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G Walzl

Publications and source records attributed to G Walzl.

15 recordsLinked to original sources
PubMed2006

Changes in leucocyte and lymphocyte subsets during tuberculosis treatment; prominence of CD3dimCD56+ natural killer T cells in fast treatment responders.

The immune responses against pulmonary tuberculosis are still poorly defined. This study describes changes in leucocyte and lymphocyte subsets during treatment to find reliable immunological markers for the disease and treatment response. Flow cytometric peripheral blood immune phenotyping, routine haematology and sputum microbiology were performed on 21 HIV-negative adult tuberculosis (TB) patients with positive sputum cultures during therapy in comparison with 14 healthy purified protein derivative (PPD)-positive volunteers. Patients at diagnosis showed high absolute neutrophil and monocyte counts which fell during treatment but low lymphocyte subset counts which increased [except natural killer (NK) and NK T cells]. High counts of a population of CD3(dim)/CD56+ NK T cells at diagnosis correlated significantly with negative sputum culture after 8 weeks of treatment. A multivariate classification technique showed improved correlation when NK cells were taken into account. In conclusion, peripheral blood white cell counts change significantly during treatment and counts at diagnosis, especially CD3(dim)/CD56+ NK T cells, hold promise in predictive models of TB treatment response.

Adolescent↗
PubMed2006

Immune markers measured before treatment predict outcome of intensive phase tuberculosis therapy.

The development of a statistical model based on simple immunological markers which could predict the response to tuberculosis treatment would facilitate clinical trials of new anti-tuberculosis drugs. We have examined the ability of immunological biomarkers, measured at diagnosis and after 4 weeks of treatment, to predict sputum smear status at week 8. Eighteen tuberculosis patients with positive Ziehl-Nielsen (ZN)-stained sputum smears 8 weeks after initiation of treatment (slow response) were matched for age, gender, sputum smear grade and extent of disease on chest radiograph to 18 patients with negative sputum smears at week 8 (fast response). In addition to total white blood cell (WBC) counts and absolute lymphocyte, monocyte and neutrophil numbers, concentrations of six serum markers were measured by enzyme-linked immunosorbent assay (ELISA) in all patients (soluble interleukin-2 receptor alpha (sIL-2Ralpha), granzyme B, soluble tumour necrosis factor alpha receptors 1 and 2 (sTNF-R1 and -2), nitrotyrosine and interferon-gamma (IFN-gamma). At diagnosis, 4 biomarkers (sTNF-R1, total WBC, absolute monocyte and absolute neutrophil numbers) were significantly higher in slow response patients. At week 4, total WBC count and absolute monocyte and neutrophil numbers remained significantly higher in slow responders. Discriminant analysis of the diagnosis and week 4 data provided models for classification of slow response patients with 67% and 83% predictive accuracy. We suggest that treatment response phenotypes can be determined before the start of treatment. Reliable predictive models would allow targeted interventions for patients at risk for slow treatment response to standard tuberculosis therapy.

Adult↗
PubMed2003

Diagnostic tools in tuberculous pleurisy: a direct comparative study.

Thoracoscopy is the most accurate yet most expensive tool for establishing the diagnosis of tuberculous (TB) pleurisy. However, most high TB-incidence regions have limited financial resources, lack the infrastructure needed for routine thoracoscopy and require an alternative, cost-effective diagnostic approach for pleural effusions. Altogether, 51 patients with undiagnosed exudative pleural effusions were recruited for a prospective, direct comparison between bronchial wash, pleural fluid microbiology and biochemistry (adenosine deaminase (ADA) and cell count), closed needle biopsy, and medical thoracoscopy. The final diagnosis was TB in 42 patients (82%), malignancy in five (10%) and idiopathic in four patients (8%). Sensitivity of histology, culture and combined histology/culture was 66, 48 and 79%, respectively for closed needle biopsy and 100, 76 and 100%, respectively for thoracoscopy. Both were 100% specific. Pleural fluid ADA of > or = 50 U x L(-1) was 95% sensitive and 89% specific. Combined ADA, lymphocyte/neutrophil ratio > or = 0.75 plus closed needle biopsy reached 93% sensitivity and 100% specificity. A combination of pleural fluid adenosine deaminase, differential cell count and closed needle biopsy has a high diagnostic accuracy in undiagnosed exudative pleural effusions in areas with high incidences of tuberculosis and might substitute medical thoracoscopy at considerably lower expense in resource-poor countries.

Adenosine Deaminase↗
PubMed2001

Inhibition of T1/ST2 during respiratory syncytial virus infection prevents T helper cell type 2 (Th2)- but not Th1-driven immunopathology.

T cells secreting interleukin (IL)-4 and IL-5 (T helper cell type 2 [Th2] cells) play a detrimental role in a variety of diseases, but specific methods of regulating their activity remain elusive. T1/ST2 is a surface ligand of the IL-1 receptor family, expressed on Th2- but not on interferon (IFN)-gamma-producing Th1 cells. Prior exposure of BALB/c mice to the attachment (G) or fusion (F) protein of respiratory syncytial virus (RSV) increases illness severity during intranasal RSV challenge, due to Th2-driven lung eosinophilia and exuberant Th1-driven pulmonary infiltration, respectively. We used these polar models of viral illness to study the recruitment of T1/ST2 cells to the lung and to test the effects of anti-T1/ST2 treatment in vivo. T1/ST2 was present on a subset of CD4(+) cells from mice with eosinophilic lung disease. Monoclonal anti-T1/ST2 treatment reduced lung inflammation and the severity of illness in mice with Th2 (but not Th1) immunopathology. These results show that inhibition of T1/ST2 has a specific effect on virally induced Th2 responses and suggests that therapy targeted at this receptor might be of value in treating Th2-driven illness.

Animals↗
PubMed2001

Mucosal delivery of a respiratory syncytial virus CTL peptide with enterotoxin-based adjuvants elicits protective, immunopathogenic, and immunoregulatory antiviral CD8+ T cell responses.

In an effort to develop a safe and effective vaccine against respiratory syncytial virus (RSV), we used Escherichia coli heat-labile toxin (LT), and LTK63 (an LT mutant devoid of ADP-ribosyltransferase activity) to elicit murine CD8(+) CTL responses to an intranasally codelivered CTL peptide from the second matrix protein (M2) of RSV. M2(82-90)-specific CD8(+) T cells were detected by IFN-gamma enzyme-linked immunospot and (51)Cr release assay in local and systemic lymph nodes, and their induction was dependent on the use of a mucosal adjuvant. CTL elicited by peptide immunization afforded protection against RSV challenge, but also enhanced weight loss. CTL-mediated viral clearance was not dependent on IFN-gamma since depletion using specific mAb during RSV challenge did not affect cellular recruitment or viral clearance. Depletion of IFN-gamma did, however, reduce the concentration of TNF detected in lung homogenates of challenged mice and largely prevented the weight loss associated with CTL-mediated viral clearance. Mice primed with the attachment glycoprotein (G) develop lung eosinophilia after intranasal RSV challenge. Mucosal peptide vaccination reduced pulmonary eosinophilia in mice subsequently immunized with G and challenged with RSV. These studies emphasize that protective and immunoregulatory CD8(+) CTL responses can be mucosally elicited using enterotoxin-based mucosal adjuvants but that resistance against viral infection may be accompanied by enhanced disease.

Adjuvants, Immunologic↗
PubMed2001

Overexpression of heat-shock proteins reduces survival of Mycobacterium tuberculosis in the chronic phase of infection.

Elevated expression of heat-shock proteins (HSPs) can benefit a microbial pathogen struggling to penetrate host defenses during infection, but at the same time might provide a crucial signal alerting the host immune system to its presence. To determine which of these effects predominate, we constructed a mutant strain of Mycobacterium tuberculosis that constitutively overexpresses Hsp70 proteins. Although the mutant was fully virulent in the initial stage of infection, it was significantly impaired in its ability to persist during the subsequent chronic phase. Induction of microbial genes encoding HSPs might provide a novel strategy to boost the immune response of individuals with latent tuberculosis infection.

Animals↗
PubMed2000

Influenza virus lung infection protects from respiratory syncytial virus-induced immunopathology.

The effect of infection history is ignored in most animal models of infectious disease. The attachment protein of respiratory syncytial virus (RSV) induces T helper cell type 2-driven pulmonary eosinophilia in mice similar to that seen in the failed infant vaccinations in the 1960s. We show that previous influenza virus infection of mice: (a) protects against weight loss, illness, and lung eosinophilia; (b) attenuates recruitment of inflammatory cells; and (c) reduces cytokine secretion caused by RSV attachment protein without affecting RSV clearance. This protective effect can be transferred via influenza-immune splenocytes to naive mice and is long lived. Previous immunity to lung infection clearly plays an important and underestimated role in subsequent vaccination and infection. The data have important implications for the timing of vaccinations in certain patient groups, and may contribute to variability in disease susceptibility observed in humans.

Animals↗
PubMed2000

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Journal Article↗
PubMed1999

Staphylococcus lugdunensis endocarditis in a young, previously healthy female.

Reported here is a case of native valve infective endocarditis in which Staphylococcus lugdunensis was isolated from blood cultures as well as from the mitral valve. It is suggested that tube coagulase-negative staphylococci isolated from blood cultures of patients with infective endocarditis be considered carefully for possible clinical significance. The use of the ornithine carboxylase test as a simple screening method for identification of Staphylococcus lugdunensis is recommended.

Adult↗
PubMed1996

Corticosteroids in the treatment of tuberculous pleurisy. A double-blind, placebo-controlled, randomized study.

Although several studies on tuberculous (TB) pleurisy suggest that the addition of corticosteroids to anti-TB therapy may have beneficial effects, these agents are not used routinely. To assess the effects of short-term oral prednisone therapy in TB pleurisy, 74 patients were randomly assigned in a double-blind fashion to treatment with either placebo or prednisone at a dose of 0.75 mg/kg/d for up to 4 weeks with gradual reduction over an additional 2 weeks. All subjects received a standard 3-drug anti-TB chemotherapy regimen for 6 months. TB pleurisy was diagnosed by histologic study and/or culture of pleural biopsy specimens obtained at thoracoscopy. Complete drainage of the effusion was performed simultaneously. Outcome measures were assessed periodically for 24 weeks, including indexes of morbidity and pleural thickening. After randomization, four patients were excluded from the final analysis. Of the 70 patients analyzed, 34 received prednisone and 36 received placebo. Demographic and clinical characteristics of the treatment groups were comparable at the time of hospital admission. Although a statistically significant improvement in symptoms occurred earlier in the prednisone group (8 weeks) than in the placebo group (12 weeks), between-group comparison showed no significant differences at any of the follow-up evaluations. The proportion of subjects in the prednisone group (53.1%) with residual pleural thickening at 6 months did not differ significantly from that of the placebo group (60%). Pleural effusions did not recur in any of the patients. Initial complete drainage of the effusion was associated with greater symptomatic improvement than any subsequent therapy. We conclude that standard anti-TB therapy and early complete drainage is adequate for the treatment of TB pleurisy. The addition of short-term oral prednisone therapy neither results in clinically relevant earlier symptom relief nor confers a beneficial effect on residual pleural thickening.

Adult↗
PubMed1995

The prevalence of antibodies to hepatitis C virus at two haemodialysis units in South Africa.

The prevalence of antibodies against hepatitis C virus (HCV) was determined in 103 haemodialysis patients who attended two dialysis units in South Africa. With the use of a second-generation enzyme-linked immunosorbent assay (UBI HCV EIA, Organon Teknika, The Netherlands) and a 4-recombinant immunoblot assay (Chiron Corporation, USA), antibodies to HCV were found in 22 patients (21%). Statistically significant associations with anti-HCV carrier status were duration of dialysis (P = 0.0005) and number of blood transfusions received (P = 0.008). With stepwise logistic regression analysis it was not possible to separate the effects of HCV status associated with these two variables. A transient elevation in alanine aminotransferase (ALT) occurred in 8 of the 22 anti-HCV-positive patients, compared with 14 of the 81 anti-HCV-negative patients (P = 0.054). As yet, no patients have clinical evidence of ongoing liver disease or persistently elevated ALT levels. Of the 45 dialysis staff members tested, none was positive for anti-HCV.

Adolescent↗
PubMed1989

[The inadequate status of information of interested lay persons about the educational campaign regarding risk factors for cardiovascular diseases].

181 interested individuals (75 males, 106 females; range 16 to 84 years) responded to a questionnaire issued by the Styrian Cardiovascular Lay Society. The main topic of the questionnaire concerned information gained via media, about the possible risk factors related to cardiovascular diseases and about any changes in life style consequent to this information. The results show that the general knowledge in this field especially in younger subjects is disappointing and that there is need for further intensive information and education.

Adolescent↗
PubMed1988

[Status of information of interested lay persons: results of a questionnaire survey by the Styrian Heart Association].

181 interested individuals (75 males, 106 females; range 16 to 84 years) responded to a questionnaire issued within the information and instruction courses of the Styrian Cardiovascular Non-professional Society. The main topic of the questionnaire concerned information gained via media, possible risk factors leading to cardiovascular diseases and any changes in living conditions due to such facts. The results show clearly that the general knowledge in this field especially in younger subjects is disappointing and further intensive information and instruction would be urgently required.

Adolescent↗