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Biomedical subjects

E Wenzel

Publications and source records attributed to E Wenzel.

At least 73 records · Page 4Linked to original sources

Comparison of the effects of sodium pentosanpolysulfate and unfractionated heparin on venous thrombosis; an experimental study in rats.

Sodium pentosanpolysulfate (Fibrezym) and unfractionated heparin (Liquemin) had significant antithrombotic efficacy in rats. 1 mg/kg body weight (BW) FibrezymR had its maximal effect 2-4 hours after subcutaneous administration; 200 U/kg BW LiqueminR s.c. were most effective 4-6 hours after application. Both drugs caused frequent embolic break-offs of thrombi during the time periods of maximal antithrombotic efficiency.

Animals↗

Positive phase II study in the treatment of advanced malignant melanoma with fotemustine.

To date, dacarbazine (DTIC) has been the most effective drug in the treatment of advanced metastatic melanoma, achieving response rates of up to 28% (mean, 21%). Multidrug responses were generally no better than those obtained using monotherapy. A quite promising clinical trial was conducted using the new nitrosourea fotemustine. A total of 19 patients presenting with advanced malignant melanoma (clinical stage IV according to the 1987 UICC classification system) underwent treatment involving a more rapid infusion of the drug and a reduction in the rest period from 5 to 3 weeks. This monotherapy with fotemustine yielded two complete responses and seven partial responses; in addition, four patients showed no change and six cases progressed after the induction cycle (median duration of response to date, 7.6 months, including four cases that have not relapsed). Fotemustine was well tolerated by the patients, with the only mild side effects being thrombocytopenia, leukocytopenia and easily controlled nausea/vomiting. Preclinical studies performed previously indicated that fotemustine inhibits enzymes involved in the ribonucleotide reduction pathway (i.e. DNA synthesis), whereby responding patients (n = 3) appeared to favor the thioredoxin reductase/thioredoxin electron transfer to ribonucleotide reductase, whereas non-responders (n = 4) expressed the alternate glutathione reductase/glutaredoxin mechanism. The 47% response rate obtained in these studies vs the 24% reported previously for fotemustine may reflect variations in enzymes in the ribonucleotide reduction pathway in different patients. However, the efficacy of fotemustine against advanced melanoma warrants more extensive trials of this drug, especially since the quality of life of the patients during and after chemotherapy was not severely affected.

Adult↗

Isolation, partial purification, and characterization of the cytochrome P-450-dependent monooxygenase system from the midgut of the earthworm Lumbricus terrestris.

1. Cytochrome P-450 was purified from microsomes of the midgut of the earthworm Lumbricus terrestris up to a maximal specific content of 5.5 nmol P-450/mg protein. 2. At least 3 different cytochromes P-450 with apparent molecular weights of 48,000, 51,000 and 53,000 were identified by SDS-PAGE. 3. Western blot analysis with various polyclonal antibodies did not show structural epitopes common to the cytochromes P-450 of rodents or yeast and L. terrestris. 4. The microsomes contained about 43 pmol P-450/mg protein corresponding to 0.51 nmol P-450/g midgut and 64 pmol P-450/g body weight, respectively, and converted benzyloxyresorufin into resorufin with a Vmax of 2.12 pmol resorufin/min.mg protein and a Km of 770 nM benzyloxyresorufin at 25 degrees C, pH 8.0. 5. The microsomes exhibited a NADPH-cytochrome P-450 reductase activity of 9.4 nmol cytochrome c/min.mg protein. 6. The apparent molecular weight of the threefold-purified reductase was 63,000.

Animals↗

Hirudin--a potential stabilizing factor for platelet preservation in transfusion.

The influence of additional hirudin in low doses on platelet and coagulation parameters was studied in platelet concentrates (PC) prepared by cytapheresis using citrate-dextrose solution formula A. The in vitro release of platelet factor 4 and beta-thromboglobulin was markedly lowered and morphological platelet alterations, as assessed by platelet size studies were considerably less accentuated in the presence of hirudin over a 5-day storage period; this suggests a possibly protecting effect on platelet function. No clear activation of the coagulation and fibrinolysis system was evident during PC storage with and without hirudin since thrombin-antithrombin III complexes and D-dimers did not markedly change.

Blood Coagulation↗

[Variance, factors of influence and clinical relevance of plasma viscosity].

The problem of measuring plasma viscosity has been solved through the use of capillary and falling-ball viscosimeters which have a determination variance of less than 1%. On account of the influence of overeating, forced thirst, psychological and physical stress plasma viscosity should be determined in the morning; the patient should be fasting and well hydrated. Plasma viscosity is influenced by diseases with alterated plasma protein composition. An elevated viscosity also significantly increases the risk of developing an arterial occlusion. Since the physician can both decrease and increase plasma viscosity, it should be determined parallel to therapy. Accordingly, plasma viscosity is one of the most important rheological parameters.

Adult↗

Contributions to biorheology during hemodialysis.

Thrombogenicity is the property of a foreign surface to induce clotting processes or formation of aggregates after contact with blood. Beside the sort of anticoagulation patient's prethrombotic state, rheological factors as well as physicochemical properties of foreign membranes decisively influence thrombogenicity. We examined the influence of chronic renal failure and different hemodialyzers and blood transfusion therapy during hemodialysis on hemorheological parameters. Different membranes cannot be discriminated by the used hemorheological parameters. We clearly could demonstrate the close relationship between the hemofiltration rate and an increase of viscosity. Blood transfusion therapy or elevated hematocrit in combination with increased hemofiltration rate have influence on the flow behaviour of blood, especially in disturbed microcirculation.

Biocompatible Materials↗

[Hemorheologic and circulatory effects of hemodilution with medium molecular weight hydroxyethyl starch in two concentrations (HAES 200/0.62 10% and 6%)].

This study was designed to investigate whether the positive effect occurring after infusion of a 10% hydroxyethyl starch solution 200.000/0.62 on cutaneous capillary blood flow could still be increased by using a 6% solution having a lower initial viscosity (HES 6% 200.000/0.62). A single blind study of 10 female volunteers was carried out to study the influence of a hypervolemic hemodilution using 500 ml of a 10% solution hydroxyethyl starch solution at first and that of 6% hydroxyethyl starch solution on macro- and microcirculation, transcutaneous oxygen partial pressure and blood fluidity. After hydroxyethyl starch infusion blood flow in the macro- and microvessels increased significantly. This increase occurred considerably earlier after administration of 6% solution than after infusion of 10% solution. Thus blood flow had already increased after 1 hour and continued to show a tendency of increase over about three hours. 6 hours after end of infusion blood flow had almost dropped to its initial value. The volume effect of the 6% solution immediately after infusion was less pronounced than that after infusion of the 10% solution, but it reached the value of the 10% solution at a later point in time. The course of the haematocrit reflected this process. Average decrease in haematocrit value compared to that following the 10% solution was not as pronounced at hour 3. After 6 hours the decreases were comparable. Similar observations were made of plasma viscosity and platelet aggregation. One hour after infusion plasma viscosity and erythrocyte aggregation had hardly changed but haematocrit had clearly dropped. Thus, blood viscosity at this point in time was essentially lowered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Therapeutic use of fresh plasma and "virus-safe" plasma].

The use of plasma and factor concentrates for the treatment of coagulation disorders is well established, but many questions remain. The indications for fresh frozen plasma are still not clearly established and excessive use is rampant. The safety of all blood products has not yet been firmly established. Peer review of transfusion practice in a hospital can be achieved by a Hospital Transfusion Committee. The review and analysis of the statistical reports of the transfusion service and strategies for enhancing quality of patient care will be presented.

Algorithms↗

Clinical relevance of biological incompatibility and role of a central register.

Different aspects relevant for the assessment and characterization of biomaterials are presented. Quite a number of basic concepts that play an important role when detecting unwanted adverse effects of drugs have to be taken into consideration when registering and evaluating unwanted effects of biomaterials. The institutionalization of the Central Bioregister at the University of Saarland is described. This Bioregister is a so-called "spontaneous" ad hoc recording system whose efficiency depends largely on the collaboration of physicians. Thus, the efficiency and rationality of the use of biomaterials can certainly be improved. The possibility of registering even rarely occurring unwanted effects as well as new indications will result in and allow a more general and/or a more specific therapy, depending on the biomaterial.

Adverse Drug Reaction Reporting Systems↗

Influence of garlic powder on cutaneous microcirculation. A randomized placebo-controlled double-blind cross-over study in apparently healthy subjects.

In a randomized placebo-controlled double-blind cross-over study it could be shown that 5 h after the administration of garlic powder (Kwai, Sapec; total dose of 900 mg garlic powder) a significant increase in capillary skin perfusion by 55% occurs in the healthy volunteers. Placebo did not cause any changes. The difference between the two study phases is also significant. The increased erythrocyte velocity results from vasodilation of precapillary arterioles which increases diameter of erythrocyte column by an average of 8.6%. Simultaneously inflow of interstitial fluidity accompanied by a significant decrease in haematocrit and plasma viscosity occurs (rheoregulation).

Adult↗

Effect of garlic on thrombocyte aggregation, microcirculation, and other risk factors.

Significant positive effects could be achieved in a placebo-controlled double-blind study through the administration of 800 mg of garlic powder over a period of four weeks. Spontaneous thrombocyte aggregation disappeared, the microcirculation of the skin increased by 47.6% (from 0.63 +/- 0.13 to 0.93 +/- 0.22 mm/s), plasma viscosity decreased by 3.2% (from 1.25 +/- 0.34 to 1.21 +/- 0.43 mPas), diastolic blood pressure by 9.5% (from 74 +/- 9 to 67 +/- 5 mmHg), and blood glucose concentration by 11.6% (from 89.4 +/- 8.8 to 79.0 +/- 11.9 mg/dl). The vascular protection of garlic as atherosclerosis prevention by influencing the mentioned risk parameters for cardiovascular diseases must be pointed out. Especially interesting is the thrombocyte aggregation inhibiting effect. Thus, the application of garlic may be useful in case of acetylsalicyclic acid intolerance.

Adult↗

Comparison of different prothrombin complex concentrates--in vitro and in vivo studies.

The potency and tests for thrombogenicity were studied prospectively in 7 different (two lots of each brand, A-G) prothrombin complex concentrates (PCC). Human albumine (H) and a factor IX concentrate (I), served as controls. The potency of coagulation factors and inhibitors varied considerably. Two brands (E, F) contained no protein S, additionally one brand contained no protein C. Two preparations exhibited high amidolytic activities, especially towards the thrombin-sensitive chromogenic substrate S-2238, in vitro. These activities could be quenched in part by the addition of hirudin or antithrombin III. The heparin and antithrombin III content of the PCCs was significantly different, and, after addition of antithrombin III an increase of thrombin-antithrombin III complexes in 2 preparations (B, D) was observed in vitro. Additionally, three brands (B, D, F) caused more severe cardio-pulmonary reactions in rabbits, associated with an increase of fibrin split products for brands B and D. We conclude that the use of these preparations in patients, in whom an acquired protein C or S defect, or a hypercoagulable state, can be suspected, cannot be recommended.

Animals↗

Modern strategies for treatment of acute myocardial infarction: significance of haemostaseological and rheological findings.

In spite of equivalent clinical efficacy of various thrombolytic agents for the treatment of acute myocardial infarction there is evidence of different drug-depending influences on the haemostatic and fibrinolytic system. In the present study 40 patients with acute myocardial infarction have been investigated. 20 patients received 750,000 and 1.5 mio U streptokinase (SK), respectively, 10 patients 30 mg anisoylated plasminogen streptokinase activator complex (BRL 26921) and 10 patients a combination of 200,000 U urokinase (UK) and 4.5 mio U pro-urokinase (PUK) as a short-term intravenous treatment. Reperfusion of coronary arteries has been achieved in 70 to 100 percent. Major not fatal bleedings occurred in 2 patients. One patient died within 72 hours after beginning of the myocardial infarction. The longest duration of fibrinolytic activity was observed in the BRL 26921 group (half-disappearance time close to 2 h). It was significantly shorter in the SK groups showing a dose-dependency. Plasma concentration of fibrinogen dropped beyond normal levels following SK and BRL 26921, but not under UK/PUK. Plasma viscosity correlated with fibrinogen decrease and displayed a dose-depending relationship with the presence of SK. Haemorheological effects are suggested to be important for the clinical efficacy of thrombolytic therapy in myocardial infarction.

Anistreplase↗

[Coincidence of hypertensive changes of the eye fundus and regulation disorders of peripheral microcirculation: I--Skin].

In cases of arterial hypertension, funduscopy is an established method of estimating systemic vascular lesions. In this study the relation between the extent of retinal vascular changes and dynamic processes in the microcirculation of the skin was investigated by nailfold capillaroscopy in 88 patients. With increasing vascular changes a progressive loss of vasodilator reserve and transcutaneous partial pressure was observed (no morphologic changes--fundus hypertonicus II--fundus hypertonicus III). It thus appears possible to evaluate the functional state of the macro- and microcirculation by funduscopy.

Adult↗

Haemodilution with medium molecular weight hydroxyethyl starch in patients with peripheral arterial occlusive disease stage IIb.

The basic therapy of peripheral arterial occlusive disease stage IIb, according to Fontaine, is exercise. It should be determined whether a mild hypervolaemic haemodilution with hydroxyethyl starch or Ringer lactate can produce a further increase in walking distance. For this purpose, three groups of 25 patients each were formed. One group exercised three times weekly and the second group, in addition to exercise, underwent a mild hypervolaemic to isovolaemic dilution therapy with HES for a period of 6 weeks. In the final group the haematocrit was reduced to the same extent by venesections and volume substitution using Ringer lactate. The walking distance in the HES group increased from 216 m to 311 m (44%), in the Ringer lactate group from 214 m to 258 m (20%), and in the exercise group from 213 m to 242 m (14%). On comparison of the groups, the increase in pain-free walking distance in the HES group differs significantly (P less than 0.05) from that achieved in the other groups. It was demonstrated that haemodilution with HES in combination with exercise brings about a clinical effect three times that achieved by exercise alone. Venesection with subsequent administration of Ringer lactate and exercise is superior to exercise alone but markedly inferior to the combination therapy with HES.

Adult↗

[The clinical rheological laboratory].

To quantify the fluidity of blood it is not suitable to measure whole blood viscosity as blood is no Newton's fluid. For this reason, it is necessary to measure characteristic blood flow parameters direct. This study presents methods of measurement for plasma viscosity, haematocrit, thrombocyte aggregation, erythrocyte rigidity, erythrocyte aggregation and leukocyte adhesivity.

Blood Viscosity↗

[Error analysis, biological modification factors and variance of peri-ungual video-capillary microscopy].

Error analysis or the evaluation of the precision of microscopic measurements must distinguish between technical errors inherent in the measuring system, and biological variability. The technical error inherent in the overall system in the case of linear measurements is smaller than the lengths to be measured by 1 or 2 orders of magnitude. Thus, the erythrocyte column lengths can be correctly, reproducibly and linearly quantified over the entire measuring range. The biological influencing factors can largely be taken into account or excluded by suitable standardisation of the measuring process. Despite a considerable individual fluctuation in the erythrocyte velocity, there is, on average, no significant dependence of the measuring parameter within the daily profile or from day to day. Differences in capillary perfusion in the presence of diseases associated with microcirculatory disorders or a therapeutic influence on erythrocyte velocity can thus be reliably demonstrated.

Capillaries↗

The development of a central register for side effects of biomaterials.

Examination of the interaction between biomaterials and tissues from a clinical realistic as well as scientific viewpoint to complement the highly advanced experimental and biochemical basis research is an undertaking that has suffered a considerable amount of neglect in the past. Attempts to realize internationally a Central Registry for documenting clinically relevant side effects will be reported in detail. Implementation of the registry involves the review of present literature (prospective clinical studies, retrospective studies and case reports). An "incompatibility incident report/questionnaire" has been developed according to the guidelines of the "Report on Pharmacological Side Effects" of the Pharmaceutical Commission of the German Medical Association. The aims of registering and evaluating these reports will be demonstrated and discussed in detail.

Biocompatible Materials↗