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Biomedical subjects

M Kundi

Publications and source records attributed to M Kundi.

At least 19 recordsLinked to original sources
PubMed2006

The role of Foxp3+ T cells in long-term efficacy of prophylactic and therapeutic mucosal tolerance induction in mice.

BACKGROUND: Mucosal tolerance induction is suggested as treatment strategy for allergic diseases. Using a murine model of birch pollen (BP) allergy we investigated the long-term efficacy and the underlying mechanisms of mucosal tolerance induction with two structurally different molecules in a prophylactic and in a therapeutic set-up. METHODS: The three-dimensional major BP allergen Bet v 1 or a nonconformational hypoallergenic fragment thereof was intranasally applied before (prophylaxis) or after sensitization (therapy). RESULTS: In the prophylactic application both the Bet v 1 allergen and the fragment prevented allergic sensitization, and this effect lasted for 1 year. In the therapeutic approach established allergic immune responses were also suppressed after treatment with either of the molecules. However, a long-lasting curative effect (6 months) was only achieved with the Bet v 1 allergen but not with the Bet v 1 fragment. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis of splenocytes revealed that tolerance induction with the Bet v 1 allergen was associated with enhanced expression of transforming growth factor (TGF)-beta, interleukin (IL)-10, and Foxp3 mRNA in CD4+ T cells, whereas treatment with the fragment led to the induction of either Foxp3 (prophylaxis) or IL-10 (therapy) alone. CONCLUSION: From these data we concluded (i) that the mechanisms underlying peripheral tolerance are linked to the conformation of the antigen, (ii) that mucosal tolerance is mediated by separate regulatory cell subsets, and (iii) that the long-term efficacy of immunosuppression is associated with the presence of Foxp3+ T cells.

Administration, Intranasal↗
PubMed2006

Subjective symptoms, sleeping problems, and cognitive performance in subjects living near mobile phone base stations.

BACKGROUND: The erection of mobile telephone base stations in inhabited areas has raised concerns about possible health effects caused by emitted microwaves. METHODS: In a cross-sectional study of randomly selected inhabitants living in urban and rural areas for more than one year near to 10 selected base stations, 365 subjects were investigated. Several cognitive tests were performed, and wellbeing and sleep quality were assessed. Field strength of high-frequency electromagnetic fields (HF-EMF) was measured in the bedrooms of 336 households. RESULTS: Total HF-EMF and exposure related to mobile telecommunication were far below recommended levels (max. 4.1 mW/m2). Distance from antennae was 24-600 m in the rural area and 20-250 m in the urban area. Average power density was slightly higher in the rural area (0.05 mW/m2) than in the urban area (0.02 mW/m2). Despite the influence of confounding variables, including fear of adverse effects from exposure to HF-EMF from the base station, there was a significant relation of some symptoms to measured power density; this was highest for headaches. Perceptual speed increased, while accuracy decreased insignificantly with increasing exposure levels. There was no significant effect on sleep quality. CONCLUSION: Despite very low exposure to HF-EMF, effects on wellbeing and performance cannot be ruled out, as shown by recently obtained experimental results; however, mechanisms of action at these low levels are unknown.

Adolescent↗
PubMed2005

Blood concentrations of polycyclic musks in healthy young adults.

Knowledge on the concentration of polycyclic musk fragrance compounds in human blood is sparse. This study examined the concentrations of six polycyclic musks in blood samples from healthy volunteers. Blood was taken from hundred healthy students of the Medical University of Vienna. The lipophilic fraction was extracted and after purification analyzed by GC-MS. Study participants also completed a questionnaire on the use of cosmetics, about nutrition and other life-style aspects. Two compounds -- galaxolide and tonalide -- were identified in higher percentages of the blood plasma samples. Maximum plasma levels over 100 ng/l were also only found for galaxolide (4100 ng/l) and tonalide (800 ng/l). Women showed significantly higher levels than men. In a statistical multivariate approach only use of body lotion and age were predictive of positive galaxolide concentrations. For tonalide no significant predictor could be found. The findings mirror the replacement of nitro musk fragrances by polycyclic musks, mainly galaxolide. The high concentrations of galaxolide in human blood raise concern since few toxicological data are available.

Adult↗
PubMed2004

Immunogenicity and safety of a booster vaccination against tick-borne encephalitis more than 3 years following the last immunisation.

This study investigated the immune response and safety in 430 adults, when boosted more than 3 years after primary or booster TBE immunisation as measured by neutralization test (NT) and ELISA. Tested by NT, the post-booster day 21 geometric mean titer (GMT) was 331 and 142 for the 18-49 and > or =50 years old, respectively. The post-/pre-booster geometric mean titer ratio (GMR) was 2.29 for the 18-49 years old and 3.21 for the > or =50 years old. An at least four-fold increase of neutralizing TBE antibodies was observed in only 26 and 38% of subjects aged 18-49 and > or =50 years, respectively. The booster effect in subjects with only the primary vaccination course prior to study entry clearly depended on the time elapsed since last TBE vaccination with an estimated annual decline rate of 15%. In subjects with at least one additional booster vaccination virtually no antibody decline was observed. This study clearly indicates that (1) adults may be effectively and safely boosted with a different TBE vaccine and (2) following four immunisations protective antibodies can be detected far beyond a period of 3 years, thus, strongly supporting the reconsideration of currently recommended booster intervals.

Adolescent↗
PubMed2004

Persistence of protective immunity following vaccination against tick-borne encephalitis--longer than expected?

A descriptive evaluation of protective immunity was performed on subjects with a complete primary tick-borne encephalitis (TBE) immunization (and additional regular boosters) more than 3 years after primary or booster TBE immunization, as measured by neutralization test and two different ELISA systems. The study population (n = 430) was stratified for age (i.e., 18-49 or 50 years of age) and for the number of years since last TBE vaccination. GMTs (NT) of all subgroups (at the time of the present evaluation) were above detection limit: 144 and 44 for the 18-49- and 50-year-old subjects, respectively. One percent of subjects aged 18-49 years, and 6% of subjects aged 50 years were ELISA-negative. A detailed sub analysis revealed that subjects with either low NT and/or negative to borderline ELISA test results are usually older and constitute a higher number of subjects without any TBE booster vaccination compared to the respective test-positive subject group. From the fourth year (exceeding 3 years after last vaccination) titers show a decline rate of 6-7%. This study indicates that after multiple TBE (booster) immunizations protection surpasses the currently advised TBE booster interval of 3 years, thus supporting reconsideration of the recommendations for booster intervals.

Adolescent↗
PubMed2004

Component-resolved diagnosis of house-dust mite allergy with purified natural and recombinant mite allergens.

BACKGROUND: Mites belong to the most frequent and potent allergen sources. Immunotherapy with mite allergen extracts is frequently performed if allergen avoidance is not possible or successful. However, highly controversial results have been reported for mite-specific immunotherapy. OBJECTIVE: The aim of this study was to develop diagnostic concepts that may contribute to an improved selection of patients for immunotherapy with Der p allergen extracts and that may be used for immunological monitoring of patients undergoing this treatment. METHODS: The IgE reactivity profiles to Der p extract were determined in a Middle European mite-allergic population by IgE immunoblotting and by using a panel of seven purified natural or recombinant Der p allergens (nDer p 1, nDer p 4, rDer p 2, rDer p 5, rDer p 7, rDer p 8, rDer p 10). Furthermore, we investigated the sensitization and cross-reactivity to house-dust- and storage-mite allergen extracts by CAP FEIA measurements and by IgE competition studies. RESULTS: More than 95% of the patients could be diagnosed with a combination of nDer p 1 and rDer p 2. With the methods used, we could discriminate mite-allergic patients who were mainly sensitized to the major Der p allergens (Der p 1, Der p 2) from patients with a broad sensitization profile, including highly cross-reactive allergens (e.g. Der p 10: tropomyosin) as well as reactivity to storage mites. CONCLUSIONS: Diagnostic tests containing the major mite allergens (i.e. Der p 1, Der p 2) and highly cross-reactive mite allergens (e.g. Der p 10) may improve the diagnostic selection of patients for immunotherapy with Der p extracts. These tests may also be used for the immunological monitoring of patients undergoing immunotherapy.

Adolescent↗
PubMed2004

Decreased interferon-gamma response in respiratory syncytial virus compared to other respiratory viral infections in infants.

An inappropriate interferon-gamma response has been implicated in the pathogenesis of severe respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI). To assess whether this is unique for RSV primary LRTI compared to a first non-RSV LRTI, intracellular interferon-gamma was determined by flow cytometry in peripheral blood mononuclear cells from 32 infants with a primary RSV infection, 28 with a first non-RSV LRTI due to adenoviral, parainfluenzaviral and rhinoviral infection and 13 healthy infants. Interferon-gamma responses were increased significantly during adenoviral, parainfluenzaviral and the majority of the rhinoviral infections, but remained low during RSV and severe rhinoviral infection. Low interferon-gamma responses were associated with a more severe clinical course of LRTI. This indicates that depending on the nature of the viral pathogen, respiratory virus infections in infants differ significantly with regard to the quantity of the interferon-gamma production and that this may contribute to the clinical course of the disease.

Adenoviridae Infections↗
PubMed2003

Oral anticoagulation in older patients with vascular or cardiovascular diseases. Aged over 70 years: same risk? Same benefit?

AIM: The purpose of the study was to assess patients aged over 70 years and younger patients for possible differences in several aspects concerning anticoagulant therapy. METHODS: Two-hundred and twenty-three patients with anticoagulant treatment for an average duration of 2.6 years at an angiologic outpatient clinic were subdivided into 2 groups (above 70 years n=114; below 70 years n=109). The 2 groups were compared with regard to patient-specific data, treatment-related and compliance parameters as well as complications. RESULTS: The group of older patients included a higher number of female patients, presented with a less favorable risk profile and revealed tendency or significance in showing better compliance data. No differences were found for the incidence of bleeding complications, while recurrences were more frequent in patients below the age of 70 years. Treatment-related parameters reflecting quality and stability of anticoagulant therapy (standard deviation of international ratio (INR), frequency of laboratory controls) represent predictors of bleeding risk being of more critical importance than the age of the patient. Recurrent events also showed correlation with same relevant parameters. Younger patients undergoing the same intensity of treatment for similarly distributed indications show a higher rate of recurrences. CONCLUSION: The lower recurrence rate in older patients is consistent with the observation that anticoagulant therapy is more profitable in elderly with atrial fibrillation. Since older patients being treated with the same therapy intensity for comparable periods of time showed no higher bleeding risk than that seen for younger patients, we believe that there is no need for specific guidelines for older patients provided treatment is carefully monitored and controlled.

Administration, Oral↗
PubMed2002

Double-blind, randomised, placebo controlled low level laser therapy study in patients with primary Raynaud's phenomenon.

BACKGROUND: No causal treatment of primary Raynaud's phenomenon is available due to its unclear aetiology. Low level laser therapy (LLLT) is applied in a multitude of medical conditions often without sufficient evidence of efficacy and established mechanisms. To asses the effect of this therapy in patients with primary Raynaud's phenomenon a randomised, double blind, placebo controlled cross over study was designed. PATIENTS AND METHODS: Absolute and relative frequency and intensity of vasospastic attacks during three weeks of either LLLT or placebo therapy and results of infrared thermography before onset and at the end of both therapy sequences were evaluated in 15 patients with primary Raynaud's phenomenon. RESULTS: Frequency of Raynaud's attacks was not significantly affected by low level laser therapy. Compared to placebo a significantly lower intensity of attacks during laser irradiation was observed, but no transfer effect occurred. Additionally the mean temperature gradient after cold exposure was reduced after laser irradiation, while the number of fingers showing prolonged rewarming was unaffected. CONCLUSION: Though further studies are necessary to confirm these results we could demonstrate for the first time in a double blind placebo controlled clinical trial that low laser therapy is a potential candidate for an effective therapy of Raynaud's phenomenon, although effects seem to be of short duration.

Adult↗
PubMed2002

Serum tryptase measurements in patients with myelodysplastic syndromes.

Abnormal differentiation and maturation of hemopoietic cells are characteristic features of myelodysplastic syndromes (MDS). Tryptases (alpha- and beta-type) are lineage-restricted serine proteases primarily expressed in mast cells (MC). We have analyzed expression of tryptase in 89 de novo MDS patients (refractory anemia (RA), n = 30; RA with ringed sideroblasts (RARS), n = 21; RA with excess of blasts (RAEB/RAEB-t), n = 27; chronic myelomonocytic leukemia (CMML), n = 11). Serum levels of total tryptase (alpha - protryptase + beta - tryptase) were measured by FIA. The numbers of tryptase+ cells were determined in paraffin-embedded bone marrow (bm) sections by immunohistochemistry and morphometry. In healthy individuals, serum total tryptase levels ranged between < 1 and 15 ng/ml (5.6 +/- 2.8 ng/ml). Tryptase levels of > 20 ng/ml were detected in 5/22 patients with RA (22.7%), 4/17 with RARS (23.5%), 0/16 with RAEB/RAEB-t, and 3/8 with CMML (37.5%). Thus, serum tryptase concentrations were higher in RA (16.6 +/- 14.3 ng/ml), RARS (12.9 +/- 8.2), and CMML (16.5 +/- 7.6) compared to RAEB/-t (8.7 +/- 3.8). By morphometry, elevated numbers of tryptase+ bm cells were detected in all MDS groups (RA: 139 +/- 131; RARS: 118 +/- 98; RAEB/RAEB-t: 80 +/- 79; CMML: 105 +/- 114 cells/mm2) compared to controls (54 +/- 51 cells/mm2). As assessed by Northern blotting and protein analysis, bm cells in MDS primarily produced alpha-(pro)tryptase, but little or no beta-tryptase. Together, our data show that elevated levels of tryptase are detectable in a group of patients with MDS probably because of an increase in neoplastic (mast) cells producing the enzyme(s). In addition, serum tryptase levels appear to correlate with MDS variants. Follow up studies should clarify whether an elevated tryptase concentration in MDS is of prognostic significance.

Adult↗
PubMed2002

Moulds in housing: visual inspection and spore counts comparison--implications for future strategies in the public health setting.

OBJECTIVES: Among the problems of health related to living conditions presented to a public consulting centre for environmental medicine in Vienna, the main point at issue was damp housing and mould growth. On answering this demand indoor exposure to fungal spores was identified by visual semi-quantitative assessment of fungal growth on the one hand and quantitative measurement of viable spores on the other hand. The validity and practicability of this approach was investigated. METHOD: We applied these two simple methods in a standardised form and compared the results in a field study, which has been conducted between 1995 and 1999. In 197 rooms in Viennese flats (183 of which were claimed to be "mouldy") fungal spore concentrations were measured by RCS-impactor and Rose-Bengal-agar. Outdoor measurements were taken simultaneously outside the buildings and were used for reference. RESULTS: Independent classification of visible growth of mould in flats correlated significantly (r = 0.635; p < 0.0001) with the ratio of indoor/ outdoor concentration of fungal spores. CONCLUSIONS: It is usually possible to classify the severity of the problem just by local inspection. Visible plaques should always be an indication for sanitary measures. However, spore counting is indicated for quantifying health relevant exposures, for scientific comparisons and in documentation and follow up such as for litigation purposes. Quantitative data bear more credibility and so help to prove the need of sanitation.

Air Pollutants↗
PubMed2001

Increase of chlamydial LPS antibodies in patients with acute coronary syndrome without detection of chlamydial DNA in atherectomy samples.

BACKGROUND: Chlamydia pneumoniae, a respiratory pathogen, has been connected with the pathogenesis of coronary artery disease (CAD). Previous studies indicated a correlation between antibodies to chlamydial LPS and the risk of cardiovascular disease. The aim of this study was to determine whether C. pneumoniae plays a direct role in the pathology of acute coronary syndromes (ACS). METHODS AND RESULTS: Twenty-five consecutive patients (median age 56 years) with ACS (17 acute myocardial infarction, 8 unstable angina) were included in the study and underwent directional coronary atherectomy. Tissue and blood samples were subjected to conventional and real time polymerase chain reaction (PCR) for C. pneumoniae. Antichlamydial immunoglobulin A (IgA) and IgG were examined by LPS enzyme immunoassay (EIA) and microimmunofluorescence (MIF) at intervention and on days 20, 45 and 180 thereafter. DNA of C. pneumoniae was detected neither in atherectomy samples nor in peripheral blood. Serologic results with LPS EIA showed a rapid and significant increase in specific IgA and IgG within 20 days including seroconversion in six cases (4 IgA, 2 IgG). Positive IgA and IgG MIF levels (30% and 87%) remained stable throughout the observation period. CONCLUSIONS: We conclude that negative detection of chlamydial DNA excludes a direct role of chlamydia in ACS. Our findings of rapid LPS antibody increase suggest a role of chlamydial LPS antigen which appears to be released during the acute event e.g. from damaged tissue, indicating a renewed accessibility to the immune system. An indirect role of chlamydia in the further aetiologic process of CAD seems possible.

Acute Disease↗
PubMed2001

Khat (Catha edulis) consumption causes genotoxic effects in humans.

We used the micronucleus (MN) test to determine the genetic damage caused by khat, a widely consumed psychostimulant plant, in exfoliated cells of volunteers who chewed the drug on a regular basis. In the first study in which we compared the frequency of MN in buccal and bladder mucosa cells in 20 khat consumers (10-160 g/day) and 10 controls, a pronounced (8-fold) increase in micronucleated buccal mucosa cells was seen among khat consumers; khat consumption did not lead to a detectable elevation of micronucleated bladder mucosa cells. Among heavy khat chewers, 81% of the MN had a centromere signal indicating that khat is aneuploidogenic. To investigate the effect of simultaneous consumption of tobacco and alcoholic beverages, we compared the MN frequency in buccal cells of 25 khat consumers (20-85 g/day) who smoked cigarettes (15-60/day) and drank alcoholic beverages (15-80 g of pure ethanol/day) with a control group (control group I) of 25 individuals matched for age, body weight, tobacco and alcohol consumption and with another control group of 25 individuals (control group II) not consuming any of the drugs. The frequency of buccal mucosa cells with MN was higher in control group I than in group II and the effect of khat, tobacco and alcohol was found to be additive. A time-kinetics study on khat-induced MN showed that the highest frequency of MN was observed during the fourth week after consumption. In light of the large body of evidence on the close association between genetic damage and cancer, these results suggest that khat consumption, especially when accompanied by alcohol and tobacco consumption, might be a potential cause of oral malignancy.

Adult↗
PubMed2001

Antibody-response to three recombinant hepatitis B vaccines: comparative evaluation of multicenter travel-clinic based experience.

The immunogenicity of three currently used hepatitis B vaccines was compared in an unselected study population in an every day travel clinical setting. Five hundred and eighteen vaccinees received Engerix-B (EB), 990 received Twinrix (TWX), and 366 were immunised with Gen-HB-Vax (GHB). Overall, 88.6% of the vaccinees, tested within the first 6 months after completion of the vaccination series, developed protective levels of anti-HBs (> or = 10 mIU/ml). However, GHB recipients showed significantly lower seroprotection rates (SPR) than EB and TWX recipients (79.3% vs. 87.7% vs. 92.3%, P < 0.000001). GMTs for anti-HBs, tested within 6 months after the third vaccination, showed the lowest results in the GHB group, followed by EB and TWX (142 vs. 523 vs. 1008 mIU/ml, P < 0.000001). TWX vaccinees, however, showing a higher antibody decline rate than EB recipients within the first years after completion of the full immunisation course (30% vs. 25%; P = 0.0538). This study confirms an overall good immune response to the 20 microg-dose vaccine, in the course of a regular clinical setting. The significant difference in SPRs and GMTs to the 10 microg-dose vaccine, however, may influence future immunisation practices for the elderly.

Adolescent↗
PubMed2001

Genotoxic effects of methyl isothiocyanate.

Aim of the study was to investigate the genotoxic effects of methyl isothiocyanate (MITC), a compound widely distributed in the environment as a constituent of certain vegetables, a soil fumigant and breakdown product of carbamate pesticides. MITC caused only marginal mutation induction in reversion assays with Salmonella strains TA100 and TA98 and, the maximum effect (<2-fold increase over the background rate) was seen at 100microg/ml. In differential DNA-repair assays with E. coli (strains 343/763 uvrB/recA and 343/765 uvr(+)/rec(+)), a pronounced dose-response effect (induction of repairable DNA-damage) was seen at low concentrations (>/=4microg/ml). In both bacterial assays, addition of activation mix (rat liver S-9) led to a reduction of the genotoxic effects. In micronucleus assay and in single cell gel electrophoresis assay with human hepatoma cells (HepG2), clear cut positive results were obtained at exposure concentrations of <5microg/ml. On the contrary, only marginal effects were seen in differential DNA-repair host-mediated assays where E. coli indicator cells were recovered from different inner organs of mice that had been treated orally with a high dose (90mg/kg bw) of the test compound. Further in vitro experiments showed that MITC is inactivated by body fluids (saliva, gastric juice) and that its DNA-damaging properties are attenuated by non-enzymatic protein binding. Since exposure of HepG2 cells to MITC led to formation of thiobarbituric acid reactive substances, it is likely that its DNA-damaging effects involve lipid peroxidation processes. Overall, our findings show that MITC induces only marginal effects at extremely high (almost lethal) doses in inner organs in vivo, but it causes DNA-damage at low concentrations in vitro.

Adult↗