Diagnostic value of brush border enzymes of the proximal renal tubules in rheumatoid arthritis.

BACKGROUND: Proximal tubules of the kidney have a dominant function in the excretion of different enzymes in the urine. These enzymes can be used as markers for secondary renal damage under the action of different diseases, medicines, and toxins. The aim of this study was to evaluate the values of alanine aminopeptidase (AAP), gamma-glutamyl transferase (gamma-GT), and beta2 microglobulin (beta2m) in urine of patients with untreated rheumatoid arthritis (RA) and to define the possible association between untreated rheumatoid arthritis and tubular function at the brush border region. METHODS: We used a kinetic assay for AAP, standard methods by the International Federation for Clinical Chemistry (IFCC) for gamma-GT and Microparticle Enzyme Immunoassay (MEIA), (Abbott A(x)SYM System) for the determination of beta2m in urine of 70 participants (35 untreated RA patients and 35 healthy volunteers (HC)). RESULTS: From the total of 35 RA patients, AAP enzymuria was found in 24 patients with test sensitivity (68.57%), gamma-GT in 16 patients with test sensitivity (45.71%), while the presence of urinary beta2m was found in a very low percentage of cases. Out of 18 rheumatoid factor (RF) negative patients, 14 patients were AAP and 10 patients were gamma-GT positive, while the presence of beta2m in urine was not detected. Among 17 RF positive RA patients, the presence of AAP and gamma-GT was noticed in 10 and 6 patients, respectively, while the presence of beta2m in urine was not detected. CONCLUSIONS: In conclusion, AAP had a higher sensitivity than gamma-GT and beta2m in detection of asymptomatic renal lesions in untreated RA.

New DXA Diagnostic Indexes of Abdominal Obesity.

Aim: Cushing's syndrome (CS) is associated with weight gain and extreme central, visceral, abdominal obesity which is confirmed with dual-energy X-rays absorptiometric (DXA) diagnostic cut-off point (CP) values of central obesity indexes (COI), determined as an android to gynoid tissue and fat mass ratios. These best differentiate CS from non-CS obese women matched with CS according to their age and BMI. The aim of this study was to determine the CP values of new DXA indexes of central, abdominal obesity as a ratio of android and trunk to legs as well as trunk and legs to total tissue and fat mass that best differentiate CS and matched non-CS obese women in order to confirm central abdominal obesity, and to determine their normal CP values that best differentiate healthy non-obese women from CS and non-CS obese women, and to exclude abdominal obesity completely. Material and Methods: DXA indexes of abdominal obesity, calculated as а ratio of regional body fat and tissue mass compartments android to legs (A/L), trunk to legs (Tr/L), trunk to total (Tr/To) and legs to total (L/To) values were determined among 4 groups. Each group consisted of 18 women: 1st group of CS, 2nd group of obese women (O1) not different according to their age and BMI from CS, 3rd group of obese women (O2) with higher BMI of 35 ± 1.2 kg and a 4th group of non-obese, healthy women (C) with a normal BMI. Diagnostic accuracy (DG) of CP values of DXA indexes of abdominal obesity and indexes of normal body fat distribution (BFD) were determined. Results: A/L, Tr/L, Tr/To, and L/To DXA indexes were significantly different between CS and O1 as well as between non-CS women O2 compared to O1 and C. These indexes had a highly significant correlation among each other and also in relation to their BMI (p < 0.0001). A/L-Tm CP value of 0.3 best differentiated the CS from group O1, with the highest DG of 100 % and an A/L-Fm CP value of 0.26 differentiated them with a DG of 94.44% and sensitivity of 100 %. An A/L-Tn CP value of 0.23 and an A/L-Fn CP value of 0.25 best differentiated CS and C as well as O2 and C for the highest DG of 100 %. Conclusions: DXA indexes A/L, Tr/L, Tr/To and L/To values were significantly different among the four groups. These values correlated significantly among them and with their BMI in non-CS groups, thus confirming a BMI increase association with a more pronounced abdominal BFD. An A/L-Tm CP value of 0.3 and an A/L-Fm CP value of 0.26 were discovered as the best DXA diagnostic indexes of extreme abdominal obesity in CS and these could also be used in discovering abdominal BFD in non-CS obese women with metabolic syndrome (MS). An A/L-Tn CP value of 0.23 and an A/L-Fn CP value of 0.25 were discovered as the best DXA diagnostic indexes of normal BFD which completely excluded abdominal obesity.

Influence of Prognostic Factors on OverallSurvival in Myelodysplastic Syndromes.

BACKGROUND: Accurate prediction of a patient's prognosis is useful to define the risk posed by the disease. Age, gender, peripheral blood cytopenia, proportion of bone marrow (BM) blasts, performance status, comorbidities, transfusion dependence, specific karyotype abnormalities and molecular biomarkers can refine the prediction of prognosis in MDS. AIM: to assess the influence of the some prognostic factors like age, gender, cytopenia, BM blast percentage, transfusion dependence, ferritin, hemoglobin (Hb), lactate dehydrogenase (LDH), albumin and specific karyotype abnormalities in myelodysplastic syndromes on overall survival (OS). PATIENTS AND METHODS: we retrospectively analyzed the cohort of 108 patients diagnosed between 1.1.2011 and 31.12.2013 at the University Clinic of Hematology, Ss Cyril and Methodius University, Skopje, Macedonia. They were evaluated for clinical and hematologic features at diagnosis and at leukemic transformation. RESULTS: in the study group 62 were man and 46 women. Male to female ratio was 1.35 to 1. The differences in OS between men and women were significant (p = .03015). The mean age at diagnosis was 66,6 years. According to the age OS was 16,4 months. FAB subtypes influenced OS significantly (p = .03015). OS inversely correlated with BM blast percentage (p= .02327). Cytopenia had no impact on OS (p=.33755). Hb as a whole and groups with different levels of Hb had no influence on OS (p = .12142) and (p= .07535), respectively. The group with ferritin <500 µg/L had better OS (p=.04720). Transfusion dependence, LDH and albumin had no impact on OS. Leukemic transformation was noticed in 10 (9,3%) patients. Mortality was 36,1%. CONCLUSION: gender, FAB subtypes, BM blast percentage and the serum levels of ferritin had an influence on OS, while age, hemoglobin level, transfusion dependence, LDH and albumin had no impact on OS.

Symmetric dimethyl arginine and N-acetyl-ß-D-glucosaminidase lysozimuria of proximal renal tubules as a target for nephrotoxicity in patients with rheumatoid arthritis treated with disease modifying antirheumatic drugs.

BACKGROUND: The aim of this study was to determine the effect of initial therapy with some disease modifying antirheumatic drugs (DMARDs) (Methotrexate and Ketoprofen) on glomerular and tubular integrity in patients with Rheumatoid arthritis (RA). OBJECTIVES: To determine whether there is a change in clinical and laboratory indicators of renal function in course of the follow up of treatment and whether that change correlates with the dynamics of the quantity of enzymes excreted in urine and reactants of the acute phase. MATERIALS AND METHODS: Using colorimetric method for determination of NAG, samples of 70 participants were examined (35 RA patients treated with Ketoprofen only, 35 RA patients treated with combined use of Methotrexate and Ketoprofen). The follow up was 5 time-intervals in the course of 24 weeks. RESULTS: There was moderate correlation between NAG and microalbuminuria (r=0,34) in the group of patients treated with Ketoprofen only, while statistically significant correlation (r=0,21) was seen in group of patients with combined use of Methotrexate and Ketoprofen. NAG enzymuria in size, number of patients registered, and time of appearance were greater and appears earlier in the group with the combined use of Methotrexate and Ketoprofen compared with the mono-therapy with Ketoprofen. Mean urinary NAG induction was increasing with the concomitant use of Methotrexate and Ketoprofen. CONCLUSIONS: Methotrexate is more potent NAG inductor than Ketoprofen and provokes greater tubular enzymuria than Ketoprofen.

Determination of the diagnostic values of asymmetric dimethylarginine as an indicator for evaluation of the endothelial dysfunction in patients with rheumatoid arthritis.

Introduction. To compare the diagnostic values of laboratory variables, to present evaluations of the diagnostic test for asymmetric dimethyl arginine (ADMA), rheumatoid factor (RF), C-reactive protein (CRP), and DAS28 index, and to define the effect of untreated rheumatoid arthritis on endothelial function. In order to determine whether ADMA changes depending on the disease evolution, ADMA was used as an indicator for endothelial dysfunction. Methods. Using an ELISA technology of DLD-Diagnostika-GMBH for the detection of ADMA, 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. Results. Out of 35 examined patients with RA, RF appeared in 17 patients (sensitivity of the test, 51.42%). In 20 of the 35 examined patients with RA, we found the presence of ADMA (sensitivity of the test, 57.14%). Anti-CCP antibody was present in 24 examined patients with RA (sensitivity of the test, 68.57%). Conclusion. ADMA has equal or very similar sensitivity and specificity to RF in untreated RA (sensitivity of 57.14% versus 48.57%, specificity of 88.57% versus 91.42%) in the detection of asymptomatic endothelial dysfunction in untreated RA.

Hairy cell leukemia treatment: where we are now?

Hairy cell leukemia (HCL) is a very rare type of leukemia, in which abnormal B lymphocytes, present in the bone marrow, spleen, and peripheral blood stream, get worse slowly or do not get worse at all. HCL is the disease where patients have pancytopenia with splenomegalia over 90% percent, palpable lymphadenopathy occur in 35% of patients, some form of serious infection eventually developed in over 50% of patients and was the most common cause of death in patients. HCL is dominantly a male disease, with the male-female ratio, ranging from 4:1 to 7:1. Treatment and prognosis of HCL depends on: the number of HC in the peripheral blood or bone marrow, if the spleen is enlarged and on the existence of the visible leukemia infection symptoms. Prognostic factors are similar to the above mentioned and also if the basic disease HCL is aggressive or the number of HC grow slowly and there is no need for treatment. Starting from September 1985 till September 2010, we observed a group with total number of 28 patients (22 males and 6 females) at the age of 30-76 (median range 46 years), all with HCL disease. From the total number of participants, 20 patients (71,43%) received hemotherapy, Cladribine and 8 patients (28,57%) received different type of therapy, such as immunomodulator therapy, surgery or combination of both, without Cladribine. Most effective therapy for HCL, from all of the above mentioned was definitely Cladribine which is dominant with a resulting response rates of 80-100%, where 70-90% of patients were achieving a complete remission, as defined by a complete disappearance of hairy cells in the bone marrow.