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Biomedical subjects

Michael Kundi

Publications and source records attributed to Michael Kundi.

At least 37 records · Page 2Linked to original sources
PubMed2005

Quantitation of minimal residual disease in acute myeloid leukemia by tryptase monitoring identifies a group of patients with a high risk of relapse.

PURPOSE: Recent data suggest that tryptase is produced by blast cells in a group of patients with acute myeloid leukemia (AML). In these patients, serum tryptase levels are elevated at diagnosis and decrease to normal (<15 ng/mL) or near normal values in those achieving complete hematologic remission (CR) after chemotherapy. PATIENTS: In this study, we examined the value of tryptase as a marker of minimal residual AML. In 61 patients with de novo AML exhibiting elevated serum tryptase (>15 ng/mL) at diagnosis, tryptase levels were measured serially during and after chemotherapy by a fluoroenzyme immunoassay. RESULTS: Of the 61 patients, 42 (68.9%) entered hematologic CR in response to induction chemotherapy. Twenty-nine of these 42 patients also entered biochemical remission (BR) defined by a decrease of tryptase levels to normal (<15 ng/mL). The remaining 13 patients exhibited elevated enzyme levels despite of hematologic CR. As assessed by multivariate analysis, the elevated tryptase in CR was found to be an independent prognostic variable concerning disease-free survival. Thus, AML relapses occurred in 15 of 29 patients with CR + BR (52%) and in 12 of 13 patients with CR without BR (92%), resulting in a significantly reduced probability of continuous CR for patients with CR without BR (P < 0.05). In all patients with continuous hematologic CR, tryptase levels remained constantly normal, whereas a recurrent elevation of tryptase in CR was invariably followed by a hematologic relapse. CONCLUSION: A persistently elevated tryptase level in AML in CR is indicative of minimal residual AML and associated with a high risk of relapse.

Acute Disease↗
PubMed2005

Dimensions of engorging Ixodes ricinus as a measure of feeding duration.

Knowledge of the duration of tick feeding can contribute to assessment of disease transmission risk, and may be estimated from changes in body dimensions during engorgement. Application of this approach to the European tick, Ixodes ricinus, is described here. Nymphal and adult female I. ricinus ticks were detached at predetermined intervals from laboratory rabbits and their state of engorgement estimated by calculating either the scutal index (the ratio of the width of the scutum to the length of the idiosoma) or the coxal index (the ratio of the width of the scutum to the distance between the basal coxae of the fourth pair of legs - the coxal gap). The coxal index proved to be more accurate in estimating duration of feeding over the first 24h, but the scutal index was more accurate later in feeding. The coxal index may be used in combination with the scutal index to estimate the period of time that ticks removed from patients have been feeding, thus assisting with the assessment of pathogen transmission risk.

Animals↗
PubMed2005

Coffee consumption induces GSTP in plasma and protects lymphocytes against (+/-)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide induced DNA-damage: results of controlled human intervention trials.

A number of animal studies indicate that coffee protects against chemical induction of cancer; also human studies suggest that coffee consumption is inversely related with the incidence of different forms of cancer. The protective effects were attributed to induction of glutathione-S-transferases (GSTs) and aim of the present human study was to find out if coffee causes induction of GSTs and protects against DNA-damage caused by (+/-)-anti-B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), the DNA-reactive metabolite of benzo(a)pyrene. Ten participants consumed 1L unfiltered coffee/d over 5 days. Before and after the intervention, saliva and blood were collected and the overall GST activity was measured with 1-chloro-2,4-dinitrobenzene (CDNB). Additionally, GSTP and GSTA were determined in plasma with immunoassays. In blood, only weak (p=0.042) induction of GST (CDNB) was found. Furthermore, pronounced (three-fold) induction of GSTP was observed in blood, whereas GSTA was not altered. No correlations were seen between induction of GST (CDNB) and GSTP activities and the GSTP1 genotypes of the participants. Also clinical parameters (creatinine, alanine, aminotransferase, aspartate aminotransferase, alkaline phosphatase), which are markers for organ damage, were monitored. None of them was altered by coffee, but serum cholesterol levels were slightly (not significantly) enhanced. In a second trial (n=7), GSTP induction by unfiltered and paper filtered coffees, differing in cafestol and kahweol contents, were compared. The participants consumed 1L coffee/d over 3 days. Again significant (three-fold) induction of GSTP was observed. The effects seen with the two coffees were identical, indicating that the diterpenoid concentrations are not responsible for the effects. In a further trial (n=7), the effect of coffee (unfiltered, 1L/d, 5 days) on BPDE induced DNA-migration was studied in comet assays. A 45% reduction effect was observed. Our findings show that coffee induces GSTP in humans and indicate that consumption may lead to protection towards polycyclic aromatic hydrocarbons.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2005

Suppression of human melanoma tumor growth in SCID mice by a human high molecular weight-melanoma associated antigen (HMW-MAA) specific monoclonal antibody.

The lack of efficacy of available therapies for the treatment of malignant melanoma has emphasized the need to develop novel therapeutic strategies to prevent melanoma growth. We have tested whether the anti-HMW-MAA mAb 225.28S is able to inhibit human melanoma tumor growth in SCID mice because in vitro data suggested that this antigen plays a role in spreading, migration and invasion of melanoma cells. Tumors were established by subcutaneous injection of the human melanoma cell line 518A2 into SCID mice. When tumors reached a size of 5 mm, the mAb 225.28S was administered intravenously 4 times in 3 day intervals at 100 microg/injection. Within 14 days after the first administration of the mAb 225.28S, tumor growth was reduced by 52% as compared to control mice. Three hundred and seven genes of >20,000 genes contained on the GeneChip were changed in their expression level at least 2-fold after administration of the mAb 225.28S. The encoded proteins were mostly components or modifiers of the extracellular matrix, tumor suppressors, and melanogenesis associated proteins. Surprisingly, the administration of the control mAb that did not lead to a significant tumor growth inhibition in vivo resulted in the modulation of two-thirds of these genes. This is the first report of suppression of human melanoma tumor growth in SCID mice by the mAb 225.28S. Our results suggest that anti-HMW-MAA mAbs may represent useful reagents to apply passive immunotherapy to patients with malignant melanoma.

Animals↗
PubMed2005

Anti-ulcer drugs promote IgE formation toward dietary antigens in adult patients.

Recently, we have demonstrated that anti-ulcer drugs, such as H2-receptor blockers and proton pump inhibitors, promote the development of immediate type food allergy toward digestion-labile proteins in mice. The aim of this study was to examine the allergological relevance of these findings in humans. In an observational cohort study, we screened 152 adult patients from a gastroenterological outpatient clinic with negative case histories for atopy or allergy, who were medicated with H2-receptor blockers or proton pump inhibitors for 3 months. IgE reactivities to food allergens before and after 3 months of anti-acid treatment were compared serologically. Ten percent of the patients showed a boost of preexisting IgE antibodies and 15% de novo IgE formation toward numerous digestion-labile dietary compounds, like milk, potato, celery, carrots, apple, orange, wheat, and rye flour. Thus, the relative risk to develop food-specific IgE after anti-acid therapy was 10.5 (95% confidence interval: 1.44-76.48). The long-term effect was evaluated 5 months after therapy. Food-specific IgE could still be measured in 6% of the patients, as well as significantly elevated serum concentrations of ST2, a Th2-specific marker. An unspecific boost during the pollen season could be excluded, as 50 untreated control patients revealed no changes in their IgE pattern. In line with our previous animal experiments, our data strongly suggest that anti-ulcer treatment primes the development of IgE toward dietary compounds in long-term acid-suppressed patients.

Adult↗
PubMed2005

Single versus dual respiratory virus infections in hospitalized infants: impact on clinical course of disease and interferon-gamma response.

BACKGROUND: Dual respiratory viral infections are frequently associated with lower respiratory tract illness in infants. This study aimed to determine the impact of a dual respiratory viral infection on specific aspects of the infant's immune response and the clinical course of illness. METHODS: A prospective study was performed with 772 infants hospitalized from October 2000 through July 2004. Sensitive polymerase chain reaction methodology revealed the presence of a single respiratory virus in 443 (57%) of 772 cases, whereas dual infections were identified in 153 (20%) of cases. From 250 infants with confirmed respiratory viral infection, fresh heparinized blood was analyzed for interferon-gamma (IFN-gamma) responses by flow cytometry. Of these, 191 patients had a single infection with respiratory syncytial virus (RSV), rhinoviruses, adenoviruses or influenza viruses; and 59 patients had a dual infection with RSV and rhinoviruses, RSV and adenoviruses, influenza viruses and rhinoviruses or adenoviruses and rhinoviruses. The clinical features and peripheral lymphocyte IFN-gamma responses were compared among infants with single or dual infections. RESULTS: It was found that dual infections with non-RSV respiratory viruses induced peripheral blood mononuclear cell IFN-gamma responses that mimic those of single infections, whereas coinfection with RSV was associated with reduced IFN-gamma responses and a more severe clinical course of lower respiratory tract disease. CONCLUSIONS: The results indicate that the clinical characteristics and the IFN-gamma response differ significantly in single and dual respiratory viral infection, depending on the nature of the simultaneously detected viruses. In dual infections, RSV involvement was associated with a decreased IFN-gamma response in peripheral blood mononuclear cell and an increase in severity of illness.

Female↗
PubMed2004

Sudden and unexpected deaths after the administration of hexavalent vaccines (diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilius influenzae type b): is there a signal?

UNLABELLED: Deaths in temporal association with vaccination of hexavalent vaccines have been recently reported. The objective of this paper is to assess whether these temporal associations can be attributed to chance. Standardised mortality ratios (SMR) for deaths within 1 to 28 days after administration of either of the two hexavalent vaccines in the 1st and 2nd year of life were determined using the respective annual rates for sudden unexpected deaths (SUDs) from the national vital statistics. The distribution of SUD cases and the vaccination uptake by month were estimated from surveys and sales figures for the individual vaccines. Sensitivity analyses were performed to account for limitations in the data sources. For one of the vaccines, Vaccine B, all SMRs were well below one. For the other, Vaccine A, SMRs exceeded one insignificantly on the 1st day after vaccination in the 1st year of life. In the 2nd year of life, however, the SMRs for SUD cases within 1 day of vaccination with vaccine A were 31.3 (95% CI 3.8-113.1; two cases observed; 0.06 cases expected) and 23.5 (95% CI 4.8-68,6) for within 2 days after vaccination (three cases observed; 0.13 cases expected). Extensive sensitivity analyses could not attribute these findings to limitations of the data sources. CONCLUSION: These findings based on spontaneous reporting do not prove a causal relationship between vaccination and sudden unexpected deaths. However, they constitute a signal for one of the two hexavalent vaccines which should prompt intensified surveillance for unexpected deaths after vaccination.

Age Distribution↗
PubMed2004

Antibody maturation and viremia after primary cytomegalovirus infection, in immunocompetent patients and kidney-transplant patients.

To investigate antibody maturation and serum levels of cytomegalovirus (CMV) DNA after primary CMV infection, we studied 51 immunocompetent and 27 kidney-transplant patients. Compared with the immunocompetent patients, the transplant patients had significantly more-prolonged and -variable antibody maturation, clearly longer durations of viremia, and higher levels of CMV DNA; however, antibody maturation continued for >1 year even in immunocompetent patients. Long-term ganciclovir prophylaxis in the transplant patients was associated with either delayed immunoglobulin-G seroconversion, inhibition of antibody maturation (n=2), or immunoglobulin-class switching (n=1). In conclusion, antibody maturation continues in immunocompetent patients for a period longer than previously had been thought and is significantly delayed or even inhibited in kidney-transplant patients.

Adult↗
PubMed2004

Prospective surveillance of incidence, serotypes and antimicrobial susceptibility of invasive Streptococcus pneumoniae among hospitalized children in Austria.

OBJECTIVES: This study was undertaken to analyse incidence rates, serotype distribution and antimicrobial resistance patterns of invasive Streptococcus pneumoniae isolates from hospitalized children up to 5 years of age with invasive pneumococcal disease (IPD), including meningitis, in Austria. METHODS: From February 2001-January 2003, nationwide prospective surveillance was conducted that included all paediatric hospitals and clinical microbiological laboratories. All invasive pneumococci isolated were serotyped and tested for antimicrobial susceptibility. RESULTS: The mean annual incidence rates of IPD per 10 000 population for the age groups <24 months and <60 months were 14.5 (7.7 for meningitis) and 13.7 (6.0 for meningitis), respectively. The case fatality rate was 6% for IPD and 12% for meningitis. Of all IPD cases, 69.6% (73.1% for meningitis) were covered by serotypes and 83.9% (88.5% for meningitis) by cross-protection of vaccine-related serotypes. Intermediate penicillin G susceptibility (MIC 0.12-1 mg/L) was found in 12/56 strains. No penicillin G-resistant strains were found. A total of 19/56 isolates showed decreased susceptibility to macrolide agents (MIC >/= 1 mg/L). CONCLUSIONS: The IPD incidence rate was similar, and serotype coverage of the 7-valent conjugated vaccine marginally superior, to Germany. The surprisingly high level of antimicrobial resistance among invasive isolates considerably amplifies the potential impact of a childhood pneumococcal vaccination programme in Austria.

Anti-Infective Agents↗
PubMed2004

Effect of common Brassica vegetables (Brussels sprouts and red cabbage) on the development of preneoplastic lesions induced by 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in liver and colon of Fischer 344 rats.

Aim of the present study was the investigation of effects of juices from commonly consumed Brassica vegetables (two cultivars of Brussels sprouts and two cultivars of red cabbage) on formation and development of preneoplastic lesions in colons (aberrant crypt foci, ACF) and livers (glutathione-S-transferase placental form, GST-P+) in male F344 rats. The foci were induced by 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a widespread carcinogenic heterocyclic aromatic amine which is found in fried meats. Recently, we reported on pronounced protective effects in the two-organ foci model when the vegetable juices were given during the carcinogen treatment but several findings by other groups indicated that breakdown products of glucosinolates contained in Brassica vegetables cause tumour promotion in various organs of laboratory rodents. In the present study, the animals received the juices in the drinking water (5%) over a period of 20 days after treatment with IQ (100 mg/kg bw on 10 alternate days). To increase the foci yield (which facilitates the detection of modifying effects), the animals were fed with a modified (high fat, fibre free) AIN-76 diet. With exception of the sprout variety "Cyrus", all juices lowered the number of GST-P+ foci as well as the foci area in the liver, but none of these effects was statistically significant. In the colon, none of the juices had an impact on crypt multiplicity (number of crypts/focus), whereas the number of ACF was decreased; only with the sprout variety Maximus the protective effect was significant (reduction 49%). The present findings show that administration of vegetable juices to the animals after the carcinogen does not increase the number and size of IQ-induced preneoplastic lesions in liver and colon.

Animals↗
PubMed2004

Public perception of risk concerning celltowers and mobile phones.

OBJECTIVE: The controversy about health risks of electromagnetic fields (EMF) has contributed in raising fears concerning emissions from celltowers. The study was to examine whether or not neighbours of celltowers are particularly concerned about adverse health effects of mobile phones and their base stations. METHODS: Prior to information delivered by medical doctors of the Institute of Environmental Health at public hearings a questionnaire was handed out to participants asking for their personal rating of several environmental health risks including those of mobile telecommunication (n = 123, response rate approx. 48%). Medical students (n = 366) served as a contrast group. RESULTS: Participants rated health risk for both, mobile phones and celltowers higher as students. A trend for higher ratings was also seen with older subjects and female sex. The risk ratings of both exposures correlated well with each other. The magnitude of the perceived risks, however, resembled that of other ubiquitous exposures like traffic noise and air pollution. CONCLUSION: Contrary to the claims of the telecommunication industry, opponents of celltowers generally do not express unusual fears concerning electromagnetic field exposure. The outcome of our study indicates that the risk rating is comparable with other perceived common hazards of the civilised world. It is hypothesised that offering information and participation to the concerned population will be efficient in reducing exaggerated fears.

Adult↗
PubMed2004

Degree of atherosclerosis predicts short-term commitment for smoking cessation therapy.

BACKGROUND: Only little is known about factors that influence the smokers' propensity to start smoking cessation therapy and stay within such programs. METHODS: One hundred fifteen subjects that were current smokers and presented at the angiologic outpatient unit were enrolled in a prospective cohort study. All patients were invited to take part in a smoking cessation program. Patients' history, noninvasive vascular, cardiac, and pulmonary parameters, state of atherosclerotic disease (SMART-score), smoking history, and Fagerström index were obtained and the carbon monoxide breathing test was performed. RESULTS: Lower age and heavy smoking were associated with less propensity to start smoking cessation therapy. The degree of atherosclerosis significantly predicted short-term commitment to smoking cessation therapy (relative risk for discontinuation: 0.82; 95% CI: 0.70-0.96). Single factors predictive for staying within the therapy were peripheral arterial occlusive disease and hyperlipidemia, while neither prior myocardial infarction nor pulmonary function was associated with compliance. Fifty-four percent of patients that completed 3 months of therapy quit smoking. CONCLUSIONS: Counseling in smokers with preexistent or newly diagnosed atherosclerotic diseases or risk factors should include their specific vascular condition and information on positive consequences on the progress of these conditions. Counseling for initiation of smoking cessation therapy should apply different strategies as used in the maintenance phase of therapy.

Arteriosclerosis↗
PubMed2004

Low level laser therapy in primary Raynaud's phenomenon--results of a placebo controlled, double blind intervention study.

OBJECTIVE: To assess the efficacy of low level laser therapy in patients with primary Raynaud's phenomenon and predict the success of laser therapy by clinical characteristics. METHODS: Forty-eight patients were included in a randomized placebo controlled, double blind crossover study. Laser and sham therapy each were applied 5 days a week for 3 weeks. Clinical symptoms, exposure to triggers, and frequency and intensity of attacks were recorded in diaries. Results of infrared thermography before onset and at the end of both irradiation sequences were evaluated. Primary endpoint was the average intensity of attacks; secondary endpoints were average number of attacks and thermography results. Age, sex, duration of symptoms, age at onset of symptoms, evoking conditions other than cold, maximum temperature drop after cold provocation, and rewarming time after cold provocation were tested as potential predictors. RESULTS: Number of attacks and their intensity were significantly reduced during laser therapy compared to sham treatment. Thermographic parameters did not reach statistical significance. In a stepwise multiple regression analysis, evoking conditions other than cold (stress, wetness as additional triggers), rewarming time, and temperature decrease after cold provocation were significant predictors of therapeutic efficacy. CONCLUSION: Low level laser therapy reduces frequency and severity of Raynaud attacks. The effect is most pronounced in patients with signs of decreased threshold for vasospasm and less effective in patients with delayed hyperemia.

Analysis of Variance↗