Strong genetic contribution has been demonstrated to influence the development of autoimmune thyroid disease (AITD) as well as thyroid autoantibody production. In order to assess the relation between ...CT60 cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism and thyroid autoantibody production, we investigated 180 consecutive newly diagnosed patients with two forms of AITD, 105 with Hashimoto's thyroiditis (HT) and 75 with postpartum thyroiditis (PPT). We evaluated thyroid function, measured antibodies against thyroid peroxidase (TPO) and thyroglobulin (Tg), and determined CT60 CTLA-4 gene polymorphism. In HT, TPO antibody median value was significantly lower in the AA compared to the AG and GG genotypes (65, 122 and 319 U/ml, P < 0·005), while the Tg antibody median value was lower in the AA compared to the AG genotype (91 and 189 U/ml, P < 0·02). In PPT, the frequency of thyroid autoantibody-positive patients was higher among G-allele-carrying genotypes (P < 0·04). Similar to HT, the TPO antibody median value was lower in the AA compared to the AG and GG genotypes (12, 130 and 423 U/ml, P < 0·006). Hypothyroid PPT patients were more often thyroid autoantibody-positive (P < 0·005) and the TPO antibody median value was higher compared to hyperthyroid PPT patients (500 and 32 U/ml, P < 0·0001). The frequency of the G-allele was significantly higher among hypothyroid patients (P < 0·05). Our data suggest that in both HT and PPT, the CT60 CTLA-4 gene polymorphism contributes importantly to thyroid autoantibody production. In PPT, the genotype also seems to influence thyroid function, as patients with the polymorphous allele are more prone to develop hypothyroid form of PPT.
Summary
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.
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.
45 adult patients (20 with bacterial and 25 with tick-borne encephalitis, TBE) were included in this prospective study.
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.
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.
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.
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.
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.
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.
Objective: Complete allograft denervation occurs during heart transplantation. Partial ventricular sympathetic reinnervation may develop one year or later after transplantation and can be measured ...with iodine-123-meta-iodobenziylguanidine (MIBG) uptake. Aim of this study was to assess sinus node sympathetic reinnervation measured with heart rate variability and ventricular sympathetic reinnervation evaluated with MIBG. Methods: Twelve patients and 14 healthy controls were included. In patients, MIBG scintigraphy with early and late imaging was performed. Heart to mediastinum ratio (HMR) was calculated and patients were divided in groups with (HMR≫1.3) and without left ventricular reinnervation (HMR≪1.3). Bipolar ECG with high sampling rate and resolution was recorded over 8.5min in supine position and in upright position after 10min interval. R–R intervals in time domain and heart rate variability in frequency domain through spectral power analysis of R–R intervals were analysed to evaluate sinus node reinnervation. Spectral power in low frequency range (0.04–0.15Hz) above 4.5ms2 was considered as sinus node sympathetic reinnervation. Results: Six (50%) patients had evidence of left ventricular sympathetic reinnervation on scintigraphy. Sinus node sympathetic reinnervation based on heart rate variability was detected in 6 (50%) patients in supine, and in 4 (33%) patients in upright body position. Four patients groups were discerned: (1) with ventricular and sinus node sympathetic reinnervation, (2) with sinus node sympathetic reinnervation, (3) with ventricular sympathetic reinnervation and (4) without atrial or ventricular sympathetic reinnervation. Ventricular reinnervation process was time dependent and sinus node reinnervation was not. Conclusions: Simultaneous ventricular sympathetic reinnervation assessed by MIBG and sinus node sympathetic reinnervation assessed by heart rate variability in supine as in upright position were detected only in two patients (17%). The results of our study show that eventual sinus node sympathetic reinnervation and left ventricular sympathetic reinnervation do not occur simultaneously.
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.
The aim of the study was to evaluate the diagnostic accuracy of interleukin-6 (IL-6) and lipopolysaccharide-binding protein (LBP) in children with acute appendicitis (AA) and to compare this with the ...diagnostic accuracy of routinely used C-reactive protein (CRP) and white blood cell (WBC) count. Eighty-two consecutive children admitted to our Department because of suspected AA were enrolled in this prospective study and classified into two groups: group 1 (49 children who underwent surgery for AA) and group 2 (33 children with no surgery with diagnosis of non-specific abdominal pain or sonographic mesenteric lymphadenitis). There were no negative appendectomies during the time of the study. The patients were further classified into three subgroups: subgroup 1A (43 patients with advanced AA), subgroup 2A (11 patients with mesenteric lymphadenitis) and subgroup 2B (10 patients with non-specific abdominal pain). The perforation rate was 32.7 %. WBC count and serum CRP, IL-6 and LBP were measured on admission. Area under receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity and predictive values were evaluated. Serum IL-6 and LBP were significantly higher in group 1 than in group 2. The highest AUC for AA was that for IL-6 (0.776), followed by WBC count (0.684), CRP (0.637) and LBP (0.635). In conclusion, only IL-6, determined on admission, showed medium diagnostic accuracy, while other laboratory markers showed low diagnostic accuracy for AA in children. The new laboratory markers therefore do not significantly improve the diagnosis of AA.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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. 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. 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. 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.
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.
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