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1.
Adv Exp Med Biol ; 832: 15-23, 2015.
Article in English | MEDLINE | ID: mdl-25300684

ABSTRACT

Measurement of high sensitivity CRP (hsCRP) and lipoprotein-associated phospholipase A2 (LpPLA2) provides information on systemic inflammation and stability of atherosclerotic plaques. Data analyzing the effect of smoking on these parameters are sparse. The aim of our study was the analysis of these parameters in active smokers and never-smokers. The study included 777 smokers and 1,178 never-smokers, of whom 221 and 302 died during a follow-up, respectively. The values of LpPLA2 and hsCRP were significantly higher in smokers than in never-smokers. Mortality was highest in smokers and never-smokers with elevation of both biomarkers. Multivariate adjusted hazard ratios for patients in the highest tertile of both hsCRP and LpPLA2 compared with patients in the lowest tertile of both markers were 1.85 (1.04-3.28) in never-smokers and 1.94 (1.10-3.45) in smokers. Our data confirmed the predictive value of hsCRP and LpPLA2. However, there were a relevant number of patients with an increase of only one of these parameters. Therefore, beside other risk factors for cardiovascular disease, both parameters should be determined at least in high risk patients.


Subject(s)
1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics , C-Reactive Protein/genetics , Cardiovascular Diseases/genetics , Smoking/adverse effects , 1-Alkyl-2-acetylglycerophosphocholine Esterase/blood , Aged , Biomarkers/blood , C-Reactive Protein/metabolism , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Case-Control Studies , Female , Gene Expression , Humans , Male , Middle Aged , Proportional Hazards Models , Risk Factors , Survival Analysis
2.
Exp Clin Endocrinol Diabetes ; 119(10): 649-55, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22068558

ABSTRACT

OBJECTIVE: Evidence is emerging that aldosterone contributes to the development and progression of atherosclerosis and cardiovascular disease. Little is known, however, regarding an association between circulating aldosterone levels and soluble cellular adhesion molecules in humans. METHODS: We investigated the relationship between plasma aldosterone concentration (PAC) and soluble cellular adhesion molecules in a large cohort of patients referred to coronary angiography. After exclusion of patients with ongoing mineralocorticoid receptor blocker use, oral contraceptive or hormone replacement therapy, 1,733 patients (mean age: 62.5±10.8 years; 26.4%% women; mean PAC: 101.5±93.5 pg/mL) remained eligible for analyses. RESULTS: Pearson correlation analysis as well as age and gender adjusted partial correlation analysis revealed a positive association between PAC and soluble (s) E-, L- and P-selectin levels but not with sICAM-1 and sVCAM-1, respectively. In multivariate adjusted analyses of covariance (ANCOVA) sE- (p=0.026), sL- (p=0.049) and sP-selectin (p<0.001) levels increased steadily from the first (reference) to the third gender-specific tertile of PAC. No significant variation across PAC tertiles was found for sICAM-1 (p=0.767) and sVCAM1 (p=0.425) levels, respectively. Finally, multivariate regression analyses revealed circulating aldosterone as an important predictor for soluble selectin levels. CONCLUSION: Our findings in a large cohort of patients indicate that upregulation of selectins might represent a novel mechanism of aldosterone mediated development and progression of atherosclerosis. In view of aldosterone as a novel cardiovascular risk factor independent of angiotensin II, our findings warrant further interventional studies which should evaluate anti-atherosclerotic effects of aldosterone blocking treatment strategies in humans.


Subject(s)
Aldosterone/blood , Atherosclerosis/blood , E-Selectin/blood , Heart Failure/blood , L-Selectin/blood , P-Selectin/blood , Up-Regulation , Aged , Atherosclerosis/diagnostic imaging , Atherosclerosis/epidemiology , Atherosclerosis/physiopathology , Cohort Studies , Coronary Angiography , E-Selectin/chemistry , Europe/epidemiology , Female , Heart Failure/diagnostic imaging , Heart Failure/epidemiology , Heart Failure/physiopathology , Humans , Intercellular Adhesion Molecule-1/blood , Intercellular Adhesion Molecule-1/chemistry , L-Selectin/chemistry , Male , Middle Aged , Models, Biological , P-Selectin/chemistry , Prevalence , Risk Factors , Severity of Illness Index , Solubility , Vascular Cell Adhesion Molecule-1/blood , Vascular Cell Adhesion Molecule-1/chemistry
3.
Horm Metab Res ; 42(7): 502-6, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20352598

ABSTRACT

Two strongly correlated polymorphisms located within the gene of the glucokinase regulator protein (GKRP), rs780094 and rs1260326, are associated with increased plasma triglyceride levels and provide a genetic model for the long-term activation of hepatic glucokinase. Because pharmacological glucokinase activators are evaluated for the treatment of diabetes, the aim of the study was to assess if these polymorphisms could provide evidence for an increased cardiovascular risk of long-term glucokinase activation. Therefore, these polymorphisms were tested in 3 500 patients of the Ludwigshafen Risk and Cardiovascular Health study, which was designed to assess cardiovascular risk factors. The two variants were associated with a significant increase of both plasma triglycerides (p<0.0001) and VLDL triglyceride levels (p<0.0001). Plasma free fatty acid concentrations were also significantly elevated (p<0.0078). LDL and HDL cholesterol levels were unchanged. No association was found with respect to coronary stenosis, myocardial infarction, left ventricular wall hypertrophy, and hypertension. In conclusion, long-term genetic glucokinase activation by the GKRP polymorphisms was not associated with an increased cardiovascular risk in the study population.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/genetics , Fatty Acids, Nonesterified/blood , Glucokinase/metabolism , Polymorphism, Genetic , Triglycerides/blood , Adaptor Proteins, Signal Transducing/metabolism , Aged , Aged, 80 and over , Cardiovascular Diseases/blood , Cohort Studies , Female , Germany , Health Surveys , Humans , Male , Middle Aged , Prospective Studies , Risk Factors
4.
J Thromb Haemost ; 7(1): 41-8, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18983494

ABSTRACT

BACKGROUND: There is increasing evidence that lipoprotein-associated phospholipase A2 (LpPLA2) is associated with cardiovascular disease. However, it is still unclear whether LpPLA2 is simply a marker or has a causal role as either a pro- or anti-atherogenic factor. METHODS: We analyzed the association of five polymorphisms (-1357G>A, -403T>C, Arg92His, Ile198Thr, Ala379Val) and related haplotypes at the PLA2G7 locus with angiographic coronary artery disease (CAD), plasma LpPLA2 activity, and long-term survival in 3234 patients scheduled for coronary angiography. RESULTS: The promoter variant -403C and His(92) were associated with a decrease and Val(379) with an increase in plasma LpPLA2 activity. Both coding variants revealed a clear gene-dose effect. Interestingly, the rare Thr(198) allele, which was not associated with any change in plasma LpPLA2 activity, was more frequent in subjects without CAD (P = 0.009), with an adjusted odds ratio for CAD of 0.69 (95% CI: 0.49-0.96; P = 0.029). None of the analyzed variants showed any robust association with all-cause or cardiovascular mortality. CONCLUSION: Irrespective of the significant association between some variants with plasma LpPLA2 activity, it is still unclear whether these polymorphisms or haplotypes are associated with the risk and outcome of cardiovascular disease in Caucasians.


Subject(s)
1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics , Cardiovascular Diseases/genetics , Polymorphism, Genetic , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Gene Dosage , Haplotypes , Humans , Promoter Regions, Genetic/genetics , Survival Rate
5.
Exp Clin Endocrinol Diabetes ; 117(3): 113-8, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18726867

ABSTRACT

BACKGROUND: The L162V single nucleotide polymorphism in PPARA is suggested to play an important role in the pathogenesis of type 2 diabetes, obesity, and body fat composition. However, clinical evidence is controversial. OBJECTIVE: Our aim was to investigate the relationships of the L162V SNP with type 2 diabetes, pre-diabetes phenotypes, adiposity, and plasma lipid levels. In addition, we studied the associations of the L162V SNP with body fat composition, intramyocellular lipids, and liver fat content. Furthermore, we examined if the L162V SNP was associated with changes in BMI, insulin secretion, insulin resistance, body fat composition, intramyocellular lipids, and liver fat content in response to lifestyle intervention. MATERIAL AND METHODS: Data from two large cross sectional studies, the combined TULIP/TUEF cohorts, and the LURIC study were analysed. Prospective data were obtained from TULIP participants who underwent a lifestyle intervention. A total of 4,779 subjects were studied. BMI was measured in all subjects. Type 2 diabetes was diagnosed in a subgroup of the LURIC study. In the TULIP study total body fat, non-visceral adipose tissue, and visceral adipose tissue were measured with magnetic resonance tomography. Liver fat and intramyocellular lipid content were quantified with (1)H magnetic resonance spectroscopy. Insulin sensitivity and insulin secretion were estimated from oral glucose tolerance testing. RESULTS: The L162V SNP was neither associated with type 2 diabetes or BMI nor with body fat composition, intramyocellular lipids or liver fat content. CONCLUSIONS: According to our study, the L162V SNP does not have a strong impact on the pathogenesis of type 2 diabetes or obesity.


Subject(s)
Body Fat Distribution , Body Mass Index , Diabetes Mellitus, Type 2 , PPAR alpha/genetics , PPAR alpha/metabolism , Polymorphism, Single Nucleotide/genetics , Adult , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Female , Humans , Leucine/genetics , Leucine/metabolism , Male , Middle Aged , Risk Factors
6.
J Thromb Haemost ; 6(2): 291-6, 2008 02.
Article in English | MEDLINE | ID: mdl-18021303

ABSTRACT

BACKGROUND: Whether factor XII (FXII) activity, its 46C>T polymorphism and activated FXII (FXIIa) are associated with coronary heart disease (CHD) remains to be determined. METHODS: FXII, FXIIa and the FXII 46C>T polymorphism were determined in a hospital-based cohort of 2615 patients undergoing coronary angiography. RESULTS: Fifty-seven per cent of the participants were identified as wild-type (46CC), 38% as heterozygous (46CT) and 5% as homozygous (46TT) for FXII 46C>T. FXII and FXIIa levels were significantly lower in carriers of the T-allele: 132 (97-151) U dL(-1) FXII in 46CC, 87 (77-99) U dL(-1) FXII in 46CT and 53 (42-67) U dL(-1) FXII in 46TT carriers (P < 0.001), and 2.8 (2.3-3.5) microg L(-1) FXIIa in CC, 2.1 (1.6-2.6) microg L(-1) FXIIa in CT and 1.2 (0.9-1.5) microg L(-1) FXIIa in TT carriers (P < 0.001; medians, lower and upper quartiles). Patients with stable CHD (n = 935), a history of myocardial infarction (n = 785) or who were suffering from acute coronary syndromes (ACS; n = 323) had significantly lower FXII levels than controls (n = 572). The differences remained statistically significant after adjustments for age, sex, diabetes mellitus, smoking, hypercholesterolemia and hypertension. Significantly reduced FXIIa levels in ACS patients lost significance once adjusted for covariates. FXII genotype was not associated with any clinical phenotype. CONCLUSION: Lower FXII activity represents an independent risk for CHD and ACS. This is not the case for FXIIa levels or the FXII 46C>T variation.


Subject(s)
Coronary Disease/epidemiology , Factor XII Deficiency/epidemiology , Factor XII/physiology , Factor XIIa/physiology , Polymorphism, Single Nucleotide , Aged , Cardiovascular Diseases/epidemiology , Comorbidity , Factor XII/analysis , Factor XII/genetics , Factor XIIa/analysis , Female , Follow-Up Studies , Gene Frequency , Genetic Predisposition to Disease , Genotype , Germany/epidemiology , Humans , Hypercholesterolemia/epidemiology , Hypertension/epidemiology , Male , Middle Aged , Prospective Studies , Risk , White People/genetics
7.
Transplant Proc ; 39(7): 2197-201, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17889136

ABSTRACT

Worldwide, specific pediatric allocation schemes successfully try to minimize waiting time for children with end-stage renal disease (ESRD). The article is a review of current issues in pediatric kidney transplantation. The procedure is the treatment of choice for children and adolescents with ESRD, with 1- and 3-year graft survival rates of 95% and 90% and recipient survival after 5 and 10 years of 95% and 90%. Preoperative surgery is often necessary to minimize negative effects of congenital anomalies. No minimum age exists for pediatric transplantation, but most often the recipient body weight is ideally above 10 to 15 kg. Technical concepts should include extravesical anastomosis, stenting of the ureter, and potentially intraperitoneal placement of the graft. Immunosuppression has constantly improved. The aim is a tailored regimen to reduce side effects and improve compliance, which necessitates intense counseling of the child and the parents prior to, during, and after transplantation as many adolescents lose their graft due to noncompliance. Intense follow-up must also exclude infections, especially with herpes and polyoma viruses. For the future, age matching may be only one promising concept to improve results. As only a small number of children require the procedure in each country, multinational studies should be initiated to optimize outcomes in children and adolescents.


Subject(s)
Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/surgery , Kidney Transplantation/immunology , Adolescent , Anesthesia/methods , Child , Contraindications , Graft Survival/immunology , Humans , Intraoperative Complications , Kidney Failure, Chronic/etiology , Kidney Transplantation/methods
8.
Pediatr Transplant ; 10(8): 978-81, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17096771

ABSTRACT

Human parvovirus B19 is a common cause of benign erythema infectiosum (fifth disease) in otherwise healthy children. Immunocompromized patients are at risk of developing chronic infections leading to chronic hyporegenerative anemia. We report the case of a nine-year-old boy who presented five days after renal transplantation with seizures and signs of encephalitis on MRI. The clinical course was characterized by anemia and seroconversion for parvovirus B19 accompanied by a high viral load (>10(9) copies per milliliter). A transfusion of red blood cells that the patient required after transplantation was found to be negative for parvovirus B19, leaving the donated organ as the most likely source of infection. Reduction of the immunosuppressive regimen led to complete recovery of the patient with a stable RBC count upon discharge. Parvovirus B19 infections should be considered in the differential diagnosis of seizures after solid organ transplantation.


Subject(s)
Encephalitis, Viral/diagnosis , Kidney Transplantation/adverse effects , Parvoviridae Infections/diagnosis , Parvovirus B19, Human , Anemia/etiology , Child , Encephalitis, Viral/etiology , Encephalitis, Viral/therapy , Humans , Kidney Failure, Chronic/surgery , Leukopenia/etiology , Magnetic Resonance Imaging , Male , Parvoviridae Infections/etiology , Parvoviridae Infections/therapy
9.
Pharmacogenomics J ; 6(6): 397-400, 2006.
Article in English | MEDLINE | ID: mdl-16702982

ABSTRACT

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.


Subject(s)
Polymorphism, Genetic , Serotonin Plasma Membrane Transport Proteins/genetics , Smoking/genetics , Adult , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Male , Middle Aged
10.
Urologe A ; 45(1): 18-24, 2006 Jan.
Article in German | MEDLINE | ID: mdl-16315064

ABSTRACT

The reasons for end-stage renal disease in pediatric patients differ from adults. The therapy of choice is renal transplantation. A total of 117 children and adolescents were treated with renal transplantation in 2003 in Germany. Immunosuppressive therapy and related comorbidities are the main problems in pediatric patients. The following article provides a summary of transplantation in children, preparation, and follow-up.


Subject(s)
Graft Rejection/mortality , Graft Rejection/prevention & control , Graft Survival/drug effects , Immunosuppressive Agents/administration & dosage , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/therapy , Kidney Transplantation/mortality , Adolescent , Chemotherapy, Adjuvant , Child , Clinical Trials as Topic , Germany/epidemiology , Graft Enhancement, Immunologic/statistics & numerical data , Humans , Practice Guidelines as Topic , Practice Patterns, Physicians' , Treatment Outcome
11.
Urologe A ; 45(1): 46-52, 2006 Jan.
Article in German | MEDLINE | ID: mdl-16328213

ABSTRACT

Ten years ago the first laparoscopic living donor nephrectomy (LDN) was performed. Today, LDN is a routine operation in many US-American transplantation centers and an increasing number of centers in Europe are practicing LDN. In this article the different aspects of LDN for donor, kidney, recipient and operating surgeon are evaluated. We performed a literature research concerning LDN and the different aspects. Our own experience, as the largest LDN center in Germany, is part of the evaluation. Laparoscopic extraction of a kidney from a living donor is as safe for the donor as the open approach. At the same time, LDN offers multiple advantages like reduced pain and shorter convalescence. For the donated kidney and the recipient no disadvantages occur from the laparoscopic technique, as long as special intra- and perioperative demands are met. For the operating surgeon multiple developments have expanded the technical armentarium. LDN is safe for donor, recipient and kidney. Central issue of an optimal LDN is sufficient experience with laparoscopic urological techniques.


Subject(s)
Directed Tissue Donation/trends , Kidney Transplantation/trends , Laparoscopy/trends , Nephrectomy/trends , Practice Patterns, Physicians'/trends , Tissue Donors , Germany , Practice Guidelines as Topic
12.
J Thromb Haemost ; 3(7): 1522-9, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15978110

ABSTRACT

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.


Subject(s)
Integrin alpha2beta1/genetics , Myocardial Infarction/diagnosis , Myocardial Infarction/genetics , Platelet Glycoprotein GPIIb-IIIa Complex/genetics , Polymorphism, Genetic , Age of Onset , Aged , Alleles , Angiography , Blood Donors , Case-Control Studies , Coronary Artery Disease/genetics , Female , Follow-Up Studies , Genotype , Heterozygote , Humans , Male , Middle Aged , Multivariate Analysis , Myocardial Infarction/epidemiology , Odds Ratio , Polymorphism, Single Nucleotide , Risk , Risk Factors , Time Factors , Treatment Outcome
13.
Diabetologia ; 47(11): 1969-73, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15565371

ABSTRACT

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.


Subject(s)
Diabetes Mellitus, Type 2/genetics , Integrin beta3/genetics , Polymorphism, Genetic , Aged , Blood Pressure , Diabetes Mellitus, Type 2/immunology , Diabetes Mellitus, Type 2/physiopathology , Female , Humans , Male , Middle Aged , Reference Values , Risk Factors , Smoking
14.
Diabetologia ; 47(9): 1574-80, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15349727

ABSTRACT

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.


Subject(s)
Chemokine CCL2/genetics , Diabetes Mellitus, Type 2/genetics , Insulin Resistance/physiology , Polymorphism, Single Nucleotide/genetics , Adenine , Aged , Cohort Studies , Diabetes Mellitus, Type 2/blood , Female , Glucose/metabolism , Guanine , Homeostasis , Humans , Hyperinsulinism/genetics , Male , Middle Aged
15.
Pharmacogenomics J ; 3(5): 284-96, 2003.
Article in English | MEDLINE | ID: mdl-14583798

ABSTRACT

Cholesteryl ester transfer protein (CETP) plays a central role in high-density lipoprotein (HDL) metabolism. Single nucleotide polymorphisms (SNPs) and haplotypes in the CETP gene were determined in 98 patients with untreated dyslipidemias and analyzed for associations with plasma CETP and plasma lipids before and during statin treatment. Individual CETP SNPs and haplotypes were both significantly associated with CETP enzyme mass and activity. However, only certain CETP haplotypes, but not individual SNPs, significantly predicted the magnitude of change in HDL cholesterol (HDL-C) and triglycerides. After adjusting for covariates and multiple testing, the TTCAAA haplotype showed a gene-dose effect in predicting the HDL-C increase (P=0.03), while the TTCAAAGGG and AAAGGG haplotypes predicted a decrease in triglycerides (P=0.04 both). This is the first study to demonstrate that SNP haplotypes derived from allelic SNP combinations in the CETP gene were more informative than single SNPs in predicting the response to lipid-modifying therapy with statins.


Subject(s)
Carrier Proteins/genetics , Glycoproteins , Haplotypes/genetics , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Lipids/genetics , Aged , Cardiovascular Diseases/blood , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/genetics , Cholesterol Ester Transfer Proteins , Cohort Studies , Female , Genetic Variation/genetics , Humans , Lipids/blood , Male , Middle Aged , Predictive Value of Tests
16.
Curr Med Res Opin ; 18(4): 242-8, 2002.
Article in English | MEDLINE | ID: mdl-12201626

ABSTRACT

BACKGROUND: Myocardial infarction (MI) is a complex disease caused by interaction of a number of genetic and environmental factors. This disease has reached epidemic proportions in South African Indian descendants. The aim of this study was to survey the prevalence of coronary heart disease risk factors in a sub-group of young Indian patients (< or = 45 years) who presented to the Coronary Care Unit at the R. K. Khan Hospital in Durban, a major referral centre for patients with acute MI in the province of Natal. METHODS AND RESULTS: A total of 245 patients < or = 45 years of age were recruited from patients consecutively admitted to the Coronary Care Unit at the R. K. Khan Hospital, Durban, KwaZulu Natal, South Africa between 1996 and 1999 with a diagnosis of acute MI. All patients were of Indian origin living in the Durban area in the province of KwaZulu-Natal. Demographic and risk factor data were obtained from all patients and included anthropometric measures, family history and the traditional cardiovascular risk factor assessment (smoking, lipids, hypertension, and diabetes mellitus). Clinical data included in-hospital presentation, management and complications and angiographic classification of coronary atherosclerosis. The most prevalent risk factors were previous: smoking (74%), and hypertriglyceridaemia (54%). Only 14% of the population presenting with an acute MI were women. Smoking was more common among men (81%) than in women (35%). Abnormal high density lipoprotein (HDL) cholesterol levels were detected in 38% of the patients with a dear gender difference: 43% and 9%, in men and women, respectively. In contrast hypertension was more prevalent in young women with MI than in men: 38% and 19%, respectively. Coronary angiography was performed in 79 patients on admission; a single vessel stenosis was found in 28%, two vessel disease in 20% and triple vessel disease in 52%, respectively. On admission, 92% of patients were in Killip class I. Overt heart failure and cardiogenic shock were uncommon and were seen in 3.3% and 0.8%, respectively. Patients who received thrombolytic therapy had fewer complications (8%) compared to those who did not (11%). However, the difference towards a benefit of thrombolysis did not reach significance. Recurrent angina (6%) was the commonest complication, while ventricular arrhythmias were observed in 2% of patients. There was a strong familial link: 54% of the patients had a family background of coronary heart disease (CHD) while 42% and 41% had family members who suffered from diabetes mellitus and hypertension, respectively. CONCLUSION: Smoking and dyslipidaemia (predominantly hypertriglyceridaemia, and low HDL-cholesterol) were the most common cardiovascular risk factors of MI in young South African Indians. A strong familial link was observed not only for a history of CHD/MI, but also for hypertension and diabetes mellitus, supporting a genetic basis for the development of premature CHD. Therefore, further analysis of potential genetic factors such as variance of genes involved in vascular homeostasis, haemostatic factors, lipid metabolism and other metabolic factors seems warranted.


Subject(s)
Myocardial Infarction/ethnology , Adult , Female , Humans , India/ethnology , Male , Myocardial Infarction/etiology , Prevalence , Risk Factors , South Africa/epidemiology , Statistics, Nonparametric
17.
Urologe A ; 41(2): 107-12, 2002 Mar.
Article in German | MEDLINE | ID: mdl-11993087

ABSTRACT

Once laparoscopic radical prostatectomy has been mastered, the step to performing a radical cystectomy is not that far. The challenge is to create the urinary diversion by laparoscopy. In this report we describe our experience with 11 laparoscopic radical cystectomies and intracorporeal construction of a continent urinary diversion (Mainz pouch II) as a treatment option in patients with muscle-invading bladder cancer. All 11 procedures could be performed successfully. A conversion to open surgery was not required in any case. The mean surgery time was 6.7 h. Except for two pouch fistulas we did not observe any intra- or postoperative complications. The functional as well as the oncological results are convincing. Less morbidity and faster recovery are the main advantages of this minimally invasive procedure. In addition, the low levels of blood loss, fluid shifts, and electrolyte loss considerably reduce cardiovascular stress. Radical cystectomy and construction of a continent urinary diversion represent the limit of technically feasible laparoscopy and should be done exclusively in specialized centers.


Subject(s)
Carcinoma, Transitional Cell/surgery , Cystectomy/trends , Laparoscopy/trends , Urinary Bladder Neoplasms/surgery , Urinary Reservoirs, Continent/trends , Aged , Carcinoma, Transitional Cell/pathology , Feasibility Studies , Female , Forecasting , Humans , Male , Middle Aged , Neoplasm Staging , Postoperative Complications/etiology , Urinary Bladder Neoplasms/pathology
18.
Urologe A ; 41(1): 48-54, 2002 Jan.
Article in German | MEDLINE | ID: mdl-11963775

ABSTRACT

Systematic development of laparoscopy during the last decade has led to establishing laparoscopic radical prostatectomy (LRP) as a surgical procedure. On the basis of extensive experience at our center, the advantages of the minimally invasive method are described as well as the problems still in existence. Reduced trauma caused by laparoscopic access in combination with clearly reduced blood loss has resulted in less morbidity after laparoscopic procedures. This is reflected in a shorter postoperative stay in hospital and faster convalescence. LRP as an ambitious and complex procedure has an average complication rate of 12%, which shows that the method has surpassed the stage of experimental surgery. By direct comparison, the costs of LRP are higher than for the open surgical procedure, but on the whole this is economically balanced by the lower morbidity, shorter hospital stay, and faster convalescence. The progress in technology to be expected in the field of laparoscopy will further increase quality, precision, and safety of LRP and thus contribute to the establishment of laparoscopic radical prostatectomy as a surgical method of choice.


Subject(s)
Laparoscopy , Prostatic Neoplasms/surgery , Adult , Aged , Humans , Male , Middle Aged , Neoplasm Staging , Outcome and Process Assessment, Health Care , Postoperative Complications/etiology , Prostatic Neoplasms/pathology
19.
Blood Coagul Fibrinolysis ; 13(2): 81-7, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11914649

ABSTRACT

The role of haemostatic factors for arterial thrombosis, especially the prevalence of activated protein C (APC) resistance in patients with coronary artery disease (CAD), is controversial. Between November 1996 and August 1997, 665 patients were analyzed. Diagnosis of CAD was confirmed by coronary angiography, exclusion of CAD was accepted in the presence of negative stress testing or a negative coronary angiography. CAD was present in 370 (56%) and excluded in 295 (44%) patients. Patients with CAD were older (64 +/- 9.2 versus 57.7 +/- 16 years; P

Subject(s)
Coronary Artery Disease/etiology , Hemostasis , Aged , Biomarkers/blood , Blood Coagulation Factor Inhibitors/blood , Blood Coagulation Factors/metabolism , Case-Control Studies , Coronary Artery Disease/blood , Coronary Artery Disease/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Odds Ratio , Prospective Studies , Risk Factors
20.
Eur Urol ; 40(1): 46-52; discussion 53, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11528176

ABSTRACT

PURPOSE: The laparoscopic access for radical prostatectomy offers an alternative to the open surgical procedure with less morbidity. We report on our experience with 125 laparoscopic prostatectomies, especially with respect to making the laparoscopic approach a routine procedure and with a view to the oncological and functional results. MATERIAL AND METHODS: From June 1999 to September 2000, we performed 125 laparoscopic prostatectomies. These included only patients with cancer stages T1 or T2. The mean PSA concentration was 10.5 ng/ml. Forty-four percent of the patients had undergone previous abdominal and 19% previous transurethral surgery. For our laparoscopic prostatectomies we used the descending technique. Free-hand laparoscopic suturing and in situ knot-tying technique were used for the urethrovesical anastomosis. The mobilized specimens were removed in an endobag via a muscle splitting incision. RESULTS: All 125 procedures could be completed successfully. No case required conversion to open surgery. The average operating time was 255 min, the last 40 procedures taking 200 min only. Mean blood loss was 185 ml. Two patients (2%) required postoperative blood transfusion. After an initial learning curve, catheter remained in place for an average of 5.5 days, and the average postoperative stay in hospital was 8 days. Intraoperative complications were seen in 5 patients (4%). In 13 patients (10.4%) postoperative complications were observed. 86% of the patients are continent 6 months postoperatively. Preservation of the neurovascular bundle and sexual potency is possible. CONCLUSION: Laparoscopic radical prostatectomy is an ambitious procedure with a steep learning curve, especially for the laparoscopic dissecting and suturing technique. The excellent sight for dissection results in a reduced blood loss and faster convalescence with an overall lower morbidity. Also with regard to oncological and functional (continence) results the minimally invasive access is at least equivalent to the open procedure. In our opinion, laparoscopic prostatectomy will be the future method of choice for radical prostatectomy.


Subject(s)
Laparoscopy , Prostatectomy/methods , Prostatic Neoplasms/surgery , Adult , Aged , Humans , Male , Middle Aged
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