Biomedical subjects

W Mlekusch

Publications and source records attributed to W Mlekusch.

At least 19 recordsLinked to original sources

PubMed2005

Haem oxygenase-1 genotype and cardiovascular adverse events in patients with peripheral artery disease.

BACKGROUND: A functional GT dinucleotide length polymorphism in the haem oxygenase-1 (HO-1) gene promoter is thought to be involved in the pathogenesis of cardiovascular disease. Short (< 25) (GT)n repeats are suggested to facilitate enhanced HO-1 up-regulation in response to injury and confer potent anti-inflammatory and antioxidative effects. MATERIALS AND METHODS: We investigated the association between the HO-1 GT-polymorphism and cardiovascular outcome in 472 patients with advanced peripheral artery disease. Cardiovascular risk profile and DNA samples for determination of the HO-1 genotype (carrier vs. noncarrier of a short (GT)n repeat allele) were obtained at baseline, and patients were followed for median 21 months for the occurrence of coronary events (myocardial infarction, percutaneous coronary interventions and coronary artery bypass graft), cerebrovascular events (stroke or carotid revascularization) and all-cause mortality. RESULTS: Coronary events occurred in 48 patients (9%), cerebrovascular events in 40 patients (9%) and 59 patients (13%) died. In total, 173 major adverse cardiovascular events (MACE) occurred in 133 patients (28%). Carriers of the short (GT)n repeat allele had a 0.46-fold reduced adjusted hazard ratio for coronary events (P = 0.016) as compared to noncarriers. No significant difference was found for cerebrovascular events, mortality and overall MACE. CONCLUSION: Apparently, the HO-1 genotype exerts potentially protective effects against coronary adverse events in patients with peripheral artery disease. Homozygous and heterozygous carriers of < 25 (GT)n repeats had lower rates of myocardial infarction, percutaneous coronary interventions and coronary bypass operations compared to patients with longer (GT)n repeats.

Aged↗

PubMed2004

Long-term follow-up after percutaneous transluminal angioplasty of the distal abdominal aorta.

Aortoiliac disease can be either treated with surgery-endarterectomy for localized aortic disease or with bypass graft placement for more extensive aortoiliac disease--or with percutaneous transluminal angioplasty (PTA), which has become an established method. Long term results of surgery are well documented in literature, but long term results of distal aortic PTA are scarce, furthermore angiographic follow-up is very uncommon. We report about a patient with isolated aorta abdominalis stenosis due to atherosclerotic disease who underwent PTA in 1982 and had an angiographic follow-up four and twenty years later, thus we demonstrate that patency can be obtained even after twenty years.

Aged↗

PubMed2004

Effects of intravenous prostaglandin E1 on arterial compliance: a randomized controlled trial.

BACKGROUND: Prostanoids are in widespread use for the treatment of critical limb ischemia and are suggested to improve arterial compliance. However, dose- and time-dependency of these drug effects are indeterminate. We investigated the influence of intravenous application of prostanoids on arterial compliance parameters in patients with critical limb ischemia due to peripheral artery disease (PAD). PATIENTS AND METHODS: We included 82 consecutive patients with PAD Fontaine stage III and IV in a patient-blinded, randomized controlled trial. Patients were randomly assigned to either single dose intravenous treatment with 40 microg (n = 29) or 60 microg (n = 27) of Alprostadil (PGE1) in 250 ml 0.9% saline over 2 hours, or 250 ml 0.9% saline solution as a placebo group (n = 26). Large and small artery compliance was measured by peripheral pulse contour analysis at baseline, at one hour during intravenous infusion of Alprostadil, immediately after and 24 hours after the end of the infusion. For study purposes the patients received Alprostadil only once during the observation period of 2 days. RESULTS: Large artery compliance, blood pressure, heart rate and cardiac output were unaffected by PGE1 administration irrespectively of drug-dosage or time interval. Small artery compliance increased at 1 hour during intravenous application of Alprostadil (40 microg Alprostadil p = 0.001; 60 microg Alprostadil p < 0.0001) compared to placebo and increased median +47% (IQR +5% to +100%) after administration of 40 microg Alprostadil and median +32% (IQR -11% to +88%) after 60 microg Alprostadil (p = 0.5). Immediately after the end of Alprostadil infusion small artery compliance decreased to baseline levels. CONCLUSIONS: Prostaglandin E1 causes a significant improvement of small artery compliance during the time of intravenous application. However, this effect rapidly diminishes after the end of administration and no dose-dependency between 40 microg and 60 microg Alprostadil is observed.

Adaptation, Physiological↗

PubMed2002

Reduction in renal function after renal arteriography and after renal artery angioplasty.

OBJECTIVE: To investigate the incidence and risk factors for renal function deterioration after renal angiography and angioplasty or stenting. METHODS: A retrospective study of 85 consecutive patients undergoing selective renal artery arteriography (n = 53) or renal artery angioplasty % (PTRA) stenting (n = 32) for renal artery stenosis. Multivariate logistic regression analysis was used to determine independent predictors of deterioration of renal function, defined as an increase of serum creatinine by at least one third within 24 h. RESULTS: Deterioration of renal function occurred in 13 patients (15%), [8/53 (15%) after angiography and 5/32 (16%) after PTRA/stenting]. Only pre-existing renal impairment (se-creatinine > or = 177 mumol/l) (Odds ratio: 40; 95% confidence interval 1.2-72, p = 0.02) and administered dosage of contrast agent (more than 225 ml) (OR 67; 95% CI 11.8-100, p = 0.02) were independently associated with renal function deterioration. CONCLUSION: Transient renal dysfunction after renal artery angiography or PTRA/stenting occurs in about 15% of patients, but persistent renal failure is uncommon. Pre-existing renal impairment and amount of contrast agent are independent risk factors. Endovascular treatment of renal artery stenosis is not associated with a higher risk of renal deterioration compared to selective renal angiography.

Aged↗

PubMed2002

Clinical outcome and prognostic factors for ischaemic ulcers treated with PTA in lower limbs.

OBJECTIVE: To analyse the clinical outcome of patients with ischaemic ulcers (Fontaine stage IV) undergoing percutaneous transluminal angioplasty (PTA). METHODS AND DESIGN: Retrospective cohort study of 40 patients (21 males) treated between January 1998 and December 1998. Cardiovascular risk factors, co-morbid, baseline laboratory, angiographic data and technical success were recorded. Patients were followed for a median of 20 (inter quartile range (IQR) 8-26) months. RESULTS: Cumulative ulcer healing rates at 3, 6, 12, and 24 months were 15, 40, 54 and 81%, respectively. The median time to healing was 5 (IQR 2-7) months. Cumulative restenosis at 1, 3, 6 and 12 months was 3, 10, 29 and 52%, respectively. Nine patients (22%) suffered ulcer reappearance. Lipoprotein (a) serum levels > 30 mg/dl (HR 0.2, 95% CI 0.05-1.0, p = 0.05) and diabetes mellitus (HR 0.2, 95% CI 0.5-0.7, p = 0.01) were associated with delayed ulcer healing. CONCLUSION: PTA leads to ulcer healing in the majority of patients. Elevated lipoprotein (a) levels > 30 mg/dl and diabetes mellitus are independently associated with ulcer persistence.

Aged↗

PubMed2001

Heme oxygenase-1 gene promoter microsatellite polymorphism is associated with restenosis after percutaneous transluminal angioplasty.

PURPOSE: To determine if an association exists between postdilation restenosis and heme oxygenase-1 (HO-1), which is induced by balloon injury and inhibits neointimal formation through the action of endogenous carbon monoxide. A dinucleotide repeat in the promoter region of the HO-1 gene shows a length polymorphism that modulates the level of gene transcription. METHODS: This cohort study included 96 consecutive patients (64 men; median age 69 years, interquartile range 60-75) who underwent successful balloon dilation in the femoropopliteal segment. Six-month patency was evaluated using oscillography, ankle-brachial index, and duplex sonography. The association of patency and the length of (GT) repeats in the HO-1 gene promoter was assessed in univariate and multivariate analyses. RESULTS: Restenosis was found in 23 (24%) patients within the first 6 months. Patients with short (<25 GT) dinucleotide repeats in the HO-1 gene promoter on either allele had restenosis significantly less often than patients with longer (> or = 25 GT) dinucleotide repeats (p = 0.01). Multivariate analysis revealed a significantly reduced risk for restenosis in these patients compared to patients without the short allele (odds ratio 0.2, 95% Cl 0.06 to 0.70, p = 0.007). CONCLUSIONS: Genetic risk factors for restenosis after percutaneous transluminal angioplasty have not been investigated. In this patient population, short repeat alleles of the heme oxygenase-1 gene promoter polymorphism were associated with reduced postdilation restenosis at 6 months. Upregulation of HO-1 may be an important protective factor after balloon angioplasty by inhibition of vascular smooth muscle cell proliferation.

Aged↗

PubMed2001

Restenosis after percutaneous transluminal angioplasty in the femoropopliteal segment: the role of inflammation.

PURPOSE: To determine the value of baseline C-reactive protein (CPR), fibrinogen, and white blood cell (WBC) counts in predicting 1-year patency after percutaneous transluminal angioplasty (PTA) in the femoropopliteal segment. METHODS: In a retrospective cohort study, 168 consecutive patients (103 men; median age 70 years, interquartile range 61-77) who underwent successful PTA of the femoral and/or popliteal arteries were analyzed. Twelve-month patency was evaluated using oscillography, ankle brachial index, duplex sonography, and angiography. The predictive value of inflammatory markers was assessed in a multivariate model controlling for cardiovascular risk factors, technical success, and hemodynamic factors. RESULTS: Transient WBC elevation was found 6 hours after PTA, but this returned to baseline after 24 hours. Fibrinogen was elevated at 24 hours. Duplex scanning disclosed restenosis in 66 (39%) patients within the first 12 months after PTA. Only residual postdilation stenosis (> or = 30%) in the target segment (odds ratio 3.6, p=0.001) and baseline CRP levels (odds ratio 4.2, p=0.02) were independent predictors of outcome; neither WBC counts nor fibrinogen levels at any time point was associated with restenosis. CONCLUSIONS: Primary technical success and postinterventional hemodynamic flow at the dilated segment seem to be more important for intermediate-term patency than atherogenic risk factors. The predictive value of preprocedural serum CRP levels on restenosis should be further investigated.

Aged↗

PubMed2001

Predicting renal failure after balloon angioplasty in high-risk patients.

PURPOSE: To assess the incidence and predictors of acute renal failure after percutaneous transluminal angioplasty (PTA) in a cohort of patients with generalized atherosclerosis. METHODS: A retrospective review of 213 consecutive patients (127 men; median age 71 years, interquartile range 63-77) undergoing femoropopliteal PTA was undertaken. Renal function was measured by creatinine clearance at baseline and 24 hours after the intervention; acute renal dysfunction was defined as > or = 20% decrease of creatinine clearance. The predictive value of potential risk factors was determined in a multivariate model adjusting for comorbidities, pre-existing renal impairment, and angiographic data. RESULTS: Overall serum creatinine values and creatinine clearance remained stable within 24 hours after PTA. Acute renal dysfunction occurred in 25 (12%) patients. Two (1%) patients developed oliguria; one required transient hemodialysis and developed persistent renal failure. Pre-existing impaired renal function (OR 12.2, p < 0.0001) and contrast dosage (OR 1.1, p = 0.03) were independent predictors of acute renal failure; hypertension (OR 7.9, p = 0.06) and congestive heart failure (OR 4.5, p = 0.06) were associated factors. CONCLUSIONS: While transient acute renal dysfunction occurs in approximately 10% of patients with peripheral artery disease within 24 hours after angioplasty, persistent renal failure or end-stage renal disease is rare.

Acute Kidney Injury↗

PubMed1998

The life-shortening effect of reduced physical activity is abolished by a fat rich diet.

In female mice on a control diet (3.6% fat) reduced physical activity leads to a reduction of the average life span. So the average age at death of an inactive group is 500 +/- 166 compared to 565 +/- 175 days in an active control group. If the animals are kept on a fat rich diet (12.4% fat) this effect of physical activity restriction is no longer observable and the average age at death is 570 +/- 142 days, within the range of the control animals. The increased fat intake seems to reduce the stress or to increase the resistance to stress in the activity restricted animals. So stress is a crucial determinant of life span.

Animals↗

PubMed1997

Spin trapping study of antioxidant properties of neopterin and 7,8-dihydroneopterin.

Previously, it has been shown that pteridine derivatives are capable of modulating the action of free radicals and both prooxidant and antioxidant properties have been described. However, the mechanism of manifestation of these properties is still unclear. We studied the radical scavenging properties of 7,8-dihydroneopterin and neopterin using the spin trap 5,5-dimethyl-1-pyrroline-1-oxide (DMPO). It was found that dihydroneopterin acts generally as a radical scavenger. In the presence of dihydroneopterin the ESR signal was reduced by 30 to 90% compared to the control signal. The rate constants for the reactions of 7,8-dihydroneopterin with superoxide (10(3) M(-1) s(-1)) and peroxyl radicals (10(7) M(-1) s(-1)) were determined. Neopterin in contrast showed no reduction of the ESR signal except with superoxide radicals produced by xanthine oxidase. However, this effect was shown to be due to an inhibition of enzyme rather than to radical scavenging. Our results provide a basis for understanding previous observations of radical scavenger activity of 7,8-dihydroneopterin.

Antioxidants↗

PubMed1996

A glucose-rich diet shortens longevity of mice.

High plasma levels of glucose and insulin over long-time periods play an important role in the genesis of diabetic complications. There is evidence that the long term consumption of glucose-rich diet by rats is detrimental to insulin sensitivity. We investigated the effect of a glucose-rich diet on longevity of 70 female mice which were compared to 70 mice on a control diet. The average age of death of the control group was 568 +/- 139 days compared to 511 +/- 170 for the glucose group and the seven oldest mice of the control group died at age 890 +/- 52 days, while the seven oldest mice of the glucose group died at 833 +/- 49 days. These differences are statistically significant (P < or = 0.05). Our work shows that a life-long intake of a diet with 20% of total energy derived from glucose leads to a significant reduction of the average and maximal life-span in female mice and thus, supports previous observations of detrimental effects of high glucose intake over long periods.

Animals↗

PubMed1996

The effect of reduced physical activity on longevity of mice.

Reduced physical activity leads, in female mice, to a reduction of the average and maximal life span. The average age at death of the inactive experimental group was 497 +/- 121 days (mean +/- S.D.) compared to 557 +/- 139 days in the active control group, and the six oldest inactive experimental mice died at age 732 +/- 50 days, while the six oldest active control mice died at 890 +/- 52 days. The restriction of mobility was connected with a higher growth rate and a higher body weight in spite of a significant decrease in food intake. In spite of a reduced food intake leading to a reduced whole body metabolism, the results show that mobility restriction shortens life span in female mice.

Analysis of Variance↗

PubMed1996

Effects of pteridines on chloramine-T-induced growth inhibition in E. coli strains: correlations with molecular structure.

Little is known about the biological significance of most pteridines, despite their ubiquitous occurrence in living cells. Seventeen different pteridines were tested for their ability to modulate the growth inhibitory effect of the disinfectant chloramine-T on three different strains of Escherichia coli bacteria. We found striking differences between the pteridine derivatives: whereas aromatic pterins with a hydroxy function at side chain atom C2' increased the growth inhibition, those with a 7,8-dihydro structure exerted a suppressive effect. These results are in excellent agreement with previously observed effects of pteridine derivatives on chloramine-T-induced luminol-dependent chemiluminescence, and together, are highly suggestive of a general interaction of these compounds with oxygen or chlorine free radicals. This interaction is likely to have biological significance and might offer an explanation for the widespread occurrence of pteridines.

Anti-Infective Agents, Local↗

PubMed1995

The conformational flexibility of 5,6,7,8-tetrahydrobiopterin and 5,6,7,8-tetrahydroneopterin: a molecular dynamical simulation.

5,6,7,8-Tetrahydrobiopterin is an essential cofactor of diverse enzymes. Of the eight possible stereoisomers, only the 6R,1'R,2'S-configuration is biologically active. Other stereoisomers, as well as other reduced pterins such as, e.g. 5,6,7,8-tetrahydroneopterin, fail to exhibit significant cofactor activity. Different theoretical models (molecular mechanics, semi-empirical quantum chemical calculations) investigating the stereostructure of tetrahydrobiopterin have yielded diverging answers. It has been claimed on the basis of semi-empirical quantum chemical calculations that conformational properties, and thus particular features in overall shape, might be responsible for the unique biological properties of natural tetrahydrobiopterin in contrast, e.g. to 6R,1'S,2'R-5,6,7,8-tetrahydroneopterin. Molecular dynamical simulations of both molecules at realistic temperatures demonstrate, however, that they possess sufficient conformational flexibility as to render questionable any biological significance of mere conformational properties.

Biopterins↗

PubMed1993

Effect of a high fat diet on phospholipid class distribution and fatty acid composition in rat liver.

1. Long term consumption (20 weeks) of a high fat diet (65% of the energy content as fat) rich in either saturated [30% (w/w) coconut oil] or unsaturated [30% (w/w) sunflower oil] fatty acids resulted in strikingly similar alterations in the phospholipid class distribution and fatty acid composition in the liver of male Wistar rats. 2. The effect of these two diets was compared to a control group maintained on a 2% fat diet (w/w) for the same time interval. 3. In spite of the difference in the PUFA/SFA (polyunsaturated fatty acid/saturated fatty acid) ratio between the two high fat diets (0.1, saturated fatty acid diet; 5.4, unsaturated fatty acid diet), both diets resulted in a similar PUFA/SFA ratio in liver phospholipids, a similar reduction in palmitic acid (16:0), oleic acid (18:1, n-9) and arachidonic acid (20:4, n-6) and an elevation in stearic acid (18:0), linoleic acid (18:2, n-6) and docosahexaenoic acid (22:6, n-3). 4. Further, changes in the phospholipid classes were also similarly affected by both high fat diets.

Animals↗

PubMed1989

The coenzyme nicotinamide adenine dinucleotide (NADH) improves the disability of parkinsonian patients.

The coenzyme nicotinamide adenine dinucleotide (NADH) has been used in an open label trial as novel medication in 34 patients with Parkinson's disease, using an intravenous administration technique. In all patients a beneficial clinical effect was observed. 21 patients (61.7%) showed a very good (better than 30%) improvement of disability, 13 patients (38.3%) a moderate (up to 30%) improvement. Concomitant with the improvement of the disability the urine level of homovanillic acid (HVA) increased significantly in all patients (in some patients by more than a 100%). The daily "on phases" of the patients could be increased from 2 up to 9 hours in the individual patients by NADH administration.

Aged↗

PubMed1989

The influence of noise stress on plasma epinephrine and its binding to plasma protein in the rat.

The influence of a hypersonic noise stress on plasma epinephrine level and on the distribution of i.v. administered radioactive epinephrine between the free and the protein bound form was studied in the rat. The noise stress caused an elevation of epinephrine by 180%. The radioactive hormone was removed more slowly from the vascular compartment of the stressed animals, concomitantly the protein bound fraction increased.

Animals↗

PubMed1988

Effect of skim milk and whey diets on plasma lipid levels of rabbits in a cross-over study.

The influence of a skim milk and a whey-based diet on plasma lipids and lipoproteins in rabbits was investigated in a crossover design, in which the diets were switched after 12 weeks. The whey diet increased plasma lipid levels regardless of when it was consumed in the feeding protocol. The milk diet, on the other hand, modestly elevated the lipid levels if provided in the first half of the feeding protocol, but reduced lipid levels if given in the second half of the feeding regime. Both diets also induced similar changes in lipoprotein patterns when given in the first half of the feeding protocol, but opposite effects during the second half. Atherosclerotic changes were also observed in the aorta of animals receiving the whey diet during the second half of the experimental protocol.

Animals↗