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  • Author: Todor Gruev x
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The Diagnostic Value of Anti-Cyclic Citrullinated Peptide Antibodies (anti-CCP) in Patients with Rheumatoid Arthritis

A cross-sectional study was carried out to analyze the prevalence of anti-CCP antibodies and IgM RF in the sera of 160 randomly selected patients from the Rheumatology Department: 60 with RA, 50 with other rheumatic diseases (non-RA), 50 healthy controls (HC). The mean age of the group was 50.06+/-11.9 years. There were 141 females (88.1%) and 19 males (11.9%). RA patients fulfilled the revised ACR criteria. The mean duration of the disease was 82.4 months. Anti-CCP ELISA kit and IgM RF Latex test were used. The mean anti-CCP values were as follows: RA 60.4+/-57.6, non-RA 2.1+/-3.6, HC 1.3 +/-0.4 U/mL. Respectively, the mean values of IgM RF were: RA 515.8+/-525, non-RA 102+/-294, HC 15+/-57.5. Forty out of 60 (66.6%) RA patients were anti-CCP positive. Forty one out of 60 (68.3%) RA patients were positive for IgM RF. As expected, anti-CCP showed comparable sensitivity (66.8% vs. 68.3%) and higher specificity (98% vs. 87%) than IgM RF, at optimal cut-off values. The presence of either anti-CCP or IgM RF increased the testing sensitivity for the diagnosis of RA to 76.6%. AUC was greater for anti-CCP than for IgM RF (0.92 vs. 0.82).

The Diagnostic Value of the Second Generation Anti-CCP Test in Rheumatoid Arthritis

The purpose of this research was to compare the diagnostic values of laboratory variables, to present quantitative evaluations of the diagnostic test with reference to sensitivity, and specificity, the predictive value of the positive and negative test and precision of the test for anti-cyclic citrullinated peptide (anti-CCP 2) antibodies, rheumatoid factor (RF), C-reactive protein (CRP), DAS 28 index, in early diagnosis of untreated rheumatoid arthritis (RA). Using the ELISA technology of DIA-STAT Anti-CCP (Axis-Shield Diagnostics), the serum has been examined in 70 participants (35 RA who were not treated, 35 healthy controls). RF was defined with the test for agglutination (Latex RF test) in the same participants. In 23 of the 35 examined patients with RA, we found presence of anti-CCP 2 antibodies (sensitivity of the test 65.71%), while RF appeared in 17 patients (sensitivity of the test 48.57%). Twelve patients were anti-CCP 2 and RF positive, 11 were anti-CCP 2 positive but RF negative. Five patients were anti-CCP 2 negative and RF positive. Out of 18 RF negative patients, 11 were anti-CCP 2 positive. In 17 RF positive patients, anti-CCP 2 antibodies were positive in 12 patients. In the healthy control group, 1 patient was anti-CCP 2 positive, while 2 patients were RF positive. Anti-CCP 2 antibodies have higher sensitivity and specificity than RF in RA.

Effects of Glucocorticoid Immunosuppression on Serum Cystatin C Levels

The aim of the present study is to describe the influence of glucocorticoid immunosuppression on serum cystatin C concentration in renal transplant patients. To evaluate the influence of immunosuppressive regimens, especially glucocorticoids, on serum cystatin C level, 38 clinically stable patients on immunosuppression therapy with low-dose glucocorticoids were compared to 30 clinically stable patients receiving cyclosporin A alone, and 18 clinically stable patients receiving cyclosporin A together with azathioprine. Clinical stability was defined as the absence of acute rejection, febrile infection, and cyclosporin A toxicity, as well as stability of creatinine clearance as estimated by the formula of Cockroft and Gault. All groups were compared for estimated creatinine clearance (CrCl) values and had comparable gender, age and time since transplantation. The group receiving short-course, high-dose methylprednisolone was analyzed at four time points: a) before methylprednisolone commencement (median, 15 days); b) the day methylprednisolone was introduced (before medication); c) after 3 days of methylprednisolone therapy; and d) on a follow-up 9-10 days after the last dose. Intravenous administration of high-dose methylprednisolone led to significant differences in cystatin C levels at different time points (before administration, after three doses, and 8 days after discontinuation). Glucocorticoid medication in adult renal transplant patients is associated in a dose-de pendent manner with increased cystatin C, leading to systematic under estimation of GFR. Moreover, our data illustrate the need for specific reference intervals in patients on glucocorticoid therapy. In clinical routine settings, as well as in future clinical studies, it is important to take glucocorticoid medication into account when interpreting serum cystatin C concentrations in renal transplant patients presumably, as well as in other patient groups.

Association Between Osteoarticular Scores and Acute Phase Reactant Levels in Rheumatoid Arthritis

The aim of this prospective control study was a quantitative evaluation of the activity of rheumatoid arthritis (RA) in certain time intervals, using articular indexes (set of 28 sensitive and 28 swollen joints), laboratory parameters (Hb, Hct, Er, Le and Plt) and acute phase reactants (ESR, RF, CRP); to determine which of the acute phase reactants is the most useful biochemical marker for the evaluation of disease activity in RA; to quantify the therapeutical and laboratory differences in certain time intervals in the group with and without immunomodulatory therapy with Methotrexate. Sixty patients with RA were included, 27 of who were treated with non-steroid antiinflammatory drugs (NSAIDs) and Methotrexate (MTX). The control group consisted of 33 patients treated only with NSAIDs because of irregular controls. In the first group of patients the disease activity was estimated at four time intervals, and in the control group of patients at three time intervals following the scores of the articular indexes, blood cell counts, ESR and CRP in every patient. In the first group of patients decreased activity of RA was found upon every following control with a consecutive decrease in mean values of the scores of articular indexes with statistically significant differences at the four time intervals. Considering laboratory parameters, there were statistically significant differences in the mean values of Hb, Er, Plt, ESR, (p=0.0462, p=0.0076, p= 0.0058, p= 0.0003). Mean values of CRP did not show statistically significant differences, but the number of patients who were CRP negative increased (there were great standard deviations). In the group of patients treated only with NSAIDs, there were statistically significant differences in the mean values of the scores of articular indexes with an increse at every following control (in favour of progression of the disease). There were no statistically significant differences considering blood cell counts, ESR and CRP (in favour of permanently active disease). In conclusion, CRP is the most useful marker for the prospective follow-up of patients with RA.

Sarcoidosis of the Thyroid Gland and Concomitant Hürthle Cell Adenoma: Case Report

Sarcoidosis is a multisystem disorder, characterized by the presence of noncaseating epithelioid-cell granulomas. The etiology remains unclear, although it is recognized as a disease of activated T lymphocytes. There is a diverse range of possible presentations with respiratory, gastrointestinal, reproductive, endocrine and other complications. The thyroid is an uncommon site of the disease with only 4% incidence according to some autopsy series. We present a case of a 55-year-old female patient with sarcoidosis of the thyroid gland and concomitant Hürthle cell adenoma. Upon performing a routine thyroid scintigraphy, a cold nodule has been observed. The diagnosis of the underlying disease was established by correlating the anamnesis data, patient's clinical history, fine needle aspiration biopsy and pathological examination of the thyroidectomy specimen. To our knowledge, the association has rarely been previously reported, indicating that thyroid involvement should be suspected in sarcoidosis patients who present with cold nodules.

Bone Turnover Markers Relations to Postmenopausal Osteoporosis

Osteoporosis is a systemic disease characterized by low bone mass and high bone turnover markers in postmenopausal women (PM). The relationship between biochemical bone markers C-telopeptides of type 1 collagen (CTX) and osteocalcin (OC), and bone mineral density (BMD) in the postmenopausal period was examined in 104 PM women divided into three groups according to their BMD: group A - control PM with normal bone density, group B - osteopenic PM and group C - osteoporotic PM. Mean CTX values were highest in group C (0.54±0.24 ng/mL) compared to group B (0.44±0.21 ng/mL) (p<0.0001), and group A (0.33±0.13 ng/mL) (p<0.029). Mean OC levels in group C (26.83±9.91 ng/mL) were significantly higher compared to group A (20.47±7.03 ng/mL) (p<0.011) but not significantly higher compared to group B (24.11±8.38 ng/mL) (p>0.05). Postmenopause duration was longest in group C (13.1±8.31 yrs) compared to group B (9.6±6.24 yrs), and group A (8.15±6.86 yrs). Postmenopausal women developed osteoporosis with longer menopause duration. PM osteoporotic women were characterized by increased levels of bone turnover markers indicating increased rate of bone remodeling, which resulted in excessive bone resorption, and loss of bone mass. Long-term persistence of high bone resorption marker CTX, insufficiently compensated with bone formation marker OC, enabled osteoporosis development.

Impact of Thyroid Dysfunction on Serum Cystatin C, Serum Creatinine and Glomerular Filtration Rate

Aim. The aim of this cross-sectional, prospective, randomized, longitudinal study was to asses serum cystatin C (Cys C) and creatinine concentrations and glomerular filtration rate (GFR) in thyroid dysfunction.

Material and Methods. We have measured Cys C, creatinine and GFR using the 99mTc-DTPA technique in 35 patients (26 females and 9 males; 43 ± 11 years), 15 with newly diagnosed hyperthyroidism (TSH < 0.07 mIU/L, fT4 > 24 pmol/L) and 20 with newly diagnosed hypothyroidism (TSH > 4.5 mIU/L, fT4 < 9 pmol/L), at baseline and when they became euthyroid (TSH 0.4-4.5 mIU/L, fT4 9-24 pmol/L). The patients had no history of kidney disease and were subdivided into 2 groups: age (>50 and <50 years) and fT4 (40-100 pmol/L; >100 pmol/L) - hyperthyroid and TSH (4.5 - 48 mIU/L; > 48 mIU/L) - hypothyroid group. Thirty five age- and sex-matched normal subjects served as controls.

Results. Increased creatinine levels in hypothyroid patients 115 ± 12 μmol/L decreased after treatment to 95 ± 14 μmol/L and reduced values in hyperthyroid patients 53.6 ± 12 μmol/L increased after treatement to 75.2 ± 14 μmol/L (p<0.05). Cys C ranged from 0.88 ± 0.7 mg/L before to 1.24 ± 0.5 mg/L after treatment in hypothyroid and 1.65 ± 0.5 mg/L before to 0.96 ± 0.5 mg/L after treatment in hyperthyroid patients (p<0.01). Hyperthyroid subjects exhibited significant increase in GFR ranging from 144.1 ± 18 mL/min before to 123.7 ± 24 mL/min after treatment. Hypothyroid group exhibited significant decrease in GFR ranging from 81.1 ± 28 mL/min before to 103.7 ± 24 mL/min after treatment (p<0.01). The significant difference between GFR values assessed by the isotope technique and values assessed by the serum markers indicates that further work needs to be performed to confirm which method is giving the true reflection of GFR in thyroid dysfunction.

Alanine Aminopeptidase, γ-Glutamyl Transferase and β2-microglobulin as Diagnostic Markers in Patients with Rheumatoid Arthritis

The purpose of this research is to evaluate the values of alanine aminopeptidase (AAP), γ-glutamyl transferase (γ-GT), and β2-Microglobulin in urine (β2-M), in untreated rheumatoid arthritis (RA) and to define the effect of untreated rheumatoid arthritis on the tubular function and brush border region. We used a kinetic assay for AAP, standard methods by the IFCC for γ-glutamyl transferase and MEIA for the determination of β2-Microglobulin in urine in 70 participants (35 untreated RA patients, 35 healthy individuals). From the total of 35 RA patients, 24 patients had AAP (sensitivity of the test 68.57%), 16 patients had γ-GT enzymuria (sensitivity of the test 45.71%), while the presence of β2-Microglobulin in urine was found in a very low percentage. Out of 18 RF negative patients, 14 patients are AAP positive, 10 patients were γ-GT positive, while the presence of β2-Microglobulin in urine was not detected. Among 17 RF positive RA patients, the presence of AAP was noticed in 10, the presence of γ-GT in 6 patients, while the presence of β2-Microglobulin in urine was not detected. AAP has higher sensitivity than γ-GT and β2-Microglobulin in the detection of asymptomatic renal lesions in untreated RA.

Association Between Sharp's Radiographic Index and Acute Phase Reactants in Rheumatoid Arthritis

The aim of this study was to evaluate the activity of rheumatoid arthritis (RA) by hand radiography (Sharp's radiographic index), and assessment of acute phase reactants - erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF), and to determine their value as prognostic markers for disease outcome in patients with early RA treated with disease modifying antirheumatic drugs (DMARDs)-Methotrexate (MTH); to register and quantify clinical, radiographic and laboratorial differences in certain time intervals in a group of patients treated with immunomodulation therapy with MTH; to determine which of the acute phase reactants would be the most useful marker for evaluation of disease activity in long-term follow-up in RA patients; to select high-risk groups with aggressive course of disease, in order to emphasize the necessity of early and aggressive treatment. Thirty patients with early RA (disease evolution up to 1 year) were evaluated in several time intervals. The score of the Sharp's index showed greater radiographic progression of the joint damage of hands in time intervals between 0-time and 12 months (p=0.0167) and between 0-time and 18 months (p=0.0089). Statistical analysis showed differences in values of CRP in four time intervals (p=0.00002). Considering CRP, there were statistically significant differences among mean values in four time intervals (p=0.0428) (standard deviations showed greater variations). There were no statistically significant differences among mean values of RF in four time intervals (p=0.573). At 0-time in 3 (10%) patients progression of the Sharp's index was found, after 6 months in 13 (39%) patients, while after 12 and 18 months progression of the Sharp's index was found in an identical number of patients, 15 (50%). In most patients high values of CRP and RF were found. Progression of the radiographic damage is especially expressed in patients with high values of ESR, CRP, RF and existence of previous erosions of hands, which are predictors for aggressive course of disease. CRP is the most useful marker for the evaluation of RA activity in the long-term followup of RA patients.

The Diagnostic Value of N-Acetyl-β-D-Glucosaminidase and Microalbumin Concentrations in Rheumatoid Arthritis

The purpose of this research was to compare the diagnostic values of laboratory variables, to present quantitative evaluations of the diagnostic sifted test with reference to sensitivity and specificity, the predictive value of the positive and negative test and precision of the test for N-acetyl-β-D-glucosa-minidase (NAG), microalbumin, rheumatoid factor (RF), Creactive protein (CRP), DAS 28 index, in early diagnosis of untreated rheumatoid arthritis (RA), and to define the effect of untreated rheumatoid arthritis on glomerular and tubular function. Using a colorimetric assay for the determination of Nacetyl-β-D-glucosaminidase and an immunoturbidimetric assay for the determination of urinary albumin, the samples of serum and urine have been examined in 70 participants (35 RA who were not treated, 35 healthy controls). RF was defined with the test for agglutination (Latex RF test) in the same participants. Out of 35 examined patients with RA, in 13 we found the presence of NAG enzymuria (sensitivity of the test 37.14%), while microalbuminuria appeared in 4 patients (sensitivity of the test 11.42%). RF appeared in 17 patients (sensitivity of the test 48.57%). Four patients were NAG and RF positive, while 3 patients were microalbuminuria and RF positive. Among 18 RF negative patients, 9 patients were NAG positive, and 1 patient presented with microalbuminuria. Among 17 RF positive RA, the presence of NAG was found in 4 patients, and the presence of microalbuminuria in 3 patients. Among 18 RF negative RA, NAG enzymuria appeared in 9 patients. Microalbuminuria was present in 1 patient. In the healthy control group, 8 patients were NAG positive, 2 patients were positive for microalbuminuria. RF appeared in 2 patients. NAG has higher sensitivity than microalbuminuria in the detection of asymptomatic renal lesions in untreated RA.