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Biomedical subjects

G Wiedermann

Publications and source records attributed to G Wiedermann.

At least 91 records · Page 5Linked to original sources

Risks and benefits of vaccinations.

Any medical intervention is expected to prevent sickness and complications of a disease rather than to induce them. This is true for therapy as well as prophylaxis. Special formulas have been developed to calculate the risks and benefits of vaccinations simply but with sufficient accuracy. The risk ratio (Q) tells how many times the risk of contracting certain complications or even death from a disease is greater in unvaccinated than in vaccinated individuals. The risk difference (D) directly expresses the number of complications or deaths that may be prevented by a certain vaccination. It is even possible to evaluate the epidemiologic trend of a disease and to calculate or estimate the point of time when the risks of disease and vaccination are just balanced, ie, when a vaccination has lost its beneficial effect. Vaccinations against measles, poliomyelitis and tick borne encephalitis in Austria are highly beneficial. BCG vaccination is still beneficial on a low level in Austria as far as protection against tuberculosis is concerned. This effect will persist for the rest of this century. The benefit of pertussis vaccination depends on the local epidemiologic situation. It has expired for non-risk groups in Austria since 1976 but continues to persist in the US.

Austria↗

Tolerability of long-term prophylaxis with fansidar: a randomized double-blind study in Nigeria.

A randomized double-blind study was performed to compare the side effects of long-term chemoprophylaxis of malaria with Fansidar (1 tablet a week) with those of a 300-mg weekly chloroquine regimen. This study was designed as a field trial with Austrian industrial workers in Nigeria and included 173 volunteers, 86 taking Fansidar and 87 taking chloroquine for 6 to 22 months. Only a few complaints were reported during that time, gastrointestinal disorders predominating in the Fansidar group and insomnia in the chloroquine group (3 cases each). The other complaints in both groups included one case each of skin rash and of visual disturbance, as well as one case of facial erythema after alcohol consumption in the Fansidar group and one of hair loss in the chloroquine group. Laboratory checks were performed at 3-monthly intervals, and included white and red cell counts, platelet counts and determination of GOT, GPT and alkaline phosphatase. There were no signs of drug-associated liver damage. In the Fansidar group there occurred a slight and transient decrease in the red cell count and in the chloroquine group a slight and transient decrease in the white cell count. Although statistically significant, these changes were without clinical significance. It is noteworthy that there were no cases of leucopenia in the Fansidar group. With the exception of one volunteer, who had discontinued his prophylactic drug regimen, malaria did not occur. Antibodies against blood stage parasites as determined by the indirect immunofluorescence test (IIFT), however, could be found at different stages of the study, which indicates that these two antimalarials are not causal prophylactic agents.

Adolescent↗

[Entamoeba histolytica: II. Effect of humoral immune mechanisms on cytotoxic activity].

The time dependency of the cytotoxic action of E. histolytica against tissue culture cells of mammalian origin was assessed in a 51Cr-release assay. Obviously, the amebae-dependent cytotoxic activity within the first 30-60 min of the assay against K562 (an erythroleukemic cell line) and MH1C1 (a rat hepatoma cell line) correlated with the pathogenicity of the respective amebae in vivo as measured by the hamster liver infectivity test. The in vivo apathogenic strain of E. histolytica (HK9) exhibited a delayed cytotoxic action in comparison with the in vivo pathogenic strain (SFL3), which revealed approximately 50% of maximum 51Cr-release after 10 min of the assay. Peripheral blood lymphocytes and HeLa cells proved to be not suitable to discriminate between pathogenic and apathogenic strains in vitro. Human antibodies directed against E. histolytica were capable of inhibiting the cytotoxic action of pathogenic amebae against K562 and MH1C1 within the first 30-60 min of the assay, revealing a kinetic pattern nearly identical with that observed with apathogenic amebae against K562. Possibly, this antibody-mediated inhibition of the cytotoxic action of E. histolytica against target cells reflects one of the defence mechanisms of the host against invasive amebiasis.

Animals↗

[A new ELISA micromethod for the determination of tetanus antibodies].

Due to its simplicity, accuracy and economy, the ELISA technique is a suitable method also for the determination of tetanus antibodies. By the method described, a titration curve is established from each serum to be investigated as well as from a standard serum. The horizontal distance between standard and unknown serum expressed in log2 titre steps is called titre difference. From this titre difference and the concentration of the standard serum the concentration of the unknown serum can be calculated. By means of an appropriate computer this evaluation can be done automatically. The variation coefficient with regard to concentration was 18.3%. A comparison with the toxin neutralisation test showed a correlation coefficient of 0.87. The application of this method to various problems is described.

Antibodies, Bacterial↗

[Entamoeba histolytica: I. Mechanism of cytotoxic activity].

Cytotoxic action against K562-tissue culture cells was investigated under various conditions with a Chromium-release-assay. When amoebae and target cells were centrifuged together, pathogenic strains of amoebae induced a very fast increase of target cell lysis (up to 50% of maximum lysis after 10 minutes). Only a minor degree of target cell lysis resulted, however, when amoebae and K562 cells were kept in suspension. When amoebae were eliminated selectively by addition of complement 10 minutes after starting the experiment, this fast increase of lysis could not be prevented. These observations suggest that the cytotoxic action might take place in two distinct phases. The first step ("lethal hit") seems to be temperature-independent, whereas a temperature of 37 degrees C is necessary for the second step to occur during which cytoplasmic material is released (chromium release). The presence of amoebae is not necessary for the second step. When amoebae together with and target cells are kept in suspension, amoebae lost their capability of setting the "lethal hit" with increasing time of coincubation. It seems, as if the "lethal hit" cannot be accomplished effectively under the conditions of suspension: cytotoxic substances released by the amoebae cannot be transferred to the target cells and are lost in the fluid phase. Thereby, the amoebae are depleted of such substances. Thus, a stable contact between amoebae and target cells for at least a few minutes seems to be necessary for the expression of cytotoxicity.

Amebiasis↗

Immunogenicity and side-effects of a new tetravalent meningococcal polysaccharide vaccine.

A new tetravalent meningococcal polysaccharide vaccine containing groups A, C, W 135, and Y was administered to 40 healthy adults. The vaccine was well tolerated and bactericidal assay showed mean titre increases for the meningococcal polysaccharide groups A, C, W 135, and Y of 5.0, 7.8, 8.2, and 5.9 log(2) titre steps, respectively. The immunogenicity and side-effects of the vaccine were similar to those associated with monovalent and bivalent vaccines containing group A and C meningococcal polysaccharides.

Adult↗

Immunoglobulin allotypes and immune response to meningococcal polysaccharides A and C.

Serum samples were collected from 113 healthy Caucasian volunteers before and after vaccination with meningococcal polysaccharides (MPS) group A and group C. Antibodies to MPS group A and group C were measured and sera were typed for several Gm and Km(1) allotypes. A significant association was found between the Gm 1,3,17; 5,13,14,21 phenotype and low immune responsiveness to MPS group A. These results suggest the possible existence of an immunoglobulin allotype-linked immune suppression (Is) gene(s) in man.

Adult↗

Immunogenicity and reactogenicity of new multivalent pneumococcal vaccines.

In a study conducted in two phases at one month's interval, 22 healthy adult volunteers received a tetravalent (1, 3, 4, 12F) polysaccharide pneumococcal vaccine; 21 other subjects received another tetravalent (14, 18C, 19F, 23F) vaccine and 25 received a pentadecavalent vaccine (1, 3, 4, 6A, 7F, 8, 9N, 11A, 12F, 14, 15F, 18C, 19F, 23F). Placebo was given under single blind conditions to eleven subjects in the first phase of the study and to 24 subjects in the second phase of the study. The vaccines were well tolerated giving rise to transient local reactions in a small proportion of subjects. Results obtained indicate that all 15 polysaccharides are satisfactorily immunogenic. Results so far obtained can be described as encouraging. Further studies to investigate the reactogenicity and immungenicity of multivalent pneumococcal polysaccharide vaccines with a greater number of serotypes are under way.

Adolescent↗

[Effect of BCG vaccination of the newborn infant on the incidence and course of juvenile leukemias].

As a retrospective study the clinical data of 613 leukaemic children were collected. 269 of them were born in Austria, fell sick between 1967 and 1976 and were not older than 5 years at the onset of disease. BCG-vaccination, which is performed in Austria within the first three days after birth, was checked by means of hospital reports, birth protocols and central BCG record. All data were stored and evaluated by electronic data processing. Besides a significant decrease of mortality, which we could demonstrate in earlier studies, the following correlations between BCG-vaccination of newborn and leukaemia were found: Reduction of morbidity, decrease of case fatality, increase of 5 years survival rate, increase of mean survival time, delayed onset of disease, decrease of frequency of myeloic and chronic leukaemia. With the exception of the slight reduction of morbidity all correlations are significant.

BCG Vaccine↗

Comparison between human IgM and IgG antibodies to dextran, regarding their activities in antibody-dependent cellular cytotoxicity (ADCC).

Human sera containing dextran-reactive antibodies of various immunoglobulin classes were tested for their capacity to induce ADCC against dextran-coated chicken red blood cells (CRBC). It was found that only IgG antibodies were active in ADCC, while IgM antibodies were not, thus providing further evidence that IgM antibodies do not contribute to ADCC even when human antibodies are used.

Animals↗

Lack of evidence for IgM-induced ADCC: studies with monoclonal and polyclonal antibodies.

Different kinds of IgM antibodies were tested for their activity in antibody-dependent cellular cytotoxicity (ADCC): firstly an anti-benzylpenicilloyl (BPO) IgM antibody from immune rabbit serum purified by affinity, ion exchange, and molecular-sieving chromatography, secondly two monoclonal rat anti-BPO IgM antibodies and thirdly a human antidextran antibody prepared from a patient showing restriction of anti-dextran antibodies to the IgM class. Human lymphocytes or purified monocytes served as effector cells. While the two monoclonal rat and the human IgM antibodies showed no ADCC-mediating capacity, ADCC was induced by the rabbit anti-BPO IgM antibody when high antibody concentrations were used. This activity was abolished by further purification using an anti-rabbit IgG (Fc) immunosorbent. The initially observed activity was shown to be likely due to traces of aggregated anti-BPO IgG, which cannot be detected by the methods commonly used. Preincubation of lymphocytes for 24 hr increased the number of EA (IgM)] rosette forming cells but failed to induce IgM-mediated ADCC. Furthermore, evidence for amplification of low-dose IgG-ADCC by IgM could not be found.

Antibodies↗

[Hepatitis A: antibody conversion under gamma globulin (author's transl)].

55 soldiers of the Austrian UNO contingent to the Near East, stationed on the Golan Heights for 6 months were examined before and after their period of duty for hepatitis A antibodies and the liver specific enzymes GOT, GTP and gamma-GT were determined. All received prophylactic gamma globulin to prevent infectious hepatitis at a dosage of 0.05 ml/kg body weight before flying out and after three months. No cases of hepatitis occurred, but 4 sero-negative subjects displayed antibody conversion. No concomitant changes in the liver enzyme values were recorded, however. These findings are discussed.

Adult↗

Adenine and hypoxanthine metabolism in phythohemagglutinin-stimulated and unstimulated human lymphocytes.

The uptake and subsequent metabolism of adenine and hypoxanthine in phytohemagglutinin-stimulated and unstimulated peripheral human blood lymphocytes, freshly prepared or cultured, were studied. To investigate the initial step of nucleic acid metabolism the incorporation of 14C-purines into the acid soluble material was examined. No preferential uptake of adenine or hypoxanthine was observed in freshly prepared and cultured lymphocytes during an incubation of 1 h. However, cultured cells utilized approximately 1/3 of the purines compared to freshly drawn cells. Within the cells 2/3 of adenine and 1/2 of hypoxanthine were metabolized to nucleotides (mainly AMP and ADP). Incubation of lymphocytes with PHA for 1 h produced in the freshly prepared cells an increase of adenine- and hypoxanthine-uptake to 191% and 153%, in 48 h stimulated cells to 158% and 132%. There was, however, no change in the relative rates of the metabolic routes though the intracellular concentrations of nucleotides formed increased with adenine as substrate to 152% and with hypoxanthine to 161% during a 1 h stimulation. In contrast no enhanced formation of acid soluble nucleotide formation could be observed with PHA stimulation during 48 h. The increased rates of purine uptake and metabolism apparent 1 h after addition of mitogen may be due to an altered transport mechanism at the beginning of the transformation as an adaptive response to the increased requirements for the synthetic processes soon to follow. Once the lymphocytes are transformed no demand of purines is necessary and the uptake and metabolism is switched off.

Adenine↗

Modulation of NK and K cell activity by trypsin treatment of effector cells.

The effect of trypsin-treated human peripheral blood lymphocytes on spontaneous cell-mediated cytotoxicity (SCMC) and antibody-dependent cellular cytotoxicity (ADCC) was investigated using benzylpenicilloyl (BPO)-coated HeLa cells as targets. For ADCC-experiments an anti-BPO-IgG was purified from rabbit hyperimmune sera by affinity and subsequent ion exchange chromatography and used in different concentrations. After treatment of lymphocytes with high enzyme concentrations (21,500 U/2 X 10(6) lymphocytes/ml) both SCMC (mediated by NK cells) and ADCC (mediated by K cells) were markedly reduced in 3 hours as well as 18 hours 51Cr-release assays. Since decrease of K cell activity in this kind of assay might be due to impairment of SCMC, the effect of trypsin treatment was reevaluated in an NK-free system using BPO-coated lymphocytes as target cells and lymphocytes from the same donor as effector cells. Once again, in this system the K-cell activity was significantly reduced. Chessboard titration resulted in either enhancement of depression of ADCC depending on the dose of enzyme and IgG concentrations. In addition it could be seen from these dose response studies with different IgG concentrations (10--10,000 ng/ml) and different proteolytic activities (170--21,500 U/2 X 10(6) lymphocytes/ml) that the use of high IgG concentrations and low proteolytic activities might simulate resistance of K cells to trypsin treatment. The data presented indicate that the IgG-mediated ADCC should no longer be designated as "trypsin-resistant".

Animals↗