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Biomedical subjects

G Wittmann

Publications and source records attributed to G Wittmann.

At least 37 records · Page 2Linked to original sources

The effect of methylene blue phototreatment on plasma proteins and in vitro coagulation capability of single-donor fresh-frozen plasma.

BACKGROUND: Photodynamic virus inactivation of fresh-frozen plasma (FFP) may result in its impaired coagulation capability. STUDY DESIGN AND METHODS: Double-volume plasmapheresis samples from 11 donors were divided in pairs of 250 mL. One group underwent methylene blue (MB) phototreatment (MB-FFP). The other group was treated according to the standards of the American Association of Blood Banks for preparation and storage of FFP. Parameters of hemostasis and clinically important plasma proteins were tested in native plasma, thawed MB-FFP, thawed FFP, and twice-frozen and thawed FFP (FFP-II). RESULTS: Mean activities of factor V (73.4 vs. 94.5%; p < 0.01), factor VIII (58.1 vs. 86.7%; p < 0.001), and fibrinogen (1.8 vs. 2.8 g/L; p < 0.001) were reduced in MB-FFP as compared to those in FFP. The comparison of MB-FFP to FFP-II revealed reduced activities of factor VIII (58.1 vs. 85.2%; p < 0.001) and fibrinogen (1.8 vs. 2.8 g/L; p < 0.001) but no changes in factor V. Activated partial thromboplastin time in MB-FFP was prolonged beyond the upper normal range (+5.3 sec; p < 0.001) and prothrombin time increased in MB-FFP versus FFP (+0.96 sec; p < 0.001). CONCLUSION: MB phototreatment reduces the in vitro coagulation capacity of FFP, most likely as a result of the effects of an additional freezing and thawing procedure and photooxidation-induced protein damage.

Blood Coagulation↗

Identification of antibodies toward private and public class I HLA epitopes in sensitized patients.

BACKGROUND: Antibodies to HLA determinants may decrease the increment after platelet transfusion and are correlated with increased rates of rejection in renal transplantation. Cross-match tests and HLA antibody specification are used to identify compatible donors for sensitized patients. However, search for cross-match negative donors may be ineffective, and many sera containing antibodies toward public HLA epitopes give no clear results in conventional specificity analysis. MATERIALS AND METHODS: We tested a series of 4,625 sera from 1,073 patients with hematological, malignant or other diseases using a fluorescence lymphocytotoxicity test (LCT). We applied an evaluation program incorporating a list of public antigens belonging to known cross-reacting groups (CREGs) to detect antibodies toward private and just as well public epitopes. RESULTS: In 694 sera (15.0%) from 240 patients the panel reactivity (PRA) in LCT assay was higher than 5%. PRA was > or = 50% in 258 (37.2%) and < 50% in 436 sera (62.8%). In both groups we identified specific antibodies toward public HLA class I epitopes. Overall antibody specification was successful in 429 of 694 sera (61.8%) and in 175 of 240 patients (72.9%), respectively. The rate of antibodies against public epitopes shared by more than one HLA class I gene product was 203/694 (29.3%) with respect to tested sera and 83/240 (34.5%) with respect to patients. The rate of public epitope antibodies was highest in sera with PRA values from 30 to 90% showing public epitope specificity in 159 of 353 sera (45.0%). CONCLUSIONS: We conclude that antibodies toward public HLA class I determinants are detectable not only in highly sensitized patients. The described program may increase the rate of antibody specification and facilitate the platelet supply in platelet refractory patients.

Blood Grouping and Crossmatching↗

[HLA and transfusion].

Using published data, the role of the HLA system for transfusion of cellular blood components is described. Transfusion-associated immunomodulation and the causative role of HLA in other side effects of transfusion therapy are discussed, using review articles and original papers from the German and English literature as sources. The HLA system has important implications for transfusion therapy. Sensibilization of recipients with consecutive formation of HLA antibodies impairs the support of thrombocytopenic patients and may cause febrile transfusion reactions. HLA antibody formation in donors may result in transfusion-induced acute lung injury. The transfusion of viable lymphocytes may cause graft-versus-host disease in immunocompromised recipients or after directed donations from relatives, in rare cases even without these conditions. The clinical implications of transfusion-associated immunomodulation are judged differently.

Blood Component Transfusion↗

[18 months experience with a new single needle cytapheresis system (Fresenius AS 104 SN)].

BACKGROUND: Since October 1991 the third-generation cell separator Fresenius AS 104 offers a single-needle (SN) option for thrombocytapheresis. Here we present our first 18-month experience with this new single-needle system. MATERIALS AND METHODS: We performed 395 thrombocytaphereses in 225 donors. The influence of blood flow, cycle volume, and interface position on efficacy and leukocyte contamination was evaluated. RESULTS: 395 thrombocytaphereses were performed with an average thrombocyte yield of 3.00 +/- 0.69 x 10(11) platelets and a leukocyte contamination of 1.66 +/- 3.1 x 10(8) per concentrate. Blood flow rates of 50 ml/min (vs. 60 ml/min) and an interface position of 6:2 (vs. 7:1) resulted in a lower leukocyte contamination, but without statistical significance. CONCLUSION: The SN program of the AS 104 provides high thrombocyte yields and less leukocyte contamination than other SN systems, but 77% of the concentrates still contain more than 0.5 x 10(8) leukocytes.

Adult↗

[Various clusters of immunoreactivity in the aged and their relation to HLA antigens and erythrocyte antigens].

In blood samples of members of the Berliner Altersstudie (BASE) (n = 427, 204 males, 223 females; mean = 85.2 years, range = 76-96 years, SD = 3.3 years), red cell, HLA-A, -B, -Cw and -Dr antigens were determined by standard methods. Lymphocyte reactivity was measured by 3H-thymidine uptake into DNA of lymphoblastic cells stimulated by 12 different mitogens and antigens. Cluster analysis, confirmed by t and F tests, defined 3 distinct clusters of lymphocyte reactivity. Clusters showed significantly different cumulations of 3 or more increased characteristic red cell and HLA antigens, and trends toward a decreased overall immunoresponsiveness in elder people. Like in middle-aged individuals, immunoresponsiveness in elder individuals can be dissected into at least 3 functionally different clusters which are not influenced by lymphocyte subsets or in vivo cell activation but by the patterns of both red cell and HLA antigens.

Aged↗

[MLC reactivity demonstrates transfusion-induced immunosuppression].

The improved graft survival in preoperatively transfused renal transplant recipients led to the hypothesis that blood transfusions have an immunosuppressive effect. We examined 12 patients undergoing cardiac surgery, who received autologous red cells and one homologous HLA class-I-matched platelet concentrate. None of these patients produced red cell or lymphocytotoxic antibodies. Using the mixed lymphocyte culture (MLC) we observed a reduced lymphocyte responce to cells of the platelet donor during the first 4 days after transfusion. The MLC reactivity recovered on days 4-5 to the initial strength and reached over 200% of the initial strength from day 6 on. It must be assumed that these changes in MLC reactivity represent the early signs of the transfusion-induced immunosuppression. As intraoperative transfusions might correlate with cancer relapse, further studies must show whether this immunosuppressive effect can be avoided by the application of filtered leucocyte-depleted red cell transfusions.

Blood Transfusion↗

[Effect of various rabbit complement batches of HLA class I antigen determination in lymphocytotoxicity testing].

HLA class I lymphocytotoxicity testing is strongly complement-dependent. We tested 13 commercially available rabbit complement batches (7 distributors) using a panel of 14 donors with decisive patterns of HLA antigens. We defined a scoring system that weights the different possible faulty reactions. The rating score ranged from 12.45 to 46.55 (median 16.09). Comparing the reactions in batches with low and high rating scores gave statistically significant differences (chi 2 test, p < 0.05). Our complement reaction score may be helpful to find the optimal complement batch for HLA class I lymphocytotoxicity testing.

Animals↗

[Attempts in developing a standardized test system of immunologic reactivity].

Stimulation of lymphocytes with mitogens and antigens is an established model for in vitro testing of immunoreactivity. Due to the great variability of blastogenic response the interpretation of these results is difficult. Our results suggest that multivariate experiments and statistics improve the interpretation.

Antigens, Bacterial↗

[Strong and weak histocompatibility antigens and immune response].

In blood samples of 88 healthy donors various red cell, HLA-A, -B, -Cw and -Dr antigens were determined by standard methods. Lymphocyte reactivity was measured by 3H-thymidine uptake into DNA of lymphoblastic cells stimulated by 14 different mitogens and antigens. Cluster analysis confirmed by t test and F test defined 3 distinct clusters of lymphocyte reactivity. Cluster 1 in 70% [relative risk (r.r.) 109, p < 0.001] and cluster 3 in 92% (r.r. 33, p < 0.01) showed significantly different cumulations of 3 or more increased characteristic red cell and HLA antigens. Our data suggest that the patterns of both red cell and HLA antigens play a major role in defining immunoreactivity.

HLA Antigens↗

Spread and control of Aujeszky's disease (AD).

The review deals with practical aspects of control and eradication of Aujeszky's disease (AD) and the various factors concerned with it. These are resistance of virus to environmental conditions, amounts of virus necessary for infection, virus excretion, virus latency, mode of virus transmission, and vaccination. Notification of AD is a precondition of control. Several measures are necessary on the infected farm to prevent virus spread. Eradication can be done by slaughter of all the seropositive animals. However, until recently this is impossible in severely infected vaccinated areas on economic reasons. The development of glycoprotein-deleted vaccines now allows the differentiation between vaccinated and infected animals by ELISA. Thus, a combination of vaccination and removal of infected pigs is possible, resulting in a more economic way of expanded eradication.

Animals↗

[Virus carriers in foot-and-mouth disease. Review].

FMDV infection can cause a long lasting virus carrier state in the oesophageal-pharyngeal (OP) region of cattle, sheep, goats, African buffalo, wildebeest and kudu. Virus can be recovered from OP fluids with low titres for several months up to more than 2 years. During this time phases of positive virus recovery are interrupted by negative phases. The number of virus carriers decreases as time progresses. The virus carrier state is always accompanied by FMDV antibodies in serum and OP fluid. Vaccinated animals also become virus carriers after FMDV infection, to the same extent as unvaccinated animals. No virus carrier state has been proven in pigs, but it cannot be excluded in some species of deer. Epizootic importance of carrier animals (in FMD) has not been found. Experimental contact transmissions of carrier virus to cattle, sheep and goats have failed. Only buffalo transmit carrier virus to the own species and perhaps to cattle. Nevertheless, virus carriers represent a natural reservoir of FMDV in infected areas and a potential source of antigenically altered virus variants, since continuous variations of the virus and selection of virus mutants take place in the animal during the carrier state.

Animals↗

Evaluation of the efficacy and safety of loratadine in perennial allergic rhinitis.

Loratadine, a new nonsedating antihistamine, was evaluated for efficacy and safety in 228 patients with perennial allergic rhinitis. Taken at a dose of 10 mg once daily, loratadine was significantly more effective than placebo and comparable to terfenadine, 60 mg taken twice daily, in reducing combined symptom scores in this patient population. Efficacy was maintained throughout the 28-day course of treatment. The overall incidence of side effects with loratadine was low (14%) with few occurrences of sedation (3%) and dry mouth (4%).

Adolescent↗

Effect of muscarinic receptor stimulation on release of cysteinyl-leukotrienes and thromboxane B2 from anaphylactic guinea-pig hearts.

The effects of muscarinic receptor stimulation by infusions of methacholine (6.25 x 10(-8) mol/min or 1.9 x 10(-7) mol/min) into isolated perfused, spontaneously beating sensitized guinea-pig hearts on the anaphylactic release of cysteinyl-leukotrienes (LT) and thromboxane (TX) B2 were investigated. Methacholine increased coronary flow and decreased heart rate under basal conditions. Furthermore, infusions of methacholine (1.9 x 10(-7) mol/min) significantly increased the anaphylactic release of TXB2 as well as of immunoreactive cysteinyl-LT, which were demonstrated by reversed phase high pressure liquid chromatography to consist of a mixture of LTC4, LTD4 and LTE4. Infusions of atropine (1.3 x 10(-7) mol/min) alone did not significantly affect coronary flow and heart rate prior to ovalbumin injection nor anaphylactic release of cysteinyl-LT. The anaphylactic release of TXB2 was, however, significantly decreased in the presence of atropine. Atropine (1.3 x 10(-7) mol/min) infused in addition to methacholine (1.9 x 10(-7) mol/min) abolished the effects of the muscarinic receptor agonist on spontaneous heart rate and significantly antagonized the increase in coronary flow prior to ovalbumin injection. Similarly, the simultaneous infusion of atropine abolished the effects of methacholine on the anaphylactic release of TXB2 and cysteinyl-LT. After antigen challenge hearts infused with methacholine, atropine or the combination of both drugs did not exhibit any differences with respect to anaphylactic changes of heart rate or the time course of anaphylactic coronary flow reduction. Thus, in the isolated perfused anaphylactic guinea-pig heart, muscarinic receptor stimulation significantly enhanced the release of the arachidonic acid-derived mediators TXB2 and cysteinyl-LT.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis↗

Aujeszky's disease vaccination and infection of pigs with maternal immunity: effects on cell- and antibody-mediated immunity.

SCC, ADV-SCC, ADV-ADCC and ADV-LYST as well as ND50-titres of neutralizing serum antibodies were examined in 36 passively immune pigs, 25 of which were vaccinated at 3 weeks of age and partly revaccinated 3 weeks later. Twenty-five vaccinated animals and 8 non-immune control pigs were challenged with infectious ADV. Independent of the state of maternal immunity the cytotoxic response of the white blood cells from all the animals was low at WPP 3 but rose with increasing age. ADV-LYST occurred only in some of the animals. A single vaccination evoked no significant effect on our immune parameters, but revaccination led to higher ADV-LYST and ADV-ADCC. In pigs vaccinated at WPP 3 the neutralizing serum titres decreased gradually, similar to unvaccinated animals, indicating that the antibodies were of maternal origin. However, after vaccination at WPP 6, no further decline of ND50-titres could be detected, pointing to a limited antibody production. Animals vaccinated at WPP 3 and revaccinated 3 weeks later showed a significant increase of serum neutralizing titres. Whereas the controls showed typical symptoms of Aujeszky's disease, the immune animals, especially the unvaccinated passively immune pigs, showed only elevated temperatures and most of them excreted small amounts of ADV. The development of cellular immunity after infection was rather similar within the maternally immune group independent whether the animals had been vaccinated or not, but ADV-ADCC and ADV-LYST showed a more rapid progress within the vaccinated group than in the non-vaccinated group and the non-immune control group. Infection resulted in significantly higher ND50 titres in vaccinated and revaccinated animals than in unvaccinated animals, indicating a secondary response in those pigs. Thus, ADV sensitization of lymphocytes had been evoked by vaccination despite the presence of maternal antibody. The interpretation of the results was complicated by great individual and litter-dependent variations of the immune parameters.

Animals↗