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Biomedical subjects

T C Wascher

Publications and source records attributed to T C Wascher.

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↗
PubMed2005

Biphasic insulin aspart compared to biphasic human insulin reduces postprandial hyperlipidemia in patients with Type 2 diabetes.

BACKGROUND: Premixed insulin analogues reduce postprandial hyperglycemia in patients with Type 2 diabetes in comparison to premixed regular insulin. Insulin also plays an important role in the regulation of postprandial lipid metabolism. It is known that increased levels of postprandial insulin reduce postprandial hyperlipemia but, on the other hand, no information exists with regard to the possible effect of insulin analogues in comparison to human insulin. MATERIALS AND METHODS: 12 subjects (3 men; age 59 +/- 5 years; BMI 30.5 +/- 5.9 kg/m2, duration of diabetes 9 +/- 1 years, HbA1c 8.33 +/- 1.1 %) already on therapy with premixed insulin were treated either with biphasic human insulin (BHI30) or with biphasic insulin aspart (BIAsp30) (1.3 IU fast acting insulin/12 g KH) in the setting of a standardized test meal. Serum levels of glucose, insulin, C-peptide and triglycerides as well as retinylpalmitate in plasma and chylomicron remnants were determined before and up to 8 hours after the meal. RESULTS: As was to be expected, therapy with BIAsp30 reduced the maximum increase of postprandial glucose from 7.10 +/- 2.00 mmol/l to 5.27 +/- 1.83 mmo/l (p = 0.007) compared to BHI30 insulin. In the same way, the maximum increase of triglycerides (from 2.33 +/- 1.03 to 1.65 +/- 0.69 mmol/l, p = 0.014) was reduced. The AUC 0 - 8 for triglycerides was not significantly influenced (34.20 +/- 19.86 vs. 31.46 +/- 16.21 mmol x 8 h/l) but the incremental area over baseline (AOB 0 - 8) was significantly reduced from 8.02 +/- 4.35 to 6.12 +/- 3.94 mmol x 8 h/l (p = 0.024). CONCLUSIONS: Compared to conventional human premixed insulin the prandial therapy with biphasic insulin aspart results not only in an improvement of glucose tolerance but also in a significant reduction of postprandial hyperlipemia.

Biphasic Insulins↗
PubMed2005

Intense cholesterol lowering therapy with a HMG-CoA reductase inhibitor does not improve nitric oxide dependent endothelial function in type-2-diabetes--a multicenter, randomised, double-blind, three-arm placebo-controlled clinical trial.

Disturbances in nitric oxide (NO) metabolism resulting in endothelial dysfunction play a central role in the pathogenesis of atherosclerosis in hypercholesterolemia and in individuals with type 2 diabetes. It is unclear whether lipid lowering therapy with HMG-CoA-reductase inhibitors might improve endothelial function in subjects with type 2 diabetes as it is demonstrated in non-diabetic subjects with hypercholesterolemia. We examined the influence of 0.2 mg and 0.8 mg cerivastatin on endothelial function in a multicenter, randomised, double-blind, and three-arm placebo-controlled clinical trial. Endothelial function was assessed by nitric oxide-dependent flow mediated vasodilatation (FMD) of the brachial artery. A total of 103 patients with type 2 diabetes were enrolled in the study. Bayer Company undertook a voluntary action to withdraw cerivastatin from market, therefore the study was terminated earlier. At this point 77 patients were randomised, of which 58 completed the study (mean age 60 +/- 8 years, HbA1c 7.4 +/- 0.9 %). At baseline mean FMD was disturbed in all three therapy arms (5.18 +/- 2.31 % in the placebo group, 3.88 +/- 1.68 in the 0.2-mg cerivastation group, and 4.86 +/- 2.25 in the 0.8-mg cerivastatin group). Despite a significant reduction in cholesterol and LDL-cholesterol-levels after 12 weeks of treatment (decrease in LDL-cholesterol - 26.8 +/- 13.9 % in the 0.2-mg group and - 40.3 +/- 16.0 % in the 0.8-mg group, p = 0.0001, ANCOVA) there was no difference in flow mediated vasodilatation (p = 0.52 and p = 0.56 vs. placebo, respectively, ANCOVA). HbA1c, CRP, and HDL-cholesterol did not change during the study. Furthermore no difference in safety profile between cerivastatin and placebo was found. Despite a significant improvement in lipid profile under statin therapy, no improvement of endothelial dysfunction in terms of nitric oxide bioavailability could be detected.

Blood Glucose↗
PubMed2005

Reduction of postchallenge hyperglycaemia prevents acute endothelial dysfunction in subjects with impaired glucose tolerance.

OBJECTIVES: To investigate whether selective reduction of postchallenge hyperglycaemia influences acute endothelial dysfunction, a very early manifestation of vascular disease, in patients with impaired glucose tolerance. METHODS: In a randomized, double-blind, placebo-controlled, cross-over study the acute effect of 200-mg acarbose was investigated in 28 subjects with diagnosed impaired glucose tolerance. Flow-mediated dilation (FMD) of the brachial artery was determined as a measure of endothelial function before and 2 and 3 h after ingestion of 100-g saccharose. Asymmetrical dimethylarginine (ADMA) was measured by high-performance liquid chromatography. RESULTS: A negative correlation was observed between the changes of glucose and FMD (r = 0.416, P = 0.0018) 2 h after ingestion of saccharose. At 3 h, neither blood glucose nor FMD were different from baseline. Changes of both blood glucose (P = 0.0007) and FMD (P = 0.046) were significantly lower after administration of acarbose. Subgroup analysis revealed that the effect of acarbose was restricted to those subjects with an increase of blood glucose above the median increase of glycaemia. No changes of plasma ADMA were observed. CONCLUSIONS: Our data clearly demonstrate that the postchallenge alteration of vascular function in patients with impaired glucose tolerance is caused by the acute elevation of glycaemia but not mediated by ADMA.

Acarbose↗
PubMed2005

Low-fat, high-carbohydrate (low-glycaemic index) diet induces weight loss and preserves lean body mass in obese healthy subjects: results of a 24-week study.

BACKGROUND: The traditional treatment for obesity which is based on a reduced caloric diet has only been partially successful. Contributing factors are not only a poor long-term dietary adherence but also a significant loss of lean body mass and subsequent reduction in energy expenditure. Both low-fat, high-carbohydrate diets and diets using low-glycaemic index (GI) foods are capable of inducing modest weight loss without specific caloric restriction. The purpose of this study was to investigate the feasibility and medium-term effect of a low-fat diet with high (low GI) carbohydrates on weight loss, body composition changes and dietary compliance. METHODS: Obese patients were recruited from two obesity outpatient clinics. Subjects were given advise by a dietician, then they attended biweekly for 1-hour group meetings. Bodyweight and body composition were measured at baseline and after 24 weeks. RESULTS: One hundred and nine (91%) patients completed the study; after 24 weeks the average weight loss was 8.9 kg (98.6 vs. 89.7 kg; p < or = 0.0001). There was a significant 15% decrease in fat mass (42.5 vs. 36.4 kg; p < or = 0.0001) and a decrease in lean body mass of 5% (56.1 vs. 53.3 kg; p < or = 0.0001). DISCUSSION: In this 6-month study, a low-fat, low-GI diet led to a significant reduction of fat mass; adherence to the diet was very good. Our results suggest that such a diet is feasible and should be evaluated in randomized controlled trials.

Adult↗
PubMed2004

Diminished response to activated protein C is not correlated with severity of peripheral arterial occlusive disease.

INTRODUCTION: Poor response to activated Protein C (APC) is a well established risk factor for venous thromboembolism. More recently, the hypercoagulable state which results from diminished response to APC has also been associated with arterial thrombosis. Some studies showed a clear association between low response to APC with advanced arterial disease, others, however, failed to support these data. Thus, there is ongoing dispute about the impact of a hypercoagulable state upon progression of atherosclerosis. MATERIAL AND METHODS: We investigated APC ratios and the existence of Factor V Leiden in 800 patients with documented peripheral arterial occlusive disease (PAD). Clinical symptoms according to Fontaine stages II (intermittent claudication), III (rest pain) and IV (gangrene) and the ankle/brachial index served as parameters for the severity of PAD. RESULTS: There was no association between low response to APC or existence of Factor V Leiden and the clinical stage of PAD or ankle/ brachial index. CONCLUSION: Our data suggest that poor response to APC is not correlated with the severity of peripheral arterial occlusive disease.

Activated Protein C Resistance↗
PubMed2003

Lack of association of the Glu298Asp polymorphism of endothelial nitric oxide synthase with manifest coronary artery disease, carotid atherosclerosis and forearm vascular reactivity in two Austrian populations.

OBJECTIVE: Conflicting data exists about the possible contribution of the homozygous Asp/Asp genotype of the Glu298Asp polymorphism of endothelial nitric oxide synthase to human atherosclerotic vascular disease. We investigated the polymorphism in two independent study populations: a case-control study including patients with angiographically verified coronary artery disease (CAD) on the one hand and a cross-sectional epidemiological study on the other hand. METHODS: The Glu298Asp polymorphism was determined by PCR-RFLP as established. In the case-control study (240 patients and 248 controls) a possible association between the polymorphism and CAD, and age of onset of CAD and myocardial infarction was investigated. In the cross-sectional epidemiological study (932 subjects) intima-media thickness (IMT) of the carotid artery as well as morphological plaque burden and forearm vascular reactivity (peak postischemic reactive hyperaemia, determined by venous occlusion plethysmography) were measured. RESULTS: In the case-control study genotype distribution (Glu/Glu; Glu/Asp; Asp/Asp) was not different between the CAD patients (43/46/11%) and the controls (49/41/10%, P = NS). No association of the polymorphism with age of onset of CAD or myocardial infarction was found. In the epidemiological study no influence of the genetic variant on IMT was observed after correction for classical determinants of IMT (average IMT: Asp/ Asp: 0.077 +/- 0.011 mm; Glu/Glu and Glu/Asp: 0.080 +/- 0.012 mm, P = NS). Forearm vascular reactivity was also not different between homozygous Asp/Asp subjects and Glu/Glu and Glu/Asp subjects (peak-reactive hyperaemia 20.1 +/- 7.3 mL min-1 100 mL-1 vs. 20.0 +/- 6.5 mL min-1 100 mL-1, P = NS). CONCLUSIONS: Our results suggest that there is no association of the Glu298Asp polymorphism with coronary or carotid atherosclerosis or forearm vascular reactivity in these populations recruited in a country with a rather high risk for atherosclerosis. We suggest additional investigations to be performed in populations at different risk for coronary events to further elucidate the possible contribution of this polymorphism to vascular disease.

Adult↗
PubMed2002

The V34L polymorphism of factor XIII and peripheral arterial disease.

BACKGROUND: Factor XIII catalyzes crosslinking of fibrin in the last steps of the coagulation process. A common polymorphism in the gene for factor XIII A subunit (F13A1 V34L) has been associated with a decreased risk for coronary artery disease, cerebrovascular disease, and deep venous thrombosis. METHODS: To analyze the role of this polymorphism in peripheral arterial disease (PAD) we performed a case-control study including 873 patients with documented PAD and a total of 523 controls without vascular disease. The F13A1 genotype was determined by an allele-specific polymerase chain reaction. RESULTS: Genotype distribution and allele frequencies were not significantly different between patients (VV: 51.9%; VL: 40.7%; LL: 7.4%) and controls (VV: 54.7%; VL: 39.2%; LL: 6.1%). Mean age at onset of the disease was significantly higher in LL homozygous subjects than in VV homozygous subjects (67.3 versus 64.1 years, p=0.017). Heterozygous subjects had an intermediate age at onset (65.1 years), suggesting a gene-dose effect. The association of the L34 variant with onset of PAD remained significant after adjustment for other risk factors. The effect was stronger in men than in women. CONCLUSIONS: We conclude that the F13A1 V34L polymorphism was not associated with the presence of PAD in our study, but may be linked to a later onset of the disease.

Aged↗
PubMed2001

Role of factor XIII Val34Leu polymorphism in retinal artery occlusion.

BACKGROUND AND PURPOSE: Factor XIII (FXIII) Val34Leu, a common polymorphism in the gene for factor XIII, has been associated with a lower risk of stroke, myocardial infarction, and deep vein thrombosis. Ineffective fibrin cross-linking has been suggested to be causative. The aim of the present case-control study was to investigate the role of FXIII Val34Leu polymorphism in patients with retinal artery occlusion. METHODS: A total of 108 patients with retinal artery occlusion and 313 age- and sex-matched controls were genotyped for the FXIII Val34Leu polymorphism. Factor XIII Val34Leu genotypes were determined by use of allele-specific polymerase chain reaction. RESULTS: Homozygous Leu genotype was found significantly more often in control subjects than in patients with retinal artery occlusion (P=0.018), with an odds ratio of 0.22 (95% confidence interval 0.07 to 0.74). Distribution of the Val/Val and Val/Leu genotypes did not differ significantly between groups. CONCLUSIONS: Because prevalence of homozygous Leu genotype was significantly higher in controls, we conclude that the Leu/Leu genotype is associated with a protective effect against retinal artery occlusion.

Adult↗
PubMed2001

Acute effects of nicorandil on glucose tolerance in subjects with borderline fasting blood glucose levels.

The acute effect of the anti-ischemic potassium channel opener nicorandil on glucose tolerance and post-challenge insulin levels was investigated in 11 subjects (6 males and 5 females, age 59 +/- 2 years) with borderline fasting blood glucose in a single blinded randomised study. All participants were submitted to two oral glucose tolerance tests in randomised order, once without any premedication and once 30 minutes after oral administration of 20 mg nicorandil. This single dose of nicorandil significantly increased blood glucose levels at 120 minutes (173 +/- 16 vs. 150 +/- 11 mg/dl, p < 0.05 by ANOVA) and 180 minutes (106 +/- 11 vs. 88 +/- 7 mg/dl, p < 0.05 by ANOVA) after ingestion of 75 mg of glucose. Serum insulin levels were not significantly altered. In conclusion we suggest that controlled studies in patients with coronary artery disease should be performed to investigate whether long term treatment with nicorandil increases progression rates from impaired glucose tolerance to type-II diabetes and/or from normal to impaired glucose tolerance with a possibly negative impact on the course of cardiovascular disease in comparison to conventional anti-anginal drugs.

Administration, Oral↗
PubMed2001

Postprandial impairment of resistance vessel function in insulin treated patients with diabetes mellitus type-2.

Reduced postischaemic reactive hyperaemia, is considered a marker of impaired resistance vessel function. Acute postprandial hyperlipidaemia has been shown to induce vascular dysfunction. In the present study, the impact of postprandial hyperglycaemia on resistance vessel reactivity was investigated in insulin treated type-2 diabetic patients. The study was performed in 16 insulin treated type-2 diabetics (eight male/eight female, age 47 +/- 3 years, HbA1c 7.2 +/- 0.2) and 16 controls. Reactive hyperaemia was measured in the forearm by venous occlusion plethysmography after 5 min of ischaemia in the fasting state and 90 min after a test meal. In diabetics, blood glucose increased from 8.7 +/- 1.1 to 15.3 +/- 1.0 mmol l-1 (P<0.001) postprandially. This resulted in (i) a significant increase of resting blood flow (3.4 +/- 0.3 to 4.8 +/- 0.4 ml min-1 100 ml-1, P<0.01) and (ii) in a reduced peak reactive hyperaemia (52.3 +/- 7.4 to 36.8 +/- 4.3 ml min-1 100 ml-1, P<0.005). In controls, a similar effect of the meal on resting flow was observed but reactive hyperaemia was unaltered. In the absence of a test meal, basal flow as well as peak reactive hyperaemia remained unchanged in diabetic as well as in non-diabetic subjects. Our data provide evidence that in the postprandial state resistance vessel reactivity becomes reduced in insulin treated type-2 diabetic patients.

Adult↗
PubMed2001

Effects of a high-fat meal on resistance vessel reactivity and on indicators of oxidative stress in healthy volunteers.

High fat meals postprandially impair macrovascular endothelial function and a link to increased oxidative stress is suggested. Few information, on the other hand, exists on the effect of postprandial hyperlipidaemia on resistance vessel function. Under normal circumstances this vascular bed regulates tissue perfusion and, by controlling flow, impacts on macrovascular nitric oxide formation. The impact of a high fat meal (1200 kcal, 90 g fat, 46 g protein and 47 g carbohydrates) on postprandial resistance vessel reactivity and on indicators of oxidative stress was studied in 11 healthy subjects by venous-occlusion plethysmography using another six subjects as time control group. Ingestion of the test meal resulted in a pronounced increase of serum triglycerides from 1.05 +/- 0.61 mmol l(-1) in the fasting state to peak postprandial values of 1.94 +/- 0.41 mmol l(-1) (P < 0.001) reached after 4 h and a return to baseline after 8 h. Fasting peak reactive hyperaemia (RH) was 19.6 +/- 2.4 ml min(-1) (100 ml)(-1). Two hours after ingestion of the test meal peak RH was transiently reduced to 16.8 +/- 2.2 ml min(-1) (100 ml)(-1) (P < 0.05). No alteration of resting forearm perfusion was observed. The time course of peak RH suggested a potential biphasic effect of the test meal with an early impairment and a late increase of RH. Ingestion of a lipid rich test meal did not exert any influence on either total plasma antioxidant capacity given in trolox equivalents (513 +/- 26 micromol l(-1) at baseline) or on plasma peroxides measured as H2O2 equivalents (469 +/- 117 micromol l(-1)). Our results suggest that ingestion of a meal containing 90 g of fat results in a transient impairment of reactive hyperaemia in healthy subjects but these vascular alterations are not accompanied by signs of systemically increased oxidative stress.

Adult↗
PubMed2001

NADH/NADPH oxidase p22 phox C242T polymorphism and lipid peroxidation in coronary artery disease.

The nicotinamide adenine dinucleotide (NADH)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system is a major source of superoxide anion (.O2-) production in the human vasculature and may therefore influence lipid peroxidation and severity of atherosclerosis. This study aimed to investigate a hypothetical influence of the p22 phox C242T polymorphism on the generation of malondialdehyde (MDA), extent and clinical onset of coronary artery disease (CAD) in patients. We studied 108 male Caucasians with angiographically documented CAD and 45 controls free of vascular disease under 60 years of age. p22 phox C242T genotypes and MDA levels were determined. Additional information was obtained from each subject on classic risk factors and clinical events of CAD. Genotype distribution in CAD-patients and controls was thymine-thymine (TT): 13.8% (13.3%), cytosine-thymine (CT): 46.3% (53.3%) and cytosine-cytosine (CC): 39.8% (33.3%), respectively. No significant influence was seen of the p22 phox C242T polymorphism on corresponding mean MDA levels in both groups. Furthermore, age at onset of first time angina pectoris (AP) and myocardial infarction (MCI) was not significantly different between genotype groups. It is concluded that the C242T polymorphism of the p22 phox gene is not associated with lipid peroxidation as measured by MDA, and is not a genetic risk marker for CAD Caucasians.

Adult↗