), and HDL-cholesterol (P = 0.0127) were independent determinants of oxLDL/LDL ratio. In women, only body mass index (P < 0.0001), HDL-cholesterol (P = 0.0005), and smoking (P = 0.0025) were significantly associated with oxLDL/LDL ratio. The C282Y mutation (wild-type versus C282Y heterozygotes) was not associated with oxLDL/LDL ratio in both sexes. Conclusion: Serum ferritin concentration and Hp polymorphism are independently associated with circulating oxLDL levels in males. [Copyright &y& Elsevier]

Background: Uric acid is frequently elevated in hypertension. In addition to renal and metabolic disturbances, lower limb ischemia might contribute to hyperuricemia among hypertensives complicated by peripheral arterial disease (PAD). Objective: To test the hypothesis that uric acid status is related to lower limb function in hypertensives with PAD. Methods: Serum and 24-h urine uric acid levels and other risk factors were examined in 145 hypertensives free of PAD and 166 hypertensives with PAD. Ankle/brachial index (ABI) and absolute claudication distance (in PAD) on a treadmill test (ACD) were assessed. Results: In multiple regression analysis for serum uric acid in the total group, PAD emerged as an independent determinant (P=0.03) next to age (P=0.005), triglycerides (P=0.04), and insulin (P=0.02). Serum uric acid concentrations were higher in hypertensives with PAD (404±101 vs. 347±80 μmol/l, P<0.001) independent of components of the metabolic syndrome (body mass index, triglycerides, insulin) and of age, gender, diabetes mellitus, pulse pressure, cholesterol, C-reactive protein, and treatment. After adjustment for kidney function by uric acid/creatinine ratio, values remained higher in hypertensives with PAD (P=0.01). Uric acid excretion was higher in the PAD group (P<0.001), whereas uric acid clearance was comparable between both groups. In multiple regression analysis for ACD (357±183 m) in the PAD group, serum uric acid (P=0.02), C-reactive protein (P<0.0001), age (P=0.02), and smoking (P=0.004) were independently associated. ABI (0.62±0.17) was not related to uric acid in PAD patients. Conclusion: Hyperuricemia is more pronounced in hypertensives complicated by PAD and is associated with worse functional status of the peripheral circulation. [Copyright &y& Elsevier]

Objective: Reported associations of oxidized low-density lipoprotein (oxLDL) with noninvasive measures of atherosclerosis are inconsistent. In the Asklepios Study cohort of asymptomatic subjects aged 35 to 55 years, we evaluated the relationship of circulating oxLDL with subclinical atherosclerosis in the carotid and femoral arteries., Methods and Results: Participants (n=2524, 51.5% females) completed a study questionnaire and underwent a clinical examination, blood analysis of oxLDL (mAb-4E6) and other risk markers, and ultrasound examination of intima-media thickness (IMT) and plaques in the left and right carotid and femoral arteries. oxLDL concentrations were highest in subjects with femoral plaques (n=658). In the group of subjects with carotid plaques (n=476), elevated oxLDL concentrations are related to concomitant femoral plaques detected in 54% of these subjects. Multivariate regression analyses (including anthropometric, hemodynamic, biochemical, and lifestyle variables) showed that femoral plaques are independently related to oxLDL whereas femoral IMT, carotid IMT, or carotid plaques were not independently associated with oxLDL., Conclusions: Circulating oxLDL is independently associated with femoral plaque and not with carotid artery wall damage.

The professional duties of the specialists in clinical chemistry differ from country to country in Europe. One of the main goals of the Strategic Plan of the Forum of the European Societies of Clinical Chemistry and Laboratory Medicine (FESCC; IFCC-Europe) is to promote a high scientific and professional standard in the field of clinical chemistry and laboratory medicine in Europe. This can be stimulated by the knowledge of the local conditions in each country and by striving towards a strong and harmonised position in all the European countries. In order to enhance the knowledge of the managerial situation of the specialists in clinical chemistry in Europe, FESCC launched a survey in September 2000. This survey provides information about the position of the specialists in clinical chemistry in the various disciplines in the medical laboratories and in hospitals, and about the advisory tasks and the managerial education during the post-graduate training in clinical chemistry. Of the 35 FESCC member countries 33 have participated in the survey (94%). The results show a rather heterogeneous situation in Europe caused by the local historical developments, the differences in academic background and the relative numbers of private and physicians' office laboratories. Large differences exist between the European countries in the disciplines of laboratory medicine that are headed by a specialist in clinical chemistry. In the different countries the clinical chemistry laboratories are headed by specialists in clinical chemistry in between 20% and 100% of the laboratories. The haematology, immunology, microbiology, therapeutic drug monitoring, molecular biology and haemostasis laboratories and departments of blood banking are headed by specialists in clinical chemistry in between 0% and 100% of the laboratories. The responsibilities for the various managerial tasks of the specialists in clinical chemistry show no uniformity in Europe. In the majority of the countries the general management, the purchase of equipment and reagents and the education of technicians are in >90% the responsibility of the specialists in clinical chemistry. In most countries the majority of the specialists in clinical chemistry are members of the medical staff of the hospitals and have a position equivalent to the position of specialists in other medical disciplines. In some countries, however, it only holds true for the specialists with a medical background. In 79% of the countries the law regulates the profession of the specialists in clinical chemistry and in 60% of the countries the law regulates their position in the medical staff of the hospital. The advisory tasks to physicians, general practitioners and other users of laboratory tests are practised by >90% of the laboratories in 64% of the countries. Information is given directly to the patients by >90% of the laboratories in 30% of the countries. Only in a few countries laboratories give information to the public. The post-graduate training in clinical chemistry includes a managerial training in 58% of the countries, the study of information technology in 61% of the countries and an economy and/or a business administration study in 15% of the countries. In 27% of the countries no managerial education forms part of the post-graduate study in clinical chemistry. Harmonisation of the managerial aspects of the profession is one of the challenges for the European specialists in clinical chemistry. A European syllabus for post-graduate training could be helpful.