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Reinhard Würzner

Publications and source records attributed to Reinhard Würzner.

At least 19 recordsLinked to original sources
PubMed2007

Co-infection with two Chlamydophila species in a case of fulminant myocarditis.

OBJECTIVE: The aim of this study is to describe a case of fulminant myocarditis caused by co-infection with Chlamydophila pneumoniae and Chlamydophila psittaci in order to facilitate diagnosis and clinical management of patients suffering from this rare but life-threatening condition. DESIGN: Case report. SETTING: Intensive care unit of Innsbruck Medical University. PATIENT: A 24-yr-old patient admitted with septicemia and cardiac failure. INTERVENTIONS: Cardiopulmonary resuscitation, extracorporal membrane oxygenation, implantation of an extracorporal cardiac assist device, and antibiotic treatment with erythromycin. MEASUREMENTS AND MAIN RESULTS: Cp. pneumoniae and Cp. psittaci were identified by means of polymerase chain reaction and electron microscopy in the patient's myocytes. Successful weaning off the ventricular assist device was performed within 2 wks after commencement of antibiotic therapy. CONCLUSIONS: This case report demonstrates co-infection with Cp. pneumoniae and Cp. psittaci to be a hitherto unknown cause of fulminant myocarditis. There is a particular risk of misdiagnosis of viral myocarditis, which must be avoided. Patients should be transferred to a center where extracorporal membrane oxygenation therapy and molecular diagnosis of all members of the family Chlamydiaceae are available.

Adult↗
PubMed2006

Emerging Shiga toxin-producing Escherichia coli serotypes in Europe: O100:H- and O127:H40.

Novel and as yet rare non-O157 Shiga toxin (Stx)-producing Escherichia coli (STEC) serotypes are emerging in Europe. Two different sorbitol-fermenting STECs, O100:H- carrying the virulence gene stx2 and O127:H40 carrying stx1 and eae genes (found in two related subjects), were isolated from patients' stool samples. Non-O157 STEC infections in humans are currently under-diagnosed. This report highlights the need for, and importance of, screening for Shiga toxins or serotypes other than just O157.

Aged↗
PubMed2006

Prevalence, structure and expression of urease genes in Shiga toxin-producing Escherichia coli from humans and the environment.

A component of the ure gene cluster in E. coli, ureC, encodes a subunit of urease. We have investigated the distribution of ureC in 202 Shiga toxin-producing E. coli (STEC) strains from Austria belonging to 61 different serotypes. These strains were of human (n=150), animal (n=38), and food (n=14) origin. ureC was present in all 72 E. coli O157:H7 and O157:NM (non-motile) strains, as well as in all 29 strains of serotypes O26:H11/NM, O111:H8/NM and O145:NM. In contrast, none of eight sorbitol-fermenting E. coli O157:NM were ureC-positive. ureC occurred significantly more frequently among STEC that carry eae (113 of 132; 85.6%) than among eae-negative STEC strains (four of 70; 5.7%; p<0.0001). However, only 4 (2%) of the 202 strains (3.4% of ureC positive strains) expressed urease activity. There was no significant association (p=0.56) between urease expression and the source of the isolates (humans vs. animals). Nucleotide sequence analysis of PCR amplicons derived from all seven genes of the ure cluster in STEC of 10 different serotypes demonstrated a high degree of homology (>or=99%), indicating a recent acquisition of not necessarily expressed ure genes.

Adhesins, Bacterial↗
PubMed2006

Booster vaccination in the elderly: their success depends on the vaccine type applied earlier in life as well as on pre-vaccination antibody titers.

BACKGROUND: Recent retrospective studies demonstrate that elderly persons have a shortened protection period following vaccination with recall antigens. METHODS: We now analysed the effect of booster vaccination with a multivalent vaccine containing tetanus, dipththeria, pertussis and polio antigens in 252 healthy elderly persons. The magnitude of the humoral immune response was assessed by antibody measurements. RESULTS: Comparison with a small control group of 21 younger persons demonstrates that pre- and post-vaccination antibody concentrations are lower in elderly persons for all antigens except polio, for which higher pre- and similar post-vaccination antibody levels are observed. Using multiple linear regression analysis we also show that the magnitude of the humoral immune response in elderly persons greatly depends on pre-vaccination antibody concentrations in the case of tetanus, diphtheria and pertussis, but much less so in the case of polio, against which priming and preceding booster immunizations were performed with attenuated live vaccine. CONCLUSION: Regular booster vaccinations throughout life are of clinical importance to maintain the ability to respond to recall antigens in old age. Longer lasting protection and good responsiveness to boosting in spite of low antibody titres can be expected following exposure to live vaccine earlier in life.

Adult↗
PubMed2006

Cognitive deterioration in Alzheimer's disease is accompanied by increase of plasma neopterin.

The pro-inflammatory reaction of the immune system is a feature of healthy aging and might influence the progression of Alzheimer's disease (AD). Neopterin is a pteridine derivative, released from macrophages upon stimulation with pro-inflammatory cytokine interferon-gamma. Forty-three probable AD patients were investigated at baseline and follow up (14.5+/-0.5 months; mean+/-s.e.m.). We assessed the clinical progression by the Consortium to Establish a Registry for Alzheimer's disease (CERAD) battery and compared cognitive changes to serum concentrations of neopterin, C-reactive protein (CRP) and antibody to cytomegalovirus (CMV). The mean neopterin concentrations increased significantly from 9.8+/-1.0 to 13.6+/-2.1 nM (p=0.04). In contrast, mean CRP concentrations at baseline was 0.46+/-0.1 and non-significantly decreased to 0.28+/-0.04 mg/dl. Of AD patients 70% were CMV IgG-seropositive at baseline and CMV-antibody concentrations correlated with levels of neopterin (Spearman r=0.386, p=0.016). CERAD scores did not correlate with any of immune parameters at baseline. At follow up, the increase of neopterin correlated significantly with the decrease in the total CERAD and MMSE scores, according to the clinical progression (r=-0.353, p<0.05 and r=-0.401, p<0.01, respectively). Subdividing the sample with respect to baseline MMSE scores, neopterin concentrations significantly increased only in the group of MMSE<20. In the multiple testing covariated for age, gender, Apolipoprotein E-epsilon4 allele, time difference between both measurements, neopterin remained significantly associated with cognitive decline. In summary, neopterin concentrations correlated with cognitive decline in AD patients, which might be due to high CMV seropositivity in that population.

Aged↗
PubMed2006

Human granulocytic anaplasmosis in Austria: epidemiological, clinical, and laboratory findings in five consecutive patients from Tyrol, Austria.

We report five consecutive cases of Anaplasma (A.) phagocytophilum infection (the causative agent of human granulocytic anaplasmosis (HGA)) from western Austria. All infections were acquired between June and August in 2003 and 2004 in the Inn valley (Tyrol, Austria). Four patients required hospitalisation, one patient was treated as an outpatient. During the acute stage of illness, laboratory findings included thrombocytopenia (5/5), elevated C-reactive protein (5/5), elevated neopterin (5/5), elevated lactate dehydrogenase (4/5), and elevation of liver enzymes (4/5). Leukopenia (3/5) and elevated procalcitonin (2/5) were less frequently observed. All patients were treated with tetracyclines, which led to prompt improvement of the clinical conditions. Anti-platelet antibodies were observed in one of four patients, but remained unchanged after complete covalescence.

Adult↗
PubMed2006

Serological evidence for tick-borne encephalitis, borreliosis, and human granulocytic anaplasmosis in Mongolia.

Five hundred and forty-five serum samples from donors from various parts of Mongolia were investigated for antibodies against the tick-borne encephalitis (TBE) virus, Borrelia burgdorferi, and Anaplasma phagocytophilum. Seroprevalence against TBE was 5.1% in the province of Selenge and 0.9% in Bulgan province, seroprevalence against B. burgdorferi was 1.9% in Selenge province and Bulgan province, 13.9% in Dornogov province, and 3.0% in Tov province and Ulaanbaatar. Seroprevalence against A. phagocytophilum was 2.3% in Selenge province, 5.6% in Bulgan province, 2.8% in Dornogov province, and 3.0% in Tov province and Ulaanbaatar. We conclude that all three pathogens are endemic in Mongolia.

Anaplasma phagocytophilum↗
PubMed2006

Complement escape of human pathogenic bacteria by acquisition of complement regulators.

Pathogenic micro-organisms employ a broad range of strategies to survive in and to persistently infect the human host. Far from being completely understood by which highly sophisticated means invading pathogens overcome the host's destructive immune defence, there is a growing body of evidence on particular mechanisms which play a pivotal role for immune evasion. This review focuses on evasion of medically and scientifically important bacteria by acquisition of host derived fluid-phase complement regulatory proteins, in particular factor H, FHL-1, and C4b binding protein. Expression of microbial surface molecules binding to human complement regulators and thus fixing them in a functionally active state allows pathogens to inhibit and finely regulate complement activation directly on their surface. Further studies on the utilization of host complement regulatory proteins will likely have a marked impact on a more efficient and specific clinical treatment.

Bacteria↗
PubMed2006

Terminal complement complex (C5b-9) in children with recurrent hemolytic uremic syndrome.

Recurrent hemolytic uremic syndrome (recHUS) is a heterogeneous group of disorders. The pathogenesis of recHUS is not fully understood. recHUS has a high risk of development of terminal renal insufficiency and other sequelae. Abnormalities in complement factor H or in membrane-bound complement inhibitors with consecutive complement activation can be found in approximately 30 to 50% of the patients. Starting in 2001, we evaluated 42 patients with recHUS from five European countries (Germany, Austria, Hungary, Switzerland, and the Czech Republic). We measured the terminal complement complex (TCC) by an enzyme-linked immunosorbent assay using a neoepitope-specific anti-C9 antibody in 17 patients in plasma (native complement activation), serum (after coagulation), and zymosan-activated serum (Z-serum; after stimulation of coagulation). We compared the results to those of 16 healthy persons. In patients with recHUS (eight males, nine females) with a median age of 10.8 years, the TCC values were higher in plasma (0.57 versus 0.48 microg/mL; P = 0.04) and serum (3.1 versus 2.2 microg/mL) than in those of the control group, with a median age of 28.6 years (six males, 10 females) The TCC values in patients with low C3 compared with patients with normal C3 levels were even higher in plasma and serum, and the ratio was much lower. Children with recHUS have higher concentrations of TCC in plasma and serum. The ratio of Z-serum to serum showed significantly lower values in children with recHUS (96.01 versus 150.3; P = 0.01). These findings indicate a higher grade of complement activation and consumption in recHUS, suggesting that TCC may mediate cell toxicity. This may play an important role in the inferior outcome of these patients. The isolated substitution of factor H, or other complement inhibitors to block TCC formation, may represent useful therapies for these patients.

Adolescent↗
PubMed2006

A comparison of Listeria monocytogenes serovar 4b isolates of clinical and food origin in Austria by automated ribotyping and pulsed-field gel electrophoresis.

In this study, two typing methods, automated ribotyping and pulsed-field gel electrophoresis (PFGE), were evaluated for the subtyping of Listeria monocytogenes serotype 4b. The strains originated from patients and food samples collected in Austria during 2001-2005 and from Europe and North America in the World Health Organization collaborative study on the subtyping of this species. The largest group of Austrian clinical isolates was of the same PFGE subtype as those isolated from foodborne outbreaks in Switzerland and in the United States. Another subtype of clinical isolates from Austria was indistinguishable to that obtained from isolates responsible for a foodborne outbreak in the United States in 1985. Although the discriminatory power of PFGE was higher than that of automated ribotyping, some PFGE types were differentiated by ribotyping. Thus, combining data obtained by both automated ribotyping and PFGE increases the strain discrimination. Still, many of the Austrian strains remain indistinguishable from strains of foodborne outbreaks in other countries although there is no known epidemiological relation. This complies to previous studies which show the highly clonal nature of L. monocytogenes 4b strains which are responsible for both large outbreaks and sporadic cases.

Animals↗
PubMed2006

Cytolethal distending toxins in Shiga toxin-producing Escherichia coli: alleles, serotype distribution and biological effects.

To assess the prevalence of cytolethal distending toxin (CDT) among Shiga toxin-producing Escherichia coli (STEC), 202 STEC strains were investigated using PCRs targeting various cdt alleles (cdt-I to cdt-V). Seven of the 202 strains contained cdt-III and an additional seven contained cdt-V. All 14 cdt-positive strains produced biologically active CDT, as demonstrated by a progressive distension of cultured Chinese hamster ovary cells. The CDT-positive STEC belonged to eight different serotypes, including sorbitol-fermenting O157 : NM (non-motile). The data demonstrate that CDT is present in some STEC serotypes only. However, more studies are required to evaluate whether CDT presence is associated with severe disease.

Alleles↗
PubMed2006

The vesicle transport protein Vac1p is required for virulence of Candida albicans.

The putative vesicle transport protein Vac1p of the human pathogenic yeast Candida albicans plays an important role in virulence. To determine the cellular functions of Vac1p, a null mutant was generated by sequential disruption of both alleles. The vac1 null mutant strain showed defective endosomal vesicle transport, demonstrating a role of Vac1p in protein transport to the vacuole. Vac1p also contributes to resistance to metal ions, as the null mutant strain was hypersensitive to Cu(2+), Zn(2+) and Ni(2+). In addition, the loss of Vac1p affected several virulence factors of C. albicans. In particular, the vac1 null mutant strain showed defective hyphal growth, even when hyphal formation was induced via different pathways. Furthermore, Vac1p affects chlamydospore formation, adherence to human vaginal epithelial cells, and the secretion of aspartyl proteinases (Saps). Avirulence in a mouse model of systemic infection of the vac1 null mutant strongly suggests that Vac1p of C. albicans is essential for pathogenicity. In summary, the Vac1p protein is required for several cellular pathways, in particular those that control virulence and pathogenicity. Consequently, Vac1p is a novel and interesting target for antifungal drugs.

Animals↗
PubMed2006

C-reactive protein and leukocytes do not reliably indicate severity of influenza a infection in childhood.

Influenza in children may mimic other infections leading to insufficient treatment. Determination of parameters that facilitate diagnosis and indicate severity would be useful to optimize treatment modalities. We prospectively screened 432 children for influenza infection. Forty-six children at the age of 4 weeks to 14 years (median, 18 months) with confirmed influenza A infection were analyzed. A clinical score of illness severity was calculated from the symptoms presented. To evaluate the dependency of the clinical score on C-reactive protein value, leukocyte count, age, and days of hospitalization, correlation and regression analyses were carried out. Neither the C-reactive protein values (median, 0.85 mg/dL; range, 0.2-18.6; r=0.14; p=0.35) nor the leukocyte counts (median, 7.95 G/L; range, 3.5-17.6; r=-0.14, p=0.34) correlated significantly with the clinical score of influenza severity. Thus, in daily clinical practice, C-reactive protein and leukocytes seem to be insufficient parameters to describe the clinical severity of influenza A infection in children.

Adolescent↗
PubMed2005

CD25-expressing CD8+ T cells are potent memory cells in old age.

We have recently described an IL-2/IL-4-producing CD8+CD25+ non-regulatory memory T cell population that occurs in a subgroup of healthy elderly persons who characteristically still have a good humoral response after vaccination. The present study addresses this specific T cell subset and investigates its origin, clonal composition, Ag specificity, and replicative history. We demonstrate that CD8+CD25+ memory T cells frequently exhibit a CD4+CD8+ double-positive phenotype. The expression of the CD8 alphabeta molecule and the occurrence of signal-joint TCR rearrangement excision circles suggest a thymic origin of these cells. They also have longer telomeres than their CD8+CD25- memory counterparts, thus indicating a shorter replicative history. CD8+CD25+ memory T cells display a polyclonal TCR repertoire and respond to IL-2 as well as to a panel of different Ags, whereas the CD8+CD25- memory T cell population has a more restricted TCR diversity, responds to fewer Ags, and does not proliferate in response to stimulation with IL-2. Molecular tracking of specific clones with clonotypic primers reveals that the same clones occur in CD8+CD25+ and CD8+CD25- memory T cell populations, demonstrating a lineage relationship between CD25+ and CD25- memory CD8+ T cells. Our results suggest that CD25-expressing memory T cells represent an early stage in the differentiation of CD8+ cells. Accumulation of these cells in elderly persons appears to be a prerequisite of intact immune responsiveness in the absence of naive T cells in old age.

Aged↗
PubMed2005

Antifungal activity of the local complement system in cerebral aspergillosis.

Dissemination of aspergillosis into the central nervous system is associated with nearly 100% mortality. To study the reasons for the antifungal immune failure we analyzed the efficacy of cerebral complement to combat the fungus Aspergillus. Incubation of Aspergillus in non-inflammatory cerebrospinal fluid (CSF) revealed that complement levels were sufficient to obtain a deposition on the surface, but opsonization was much weaker than in serum. Consequently complement deposition from normal CSF on fungal surface stimulated a very low phagocytic activity of microglia, granulocytes, monocytes and macrophages compared to stimulation by conidia opsonized in serum. Similarly, opsonization of Aspergillus by CSF was not sufficient to induce an oxidative burst in infiltrating granulocytes, whereas conidia opsonized in serum induced a clear respiratory signal. Thus, granulocytes were capable of considerably reducing the viability of serum-opsonized Aspergillus conidia, but not of conidia opsonized in CSF. The limited efficacy of antifungal attack by cerebral complement can be partly compensated by enhanced synthesis, leading to elevated complement concentrations in CSF derived from a patient with cerebral aspergillosis. This inflammatory CSF was able to induce (i) a higher complement deposition on the Aspergillus surface than non-inflammatory CSF, (ii) an accumulation of complement activation products and (iii) an increase in phagocytic and killing activity of infiltrating granulocytes. However, levels and efficacy of the serum-derived complement were not reached. These data indicate that low local complement synthesis and activation may represent a central reason for the insufficient antifungal defense in the brain and the high mortality rate of cerebral aspergillosis.

Antibodies, Fungal↗
PubMed2005

Membranoproliferative glomerulonephritis type II (dense deposit disease): an update.

Membranoproliferative glomerulonephritis type II (MPGN II) is a rare disease characterized by the deposition of abnormal electron-dense material within the glomerular basement membrane of the kidney and often within Bruch's membrane in the eye. The diagnosis is made in most patients between the ages of 5 and 15 yr, and within 10 yr, approximately half progress to end-stage renal disease, occasionally with the late comorbidity of visual impairment. The pathophysiologic basis of MPGN II is associated with the uncontrolled systemic activation of the alternative pathway (AP) of the complement cascade. In most patients, loss of complement regulation is caused by C3 nephritic factor, an autoantibody directed against the C3 convertase of the AP, but in some patients, mutations in the factor H gene have been identified. For the latter patients, plasma replacement therapy prevents renal failure, but for the majority of patients, there is no proven effective treatment. The disease recurs in virtually all renal allografts, and a high percentage of these ultimately fail. The development of molecular diagnostic tools and new therapies directed at controlling the AP of the complement cascade either locally in the kidney or at the systemic level may lead to effective treatments for MPGN II.

Child↗
PubMed2005

Phosphatidylinositol 3-kinase VPS34 of Candida albicans is involved in filamentous growth, secretion of aspartic proteases, and intracellular detoxification.

The phosphatidylinositol (PI) 3-kinase Vps34p of Candida albicans influences vesicular intracellular transport, filamentous growth and virulence. To get a clearer understanding how these phenomena are connected, we analysed hyphal growth in a matrix under microaerophilic conditions at low temperature, the detoxification of metal ions and antifungal drugs, the secretion of aspartic proteinases (Saps), as well as expression of adhesion-associated proteins of the C. albicans vps34 null mutant strain. The hyphal growth in a matrix, which is repressed in the wild-type strain by Efg1p, was derepressed in the mutant. CZF1, which encodes an activator of hyphal growth in a matrix, was up-regulated in the mutant. In addition, CZF1 expression was pH-dependent in the wild-type. Expression of EFG1 was not changed. Examination of Saps secretion showed a reduction in the vps34 null mutant. Determination of sensitivity against metal ions and antimycotic drugs revealed defects in detoxification. Expression studies indicated that the vps34 mutant reacts to the phenotypical defects with an up-regulation of genes involved in these processes, including the aspartyl proteinases SAP2 and SAP9, adhesion proteins ALS1 and HWP1, and the ABC transporters CDR1 and HST6. We also found an increased expression of the PI 4-kinase LSB6 indicating a complex feed-back mechanism for the compensation of the multiple defects arising from the lack of the PI3-kinase VPS34.

Antifungal Agents↗