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| 2. |
- Askarieh, Galia, 1983, et al.
(författare)
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Systemic and intrahepatic interferon-gamma-inducible protein 10 kDa predicts the first-phase decline in hepatitis C virus RNA and overall viral response to therapy in chronic hepatitis C.
- 2010
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 51:5, s. 1523-1530
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Tidskriftsartikel (refereegranskat)abstract
- High systemic levels of interferon-gamma-inducible protein 10 kDa (IP-10) at onset of combination therapy for chronic hepatitis C virus (HCV) infection predict poor outcome, but details regarding the impact of IP-10 on the reduction of HCV RNA during therapy remain unclear. In the present study, we correlated pretreatment levels of IP-10 in liver biopsies (n = 73) and plasma (n = 265) with HCV RNA throughout therapy within a phase III treatment trial (DITTO-HCV). Low levels of plasma or intrahepatic IP-10 were strongly associated with a pronounced reduction of HCV RNA during the first 24 hours of treatment in all patients (P < 0.0001 and P = 0.002, respectively) as well as when patients were grouped as genotype 1 or 4 (P = 0.0008 and P = 0.01) and 2 or 3 (P = 0.002, and P = 0.02). Low plasma levels of IP-10 also were predictive of the absolute reduction of HCV RNA (P < 0.0001) and the maximum reduction of HCV RNA in the first 4 days of treatment (P < 0.0001) as well as sustained virological response (genotype 1/4; P < 0.0001). To corroborate the relationship between early viral decline and IP-10, pretreatment plasma samples from an independent phase IV trial for HCV genotypes 2/3 (NORDynamIC trial; n = 382) were analyzed. The results confirmed an association between IP-10 and the immediate reduction of HCV RNA in response to therapy (P = 0.006). In contrast, pretreatment levels of IP-10 in liver or in plasma did not affect the decline of HCV RNA between days 8 and 29, i.e., the second-phase decline, or later time points in any of these cohorts. CONCLUSION: In patients with chronic hepatitis C, low levels of intrahepatic and systemic IP-10 predict a favorable first-phase decline of HCV RNA during therapy with pegylated interferon and ribavirin for genotypes of HCV.
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| 3. |
- Dotevall, Annika, 1957, et al.
(författare)
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A retrospective analysis of a consecutive series of patients splenectomized for various hematologic disorders.
- 1987
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Ingår i: Acta haematologica. - 0001-5792. ; 77:1, s. 38-44
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Tidskriftsartikel (refereegranskat)abstract
- At our hospital, 47 out of 184 consecutive splenectomies performed over 7 recent years were carried out on patients afflicted with various hematologic diseases. The results of these 47 splenectomies were the subject of a careful retrospective analysis. The majority of the splenectomies (81%) were therapeutic. Cytopenia, particularly thrombocytopenia, was the most common indication for surgery. As a whole, good therapeutic responses with rapid improvements in peripheral blood picture and/or diminished symptoms of pressure discomfort from an enlarged spleen were obtained. There was no peri- or postoperative mortality; 23% major and 26% minor postoperative complications were recorded. In patients with perioperative bleeding and various postoperative complications, the spleens were larger than in subjects who run an uneventful peri- and postoperative course. During the follow-up period, 4 septicemias occurred in 3 patients. In 2 of these patients, the septicemias coincided with a cholecystitis and a pneumonia, respectively. None of the infections was lethal. It is concluded that elective splenectomy for hematologic disease in well selected and carefully prepared patients is beneficial and can be performed without mortality or major hazards.
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| 4. |
- Gilles, Stefanie, et al.
(författare)
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Pollen exposure weakens innate defense against respiratory viruses.
- 2020
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 75:3, s. 576-587
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Tidskriftsartikel (refereegranskat)abstract
- Hundreds of plant species release their pollen into the air every year during early spring. During that period, pollen allergic as well as non-allergic patients frequently present to doctors with severe respiratory tract infections.To assess whether pollen may interfere with antiviral immunity.We combined data from real life human exposure cohorts, a mouse model and human cell culture to test our hypothesis.Pollen significantly diminished interferon-λ and pro-inflammatory chemokine responses of airway epithelia to rhinovirus and viral mimics and decreased nuclear translocation of interferon regulatory factors. In mice infected with respiratory syncytial virus, co-exposure to pollen caused attenuated antiviral gene expression and increased pulmonary viral titers. In non-allergic human volunteers, nasal symptoms were positively correlated with airborne birch pollen abundance, and nasal birch pollen challenge led to down-regulation of type I and -III interferons in nasal mucosa. In a large patient cohort, numbers of rhinovirus-positive cases were correlated with airborne birch pollen concentrations.The ability of pollen to suppress innate antiviral immunity, independent of allergy, suggests that high-risk population groups should avoid extensive outdoor activities when pollen and respiratory virus seasons coincide.
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| 5. |
- Guedj, H., et al.
(författare)
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The impact of fibrosis and steatosis on early viral kinetics in HCV genotype 1-infected patients treated with Peg-IFN-alfa-2a and ribavirin
- 2012
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504. ; 19:7, s. 488-496
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Tidskriftsartikel (refereegranskat)abstract
- . Hepatitis C viral (HCV) kinetics after initiation of interferon-based therapy provide valuable insights for understanding virus pathogenesis, evaluating treatment antiviral effectiveness and predicting treatment outcome. Adverse effects of liver fibrosis and steatosis on sustained virological response have been frequently reported, yet their impacts on the early viral kinetics remain unclear. In this study, associations between histology status and early viral kinetics were assessed in 149 HCV genotype 1infected patients treated with pegylated interferon alfa-2a and ribavirin (DITTO trial). In multivariate analyses adjusted for critical factors such as IL28B genotype and baseline viral load, presence of significant fibrosis (Ishak stage > 2) was found to independently reduce the odds of achieving an initial reduction (calculated from day 0 to day 4) in HCV RNA of =2 logIU/mL (adjusted OR 0.03, P = 0.004) but was not associated with the second-phase slope of viral decline (calculated from day 8 to day 29). On the contrary, presence of liver steatosis was an independent risk factor for not having a rapid second-phase slope, that is, =0.3 logIU/mL/week (adjusted OR 0.22, P = 0.012) but was not associated with the first-phase decline. Viral kinetic modelling theory suggests that significant fibrosis primarily impairs the treatment antiviral effectiveness in blocking viral production by infected cells, whereas the presence of steatosis is associated with a lower net loss of infected cells. Further studies will be necessary to identify the biological mechanisms underlain by these findings.
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| 6. |
- Hjalmarsson, E, et al.
(författare)
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A 5-Year Open-Label Follow-up of a Randomized Double-Blind Placebo-Controlled Trial of Intralymphatic Immunotherapy for Birch and Grass Allergy Reveals Long-term Beneficial Effects
- 2023
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Ingår i: Journal of investigational allergology & clinical immunology. - : Esmon Publicidad, SA. - 1018-9068. ; 33:5, s. 362-372
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intralymphatic immunotherapy (ILIT) has been proposed as a novel, less time-consuming alternative to conventional allergy immunotherapy (AIT). Few previous studies have evaluated its long-term effects. The objective of the study was to complete a 5-year follow-up of a previously performed randomized, double-blind placebo-controlled trial of ILIT for a combination of birch and grass allergens. Methods: Fifty-eight patients with allergic rhinitis were treated with either placebo or a combination of ALK Alutard Birch and Grass 1000 SQ-U, three intralymphatic injections with one-month intervals. A year after the vaccination, symptoms induced by nasal provocation were significantly reduced. 5-6 years later, 20 out of 26 actively treated patients were followed up with a nasal provocation test (NPT), seasonal registration of the combined symptoms and medications score (CSMS), IgE and IgG4 levels in the blood and immunological markers in blood and lymph nodes and compared with 13 unvaccinated controls Results: The ILIT induced reduction in the NPT response seen in year one could not be convincingly reproduced in year five. The new CSMS scores were markedly lower among the previously treated patients than for the control group. Further, grass-specific IgG4 was increased, grass-specific IgE decreased, FcεR1 on basophils reduced, and the amount of memory T-cells in the lymph nodes increased. Conclusion: The combination of seasonal derived clinical data and immunological parameters supports the notion of a long-lasting effect of ILIT. These data support the concept of ILIT as a good alternative to traditional AIT in pollen-induced allergic rhinitis.
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| 7. |
- Hjalmarsson, E, et al.
(författare)
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A 5-Year Open-Label Follow-up of a Randomized Double-Blind Placebo-Controlled Trial of Intralymphatic Immunotherapy for Birch and Grass Allergy Reveals Long-term Beneficial Effects
- 2023
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Ingår i: Journal of investigational allergology & clinical immunology. - : Esmon Publicidad, SA. - 1018-9068. ; 33:5, s. 363-372
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intralymphatic immunotherapy (ILIT) has been proposed as a novel, less time-consuming alternative to conventional allergy immunotherapy (AIT). Few previous studies have evaluated its long-term effects. The objective of the study was to complete a 5-year follow-up of a previously performed randomized, double-blind placebo-controlled trial of ILIT for a combination of birch and grass allergens. Methods: Fifty-eight patients with allergic rhinitis were treated with either placebo or a combination of ALK Alutard Birch and Grass 1000 SQ-U, three intralymphatic injections with one-month intervals. A year after the vaccination, symptoms induced by nasal provocation were significantly reduced. 5-6 years later, 20 out of 26 actively treated patients were followed up with a nasal provocation test (NPT), seasonal registration of the combined symptoms and medications score (CSMS), IgE and IgG4 levels in the blood and immunological markers in blood and lymph nodes and compared with 13 unvaccinated controls Results: The ILIT induced reduction in the NPT response seen in year one could not be convincingly reproduced in year five. The new CSMS scores were markedly lower among the previously treated patients than for the control group. Further, grass-specific IgG4 was increased, grass-specific IgE decreased, FcεR1 on basophils reduced, and the amount of memory T-cells in the lymph nodes increased. Conclusion: The combination of seasonal derived clinical data and immunological parameters supports the notion of a long-lasting effect of ILIT. These data support the concept of ILIT as a good alternative to traditional AIT in pollen-induced allergic rhinitis.
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| 8. |
- Hjalmarsson, E, et al.
(författare)
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A five-year open follow up of a randomized, double-blind placebo-controlled trial of intralymphatic immunotherapy for birch and grass reveals remaining beneficial effects
- 2022
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Ingår i: Journal of investigational allergology & clinical immunology. - : Esmon Publicidad, SA. - 1018-9068. ; , s. 0-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intralymphatic immunotherapy (ILIT) has been proposed as a novel, less time-consuming alternative to conventional allergy immunotherapy (AIT). Few previous studies have evaluated its long-term effects. The objective of the study was to complete a 5-year follow-up of a previously performed randomized, double-blind placebo-controlled trial of ILIT for a combination of birch and grass allergens. Methods: Fifty-eight patients with allergic rhinitis were treated with either placebo or a combination of ALK Alutard Birch and Grass 1000 SQ-U, three intralymphatic injections with one-month intervals. A year after the vaccination, symptoms induced by nasal provocation were significantly reduced. 5-6 years later, 20 out of 26 actively treated patients were followed up with a nasal provocation test (NPT), seasonal registration of the combined symptoms and medications score (CSMS), IgE and IgG4 levels in the blood and immunological markers in blood and lymph nodes and compared with 13 unvaccinated controls Results: The ILIT induced reduction in the NPT response seen in year one could not be convincingly reproduced in year five. The new CSMS scores were markedly lower among the previously treated patients than for the control group. Further, grass-specific IgG4 was increased, grass-specific IgE decreased, FcεR1 on basophils reduced, and the amount of memory T-cells in the lymph nodes increased. Conclusion: The combination of seasonal derived clinical data and immunological parameters supports the notion of a long-lasting effect of ILIT. These data support the concept of ILIT as a good alternative to traditional AIT in pollen-induced allergic rhinitis.
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