The tuberculin skin test (TST) has low specificity. QuantiFERON-TB Gold (QFT-G) and T-SPOT.TB are based on interferon (IFN)-gamma responses to Mycobacterium tuberculosis-specific antigens. A novel ...in-tube format of QFT-G (QFT-GIT) offers logistical advantages.
To compare TST, QFT-GIT, and T-SPOT.TB in bacillus Calmette-Guérin unvaccinated contacts and correlate results with measures of recent exposure.
When a supermarket employee with smear-positive tuberculosis had infected most close contacts, a contact investigation among more than 20,000 customers was performed. We recruited subjects randomly on the day of TST administration (n = 469) and subjects with TST of more than 0 mm on the day of TST reading (n = 316). QFT-GIT and T-SPOT.TB were performed. Demographic data and measures of exposure were collected. TST results were analyzed at a cutoff of 10 or 15 mm. Blood tests were interpreted following the manufacturers' criteria and by varying cutoff levels.
Among 785 study participants, TST results were associated with age, whereas positive IFN-gamma responses were significantly associated with cumulative shopping time, most markedly for QFT-GIT. Among participants with a TST of 15 mm or greater, sensitivity of QFT-GIT and T-SPOT.TB was 42.2 and 51.3%, respectively. Interassay agreement was 89.6% (kappa = 0.59). By varying cutoff values, agreement between the IFN-gamma assays was optimal at 93.6% (kappa = 0.71) using a cutoff of 0.20 IU/ml for QFT-GIT and 13 spots for T-SPOT.TB.
Blood test results were associated with exposure, whereas the TST was not. A possible lack of sensitivity of IFN-gamma assays in detecting individuals with TST of 15 mm or greater, despite negative bacillus Calmette-Guérin vaccination status, warrants further investigation into alternative cutoff values.
Prophylactic donor lymphocyte infusion (DLI) starting at 6 months after T cell-depleted allogeneic stem cell transplantation (TCD-alloSCT) can introduce a graft-versus-leukemia (GvL) effects with low ...risk of severe graft-versus-host-disease (GvHD). We established a policy to apply low-dose early DLI at 3 months after alloSCT to prevent early relapse. This study analyzes this strategy retrospectively. Of 220 consecutive acute leukemia patients undergoing TCD-alloSCT, 83 were prospectively classified to have a high relapse risk and 43 were scheduled for early DLI. 95% of these patients received freshly harvested DLI within 2 weeks of the planned date. In patients transplanted with reduced intensity conditioning and an unrelated donor, we found an increased cumulative incidence of GvHD between 3 and 6 months after TCD-alloSCT for patients receiving DLI at 3 months compared to patients who did not receive this DLI (0.42 (95%Confidence Interval (95% CI): 0.14–0.70) vs 0). Treatment success was defined as being alive without relapse or need for systemic immunosuppressive GvHD treatment. The five-year treatment success in patients with acute lymphatic leukemia was comparable between high- and non-high-risk disease (0.55 (95% CI: 0.42–0.74) and 0.59 (95% CI: 0.42–0.84)). It remained lower in high-risk acute myeloid leukemia (AML) (0.29 (95% CI: 0.18–0.46)) than in non-high-risk AML (0.47 (95% CI: 0.42–0.84)) due to an increased relapse rate despite early DLI.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background. Ribavirin is active in vitro against hantaviruses, but the findings of an open trial of the use of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome (HCPS) ...were inconclusive. Methods. Subjects with suspected HCPS in the prodrome or cardiopulmonary phase but without shock were eligible for randomization to receive either intravenous ribavirin (33 mg/kg ⩽2 g, followed by 16 mg/kg ⩽1 g given every 6 h for 4 days and by 8 mg/kg ⩽.5 g given every 8 h for 3 days) or placebo (administered for 7 days or until the initial Sin Nombre virus antibody test result was confirmed to be negative). The primary outcome was survival at day 28 of the study without the need for extracorporeal membrane oxygenation (ECMO). Results. Thirty-six subjects were enrolled in the trial from March 1996 through July 2001, at which point the study was terminated prematurely because of both the slow rate of accrual of subjects and the findings of a futility analysis. Of the 36 subjects enrolled, 23 (all of whom were enrolled during the cardiopulmonary stage of HCPS) had HCPS confirmed by serologic testing. The severity of illness at entry into the study was similar among the 10 subjects with HCPS who received ribavirin and the 13 subjects with HCPS who received placebo. The proportion of subjects who survived and who did not require ECMO was similar among ribavirin recipients and placebo recipients (70% vs. 62%, respectively); 2 ribavirin recipients and 2 placebo recipients died, including 3 of 7 subjects treated with ECMO. The frequency of adverse events, including anemia, was similar between treatment groups. Conclusions. The rate of accrual of subjects in the present study was inadequate to clearly assess the safety or efficacy of ribavirin in the treatment of HCPS. However, ribavirin was well tolerated, and the lack of trends supporting the use of intravenous ribavirin suggests that it is probably ineffective in the treatment of HCPS in the cardiopulmonary stage.
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Deregulated Notch signaling occurs in the majority of human T-ALL. During normal lymphoid development, activation of the Notch signaling pathway poses a T-cell fate on hematopoietic progenitors. ...However, the transcriptional targets of the Notch pathway are largely unknown. We sought to identify Notch target genes by inducing Notch signaling in human hematopoietic progenitors using two different methods: an intracellular signal through transfection of activated Notch and a Notch-receptor dependent signal by interaction with its ligand Delta1. Gene expression profiles were generated and evaluated with respect to expression profiles of immature thymic subpopulations. We confirmed HES1, NOTCH1 and NRARP as Notch target genes, but other reported Notch targets, including the genes for Deltex1, pre-T-cell receptor alpha and E2A, were not found to be differentially expressed. Remarkably, no induction of T-cell receptor gene rearrangements or transcription of known T-cell specific genes was found after activation of the Notch pathway. A number of novel Notch target genes, including the transcription factor TCFL5 and the HOXA cluster, were identified and functionally tested. Apparently, Notch signaling is essential to open the T-cell pathway, but does not initiate the T-cell program itself.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Hantavirus pulmonary syndrome (HPS) is characterized by the rapid onset of pulmonary edema and a high case-fatality rate. Hantavirus antigens have been demonstrated in pulmonary capillary endothelial ...cells, but the mechanisms causing capillary leakage remain unclear. Immunohistochemical staining was used to enumerate cytokine-producing cells (monokines: interleukin IL-1α, IL-1β, IL-6, and tumor necrosis factor TNF-α; lymphokines: interferon-γ, IL-2, IL-4, and TNF-β) in tissues obtained at autopsy from subjects with HPS. High numbers of cytokine-producing cells were seen in the lung and spleen tissues of HPS patients, but only low numbers in the livers and kidneys. A modest increase in the numbers of cytokine-producing cells was detected in the lungs of patients who died with non-HPS acute respiratory distress syndrome (ARDS), and very few (or no) cytokine-producing cells were detected in the lungs of patients who died of causes other than ARDS. These results suggest that local cytokine production may play an important role in the pathogenesis of HPS.
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SETTING: Following a large-scale contact investigation, individuals with a positive tuberculin skin test (TST) result were offered preventive tuberculosis treatment.OBJECTIVE: To investigate the ...effect of isoniazid (INH) treatment and the effect of time on interferon gamma release
assay (IGRA) results during follow-up.DESIGN: TST-positive subjects (n = 122) detected during the large-scale contact investigation were included in the study. Blood was obtained every 6 months over 2 years to perform both tests.RESULTS: Preventive INH treatment was completed
by 36 of the 122 (29.5%) subjects, 71 (58.2%) were followed up with 6-monthly X-ray screening and 15 (12.3%) did not complete INH treatment. The overall percentage of individuals with a positive result remained stable during the 2 years, at approximately 45-50%, but individual responses
varied over time. The majority of initially low IGRA results remained below the cut-off value, initially high IGRA results remained positive, while initially intermediate IGRA results were followed by more dynamic patterns.CONCLUSION: This study showed a highly variable pattern of IGRA
responses over time and suggests limited value for their use during follow-up of latently infected individuals. However, the significance of different kinetic patterns observed among subjects with intermediate initial IGRA results warrants further study.
The objective of this study was to examine the association between socioeconomic status (SES) and the onset of depression in older adults and to determine the relative contribution of psychosocial ...factors, physical health status, and behavioral factors in explaining this link.
Data were from 2593 men and women, aged 55–85 years, participating in the Longitudinal Aging Study Amsterdam. Two indicators of SES were used: education and income. The onset of depression was measured over 9 years of follow-up.
Adjusted hazard ratios of incident depression were significantly higher in those with low education and low income. Psychosocial factors explained on average 16% of the SES differences in incident depression, physical health status on average 7%, and behavioral factors less than 5%.
In older adults, low SES predicted the incidence of depression. Part of this association was explained by psychosocial factors and physical health status.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Hantavirus pulmonary syndrome (HPS) is a rare but acute fulminant disease caused by Sin Nombre virus (SNV). To understand the role of the viral load in the pathogenesis of HPS, the load of virus in ...the blood of patients with HPS was measured. A quantitative reverse transcription-polymerase chain reaction assay was developed for SNV, because SNV is difficult to grow in cell culture. Thirty-eight samples from 26 patients with HPS were analyzed. Twenty of the 26 initial samples were positive for viral RNA (7 of 9 samples were obtained from patients with fatal cases, and 13 of 17 were obtained from survivors). Mean viral RNA copy numbers were 106.1±1.4/mL in positive cases (106.7±1.4/mL in fatal cases, 105.8±1.3/mL in survivors) and were correlated with peak hematocrit (P < .05) and with the lowest platelet count (P = .05). In 8 survivors who had serial samples obtained, viral RNA copy numbers decreased promptly after resolution of fever.
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Summary
We examined if lifelong physical activity is important for maintaining bone strength in the elderly. Associations of quantitative computerized tomography-acquired bone measures (vertebral and ...femoral) and self-reported physical activity in mid-life (mean age, 50 years), in old age (≥65 years), and throughout life (recalled during old age) were investigated in 2,110 men and 2,682 women in the AGES–Reykjavik Study. Results conclude lifelong physical activity with continuation into old age (≥65 years) best maintains better bone health later in life.
Introduction
Skeletal loading is thought to modulate the loss of bone in later life, and physical activity is a chief means of affecting bone strength by skeletal loading. Despite much discussion regarding lifelong versus early adulthood physical activity for preventing bone loss later in life, inconsistency still exists regarding how to maintain bone mass later in life (≥65 years).
Methods
We examined if lifelong physical activity is important for maintaining bone strength in the elderly.
Results
The associations of quantitative computerized tomography-acquired vertebral and femoral bone measures and self-reported physical activity in mid-life (mean age, 50 years), in old age (≥65 years), and throughout life (recalled during old age) were investigated in 2,110 men and 2,682 women in the AGES–Reykjavik Study.
Conclusion
Our findings conclude that lifelong physical activity with continuation into old age (≥65 years) best maintains better bone health in the elderly.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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