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G Rudofsky

Publications and source records attributed to G Rudofsky.

At least 19 recordsLinked to original sources
PubMed2006

Postprandial mononuclear NF-kappaB activation is independent of the AGE-content of a single meal.

OBJECTIVE: Dietary uptake of Advanced Glycation Endproducts (AGE) is supposed to potentially contribute to inflammatory reactions linked to vascular dysfunction and late diabetic complications. One mechanism by which dietary AGE might exert these effects is by activation of the proinflammatory transcription factor NF-kappa-B. The aim of this study was to analyze the postprandial effects of a casein meal with low or high AGE content on postprandial NF-kappaB activation in peripheral blood mononuclear cells (pBMC) of healthy volunteers. RESEARCH DESIGN AND METHODS: Casein was heated for 40 h at 50 degrees C in the presence of sorbitol or glucose, resulting in either minimal (Sorbitol [S]-casein) or large (glucose [G]-casein) amounts of AGE-modified casein. Nine healthy volunteers ate 250 g of both types of casein, whereas both meals were separated at least by 2 weeks. Plasma and pBMC were taken before and 2 h after each meal. Thereafter, the defined AGE carboxymethyllysine (CML) was determined by ELISA and Western blot. NF-kappaB activation in pBMC was assayed using Electrophoretic Mobility Shift Assays (EMSA) and Western blot analysis. RESULTS: S-casein contained only minor amounts of CML and no pentosidine, while G-casein contained large amounts of both. 2 h after ingestion, the S-casein or the G-casein-meal, both, resulted in a non-significant increase in plasma CML and in the intracellular CML-content of pBMC. This was paralleled by a highly significant increase in postprandial mononuclear NF-kappaB-binding activity. Remarkably, neither the extent of NF-kappaB induction (178% for S-casein, 188% for G-casein), nor composition of the NF-kappaB heterodimer (mainly consisting of NF-kappaB p50/p65) were significantly different after intake of S-casein or G-casein. Consistently, Western blots confirmed an increased NF-kappaBp65 nuclear translocation and a decrease of NF-kappaBp65 in the cytoplasm, while no difference in postprandial NF-kappaB nuclear translocation was observed following intake of S-casein or G-casein. CONCLUSION: Postprandial mononuclear NF-kappaB activation after a single meal is independent of the AGE-content of the ingested protein.

Active Transport, Cell Nucleus↗
PubMed2006

Spontaneous dissection of the popliteal artery in a young man. A rare cause of the blue toe syndrome.

Spontaneous arterial dissection in peripheral arteries of the extremities is an extremely rare event. We report a case of a spontaneous dissection of a nonaneurysmal popliteal artery in an otherwise healthy 36-year-old man that came to clinical attention as an acute blue toe syndrome. The diagnosis was primarily made by high-resolution duplex ultrasound that revealed a dissection flap (length: 15.5 mm; thickness: 0.4 mm) together with the partially thrombosed false lumen at the dorsal wall of the left popliteal artery (degree of local diameter reduction: 56%). Further work-up by means of contrast-enhanced MR-A and conventional DSA confirmed a moderate stenosis of the popliteal artery compatible with focal dissection and excluded other causes such as popliteal artery entrapment syndrome. Under full-dose intravenous anticoagulation with unfractionated heparin that was switched to oral anticoagulation with vitamin K antagonists (target INR: 2-3) and conservative management of the blue toe the patient made a gradual, but eventually complete clinical recovery over 8 weeks.

Adult↗
PubMed2005

No association of the 94T/G polymorphism in the adiponectin gene with diabetic complications.

AIM: This study examined a possible association of the T/G polymorphism at nucleotide 94 in the adiponectin gene with the prevalence of diabetic complications. METHODS: The study was performed in 696 patients with type 1 diabetes and type 2 diabetes. Genotyping was performed by means of polymerase chain reaction and subsequent cleavage by using SmaI restriction endonuclease. RESULTS: The 94G/G genotype was significantly more prevalent in patients with type 2 diabetes (2.2%) than in type 1 diabetics (0.0%) (p = 0.02), whereas no differences were found for frequencies of the 94T/T and the 94G/T genotypes, respectively. In patients with type 1 diabetes, 45 of 239 patients were heterozygous for the 94T/G polymorphism (carrier rate (CR): 18.8%; allele frequency (AF): 0.094). In type 2 diabetics, 71 of 457 patients were heterozygous and 10 patients were homozygous for the 94G/G genotype (CR: 17.7%; AF: 0.10). No association with diabetic nephropathy, diabetic neuropathy or diabetic retinopathy was found for either genotype in patients with type 1 and type 2 diabetes. CONCLUSIONS: The 94T/G polymorphism in the adiponectin gene is not associated with diabetic complications. The significance of a higher prevalence of the G allele in type 2, compared to type 1 diabetes remains to be clarified.

Adult↗
PubMed2005

Continuous passive motion in the prevention of deep-vein thrombosis: a randomised comparison in trauma patients.

There is a high risk of venous thromboembolism when patients are immobilised following trauma. The combination of low-molecular-weight heparin (LMWH) with graduated compression stockings is frequently used in orthopaedic surgery to try and prevent this, but a relatively high incidence of thromboembolic events remains. Mechanical devices which perform continuous passive motion imitate contractions and increase the volume and velocity of venous flow. In this study 227 trauma patients were randomised to receive either treatment with the Arthroflow device and LMWH or only with the latter. The Arthroflow device passively extends and plantarflexes the feet. Patients were assessed initially by venous-occlusion plethysmography, compression ultrasonography and continuous wave Doppler, which were repeated weekly without knowledge of the category of randomisation. Those who showed evidence of deep-vein thrombosis underwent venography for confirmation. The incidence of deep-vein thrombosis was 25% in the LMWH group compared with 3.6% in those who had additional treatment with the Arthroflow device (p < 0.001). There were no substantial complications or problems of non-compliance with the Arthroflow device. Logistic regression analysis of the risk factors of deep-vein thrombosis showed high odds ratios for operation (4.1), immobilisation (4.3), older than 40 years of age (2.8) and obesity (2.2).

Adult↗
PubMed2004

Microcirculation and tolerability following i.v. infusion of PGE1 and iloprost: a randomized cross-over study in patients with critical limb ischemia.

In a randomized cross-over study, the effect of PGE(1) and iloprost on microcirculation as well as the tolerability was investigated in 36 patients with peripheral arterial occlusive disease stage III and IV according to Fontaine. Patients received PGE(1) and iloprost by single 3-h i.v. infusions on two different days at doses recommended by the manufacturers or in previous studies (PGE(1): first hour 20 microg, next 2h 30 microg each. Iloprost: first hour 0.5 ng/kg/min, next 2h 1.0 ng/kg/min). Transcutaneous oxygen pressure (tcPO(2)) values increased much more with PGE(1). Median tcPO(2) increase over baseline 30 min after the end of infusion was 9 and 2 mmHg for PGE(1) and iloprost, respectively, corresponding to median AUC differences from baseline of 1050 and 210 min mmHg. Because of its exploratory character, the study was not powered to test for significance. Adverse effects occurred in 19.4% (PGE(1)) and 30.6% (iloprost) of patients. Dose reduction was required in 3 patients receiving iloprost (hypotension, nausea, irritation of the infused vein), and in none receiving PGE(1).

Aged↗
PubMed2004

A 63bp deletion in the promoter of rage correlates with a decreased risk for nephropathy in patients with type 2 diabetes.

Several polymorphisms have been identified in the RAGE-promoter region that might modulate the outcome of disease. Here we analyse the association of a 63bp deletion (delta63) spanning from bp - 407 to bp - 345 with diabetic nephropathy. The deletion was determined using the polymerase chain reaction (PCR) in a cross-sectional study with 1087 patients with type 1 diabetes (n = 559) and type 2 diabetes (n = 528). 475 patients with osteoporosis served as disease independent control. The prevalence of the heterozygous genotype did not significantly differ between the three groups (type 1: 2.15 %, type 2: 2.27 %, controls: 1.47 %), indicating that heterozygous delta63 is not related to the manifestation of diabetes. Homozygous carriers were not identified in this study. The heterozygous delta63 genotype, was associated with a reduced prevalence of diabetic nephropathy in patients with type 2 diabetes (OR = 0.06; 95 % CI: [0.05, 0.07]), but not in patients with type 1 (OR = 1.49; 95 % CI: [1.14, 1.94]). We conclude, that patients with type 2 diabetes and the 63bp deletion in the promoter of RAGE seem to be protected from diabetic nephropathy. The observed difference between type 1 and type 2 diabetes might point to diverse pathomechanisms of nephropathy in both types of diabetes.

Diabetes Mellitus, Type 1↗
PubMed2004

Reduction of postprandial hyperglycemia in patients with type 2 diabetes reduces NF-kappaB activation in PBMCs.

AIMS/HYPOTHESIS: Short-lasting hyperglycemia results in activation of the transcription factor NF-kappaB in peripheral blood mononuclear cells. We therefore studied whether the postprandial increase in glucose is sufficient to induce mononuclear NF-kappaB activation and whether blunting postprandial hyperglycemia with the alpha-glucosidase inhibitor acarbose reduces NF-kappaB activation. METHODS: 20 patients with type 2 diabetes were included in a double-blind randomized trial receiving 100 mg acarbose or placebo three times a day over a period of eight weeks. Peripheral blood mononuclear cells were isolated before and 120 minutes after a standardized breakfast. NF-kappaB binding activity was estimated by electrophoretic mobility shift assay and NF-kappaB-p65; translocation was determined by Western blot. RESULTS: Eight weeks of treatment with acarbose significantly reduced postprandial hyperglycemia (p = 0.004 when compared to placebo), postprandial mononuclear NF-kappaB-binding activity (p = 0.045) and nuclear translocation of NF-kappaB-p65 (p = 0.02). CONCLUSION: Reduction of postprandial glucose peak levels by acarbose reduces postprandial mononuclear NF-kappaB activation.

Acarbose↗
PubMed2004

Risk factors for varicose veins.

AIM: To determine the prevalence of varicose veins in the German population and specify possible risk factors the data of the Duesseldorf/Essen civil servants study were analysed. METHODS: From December 1989 to July 1993 a total of 9 935 employees were recruited. All volunteers filled out a questionnaire regarding family history and risk factors and were clinically examined. Venous findings were classified and adapted to the CEAP-classification. For the analysis of risk factors only volunteers classified as CEAP-class 0 or as CEAP-class II were considered: 4 250 men, 10% belonged to CEAP-class II and 2 380 women including 16% CEAP-class II. RESULTS: In general, age and gender were the most relevant risk factors for varicose veins. Odds ratio age: male: 3.4 (95%-CI: 2.6-4.4), age female 6.5 (95%-CI: 5.0-8.5), gender 2.3 (95%-CI 1.9-2.7). In addition in females the most frequent risk factors were oral contraception and in both genders a predominately sitting posture at work. Regarding the family history, varicose veins by the mother was most frequent compared to varicose veins by the father or both. After adjusting for age and gender heridity became the most important risk factor with an odds ratio of 5.2 (95%-CI:3.7-7.3-4.50) in case of varicose veins present in both parents, followed by a standing posture at work 2.2 (95%-CI: 1.2-3.9). In contrast, smoking also reached a significant level, but with a decreased odds ratio of 0.66 (95%-CI: 0.57-0.77) indicating a protective effect. CONCLUSION: In addition to age and gender a family history of varicose veins is the most important risk factor in the total population. Despite significant influence of other risk factors their relevance for varicose veins in the investigated population is low either due to low frequencies or low odds ratios.

Adult↗
PubMed2003

Glimepiride reduces mononuclear activation of the redox-sensitive transcription factor nuclear factor-kappa B.

AIMS: Glimepiride has the lowest ratio of insulin release to glucose decrease compared with other sulphonylureas. This prompted us to study in vitro and in vivo in a placebo-controlled study the effect of glimepiride on the redox-sensitive transcription factor nuclear factor-kappa B (NF-kappaB). METHODS: Fifteen patients with type 2 diabetes on glibenclamide with a stable HbA1c over the last 6 months were included. After sampling for determination of baseline values, 10 patients were changed to an equivalent dose of glimepiride, while the placebo group was maintained at glibenclamide plus placebo. The glimepiride dose in these patients was adjusted so that no change in glucose control occurred, allowing for direct comparison. The others were kept on glibenclamide and received additional placebo. After 4 weeks of glimepiride or glibenclamide plus placebo, a second blood sample was taken. Mononuclear cells were isolated and assayed in a tissue-culture-independent electrophoretic mobility shift assay (EMSA)-based detection system for NF-kappaB binding activity, and by Western Blot for nuclear localization of NF-kappaB-p65, the cytoplasmic content of IkappaBalpha and the NF-kappaB-controlled haemoxygenase-1. Glimepiride dose-dependent inhibition of carboxymethyllysin (CML) albumin or tumour necrosis factor alpha (TNFalpha)- and H2O2-induced activation of NF-kappaB binding were determined, using isolated peripheral blood mononuclear cells from healthy volunteers, and transcriptional activity of bovine aortic endothelial cells either left untreated or induced with CML albumin incubated with or without glimepiride. Furthermore, in-vitro studies were implemented to demonstrate radical quenching properties of glimepiride in the cell-free 2,2'-azo-bis(2-aminopropane)-dihydrochloride system. RESULTS: Baseline glucose and HbA1c remained stable in the patients switched from glibenclamide to a corresponding dose of glimepiride or kept on glibenclamide plus placebo. While in the group of patients only taking glibenclamide plus placebo the NF-kappaB binding activity did not change significantly (p = 0.58), the NF-kappaB binding activity in the group of patients taking glimepiride was reduced from 19.3 relative NF-kappaB-p65-equivalents to 15.5 relative NF-kappaB-p65-equivalents (p = 0.04). The nuclear translocation of NF-kappaB-p65 was reduced from 100% at baseline to 58% after 4 weeks (p = 0.04); the cytoplasmic localization of NF-kappaB-p65 increased from 100% to 129% (p = 0.03) and the cytoplasmic content of IkappaBalpha increased from 100% to 109% (p = 0.06). The redox-sensitive haemoxygenase-1 antigen was reduced from 100% to 82% (p = 0.04). To prove directly that glimepiride reduces NF-kappaB activation, we isolated peripheral blood mononuclear cells (PBMC) from healthy volunteers. In vitro, glimepiride reduced TNFalpha-(1 nmol/l) and CML albumin (800 nmol/l)-induced NF-kappaB activation dose dependently, being half maximal at 120 micromol/l. H2O2-mediated NF-kappaB activation was only partially reduced. In addition, glimepiride reduced NF-kappaB-dependent gene expression using a NF-kappaB-driven luciferase reporter system. Finally, a cell-free detection system showed that glimepiride has radical quenching properties. CONCLUSION: Glimepiride can affect the activation of the redox-sensitive transcription factor NF-kappaB in vitro and in vivo.

Aged↗
PubMed2003

Peripheral veins: influence of gender, body mass index, age and varicose veins on cross-sectional area.

To investigate changes in the size of the deep and superficial venous systems associated with gender, age, body mass index and varicose veins, changes to the cross-sectional area of the femoral and the long saphenous veins were analysed in the Duesseldorf/Essen civil servant study population. Between December 1989 and July 1993 a total of 9935 employees were recruited; 9261 were then evaluated for this analysis. Diameters of the long saphenous and femoral veins were determined 2-3 cm distal to the confluence in lying (after 15 min rest) and standing (after 5 min) positions. Cross-sectional areas (CSA) were calculated. A total of 63% of all people were assigned to CEAP (clinical, etiological, anatomical pathophysiological) class 0, 27% to class 1, 8.5% to class 2, while 1.5% belonged to higher CEAP classes. In people without varicose veins (CEAP class 0) the CSA of the femoral and long saphenous veins were smaller in females than in males. In people with a normal body mass index (BMI) (20-25) the mean CSA of the femoral and long saphenous veins in a standing position was similar from the third up to the sixth decade of life. The volume increase due to a standing position expressed as the absolute increase in CSA of the femoral and long saphenous veins was not age-related, either. The relative volume increase expressed as a ratio remained unchanged with age. There was a strong relationship between the CSA of both veins and increasing BMI. In a lying position, the CSA of the femoral and long saphenous veins increased only slightly with increasing CEAP classes. In a standing position, the CSA of both veins increased even in CEAP class 1 (p < 0.001). In a stepwise multivariate regression analysis, the CSA of both veins in a standing position was not age-related but associated with BMI, CEAP classes and gender. The absolute increase in CSA was influenced by all four variables, but BMI and gender were most important. In Conclusion, this study shows that aging is not necessarily associated with an increase in venous CSA of the deep and superficial venous system. BMI is the most important determinant for an increase in CSA in standing position. Varicosity of the superficial venous system is always associated with similar changes in the deep venous system.

Adult↗
PubMed2003

Klippel-Trenaunay syndrome and pregnancy.

General recommendations on how to deal with pregnancy in patients with Klippel-Trenaunay syndrome (KTS) are rare. We describe the case of a 32-year-old female with KTS, involving the head and the left arm and leg, delivering a healthy female child, and are reviewing the recent literature. The risk to deliver an ill child is low in women with KTS. At the end of the 1st trimester a sonographic investigation can exclude angiodysplastic alterations of the fetus. If the fetus shows changes compatible with KTS, a termination can be discussed because the risk of fatal complications after delivery is high. During pregnancy the careful monitoring of coagulopathic disorders is necessary. Prior to delivery an MR-scan may be useful to detect angiodysplastic vascular structures next to the spinal cord, pelvic structures or the lower abdominal wall, which might complicate peridural anesthesia or caesarean section.

Adult↗
PubMed2003

The role of comorbidity burden for patients with symptomatic peripheral arterial disease (PAD). A quantitative approach.

AIM: Comorbidity will play an increasingly important role in PAD management. Therefore, we aimed 1) to address the comorbidity load of PAD patients quantitatively and comprehensively, 2) to delineate the effects of composite comorbidity measures on general and disease-specific aspects of quality of life and on crude markers of resource allocation. METHODS: One hundred and one consecutive symptomatic PAD patients (80 males, 21 females; mean age: 66.4 +/- 9.1 years) were assessed by means of a cumulative illness rating scale (CIRS: 14 items; individual item rating from 1 for no through 5 for life-threatening impairment). Outcome measures were the illness severity score (CIRS-IS, mean of all single item scores) and the comorbidity index (CIRS-CI, number of single items with a score of 3, 4 or 5). These comorbidity indices of the PAD patients were compared with those of both 89 elderly community-dwelling volunteers (44 males, 45 females, mean age 77.4 +/- 5.3 years) we had investigated previously and 439 geriatric residents (121 males, 318 females; mean age 84.1 +/- 5.7 years) reported by Parmelee et al. in 1995. Furthermore, the PAD patients estimated their quality of life (LQ), subjective health status (HS), leg pains during either rest or walking on rating scales (ranging from 0 for the best to 10 for the worst result). RESULTS: PAD patients showed very high comorbidity indices and illness severity scores (CIRS-CI: 3.98 +/- 1.60; CIRS-IS: 1.86 +/- 0.29). These proved to be greater than those of both fit community-dwelling elderly subjects (CIRS-CI: 1.82 +/- 1.46; CIRS-IS: 1.62 +/- 0.22) and older institution residents (CIRS-CI: 2.17 +/- 1.85; CIRS-IS: 1.64 +/- 0.34). Furthermore, both CIRS-CI and CIRS-IS were significantly greater in patients with more advanced PAD stage. These indices of comorbidity load were also associated with quality-of-life impairments (r=0.253, p=0.0186), degree of ischemic rest pain (r=0.251, p=0.0196), extent of medication usage (r=0.511, p<0.0001) as well as duration of in-hospital stay (r=0.271, p=0.0084). CONCLUSION: PAD patients have a markedly increased comorbidity burden. This was greater in the more advanced PAD stages and significantly associated with quality-of-life reductions and the extent of resource allocation. A quantitative approach to the comorbidity load in PAD patients appears to be possible by means of such a scale and useful for both clinical and socioeconomic purposes.

Aged↗