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Open access

Dragana Milosevic and Violeta Lukic Panin

Summary

Background

Diabetes mellitus (DM) with its micro- and macrocomplications is the leading global epidemic of the 21st century. The aim of the research is to determine possible changes in the complete blood count (CBC) parameters depending on glycemic controlin patients with Type 2 diabetes mellitus (T2DM).

Methods

The study included a total of 178 patients with T2DM, both gender over the age of 40 years, from the Health Care Center »Dr Milorad Mika Pavlović« Indjija, Serbia. To notice the possible correlation between the CBC parameters and glucose control in T2DM, the subjects were divided in two groups with HbA1c ≤ 7% and with HbA1c>7%. We analysed CBC parameters, parameters of glycoregulation, lipid status using standard biochemical methods, performed anthropometric measurements and collected patients data by questionnaire and electronic patient card.

Results

There was statistical difference between HbA1c groups for PMDW (p=0.045), HDL (p=0.0067). Using univariate linear regression it is shown that PCT was correlated with WBC (p=0.0005), neutrophils (p=0.046), monocytes (p=0.003); MPM was associated with MPV (p=0.0005); MPC (p=0.0005), PDW (P=0.0005), GLU0 (p=0.034), HDL-C (p=0.005); PMDW was correlated with HbA1c% (p=0.049), GLU0 (p=0.013), HDL-C (p=0.001), BW (p=0.043) in all patients.

Conclusions

Based on our study results it may be concluded that some of the parameters of CBC could be useful tool in following glycemic control of diabetics.

Open access

Manca Garbajs, Primoz Strojan and Katarina Surlan-Popovic

Abstract

Background

In the study, the value of pre-treatment dynamic contrast-enhanced (DCE) and diffusion weighted (DW) MRI-derived parameters as well as their changes early during treatment was evaluated for predicting disease-free survival (DFS) and overall survival (OS) in patients with locoregionally advanced head and neck squamous carcinoma (HNSCC) treated with concomitant chemoradiotherapy (cCRT) with cisplatin.

Patients and methods

MRI scans were performed in 20 patients with locoregionally advanced HNSCC at baseline and after 10 Grays (Gy) of cCRT. Tumour apparent diffusion coefficient (ADC) and DCE parameters (volume transfer constant [Ktrans], extracellular extravascular volume fraction [ve], and plasma volume fraction [Vp]) were measured. Relative changes in parameters from baseline to 10 Gy were calculated. Univariate and multivariate Cox regression analysis were conducted. Receiver operating characteristic (ROC) curve analysis was employed to identify parameters with the best diagnostic performance.

Results

None of the parameters was identified to predict for DFS. On univariate analysis of OS, lower pre-treatment ADC (p = 0.012), higher pre-treatment Ktrans (p = 0.026), and higher reduction in Ktrans (p = 0.014) from baseline to 10 Gy were identified as significant predictors. Multivariate analysis identified only higher pre-treatment Ktrans (p = 0.026; 95% CI: 0.000–0.132) as an independent predictor of OS. At ROC curve analysis, pre-treatment Ktrans yielded an excellent diagnostic accuracy (area under curve [AUC] = 0.95, sensitivity 93.3%; specificity 80 %).

Conclusions

In our group of HNSCC patients treated with cisplatin-based cCRT, pre-treatment Ktrans was found to be a good predictor of OS.

Open access

Samar Damiati

Summary

Background

Although vitamin D in not a traditional marker for cardiovascular and renal diseases, several studies have proposed a correlation between vitamin D deficiency and these diseases due to the effect of vitamin D on endothelial function. Asymmetric and symmetric dimethyl arginine (ADMA and SDMA, respectively) are endogenous markers of endothelial dysfunction, and are considered as future markers for the assessment of cardiovascular and renal diseases. The present study investigated the association of kidney function tests (urea and creatinine) and dimethylarginine toxins (ADMA and SDMA) in women with vitamin D insufficiency or deficiency. Indeed, sex hormones (estrogen and testosterone) were analyzed in the participants.

Methods

Women were divided into two groups: premenopausal women (younger than 50 years) and postmenopausal women (older than 50 years). Urea, creatinine, estrogen, testosterone, ADMA, and SDMA levels were analyzed when vitamin D level was deficient or insufficient in the participants.

Results

The premenopausal women group showed no significant correlations between dimethylarginine toxins and renal failure tests or sex hormones. In the elderly (postmenstrual) women group, only SDMA was significantly correlated with urea and creatinine, while both ADMA and SDMA were not correlated with sex hormones.

Conclusions

Although ADMA and SDMA are promising candidates of endothelial dysfunction and are increased in menopause and aging, no direct link between ADMA and further progression of renal failure was observed in women with low vitamin D levels. In contrast, a possible direct correlation between SDMA and renal dysfunction was noticed, but only in an age-dependent manner.

Open access

Nada Majkić-Singh

Summary

During 15th Belgrade Symposium for Balkan Region (April 11 and 12, 2019, Belgrade, www.dmbj.org.rs) Society of Medical Biochemists of Serbia organized scientific and professional program with aim to discuss laboratory medicine topics of mutual interest for all the countries of the Region, such as:

  • Laboratory Medicine Planning and Organization

  • Type of Medical Laboratory and Strategy

  • Laboratory Medicine Management

  • Leadership Skills

  • Accreditation and Competences

  • Environmental Health and Safety

  • Laboratory Standards in Balkan Countries

  • Experiences of Young Scientists

  • Students Achievements

Together with the countries from Balkan Region the countries from our neighborhood as Italy, Austria, Hungary, Cyprus and Israel have been invited to discuss this important topics and exchange the mutual experiances with aim to improve the laboratory medicine in our countries and to help our colleagues to improve daily laboratory practice in our countries. Also participation in the Symposium took colleagues from France and Belgium.

Open access

Mohamed A.F. Mourad and Mahmoud M. Higazi

Abstract

Background

This study aimed to evaluate the efficacy of three MR imaging parameters, which are tumour thickness, para-lingual distance and apparent diffusion coefficient (ADC) value for prediction of cervical lymph nodes metastasis in cancer tongue patients.

Patients and methods

Fifty patients with proved cancer tongue by histopathological examination underwent MRI examination. T1 and T2- weighted MRI, diffusion-weighted images and post-contrast T1 fat suppression sequences were used.

Results

The patients were classified according to lymph nodes involvement as seen by MRI into two groups. Significant differences between positive and negative nodes groups were observed regarding tumour thickness and para-lingual distance (p-values = 0.008 and 0.003 respectively). ROC curve analyses revealed cut-off values >13.8 mm and ≤ 3.3 mm for tumour thickness and para-lingual distance respectively for prediction of nodes involvement. No significant differences between patients with and without cervical lymph nodes metastasis were found regarding corresponding ADC value of the tumour (p-value = 0.518).

Conclusions

Para-lingual distance and tumour thickness are factors that could influence pre-operative judgment and prognosis of tongue cancer patients. ADC value of the tumour itself seem not to be a reliable index of cancer progression to regional lymph nodes.

Open access

Martina Rebersek, Tanja Mesti, Marko Boc and Janja Ocvirk

Abstract

Background

Histological parameters of primary tumour and nodal metastases are prognostic factors for survival of operable colorectal (CRC) patients, but not predictive for response rate of systemic therapy. KRAS mutations in codons 12 and 13 were first recognized as a predictive factor for resistance to anti-EGFR monoclonal antibodies. Not all patients with wild-type KRAS (wtKRAS) respond to anti-EGFR antibody treatment. Additional mechanisms of resistance may activate mutations of the other main EGFR effectors pathway, such as other mutations in RAS gene, mutations in P13K and PTEN expression.

Patients and methods

In the prospective study prognostic and predictive impact of histological parameters of primary tumour, KRAS and BRAF mutations on overall survival (OS) and objective response (OR) rate of metastatic CRC (mCRC) patients treated with 1st line systemic therapy were analysed. We additionally retrospectively analysed other mutations in RAS genes and their impact on survival and time to progression.

Results

From November 2010 to December 2012, we enrolled 154 patients in the study, 95 men and 59 women. Mutations in KRAS gene and V600E BRAF gene were found in 42% and in 3% of patients, respectively. Median OS of the patients with T1, T2 and T3 tumour was 65.4 months (95% CI, 55.7–75.6) while in patients with T4 tumour, lymphangiosis, vascular and perineural invasion it has not been reached yet. Median OS of the patients with G1, G2 and G3 of tumour differentiation was 65.6 (95% CI, 53.7–77.5) and 25.3 months (95% CI, 16.6–34.1), respectively. Median OS of the patients with stage N0, N1 and N2 was 65.6 (95% CI, 56.4–74.8) and 58.0 months (95% CI, 21.9–94.2), respectively. Median OS of wtKRAS and mutated KRAS patients was 56.5 (95% CI, 48.2–64.9) and 58 months (95% CI, 52.6–63.4), respectively. Median OS of mutated codon 12 and codon 13 patients was 57 (95% CI, 50.9–64.4) and 44 months (95% CI, 40.1–48.4), respectively. Median OS of wtBRAF and of mutated BRAF patients was 59.2 (95% CI, 52.5–65.9) and 27.6 months (95% CI, 12.6–42.5), respectively. wtKRAS significantly affected the response to the first systemic therapy (p = 0.028), while other parameters did not affected it, p= 0.07. In 14 patients (17%), additional mutations in NRAS gene, codon 61 and codon 146 were found. Median OS of wtNRAS, codon 61 and 146 patients was 67.1 months (50.3–67.6) while median OS of mutated NRAS patients has not been reached yet (p = 0.072). Median time to progression of wtNRAS, codon 61 and 146 patients was 11.7 months (10.4–14.5) while median time to progression of mutated NRAS patients was 7.9 months (6.1–11.0), (p = 0.025).

Conclusions

Mutated BRAF, N2 and G3 of primary tumour were poor prognostic factors for OS in mCRC patients. wtKRAS significantly affected the response to the first line systemic therapy. Histological parameters included in the analysis and mutated BRAF did not affect significantly the efficacy of 1st line systemic therapy in mCRC patients.

Open access

Dragana Popovic, Katarina Lalic, Aleksandra Jotic, Tanja Milicic, Jelena Bogdanovic, Maja Đorđevic, Sanja Stankovic, Veljko Jeremic and Nebojsa M. Lalic

Summary

Background

We analyzed cardiovascular inflammatory (C-reactive protein (CRP), interleukin 6 (IL-6)), haemostatic (homocysteine) risk markers in lean and obese patients at admission and acute hyperglicemic crisis (AHC) resolving, involving diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS).

Methods

In that context, we included group A: N = 20 obese, B: N=20 lean patients with DKA; C: N = l0 obese, D: N=10 lean patients with HHS; E: N = 15 obese, F: N=15 lean controls. CRP IL-6, homocysteine were determined by ELISA.

Results

Our results showed that CRP IL-6, and homocysteine levels decreased in all groups: (A: p<0.001; B: p<0.001, C: p<0.05; D: p<0.001 mg/L), (A: p<0.001 B: p<0.001, C: p<0.001, D: p<0.01 pg/mL), (A: p<0.001, B: p <0.001; C: p<0.05, D: p=0.001 μmol/L), respectively, at resolving AHC. However, CRP persisted higher (p<0.001, p<0.01), IL-6 lower (p<0.05, p<0.001), while homocysteine levels turned out to be similar to controls.

Conclusions

AHC is associated with increased inflammatory and hemostatic cardiovascular risk markers. Also, insulin therapy in AHC has had more pronounced favorable effect on IL-6 and homocystein than on CRP

Open access

Mateja Prunk, Milica Perisic Nanut, Jerica Sabotic, Urban Svajger and Janko Kos

Abstract

Background

Cystatin F is a protein inhibitor of cysteine peptidases, expressed predominantly in immune cells and localised in endosomal/lysosomal compartments. In cytotoxic immune cells cystatin F inhibits both the major pro-granzyme convertases, cathepsins C and H that activate granzymes, and cathepsin L, that acts as perforin activator. Since perforin and granzymes are crucial molecules for target cell killing by cytotoxic lymphocytes, defects in the activation of either granzymes or perforin can affect their cytotoxic potential.

Materials and methods

Levels of cystatin F were assessed by western blot and interactions of cystatin F with cathepsins C, H and L were analysed by immunoprecipitation and confocal microscopy. In TALL-104 cells specific activities of the cathepsins and granzyme B were determined using peptide substrates.

Results

Two models of reduced T cell cytotoxicity of TALL-104 cell line were established, either by treatment by ionomycin or by immunosuppressive transforming growth factor beta. Reduced cytotoxicity correlated with increased levels of cystatin F and with attenuated activities of cathepsins C, H and L and of granzyme B. Co-localisation of cystatin F and cathepsins C, H and L and interactions between cystatin F and cathepsins C and H were demonstrated.

Conclusions

Cystatin F is designated as a possible regulator of T cell cytotoxicity, similar to its role in natural killer cells.

Open access

Barbara Senk, Katja Goricar, Viljem Kovac, Vita Dolzan and Alenka Franko

Abstract

Background

Malignant mesothelioma (MM) is an asbestos related aggressive tumor with poor prognosis. The aim of this study was to investigate if aquaporin 1 (AQP1) genetic polymorphisms influence the risk of MM and the response to cisplatin based MM treatment.

Patients and methods

The case-control study included 231 patients with MM and a control group of 316 healthy blood donors. All subjects were genotyped for three AQP1polymorphisms (rs1049305, rs1476597 and rs28362731). Logistic and Cox regression were used in statistical analysis.

Results

AQP1 rs1049305 polymorphism was significantly associated with MM risk in dominant model adjusted for gender and age (OR = 0.60, 95% CI = 0.37–0.96, Padj = 0.033). This polymorphism was also significantly associated with cisplatin based treatment related anaemia (unadjusted: OR = 0.49, 95% CI = 0.27–0.90, P = 0.021; adjusted: for CRP: OR = 0.52, 95% CI = 0.27–0.99, P = 0.046), with leukopenia (OR = 2.09, 95% CI = 1.00–4.35, P = 0.049) in dominant model and with thrombocytopenia (OR = 3.06, 95% CI = 1.01–9.28, P = 0.048) and alopecia (OR = 2.92, 95% CI = 1.00–8.46, P = 0.049) in additive model. AQP1 rs28362731 was significantly associated with thrombocytopenia (unadjusted: OR = 3.73, 95% CI = 1.00–13.84, P = 0.049; adjusted for pain: OR = 4.63, 95% CI = 1.13–19.05, P = 0.034) in additive model.

Conclusions

AQP1 may play a role in the risk of MM. Furthermore, AQP1 genotype information could improve the prediction of MM patients at increased risk for cisplatin toxicity.

Open access

Marko Baralić, Voin Brković, Vesna Stojanov, Sanja Stanković, Nataša Lalić, Petar Đurić, Ljubica Đukanović, Milorad Kašiković, Milan Petrović, Marko Petrović, Milan Stošović and Višnja Ležaić

Summary

Background

Vascular calcification (VC) is highly prevalent in dialysis (HD) patients, and its mechanism is multifactorial. Most likely that systemic or local inhibitory factor is overwhelmed by promoters of VC in these patients. VC increased arterial stiffness, and left ventricular hypertrophy. Thus, the present study aimed to investigate the association of VC and myocardial remodeling and to analyze their relationship with VC promoters (fibroblast growth factor 23-FGF23, Klotho, intact parathormon-iPTH, vitamin D) in 56 prevalent HD patients (median values: age 54 yrs, HD vintage 82 months).

Methods

Besides routine laboratory analyzes, serum levels of FGF 23, soluble Klotho, iPTH, 1,25-dihydroxyvitamin D3; pulse wave velocity (PWV); left ventricular (LV) mass by ultrasound; and VCs score by Adragao method were measured.

Results

VC was found in 60% and LV concentric or eccentric hypertrophy in 50% patients. Dialysis vintage (OR 1.025, 95%CI 1.007–1.044, p=0.006) FGF23 (OR 1.006, 95% CI 0.992–1.012, p=0.029) and serum magnesium (OR 0.000, 95%CI 0.000–0.214, p=0.04) were associated with VC. Changes in myocardial geometry was associated with male sex (beta=-0.273, 95% CI -23.967 1.513, p=0.027), iPTH (beta 0.029, 95%CI -0.059–0.001, p=0.027) and vitamin D treatment (beta 25.49, 95%CI 11.325–39.667, p=0.001). Also, patients with the more widespread VC had the highest LV remodeling categories. PWV was associated patient’s age, cholesterol, diastolic blood pressure, LV mass (positively) and serum calcium (negatively), indicating potential link with atherosclerotic risk.

Conclusions

Despite to different risk factors for VC and myocardial remodeling, obtained results could indicate that risk factors intertwine in long-term treatment of HD patients and therefore careful and continuous correction of mineral metabolism disorders is undoubtedly of the utmost importance.