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E Wenzel

Publications and source records attributed to E Wenzel.

At least 19 recordsLinked to original sources
PubMed2006

The Retention Index Test Homburg (RTH-II): Response to clopidogrel and comparison with aggregometry and CD62P-expression.

The Retention Index Test Homburg (RTH-II) is quoted to detect effects of shear stress on platelets, which involve ADP receptor signaling. RTH-II might be a tool for monitoring antiplatelet therapy for compounds that interfere with ADP induced platelet activation and secretion. In a series of investigations, we used an ADP (2 microM) triggered RTH-II in parallel with light-transmittance aggregometry and flow cytometry in subjects before and after clopidogrel. A loading dose of 225 mg clopidogrel leads to a significant reduction (p < 0.01) in the ADP-stimulated retention index (RI) from 69 +/- 15 to 48 +/- 21%, in the aggregation response to 5 microM ADP (from 50 +/- 20 to 29 +/- 21%) and the expression of CD62P (from 64 +/- 11 to 41 +/- 17%). Correlation analysis showed that the RI corresponds significantly to CD62P-expression (p < 0.01) but not to aggregation. We also found a strong correlation (p < 0.01) between the ADP-stimulated RI and the expression of CD62P after stimulation with 2 microM ADP, whereas no correlation was seen for RI vs. binding of PAC-1 or aggregation. Platelets not retained in the filter had lower CD62P expression than measured in the sample before the filter passage (54 vs. 35%). A direct interaction of CD62P with platelet ligands might lead to enhanced retention in RTH and explain the correlation of RI with CD62P expression. The RTH-II might be a simple and easy to handle platelet function assay for monitoring effects on P2Y(12)-inhibitors on platelet degranulation, perhaps in addition to aggregometry.

Adenosine Diphosphate↗
PubMed2005

[Transpupillary thermotherapy (TTT) for uveal melanomas. Long term results of a single TTT with an adapter for a conventional infrared laser].

BACKGROUND: An increasing number of orbital recurrences after TTT have been reported; the aim of our paper was to present our long-term results after a maximum follow-up of 8 years and 2 months. PATIENTS AND METHOD: Among 18 eyes, 10 tumors were classified as small, and 8 as medium sized (with a maximum prominence of 5.6 mm): 5 melanomas had a juxtapapillary location, 6 a macular (or juxtamacular) location, and 7 were located in the midperiphery of the fundus. RESULTS: After a median follow-up of 7 years in seven tumors a complete regression (scar formation) could be achieved, and in six a partial regression (with a maximum residual prominence of 2.9 mm) could be seen. In three patients a recurrence was treated either by another TTT or a Ruthenium-106 plaque; in another two recurrences, enucleation had to be performed. In none of the cases has an orbital recurrence occurred so far. CONCLUSION: To prevent recurrences, adequate technique and appropriate selection of patients are mandatory in our opinion (no tumors higher than 3 mm). The higher the tumor prominence, the greater the chance of recurrences. Amelanotic melanomas and macular melanomas seem to respond poorly to thermotherapy.

Adult↗
PubMed2004

[Platelet retention test Homburg (RTH) and drug monitoring of platelet adhesive properties of von Willebrand factor].

Platelet plug formation is initiated by the process of platelet adhesion, mainly mediated by the von Wille-brand factor (VWF). Therefore, apart from established criteria the platelet adhesion property is a further criterion to determine VWF e. g. in diagnosis and treatment of von Willebrand disease (VWD). The new platelet retention test Homburg (RTH) is designed to close this gap. It is characterized by its non-thrombogenic filter with interconnecting pores, which retains platelets from blood when pressed through this filter due to the resulting shear stress. The RTH, in particular, proved to be highly sensitive in detecting the platelet adhesive property of VWF after its release from endogenous storage sites by desmopressin or infusion in VWD patients or its supplementation in vitro.

Drug Monitoring↗
PubMed2003

Dietary soy oil content and soy-derived phytoestrogen genistein increase resistance to alopecia areata onset in C3H/HeJ mice.

Alopecia areata (AA) is a complex, multi-factorial disease where genes and the environment may affect susceptibility and severity. Diet is an environmental factor with the potential to influence disease susceptibility. We considered dietary soy (soya) oil content and the soy-derived phytoestrogen genistein as potential modifying agents for C3H/HeJ mouse AA. Normal haired C3H/HeJ mice were grafted with skin from spontaneous AA affected mice, a method previously shown to induce AA. Grafted mice were given one of three diets containing 1%, 5% or 20% soy oil and observed for AA development. In a separate study, mice on a 1% soy oil diet were injected with 1 mg of genistein three times per week for 10 weeks or received the vehicle as a control. Of mice on 1%, 5%, and 20% soy oil diets, 43 of 50 mice (86%), 11 of 28 mice (39%), and 2 of 11 mice (18%) developed AA, respectively. Four of 10 mice injected with genistein and 9 of 10 controls developed AA. Mice with AA had hair follicle inflammation consistent with observations for spontaneous mouse AA, but no significant association was observed between the extent of hair loss and diet or genistein injection. Mice that failed to develop AA typically experience white hair regrowth from their skin grafts associated with a moderate macrophage and dendritic cell infiltration. Soy oil and derivatives have previously been reported to modify inflammatory conditions. Hypothetically, soy oil compounds may act on C3H/HeJ mice through modulating estrogen-dependent mechanisms and/or inflammatory activity to modify AA susceptibility.

Alopecia Areata↗
PubMed2002

Effect of heat-treated proteins on selected parameters of the biotransformation system in the rat.

The intake of heat-damaged proteins from food causes various effects, like the loss of essential amino acids and a reduced protein digestibility. There is also an influence on gastrointestinal microorganisms and different digestion enzymes. Until now, very little is known about the influence of heat-treated proteins on the enzymes of the biotransformation system. In the present study, the influence of protein-bound L-lysino-D,L-alanine, N(epsilon)-fructoselysine, and N(epsilon)-carboxymethyllysine (CML) on selected enzymes of the biotransformation in liver, kidney, and intestinal mucosa of male Wistar rats was examined. The contents of cytochrome P-450 and cytochrome b(5) and the activity of NADPH-cytochrome c reductase served as indicators of phase I biotransformation. The influence on phase II biotransformation was shown by the content of glutathione and the glutathione S-transferase activity. The results showed that treatment with heat-damaged proteins mainly affected phase II biotransformation enzymes with CML, yielding the strongest effect. The activity of glutathione S-transferase in the kidney was 86% higher in animals treated with diets containing 4,930 mg.kg(-1) protein-bound CML than in animals of the control group which received a diet without any detectable CML. In addition, a higher level of glutathione was found in the kidneys of animals fed on diets containing CML. The glutathione S-transferase activity was 64% higher in the intestinal mucosa of animals fed on protein-bound N(epsilon)-fructoselysine (2,700 mg.kg(-1)). The glutathione S-transferase activity was higher (p >0.05) in the intestinal mucosa of animals fed on protein-bound L-lysino-D,L-alanine (2,582 and 12,474 mg.kg(-1)). In conclusion, ingestion of heat-treated proteins led to an activation of the enzymes of phase II biotransformation. Whether or not the released pure compounds or the degradation products of the test proteins are responsible for the altered enzyme activities remains to be evaluated.

Animals↗
PubMed2001

Effects of an onion-olive oil maceration product containing essential ingredients of the Mediterranean diet on blood pressure and blood fluidity.

Twenty-four patients with arterial hypertension (WHO class I) received either 4 capsules of an onion-olive oil maceration product, containing essential ingredients of the Mediterranean diet, or placebo daily over a period of one week. In order to investigate the acute effect on arterial blood pressure, measurements were performed before and 5 h after the administration of the first dose of 4 capsules verum or placebo, respectively. For the evaluation of the long term effect further blood pressure measurements were performed after one week's treatment with a daily dose of 4 capsules. After a wash-out phase of 2 weeks followed by a crossover, the second study phase, which was identical in design, was carried out. In addition patients were instructed to measure their blood pressure 4 times daily at home for the whole study period. Haemorheological parameters (platelet aggregation, erythrocyte aggregation, plasma viscosity and haematocrit) were also determined at the measuring points mentioned above. The onion-olive oil maceration product led to a significant decrease in systolic blood pressure. There was also a trend towards a decrease in diastolic blood pressure. The improved blood fluidity observed resulted from a decrease in haematocrit. All effects could be shown immediately and after one week's administration.

Adult↗
PubMed2000

Molecular biology and clinical manifestation of hereditary factor VII deficiency.

Inherited factor VII (FVII) deficiency is a rare autosomal recessive disorder. Mutations and polymorphisms of the FVII gene were characterized in more than 40 unrelated patients with FVII deficiency. Among the 29 different mutations, the most frequent were Ala294 Val, Ala294Val;404delC, IVS7+7, and Val281 Phe. Four novel mutations (IVS2+1G>C, Arg247 Cys, Glu265 Lys, Asp343 His) were detected. The relationships between genotypes of mutations and polymorphisms of the FVII gene, FVII deficiency, and clinical phenotype were investigated. Homozygosity of the Phe4 Leu, IVS4+1G>A, Cys135 Arg, Ala244 Val, and Ala294 Val;404delC and the double heterozygosity of Tyr68 Cys / IVS3-1G>A, Val252 Met / IVS2+5G>T, Val281 Phe / Cys135 Arg, Ala294 Val / Val281 Phe, Ala294 Val;404delC / Val281Phe, Ala294 Val;404delC / Arg152 stop, Ala294Val;404delC / Gln(-35) stop, Ala294 Val / Val252 Met, Ala294 Val / Gly156 Asp, and Thr359 Met / Asp242 His were related to clinical symptoms. Double heterozygotes for Arg247 Cys / IVS2+1G>C, Ala206 Thr / Pro303 Arg, Leu(-20) Pro / Val252 Met as well as IVS7+7 /Ala294 Val, IVS7+7 /Ala206 Thr, and IVS7+7 / Met298 Ile were asymptomatic. The clinical symptomatology is rather poor in correlation with the FVII activity. Concerning the clinical phanotype, a correlation seems to exist between specific mutations and clinical symptoms.

Factor VII↗
PubMed2000

Heparin-induced thrombocytopenia: a critical risk/benefit analysis of patients in intensive care treated with R-hirudin.

Patients in intensive care may be at high risk of in vivo platelet activation because comorbid conditions, such as infections, septicemia, shock, disseminated intravascular coagulation, and cancer represent procoagulant states. Hyperreactivity of platelets with or without a decline of cell count may result in thromboembolic complications potentially associated with the phenomenon of heparin-induced thrombocytopenia. We analyzed the data of 10 patients highly suspected of having heparin-induced thrombocytopenia during their intensive care treatment of 29 plus or minus 22 days. In seven patients, thrombocytopenia coincided with thromboembolic complications. Six patients had additionally undergone fibrinolytic therapy before starting activated partial thromboplastin time-adapted alternative anticoagulation with r-hirudin. In three patients, the platelet count decreased without a clinical manifestation, of heparin-induced thrombocytopenia. R-Hirudin treatment monitored by activated partial thromboplastin time and prothrombin time (PT) was effective and safe. The target value for activated partial thromboplastin time was a twofold prolongation. In four of five patients with deep venous thrombosis, a partial recanalization of the lower extremity could be achieved. Three patients with pulmonary embolism associated with deep venous thrombosis in two cases and in one additional case with an acute myocardial infarction did clinically profit from fibrinolysis with recombinant tissue plasminogen activator (rtPA) and r-hirudin treatment. Two lethal events probably caused by the underlying multimorbidity could not be prevented. No recurrence of thrombosis occurred, and there were no severe bleeding complications attributed to r-hirudin treatment. Platelet counts were significantly reduced on day 9.4 plus or minus 6.4 of heparin administration in all cases (>50% decrease related to the initial values) from 224,000 plus or minus 126,000/microL to 96,000 plus or minus 61,000/microL, and increased during rhirudin treatment to mean values of 224,000 plus or minus 126,000/microL. The heparin-induced platelet activation assay (HIPAA) assay was positive in 8/10 cases, whereas the PF4 enzyme-linked immunosorbent assay showed a positive result in four of eight analyzed cases. In four cases, the assays were concordantly positive. The PF4 enzyme-linked immunosorbent assay was not performed in two cases.

Adult↗
PubMed2000

Capillary microscopic and rheological dimensions for the diagnosis of von Willebrand disease in comparison to other haemorrhagic diatheses.

It is known that angiodysplasia influence macrocirculation as well as microcirculation in patients with vWD. In the present study it was examined if intravital capillary microscopic dimensions (morphologic and dynamic) in skin (nailfold) in combination with rheologic parameters could give indications for the presence of vWD in patients with haemorrhagic diathesis. Patients with vWD (n = 100; 92 type 1: definite type 1:78 and possible type 1:14: 8 type 2A) have in comparison to patients with other haemorrhagic diathesis [thrombocytopathy (n = 122), thrombocytopenia (n = 101). severe haemophilia A (n = 50) and severe haemophilia B (n = 20). congenital dysfibrinogenaemia (n = 22), oral anticoagulation with phenprocoumone (n = 112)] and to apparently healthy subjects (n = 100) a significantly increased capillary torquation (median index: 3.5), a venolar and an arteriolar capillary dilatation (median: 16.5 microm; median: 15.1 microm) and the highest part of microscopic bleedings (extravasates) with 40% in the video capillary microscopy as morphological changes. Only the congenital dysfibrinogenaemia appears with a larger dilatation in venolar capillaries (median: 14.5 microm). Microscopic bleedings are much less common in other haemorrhagic diatheses with a frequency between 4% and 13%. In the vWD a significantly reduced duration of reactive hyperaemia (median: 150 sec). This is the only dynamic change that can be taken as a possible hint for a loss of flexibility within the precapillary vessels. A significantly reduced plasma viscosity (< 1.25 mPas) is typical for the vWD due to the increase of the shear stress in blood plasma because of the reduction of vWF-activities. Changes of the capillary morphology (dilatation, extravasates, capillary torquation) and the hypoplasmaviscosity are most sensitive for the vWD (75%, 65%, 40%, 80%) with a fairly high specifity (up to 93%) and a positive predictive value of 99%. As a conclusion it seems reasonable to discuss the introduction of video capillary microscopy as a screening test for haemostasiological and angiological centers.

Adult↗
PubMed1999

Improved therapeutic safety of oral anticoagulant therapy in Germany: the Saarland model.

In contrast to other European countries, in Germany more than 90% of oral anticoagulated patients are controlled by general practitioners. The International Normalized Ratio (INR) system in laboratory control is not in widespread use, often leading to misinterpretations of prothrombin time (PT) measurements. To improve the management of anticoagulated patients, a model was developed, consisting of different questionnaires and on the base of the INR system. Since 1993, 60 patients in our Department's outpatient anticoagulant clinic and since 1996 16 patients in the office of a general practitioner were followed for 146.32 patient years. There were no thromboembolic events and no major bleedings during follow-up. A total of 126 minor bleedings occurred in 30 patients. There were no significant differences in INR values and stable phases between the two centers; however, significantly shorter stable phases in patients with bleeding episodes were noted. Thus, this model seems to be useful also in general practitioners' hands.

Administration, Oral↗
PubMed1999

The "Phoenix" ADR database of the Drug Commission of the German Medical Profession--a clinically useful approach to optimize evidence-based medicine in Germany.

The innovative "Phoenix" database system of the Drug Commission of the German Medical Profession (AkdA) permits rapid access to data on adverse drug reactions. It enables the user to conduct searches covering a wide variety of questions within a short period of time. No one needs to be an "expert" to extract scientific knowledge from a database that currently already contains some 106,000 reports on adverse drug reactions. While our traditional apprenticeship model of physician training has served us well, an adaptation will be required for the new millennium. New tools are needed to allocate the available resources. Clinical proposals of experts or opinion leaders, guidelines, and highly graded clinical studies, like the use of clinical databases may help to improve safety and efficacy of drug administration. Evidence-based critical care medicine is therefore a potential tool for improving the effectiveness of drug therapy and for the patient's outcome. Over and above, the Phoenix database might be interpreted as an initiative instrument, which is easy to use and contributes to highlight the determinants of clinical decisions.

Databases, Factual↗
PubMed1999

Analysis and occurrence of adverse events with oral anticoagulant therapy.

The antithrombotic potential of oral anticoagulants is undisputed as the frequency of recurrent thrombosis is high unless anticoagulant therapy is continued after hospital discharge. However, the relationship between potency and/or changes in anticoagulant therapy and frequency of complications remains unclear. Optimizing the clinical management of oral anticoagulation information obtained by databases may be advantageous in addition to meeting safety criteria, as described in the "Saarland Model." The Phoenix-database implicates an association between bleeding complications and the hypertensive elderly. From 1968 to 1993 most reports about cerebral/intraspinal bleedings occurred at prothrombin (PT)-values below 20% in the elder patients (>60 years of age) (12%; 367 reports). In the Saarland Model, 60 patients were followed from our department during a 3-year period. Our findings suggest neither a correlation of the range of PT values and the bleeding events nor an association with age or hypertension. It became obvious that "stable phases" of International Normalized Ratio (INR) [+/-15% change of 4 serial controls using nearly constant weekly oral anticoagulant dosages (+/-15%)] might be considered as a valid criterion of safety. At least the individual risk profile determines the patient's fate.

Administration, Oral↗
PubMed1999

The overdosed patient and bleedings with oral anticoagulation.

Overdose or bleeding with oral anticoagulation requires gradual antagonization of the drugs. Minor bleedings are most commonly managed by temporarily discontinuing treatment and by giving vitamin K to antagonize the coumarin derivative effects. Major bleedings, in contrast, especially intracranial hemorrhages, require immediate antagonization of anticoagulation. This is also necessary in required major surgery of anticoagulated patients. Instant normalization of hemostasis in such cases is achieved by the administration of clotting factors, in particular prothrombin complex concentrates. The use of fresh frozen plasma, instead, is less useful. The treatment with prothrombin complex concentrates requires a strict risk-benefit estimation and laboratory monitoring is recommended to optimize dosage adjustment. A 2-year follow-up of 45 out-patients receiving phenprocoumon at our center revealed a total of 11 bleeding complications (11.6/100 treatment-years, 10 minor and 1 major bleeding). Discontinuing or reducing oral anticoagulation together with vitamin K were the methods most frequently used to efficiently manage hemorrhages, whereas prothrombin complex concentrates were only used in one case with major bleeding. Oral anticoagulation appeared to be an enhancing factor for an otherwise existing bleeding diathesis rather than a genuine cause for hemorrhages.

Administration, Oral↗
PubMed1999

Training of patients for self-management of oral anticoagulant therapy: standards, patient suitability, and clinical aspects.

Self-control and self-management of oral anticoagulant therapy have become more and more attractive for patients undergoing long-term treatment. In our training center, we examined 50 patients who took part in a standardized training course for self-management. Patients (36 men, 14 women) were preselected according to the guidelines of the German Association for Self-management of Oral Anticoagulation (ASA e.V.) and were all trained by the same physician. The complete course took an average of eight sessions. Patients older than 59 years needed significantly more training time in theoretical advising than younger patients; they did not need more training time in practical matters. The values between International Normalized Ratio (INR) measured in venous blood samples and by self-assessment were comparable for both groups. There was a good overall correlation between self-controlled INRs and laboratory assays, however, the self-assayed INRs were significantly lower than those from the venous blood samples.

Administration, Oral↗
PubMed1998

Comparison of a once daily with a twice daily subcutaneous low molecular weight heparin regimen in the treatment of deep vein thrombosis. FRAXODI group.

BACKGROUND: Clinical trials have been performed to compare with standard heparin a once or a twice daily regimen of low-molecular-weight heparin but no direct comparison has been done between these two low-molecular-weight heparin regimens in terms of efficacy and safety with a long-term clinical evaluation. METHODS: Patients with proximal deep vein thrombosis, confirmed by venography were randomly assigned to either nadroparin (10,250 AXa IU/ml) twice daily or nadroparin (20,500 AXa IU/ml) once daily for at least 5 days. Regimens were adjusted to bodyweight. Oral anticoagulants were started on day 1 or 2 and continued for 3 months. Patients were followed up for 3 months. The composite outcome of venous thromboembolism and death possibly related to pulmonary embolism was the primary measure of efficacy. Major bleeding was the principal measure of safety. The study was designed to show equivalence between the two regimens. RESULTS: Recurrent thromboembolic events or death possibly related to pulmonary embolism were reported in 13 patients in the once daily group (4.1%) and in 24 patients of the twice daily group (7.2%): (absolute difference 3.1% in favor of the once daily regimen; 95% confidence interval -6.6%, +0.5%). Major bleeding episodes during nadroparin treatment occurred in 4 (1.3%) and 4 patients (1.2%) in the once and twice daily groups, respectively. CONCLUSIONS: A nadroparin regimen of one injection per day is at least as effective and safe as the same total daily dose divided over two injections for the treatment of acute deep vein thrombosis.

Adolescent↗