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Biomedical subjects

E Ulvestad

Publications and source records attributed to E Ulvestad.

At least 37 records · Page 2Linked to original sources
PubMed2001

Clinical utility of diagnostic tests for rheumatoid factor.

OBJECTIVE: To investigate and compare the accuracy and usefulness of diagnostic tests for rheumatoid factor (RF). METHODS: In a cross-sectional study sera derived from patients admitted to the Section of Rheumatology were tested for presence of RF using either nephelometry or the Waaler test. Diagnostic sensitivity and predictive values of the tests were calculated and compared. The accuracy of the tests was compared using receiver-operating characteristics (ROC) methodology. RESULTS: Good agreement was found between the tests (kappa approximately 0.7). At cut-off 19 IU/mL nephelometry showed the highest sensitivity (82.4%) and specificity (95.9%) for rheumatoid arthritis (RA). In comparison, the Waaler test had a sensitivity of 60.3% and specificity of 95.9% at cut-off titer 128. The tests showed nearly equal performance characteristics when predicting SS. CONCLUSION: Although both tests exhibit good performance characteristics, nephelometry has a higher accuracy when predicting RA and SS. The common practice of using both tests for detection of RF is not recommended.

Cross-Sectional Studies↗
PubMed2000

Acute myelogenous leukemia blasts as accessory cells during in vitro T lymphocyte activation.

The ability of acute myelogenous leukemia (AML) blasts to mediate costimulatory signals during T lymphocyte activation was investigated in an experimental model where monoclonal T cell populations were stimulated with standardized activation signals (anti-CD3, anti-CD2, and anti-CD28 monoclonal antibodies and phytohemagglutinin). Proliferative T cell responses were detected for all AML patients (n = 16) when irradiated leukemia blasts were used as accessory cells during activation. T cell cytokine release was also observed for all patients when nonirradiated AML accessory cells were used, and for most patients a broad cytokine response (interleukin (IL) 2, IL4, IL10, IL13, and interferon-gamma) was detected. However, both T cell proliferation and cytokine release showed a wide variation among AML patients, and T cell responsiveness was in addition dependent both on the nature of the activation signal and on differences between individual T cell clones. The accessory cell function of AML blasts showed no correlation with the release of any single immunomodulatory soluble mediator (IL1beta, IL6, TNF-alpha, soluble IL2 receptors) or the expression of any particular adhesion/costimulatory membrane molecule (CD54, CD58, CD80, and CD86) by the blasts. However, blocking studies with anti-CD58 and anti-CD80/86 monoclonal antibodies demonstrated that both pathways can be involved when AML blasts are used as accessory cells, but the relative importance and the final effects of signaling through these pathways differ between AML populations. Although there is a wide interpatient variation, we conclude that for a majority of patients the native AML blasts can mediate adequate costimulatory signals needed for accessory cell-dependent T cell activation.

Acute Disease↗
PubMed2000

[Inappropriate use of diagnostic laboratory tests--a perspective from decision making analysis].

BACKGROUND: The increasing use of diagnostic tests is probably not only a consequence of increased morbidity. It has been speculated whether some of the increase may be due to inappropriate use of diagnostic tests. MATERIAL AND METHODS: The PubMed database was searched for literature relating to inappropriate use of laboratory tests. Bayes' theorem was used to explain the context dependence of results obtained from diagnostic tests and to calculate predictive values. RESULTS: A theoretical discussion of tests and their use in diagnostic contexts is given, and a method for evaluating the appropriateness of testing is proposed. By calculating predictive values for positive and negative test results, the use of tests can be evaluated in a common probabilistic currency. Inappropriate usage can be defined as testing that does not give probabilistically useful information. INTERPRETATION: The method will be useful for practising physicians as a basis for improving test usage.

Chemistry, Clinical↗
PubMed2000

[High dose chemotherapy with autologous stem cell support in cancer patients].

INTRODUCTION: In 1996 it was decided that high-dose chemotherapy with peripheral stem cell support should be offered by all five university hospitals in Norway. MATERIAL AND METHODS: We report on the first 49 patients from the western part of Norway treated with this modality at Haukeland University Hospital in the 1996-98 period. RESULTS: All patients had a total of > 2-10(6) CD34 positive cells/kg collected before high-dose chemotherapy. To achieve this critical stem cell dose, five patients had to have three or more stem cell collections; four of them had to be mobilised several times. Poor stem cell mobilisation was mostly marked in patients with soft tissue sarcoma and testicular cancer, but was also observed in a few heavily pre-treated patients with non-Hodgkins lymphoma. With the exception of one lymphoma patient who developed a rapid bone marrow relapse, all patients had satisfactory sign of bone marrow regeneration after reinfusion of the stem cells. This also applied to the poor mobilisors. No treatment-related deaths have occurred. Four to 38 months after high-dose therapy, 33% of patients with multiple myeloma and 52% of patients with malignant lymphoma were alive and in complete remission. Three of the four patients with soft tissue sarcoma relapsed 3-7 months after high-dose chemotherapy.

Adolescent↗
PubMed2000

[HLA-B27 in Bechterew's disease].

BACKGROUND: The role of HLA-B27 in rheumatic disease is reviewed. MATERIAL AND METHODS: The PubMed database was searched for the code words HLA-B27, ankylosing spondylitis, or their combinations. The diagnostic value of HLA-B27 for ankylosing spondylitis was calculated using Bayes' theorem. RESULTS: It is still not clear whether HLA-B27 is a contributing causal factor for ankylosing spondylitis and reactive arthritis. Knowledge of a patient's HLA-B27 status for establishing prognostic information is of uncertain clinical value. INTERPRETATION: Knowledge of HLA-B27 status has limited diagnostic value. HLA-B27 status is clinically most informative when the test result is negative, as ankylosing spondylitis can be ruled out.

CD8-Positive T-Lymphocytes↗
PubMed2000

IgG allotypes and subclasses in Norwegian patients with multiple sclerosis.

Multiple sclerosis (MS) is a multifactorial disease in which genetic and environmental factors apparently have a major influence on the susceptibility and course of the disease. In the present study we have investigated the genetic basis and subclass levels of IgG in MS. Hundred and thirty-six Norwegian patients with MS and 92 controls were genotyped for IgG allotypes of the GM and KM systems. IgG and IgG subclasses were quantified in sera from 115 MS patients and 20 controls. Neither GM nor KM allo-, haplo- or genotypes were significantly correlated with susceptibility, severity or course of the disease. The G1M (3) (3), G2M (23) (23) and G3M (5) (5) allotypes were significantly correlated with high serum levels of IgG3, whereas high IgG2 levels were correlated with G1M (3) (3) and G2M (23) (23) in both patients and controls. Serum levels of IgG subclasses were not significantly correlated with course or severity of the disease. The results indicate no major role for IgG allotypes or IgG subclass levels in the pathogenesis of MS.

Female↗
PubMed2000

lacZ-neoR transfected glioma cells in syngeneic rats: growth pattern and characterization of the host immune response against cells transplanted inside and outside the CNS.

The rat glioma cell lines BT4C and BT4Cn were stably transfected with the bacterial lacZ-neomycin resistance (neoR) gene construct. Both transfected (BT4ClacZ and BT4CnlacZ) and untransfected cell lines were injected intracerebrally and subcutaneously into rats. Survival time, morphology, growth rate and immunological properties of the tumors were studied. Survival time was significantly prolonged after intracerebral implantation of the transfected cell lines. No similar response was found in nude rats, indicating an immunological response towards the lacZ-neoR-transfected cells in immunocompetent animals. Morphological observations showed that the lacZ-neoR-transfected gliomas were smaller and had a distinct boundary with the normal brain tissue, whereas the parental cell lines revealed a more diffuse growth pattern. Immunostaining showed a higher proportion of immunocompetent cells infiltrating the lacZ-neoR-transfected tumors. After s.c. injection, the lacZ-neoR-transfected BT4C cell line had a prolonged lag phase before assuming a growth rate similar to that of the parental cells. The BT4CnvlacZ tumors initially grew fastest, but then disappeared within 3 weeks. A similar response was observed with mock-transfected tumor cells. A (3)HTdR-incorporation assay on spleen cells from rats transplanted s.c. with BT4CnvlacZ cells showed a 10-fold increase in cell activation as compared with rats with BT4Cn tumors. A humoral response towards the transfected cells was verified by Western-blot analyses.

Animals↗
PubMed2000

Soluble Fas/Apo-1 (CD95) levels during T cell activation in the presence of acute myelogenous leukemia accessory cells; contributions from local release and variations in systemic levels.

Fas (CD95/Apo-1) exists both in membrane-bound and in biologically active soluble (s) forms. Ligation of membrane-expressed Fas can induce apoptosis, and Fas-mediated signaling seems to be involved in T-cell-induced apoptosis of human acute myelogenous leukemia (AML) blasts. The local release of sFas by AML blasts may then function as a protective mechanism by competing with membrane-bound Fas for binding sites on the common Fas ligand (FasL). sFas was released by AML blasts during in vitro culture, and this release was modulated by several cytokines that can be secreted by activated T cells. Increased levels of sFas could be detected during in vitro activation of T cells in the presence of native AML accessory cells, and this was observed both for (i) mitogenic activation of CD4+ and CD8+ T cell clones derived from acute leukemia patients with therapy-induced leukopenia and (ii) allostimulated activation of T cells derived from normal donors. However, local in vivo levels of sFas will also be influenced by variations in systemic levels. High serum levels of sFas were detected in acute leukemia patients during chemotherapy-induced cytopenia, but these levels decreased during complicating bacterial infections. In contrast, serum levels of sFasL were normal in leukopenic patients. The present results support the hypothesis that local release of sFas can function as a protective mechanism against AML-reactive T cells, but the effects of this local release are, in addition, modulated by variations in systemic levels of sFas (but not sFasL).

Adolescent↗
PubMed2000

Evaluation of diagnostic tests for antinuclear antibodies in rheumatological practice.

To investigate and compare the accuracy and usefulness of diagnostic tests for antinuclear antibodies (ANA) a cross-sectional study of sera derived from patients admitted to the Department of Rheumatology was tested for the presence of ANA using either indirect immunofluorescence on HEp-2 cells, indirect immunoperoxidase techniques on HEp-2 cells and mouse kidney, or two commercial enzyme-linked immunosorbent assays (ELISA). The diagnostic sensitivity and predictive values of the tests were calculated and compared. The accuracy of tests was compared using receiver-operating characteristics (ROC) methodology. All ANA-positive sera were further analysed for the presence of antibodies against extractable nuclear antigens (anti-ENA) and anti-DNA. A moderate to good agreement was found between tests, with kappa ranging from 0.469 to 0.659. Highest sensitivity for systemic lupus erythematosus (SLE; 93.3%) and primary Sjögren's syndrome (SS; 70%) was found using immunofluorescence on HEp-2 cells. Immunofluorescence on HEp-2 cells performed statistically better than the other tests in predicting SLE but not SS. All tests except mouse kidney showed good and comparable performance in detecting sera with anti-ENA and anti-DNA. At the given cut-off values indirect immunofluorescence on HEp-2 cells performed best. All assays except mouse kidney showed performance characteristics sufficient for use in routine analysis of ANA.

Animals↗
PubMed2000

Anti-cardiolipin autoantibodies and pulmonary embolism. A case for a common cause.

A patient with primary Sjögren's syndrome developed pulmonary embolism following infection with influenza A virus. IgM anti-cardiolipin autoantibodies (aCL) evolved two weeks after hospitalisation, synchronously with antibodies against influenza A. IgG aCL developed three weeks after hospitalization, peaked during the recovery period, and gradually declined to undetectable levels 12 months after admission. Antibodies against beta2 glycoprotein I were not detected. Our results assign a high likelihood to the hypothesis that influenza A virus caused the patient's thromboembolic disease as well as development of aCL. aCL may have contributed to tissue pathology by forming immune-complexes with cardiolipin and rheumatoid factor.

Adult↗
PubMed2000

Cytokine responsiveness of mitogen-activated T cells derived from acute leukemia patients with chemotherapy-induced leukopenia.

The aim of the study was to characterize effects of exogenous cytokines on T lymphocytes derived from acute leukemia patients with chemotherapy-induced leukopenia. We investigated the cytokine responsiveness of long-term expanded CD4+ and CD8+ T cell clones and the effects of exogenous cytokines on anti-CD3-stimulated polyclonal T cell responses. After mitogenic activation in the presence of acute myelogenous leukemia (AML) blasts, most CD4+ and CD8+ clones proliferated in response to interleukin-2 (IL-2). Although a majority of the IL-2-responsive clones could also proliferate in the presence of exogenous IL-4, IL-7, IL-9, IL-10, IL-12, and IL-15, only IL-15 responses were equal to or exceeded the corresponding IL-2 responses. Exogenous cytokines were also added during T cell activation with phytohemagglutinin (PHA) + accessory leukemia cells derived from different AML patients, and all the cytokines then had divergent effects that depended on both differences between clones and differences between AML patients. However, for most of these T cell clone/AML blast combinations, IL-2 and IL-15 caused enhanced T cell proliferation. IL-2 and IL-15 also enhanced anti-CD3-stimulated polyclonal responses of nonexpanded T cells derived from cytopenic patients, whereas other cytokines had only minor effects. Our results demonstrate that cytokine-responsive T cells remain in the circulation during chemotherapy-induced cytopenia, and combination therapy including intensive chemotherapy and T cell-targeting cytokine therapy should, therefore, be possible in AML.

Clone Cells↗
PubMed2000

The cellular immune system of patients with acute leukemia and severe chemotherapy-induced leukopenia: characterization of T lymphocyte subsets responsive to IL-16 and IL-17.

The aim of the present study was to characterize the effects of IL-16 and IL-17 on CD4+ and CD8+ T cell responses in patients with acute leukemia and severe chemotherapy-induced leukopenia. We investigated (1) the function of cytokines as growth factors for preactivated monoclonal T cell populations which had been prepared by long-term in vitro culture, and (2) the ability of cytokines to modulate anti-CD3-stimulated proliferation of polyclonal, nonexpanded T cells. A subset of CD4+ and CD8+ clones could utilize IL-16 and IL-17 as growth factors after previous mitogenic activation, but for the CD4+ subset IL-16 responses were significantly higher than IL-17 responses. Cytokine-dependent proliferation was higher for the CD4+ than for the CD8+ clones in the presence of both IL-16 and IL-17. The effects of IL-16/IL-17 were modulated by the presence of exogenous IL-2 and IL-4. The IL-16-responsive CD8+ clones seemed to represent a minor subset expressing the phenotype CD4lowCD8high. The anti-CD3-stimulated polyclonal responses were generally lower for the cytopenic patients than for healthy individuals, and this decreased responsiveness was probably caused by a combination of quantitative T cell defects and suboptimal accessory cell costimulation. Although IL-16 and IL-17 could function as growth factors for a large subset of our T cell clones, both cytokines had either no or only minor effects on the polyclonal T cell responses for cytopenic patients (e.g. only weak enhancement of anti-CD3 and anti-CD3+anti-CD28 responses, no alteration of the cytokine responsiveness profile after anti-CD3 stimulation). We conclude that both IL-16 and IL-17 are potentially immunostimulatory cytokines in patients with acute leukemia and chemotherapy-induced leukopenia, but the final effects of IL-16/IL-17 on proliferative T cell responses are modulated by local immunoregulatory networks.

Acute Disease↗
PubMed1999

[Immunological investigation of hypogammaglobulinemia].

Immunoglobulin deficiency syndromes should be considered in patients with recurrent respiratory tract infections or in patients with infections caused by agents of low virulence. We present two patients with a clinical history of recurrent respiratory tract infections. Both patients had a humoral immunodeficiency characterised as common variable immunodeficiency (CVID). We give a brief survey of CVID with emphasis on the immunological investigation of hypogamma-globulinaemia. Analysis of serum, immunoglobulins should be performed in patients with recurrent infections Patients with humoral immuno-deficiency often have false negative serology for infectious agents despite obvious infections.

Adolescent↗
PubMed1999

Expression and release of adhesion molecules by human acute myelogenous leukemia blasts.

The expression and release of adhesion molecules by acute myelogenous leukemia (AML) blasts was investigated in vitro. For most patients AML blasts expressed relatively low levels of membrane-bound L-selectin and Intercellular adhesion molecule 1 (ICAM-1), but their soluble forms were detected in the supernatants for the majority of patients when AML blasts were cultured in vitro. These in vitro levels of SL-selectin and sICAM-1 were considerably lower than the normal serum levels. Divergent and relatively small alterations in SL-selectin and sICAM-1 levels were usually observed when exogenous growth factors were present during AML blast culture, whereas increased SL-selectin levels were observed after coculture of AML blasts and normal leucocytes. E- and P-selectin were neither expressed nor released by AML blasts. We conclude that AML blasts are a source of soluble adhesion molecules.

Adult↗
PubMed1999

Effects of gamma-irradiation on acute myelogenous leukemia blasts: in vitro studies of proliferation, constitutive cytokine secretion, and accessory cell function during T cell activation.

Generation of cellular immune responses against acute myelogenous leukemia (AML) blasts is a possible therapeutic approach in leukemia therapy. However, when using native AML blasts as stimulator cells during ex vivo generation of leukemia-reactive T cells, one has to ensure that the T cell population is not contaminated with proliferating AML blasts. Our results demonstrate that gamma-irradiation could be used to stop AML blast proliferation for all patients investigated. However, gamma-irradiation also caused a dose-dependent reduction in the constitutive AML blast secretion of the potentially T cell stimulatory cytokines IL-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha). At the same time, gamma-irradiation resulted in a dose-dependent decrease in anti-CD3-stimulated proliferative responses of T cell clones in the presence of AML blast accessory cells. When using 50 Gy irradiation, however, AML blast expansion was avoided, and anti-CD3 and PHA-stimulated T cell proliferation was detected in the presence of accessory AML blasts for most AML/T cell combinations investigated. When AML blasts were cultured with GM-CSF + IL-4 to develop a dendritic cell phenotype, enhanced T cell proliferation in the presence of in vitro precultured AML blasts was observed for most patients even after 50 Gy irradiation. We conclude that when using native AML blasts as accessory cells during in vitro generation of leukemia-reactive T cells, an irradiation dose of 50 Gy can be used for a majority of AML patients to avoid the risk of leukemia cell expansion during culture and with the maintenance of AML blast accessory cell function. However, when in vitro expanded cells are used in clinical trials, this antiproliferative effect should be documented with appropriate in vitro testing for every patient so that the possibility of decreased sensitivity to gamma-irradiation in exceptional patients is excluded.

Adult↗
PubMed1999

Clinical immunology of chronic cold agglutinin disease.

We studied clinical and immunological characteristics of 15 patients with chronic cold agglutinin disease (CAD). Mean age at disease debut was 68 years for female and 67 years for male patients. The patients had no signs of other autoimmune diseases. All patients had V(H)4-34 encoded IgM kappa cold agglutinins (CA) in high titre. In five patients IgM increased significantly with advancing disease. Seven patients had reduced concentrations of lymphocytes, largely of CD4 and CD8 T cells. Percentages of NK cells (CD56) and B cells (CD19) were increased in seven and three patients, respectively. In six out of nine patients a clonal expansion of kappa positive B cells was found. Serum C3 was decreased in nine patients and C4 was decreased in 11 patients, six of whom had reduced CH50. Such data indicate that patients with CAD experience a continuous low-grade complement consumption. Five patients had experienced increased haemolysis during infections. After addition of active complement to patient sera in vitro, six sera showed increased haemolytic activity. Our results indicate that some patients with CAD have a relative deficit of complement in their serum and that an increase of complement production occurs during an acute phase reaction which enhances haemolysis. Our data also indicate that both CA titre and thermal amplitude are important characteristics when predicting complement activation and clinical course in CAD.

Aged↗