370 research outputs found
T Cell Proliferation and Apoptosis in HIV-1-Infected Lymphoid Tissue: Impact of Highly Active Antiretroviral Therapy
No full textT cell turnover was studied in situ in tonsillar lymphoid tissue (LT) from HIV-1-infected individuals during 48 weeks of highly active antiretroviral therapy (HAART) and compared to that of HIV-1-negative controls. Prior to therapy, CD4 cell proliferation (%CD4+ Ki67+) and apoptosis (%CD4+ TUNEL+) were increased in HIV-1-infected LT and both parameters correlated with tonsillar viral load. CD8 cell proliferation (%CD8+ Ki67+) was increased 4- to 10-fold, mainly in the germinal centers. Apoptotic CD8+ T cell levels (%CD8+ TUNEL+) were raised preferentially in the tonsillar T cell zone. The frequency of CD8+ Ki67+ and CD8+ TUNEL+ T cells correlated with tonsillar viral load and with the fraction of CD8+ T cells expressing activation markers. During HAART, CD4 cell turnover normalized while CD8 cell turnover was dramatically reduced. However, low level viral replication concomitant with slightly elevated levels of CD8 cell turnover indicated a persistent cellular immune response in LT. In conclusion, enhanced T cell turnover may reflect effector cells related to HIV-1 infection.Anne Ma Dyrhol-Riise, Maria Ohlsson, Kathrine Skarstein, Svein J. T. Nygaard, Jan Olofsson, Roland Jonsson and Birgitt Åsjöhttp://www.elsevier.com/wps/find/journaldescription.cws_home/622806/description#descriptio
Cytokine Patterns in Tuberculosis Infection; IL-1ra, IL-2 and IP-10 Differentiate Borderline QuantiFERON-TB Samples from Uninfected Controls
No full textBackground: Interferon gamma release assays (IGRAs) do not discriminate between active tuberculosis (TB) and latent TB infection (LTBI), which limit their use in TB endemic areas. Subjects with QuantiFERON-TB (QFT) results around the diagnostic cut-off more likely show inconsistent results on serial testing which makes the interpretation of the assay difficult. We have studied potential biomarkers in patients with various stages of TB infection and with borderline QFT tests compared to those with higher values. Methods: 27 soluble biomarkers were analysed in QFT supernatants from patients with active TB (n = 18), individuals with LTBI (n = 48) and from QFT negative controls (n = 16) by the Multiplex bead assay. The LTBI group was classified into two groups according to QFT IFN-γ levels; QFT borderline (0.35–0.70 IU/mL, n = 11) or QFT high (>0.70 IU/mL, n = 36). Results: The levels of IL-1ra, IL-2, IL-13, IL-15, IFN-γ, IP-10 and MCP-1 in background corrected TB antigen stimulated supernatants (TBAg-Nil) significantly distinguished both active TB and LTBI QFT high groups from the QFT negative controls (p≤0.004). In addition, IL-1ra, IL-2 and IP-10 significantly differentiated the QFT borderline group from the controls (p≤0.001). Still, in the QFT borderline group the IL-1ra and IP-10 levels were not significant different from neither the QFT high nor the active TB group, whereas the IL-2 levels were lower (p≤0.003). The level of IP-10 showed the best separation between the QFT borderline group and the QFT negative controls (AUC 0.92) and offered 100% sensitivity for active TB. Conclusion: IL-1ra, IL-2 and IP-10 differentiate QFT borderline samples from uninfected controls and the majority of QFT borderline subjects were classified as LTBI by these markers. Still, inconsistency was seen, and further studies are needed to examine the performance of alternative markers before concluded if they could be used as diagnostics tools
Screening for latent tuberculosis in Norwegian health care workers: high frequency of discordant tuberculin skin test positive and interferon-gamma release assay negative results
No full textBackground: Tuberculosis (TB) presents globally a significant health problem and health care workers (HCW) are at increased risk of contracting TB infection. There is no diagnostic gold standard for latent TB infection (LTBI), but both blood based interferon-gamma release assays (IGRA) and the tuberculin skin test (TST) are used. According to the national guidelines, HCW who have been exposed for TB should be screened and offered preventive anti-TB chemotherapy, but the role of IGRA in HCW screening is still unclear. Methods: A total of 387 HCW working in clinical and laboratory departments in three major hospitals in the Western region of Norway with possible exposure to TB were included in a cross-sectional study. The HCW were asked for risk factors for TB and tested with TST and the QuantiFERON®TB Gold In-Tube test (QFT). A logistic regression model analyzed the associations between risk factors for TB and positive QFT or TST. Results: A total of 13 (3.4%) demonstrated a persistent positive QFT, whereas 214 (55.3%) had a positive TST (≥ 6 mm) and 53 (13.7%) a TST ≥15 mm. Only ten (4.7%) of the HCW with a positive TST were QFT positive. Origin from a TB-endemic country was the only risk factor associated with a positive QFT (OR 14.13, 95% CI 1.37 - 145.38, p = 0.026), whereas there was no significant association between risk factors for TB and TST ≥ 15 mm. The five HCW with an initial positive QFT that retested negative all had low interferon-gamma (IFN-γ) responses below 0.70 IU/ml when first tested. Conclusions: We demonstrate a low prevalence of LTBI in HCW working in hospitals with TB patients in our region. The “IGRA-only” seems like a desirable screening strategy despite its limitations in serial testing, due to the high numbers of discordant TST positive/IGRA negative results in HCW, probably caused by BCG vaccination or boosting due to repetitive TST testing. Thus, guidelines for TB screening in HCW should be updated in order to secure accurate diagnosis of LTBI and offer proper treatment and follow-up
Internettbasert læringsressurs i infeksjonsmedisin og mikrobiologi
No full textVårt prosjekt er et internettbasert læringsprogram i infeksjonsmedisino og mikrobiologi for medisinstudenter og andre som er interessert i disse fagområdene. Det skal fungere som et supplement til forelesninger, smågruppeundervisning og lærebøker i infeksjonsmedisin og mikrobiologi. Undervisningen i infeksjonsmedisin og mikrobiologi er spredt over ulike semestre, og vi ønsket derfor å opprette en ressurs der studentene kan få en oversikt over disse fagfeltene. Læringsmålene i disse to fagfeltene har vært vårt utgangspunkt for valget av de ulike emnene i E-læringssiden. Vi har brukt ulike kilder og markert dem med fotnoter fortløpende. Målet vårt er at studentene skal gis den mest kunnskapsbaserte informasjonen, men medisin er i kontinuerlig utvikling og innholdet i E-læringssiden vil dermed kunne utløpe. Innholdet kan enkelt redigeres og forandres, og revisjon vil være nødvendig i takt med endring i kunnskapsbasert medisin. Avslutningsvis har vi en samling av pasientkasuser for å gjøre læringsprogrammet interaktivt og for å understreke de viktigste temaene. Veilederne våre på denne oppgaven har vært Anne Ma Dyrhol Riise MD, førstemanuensis ved Institutt for klinisk medisin, UIO og Halvor Rollag, Professor ved mikrobiologisk avdeling, UIO. Vi ønsker å takke dem for god veiledning
Ettervern- en god overgang til voksenlivet? : Helhetlig oppfølging av ungdom med barnevernerfaring
No full textDenne rapporten oppsummerer funnene fra prosjektet «Ettervern – en god overgang til voksenlivet?» som NTNU Samfunnsforskning og UiT har gjennomført på oppdrag fra Bufdir i perioden 2014-2020. Prosjektet er gjennomført av Veronika Paulsen, Christian Wendelborg, Berit Berg, Jan Tøssebro og Joakim Caspersen ved NTNU Samfunnsforskning, og Anne Riise ved UiT. Prosjektet har som målsetting å belyse hvordan dagens ettervernstilbud fungerer, og vurdere om dagens innretning av ettervernstilbudet er egnet til å bistå ungdom i barnevernet i overgangen til voksenlivet, og til å oppnå et godt voksenliv. Dette har krevd en helhetlig tilnærming med fokus på blant annet ungdommenes behov, barnevernets tilnærminger og tiltak, og hvordan det går med ungdommene i voksenlivet. Vi har derfor benyttet ulike metodiske tilnærminger, herunder kvalitative intervjuer, registerdata og dokumentstudie.publishedVersio
IP-10 measured by Dry Plasma Spots as biomarker for therapy responses in Mycobacterium Tuberculosis infection
No full textTuberculosis (TB) has huge impact on human morbidity and mortality and biomarkers to support rapid TB diagnosis and ensure treatment initiation and cure are needed, especially in regions with high prevalence of multi-drug resistant TB. Soluble interferon gamma inducible protein 10 (IP-10) analyzed from dry plasma spots (DPS) has potential as an immunodiagnostic marker in TB infection. We analyzed IP-10 levels in plasma directly and extracted from DPS in parallel by ELISA from 34 clinically well characterized patients with TB disease before and throughout 24 weeks of effective anti-TB chemotherapy. We detected a significant decline of IP-10 levels in both plasma and DPS already after two weeks of therapy with good correlation between the tests. This was observed both in pulmonary and extrapulmonary TB. In conclusion, plasma IP-10 may serve as an early biomarker for anti-TB chemotherapy responses and the IP-10 DPS method has potential to be developed into a point-of care test for use in resource-limited settings. Further studies must be performed to validate the use of IP-10 DPS in TB high endemic countries
Self-perceived physical functioning and health status in fully ambulatory MS patients
No full textWe investigated the self-perceived health status among multiple sclerosis (MS) patients with no or mild disability according to the Expanded Disability Status Scale (EDSS) and the impact of self-rated physical functioning. A sample of fully ambulatory (EDSS ≤ 3.5) consecutive patients with MS was included after screening for major cognitive impairment. The EDSS was used to measure nervous system signs or disability, and the self-rated health status was assessed using the SF-36 Health Survey. The normative SF-36 data for the general population of Italy were used for comparison. The 197 MS patients analyzed (150 women and 47 men) had significantly lower mean SF-36 scores than the general population, except for bodily pain. The scores did not differ significantly by gender. The same analysis performed on a subsample of 105 patients (79 women and 26 men) with minimal disability in one functional system (EDSS ≤ 2.0) yielded similar results. EDSS was weakly correlated with the physical funct..
Evidence of early childhood as the susceptibility period in multiple sclerosis. Space-time cluster analysis in a Sardinian population
No full textThe authors analyzed the natural history of multiple sclerosis (MS) before onset to identify the period of susceptibility and exogenous factors that might play a role in causing the disease. Space-time cluster analysis was performed among northern Sardinians, a genetically stable Italian population that showed an increasing risk of MS between 1965 and 1999. Residence changes from birth to clinical onset were recorded for all MS patients with clinical onset between 1965 and 1999 in the province of Sassari. Closeness in space and time was defined as living in the same municipality and differing in year of birth by 1, 2, or 5 years. Analyses were performed for the period from birth to age 25 years or MS onset and in demographic and clinical subgroups. Clustering was substantial in early childhood. Clustering was most marked in the most recent cases, among women, and among patients with early age at onset, a relapsing-remitting course, and in the eastern subarea. No clustering was found wh..
Exposure to breastfeeding and risk of developing multiple sclerosis
No full textBackground: Early-life factors are reported to modulate the risk of developing multiple sclerosis (MS) among adults. The association between exposure to breastfeeding and the risk of MS is debated. We aimed to disclose whether past exposure to breastfeeding and its duration are associated with the risk of developing MS. Methods: We used a cohort design linking prospectively collected information on breastfeeding from the Cohort of Norway community-based surveys on health status (CONOR) with the Norwegian MS Registry and the population-based Medical Birth Registry of Norway that includes information on all births in Norway since 1967. MS clinical onset was collected throughout 2016. A total of 95 891 offspring born between 1922 and 1986 to mothers participating in CONOR were included. We identified 215 offspring within this cohort who developed adult-onset MS. Associations between breastfeeding and MS risk were estimated as hazard ratios using Cox proportional hazard models adjusting for maternal factors including education. Results: We found no association between having been breastfed for ≥4 months and MS risk, also after adjusting for various maternal factors (hazard ratio = 0.90; 95% confidence interval 0.68-1.19). The estimates did not change for different durations of breastfeeding. The results were similar when adjusting for other perinatal factors. Conclusion: Our study could not confirm previous findings of an association between breastfeeding and risk of MS. Breastfeeding information was less likely to be biased by knowledge of disease compared with case-control studies
T Cell Responses and Regulation and the Impact of In Vitro IL-10 and TGF-beta Modulation During Treatment of Active Tuberculosis
No full textMycobacterium tuberculosis (Mtb) is particularly challenging for the immune system being an intracellular pathogen, and a variety of T cell subpopulations are activated by the host defence mechanism. In this study, we investigated T cell responses and regulation in active TB patients with drug-sensitive Mtb (N = 18) during 24 weeks of efficient anti-TB therapy. T cell activation, differentiation, regulatory T cell (Treg) subsets, Mtb-induced T cell proliferation and in vitro IL10 and TGF-beta modulation were analysed by flow cytometry at baseline and after 8 and 24 weeks of therapy, while soluble cytokines in culture supernatants were analysed by a 9-plex Luminex assay. Successful treatment resulted in significantly reduced co-expression of HLA-DR/CD38 and PD-1/CD38 on both CD4(+) and CD8(+) T cells, while the fraction of CD4+ CD25 high CD127 low Tregs (P = 0.017) and CD4(+) CD25(high) CD127(low) CD147(+) Tregs (P = 0.029) showed significant transient increase at week 8. In vitro blockade of IL-10/TGF-beta upon Mtb antigen stimulation significantly lowered the fraction of ESAT-6-specific CD4(+) CD25(high) CD127(low) Tregs at baseline (P = 0.047), while T cell proliferation and cytokine production were unaffected. Phenotypical and Mtb-specific T cell signatures may serve as markers of effective therapy, while the IL-10/ TGF-beta pathway could be a target for early inhibition to facilitate Mtb clearance. However, larger clinical studies are needed for verification before concluding
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