On the impact of surveillance test strategies: a cost-benefit modelling analysis based upon real-world data from SARS-CoV-2.

OBJECTIVES: Active regular surveillance testing of asymptomatic and symptomatic individuals can reduce infection and onward transmission rates, as demonstrated for SARS-CoV-2. STUDY DESIGN: Cost-benefit analysis based on real-world data. METHODS: Two different surveillance-testing strategies using nucleic acid amplification tests (NAATs) performed in 14,177 hospital employees were compared for their costs and their effectiveness in preventing secondary infections. RESULTS: Compared to not testing, NAAT-based testing twice a week accompanied by contact tracing or testing five times a week without tracing of contacts were more effective in preventing infections through early identification of infected individuals. While expansion of the test frequency from two to five times per week increased the initial costs, importantly, a 49.6 % higher inhibitory effect on infection growth with a 11.1-fold reduction of potentially averted infections and resulting workforce loss was observed, demonstrating a substantial cost-benefit of the 5-tests-per-week strategy. CONCLUSIONS: Adaptation of the test frequency of SARS-CoV-2 and possibly of other pathogens with epidemic potential according to the prevailing incidences and reproduction rates in high-prevalence situations may not only be beneficial in averting potential infections in hospital employees and, subsequently, on a population level but may also represent the most cost-effective method.

Cetirizine inhibits gender-specific blood cell dynamics upon allergen contact in allergic rhinitis.

IgE-mediated inflammatory responses upon allergen contact in allergic rhinitis (AR) are associated with rapid alterations of circulating blood cell numbers detectable in a complete blood count (CBC). Aim of this study was to evaluate whether intake of antihistamines may modulate allergen-induced CBC dynamics in male and female patients. A total of N = 112 specific allergen challenges were performed in otherwise healthy AR subjects. Seventy-two (n = 72) subjects received placebo and forty (n = 40) received cetirizine (H1-receptor antagonist) per os prior to allergen exposure in a randomized, double-blind trial at the Vienna Challenge Chamber (VCC); a subgroup of twenty-five (n = 25) subjects received cetirizine and placebo on different study days (parallel group). Blood samples and symptom scores were taken at baseline and immediately after 6 h of airway challenge simulating ambient allergen contact. Female sex was associated with a pronounced circulating monocyte increase (p < .01) and male sex with an eosinophil decrease (p < .05) in the placebo group, but not in cetirizine treated subjects. The significant increase in segmented neutrophils (p < .001) and decrease in circulating erythrocytes (p < .01) upon allergen challenge was less prominent after cetirizine intake in both sexes. A more prominent thrombocyte increase in female subjects (p < .05) was noted upon allergen exposure, regardless of prior cetirizine intake. Cetirizine inhibited the mobilization of neutrophils, lymphocytes and decline in erythrocyte numbers, but did not affect thrombocyte increase upon allergen challenge. It further diminished gender-specific blood cell dynamics. Overall, as reflected in a simple CBC, cetirizine critically diminished immediate and late innate immune responses subsequent to allergen exposure.

Prognostic factors and follow-up parameters in patients with paroxysmal nocturnal hemoglobinuria (PNH): experience of the Austrian PNH network.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease characterized by a deregulated complement system, chronic Coombs-negative, intravascular hemolysis, and a variable clinical course with substantial risk to develop thromboembolic events. We analyzed diagnostic and prognostic parameters as well as clinical endpoints in 59 adult patients suffering from PNH in 5 hematology centers in Austria (observation period: 1978-2015). Median follow-up time was 5.6 years. The median clone size at diagnosis amounted to 55% and was higher in patients with classical PNH (81%) compared to patients with PNH associated with aplastic anemia (AA) or myelodysplastic syndromes (MDS) (50%). The clone size also correlated with lactate dehydrogenase (LDH) levels. In one patient, anemia improved spontaneously and disappeared with complete normalization of LDH after 16 years. Seventeen patients received therapy with eculizumab. The rate of thromboembolic events was higher in the pre-eculizumab era compared with eculizumab-treated patients but did not correlate with the presence of age-related clonal hematopoiesis or any other clinical or laboratory parameters. Peripheral blood colony-forming progenitor cell counts were lower in PNH patients compared with healthy controls. Only two patients with classical PNH developed MDS. Overall, 7/59 patients died after 0.5-32 years. Causes of death were acute pulmonary hypertension, Budd-Chiari syndrome, and septicemia. Overall survival (OS) was mainly influenced by age and was similar to OS measured in an age-matched healthy Austrian control cohort. Together, compared with previous times, the clinical course and OS in PNH are favorable, which may be due to better diagnosis, early recognition, and eculizumab therapy.

Comprehensive evaluation of chemiluminescent immunoassays for the laboratory diagnosis of Clostridium difficile infection.

For the microbiological diagnosis of a Clostridium (C.) difficile infection (CDI), a two-test algorithm consisting of a C. difficile glutamate dehydrogenase (GDH)-immunoassay followed by a toxin-immunoassay in positive cases is widely used. In this study, two chemiluminescent immunoassays (CLIAs), one for GDH and the other for the toxins A and B, have been evaluated systematically using appropriate reference methods. Three-hundred diarrhoeal stool specimens submitted for CDI diagnosis were analysed by the LIAISON CLIAs (DiaSorin). Toxigenic culture (TC) and cell cytotoxicity assay (CCTA) were used as "gold standard" reference methods. In addition, GDH and toxin A and B enzyme immunoassays (EIAs), C. diff Chek-60 and toxin A/B II (TechLab), and the Cepheid Xpert C. difficile polymerase chain reaction (PCR) were performed. C. difficile was grown in 42 (14%), TC was positive in 35 (11.7%) and CCTA in 25 (8.3%) cases. CLIAs were more sensitive but less specific than the respective EIAs. Using culture as reference, the sensitivity of the GDH CLIA was 100%. In comparison to CCTA sensitivity, specificity, positive predictive value and negative predictive value of the two-test algorithm were 88, 99.3, 91.7 and 98.9% by CLIAs and 72, 99.6, 94.7 and 97.5% by EIAs. Discrepant results by CLIAs were more frequent than that by EIAs (9% vs. 6.3%); in those cases, PCR allowed for the accurate detection of toxigenic strains. Due to performance characteristics and testing comfort, CLIAs in combination with PCR represent a favourable option for the rapid laboratory C. difficile diagnostics.

Magnetic resonance imaging of temporomandibular joint with anterior disk dislocation without reposition - long-term results.

OBJECTIVES: Anterior disk dislocation (ADD) without reposition in the temporomandibular joint (TMJ) may be associated with morphological changes in the retrodiscal region of the bilaminar zone presenting as pseudo-disk (PD). The present study was initiated to investigate the development of retrodiscal fibrosis in a period of 4-8 years and to assess if patients with a PD show differences in the clinical and radiologic findings versus patients without a PD. MATERIALS AND METHODS: In a retrospective follow-up study of 33 consecutive patients with ADD without reposition in one or both TMJs, a clinical and MRI-supported evaluation was conducted 4 to 8 years after baseline diagnosis. RESULTS: In 45 % of the TMJs with ADD without reposition, a PD could be identified. Twenty-one of 31 patients who showed pain at the baseline examination (VAS mean 56 ± 38) were pain free. The mouth opening capacity (MO) of the mandible could be increased in 80 %. There were no statistical significant differences between patients with or without PD in these clinical features. The MRI parameters effusion and translation showed a statistical tendency for more improvement in the group with PD (p = 0.061, 0.064). CONCLUSION: In about half of the patients, a structure corresponding to a pseudo-disk developed during follow-up. Pain and the mouth opening capacity improved in all patients independent of the development of a PD. CLINICAL RELEVANCE: Detection of a PD during follow-up of patients with ADD without spontaneous reposition does neither predict favorable nor worse therapy response and clinical course.

Emergence of tick-borne encephalitis in new endemic areas in Austria: 42 years of surveillance.

Human infections with tick-borne encephalitis (TBE)virus are a public health concern in certain regions of Europe, central and eastern Asia. Expansions of endemic areas and increased incidences have been associated with different factors including ecological changes supporting tick reproduction, socioeconomic changes increasing human outdoor activities and climatic changes favouring virus circulation in natural foci. Austria is among the most strongly affected countries in Central Europe, but the annual number of cases has strongly declined due to vaccination. Here,we have analysed changes of the incidence of TBE in the unvaccinated population of all federal states of Austria over a period of 42 years. The overall incidence in Austria has remained constant, but new strongly affected endemic regions have emerged in alpine valleys in the west of Austria. In parallel, the incidence in low-land regions in the north-east of the country is decreasing. There is no evidence for a shift to higher altitudes of infection sites in the traditional TBE zones,but the average altitudes of some newly established endemic areas in the west are significantly higher. Our analyses underscore the focal nature of TBE endemic areas and the potential of TBE virus to emerge in previously unaffected regions.

Viral determinants predicting hepatitis B surface antigen (HBsAg) seroclearance in HIV-/HBV-coinfected patients.

The aim of this retrospective study was the identification of clinically useful viral determinants for the prediction of hepatitis B surface antigen (HBsAg) seroclearance and sustained virological response in hepatitis B virus/human immunodeficiency virus (HBV-/HIV)-coinfected patients receiving HBV-active combined antiretroviral therapy (cART). Quantification of HBsAg, HBeAg and HBV DNA before and after initiation of HBV-active cART in a cohort of 59 HIV-/HBV-coinfected patients was performed. Calculations of receiver operating characteristics (ROC) and Kaplan-Meier analysis were used for the identification of predictors of HBsAg seroclearance for HBeAg-positive [HBeAg(+); n = 36] and HBeAg-negative [HBeAg(-);n = 23] patients. HBeAg(+) patients with an HBsAg on-treatment decline ≥ 1 log IU/mL per year achieved higher HBsAg loss rates (P = 0.0294), whereas the quantification of HBeAg had no predictive value for HBsAg seroclearance. Among HBeAg(-) patients, a pretreatment baseline cut-off level of HBsAg ≤ 100 IU/mL was highly predictive for HBsAg seroclearance. No significant influence of the HBV genotype on HBsAg seroclearance was observed among the entire cohort. Quantitative determination of HBsAg provides a clinically useful viral parameter for the prediction of HBsAg seroclearance both in HBeAg(+) and HBeAg(-) HIV-/HBV-coinfected patients receiving HBV-active cART.

The KIT D816V allele burden predicts survival in patients with mastocytosis and correlates with the WHO type of the disease.

KIT D816V is present in a majority of patients with systemic mastocytosis (SM). We determined the KIT D816V allele burden by quantitative real-time PCR in bone marrow and peripheral blood of 105 patients with mastocytosis. KIT D816V was detected in 92/105 patients (88%). Significant differences in the median allele burden were observed between disease subgroups: cutaneous mastocytosis (0.042%), indolent SM (0.285%), smoldering SM (5.991%), aggressive SM (9.346%), and SM with associated hematologic non-mast cell lineage disease (3.761%) (P < 0.001). The KIT D816V burden also correlated with serum tryptase (R = 0.5, P < 0.005) but not with mast cell infiltration in bone marrow or mediator symptoms. Moreover, the allele burden was of prognostic significance regarding survival (P < 0.01). Patients responding to cytoreductive therapy showed a significant decrease in KIT D816V (P < 0.05). To conclude, the KIT D816V burden correlates with the variant of mastocytosis, predicts survival, and is a valuable follow-up parameter in SM.

Impact of polyunsaturated vegetable oils on adiponectin levels, glycaemia and blood lipids in individuals with type 2 diabetes: a randomised, double-blind intervention study.

BACKGROUND: Low adiponectin levels are discussed as risk factor for cardiovascular events. This is of special importance in individuals with type 2 diabetes (T2DM) because they are at higher risk for cardiovascular diseases. The present study aimed to investigate the effect of two plant oils rich in polyunsaturated fatty acids (PUFA), with different content of omega-3 fatty acids, on adiponectin levels, glucose and lipid metabolism in T2DM individuals treated either with insulin or oral anti-diabetics (OAD). METHODS: Ninety-two subjects with T2DM [34 treated with insulin (T2DM-Ins) and 58 treated with OAD (T2DM-OAD)] participated in this randomised, double-blind, parallel intervention study. Individuals received either 9 g of nut oil (n-3:n-6 ratio: 1.3 : 6.1) or mixed oil (n-3:n-6 ratio: 0.6 : 5.7) per day for 10 weeks. The fatty acid profile, tocopherol, adiponectin levels and parameters regarding glucose and lipid metabolism were assessed at baseline, during and after the intervention. RESULTS: Compliance was confirmed by significant increases in γ-tocopherol and PUFA in both oil groups. An increase in adiponectin levels in T2DM-Ins participants (+6.84% in nut oil and +4.47% in mixed oil group after 10 weeks compared to baseline) was observed, albeit not significantly different from T2DM-OAD individuals (P = 0.051). Lipid and glucose metabolism were not affected by the intervention. CONCLUSIONS: The present study provides evidence that a small and easy change in dietary behaviour towards better fat quality moderately increases adiponectin levels in T2DM-Ins subjects, independently of the administered plant oil.

[Sociodemographic aspects are associated with breast cancer screening behaviour of female patients: results of a cross-sectional survey]. / Soziodemografische Aspekte stehen im Zusammenhang mit dem Brustkrebsscreeningverhalten von Patientinnen: Ergebnisse einer Querschnittsuntersuchung.

In Austria, opportunistic mammography screening for detection of early-stages breast cancer is offered for women older than 40 years. In spite of public discussions on the effectiveness of mammography screening, evidence-based educative information material for female patients available online and in print is lacking. The present study describes the influence of the 3 sociodemographic characteristics migration background, education, and age on the individual's breast cancer screening behaviour as well as on the usage of various information sources on breast cancer for patients. In total, 333 outpatients of the Department of Obstetrics and Gynaecology, General Hospital, Vienna, Austria, participated in a monocentric cross-sectional study. Regarding breast cancer screening, 93.4% (n=282) of the female patients had at least one previous mammogram. Furthermore, 86.3% of the participants regularly consulted their gynaecologist, while women with migration background reported less frequent (p=0.02), and well-educated as well as older patients reported more frequent (p<0.02) gynaecological consultations. Higher-educated women (p=0.04) and participants aged between 50 and 69 years (p<0.05) felt better informed on breast cancer-related topics, whereas a migration background was not associated with the perceived level of information. Medical doctors (67.9%) as well as pertinent folders (33%) were the most relevant information sources on breast cancer. Mass media (22.8%) were also a relevant information source on this issue, whereas the Internet (10.5%) was quite rarely referred to for this purpose. The results of the present study show that female patients perceived the medical doctor as the most important source of medical information on breast cancer. The public health-care system could facilitate positive health communication in the doctors/patient relationship by providing homogenous, quality assured educative information material.

A comprehensive and quantitative analysis of the major specificities in rabbit antithymocyte globulin preparations.

Antithymocyte globulin (ATG) preparations are used for treatment and prevention of graft rejection episodes, graft versus host disease and aplastic anemia. The immunomodulatory and immuosuppressive properties of ATGs are mediated by their interaction with a large variety of antigens expressed on immune and nonimmune cell populations. We have conducted a comprehensive analysis on antibody specificities contained in rabbit ATGs in clinical use, ATG-Fresenius (ATG-F) and Thymoglobulin (THG). We have used retroviral expression cloning to identify novel ATG antigens and demonstrate that together with ATG antigens described earlier, these molecules account for the majority of ATG antibodies directed to human cells. Moreover, we have employed cell lines engineered to express antigens at high levels to quantify the antibodies directed to each ATG antigen. We have used cell lines expressing the T cell receptor complex, CD2 and CD28 to remove antibodies to these antigens from ATG preparations and demonstrate that this treatment abrogated the ability of ATGs to induce activation and forkhead box P3 expression in T cells. Comprehensive information and differences on the antigens targeted by ATG-F and THG as well as novel approaches to assess their functional properties are the basis for a better understanding of their immunomodulatory capacities and might eventually translate into improved ATG-based regimen.

Association of human cytomegalovirus DNAaemia and specific granzyme B responses in lung transplant recipients.

In lung transplant recipients (LTRs), human cytomegalovirus (HCMV) DNAaemia could be associated with HCMV disease and reduced allograft survival. In the present study we analysed whether or not HCMV-specific granzyme B (Grz-B) responses indicating CD8(+) T cell cytotoxicity exert an impact on HCMV DNAaemia and relate to specific interferon (IFN)-γ secretion. HCMV-specific Grz-B responses were quantitated by enzyme-linked immunosorbent assay (ELISA) in 70 samples from 39 HCMV seropositive LTRs who were prospectively investigated for HCMV DNA plasma levels and IFN-γ kinetics using a standardized CD8(+) T cell assay (QuantiFERON®-CMV assay). In all LTRs who were protected from HCMV DNAaemia by early and persistent IFN-γ responses, Grz-B responses were also detected. In LTRs who developed episodes of HCMV DNAaemia, the Grz-B responses which were detected prior to viral DNA detection differed significantly in patients who experienced episodes with high (exceeding 1000 copies/ml) and low plasma DNA levels (P = 0·0290, Fisher's exact test). Furthermore, the extent of Grz-B release prior to viral DNAaemia correlated statistically with the detected levels of IFN-γ (P < 0·0001, Spearman's rank test). Of note, simultaneous detection of Grz-B and IFN-γ secretion was associated significantly with protection from high HCMV DNA plasma levels during the subsequent follow-up (P = 0·0057, Fisher's exact test), and this association was stronger than for IFN-γ detection alone. We conclude that, in addition to IFN-γ responses, Grz-B secretion by CD8(+) T cells is essential to control HCMV replication and a simultaneous measurement of IFN-γ and Grz-B could contribute to the immune monitoring of LTRs.

Analysis of plasma surfactant protein D levels in lung transplant recipients.

In lung transplant recipients (LTRs), severe clinical complications, such as microbial infections of the lung or transplant rejection, may occur. Surfactant protein D (SP-D) is a C-type lectin that is mainly produced in alveolar type II cells. Plasma SP-D levels are usually low, but may increase when the lung-blood barrier is impaired. In this study, we analyzed whether plasma SP-D concentrations reflect rejection or infection of the lung allograft. An enzyme-linked immunosorbent assay was used to measure SP-D levels in plasma samples from 58 LTRs during intervals without pathologic respiratory findings and during episodes of acute cellular rejection (ACR), microbial colonization, and microbial pneumonia. Median plasma SP-D levels were significantly increased during episodes of microbial pneumonia, but not in the absence of pathologic respiratory findings, during microbial colonization, or during ACR up to grade A2-A3 (P < 0.05). During pneumonia, an increased plasma SP-D level was detected in 60% of LTRs and this was further associated with a significantly higher risk for the patients to develop stage III bronchiolitis obliterans syndrome (BOS III) or to die within the subsequent 6 months after pneumonia (P = 0.0093). All patients with a plasma SP-D level of >300 ng/mL during pneumonia developed BOS III and/or died within 6 months of follow-up (P = 0.001). The determination of SP-D levels in plasma during pneumonia in LTRs may be of prognostic value and warrants further evaluation.

Prospective analysis of human cytomegalovirus DNAemia and specific CD8+ T cell responses in lung transplant recipients.

In lung transplant recipients (LuTRs), human cytomegalovirus (HCMV) DNAemia may be associated with HCMV disease and reduced survival of the allograft. Because T cells are essential for controlling HCMV replication, we investigated in this prospective study whether the kinetics of plasma HCMV DNA loads in LuTRs are associated with HCMV-specific CD8+ T cell responses, which were longitudinally assessed using a standardized assay. Sixty-seven LuTRs were monitored during the first year posttransplantation, with a mean of 17 HCMV DNA PCR quantifications and 11.5 CD8+ T cell tests performed per patient. HCMV-specific CD8+ T cell responses displayed variable kinetics in different patients, differed significantly before the onset of HCMV DNAemia in LuTRs who subsequently experienced episodes of DNAemia with high (>1000 copies/mL) and low plasma DNA levels (p = 0.0046, Fisher's exact test), and were absent before HCMV disease. In HCMV-seropositive LuTRs, high-level DNAemia requiring preemptive therapy occurred more frequently when HCMV-specific CD8+ T cell responses fluctuated, were detected only after HCMV DNA detection, or remained undetectable (p = 0.0392, Fisher's exact test). Thus, our data indicate that HCMV-specific CD8+ T cells influence the magnitude of HCMV DNAemia episodes, and we propose that a standardized measurement of CD8+ T cell immunity might contribute to monitoring the immune status of LuTRs posttransplantation.

Intake of a resveratrol-containing dietary supplement has no impact on DNA stability in healthy subjects.

It has been postulated that the beneficial health effects of dietary supplements and of red wines which contain resveratrol (RES) are due to the anti-oxidative properties of this phenolic compound, but evidence for protection against reactive oxygen species is mainly based on results of in vitro experiments and high-dose animal experiments. Aim of this study was to find out if intake of a RES-containing supplement protects healthy humans against oxidative DNA-damage and alters their redox status. Therefore, an intervention trial was conducted in which the participants (n=12) consumed a RES-containing supplement over a period of five days. At the start, after one day and after five days of consumption, and after a washout period DNA stability was measured in single cell gel electrophoresis (SCGE) assays with peripheral blood lymphocytes. These tests were conducted (a) under standard conditions, which reflect single- and double-strand DNA breaks, (b) after treatment of the cells with hydrogen peroxide, which enables detection of alterations of the ROS sensitivity, and (c) by use of formamidopyrimidine DNA-glycosylase (FPG), which provides information on formation of oxidatively damaged bases (pyrimidines). Furthermore, the biochemical parameters TAC (total antioxidant capacity) and oxLDL (oxidized low-density lipoprotein), which reflect the redox status, and C-reactive protein (CRP), a marker of inflammation, were monitored. The intake of the supplement had no significant impact on the DNA stability parameters and on the different biomarkers of the redox status. Our results indicate that intake of 6mg RES per day via the supplement does not cause DNA-protective or antioxidant effects. This amount is equivalent to or lower than that reached after intake of many (ca. 50%) of the RES-containing preparations which are currently on the market in Middle Europe, and is contained in 0.3-2L red wine.

Recommendations and quality criteria for micronucleus studies with humans.

Micronucleus (MN) analyses in peripheral blood lymphocytes and exfoliated cells from different organs (mouth, nose, bladder and cervix) are at present the most widely used approaches to detect damage of genetic material in humans. MN are extranuclear DNA-containing bodies, which can be identified microscopically. They reflect structural and numerical chromosomal aberrations and are formed as a consequence of exposure to occupational, environmental and lifestyle genotoxins. They are also induced as a consequence of inadequate intake of certain trace elements and vitamins. High MN rates are associated with increased risk of cancer and a range of non-cancer diseases in humans. Furthermore, evidence is accumulating that measurements of MN could be a useful tool for the diagnosis and prognosis of different forms of cancer and other diseases (inflammation, infections, metabolic disorders) and for the assessment of the therapeutic success of medical treatments. Recent reviews of the current state of knowledge suggest that many clinical studies have methodological shortcomings. This could lead to controversial findings and limits their usefulness in defining the impact of exposure concentrations of hazardous chemicals, for the judgment of remediation strategies, for the diagnosis of diseases and for the identification of protective or harmful dietary constituents. This article describes important quality criteria for human MN studies and contains recommendations for acceptable study designs. Important parameters that need more attention include sufficiently large group sizes, adequate duration of intervention studies, the exclusion of confounding factors which may affect the results (sex, age, body mass index, nutrition, etc.), the evaluation of appropriate cell numbers per sample according to established scoring criteria as well as the use of proper stains and adequate statistical analyses.

Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study.

In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk.

Human cytomegalovirus infection in lung transplant recipients triggers a CXCL-10 response.

Human cytomegalovirus (HCMV) causes significant morbidity in lung transplant recipients (LTRs). The clinical effects of HCMV replication are determined partly by a type 1 T-helper cell (Th1) response. Because the chemokine interferon-inducible protein of 10 kilodaltons (IP-10, CXCL-10) induces a Th1 response, we investigated whether HCMV triggers IP-10 in LTRs. The IP-10 concentration and HCMV DNA load were determined in 107 plasma and 46 bronchoalveolar lavage fluid (BALF) samples from 36 LTRs. Initial HCMV detection posttransplantation was significantly associated with increased plasma IP-10, regardless of whether the patients showed HCMV DNAemia (p = 0.001) or HCMV replication only in the allograft (p < 0.0001). In subsequent episodes of HCMV detection, plasma IP-10 increased regardless of whether HCMV was detected in blood (p = 0.0078) or only in BALF (p < 0.0001) and decreased after successful antiviral therapy (p = 0.0005). Furthermore, levels of HCMV DNA and IP-10 correlated statistically (p = 0.0033). Increased IP-10 levels in HCMV-positive BALF samples were significantly associated with severe airflow obstruction, as indicated by a decrease in forced expiratory volume in one second (FEV1). Our data indicate that HCMV replication in LTRs evokes a plasma IP-10 response and that, when an IP-10 response is observed in BALF, it is associated with inflammatory airway obstruction in the allograft.

Recombinant allergen-based monitoring of antibody responses during injection grass pollen immunotherapy and after 5 years of discontinuation.

BACKGROUND: Subcutaneous injection immunotherapy (SCIT) is considered as antigen-specific and disease-modifying treatment with long-lasting effect. METHODS: We used a panel of recombinant grass pollen allergens for analyzing allergen-specific IgE, IgG(1) -IgG(4) , IgM, IgA, and light-chain (kappa, lambda) responses in grass pollen-allergic patients who had received one course of injection immunotherapy (SCIT) with an aluminum hydroxide-adsorbed grass pollen extract or only anti-inflammatory treatment. Serum samples were analyzed before and after 5 months of treatment as well as after 5 years. RESULTS: After 5 months of SCIT but not of anti-inflammatory treatment, IgG(1) > IgG(4) > IgG(2) > IgA antibody responses using both kappa and lambda light chains specific for major grass pollen allergens (Phl p 1, Phl p 5, Phl p 6, Phl p 2) increased significantly, whereas specific IgM or IgG(3) levels were unaltered. Allergen-dependent basophil degranulation was only inhibited with SCIT sera containing therapy-induced allergen-specific IgG antibodies. Likewise, decreases in Phl p 1- and Phl p 5-specific IgE levels and significant (P<0.001) reduction in symptom and medication scores were found only in the SCIT group but not in the group of patients receiving anti-inflammatory treatment. After 5 years, allergen-specific IgG antibody levels in the SCIT group had returned to baseline levels and there was no significant difference regarding symptoms between the SCIT and non-SCIT groups. CONCLUSION: The results from our observational study demonstrate that only SCIT but not anti-inflammatory treatment induces allergen-specific IgG and reduces boosts of allergen-specific IgE production but that one SCIT course was not sufficient to achieve long-term immunological and clinical effects.