| 1. |
- Fohlman, Jan, et al.
(författare)
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Antiviral treatment with WIN 54954 reduces mortality in murine Coxsackie virus B3 myocarditis
- 1996
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 94:9, s. 2254-2259
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Coxsackieviruses B (CBVs) are dominant causative agents in myocarditis and are associated with pathogenesis is some cases of dilated cardiomyopathy, a clinical entity with a poor survival without heart transplantation. METHODS AND RESULTS: In vitro, the antiviral agent WIN 54 954 was shown to inhibit replication of CBV3 at a minimal inhibitory concentration value of 0.02 mg/L. Administration of WIN 54 954, 100 mg/kg BID PO, beginning on the day of infection resulted in complete protection from enteroviral mortality (P < .01). WIN 54 954 treatment did not abrogate the inflammatory reaction in the myocardium. No difference was found in the expression of surface lymphocyte subset markers. At 3 weeks, macrophages seemed to dominate the inflammatory reaction, regardless of treatment. There was no difference in CBV3 antibody titers, indicating that WIN 54 954 does not interfere with the development of protective immunity. Complement factors C3 and B were synthesized at a higher level during infection and correlated well with the degree of inflammatory reaction. CONCLUSIONS: The results show that WIN 54 954 is a potent antiviral agent with a highly significant effect on survival in CBV-induced myocarditis in the A/J mouse if treatment is started early. It is suggested that the reduction in mortality seen with WIN 54 954 administration is due to an inhibitory effect on virus replication in affected organs that does not interfere with cellular or humoral immunity.
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| 2. |
- Hammarström, Viera, et al.
(författare)
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Tetanus immunity in autologous bone marrow and blood stem cell transplant recipients
- 1998
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 22:1, s. 67-71
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Tidskriftsartikel (refereegranskat)abstract
- The aims of this study were to assess long-term immunity and reimmunization responses against tetanus toxoid in recipients of autologous stem cell grafts and to compare immune status in patients who underwent ABMT or autologous blood stem cell transplantation (APBSCT). Ninety patients were included in the study; 52 had received ABMT and 38 APBSCT. Thirty of 52 ABMT patients (58%) and 25 of 38 APBSCT patients (66%) had protective antibody levels against tetanus before transplantation (P = NS). The rate of seropositivity had decreased at 1 year after transplantation; 15 of 52 (29%) ABMT patients and 18 of 38 (47%) APBSCT patients (P = NS) were still positive after 1 year. There were no cases of spontaneous recovery in seronegative patients. Most patients were reimmunized with three doses of tetanus toxoid given at 12, 13, 14 and or 18 months after transplantation. All immunized patients had protective immunity against tetanus at 1 year after vaccination. These results suggest that humoral immunity is defective both after ABMT and after APBSCT and in both cases the loss of immunity seems to be similar. Reimmunization of patients who have undergone ABMT or APBSCT is necessary to obtain protective immunity against tetanus.
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| 3. |
- Hammarström, Viera, et al.
(författare)
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Tetanus immunity in patients with hematological malignancies
- 1998
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Ingår i: Supportive Care in Cancer. - : Springer Science and Business Media LLC. - 0941-4355 .- 1433-7339. ; 6:5, s. 469-472
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate long-term immunity to tetanus toxoid among patients with hematological disease who had been treated with conventional doses of chemotherapy. Altogether 206 patients with different hematological malignancies were included in the study. There were marked differences between the rates of seronegativity against tetanus, varying from 20% to 70% in different groups of study patients. We found that 21 of 80 (36%) patients with AML, 45 of 80 (56%) with ALL, 12 of 22 (54%) with lymphoma, 4 of 13 (31%) with myeloma and 2 of 11 (18%) with CML were not immune to tetanus. In a multivariate logistic regression model increasing age (P = 0.0001), lymphoid malignancy (P = 0.0005) and advanced disease stage (P = 0.0001) were independent risk factors for loss of tetanus immunity in patients with hematological malignancies.
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| 4. |
- Karawajczyk, G., et al.
(författare)
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The differential release of eosinophil granule proteins : Studies on patients with acute bacterial and viral infections
- 1995
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Ingår i: Clinical and Experimental Allergy. - 0954-7894 .- 1365-2222. ; 25:8, s. 713-719
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Earlier in vitro studies have suggested that the eosinophil may release its granule proteins selectively depending on the stimulus to which the cell is exposed. OBJECTIVE: The object of the present study was to study the question of selective release in vivo by means of serum measurements of the two eosinophil granule proteins eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) in acute infections. METHODS: Fourty-six subjects with acute infections were studied before treatment, 20 with bacterial infections and 26 with viral infections. Serum ECP, EPO and MPO were measured by specific RIA. RESULTS: In acute bacterial infections ECP, but not EPO, was significantly raised in serum (P < 0.0001) compared with non-infected healthy subjects. In acute bacterial infections ECP was significantly correlated to the levels of the neutrophil marker myeloperoxidase (MPO) (rs = 0.96, P < 0.0001) but not to EPO. In acute viral infections neither ECP nor EPO were on average raised. However, almost 20% the patients had elevated levels of bot proteins. In the viral infections the serum-levels of ECP and EPO were correlated (rs = 0.63, P < 0.001), but no correlation was found with MPO. CONCLUSION: It is concluded that eosinophils are activated during acute bacterial infections and that this activation results in the preferential mobilisation of ECP. The simultaneous assay of the two eosinophil proteins, ECP and EPO, may give new insight into the role of the eosinophil in disease.
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| 5. |
- Ljungman, P., et al.
(författare)
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Foscarnet for pre-emptive therapy of CMV infection detected by a leukocyte-based nested PCR in allogeneic bone marrow transplant patients
- 1996
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Ingår i: Bone Marrow Transplantation. - 0268-3369 .- 1476-5365. ; 18:3, s. 565-568
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Tidskriftsartikel (refereegranskat)abstract
- Fifteen allogeneic BMT patients in a phase II study were given foscarnet 60 mg/kg twice daily for 14 days as pre-emptive therapy against CMV disease. CMV infection was diagnosed by a leukocyte-based nested PCR. All 15 patients were evaluable for toxicity. One patient did not fulfill the inclusion criteria of two consecutively positive CMV PCR tests and therefore was not evaluable for efficacy. Thus, 14 of 15 patients were evaluable for development of CMV disease. None of the patients developed CMV disease and all 14 assessable patients had a negative CMV isolation at the end of therapy. None of the 15 patients had to discontinue therapy due to toxicity. Six patients reported mild gastrointestinal disturbances, three patients headaches, and three patients mild urethritis or hemorrhagic cystitis. Serum-electrolyte disturbances were common including abnormal magnesium, potassium and calcium levels. Two patients developed mild serum-creatinine increases requiring adjustment of the foscarnet dosage according to protocol. We conclude that a dosage of foscarnet of 60 mg/kg given twice daily seems to be safe and effective in preventing CMV disease in allogeneic BMT recipients. A study comparing foscarnet and ganciclovir is indicated.
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| 6. |
- Norrby-Teglund, Anna, et al.
(författare)
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Correlation between serum TNF alpha and IL6 levels and severity of group A streptococcal infections
- 1995
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Ingår i: Scandinavian Journal of Infectious Diseases. - 0036-5548 .- 1651-1980. ; 27:2, s. 125-130
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Tidskriftsartikel (refereegranskat)abstract
- The multiorgan failure syndrome caused by group A streptococci (GAS) designated streptococcal toxic shock syndrome (STSS) is believed to be mediated by cytokines induced by superantigens. In order to study the relationship between superantigen production, cytokine levels in patient sera, and clinical GAS manifestation we examined acute-phase sera and strains from 25 patients with GAS bacteremia. The patients had various disease manifestations, including STSS (44%), erysipelas (28%), septicemia (24%), wound infections (16%), and pneumonia (12%). Serotype T1M1 dominated, representing 56% of the isolates, but also strains of other serotypes were identified. The strains were found to produce the streptococcal pyrogenic exotoxins (Spe) A, B, and F, as determined by immuno-blot analyses. There was no difference in amounts of toxin produced between strains isolated from patients with different manifestations of disease. Levels of TNF alpha, IL1 alpha, IL6, IL8, and IFN gamma in acute-phase sera were determined by use of ELISA and RIA assays. The analyses showed higher levels of IL6 in sera from patients with STSS than in sera from patients with bacteremia without shock. TNF alpha was elevated in sera from patients with STSS, as compared to sera from patients with uncomplicated pharyngotonsillitis. No increase in the levels of IL1 alpha, IL8, and IFN gamma could be found in the patient sera and there was no difference in the level of those cytokines between the various patient categories.
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| 7. |
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| 8. |
- Pauksen, Karlis, et al.
(författare)
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Influence of the specific T cell response on seroconversion after measles vaccination in autologous bone marrow transplant patients
- 1996
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Ingår i: Bone Marrow Transplantation. - 0268-3369 .- 1476-5365. ; 18:5, s. 969-973
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Tidskriftsartikel (refereegranskat)abstract
- Six patients who were seronegative to measles after autologous bone marrow transplantation (ABMT) were vaccinated with a live attenuated measles vaccine. The specific T helper cell response was studied by measuring lymphocyte proliferation induced by measles antigen and B cell response by measles specific IgG by ELISA. Blood samples were drawn before, at 1-3 months, and at 1 year after vaccination. It was found that a pre-existing T cell response correlated with an impaired B cell response 1 year after vaccination (r = 0.83, P = 0.04), whereas no correlation was found between IgG titers before vaccination and IgG titer increase, or T cell response after vaccination. Furthermore, there was a transient negative correlation between the T cell response at 1-3 months after vaccination and the T cell response before vaccination (r = -0.90, P = 0.04) that became positive at 1 year after vaccination (r = 0.90, P = 0.02). In conclusion, in patients seronegative to measles who were revaccinated with measles vaccine after ABMT, a pre-existing T cell response correlated with an impaired B cell response, while pre-existing low-level IgG antibodies had no significant influence on the IgG titer rise. A sustained T cell response to measles antigen before vaccination may thus be one possible explanation for measles vaccine failure in ABMT patients.
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| 9. |
- Pauksen, Karlis, et al.
(författare)
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Specific T and B cell immunity to measles after allogeneic and autologous bone marrow transplantation
- 1995
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Ingår i: Bone Marrow Transplantation. - 0268-3369 .- 1476-5365. ; 16:6, s. 807-813
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Tidskriftsartikel (refereegranskat)abstract
- Lymphocyte stimulation with measles virus antigen (MLY) and ELISA for measles IgG antibodies were performed on 60 patients after allogeneic bone marrow transplantation (BMT), and on 59 patients after autologous bone marrow transplantation (ABMT). The T cell response was significantly higher in the 75 measles seropositive patients than in the 29 seronegative patients (P < 0.001), but not significantly different from the MLY in the 15 patients with uncertain serologic reactivity. When the patient group was divided according to type of transplant, the T cell response to measles was also significantly higher in seropositive patients than in seronegative patients after both ABMT (P < 0.001) and after BMT (P < 0.05). Twenty-three seronegative children who were measles vaccinated after BMT had a significantly higher T cell response to measles (7100 c.p.m.) than 17 seronegative non-vaccinated children (100 c.p.m.; P < 0.01). No significant difference was seen in the T cell response in 12 seronegative children vaccinated after ABMT (2500 c.p.m.) compared to seven children not vaccinated (2800 c.p.m.; NS). Seroconversion after vaccination was more frequent in children after BMT (20/23; 87%) compared to ABMT (5/12; 42%; P < 0.05) but no significant difference was found in the T cell response. Therefore, most patients who lost IgG antibodies to measles after bone marrow transplantation also lost their T cell response to measles. A T cell response to measles developed in most patients who seroconverted after vaccination. Failure to develop antibodies to measles in ABMT patients after revaccination may depend on a persisting T cell immunity.
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| 10. |
- Pauksen, Karlis, et al.
(författare)
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Subsets of T-cells and in vitro cytokine production after measles and varicellae-zoster virus antigen stimulation in allogeneic BMT patients
- 1999
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 31:1, s. 43-49
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Tidskriftsartikel (refereegranskat)abstract
- This study was performed to analyse differences in T-cell proliferation induced by a latent virus, varicellae-zoster virus (VZV) and a non-latent virus, measles virus, in patients after allogeneic bone marrow transplantation (BMT). The lymphoproliferative response to measles antigen, VZV-antigen (VZV-ag), and phytohemagglutinin (PHA) was measured by 3H-thymidine incorporation, and interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) analyses in supernatants after in vitro stimulation of peripheral blood mononuclear cells (PBMC) from 22 patients and 18 healthy controls. The cytokine levels were correlated with T-cell subsets by FACS analyses. At the antigen concentrations used, VZV-ag induced higher levels of IFN-gamma (p < 0.05) than did the measles antigen, whereas the levels of IL-10 were similar. Patients without a cell mediated immune (CMI) response to VZV-ag or measles antigen had lower CD4+ T-cell counts than did controls (p < 0.01 in both cases) and lower IFN-gamma production after non-specific PHA stimulation (p <0.01). The IFN-gamma and IL-10 levels after measles antigen stimulation correlated with the number of CD4+ T-cells (p < 0.01 and p < 0.05, respectively), and after VZV-ag mainly to the number of CD8+ T-cells (p < 0.01 and p < 0.05, respectively). These results suggest that there is a difference in the types of T-cells that respond to VZV-ag and measles antigen stimulation, respectively. The impaired CMI response to viral antigens seen in many patients may be explained both by a low number of CD4+ T-cells and by a cell dysfunction.
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| 11. |
- Pauksen, Karlis, et al.
(författare)
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Th1 and Th2 cytokine response after measles antigen stimulation in vitro in bone marrow transplant patients : response to measles vaccination
- 1997
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 20:4, s. 317-323
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Tidskriftsartikel (refereegranskat)abstract
- In seronegative autologous bone marrow transplanted (ABMT) patients, a sustained cell-mediated immunity (CMI) has been shown to impair the antibody response after measles vaccination. To investigate if this might be caused by a preferential Th1 cytokine response, interferon (IFN)-gamma and interleukin (IL)-10 production of peripheral blood mononuclear cells (PBMC) was analyzed after measles antigen (M-ag) stimulation in vitro. The non-specific immune response was measured by IFN-alpha, and IL-12 analyses. Fifty non-vaccinated patients following ABMT or allogeneic bone marrow transplantation (BMT) were included. IFN-gamma production was significantly higher in patients with a retained CMI to measles than in patients without (2.3 vs 0.8 IU/ml; P = 0.01). Only a non-significant tendency was seen in IL-10 production (48.6 vs 26.7 pg/ml; NS), whereas no difference was found in IFN-alpha or IL-12 production. A positive correlation between IFN-gamma and IL-10 production was found (r(s) = 0.49; P < 0.001). After vaccination of 14 ABMT children, there was an increase in PBMC IFN-gamma production in vitro (2.5 vs <0.1 IU/ml; P < 0.05), whereas no changes were seen in the IL-10, IFN-alpha, or antibody levels. These results suggest that both Th1 and Th2 cytokine production are increased by M-ag stimulation in patients with a retained CMI to measles, but the Th1 response seems to be stronger. The preferential Th1 stimulation and increase in IFN-gamma production after vaccination may lead to a reduction in the humoral immune response which may explain the negative correlation between antibody production and T cell reactivity prior to vaccination.
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| 12. |
- Xu, S. Y., et al.
(författare)
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Serum measurements of human neutrophil lipocalin (HNL) discriminate between acute bacterial and viral infections
- 1995
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - 0036-5513 .- 1502-7686. ; 55:2, s. 125-131
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Tidskriftsartikel (refereegranskat)abstract
- Human neutrophil lipocalin (HNL) is a recently identified protein from human neutrophil granules. The concentrations of HNL in the circulation were measured, in a group of patients with acute infections, using a radioimmunoassay. The concentrations of HNL in patients infected by viruses and bacteria were 93.78 +/- 45.30 micrograms l-1 (SD), 404.14 +/- 355.02 micrograms l-1 (SD) in serum, and 47.81 +/- 18.18 micrograms l-1 (SD), 145.46 +/- 194.32 micrograms l-1 (SD) in plasma, respectively. The differences between the two patient groups were highly significant. There was a significant correlation between serum HNL and plasma HNL levels in bacterial infections (r = 0.73, p < 0.0001). The HNL serum levels also correlated with those of C-reactive protein (CRP) (r = 0.59, p < 0.0001). Determination of HNL in serum was more specific and sensitive than CRP in the distinction between viral and bacterial infections. At a cut-off of 155 micrograms l-1 (HNL in serum), the positive and negative predictive values for the diagnosis of bacterial infections were 92 and 96%, respectively, which were superior to the optimal predictive values of CRP. Thus, the determination of HNL level is useful in the diagnosis of acute bacterial infections.
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