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Biomedical subjects

R Einarsson

Publications and source records attributed to R Einarsson.

102 records · Page 6Linked to original sources

Interleukin-4, soluble CD23 and interferon-gamma levels in serum during the first 18 months of life.

Serum levels of interleukin (IL)-4, interferon (IFN)-gamma and soluble CD23 (sCD23) were analysed in a prospective study of 64 infants monitored from birth to 18 months of age. The levels were low at birth and then increased, reaching a peak at either 6 or 9 months and then decreased up to 18 months of age. The children who developed atopic disease during the first 18 months of life had significantly higher IL-4 median levels than those who did not. No relationship was seen between the levels of sCD23 and IFN-gamma and allergy. Thus, the IL-4 levels in serum, but not sCD23 and IFN-gamma, were associated with allergic disease in infancy. Elevated levels were recorded before the onset of clinical symptoms, indicating that atopic disease is associated with a primary deviation of T cell function.

Humans↗

TPS and CA 19-9 measurements in the follow-up of patients with pancreatic cancer and chronic pancreatitis.

The aim of this study was to assess the value of TPS and CA 19-9 in a long-term follow-up analysis of 11 patients with chronic pancreatitis (CP) and 15 patients with pancreatic cancer (PC). In all monitored patients with chronic pancreatitis the initial TPS level was below 200 U/L, whereas CA 19-9 was elevated in two of them. In one patient a dramatic increase in the TPS concentration (820 U/L) was measured at the last follow-up visit (after 8.6 months), which led to the detection of PC. In all patients with PC the preoperative TPS level exceeded 200 U/L, whereas CA 19-9 was elevated in only nine patients. After the Kausch-Whipple operation 11 patients showed no evidence of disease and in eight of these patients both TPS and CA 19-9 were within the reference range; however, in three patients liver metastases were detected after 8-24 months from the last tumor marker measurement. In four of the 15 patients both markers were elevated at the end of the follow-up period and distant metastases were clinically confirmed. Our results indicate that in patients with CP and PC undergoing long-term follow-up, TPS reflects the clinical status of patients more accurately than CA 19-9.

Biomarkers, Tumor↗

The prognostic significance of increasing marker levels in metastatic breast cancer patients with clinically complete remission, partial remission or stable disease.

TPS, CA 15-3 and CEA were determined in metastatic breast cancer patients during treatment. After six months of follow-up the patients were divided into four groups according to the UICC criteria for treatment response. Forty-six patients with a more favorable prognosis (complete remission, partial remission or stable disease) were followed for an extended period. In 30 of the 46 patients at least one marker had increased at the end of the six-month period by at least 25% (TPS in 54%, CA 15-3 in 20%, CEA in 20%). All these 30 patients subsequently developed progression. The prognostic sensitivity was 83%, 30% and 30%, respectively, for TPS, CA 15-3 and CEA. The combination of TPS and CA 15-3 showed a sensitivity of 96%. The median lead time was about 8 months for TPS and CA 15-3, but less than 50% of the patients showed a lead time for CA 15-3 as compared to TPS. We conclude that TPS and CA 15-3 determinations are helpful for the prediction of progression during the follow-up of breast cancer patients.

Biomarkers, Tumor↗

Prognostic significance of CA 125 and TPS levels after chemotherapy in ovarian cancer patients.

The analysis of survival data of patients with epithelial ovarian cancer proved that both CA 125 and TPS were good markers for clinical outcome prediction. Patients receiving chemotherapy were analyzed for 2-year overall survival (OS). Kaplan-Meier survival analysis showed highly significant differences in OS between patients with stage I+II (survival for 2 years 68%) and stage III+IV (survival for 2 years 33%; p = 0.0008). CA 125 levels above or below 35 kU/I and TPS levels above or below 80 U/l after 3 chemotherapy courses were not significantly correlated with OS in stage I+II patients (p = 0.06 respectively 0.07). However, in the subgroup of patients with stage III+IV the cut-off levels of CA 125 and TPS were excellent discriminators of OS: With CA 125 levels below the cut-off 52% of the patients survived, while with CA 125 levels above the cut-off only 13% survived (p < 0.0001). With TPS levels below the cut-off 49% of the patients survived, while with levels above the cut-off only 19% of the patients survived (p < 0.0001). In the subset of patients with CA 125 levels less than 35 kU/I after 3 chemotherapy courses (n = 50) analysis of their TPS levels allowed further discrimination of the prognostic significance. With TPS levels below the cut-off 63% of the patients survived, while 35% of the patients survived with TPS levels above the cut-off. The sum value of CA 125 and TPS cut-off values (115) as discriminator correlated even better with survival rate: With levels below this sum value 63% of the patients survived, while this was only 17% with sum values above the summed cut-off level (p = 0.0004). The extent to which the tumor was removed at operation also correlated with the 2 years survival rate. None of the patients with a staging laparotomy (n = 10) showed a 2-years survival. The difference in OS between patients with complete debulking and partial debulking was significant: OS 51% versus 23% (p = 0.027). Prognosis was not significantly correlated with histological type.

Antineoplastic Combined Chemotherapy Protocols↗

Performance characteristics of IMMULITE TPS: a comparison with TPS IRMA.

This paper describes an automated immunoassay for the measurement of TPS developed for the IMMULITE. The IMMULITE system is a fully automated continous random access analyzer, which uses enzyme-amplified chemiluminiscent as the detection system. The IMMULITE TPS assay is a sequential, two-site chemiluminiscent enzyme immunometric assay designed for the quantitative measurement of TPS in serum. The IMMULITE TPS assay covers a clinical concentration range of 20-2400 U/L, with a lower detection limit of 6 U/L. A serum method comparison (n = 340) to the TPS IRMA assay demonstrates a correlation coefficient of 0.961 and a slope of 1.04. Samples run on IMMULITE TPS assay exhibit linearity upon dilution where recovered values fall within 15% of the theoretical sample value. The intra-assay precision of the IMMULITE TPS assay ranged from 3.3-4.7%, while the interassay precision ranged from 3.9-6.0%. By using different methods (immunoradiometric assay vs chemiluminiscent enzyme-labeled immunometric assay, one-step procedure vs sequential two-step procedure, manual vs fully automated procedure) the two TPS tumor marker tests used in this study gave quite comparable determinations for the sera from the cancer patients.

Antibodies, Monoclonal↗

Use of TPS and CA 15-3 assays for monitoring chemotherapy in metastatic breast cancer patients.

TPS and CA 15-3 have been applied for monitoring treatment in patients with advanced breast cancer and the relationship between the initial marker levels and the changes of the markers during chemotherapy has been established. Both markers have demonstrated high sensitivity for detecting visceral and bone metastases in the patients (90-95%) compared to soft tissues and locally advanced disease (45-50%). The marker combination, TPS and CA15-3, showed the highest sensitivity for detecting bone/visceral metastases (98%) and soft tissue/locally advanced metastases (75%). TPS showed a more frequent decrease in marker level (> 50%) compared to CA 15-3 as well as the highest correlation (68%) to the clinically confirmed events CR, PR compared to CA 15-3 (54%). In the subgroup of metastatic breast cancer patients, demonstrating increased marker levels (> 25%) during follow-up, TPS showed the highest correlation compared to the clinically confirmed progressive disease. In the subgroup of patients with clinically confirmed progression, contemporary measurements of the marker values resulted in correlation with the clinical findings in 78% for TPS and 58% for CA 15-3. TPS appears to be superior to CA 15-3 for follow-up of metastatic breast cancer patients. TPS and CA 15-3 marker increase preceded the clinical and/or radiological signs of distant metastases in most of the patients; 1.5 and 1.1 months, respectively. The time elapsed between tumor marker increase and clinically confirmed progression was very short, which is also related to the frequent follow-up visits for metastatic breast cancer patients receiving chemotherapy. TPS appears to indicate the changes in the disease state earlier than clinical criteria or than the established tumor burden markers. The simultaneous determination of TPS and CA 15-3 provided additive information in advanced breast cancer patients and might guide management decisions in the individual patients.

Adult↗

Serum levels of CA 125 and TPS during treatment of ovarian cancer.

Two hundred and sixty ovarian cancer patients (including all FIGO stages) were enrolled in a prospective multicentre study. In this interim study we analyzed 206 patients receiving combined chemotherapy for at least 3 courses for two-year overall survival (OS). CA 125 and TPS were applied for monitoring treatment and the relationship between marker levels, marker changes and clinical assessments was established. Preoperative CA 125 or TPS levels were not correlated with OS in FIGO stage I and II patients. After 3 chemotherapy courses the marker levels were not correlated with OS in stage I and II. Partial debulking in stage II patients was a bad prognostic factor. CA 125 or TPS levels (using a CA 125 discrimination level of 25 kU/l and a TPS discrimination level of 100 U/l) after 3 courses of chemotherapy were highly significantly correlated with OS in FIGO stages III and IV patients: CA 125 two-year OS 67% versus 26% (p < 0.0001) and TPS two-year OS 55% versus 22% (p < 0.0001). The prognostic value of CA 125 levels after 3 chemotherapy courses could be further increased by combining CA 125 and TPS levels. When both CA 125 and TPS levels were below their respective discrimination levels, the two-year overall survival was 75%. When both levels were above the discrimination level, the two-year overall survival was only 17%.

Antineoplastic Agents↗

Vascular endothelial growth factor (VEGF) concentration in sera and tumor effusions from patients with ovarian carcinoma.

VEGF is an important angiogenic cytokine with a critical role in tumor angiogenesis. VEGF concentrations were measured using an ELISA assay, detecting VEGF165 isoform, in tumor cyst and/or ascitic fluids and in sera of 86 patients with malignant neoplasms and in 53 patients with benign ovarian neoplasms. VEGF levels were significantly elevated in the sera and cyst fluids of carcinoma patients compared with patients who had benign neoplasms. In carcinoma patients, statistically higher VEGF levels were detected in tumor effusions than in corresponding sera. The differences between VEGF values in sera and tumor effusions in relation to histological subtypes of ovarian carcinoma and FIGO stages were statistically insignificant. High VEGF levels in ascitic fluids appeared to be significantly associated with shorter disease-free survival and overall survival In multivariate analysis, besides FIGO stage and age of patients, only serum VEGF concentration was an independent prognostic factor for overall survival. The elevated VEGF levels in sera and tumor effusions of patients with FIGO stages I/II indicated that angiogenesis promoted by VEGF is a continuous process, independent of clinical advancement of the disease.

Ascitic Fluid↗

Sensitivity to Parietaria officinalis and Parietaria judaica pollen allergens in a Spanish population.

To investigate the biological activity of P. judaica and P. officinalis allergen preparations, 36 Spanish patients were included in a biological standardization (BS) trial. For both species the concentration corresponding to 1000 biological units/ml (BU/ml) was found to be about 2 micrograms dry weight/ml (d.w./ml). The allergenic activity per microgram d.w. was about the same as reported for other important weed pollen extracts. The physico-chemical and immunological properties of the purified Parietaria judaica and Parietaria officinalis pollen allergen preparations used for biological standardization were investigated. The protein content was determined to 38% and 23% for P. judaica and P. officinalis respectively, while the carbohydrate content was 25% in both weed preparations. More than 40 antigens and at least 10 different allergens were detected by crossed immuno electrophoresis/crossed radio immunoelectrophoresis (CIE/CRIE) analyses. SDS-gPAGE followed by electroblotting showed important allergens between 10,000 and 75,000 d for both species. The crossreactivity as measured by skin prick test, RAST and CRIE was high.

Allergens↗

Determination of serum tumor markers TPS and CA 15-3 during monitoring of treatment in metastatic breast cancer patients.

Serum levels of tissue polypeptide specific antigen (TPS), a cytokeratin 18 marker, and CA 15-3 were determined in 42 patients with metastatic breast cancer during routine treatment follow-up. At the time of proved metastatic disease, 86% of the values for TPS were above the upper reference value as compared to 93% for CA 15-3. The combined use of TPS and CA 15-3 increased the overall sensitivity. The levels of the tumor markers followed the course of disease during a follow-up period of 6-10 months, even though the dynamics of the changes of tumor markers levels differed in some patients. An increase in the tumor marker level of 25% or more was seen in 60% (TPS) and 52% (CA 15-3), respectively of the studied patients. TPS appeared to indicate changes faster than CA 15-3. The overall results of this study suggest the combined use of TPS and CA 15-3 in the monitoring of breast cancer patients is preferable.

Aged↗

Tissue polypeptide specific antigen (TPS) detects a specific epitope structure on human cytokeratin.

A TPS-reactive protein fragment from a human colon adenocarcinoma cell line was purified to electrophoretic homogeneity. N-terminal sequence analysis of the purified 13 kDa protein fragment demonstrated that the component was a fragment of human cytokeratin 18. The M3 monoclonal antibody (detector antibody in the TPS assay) was applied for screening of an expression library. The M3-reactive phage clones were subcloned and PCR amplified. DNA-sequence analysis revealed it to contain a nucleotide fragment corresponding to human cytokeratin 18. Smaller fragment, engineered by PCR and expressed as fusion proteins, demonstrated that the M3 epitope is localized to human cytokeratin 18, amino acid residues 322-340.

Biomarkers, Tumor↗

TPS and CA 125 levels in serum, cyst fluid and ascites of patients with epithelial ovarian neoplasms.

The serum markers TPS and CA 125 were determined in serum, cyst fluid and ascites in ovarian carcinoma patients and in patients with benign ovarian neoplasms. The levels of TPS and CA 125 were significantly higher in malignant and benign tumor cysts and ascitic fluids than in corresponding patients sera (p < 0.005 for TPS, p < 0.0001 for CA 125). The concentrations of cyst fluid TPS and CA 125 were also usually higher in cancer patients than in patients with benign ovarian neoplasms. TPS and CA 125 were elevated in a higher proportion of ovarian cancer patients sera than in benign ovarian patients' sera (p < 0.001 for both markers). Serum preoperative TPS and CA 125 levels were significantly higher in patients with advanced disease (FIGO stage III/IV) than in patients with early stage disease (FIGO stage I/II, p = 0.002, p < 0.05 respectively). When histology was considered, small differences in the marker signals were noted for TPS and CA 125 with the exception of mucinous neoplasms, where TPS showed a markedly higher signal. These results suggest that the combined use of TPS and CA 125 could be of additive value for the identification of epithelial ovarian neoplasms. Postsurgical TPS sera levels achieved the normal values faster than CA 125 suggesting that determination of TPS concentration before and 3 days after surgery seems to be valuable for the evaluation of radical surgery.

Adenocarcinoma↗