Diagnostic accuracy of procalcitonin and interleukin-6 values for predicting bacteremia and clinical sepsis in febrile neutropenic children with cancer.
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Adolescent↗
Biomedical subjects
S Hojker
Publications and source records attributed to S Hojker.
Thyroid autoantibody production is influenced by exon 1 and promoter CTLA-4 polymorphisms in patients with Hashimoto's thyroiditis.
Strong genetic susceptibility to thyroid autoantibody (TAb) diathesis has been shown and one of the major genes involved is probably CTLA-4 gene. Our recent study of patients with Graves' disease has demonstrated that exon 1 CTLA-4 gene polymorphism influences higher TAb production. Here, we evaluated the influence of exon 1 and promoter CTLA-4 polymorphisms on TAb production in 109 newly diagnosed patients with Hashimoto's thyroiditis (HT). Serum TSH, thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) were measured. 49 A/G and -318 C/T polymorphisms were detected using polymerase chain reaction amplification of genomic DNA and restriction fragment length polymorphism analysis. Patients with AG and GG genotype had significantly higher TPOAb median values compared to patients with AA genotype (P < 0.003). Similarly, TgAb median value was significantly higher in AG patients and in the entire G-allele carrying group (P < 0.02). Compared to both T-allele carrying genotypes, CC genotype presented with significantly higher TPOAb median value (P < 0.02), whereas TgAb median values did not differ significantly between various genotypes. In conclusion, our results indicate that G allele influences higher TPOAb and TgAb production, whereas C allele affects especially TPOAb production in patients with HT. Therefore, our findings provide further evidence that CTLA-4 is a major TAb susceptibility gene.
Adolescent↗
(99m)Tc-rituximab radiolabelled by photo-activation: a new non-Hodgkin's lymphoma imaging agent.
PURPOSE: Rituximab was the first chimeric monoclonal antibody to be approved for treatment of indolent B-cell non-Hodgkin's lymphoma (NHL). It is directed against the CD20 antigen, which is expressed by 95% of B-cell NHLs. The aim of this study was to explore the possibility of radiolabelling rituximab with (99m)Tc for use as an imaging agent in NHL for early detection, staging, remission assessment, monitoring for metastatic spread and tumour recurrence, and assessment of CD20 expression prior to (radio)immunotherapy. METHODS: Rituximab was purified from Mabthera solution (Roche), photo-activated at 302 nm by UV irradiation and radiolabelled with (99m)Tc. The effectiveness of the labelling method was evaluated by determination of the number of free thiol groups per photoreduced antibody, radiochemical purity and in vitro stability of (99m)Tc-rituximab. RESULTS: On average, 4.4 free thiol groups per photoreduced antibody were determined. Radiolabelling yields greater than 95% were routinely observed after storage of the photo-activated antibody at -80 degrees C for 195 days. The direct binding assay showed preserved ability of (99m)Tc-rituximab to bind to CD20, with an average immunoreactive fraction of 93.3%. The internalisation rate was proven to be low, with only 5.3% of bound (99m)Tc-rituximab being internalised over 4 h at 37 degrees C. CONCLUSION: Our results demonstrate that (99m)Tc-rituximab of high radiochemical purity and with preserved binding affinity for the antigen can be prepared by photoreduction and that the method shows good reproducibility. (99m)Tc-rituximab will be further explored as an imaging agent applicable in NHL for the purposes mentioned above.
Antibodies, Monoclonal↗
Methimazole upregulates T-cell-derived cytokines without improving the existing Th1/Th2 imbalance in Graves' disease.
There is probably a systemic shift of cytokine production in patients with Graves' disease (GD) toward the Th2 cytokine response. Methimazole (MMI) is the first choice for patients with GD and presumably has some direct immunomodulatory action. The aim of this study was to evaluate the balance shift in Th1/Th2 cytokines in patients with GD after 1 yr of MMI treatment, when compared to the same balance in patients with newly diagnosed GD before treatment and in healthy controls. Peripheral blood mononuclear cells (PBMC) were isolated from 17 healthy volunteers, from 18 patients with newly diagnosed GD before treatment and from 15 euthyroid patients with GD after 1 yr of MMI treatment. The PBMC were activated with ionomycin and phorbol 12-myristate 13-acetate (PMA). The concentrations of Th1/Th2 related cytokines [interferon (IFN)-gamma, interleukin (IL)-12 vs IL-4, IL-10] in the culture supernatants were measured by ELISA. PBMC from patients with GD after treatment produced significantly more IFN-gamma and IL-4 than PBMC from patients with GD before treatment, but there were no significant differences in calculated ratios of Th1 against Th2 cytokines between these two groups. When compared to PBMC from healthy controls, PBMC from patients with GD after treatment produced significantly more IL-4 and significantly less IL-12. The calculated IL-12/IL-4 ratio after treatment was significantly lower than the same ratio from healthy controls. In conclusion, our results show no significant change in the ratio between Th1 and Th2 cytokines produced by PBMC from patients with GD after 1 yr of MMI treatment, when compared to the ratio before treatment. The ongoing prevalence of the Th2 immune response after treatment speaks against the immunomodulatory action of the drug on the systemic level.
Antithyroid Agents↗
Early changes of thyroid hormone concentrations after (131)I therapy in Graves' patients pretreated or not with methimazole.
AIM: Despite extensive use of (131)I therapy for Graves' hyperthyroidism the treatment regimen with (131)I and antithyroid drugs remain under discussion. In our prospective clinical study we followed acute thyroid hormone changes after (131)I in patients not pretreated with methimazole (MMI) and in patients with different MMI pretreatment regimens. PATIENTS, METHODS: 187 patients were treated with fixed activity of 550 or 740 MBq of (131)I. First group (71 patients) received (131)I alone. In the second group (57 patients) MMI was stopped seven days before (131)I. The third group (59 patients) received MMI until (131)I application. Initial free triiodothyronin and free thyroxin were measured in the second group 7 and 2 days before (131)I therapy and in all three groups on the day of (131)I application as well as 2, 5, 12, and 30 days afterwards. Absorbed dose was measured in each patient. RESULTS: In the non-pretreated group (131)I application was followed by a significant decrease of fT4 in 5 days and of fT3 in 2 days, higher reduction was detected in patients with higher baseline values. In MMI pretreated patients significant but clinically irrelevant increase of both thyroid hormones was detected with maximum value 7 days after discontinuation in the second group and 5 days after discontinuation in the third group. Additionally, in patients of the third group absorbed dose of (131)I was significantly lower relative to other two groups. We found no correlation between absorbed dose of (131)I and thyroid hormone changes. CONCLUSION: Our study demonstrates that (131)I application alone does not result in exacerbation of hyperthyroidism and therefore it may be considered as safe. Additionally, MMI withdrawal causes significant but clinically irrelevant elevation of thyroid hormones.
Adolescent↗
Influence of lithium on cell function in two different cell systems.
Lithium is widely used in the treatment and prophylaxis of bipolar psychiatric disorders. It accumulates in the thyroid gland and can cause goitre or thyroid dysfunction. The mechanisms of various effects of the lithium ion on thyroid cells have not been completely clarified. The aim of our work was to establish whether lithium, in the presence or absence of TSH, stimulates the synthesis of cAMP; as model systems we used a strain of rat thyroid follicular cells FRTL-5 and a line of Chinese hamster ovary fibroblasts with the human TSH receptor (CHO-R). Lithium at concentrations of 0.35 mM, 1 mM, 1.4 mM, 1.7 mM and 2 mM without TSH and at selected concentrations with TSH stimulation significantly increased cAMP synthesis in FRTL-5 and in CHO-R cells when compared with controls without lithium. These results are different from the published data, which have been unable to confirm the influence of lithium on cAMP synthesis or have even reported the inhibition of cAMP synthesis. However, in most published investigations only lithium in combination with TSH was tested. In conclusion, lithium was found to stimulate cAMP synthesis in FRTL-5 cells and in CHO-R cells.
Animals↗
Influence of lithium on growth and viability of thyroid follicular cells.
Lithium accumulates in the thyroid gland and can cause goiter or thyroid dysfunction. The aims of our work were: 1) to verify whether lithium stimulates proliferation of thyroid cells; as methods, the 3H-thymidine incorporation assay and the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) were used; as a model system the FRTL-5 (Fischer rat thyroid cells in low serum) cell line was selected, 2) to test whether lithium can have a cytotoxic effect on FRTL-5 cells, using the cytotoxicity assay with 51Cr release and the trypan blue exclusion method. Without TSH stimulation, lithium at 0.35-2 mM concentrations significantly increased the 3H-thymidine incorporation. A similar effect was observed in the case of the MTT assay: without TSH stimulation, lithium at 0.4-2 mM concentrations showed a significant stimulation of proliferation. Surprisingly, under TSH stimulation, lithium at the 2 mM concentration significantly inhibited proliferation of FRTL-5 cells. With the cytotoxicity assay, lithium was found to increase 51Cr release at 1.4-2 mM concentrations. Additionaly, the percentage of viable FRTL-5 cells at 0.35-2 mM concentrations of lithium was lower than in the controls without lithium. In conclusion, lithium was found to stimulate proliferation of FRTL-5 cells in conditions without TSH and, surprisingly, lithium in higher concentrations diminished proliferation of FRTL-5 cells under TSH stimulation. A cytotoxic effect of higher lithium concentrations was observed.
Animals↗
Early change of thyroid hormone concentration after 131I treatment in patients with solitary toxic adenoma.
AIM: In spite of extensive use of 131I for treatment of hyperthyroidism, the results of early outcome are variable. In our prospective clinical study we tested whether 131I induced necrosis causing clinical aggravation of hyperthyroidism and increasing the free thyroid hormone concentration in the serum of patients with solitary toxic adenoma not pretreated with antithyroid drugs. PATIENTS AND METHODS: 30 consecutive patients were treated with 925 MBq 131I. Serum concentration of thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), thyroglobulin (Tg), and interleukin-6 (IL-6) were measured before and after application of 131I. RESULTS: After application of 131I no clinical worsening was observed. FT4 and fT3 concentration did not change significantly within the first five days, whereas both of them significantly decreased after 12 days (p < 0.0001). Slight and clinically irrelevant increase in the level of the two thyroid hormones was observed in 9 patients. Furthermore, we observed a prolonged increase in Tg concentration and a transient increase in IL-6 concentration. CONCLUSION: Neither evidence of any clinical aggravation of hyperthyroidism nor any significant increase in thyroid hormone concentration by 131I induced necrosis of thyroid cells was found. Therefore, the application of 131I may be considered as a safe and effective treatment for patients with hyperthyroidism due to toxic adenoma.
Adenoma↗
Predictive value of serum and cerebrospinal fluid procalcitonin levels for the diagnosis of bacterial meningitis.
BACKGROUND: The value of serum and cerebrospinaL fluid (CSF) procalcitonin for differentiating between acute bacterial and viral meningitis was assessed and compared to other parameters which are usually used in clinical practice. PATIENTS: 45 adult patients (20 with bacterial and 25 with tick-borne encephalitis, TBE) were included in this prospective study. RESULTS: The median serum procalcitonin Level in patients with bacterial meningitis was 6.45 ng/ml (range 0.25-43.76 ng/ml) and in the group with viral meningitis 0.27 ng/ml (range 0.05-0.44 ng/ml). 11 patients with bacterial meningitis had an elevated procalcitonin concentration not only in serum, but also in CSF. A serum procalcitonin Level > 0.5 ng/ml had a positive predictive value for bacterial meningitis of 100% and a negative predictive value of 93%, while corresponding values for CSF procalcitonin were 100% and 74%, respectively. CONCLUSION: Serum and CSF procalcitonin concentrations > 0.5 ng/ml appear to be a reliable indicator of bacterial central nervous system (CNS) infection, with maximal positive predictive values and high negative predictive values.
Adolescent↗
Echo-enhanced ultrasound voiding cystography in children: a new approach.
The development of echo-enhancing agents has significantly improved the detection of the movement of fluid within the urinary tract by ultrasonography (US). The purpose of our study was to compare ultrasound voiding cystography (USVC) for the detection of vesicoureteric reflux (VUR) in children with direct radionuclide voiding cystography (DRVC). Ninety-nine children, aged 1.1-12.3 years, with 198 potentially refluxing units, were investigated simultaneously by DRVC and USVC. The indications for cystography were urinary tract infection, follow-up of a previously detected VUR, and screening of siblings of children with VUR. During the investigation an echo-enhancing agent (Levovist) was administered intravesically through a catheter already in place for the DRVC. The movement of both agents, radiotracer and Levovist, was registered simultaneously by a computerized gamma camera and US, respectively. The results were analyzed with DRVC representing the reference diagnostic test. The overall sensitivity and specificity of USVC for the detection of VUR were 79% and 92%, respectively. USVC may represent a reliable diagnostic tool for the detection and follow-up of VUR in children.
Child↗
Interleukin-8 and procalcitonin in early diagnosis of early severe bacterial infection in critically ill neonates.
We studied the value of serum interleukin-8 (IL-8) and procalcitonin (PCT) in the early diagnosis of early severe bacterial infection in 58 critically ill ventilated neonates. ELISA was used for determining IL-8 and immunoluminometric assay for PCT. IL-8 and PCT were compared with routinely used serum C-reactive protein (CRP). Neonates were divided into four groups: Ia--proven severe bacterial infection (n = 9), Ib--clinical sepsis (n = 16), II--respiratory distress without bacterial infection (n = 12), and III--various types of neonatal distress (n = 21). Sera were collected on admission, at 24 h and 48 h after admission. There was no significant difference between groups Ia and Ib for either parameter at any time interval. Significant difference was found between group Ia+b (septic neonates) and group II for PCT and CRP at 24 and 48 h, but not for IL-8. There was no difference between group Ia+b and group III except for CRP at 24 h. Diagnostic accuracy was best for PCT on admission and for CRP at 24 h. Serum PCT and IL-8 are not specific markers for early severe bacterial infection in critically ill neonates and are not better than CRP.
Bacterial Infections↗
Changes in Th1/Th2 cytokine balance in Graves' disease.
Graves' disease (GD) is characterised by hyperthyroidism, caused by stimulatory thyrotropin receptor (TSHR) antibodies. Recent research shows that an important factor in the pathogenesis of autoimmune diseases is the change in the balance between Th1 cytokines, which promote cell mediated immunity, and Th2 cytokines, which promote humoral immunity. There are contradictory data about this balance shift in GD. Our objective was to determine the Th1/Th2 cytokine balance shift in patients with newly diagnosed GD, when compared to the same balance in healthy controls. We isolated mononuclear cells (MNC) from the peripheral blood of healthy donors and from patients with newly diagnosed GD before treatment. The MNC were activated with ionomycin in combination with phorbol 12-myristate 13-acetate (PMA). After 40-hour incubation, the concentrations of the cytokines produced (IFN-gamma, IL-4, IL-10, IL-12) in the culture supernatants were measured by ELISA (Endogen, USA). The MNC cultures from patients with GD produced significantly less IL-12 and significantly more IL-10 and IL-4 than MNC cultures from healthy controls. All calculated ratios of Th1 against Th2 cytokines in MNC cultures from patients with GD were significantly lower than in MNC cultures from healthy controls. Our results show a systemic shift of cytokine production in patients with GD toward the Th2 cytokine response, thus confirming the key role of TSHR antibodies and humoral immunity in the pathogenesis of GD.
Cells, Cultured↗
Prevalence of autoimmune thyroid disease (AITD) in patients with mixed connective tissue disease (MCTD)
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Adult↗
Rapid radiochemical neutron activation analysis for iodine in urine by different separation techniques.
In the present work on radiochemical neutron activation analysis for the determination of iodine in urine samples, the performance of three different radiochemical separation techniques, namely, direct extraction, use of an iodinated ion-exchange resin column and Schöniger combustion, were intercompared and validated. The practical advantages of the iodinated-resin technique make it most suitable for the rapid routine determination of iodine in urine. It was further verified by participation in an international intercomparison run of urine analysis, and used in a pilot study on iodine determination in the urine of 171 Slovenian schoolchildren, where it gave results in good agreement with the catalytic method.
Child↗
Mixed connective tissue disease associated with autoimmune hepatitis and thyroiditis.
The case is reported of a 27 year old woman who had mixed connective tissue disease (MCTD) associated with chronic active hepatitis and thyroiditis. Although hepatomegaly is sometimes observed in MCTD, only four cases of MCTD and chronic active hepatitis have been described. It is thought that this is the first report of an association between MCTD, chronic active hepatitis and thyroiditis.
Adult↗
Development of non-symmetric two-dimensional filtering in Fourier transform space.
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Algorithms↗