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Biomedical subjects

E Wenzel

Publications and source records attributed to E Wenzel.

At least 37 records · Page 2Linked to original sources
PubMed1997

Environment, development and health: ideological metaphors of post-traditional societies?

Environment and health have become nearly interchangeable concepts in post-traditional societies. We are able to observe almost an obsession with them, as if individual changes in ways of life--important for the individual and significant for the culture though they may be--possessed the power to overthrow a system of economic relations that aims at growth in numerical terms rather than at development, enabling society to sustain its specific modes of private and public interaction.

Attitude to Health↗
PubMed1997

Interleukin-1beta-induced inhibition of hair growth in vitro is mediated by cyclic AMP.

Interleukin (IL)-1 has been shown to be a potent inhibitor of hair growth in vitro. We hypothesized that this cytokine might be a decisive factor causing hair loss during the lymphocytic attack in alopecia areata. Neither the intracellular pathways involved in hair growth inhibition mediated by IL-1beta nor the signal transduction processes within hair follicles in general are known. We therefore investigated the intracellular signals involved in human hair growth in vitro. Hair follicles were isolated from scalp biopsies by microdissection, and hair growth was measured daily by image analysis. We assessed intracellular signal transducing elements using specific inhibitors or activators either alone or in combination with IL-1beta. The calcium ionophore A 23187 induced a rapid and complete arrest of hair growth, and phorbol-12-myristate-13-acetate (PMA), genistein, or IL-1beta decreased hair growth by approximately 60%-80%. IL-1beta-elicited hair growth arrest was not antagonized by calphostin C, a specific inhibitor of protein kinase C. In contrast, coincubation of IL-1beta with pertussis toxin or H 1004 neutralized the effect of IL-1beta, and dibutyryl-cAMP and cholera toxin, an activator of adenylate cyclase, inhibited hair growth. These data suggest that cAMP acts as a second messenger for IL-1beta-induced inhibition of hair growth. Moreover, our data indicate that in vitro hair growth is dependent on intracellular Ca2+ levels and activation of tyrosine kinase as well as protein kinase C. We were unable to detect a signal transducing element responsible for enhanced hair growth in vitro.

Calcimycin↗
PubMed1997

Increased haemorrhagic risk after repeated infusion of highly substituted medium molecular weight hydroxyethyl starch.

Infusion of the large volumes of high molecular weight hydroxyethyl starch (HES) has been know to lead to coagulation disorders. Medium molecular starch is considered a safe alternative, even after repeated administration. In 10 patients with cerebrovascular diseases, a 10-day hemodilution was carried out using 10% HES 200/0.62. Initially, a loading dose of 500 ml was administered once over 45-60 min, followed by 500 ml maintenance dose per day for 10 days. Its high intravascular molecular weight (120,000 D) showed that cleavage of the starch is slowed due to the higher degree of substitution. The continuous increase of HES-serum concentration to 27.7 mg/ml gave evidence of a cumulation of poorly degradable molecules. Although this caused a prolonged volume effect, plasma viscosity and erythrocyte aggregation were influenced in an unfavourable way. The negative effects were not evident in their influence on the coagulation system. Under therapy, a significant 42.8% increase (p < 0.01) in activated partial thromboplastin time occurred. Factor VIII:C, von Willebrand ristocetin co-factor and von Willebrand factor antigen dropped during the therapy below the hemostasiological limit of 30% (p < 0.01), and in some patients below 10%. A high degree of substitution, particularly after repeated infusion, leads to a cumulation of large molecules that are difficult to break down and which unfavourably affect rheological and hemostasiological parameters.

Blood Coagulation↗
PubMed1996

[Late outcome of Lotheissen-McVay herniotomy 20 years postoperative].

The subject of this study consisted of 266 hernia repairs according to Lotheissen-McVay, carried out during the years 1970-1975. The survey evaluated the outcome of operations on direct and indirect inguinal hernias as well as on femoral hernias, but did not include any review of recurrent hernias. The sole aim of the survey was to evaluate the long-term results after 20 years, since the recurrence rate increases with postoperative duration. Through previous studies, partly involving the same patients, partial results on the recurrence incidence were available. The number of patients that were followed up in our study (158 = 59.4%) was limited primarily owing to the long period of time that had elapsed. This applied especially for hernia repair in older patients, since the higher mortality rate in these cases made it impossible to assess the outcome of the operation. A general total recurrence rate of 13.29% was found, of which 13.33% was for indirect inguinal hernias, 14.75% for direct inguinal hernias and 9.09% for femoral hernias. The group of patients that we reviewed was a typical cross-section of those patients who had received surgical treatment for an inguinal hernia. As far as we are aware, this study carried out more than 20 years after surgery, is the longest study of the recurrence incidence after hernia repair.

Adult↗
PubMed1996

Cytokines and growth factors influence hair growth in vitro. Possible implications for the pathogenesis and treatment of alopecia areata.

Factors that influence the growth of the anagen hair follicle or initiate the switch to a catagen growth pattern have so far not been definitely determined, but there is increasing evidence that cytokines and growth factors play an important role during these processes. Recently we detected an aberrant in situ expression pattern of cytokines of the Th1 type (IFN gamma, IL-2) plus IL-1 beta expression in untreated alopecia areata (AA), and a switch to high levels of IL-10 TGF-beta 1 expression after successful treatment with the contact allergen diphenylcyclopropenone (DCP). Hence the question arose as to whether cytokines are able to arrest hair growth and whether IL-10 or TGF beta 1 have the capacity to antagonize this process. Using whole-organ cultures of microdissected human hair follicles we studied the effect of a panel of cytokines and growth factors on hair growth and on the gross morphology of the hair follicles in vitro. IL-2, IL-10 and IFN-gamma had no effect in this regard, whereas TGF beta 1 partially inhibited hair growth and EGF, TNF alpha and IL-1 beta completely abrogated it. EGF and TNF alpha induced the formation of a club-like hair follicle, similar to catagen morphology of the hair bulb, whereas hair follicles grown in the presence of IL-1 beta or TGF beta 1 showed no particular morphological changes. We conclude that cytokines and growth factors are pivotal regulators of hair growth at least in vitro. IL-1 is suggested as playing an important role during the pathogenesis of AA. Possible mediators of therapeutic contact dermatitis (IL-10, TGF beta 1, TNF alpha, PGE2) are, at least in vitro, not able to antagonize the IL-1 beta-triggered hair growth inhibition. Therefore, we infer that these mediators rather "modulate' the immune response in AA.

Alopecia↗
PubMed1996

All medium starches are not the same: influence of the degree of hydroxyethyl substitution of hydroxyethyl starch on plasma volume, hemorrheologic conditions, and coagulation.

BACKGROUND: After the application of high volumes of high-molecular-weight starch (hetastarch), bleeding complications have repeatedly been observed. Later studies showed that the application of medium-molecular-weight starch led to far fewer disturbances of the blood coagulation system. However, the relationships among the degree of hydroxyethyl substitution, the rate of degradation, and the average in vivo molecular weight have not been investigated. STUDY DESIGN AND METHODS: A 10-day hemodilution treatment (n = 20) was carried out using two medium-molecular-weight hydroxyethyl starches (HES) with a degree of hydroxyethyl substitution of 0.5 and 0.62, respectively (10% HES 200 was used for a substitution of 0.5 and 6% HES 200 for a substitution of 0.62). After a loading dose of 500 mL was administered, 1000 mL of HES was infused daily for 4 days, and then 500 mL was infused daily for 6 days. RESULTS: The more highly substituted starch was broken down more slowly and eliminated renally. This resulted in a higher intravascular molecular weight than for the less highly substituted HES (120 vs. 84 kDa) and a greater increase in serum concentration (20.3 vs. 9.0 mg/mL). Initially, the more highly substituted 6-percent HES had a lesser effect on plasma volume (p < 0.01). Because of HES accumulation, there was no longer a significant difference between the starches by the end of treatment, even though a higher dose of the 10-percent low-substitution starch was infused. Six-percent HES caused an increase in plasma viscosity (+9%, p < 0.01) that was due to an accumulation of macromolecules. Ten-percent HES 200/0.5 had no effect on the coagulation system beyond the dilution effect. Six-percent HES, on the other hand, led to an acquired von Willebrand syndrome during the course of the 10-day therapy. Factor VIII function was reduced by 72.2 percent, von Willebrand ristocetin cofactor by 61.3 percent, and von Willebrand factor antigen by 64 percent (p < 0.01). CONCLUSION: It is the intravascular and not the initial (in vitro) molecular weight that determines the properties of HES. Especially after repeated administration, a high degree of hydroxyethyl substitution leads to an accumulation of macromolecules that affect hemorrheologic measures and the coagulation system just as adversely as high-molecular-weight starch does. Depending on the degree of substitution, medium-molecular-weight starches can have widely differing properties.

Blood Coagulation↗
PubMed1996

Influence of intravascular molecular weight of hydroxyethyl starch on platelets.

Complications concerning the blood coagulation have been observed repeatedly after administration of highly substituted, high molecular weight hydroxyethyl starch (HES), but it has not been examined as to how intravascular molecular weight and degree of substitution of HES influence platelet number and volume after repeated administration. Thirty patients with cerebrovascular diseases were treated for 10 days with hemodilution. 500 to 1500 ml of HES 200/0.62(n=10), HES 200/0.5(n=10) or HES 40/0.5(n=10) were infused daily. During the first days, the number of platelets was not lowered beyond the dilution effect, but at the end of the therapy the number of platelets had increased in all 3 groups beyond the initial value. Platelet volume was lowered significantly in the 3 groups. HES 200/0.62 caused the largest drop in platelet volume (-10%, p<0.01). A possible explanation could be that HES macromolecules are attached to platelets or are phagocytized by them. The larger platelets are then broken down and, to compensate the loss, more thrombocytes are released. A correlation between the molecular weight of HES and the breakdown rate of the platelets can be suspected, because HES 200/0.62 has the highest intravascular mean molecular weight(121 kD) and the largest effect on platelet volume.

Blood Platelets↗
PubMed1996

Decrease of fibronectin following repeated infusion of highly substituted hydroxyethyl starch.

OBJECTIVE: Fibronectin (Fn) plays an important part in unspecific defense mechanisms because of its ability to mediate the binding of foreign-body particles, bacteria, collagen, and other macromolecules to phagocytising cells of the reticulo-endothelial system (RES). The aim of the present study was to examine the effect of a 10-day hemodilution therapy on Fn concentration in humans. DESIGN: The patients were randomized and treated with either 10% hydroxyethyl starch (HES) 200/0.62 or 6% HES 200/0.62. SETTING: Neurology department of an university clinic. PATIENTS: We examined 12 patients with cerebrovascular perfusion disturbances. INTERVENTIONS: The Fn concentration was determined using simple radial immunodiffusion. RESULTS: The Fn concentration dropped significantly in all 12 patients (p < 0.01) in a dose-dependent manner beyond the dilution effect. 10% HES 200/0.62 caused a Fn decrease from 26.6 +/- 9.2 to 10.0 +/- 2.2 mg/dl (-62.2%), 6% HES reduced Fn from 25.5 +/- 9.9 to 15.0 +/- 3.2 mg/dl (-41.1%). In one patient there was a continuous decrease of Fn from 41.0 down to only 6.4 mg/dl. CONCLUSION: According to the results of animal experiments, the decrease of Fn seems to indicate depression of the RES. Besides its defense function, Fn probably plays a role in embryogenesis, wound healing, and blood clotting. Therefore, we assume that the drug-induced reduction of Fn possibly has clinical relevance.

Animals↗
PubMed1996

Growth factor mRNA levels in alopecia areata before and after treatment with the contact allergen diphenylcyclopropenone.

The early immune response in alopecia areata is characterized by a Th1 T helper cell cytokine pattern and an aberrant expression of ICAM-1 and HLA-DR molecules on lesional hair bulbs. A counteracting cytokine pattern induced by a therapeutic contact dermatitis is supposed to mediate the hair regrowth. In addition to cytokines, growth factors have been shown to influence immune responses, and we therefore investigated the expression levels for a panel of growth factors in untreated versus alopecia areata after treatment with the contact sensitizer diphenylcyclopropenone. Using semiquantitative reverse transcriptase polymerase chain reaction we detected a striking overexpression of transforming growth factor beta 1 mRNA in successfully treated patients. This cytokine has been shown to be a potent immune response modifier, which can suppress Th1 immune responses. The way in which topical immunotherapy induces hair regrowth in alopecia areata is unknown, but a lesional increased expression of transforming growth factor beta 1 may be a possible mechanism.

Administration, Topical↗
PubMed1996

[Decrease of thrombocyte volume after several days infusion of highly substituted medium molecular weight hydroxyethyl starch (HAES 200/0.62)].

Dextrans are known to inhibit platelet aggregation. However, conflicting results have been reported with hydroxyethyl starch (HES), usually administered as a single dose. To clarify this, we studied the effects of HES on platelet number, aggregation and volume during the course of long-term hemodilution therapy. Twelve patients with disturbances of cerebrovascular perfusion were randomized and divided into two groups of 6 patients each. One group was treated with 10% HES 200/0.62, the other with 6% HES 200/0.62. The patients in group 1 received a loading dose of 500 ml, followed by 500 ml daily for 10 days. Group 2 patients were infused a loading dose of 500 ml, followed by 1000 ml on days 1 to 4 and 500 ml on days 5 to 10. 10% HES had a larger volume effect. The hematocrit was lowered by 19.0%, whereas 6% HES caused a decrease of only 15.6%. 10% HES lowered the platelet number significantly (p < 0.05) by 5.8%, 6% HES did not lower the platelet number significantly. Platelet volume decreased significantly during therapy (p < 0.05) in both groups. 10% HES reduced the platelet volume by 13.9%, the reduction with 6% HES was 9.0%. Under therapy with 10% HES, platelet aggregation declined slightly, but significantly (p < 0.05), whilst no effect was seen with 6% HES. During long-term hemodilution therapy with HES, the initial decrease in platelet number, which is due to dilution, is quickly compensated. The continuous decline in mean platelet volume during therapy is probably due to colloid-osmotic shrinkage. Since there is a positive correlation between platelet size and function, the slight inhibition of platelet aggregation caused by 10% HES is possibly due to the observed decline in platelet volume.

Blood Platelets↗
PubMed1996

Influence of low and medium molecular weight hydroxyethyl starch on platelets during a long-term hemodilution in patients with cerebrovascular diseases.

It is a well-known fact that plasma substitutes reduce the number of platelets after one-time administration due to a dilution effect. So far, it has not been sufficiently investigated how a long-term hemodilution therapy affects platelet number, volume distribution and function. In 20 patients with cerebrovascular diseases a 10-day hemodilution therapy was carried out. The patients were randomly and double-blind treated with either medium molecular weight (MMW) hydroxyethyl starch (HES) 200/0.5 or low molecular weight (LMW) HES 40/0.5. On the first day of therapy, both groups showed a significant reduction in the number of platelets (-13.2% and -8.4%, respectively, p < 0.05), which was smaller than the dilution effect. During the course of the therapy, the platelet number increased, reaching its initial value. Mean platelet volume decreased in both groups significantly (MMW HES -4.7%, p < 0.05, LMW HES -4.6%, p < 0.01). The share of large platelets decreased disproportionately (MMW HES -15.4%, p < 0.01, LMW HES -11.4%, p < 0.01). Spontaneous platelet aggregation was not affected by HES. During the course of a long-term hemodilution therapy, the initial dilution-induced drop in platelet number is quickly compensated. The decline in mean platelet volume, which increases towards the end of the therapy, is due to a great extent to a decline in the number of large platelets. This in turn is probably caused by a colloid-osmotic shrinkage of the platelets and increased degradation. There were no signs for a clinically relevant impairment of platelet function.

Blood Platelets↗
PubMed1995

The effects of two phasic oral contraceptives on hemostasis and platelet function.

OBJECTIVE: To compare the effects on hemostatic parameters of a combiphasic oral contraceptive containing desogestrel and ethinyl estradiol (DSG/EE) and a triphasic oral contraceptive containing levonorgestrel and ethinyl estradiol (LNG/EE). METHODS: In an open-label, randomized, group-comparative study in 10 healthy volunteers per treatment group, the effects on parameters of coagulation, anticoagulation, fibrinolysis, antifibrinolysis and platelet function were determined at baseline, after three treatment cycles, and after a post-treatment cycle. Changes from baseline were analyzed using a paired t-test, whereas between-group differences were analyzed by means of an analysis of co-variance. RESULTS: Both OC preparations induced modest changes of some coagulation, anticoagulation, fibrinolysis and antifibrinolysis parameters, although all mean values remained within the normal range. No significant effects were observed with either OC with respect to platelet function. Statistically significant differences between the two preparations could occasionally e observed: the concentrations of antithrombin II (AT-III) and Factor VII were higher with the DSG/EE preparation than with LNG/EE preparation at the end of treatment and AT-III activity, AT-III concentration, Factor X concentration, and plasminogen activity were higher with DSG/EE than with LNG/EE in the post-treatment cycle. CONCLUSIONS: Combiphasic DSG/EE and triphasic LNG/EE, both OCs with a comparable amount of EE per cycle, had no clinically significant effect on the overall hemostatic balance.

Blood Coagulation↗
PubMed1995

Plateletpheresis-induced increase in platelet reactivity using different cell separators.

OBJECTIVE: Since plateletpheresis is being used increasingly, it is important to regard quality control to check health risks for donors and to exclude these. DESIGN: Controlled randomised prospective open comparative study. SETTING: Department of Transfusion Medicine of a University Clinic. PARTICIPANTS: 112 platelet donors were examined. INTERVENTIONS: Prior to and after plateletpheresis platelet reactivity was determined. The platelet concentrates in the two groups of 56 donors each were produced using either the cell separator 'CS-3000' and the collecting chamber PLT 30TM with the Omnix system (group I) or the cell separator 'AS-104' (group II). RESULTS: In group I five donors showed a pathologically increased platelet reactivity (p = 0.1297) after plateletpheresis. In group II there were 10 donors with a pathologically increased platelet reactivity (p = 0.0046) after plateletpheresis. The mean concentration of platelets was reduced by separation using the CS-3000 Omnix from 238 +/- 49 x 10(3)/microliters to 172 +/- 32 x 10(3)/microliters (68 +/- 27 x 10(3)/microliters) and from 243 +/- 53 x 10(3)/microliters to 180 +/- 31 x 10(3)/microliters (63 +/- 33 x 10(3)/microliters) using the AS-104. In the first case the platelet yield was 3.9 x 10(11) platelets/concentrate, in the latter case it was 2.9 x 10(11) platelets/concentrate. The 'CS-3000 Omnix' is significantly more effective in separating (58.4 +/- 15.5%) than the 'AS-104' with 44.2 +/- 7.2% (p < 0.0001). CONCLUSIONS: Since both donor groups were comparable regarding all factors recorded--especially the cardiovascular risk factors--the separation process could be responsible for the different traumatisation of platelets.

Adult↗
PubMed1995

[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↗
PubMed1995

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↗
PubMed1995

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↗