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E Wenzel

Publications and source records attributed to E Wenzel.

At least 55 records · Page 3Linked to original sources

[The legally required guidelines for reporting risks or side-effects caused by blood components].

OBJECTIVE: To prevent dangers to health resulting from the application of drugs, the legislator requires the central registration and evaluation of all drug risks, especially of side effects and reciprocal effects. Since 1988 pharmaceutical enterprises have had to denominate a qualified person ('Stufenplanbeauftragter') who is responsible for the fulfilment of obligatory reporting. In case of complaints or side effects he has to take suitable measures according to a special plan ('Stufenplan'). DATA SOURCES: The basis of this survey are the legal requirements for drugs ('Arzneimittelgesetz') and supplementary regulations which define the duties of the 'Stufenplanbeauftragter'. RESULTS: Blood components are subject to the legal requirements ('Arzneimittelgesetz') without reservations. Therefore the corresponding regulations have to be applied without modification in institutes for transfusion medicine. In this article the tasks of the 'Stufenplanbeauftragter' are summarized and practical experience of a university institute for transfusion medicine is presented. CONCLUSIONS: In connection with the transmission of viral infectious diseases it became evident that the 'Stufenplanbeauftragter' is very important for the initiation of effective measures in case of serious side effects. The security of blood components could be improved by the realization of the corresponding legal requirements in the institutes for transfusion medicine.

Adverse Drug Reaction Reporting Systems↗

Influence of sonographic contrast media on microcirculation in rats.

In an open placebo-controlled study the influence of the injection of different sonographic contrast media on the microcirculation was proved. The study was performed in 7 Sprague-Dawley rats. In order to examine this query two different sonographic contrast media in comparison to agitated electrolyte solution (as the placebo) were injected into the abdominal aorta of 7 anaesthetized rats as a 2 ml/kg bolus at 10-min intervals. Examined were a newly developed agitated ultrasound solution (AK I: an aequeous solution of a vegetable phospholipid) and a radiographic contrast agent (AK II: 741 mg Ioversol or 350 mg iodine, respectively, per ml) which is used in an agitated form as ultrasound contrast agent, too. 1 min before and until 2 min after each injection the capillary perfusion of the same vessel area in the major omentum was measured (video-recording by use of intravital microscopy). The erythrocyte velocity was determined off-line by an image analysing system. Whereas the agitated X-ray contrast medium AK II decreases the mean capillary perfusion (temporary flow stagnation in single capillaries), AK I as well as agitated electrolyte solution did not influence the capillary erythrocyte velocity in the major omentum. The gaps which appeared immediately after the injection of AK I seem to have been brought about by spherosomes of AK I. Still the spherosomes are so small that they can pass through the capillaries, or if they are larger which cannot be determined using in vivo microscopy the flow force necessary for the deformation of the bubbles is so small that the capillary perfusion is not influenced. The injection of agitated AK I does not lead to significant changes of the microcirculation.

Animals↗

HES 200/0.5 is not HES 200/0.5. Influence of the C2/C6 hydroxyethylation ratio of hydroxyethyl starch (HES) on hemorheology, coagulation and elimination kinetics.

The plasma clearance of hydroxyethyl starch (HES) depends on the initial molecular weight and the degree of substitution. So far, little attention has been paid to the clinical relevance of the C2/C6 substitution ratio of hydroxyethyl starch. 10 patients with cerebrovascular circulatory disturbance received hemodilution therapy for 10 days, consisting of 10% HES 200/0.5 (mean molecular weight 200 kD, degree of substitution 0.5) with a C2/C6 ratio of 13.4. A second group of 10 patients received a starch solution with identical initial molecular weight and degree of substitution but with a C2/C6 ratio of 5.7. After the administration of a single dose, no significant differences between the two groups were observed. After repeated administration, significant differences could be detected in hemorheology, coagulation and elimination (p < 0.01). The larger C2/C6 ratio led to a higher intravascular mean molecular weight (95 vs. 84 kD), which in turn led to a higher increase in serum concentration during the therapy (14.7 vs. 8.6 mg/ml). Hematocrit was lowered more (-30.5 vs. -23.5%) and plasma viscosity was increased more. There was also a more pronounced increase in partial thromboplastin time (+30% vs. +13%) and a factor of 2 larger decrease of factor VIII/von Willebrand factor-complex (p < 0.01), which exceeded the dilution effect. The higher C2/C6 ratio of HES 200/0.5/13.4 slows down enzymatic degradation. After repeated administration of this starch, large molecules accumulate which are inefficiently degraded. The same effect has been observed after therapy with highly-substituted HES. This accumulation of large molecules leads to a beneficial longer lasting volume effect. The disadvantages include an increase in plasma viscosity and coagulation disturbances, which cannot be explained with the respective dilution effect alone. For these reasons, the C2/C6 ratio is of clinical relevance and should be included in the product labeling in the future.

Alkylation↗

Determination of factor XIII activity by a new photometric assay in plasma and platelets of healthy blood donors.

Crosslinking of fibrin monomers by activated factor XIII (F XIIIa) is a final event in blood coagulation. So the fibrin clot gains mechanical stability and resistance to plasmin degradation which is thought to be essential for normal blood clotting and wound healing (1-3). In addition, changes in plasma F XIII activity were found in several state of disease such as collagenoses, inflammatory bowel diseases, leukemias, subarachnoidal bleeding and delayed fracture healing (4-12). Because approximately 50% of the potential F XIII activity in plasma are present in platelets (1), the additional determination of F XIII activity in platelets is of clinical interest especially concerning platelet transfusions that may exert an additional benefit due to simultaneous substitution of platelet-bound F XIII. The latter differs from plasma F XIII as a dimer containing only a-chains (a2) compared to the plasmatic tetramer carrying additional b-chains (a2b2). We applied a recently described photometric assay suitable for the routine laboratory after adaption to an autoanalyser to determine F XIII activity in plasma and platelets of 64 healthy blood donors.

Adolescent↗

Cytokine mRNA levels in Alopecia areata before and after treatment with the contact allergen diphenylcyclopropenone.

Although the nature of the noxious signal and the anatomical target in alopecia areata (AA) are still unknown, it has been assumed that CD4+ T lymphocytes surrounding and infiltrating the hair bulb might trigger the hair loss. As these T lymphocytes do not promote cytotoxic activity we hypothesize that AA is triggered by cytokines. Topical immunotherapy with diphenylcyclopropenone (DCP) is at present the most effective approach. If it is true that AA results from a distinct cytokine pattern, we can hypothesize that the beneficial effect of DCP should be mediated by locally secreted cytokines during the contact allergy. Using semiquantitative reverse transcription-polymerase chain reaction with RNA extracted from scalp biopsies from patients with AA before and after successful treatment with DCP, and from healthy controls we detected a T-cell response with increased steady state mRNA levels for interferon (IFN)-gamma, interleukin (IL)-1 beta, and IL-2 in untreated AA of the totalis type. After DCP treatment, the IFN-gamma expression was reduced but still above the constitutive level found in controls, whereas mRNA expression of IL-2, IL-8, IL-10, and tumor necrosis factor-alpha was increased. Our results point towards cytokines involved in the pathogenesis in AA. A TH1 type cytokine pattern is present in untreated AA, and this is modified by cytokines secreted during DCP treatment. IL-10 has recently been described as an immunomodulator of the TH1 response and, therefore, we hypothesize that basal keratinocytes or lesional T cells secrete bioactive IL-10 after DCP application, resulting in an inhibitory effect on lesional T lymphocytes. This hypothesis would explain the effectiveness of DCP and implies the theoretical possibility of a response to topical or intralesional application of recombinant IL-10.

Adult↗

[Autotransfusion with leap-frog technique in patients with coronary heart disease and planned aortocoronary venous bypass].

OBJECTIVE: The goal of the study is to test and control the quality of a special leap-frog technique which enables saving heterologous blood. DESIGN: In a randomized double-blind placebo-controlled study homologous blood was taken in 40 out of 100 patients with coronary heart disease before aortocoronary bypass operation. The leap-frog technique was used. Within 8 weeks 3-4 erythrocyte concentrates and 0.9-1.2 liters plasma were sampled. The volume (verum: HES 200/0.5 10%; placebo: 0.9% NaCl solution) substituted corresponding to the volume of blood donated. Each patient received 200 mg Fe2+/day p.o. RESULTS: Clinically, only patients treated with HES in stage of autologous blood sampling benefited significantly. Two patients showed adverse effects. The peri- and postoperative course was comparable. In the NaCl group one of the patients received homologous erythrocyte concentrates. None of the patients died pre-, peri- or post-operatively. CONCLUSIONS: 40% of the cardiosurgical patients could be considered for autologous blood donation. Isovolemic hemodilution with HES 200/0.5 10% was a suitable and safe measure in preoperative blood sampling. Physical exercise should be performed before and after autologous blood donation. A reduced exercise tolerance suggests that autologous blood donation should be stopped.

Adult↗

[Comparison of 2 6% middle-molecular hydroxyethyl starch solutions on elimination kinetics and flow characteristics of blood in volunteers].

OBJECTIVE: Investigation of the influence of C2/C6 occupation ratio of 2 different 6% hydroxyethyl starch (HES) solutions on elimination kinetics and blood fluidity. DESIGN: A single-blinded, prospective randomised cross-over study. SETTING: Haemostasiological-angiologic outpatient department of the university of Homburg. SUBJECTS: 6 voluntary apparently healthy subjects. INTERVENTIONS: A 500 ml infusion of 2 different HES solutions (6% HES 200/0.5 or 6% HES 200/0.62, respectively) was given intravenously within 1 h. A wash-out phase of 3 months was kept between both infusions. The concentration and distribution of the molecular weight of the intravasal HES molecules up until 24 h after the infusion as well as the blood fluidity before and after the infusion were measured. RESULTS: Besides the molecular substitution (MS), which is different for the 2 employed HES solutions, the occupation ratio of the C2 respectively C6 (C2/C6 occupation ratio) of the glucose ring influences the breakdown of the HES molecules. This influences the blood fluidity. While the decrease in haematocrit 1 h after the end of the infusion is comparable, the decrease in the haematocrit in the case of high C2/C6 occupation ratio and a high MS is maintained for a longer period of time. The increase in plasma viscosity in the case of high C2/C6 occupation ratio and high MS is more marked. CONCLUSIONS: The infusion of HES 200/0.62 leads to a significantly longer prevalence in comparison to HES 200/0.5, in combination with clearly larger degradation products in the plasma; this fact causes a more marked dilutional effect, but also a more marked increase in the plasma viscosity up to 24 h after the end of infusion. In the discussion on haemodilution therapy in patients with arterial occlusive disease the employment of HES which induces an increase in plasma viscosity is thought to be a disadvantage.

Adult↗

[Computer assisted analysis of the morphology of cutaneous capillaries in human intravital microscopy].

Reproducibility of capillaroscopic data is studied by a computer-assisted interactive quantification method. Determination of capillary tortuosity and capillary density is a quantitative method with a variation coefficient below 7%, while determination of erythrocyte column diameter has to be considered as a semiquantitative method. Problems arising during interactive evaluation as in case of bundles of capillaries or massive capillary dilatation are discussed in the paper.

Capillaries↗

[Autotransfusion using the bocksprung technique in patients with coronary heart disease and coronary artery bypass grafting].

Clinically, only patients treated with HES in stage of autologous blood sampling benefited significantly. Two patients showed adverse effects. The peri- and postoperative course was comparable. In the NaCl group one of the patients received homologous erythrocyte concentrates. None of the patients died pre-, peri- or postoperatively. 40% of the cardiosurgical patients could be considered for autologous blood donation. Isovolemic hemodilution with HES 200/0.5 10% was a suitable and safe measure in preoperative blood sampling. Physical exercise test should be performed before and after autologous blood donation. A reduced exercise tolerance suggests to stop autologous blood donation.

Blood Banks↗

Primary and secondary microcirculatory disorders in essential hypertension.

In this prospective cross-sectional study blood fluidity and peripheral microcirculation were measured in patients suffering from essential hypertension with and without macroangiopathy. The cutaneous microcirculation was evaluated by intravital microscopy and the intramuscular by pO2 needle electrode. Disorders in the microcirculation without macroangiopathy in the system of the feeding arteries are defined as primary microangiopathy. Disturbed microcirculation with macroangiopathy in the feeding arteries in one area but no detectable microcirculatory disorder in another region is defined as a secondary microcirculatory disorder. Of the 57 patients in this study 27 had a primary microcirculatory disorder. It was remarkable that all 27 hypertension patients had a microcirculatory disorder in the area of the skin. Intramuscular microcirculatory disorder on its own without affection of the skin was not detected in any case. An exclusively secondary microcirculatory disorder occurred in 16 patients. This study shows that 93% of the patients with long-term essential arterial hypertension have microcirculatory disorders. It is most interesting that about one-half of these hypertension patients had a primary microcirculatory disorder, i.e., no indication of a hemodynamically active stenosis was found in the large vessels.

Adult↗

Effects of garlic coated tablets in peripheral arterial occlusive disease.

For the first time, a weak clinical efficacy of a 12-week therapy with garlic powder (daily dose, 800 mg) is demonstrated in patients with peripheral arterial occlusive disease stage II. The increase in walking distance in the verum group by 46 m (from 161.0 +/- 65.1 to 207.1 +/- 85.0 m) was significantly higher (P < 0.05) than in the placebo group (by 31 m, from 172.0 +/- 60.9 to 203.1 +/- 72.8). Both groups received physical therapy twice a week. The diastolic blood pressure, spontaneous thrombocyte aggregation, plasma viscosity, and cholesterol concentration also decreased significantly. Body weight was maintained. It is quite interesting that the garlic-specific increase in walking distance did not appear to occur until the 5th week of treatment, connected with a simultaneous decrease in spontaneous thrombocyte aggregation. Therefore, garlic may be an appropriate agent especially for the long-term treatment of an incipient intermittent claudication.

Adult↗

Effect of garlic on platelet aggregation in patients with increased risk of juvenile ischaemic attack.

A platelet-inhibiting effect is described for garlic. In this double-blind, placebo-controlled study on 60 voluntary subjects with cerebrovascular risk factors and constantly increased platelet aggregation it was demonstrated that the daily ingestion of 800 mg of powdered garlic (in the form of coated tablets) over 4 weeks led to a significant inhibition of the pathologically increased ratio of circulating platelet aggregates and of spontaneous platelet aggregation. The ratio of circulating platelet aggregates decreased by 10.3%, from 1.17 +/- 0.08 to 1.05 +/- 0.11 (P < 0.01), and spontaneous platelet aggregation by 56.3%, from 40.7 +/- 23.3 to 17.8 +/- 23.2 degrees (P < 0.01) during the garlic phase. There were no significant changes in the placebo group. The parallel group comparison (garlic versus placebo) revealed a significantly different ratio of circulating platelet aggregates after 4 weeks of treatment (P < 0.05). After the 4-week wash-out phase the values increased again to 1.19 +/- 0.32 and 34.9 +/- 28.7 degrees, reaching the initial values (run-in phase prior to the ingestion of garlic). Since garlic is well tolerated it would be worth testing it in a controlled clinical trial for usefulness in preventing disease manifestations associated with platelet aggregation.

Brain Ischemia↗

Biochemical characterization of a novel autocrine transferrin-like growth factor in acute myeloblastic leukemia.

Serum-free conditioned media (CM) of acute myelogenous leukemia cell lines induce growth stimulation of other leukemic cell lines. A transferrin (Tf)-like iron binding kD 50 protein was found to be the main growth factor of these CM's. Purification and further characterization of this protein was performed by chromatographic methods, SDS-PAGE, peptide mapping and amino acid analysis. In addition m-RNA of leukemic cell lines was analysed by Northern blot analysis with oligonucleotide probes specific for human serum Tf and melanotransferrin (p97) respectively. No hybridization signals for these probes have been detected. Biochemical results show significant differences between human serum Tf and kD 50 growth factor with respect to retention time on reversed phase FPLC, pattern of digestion peptides in SDS-PAGE and amino acid composition, which suggests, that this protein is an additional tumor associated member of the transferrin superfamily.

Amino Acids↗

[The effect of molecular structure of hydroxyethyl starch on the elimination kinetics and fluidity of blood in human volunteers].

Influence of the Molecular Structure of Hydroxyethyl Starch on Elimination Kinetics and Blood Fluidity in Voluntary Subjects In a cross-over study 6 volunteers received an infusion of 500 ml hydroxyethyl starch of a batch with a high C2/C6-substitution ratio (10.8), or after a washout period of 3 months they received a batch with a low C2/C6-substitution ratio (5.8). The infusion solution was administered at random. The batches were identical as regards their physicochemical characteristics (HES 200/0.5 10%). The concentration and molecular weight distribution of the intravascular hydroxyethyl starch molecules were determined after infusion up to 24 h, the blood fluidity before and after infusion. The substitution ratio of the C2- or C6-atoms in the glucose ring has an effect on the degradation of the hydroxyethyl starch molecule: the molecules with a high C2/C6-substitution ratio appear to be degraded within the same period of time, the resulting degradation products, however, have a higher molecular weight. This influences the blood fluidity. While the haematocrit decrease occurring 1 h after end of infusion is comparable, it keeps up for a longer time in case of a higher C2/C6-substitution ratio. The increase of plasma viscosity is more pronounced in case of a high C2/C6-substitution ratio. Clinical consequences are discussed.

Adult↗

[Quality assurance in autologous blood collection from critically ill patients].

Quality controls of autologous blood collections in critically ill patients comprise the control of blood products, blood collection, and of the patients themselves. The control of products is defined in European guidelines, the AMG (law governing the manufacture and prescription of medicine) and GMP regulations. The products are described in the monograph of the Federal Health Office. The quality control of blood collection in patients with a critical vascular disease is important since vagotonic or hypertensive crises may occur frequently (in 10-15% of cardiosurgical patients). The quality control of the critically ill patients themselves is important in order to be able to balance benefits against risks. A phlebotomy of 500 ml may lead to a considerable deterioration of the clinical condition. The clinical condition can be controlled by simple exercise tests prior to and after the blood collection (bicycle ergometer, treadmill or climbing stairs). In our own investigations only about 25% of cardiosurgical patients (40% of patients with aortocoronary venous bypass) received autohemotherapy, and 20% of them showed a clinical deterioration during the phase of blood collection. Other problematic patients are those suffering from a tumor. A clear clinical benefit of autohemotherapy in these patients has not been demonstrated up to now; nevertheless, when a curative therapy is possible, they should be treated with autohemotherapy.

Blood Transfusion, Autologous↗

[Indications for fresh frozen plasma: evaluation of virus inactivating preparations].

When no specific factor concentrate is available fresh-frozen plasma (FFP) is indicated in the treatment of clinically relevant hemorrhagic diathesis. These disorders include congenital factor V and XI deficiencies, multiple factor defects, as disseminated intravascular coagulation and severe liver disease, and patients receiving massive transfusions, when bleeding occurs and severe abnormalities on coagulation testing are evident. FFP is beneficial when used with plasma exchange in thrombotic thrombocytopenic purpura and related disorders. Various virucidal treatments including solvent-detergent (SD), photoactivated dyes (methylene blue) or pasteurization have been evolved to improve virus safety of human plasma. More extensive studies to demonstrate efficient virus inactivation in plasma have been performed with SD compared to other methods. On the other hand, the use of single-donor FFP in methylene blue treatment is possibly superior to pooled plasma which is processed according to the SD procedure. Pasteurization enables the inactivation not only of lipid-enveloped but also of non-lipid-enveloped viruses. Virucidal treatment of plasma may cause alterations in clotting factors, fibrinolysis and protease inhibitors; however, the currently achieved recovery of procoagulant activities is approximately comparable with that found in untreated FFP. The toxicity of virucidal additives is reported to be negligible since manufacturing includes a removal procedure (SD) or comparably low amounts (methylene blue) are used in inactivation treatment.

Antiviral Agents↗

Fibrinolytic effects of pro-urokinase combined with low-dose urokinase compared to high-dose urokinase in patients with acute myocardial infarction.

20 patients (6 females, 14 males) aged between 47 and and 75 years (mean: 62.6 yrs.) with acute myocardial infarction (onset of symptoms within 6 hours) were treated intravenously with either 200,000 U urokinase (UK) and 4.5 million U pro-urokinase (pro-UK) within 60 min (group I, N = 10), or 2.5 million U UK within 5 min (group II, N = 10). Blood samples for haemostatic and fibrinolytic function tests were taken prior to and repeatedly during the 24 hours following treatment. Peak fibrinolytic activity measured by fibrin plates was equivalent in both regimens. Average decreases, with lowest levels within 60 to 120 min following thrombolytic therapy, were observed of 27% and 70% for plasminogen, of 71% and 91% for alpha-2-antiplasmin, and of 20% and 74% for fibrinogen in group I and II, respectively. The reptilase time reached maximum values of 1.5- and 4.5-fold within 60 to 180 min. Peak levels of D-dimers and thrombin-antithrombin III complexes in group II were 2.6 and 3.2 times those of group I. After 24 hours, in contrast to group I, all these parameters still remained significantly different from pretreatment values in group II. These data indicate that, contrary to high-dose UK, pro-UK in combination with low-dose UK causes minor systemic fibrinolytic effects and is, therefore, assumed to be largely clot-specific, although the fibrinolytic potential is equivalent for both regimens.

Aged↗