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Biomedical subjects

E M Kittl

Publications and source records attributed to E M Kittl.

13 recordsLinked to original sources

Serum levels of cartilage oligomeric matrix protein (COMP): a rapid decrease in patients with active rheumatoid arthritis undergoing intravenous steroid treatment.

To examine the influence of intravenous steroid-treatment (IST) on serum levels of Cartilage oligomeric matrix protein (COMP) in patients with active rheumatoid arthritis (RA). Serum levels of COMP and C-reactive protein (CRP) were measured in 12 patients with highly active RA (Steinbrocker stages II-IV) and in 5 patients with highly active reactive arthritis (ReA) (positive testing for HLA-B27) before starting daily IST. Patients received a total steroid dosage between 100 and 500 mg of prednisolone. COMP was measured by a commercially available sandwich-type ELISA-kit developed by AnaMar Medical AB, Sweden. Statistical evaluation was calculated by paired t test. In the RA group, COMP levels ranged from 6.3 to 19.4 U/l (mean 12.9 U/l), CRP from 5 to 195 mg/l (mean 77.8 mg/l), the COMP levels of the ReA group ranged from 5.1 to 7.4 U/l (mean 7.9 U/l), the CRP levels from 13 to 126 mg/l (mean 49 mg/l). We found a significant difference between the initial COMP levels in RA+ and ReA patients (P<0.005). In contrast to the ReA group, serum-COMP levels of RA+ patients (P<0.004) and the VAS (P<0.0001) decreased significantly within 2-10 days after the first treatment with steroids. The CRP levels remained unchanged in both groups. Our results indicate that the intravenous treatment with steroids in patients with highly active RA leads to a significant decrease of cartilage degradation. COMP seems to be a valuable parameter not even as a prognostic factor, but as a marker for monitoring the therapy response in patients with RA.

Adult↗

Serum protein 90K/Mac-2BP is an independent predictor of disease severity during hepatitis C virus infection.

The serum protein designated 90K/Mac-2BP has been found at elevated concentrations in the sera of patients with various types of cancer and viral infections. The importance of the 90K/Mac-2BP serum concentrations in predicting the response towards interferon-alpha treatment for hepatitis C virus (HCV) infection prompted us to utilize a new ELISA for soluble human 90K/Mac-2BP to monitor the serum concentrations of this protein in our HCV-positive patients. Seventy HCV-PCR and anti-HCV antibody positive patients were analyzed for their serum levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, cholinesterase, HCV-viral load, viral subtypes, and 90K/Mac-2BP. On correlation of age and 90K/Mac-2BP levels, we found an apparent correlation that was proved rather to be a strong dependence of 90K/Mac-2BP concentrations on disease severity/duration, which increases with age. Multiple correlation analysis demonstrated the independent nature of 90K/Mac-2BP concentrations, underscoring the potential high utility of this new marker. Our data corroborate the potential of the scavenger receptor family protein 90K/Mac-2BP as an independent predictor of disease severity during HCV infection.

Adolescent↗

[Serum soluble CD44 isoform variant 5 level in patients with seropositive rheumatoid arthritis treated with cyclosporin A].

CD44 is a widely expressed cell surface glycoprotein which is involved in many cell-cell and cell-matrix interactions. Expression of soluble CD44 splice variants is strictly regulated and is linked to a high rate of cell division. Serum levels of soluble CD44 variant 5 (sCD44v5) were determined in 14 patients with erosive RA. Patients were divided into two groups. In group 1 cyclosporin A treatment (CYA) was initiated after the first visit. In group 2 preliminary CYA was continued. Controls were performed after 6 months. We found a significant decrease of swollen joint count (SJC) and sCD44v5 in group 1. No effect of CYA was found on c-reactive protein, erythrocyte sedimentation rate and IgM-rheumatoid factor (IgM-RF). In group 2 a significant decrease of CRP was found. Therefore we conclude that measurement of sCD44v5 might be useful in monitoring RA+ patients with CYA.

Adult↗

Prospective evaluation of hemostatic system activation and thrombin potential in healthy pregnant women with and without factor V Leiden.

Normal pregnancy is associated with alterations of the hemostatic system towards a hypercoagulable state and an increased risk of venous thromboembolism. The risk of venous thrombosis is higher in pregnant women with factor V Leiden (FVL) than in those with wildtype factor V. Routine laboratory assays are not useful to detect hypercoagulable conditions. A prospective and systematic evaluation of hemostatic system activation in women with and without FVL during an uncomplicated pregnancy employing more sensitive markers of hypercoagulability, such as prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), D-Dimer, or the endogenous thrombin potential (ETP), an indicator of the plasma's potential to generate thrombin, has not been performed. We prospectively followed 113 pregnant women with (n = 11) and without (n = 102) FVL and measured F1+2. TAT, D-Dimer and the ETP at the 12th, 22nd and 34th gestational week as well as 3 months after delivery (baseline) in each subject. None of the women developed clinical signs of venous thromboembolism during pregnancy or postpartum. Pregnant women with and without FVL exhibited substantial activation of the coagulation and fibrinolytic system as indicated by a gradual increase of F1+2, TAT and D-Dimer throughout uncomplicated pregnancy up to levels similar to those found in acute thromboembolic events (p < 0.0001 by analysis of variance for each parameters). Levels of F1+2 and TAT were comparable between women with and without FVL, but levels of D-Dimer were significantly higher in women with FVL than in those without the mutation (p = 0.0005). The ETP remained unchanged in both women with and without FVL at all timepoints. Our data demonstrate a substantial coagulation and fibrinolytic system activation in healthy women with and without FVL during uncomplicated pregnancy. An elevated F1+2, TAT or D-Dimer level during pregnancy is not necessarily indicative for an acute thromboembolic event. The normal ETP in both women with and without FVL suggests that the capacity of the plasma to generate thrombin after in vitro activation of the clotting system is not affected by pregnancy. Higher levels of D-Dimer in women with FVL than in women with wildtype factor V at baseline as well as during pregnancy indicate increased fibrinolytic system activation in carriers of the mutation.

Adult↗

Serum levels of soluble CD44 variant isoforms are elevated in rheumatoid arthritis.

Serum levels of soluble CD44 variant proteins including sequences encoded by exon v5 and exon v6 (sCD44v5, sCD44v6) were determined in patients with inflammatory rheumatic diseases: 56 with rheumatoid arthritis (RA+) and 31 with miscellaneous inflammatory rheumatic diseases (MIRD). There were very significantly higher serum levels of sCD44v5 and sCD44v6 in patients with RA+ than in those with MIRD (RA+ to MIRD: sCD44v5: 81 +/- 54 ng/ml to 33 +/- 13 ng/ml; sCD44v6: 237 +/- 124 ng/ml to 166 +/- 53 ng/ml; both P << 0.001). In RA+ elevated serum levels of sCD44v5 were correlated with the inflammatory activity of disease. In 17 patients with RA+ three or four follow-up measurements of sCD44v5 were performed within 6 months. The development of sCD44v5 serum levels reflected the clinical course of disease in the patients investigated.

Adult↗

Significant elevation of tumour-associated isoforms of soluble CD44 in serum of normal individuals caused by cigarette smoking.

While performing a prospective study on sCD44 variant isoforms as tumour markers in certain malignancies, we detected relevant differences in the control group between non-smokers and smokers. For a detailed evaluation of these findings, serum levels of sCD44 variant proteins, including sequences encoded by exon v5 and exon v6, respectively, were adjusted to sex, age and smoking habit. We were able to demonstrate a significant elevation of serum levels of sCD44v5 and sCD44v6 in normal individuals due to cigarette smoking (non-smokers to smokers: sCD44v5: 33 +/- 11 microg/l to 62 +/- 30 microg/l; sCD44v6: 142 +/- 34 microg/l to 232 +/- 86 microg/l). Stepwise multiple linear regression analysis of the concentrations of sCD44v5 and sCD44v6 on the possible influence factors sex, age and smoking habit revealed cigarette smoking as the only factor influencing these isoforms (both p << 0.001). Further investigations have to elucidate a possible clinical importance of these findings in smokers. However, in patients with suspected or proven malignancy the diagnostic specifity of sCD44v5 and sCD44v6 is diminished due to this observation.

Antigens, Neoplasm↗

Increased serum levels of soluble CD44-isoform v5 in rheumatic diseases are restricted to seropositive rheumatoid arthritis.

Serum levels of sCD44v5 were measured in 134 patients with definite inflammatory rheumatic diseases (IRD) using a sandwich type ELISA. 94 patients suffered from erosive IgM-rheumatoid factor positive rheumatoid arthritis (RA+), 20 with undifferentiated seronegative polyarthritis, 12 with osteoarthropathia psoriatica and psoriasis vulgaris, 3 with systemic lupus erythematosus, 3 with scleroderma and 2 with reactive arthritis. Elevated serum levels (> 58 ng/ml to 221 ng/ml; median: 93 ng/ml) were only detected in 54/94 (57%) patients with RA+, but not in other IRD. They correlated with advanced stages of disease (Steinbrocker stages III + IV; p < 0.05), elevated CRP-levels (p < 0.01) and higher measurements of IgM rheumatoid factor.

Adult↗

Evaluation of soluble CD44 splice variant v5 in the diagnosis and follow-up in breast cancer patients.

Aberrant expression of CD44 splice variants has been detected on a variety of human tumor cells. Overexpression of specific isoforms has been shown to be associated with metastasis and poor prognosis in breast cancer. We evaluated the possible utility of soluble CD44 splice variant v5 (sCD44v5) as a circulating, tumor-associated marker in breast cancer patients. Serum levels of sCD44v5 were determined in 147 healthy volunteers, in 53 patients with nonmalignant breast disease, in 85 patients with breast cancer at presentation, in 13 patients with recurrence and in 73 patients with active metastatic disease. Statistically, the levels at presentation in stages I-IV, in benign disease, and in a female control group were not significantly different. First longitudinal studies over 1-2 years in the follow-up of 28 patients who have remained tumor-free showed considerable between-patient variation while the intrapatient levels remained within relatively narrow limits. In patients with active metastatic disease, elevated levels of sCD44v5 (> 58 ng.ml-1) were detected in 50% of the cases with marked elevation in only 26%. In these cases, sCD44v5 correlated with the extent of metastatic disease and fell during clinical response to cytoreductive therapy. In comparison with CA15-3 in the patients' follow-up serum levels of sCD44v5 proved to be much less sensitive concerning lead time, percentage of raised serum levels at the time of recurrence and in metastatic disease. The value of sCD44v5 determinations in breast cancer patients was further limited by the poor diagnostic specificity of this marker due to elevated levels in smokers and chronic inflammatory disease.

Alternative Splicing↗

[HDL cholesterol as a sensitive diagnostic parameter in malaria].

In patients with malaria the lipid parameters triglycerides, cholesterol, and HDL-cholesterol were determined routinely. At the time of admission hypertriglyceridemia, hypocholesterolemia, and an extreme decrease in HDL-cholesterol were found. This dyslipoproteinemia was present in cases of falciparum malaria, as well as in cases of benign tertian malaria. The extent of HDL-cholesterol decrease showed no correlation to the severity of the clinical course of disease. HDL-cholesterol has proven to be an independent diagnostic laboratory finding in cases of suspected malarial infection. This parameter displays high diagnostic sensitivity, but no specificity for malaria.

Adult↗

Human platelet antigen gene frequencies in the Austrian population.

Gene frequencies for the human platelet antigen systems HPA-1, -2, -3, and -5 were determined directly from DNA isolated from cord blood of more than 900 randomly selected Caucasoid newborns in Vienna, Austria. Genotyping was performed by specific amplification of the respective regions coding for platelet glycoproteins GP Ib, IIb, IIIa, and Ia by PCR. These PCR products were analyzed after restriction enzyme digestion and electrophoresis. The observed gene frequencies were: HPA-1a: 0.852, HPA-1b: 0.148; HPA-2a: 0.918, HPA-2b: 0.082; HPA-3a: 0.612, HPA-3b: 0.388; HPA-5a: 0.892, HPA-5b: 0.108. There was a good fit with the Hardy-Weinberg equilibrium. Results from serological determinations and genotyping showed no discrepancies.

Antigens, Human Platelet↗