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Biomedical subjects

G Wiedermann

Publications and source records attributed to G Wiedermann.

At least 19 recordsLinked to original sources

Compliance of Austrian tourists with prophylactic measures.

Physicians dealing with prophylactic measures for tourists going to developing countries will often not be able to foresee the outcome of their recommendations. Therefore an open study with 2,627 Austrian tourists on their flight home from a tropical destination was carried out to evaluate the behaviour of typical short-term travellers with respect to different kinds of precautionary measures. 94.1% of all tourists informed themselves before travelling abroad, but a high proportion of travellers tends to contact only their travel agency or their personal friends, this leading to inadequate information. Regarding the individual performance of precautionary measures the results indicate a few principal conclusions: Among the recommended inoculations the vaccinations against typhoid fever, poliomyelitis and tetanus are widely underestimated, the latter two in particular for adults, while compliance with the passive immunization against Hepatitis A is generally good (more than 80% of all travellers receive Hepatitis A immunoglobulins prophylactically). The most crucial point seems to be the chemoprophylaxis against malaria in as much as a) there seems to be a considerable lack of information about malaria endemic areas among physicians, b) tourists tend to use the most simple applicable drug unaware of epidemiological considerations and c) the regular intake of chemoprophylaxis declines significantly with the complexity of the intake procedure. In addition, tourists are in general well informed about nutritional risks, but only half of them will receive adequate information on the risk of sexually transmitted diseases and a basic medical travel kit.

Adolescent

Humoral immune response against a 70-kilodalton heat shock protein of Entamoeba histolytica in a group of patients with invasive amoebiasis.

In order to investigate the humoral immune response against Entamoeba histolytica a lambda ZapII cDNA library was constructed from trophozoites of the pathogenic E. histolytica strain SFL-3. The library was screened with serum IgG from a patient with invasive amoebiasis. Forty-nine immunopositive lambda clones were isolated and partial sequences from the inserts were obtained. By comparison of the sequences with the merged database MIPSX from the Martinsried Institute for Protein Sequences we were able to identify homologous proteins for 36 of the clones. Twenty-six of the clones encoded intracellular proteins, among these, the major part (16 clones) were highly homologous to the eukaryotic 70-kDa heat shock proteins (Hsps). The open reading frame of one complete clone encodes a protein of 656 amino acid residues of 71.5 kDa which has 69.8% sequence identity with the human Hsp70 protein. In a larger screening experiment only 3 out of 12 patients detected with their IgG the phage which expressed the 70-kDa heat shock protein(s).

Amino Acid Sequence

Persistence of vaccine-induced antibody to hepatitis A virus.

A level of 10 mIU hepatitis A antibodies/ml as measured by ELISA is believed to be the minimal protective concentration. If this level is considered, the mean persistence of vaccine induced antibodies is approximately 10-11 years after booster dose, 6-7 years if only the primary doses are given and 5-6 years if the minimal individual titre is taken into account.

Enzyme-Linked Immunosorbent Assay

Simultaneous vaccination against hepatitis A and B: results of a controlled study.

Hepatitis A and hepatitis B are endemic in many countries and must be considered as serious health risks for large parts of the world population. Simultaneous or combined vaccination against these two diseases would therefore be most advantageous. In order to investigate possible interactions between these vaccines with respect to their tolerability and immunogenicity, we conducted a randomized prospective study comparing single and simultaneous administration of the two vaccines. Three groups of healthy volunteers, each with 55 persons, were included in the study. All were negative for hepatitis A and hepatitis B markers and had normal serum liver enzyme values. Group I received hepatitis A vaccine (720 ELISA units) into the left deltoid muscle, group II received hepatitis B vaccine (20 micrograms) into the right deltoid muscle and group III received hepatitis A vaccine into the left, and hepatitis B vaccine into the right deltoid muscle. Three doses of the vaccines were administered at 0, 1 and 6 months. Local and systemic reactions were monitored by means of questionnaires. Blood samples for determination of antibody to hepatitis A virus (anti-HAV) and antibody to hepatitis B surface antigen (anti-HBs) and of serum SGOT and SGPT levels were drawn at months 0, 1, 2, 6 and 7. There were no serious general and only mild local reactions. The mean serum SGOT and SGPT values remained in the normal range in all groups. The seroconversion rates and mean geometric titres of the anti-HAV and anti-HBs antibodies were similar when the vaccines were administered separately or simultaneously. There were no significant differences between the compared groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

cDNA cloning of Entamoeba histolytica histone H3.

E. histolytica has an unusual nuclear structure. Although nucleosome-like particles were observed, no information about histones was available so far. In this paper we describe a cDNA clone with significant homology to H3 histones that was isolated from a lambda Zap library of pathogenic E. histolytica. The complete cDNA encodes a 15 kDa polypeptide, which is shorter by one residue than the human homologue. The amino acid sequence has only 69% identity with human H3.3 histone. Our results indicate that this divergence may contribute to the unusual chromatin structure of E. histolytica.

Animals

Molecular characterization of IgG and IgE antigens of Entamoeba histolytica.

Several surface IgG antigens of E. histolytica have been characterized. We isolated two novel cDNAs by screening a library of pathogenic E. histolytica with rabbit antiserum against a membrane preparation of pathogenic amebas. cDNA K15 encodes a large protein > 220 kDa with sequence homology to myosins and K18 encodes a protein of around 40 kDa. Serum IgG from patients suffering from amebiasis binds to both antigens. Some IgE antibodies are able to recognize homologous proteins in all eukaryotes investigated. We demonstrate that IgE antibodies from pollen allergic patients bind to plant, human, as well as E. histolytica profilins.

Allergens

Intestinal worm burden and serum cholesterol or lipid concentration in a Shipibo population (Peru).

Paired samples of stool and serum of 32 members of the Shipibo tribe resident in the rain forest of the Peruvian lowlands were tested for worm egg count and serum lipid parameters, respectively. 90% of the stool samples tested were found to contain eggs or larvae of several worm species, most commonly 3 or 4 different species. Serum lipid levels were found to be relatively low, most probably due to a low proportion of dietary fat ranging from 16-31%. Statistical analysis showed a significant inverse correlation between worm egg excretion and HDL levels which was true for hookworm, strongyloides and trichuris, but not for ascaris. The mechanisms underlying the observed association between intestinal worm load and HDL reduction are not completely understood and may include reduced HDL synthesis in the gut wall due to inflammatory and/or toxic irritation.

Cholesterol

[The Austrian vaccination plan].

In March 1991 the Supreme Board of Health issued new recommendations for immunization of children which are basically similar to those issued in 1989, but were partially reformulated. Again, BCG vaccination is not generally recommended and should be given only to individuals at high risk of contracting the disease. It is therefore not listed any more in the general recommendations (A) but only mentioned under special vaccinations (B). Special indications for BCG vaccination were clearly reformulated. Vaccinations against diphtheria-tetanus or pertussis-diphtheria-tetanus are recommended as usual, an oral pertussis vaccine is presently not available and an acellular pertussis vaccine is under study. Booster vaccinations at school entry will be performed with a low dose of diphtheria-toxoid to avoid local side reactions.

Adolescent

[Acellular pertussis vaccine].

Acellular pertussis vaccines contain antigen components of B. pertussis, usually lymphocytosis promoting factor (LPF) which is also called pertussis-toxin (PT) or pertussigen, filamentous hemagglutinin (FH) and, eventually, agglutinogens 2 and 3. Acellular vaccines are being used in Japan since 1981. Several Phase II studies have been performed and showed a better tolerability than whole cell vaccines and antibody responses of at least equal magnitude. In some of these studies good protection rates were observed. The latter were not satisfactory in a Phase III study in Sweden. This study, however, might cause some criticism in as much as only 2 vaccine doses were given and a control group with whole cell vaccine was missing. Moreover, the significance of bacterial infections in vaccinated children is doubtful, similar observations have not been made in other trials nor in Japan since introduction of the vaccine in 1981. Preliminary results of our own study with a newly developed acellular vaccine which has been permitted by the Austrian Drug Commission have shown good tolerability.

Antibody Formation

Safety and immunogenicity of an inactivated hepatitis A candidate vaccine in healthy adult volunteers.

The reactogenicity and immunogenicity of a formaldehyde-inactivated hepatitis A vaccine have been investigated. Three different dose levels of vaccine (180, 360 and 720 ELISA units) were administered to healthy volunteers according to a 0, 1, 2 and 12 month schedule. The vaccine was safe and well tolerated. Reactions observed following vaccination were essentially mild and were not dependent upon the quantity of antigen administered. All subjects had measurable titres of anti-HAV antibodies after the full vaccination course; the immune response to the vaccine was dose-related. Antibody titres in vaccinees at month 13 were between 60- and 190-fold higher than those observed in a group of subjects given anti-HAV immunoglobulin.

Adolescent

Restoration of defective cytokine activity within lepromatous leprosy lesions.

Immunohistological studies of tuberculoid leprosy lesions (TT-lesions) showed a dense, well organized granuloma consisting of a central area with epitheloid and giant cells containing interferon-gamma (IFN-Gamma) and CD3+, CD4+ T helper/inducer (Th/i) cells, a considerable proportion of which expressed the interleukin-2-receptor (IL-2 R). This central area was surrounded by round cells which consisted mainly of CD3+/CD8+ T cytotoxic/suppressor (Tc/s) lymphocytes. The overlying keratinocytes (KC) were strongly positive for HLA-DR antigens on the surface, indicating high intralesional IFN-Gamma activity. In contrast, lepromatous leprosy lesions (LL-lesions) showed a disorganized infiltrate composed by foamy cells and round cells, the latter mainly expressing the CD3+/CD8+ phenotype. IFN-Gamma activity could not be detected within the lesions. The KC overlying the infiltrate were consistently negative for HLA/DR reactivity pointing to a defective intralesional IFN-Gamma production in LL patients. Two out of four patients with LL leprosy could be sensitized with dinitrochlorobenzene (DNCB). The eliciting of DNCB skin reactions within the LL-lesion led to the recruitment of new infiltrating cells; the resulting infiltrate resembled a local reversal towards the tuberculoid pole of leprosy.

CD4-Positive T-Lymphocytes

Immune response in patients with amoebiasis: evaluation of IgG-subclasses.

In order to evaluate the immune response with respect to IgG-subclasses (IgG1-IgG4) in patients with extraintestinal amoebiasis, an ELISA technique was established. It was the aim of this pilot study to quantify the IgG subclass response and to compare the resulting pattern with other systemic protozoal infections. Our results give evidence that IgG4 contributes to more than one third of the total immune response, followed by IgG2, IgG3 and IgG1. Regarding the IgG4 response in patients with Plasmodium falciparum malaria or Chagas disease, IgG4 plays only a minor role in these systemic protozoal infections. The interpretation of a prognostic value of the high IgG4 titres in our patients is not possible at present. However, in patients with a prolonged clinical course of extraintestinal amoebiasis, extremely high IgG4 titres were observed.

Amebiasis

Interaction of different strains of Entamoeba histolytica with target cells: characterization of electrophysiological and morphological features.

Two strains of Entamoeba histolytica with pathogenic zymodemes (SFL3, HK9), one strain with non-pathogenic zymodeme ("Bru") and one non-pathogenic Entamoeba sp. strain ("cold strain"), were investigated with respect to their interaction with target cells. Three test systems were used: 1) direct microscopical observation and qualitative as well as quantitative evaluation of contact and binding events with MDCK cells as targets, 2) kinetics of cytotoxic activity as measured by means of chromium release from 51Cr-labelled K562 cells, and 3) electrophysiological observations with freshly prepared mouse liver cells. We observed that the non-pathogenic cold strain interacted only shortly with target cells (statistical events, interaction type "I"), but did not induce morphological changes, chromium release or depolarization of targets. Non-pathogenic and avirulent strain "Bru" showed, apart from type "I"-binding, the ability to establish tight (type "II") and long-lasting contact (type "III") with targets, but again without cytotoxic effects. The pathogenic but avirulent strain HK9 tightly interacted (type "II") and sometimes long-lasting with target cells, but morphological changes and chromium release were of a moderate degree during the first 20 min, and depolarization was only a rare event. In contrast, strain SFL3 produced tight and long-lasting contacts (type "III" binding), leading to cell death in 83% (type "IV" interaction) within 20 min, substantial chromium release within 10 min and rapid depolarization ("electric collapse") of target cells.

Animals

In vitro drug sensitivity of Plasmodium falciparum in Acre, Brazil.

In Acre, the westernmost state of Brazil in the Amazon region, the sensitivity of Plasmodium falciparum to chloroquine, amodiaquine, mefloquine, quinine and sulfadoxine/pyrimethamine was determined in vitro by the Rieckmann microtechnique. The study was performed between January and June 1987; the in vitro parasite responses to all antimalarial drugs were determined according to the recommendations of WHO. Of 83 isolates of P. falciparum, all were sensitive to mefloquine and of 87 isolates of P. falciparum, 84 (97%) were sensitive to quinine. The EC50 for mefloquine was 0.27 mumol/l and for quinine 4.60 mumol/l. In contrast, 65 of 89 (73%) and 70 of 83 (84%) isolates were resistant to amodiaquine and chloroquine, respectively; 11 isolates even grew at 6.4 mumol chloroquine/l. The EC50 for amodiaquine was 0.34 mumol/l and for chloroquine 0.73 mumol/l. Sulfadoxine/pyrimethamine resistance was seen in 23 of 25 (92%) cases. These data clearly indicate that in the western part of the Amazon region the 4-aminoquinolines, as well as sulfadoxine/pyrimethamine, can no longer be recommended for the treatment of P. falciparum infections.

Adolescent

Tolerability of long-term malaria prophylaxis with the combination mefloquine + sulfadoxine + pyrimethamine (Fansimef): results of a double blind field trial versus chloroquine in Nigeria.

A randomized double blind study in long term malaria chemoprophylaxis was performed to compare the tolerability of Fansimef (1 tablet containing 250 mg mefloquine + 500 mg sulfadoxine + 25 mg pyrimethamine per week) with chloroquine (300 mg per week). 211 Austrian industrial workers and their families in Warri, Nigeria, participated in this study; 101 received Fansimef and 110 chloroquine for 3-18 months (mean 41 weeks). Prophylaxis was discontinued because of adverse effects in 7 volunteers in the Fansimef group (mainly insomnia, palpitations, dizziness, nausea and headache) and in 2 volunteers of the chloroquine group (headache and loss of hair in one volunteer, nausea, dizziness and vomiting in the other). Most of the adverse effects could be due to the mefloquine component. A few minor complaints of burning eyes, nausea and gastric pain were reported in both groups. Laboratory checks performed at 3-monthly intervals showed a slight, transient and clinically irrelevant (but statistically significant) increase of serum glutamic-oxalacetic transaminase and gamma-glutamyl transpeptidase at month 3 in the Fansimef group. An attack of acute Plasmodium falciparum malaria occurred in one volunteer 6 weeks after discontinuation of prophylaxis with Fansimef. Antibodies against blood stage parasites could be demonstrated by the indirect immunofluorescence test at different stages of the study, indicating that these two antimalarials are not causal prophylactic agents.

Adolescent

Tolerability and immunogenicity of a polyvalent Pseudomonas aeruginosa extract vaccine in human volunteers.

A polyvalent 16 serotype Pseudomonas extract vaccine was administered to normal volunteers to ascertain tolerability, immunogenicity and immunisation schedule. Four groups of nine volunteers were immunised with 0.8 X 10(9) bacterial equivalents (BE), 1.2 X 10(9) BE, 1.6 X 10(9) BE or placebo, respectively, on days 0, 14 and 21. A further six volunteers were immunised with 1.6 X 10(9) BE on days 0 and 28. Tolerability was excellent, slight side effects were unrelated to vaccine concentration and decreased with the number of injections. All concentrations of vaccine gave a significantly increased titre 14 days after the first immunisation. Reimmunisation did not increase the titre, which reached a plateau at day 14. Individuals with high pre-immunisation-titres produced very high post-immunisation-titres with a conversion factor of 6.5 whilst those with low pre-immunisation-titres had a higher conversion factor of 13 but produced lower final titres. ELISA titre did not always correlate with biological activity (mouse protection assay) suggesting that effective protective antibodies are only part of the total specific antibody measured by ELISA with the polyvalent whole-cell vaccine antigen.

Adult

Lack of induction of IgE and IgG antibodies to yeast in humans immunized with recombinant hepatitis B vaccines.

Yeast-derived hepatitis B vaccines (partially purified or highly purified) at different dosages and a plasma-derived hepatitis B vaccine (control) were injected into 50 young volunteers 3 times at monthly intervals. Before and 4 weeks after this series of immunizations, blood samples were drawn and tested for presence of IgE and IgG antibodies against yeast antigens. No rise in IgE antibodies against Saccharomyces cerevisiae antigens nor in IgG antibodies against Candida albicans antigens was found. Together with former clinical results this underlines the experience that type I and type III reactions against putative yeast contaminants apparently play no major role after immunization with recombinant hepatitis B vaccines.

Adult