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Biomedical subjects

W März

Publications and source records attributed to W März.

At least 19 recordsLinked to original sources
PubMed2006

The serotonin transporter gene polymorphism is not associated with smoking behavior.

Nicotine increases serotonin release in the brain and symptoms of nicotine withdrawal may be modulated by diminished serotonergic neurotransmission. The promoter region of the serotonin transporter gene, solute carrier family neurotransmitter transporter member 4 (SLC6A4), contains a functional tandem repeat polymorphism. The long (L) variant is more actively transcribed than the short (S) variant and is associated with a higher serotonin uptake. To investigate the potential role of this polymorphism for smoking behavior, SLC6A4 genotypes were determined in two different studies, the SMOKING GENES case-control study (470 current smokers and 419 subjects who had never smoked) and the cross-sectional Ludwigshafen risk and cardiovascular health (LURIC) study (777 current smokers and 1178 subjects who had never smoked). In the SMOKING GENES case-control study, SLC6A4 genotype frequencies were not statistically different between smokers (LL: 30.9%; LS: 46.8%; SS: 16.4%) and non-smokers (LL: 36.3%; LS: 41.8%; SS: 14.3%; P=0.13). Similar results were obtained in the cross-sectional LURIC study (smokers: LL, 36.5%, LS, 45.6%, SS, 17.9%; non-smokers: LL, 33.6%, LS, 48.9%, SS, 17.6%; P=0.33). SLC6A4 genotypes were furthermore not associated with Fagerstrom Tolerance Questionnaire score, packyears, number of cigarettes smoked per day or previous attempts to quit smoking. We conclude that the SLC6A4 promoter polymorphism is not a major determinant of smoking behavior in Caucasian.

Adult↗
PubMed2006

Unmet needs in the diagnosis and treatment of dyslipidemia in the primary care setting in Germany.

OBJECTIVES AND METHODS: DETECT is a cross-sectional study of 55,518 unselected consecutive patients in 3188 representative primary care offices in Germany. In a random subset of 7519 patients, an extensive standardized laboratory program was undertaken. The study investigated the prevalence of cardiovascular disease, known risk factors (such as diabetes, hypertension and dyslipidemia and their co-morbid manifestation), as well as treatment patterns. The present analysis of the DETECT laboratory dataset focused on the prevalence and treatment of dyslipidemia in primary medical care in Germany. Coronary artery disease (CAD), risk categories and LDL-C target achievement rates were determined in the subset of 6815 patients according to the National Cholesterol Education Program (NCEP) ATP III Guidelines. RESULTS: Of all patients, 54.3% had dyslipidemia. Only 54.4% of the NCEP-classified dyslipidemic patients were diagnosed as 'dyslipidemic' by their physicians. Only 27% of all dyslipidemic patients (and 40.7% of the recognized dyslipidemic patients) were treated with lipid-lowering medications, and 11.1% of all dyslipidemic patients (41.4% of the patients treated with lipid-lowering drugs) achieved their LDL-C treatment goals. In conclusion, 80.3% of patients in the sample with dyslipidemia went undiagnosed, un-treated or under-treated.

Blood Chemical Analysis↗
PubMed2006

[Can antioxidants prevent atherosclerosis?].

In vitro studies have shown that antioxidants (e. g. beta-carotene, vitamin C and vitamin E) can interfere with some pathomechanisms of atherosclerosis and therefore might have a protective effect. From the investigated antioxidants vitamin E showed the best effect. Some animal and epidemiological studies confirmed such a protective effect in vivo especially after administration of high doses of vitamin E. However, most of the placebo-controlled studies for primary or secondary prevention failed to show a protective effect even after administration of high doses. In addition, other studies demonstrated a risk for adverse effects due to antioxidant supplementation (beta-carotene and vitamin E). Our review summarises the principle of antioxidant supplementation and a number of relevant epidemiological and clinical studies for prevention of atherosclerosis. The obtained results suggest that supplementation of antioxidants cannot be recommended for the normal population.

Adult↗
PubMed2005

[Cardiovascular high-risk constellations in primary care. DETECT Study 2003].

DETECT is a nationwide epidemiological cross-sectional and longitudinal study program in a random probability sample of 3,795 primary care settings (response rate: 60.2%). Based on a target day total assessment of n=55,518 consecutive patients (RR 93.5%) in these settings all patients underwent standardized diagnostic assessment, using self-reporting, clinical interview and laboratory measures. DETECT aims at describing the point prevalence and comorbidity of coronary heart disease (CHD), hyperlipidaemia, arterial hypertension and diabetes mellitus and at identifying the behavioural, clinical, laboratory and psychological risk factors associated with these conditions. A random subset of patients (n=7,519) also completed an extensive standardized laboratory screening program and a 12-month follow-up investigation. Findings reveal a high prevalence of hypertension (36.3%), dyslipidaemia (29.1%), diabetes mellitus (14.6%) and CHD (12.4%) in primary care as well as their close association among each other. The study describes for the first time in greater detail the prevalence of specific disorders and the frequency of high-risk constellations in primary care and allows for the evaluation of various risk scores.

Adolescent↗
PubMed2005

Association of polymorphisms of platelet membrane integrins alpha IIb(beta)3 (HPA-1b/Pl) and alpha2(beta)1 (alpha807TT) with premature myocardial infarction.

Conflicting results of an association of the human platelet antigen 1b (HPA-1b/PlA2), localized on the beta-subunit of the integrin alpha(IIb)beta3, and the alpha(2)807TT genotype of the integrin alpha2beta1 with coronary atherosclerosis and myocardial infarction have been reported. Both platelet receptor polymorphisms were genotyped in 3261 patients who had undergone coronary angiography, including 1175 survivors of a myocardial infarction, 1211 individuals with coronary artery disease but no history of myocardial infarction, and 571 control patients without angiographic coronary artery disease, and in 793 blood donors. In a case-control design, the prevalence of HPA-1b and alpha(2)807TT genotypes did not differ significantly between the patient groups with coronary artery disease or myocardial infarction and patient controls or blood donors. By contrast, using a multivariate case-only design, it was found that the median age of onset of myocardial infarction was 5.2 years earlier (P = 0.006) in carriers of the HPA-1b allele and 6.3 years earlier (P = 0.006) in carriers of the alpha(2)807TT genotype in the 264 survivors of myocardial infarction of recent onset with one- or two-vessel coronary artery disease. A significant interaction with the conventional risk factors hypercholesterolemia, smoking, diabetes, hypertension, and hyperfibrinogenemia was excluded. Human platelet antigen 1b and alpha(2)807TT are associated with premature myocardial infarction but not with coronary artery disease, suggesting a role of distinct integrin genotypes for increased platelet thrombogenicity. This association requires confirmation in follow-up studies.

Age of Onset↗
PubMed2005

Cardiovascular risk factors in primary care: methods and baseline prevalence rates--the DETECT program.

OBJECTIVES: DETECT is an epidemiological study in primary care to examine (a) the prevalence rates and comorbidity of diabetes mellitus, hypertension, hyperlipidaemia and coronary heart disease (CHD), and associated conditions; (b) the frequency of behavioural and clinical risk factors for onset and progression; (c) the 12-month course and outcome; and (d) the met and unmet needs for these patients. METHODS: Three-stage, cross-sectional clinical-epidemiological study with a prospective-longitudinal component in a nationally representative sample of N = 3795 primary care settings [response rate (RR): 60.2%] and N = 55518 patients (RR: 95.5%). Patients completed a standardized assessment, including questionnaires for patients and the physician and diagnostic screening measures (i.e. blood pressure, heart rate, body mass index and waist circumference assessments). A subsample of patients (N = 7519) also completed a standardized laboratory screening program and was followed-up after 12 months. Data were weighted to adjust for non-response, regional distribution and attrition. RESULTS: (1) Doctors and patients sample can be regarded as representative for primary care settings in Germany. (2) The clinician-rated point prevalence of hypertension is highest (35.5%), followed by hyperlipidaemia (29.1%), diabetes (14.1%) and CHD (12.1%); prevalence rates of each disorder as well as their co-incidence rates increase markedly with age. (3) The vast majority (78%) of all patients revealed multiple (3+) behavioural and clinical risk factors. CONCLUSION: The findings of DETECT underline the considerable burden for primary care doctors in managing a highly morbid patient population, with predominantly complex risk factor constellations, in routine care. Our data provide, in unprecedented detail, a basis for calculating age-, gender- and risk-group-adjusted risk-factor profiles in routine care.

Adolescent↗
PubMed2005

Midazolam and its metabolites in brain death diagnosis.

OBJECTIVE: There is only limited knowledge on the pharmacokinetics of midazolam and its active metabolites in potential organ donors. Before establishing the diagnosis of brain death, drugs interfering with the neurological assessment have to be washed out. National guidelines advise a waiting time of 12 hours. The aim of our study was to evaluate whether it is sufficient to rely on a calculated waiting time. METHODS: As examples of typical pharmacokinetics of midazolam and its metabolites, we followed the concentration over time in four potential organ donors with immunoassays and high-performance liquid chromatography (HPLC). RESULTS AND CONCLUSIONS: In each of the 4 patients studied, the elimination of midazolam and/or midazolam metabolites was delayed. As long as brain death diagnosis requires that drugs interfering with the clinical assessment must be at levels below the therapeutic range, monitoring of midazolam and metabolites appears mandatory.

Adjuvants, Anesthesia↗
PubMed2004

The PlA1/A2 polymorphism of platelet glycoprotein IIIa is not associated with the risk of type 2 diabetes. The Ludwigshafen Risk and Cardiovascular Health study.

AIMS/HYPOTHESIS: The PlA1/A2 polymorphism of platelet glycoprotein IIIa (GPIIIa) has been implicated in the pathogenesis of type 2 diabetes. We studied this polymorphism in a homogenous, extensively phenotyped cohort using the candidate gene approach. METHODS: The PlA1/A2 polymorphism was determined in 1051 patients with type 2 diabetes and in 2247 individuals without type 2 diabetes. RESULTS: In patients with type 2 diabetes, genotype frequencies were as follows: PlA1/A1 71.4%, PlA1/A2 26.0%, and PlA2/A2 2.7%. In individuals without type 2 diabetes, genotype frequencies were 71.6%, 25.7% and 2.8%, respectively. The PlA2 allele was not associated with fasting and postprandial glucose, glycated haemoglobin, insulin, proinsulin, C-peptide and calculated indices of insulin resistance or pancreatic beta cell function. The PlA2 allele was also not significantly associated with angiographic CHD (adjusted odds ratio [OR] 1.13; 95% CI, 0.93-1.39) or with a history of previous myocardial infarction (adjusted OR 1.09; 95% CI, 0.87-1.37). CONCLUSIONS/INTERPRETATION: The GPIIIa PlA1/A2 polymorphism is not associated with type 2 diabetes, glucose metabolism, angiographic CHD or myocardial infarction.

Aged↗
PubMed2004

Association between the A-2518G polymorphism in the monocyte chemoattractant protein-1 gene and insulin resistance and Type 2 diabetes mellitus.

AIMS/HYPOTHESIS: The molecular mechanisms of obesity-related insulin resistance are incompletely understood. Macrophages accumulate in adipose tissue of obese individuals. In obesity, monocyte chemoattractant protein-1 (MCP-1), a key chemokine in the process of macrophage accumulation, is overexpressed in adipose tissue. MCP-1 is an insulin-responsive gene that continues to respond to exogenous insulin in insulin-resistant adipocytes and mice. MCP-1 decreases insulin-stimulated glucose uptake into adipocytes. The A-2518G polymorphism in the distal regulatory region of MCP-1 may regulate gene expression. The aim of this study was to investigate the impact of this gene polymorphism on insulin resistance. METHODS: We genotyped the Ludwigshafen Risk and Cardiovascular Health (LURIC) cohort ( n=3307). Insulin resistance, estimated by homeostasis model assessment, and Type 2 diabetes were diagnosed in 803 and 635 patients respectively. RESULTS: Univariate analysis revealed that plasma MCP-1 levels were significantly and positively correlated with WHR ( p=0.011), insulin resistance ( p=0.0097) and diabetes ( p<0.0001). Presence of the MCP-1 G-2518 allele was associated with decreased plasma MCP-1 ( p=0.017), a decreased prevalence of insulin resistance (odds ratio [OR]=0.82, 95% CI: 0.70-0.97, p=0.021) and a decreased prevalence of diabetes (OR=0.80, 95% CI: 0.67-0.96, p=0.014). In multivariate analysis, the G allele retained statistical significance as a negative predictor of insulin resistance (OR=0.78, 95% CI: 0.65-0.93, p=0.0060) and diabetes (OR=0.80, 95% CI: 0.66-0.96, p=0.018). CONCLUSIONS/INTERPRETATION: In a large cohort of Caucasians, the MCP-1 G-2518 gene variant was significantly and negatively correlated with plasma MCP-1 levels and the prevalence of insulin resistance and Type 2 diabetes. These results add to recent evidence supporting a role for MCP-1 in pathologies associated with hyperinsulinaemia.

Adenine↗
PubMed2004

[Recommendations for statin therapy in the elderly].

Elderly patients are significantly less likely to receive statins than younger patients possibly because of doubts regarding compliance or concerns regarding the increased likelihood of adverse events and drug interactions. Poor compliance can be expected especially in patients suffering from dementia or depression as well as those whose stage of cardiovascular disease exhibits few symptoms. On the other hand, the clinical significance of CHD events is high in the elderly, and 80% of coronary deaths occur in patients aged over 65 years. The average statistical life expectancy of elderly and old patients is often underestimated. The HPS and PROSPER studies showed that statins reduce mortality and morbidity even in very elderly individuals with a high global cardiovascular risk and/or CAD. Patients up to the age of 79 years should be treated according to the same guidelines as younger patients. Statin therapy should only be considered for patients aged 80 years and older who are at a very high risk for cardiovascular events.

Aged↗
PubMed2004

Diabetes and cardiovascular risk evaluation and management in primary care: progress and unresolved issues - rationale for a nationwide primary care project in Germany.

This review highlights established and more recently recognized risk factors for coronary heart disease (CHD) relevant for patients seen in primary care, emphasizing the key role of diabetes mellitus type 2. Recent trends in risk factor research as well as current methods of risk stratification, and new systemic markers are discussed. Beyond the need for more forceful public health strategies to improve early recognition and intervention, the necessity of an integrated comprehensive investigation of the overall characteristics of cardiovascular disease, especially in primary care patients as a prerequisite for future concerted actions is pointed out. Based on this, a large-scale epidemiological investigation focusing on CHD and diabetes in the primary care sector is suggested.

Cardiovascular Diseases↗
PubMed2004

Qualitative effect of fenofibrate and quantitative effect of atorvastatin on LDL profile in combined hyperlipidemia with dense LDL.

INTRODUCTION: The association of elevated plasma triglyceride concentrations, decreased HDL-cholesterol, and dense LDL (dLDL) is referred to as the atherogenic lipoprotein phenotype. dLDL particularly plays a role in the metabolic syndrome and type 2 diabetes and may be one of the factors responsible for the increased risk for coronary artery disease in these patients. The effect of fenofibrate and atorvastatin on the LDL subfraction profile in patients with combined hyperlipidemia and a preponderance of dLDL was studied in a sequential design. METHODS: Six male patients with combined hyperlipidemia and dLDL received 160 mg/die supra-bioavailable fenofibrate. After a washout phase of 8 weeks all patients received 10 mg/die atorvastatin for another 8 weeks. At baseline, after fenofibrate, and after atorvastatin treatment LDL subfractions were analyzed by equilibrium density gradient ultracentrifugation. RESULTS: Treatment with atorvastatin and fenofibrate reduced serum cholesterol by 30 % and 21 % (p = 0.046) (p-values for differences between treatment groups), triglycerides by 32 % and 45 %, LDL cholesterol by 28 % and 16 %, and increased HDL cholesterol by 3 % and 6 %, respectively. Atorvastatin and fenofibrate treatment resulted in the following changes of apoB and LDL subfractions: LDL-1 (1.019 - 1.031 kg/L) - 31 % and + 15 % (p = 0.028); LDL-2 (1.031 - 1.034 kg/L) - 14 % and + 57 % (p = 0.028); LDL-3 (1.034 - 1.037 kg/L) - 20 % and + 30 % (p = 0.028); LDL-4 (1.037 - 1.040 kg/L) - 25 % and - 6 %; LDL-5 (1.040 - 1.044 kg/L) - 29 % and - 38 %; and LDL-6 (1.044 - 1.063 kg/L) - 39 % and - 55 % (p = 0.028). As a consequence, fenofibrate reduced LDL density significantly (p = 0.028 versus atorvastatin). CONCLUSIONS: Atorvastatin decreased all LDL-subfractions to a similar extent (quantitative effect) whereas fenofibrate reduced predominantly dLDL and changed the LDL profile towards medium dense LDL-particles (qualitative effect). Since medium dense LDL have a higher affinity to the LDL-receptor fenofibrate may have a higher antiatherogenic potential than assessed by the reduction of total LDL-cholesterol and triglycerides alone.

Adult↗
PubMed2004

Inhibition of HMG-CoA reductase with cerivastatin lowers dense low density lipoproteins in patients with elevated fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus.

OBJECTIVE: While 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors effectively decrease LDL cholesterol, it remains controversial whether these agents also lower dense LDL, which are considered particularly atherogenic. METHODS: We examined the effects of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor cerivastatin on lipids, lipoproteins, and apolipoproteins in 69 patients with elevated fasting glucose, impaired glucose tolerance, or type 2 diabetes, combined hyperlipoproteinemia and increased concentrations of dense LDL (apo B in LDL-5 plus LDL-6 > 25 mg/dl). The study was a multicenter, double-blind, randomized, parallel-group comparison of cerivastatin at 0.4 mg daily for 12 weeks (n = 34) and placebo (n = 35). RESULTS: Cerivastatin significantly reduced cholesterol (- 20 %, p < 0.001), IDL cholesterol - 37 %, p < 0.001), LDL cholesterol (- 26 %, p < 0.001), apolipoprotein B (- 25 %, p < 0.001), triglycerides (- 12 %, p < 0.05), and raised HDL cholesterol (+ 7.5 %, p < 0.05) and apolipoprotein AI (+ 7.2 %, p < 0.05). Cerivastatin signficantly lowered apolipoprotein B in all LDL subfractions (- 21 to - 28 %, p < 0.05). Absolute changes were greatest in dense LDL and the change in dense LDL made the largest contribution to the change of total LDL. The change of dense LDL was highly correlated with baseline values. There was no consistent relationship between the effect of cerivastatin on triglycerides and the decrease of dense LDL. CONCLUSIONS: The HMG CoA reductase inhibitor cerivastatin lowers total and LDL cholesterol and the concentration of dense LDL in patients with elevated fasting glucose, impaired glucose tolerance or type 2 diabetes.

Adult↗
PubMed2004

Different effects of abciximab and cytochalasin D on clot strength in thrombelastography.

Maximum amplitude (MA) in thrombelastography (TEG) consists of a plasmatic and a platelet component. To assess the magnitude of the plasmatic component, pharmacological approaches have been proposed to eliminate the platelet component. We evaluated the individual and combined effects of abciximab and cytochalasin D on the MA of TEG. Whole blood, platelet-rich plasma (PRP) and homologous platelet-poor plasma (PPP) from 20 healthy volunteers were spiked with abciximab or cytochalasin D or a combination of both and TEGs performed. Abciximab and cytochalasin D decreased MA in all samples. MA of whole blood (18.6 +/- 3.1 mm) and PRP (33.7 +/- 3.5 mm) spiked with abciximab or cytochalasin D alone (15.0 +/- 2.9 mm and 25.0 +/- 4.0 mm) were significantly higher when compared with abciximab and cytochalasin D combined (10.4 +/- 3.0 and 20.2 +/- 3.5 mm). While MA of PRP and homologous PPP were significantly (P < 0.001) different after individual administration of abciximab and cytochalasin D, combination of both abolished this difference (20.2 +/- 3.5 mm and 20.4 +/- 3.7 mm, P = 0.372). In whole blood of critically ill patients or patients undergoing major surgery there was also a significant difference of MA between abciximab alone and in combination with cytochalasin D (16.5 +/- 11.3 mm and 11.3 +/- 7.7 mm, P < 0.001). This indicates that in contrast to individual administration of abciximab or cytochalasin D, a combination of both compounds eliminates the platelet-specific effect on MA of TEG tracings.

Abciximab↗
PubMed2004

The use of atorvastatin treatment in usual care environments: pooled analysis of six prospective, observational studies in 90,535 patients.

OBJECTIVE: We investigated the pattern of use as well as the efficacy and safety of atorvastatin in unselected inpatients and outpatients in routine clinical practice in Germany. DESIGN: Six prospective, observational studies with a similar design were pooled. The studies lasted for up to 12 weeks and data from 90,535 patients (7,287 inpatients, 83,248 outpatients) were collected. The studies were performed in Germany in 2000 and 2001. Hospital or office-based physicians selected hyperlipemic patients with or without coronary heart disease (CHD) for once daily treatment with atorvastatin. Information on demographics, atorvastatin dosage, concomitant medication, concomitant diseases, cardiovascular risk factors, lipid profile as well as adverse events (AEs) and serious adverse events (SAEs) were obtained at 2-3 visits and descriptively analyzed. MAIN OUTCOME MEASURES: Absolute and relative changes in lipid parameters, percentage of patients with low-density lipoprotein cholesterol (LDL-C) values within target ranges according to the National Cholesterol Education Program (NCEP) criteria, and frequencies of AEs. RESULTS: On average, patients were treated for 22.4 days (inpatients) and 106.0 days (outpatients), respectively. The overall mean atorvastatin dose of 14.4 mg/day was well tolerated by a heterogeneous patient population with a variety of concomitant diseases and medications. Overall, 0.8% of patients suffered from one or more AEs, 0.6% were considered as treatment-related. The corresponding figures for SAEs and treatment-related SAEs were 0.1% (131 patients) and 0.01% (13 patients), respectively. Subgroup analyses did not reveal a particular safety concern in any subgroup. In total, 99% of patients judged the tolerability of atorvastatin as very good or good. The mean percentages of reduction in LDL-C at the final visit ranged between 24.8% and 28.5%. Overall, 26.3% of patients reached the NCEP LDL-C goal compared to 4.9% at baseline. Inpatients achieved the target range for LDL-C more frequently than outpatients (35.3% vs 25.6%). An underuse of atorvastatin titration in clinical practice in Germany was apparent, particularly in outpatients. CONCLUSIONS: The use of atorvastatin in usual care environments is effective and safe. There is a gap between treatment guidelines and clinical practice in Germany as reflected by the number of patients outside the target range for LDL-C. A major opportunity exists to increase the number of patients who achieve LDL-C target ranges by appropriate dose titration and/or giving patients a higher initial dose. Available guidelines need to be implemented more stringently.

Anticholesteremic Agents↗
PubMed2003

[LDL cholesterol in normal range. The lower the better? Implications of the GREACE study].

The higher an individual patient's risk, the greater the clinical effect of lipid lowering drug therapy. According to present guidelines, therapeutic decisions should be guided by the patient's overall risk. This depends not only on the LDL cholesterol, but also on the number and degree of other risk factors. This paper will show that LDL cholesterol before treatment determines the clinical efficacy of a statin: for instance, using a statin to lower the LDL cholesterol by one third gives a greater risk reduction the higher the baseline value. For a given baseline value, greater risk reduction results from a larger reduction in LDL cholesterol. LDL cholesterol measurement is thus essential before and on treatment.

Angioplasty, Balloon, Coronary↗
PubMed2003

Apolipoprotein E (apoE) uptake and distribution in mammalian cell lines is dependent upon source of apoE and can be monitored in living cells.

As part of investigations of the cellular uptake of apolipoprotein E (apoE) relevant to Alzheimer's disease we have found that different preparations of apoE are handled differently by cells expressing the LDL-receptor. Comparing recombinant, cellular and native apoE, complexed with different preparations of lipid we find that only cellular and native apoE enter a vesicular compartment. Some, but not all of these apoE containing vesicles are lysosomes. In order to further examine the intracellular fate of apoE we demonstrate that apoE-Enhanced green fluorescent protein chimeric protein can be taken up from medium by recipient cells and tracked within these cells for extended periods.

Animals↗