Srdjan Stefanovic

Contractile effects of endothelins on isolated ampullar segment of human oviduct in luteal phase of menstrual cycle

Endothelin-1 induces contractions of human oviduct ampullar segment in follicular phase of menstrual cycle, acting on ET(A) receptors. The aim of our study was to investigate effects of endothelin-1, endothelin-2 and endothelin-3 on isolated ampullar segment of human oviducts, taken from the patients in luteal phase of menstrual cycle. Fallopian tubes were taken from 20 female patients (one tube from each patient) during abdominal hysterectomy with adnexectomy, due to extensive uterine fibroids. The oviduct ampulla was mounted in an organ bath longitudinally, and the tension of the isolated preparation was recorded with the isometric transducer. Endothelin-1 produced concentration-dependent tonic contraction of the isolated ampullar segment (EC(50)=6.80 +/- 1.2 x 10(-10)M), and concentration-dependent inhibition of its rhythmic contractions (EC(50)=7.86 +/- 2.3 x 10(-10)M). Endothelin-2 produced concentration-dependent tonic contraction of the isolated ampullar segment (EC(50)=4.56 +/- 0.3 x 10(-10)M), without affecting its rhythmic contractions. Endothelin-3 did not affect either tone or rhythmic contractions of the isolated preparations. Selective antagonist for ET(A) receptor subtype, BQ 123, produced inhibition of endothelin-1 effects on both tone (pA(2)=9.50) and spontaneous rhythmic contractions (pA(2)=10.73), while selective antagonist for ET(B) receptor subtype, BQ 788, produced only inhibition of endothelin-1 effects on tone (pA(2)=9.61), while the effect of endothelin-1 on spontaneous rhythmic contractions remained unaffected. The results of our study suggest that in the luteal phase both ET(A) and ET(B) receptors regulate tone, and only ET(A) receptors regulate rhythmic activity of human oviducts ampullar segment.

Pharmacokinetics of linezolid in critically ill patients.

ABSTRACT Introduction: Linezolid is an oxazolidinone antibiotic active against Gram-positive bacteria, and is most commonly used to treat life-threatening infections in critically ill patients. The pharmacokinetics of linezolid are profoundly altered in critically ill patients, partly due to decreased function of vital organs, and partly because life-sustaining drugs and devices may change the extent of its excretion. Areas covered: This article is summarizes key changes in the pharmacokinetics of linezolid in critically ill patients. The changes summarized are clinically relevant and may serve as rationale for dosing recommendations in this particular population. Expert opinion: While absorption and penetration of linezolid to tissues are not significantly changed in critically ill patients, protein binding of linezolid is decreased, volume of distribution increased, and metabolism may be inhibited leading to non-linear kinetics of elimination; these changes are responsible for high inter-individual variability of linezolid plasma concentrations, which requires therapeutic plasma monitoring and choice of continuous venous infusion as the administration method. Acute renal or liver failure decrease clearance of linezolid, but renal replacement therapy is capable of restoring clearance back to normal, obviating the need for dosage adjustment. More population pharmacokinetic studies are necessary which will identify and quantify the influence of various factors on clearance and plasma concentrations of linezolid in critically ill patients.

Comparative analysis of the effects combined physical procedures and alpha-lipoic acid on the electroneurographic parameters of patients with distal sensorimotor diabetic polyneuropathy.

[Purpose] Painful diabetic polyneuropathy occurs as a complication in 16% of all patients with diabetes mellitus. [Subjects and Methods] A clinical, prospective open-label randomized intervention study was conducted of 60 adult patients, with distal sensorimotor diabetic neuropathy two groups of 30 patients, with diabetes mellitus type 2 with distal sensorimotor diabetic neuropathy. Patients in group A were treated with combined physical procedures, and patients in group B were treated with alpha lipoic acid. [Results] There where a statistically significant improvements in terminal latency and the amplitude of the action potential in group A patients, while group B patients showed a statistically significant improvements in conduction velocity and terminal latency of n. peroneus. Group A patients showed a statistically significant improvements in conduction velocity and terminal latency, while group B patients also showed a statistically significant improvements in conduction velocity and terminal latency. This was reflected in a significant improvements in electrophysiological parameters (conduction velocity, amplitude and latency) of the motor and sensory nerves (n. peroneus, n. suralis). [Conclusion] These results present further evidence justifying of the use of physical agents in the treatment of diabetic sensorimotor polyneuropathy.

Early Cytokine Profile Changes In Interstitial And Necrotic Forms Of Acute Pancreatitis

ABSTRACT Acute pancreatitis (AP) is a common, potentially lethal, acute inflammatory process with a highly variable clinical course. The aim of this study was to analyse early changes in the serum concentrations of pro- and anti-inflammatory cytokines in the peripheral blood of patients with the interstitial form of acute pancreatitis (IAP) and necrotic acute pancreatitis (NAP), especially in those patients who had lethal outcomes. The prospective study enrolled 52 patients who were divided into IAP (65.38% of patients) and NAP (34.62% of patients) groups. The serum levels of interleukins (IL) 6, 8 and 10, together with tumour necrosis factor (TNF)-alpha were measured on the 1st and 3rd day of hospitalisation. Significantly higher values of IL-6, IL-8 and IL-10 were found on day 1 and 3 in NAP than in IAP. IL-6 was significantly higher on both days of measurement, whereas IL-10 on the first day and IL-8 on the third day were significantly higher in the group of patients who did not survive in comparison with patients who had the interstitial form of AP. In conclusion, the data from this study showed that immune suppression and excessive immune stimulation in the first three days after admission could indicate the development of NAP and a potentially lethal outcome.

Risk factors for lethal outcome in patients with delirium tremens - psychiatrist's perspective: a nested case-control study

BackgroundThe aim was to identify potential risk factors for lethal outcome in patients with delirium tremens (DT) treated in the psychiatric setting.MethodsIn a nested case-control study, a total of 190 medical records of patients with DT hospitalized at the Psychiatric Clinic in Serbia between 2002 and 2011 were reviewed and analyzed. The characteristics of patients who died (cases) were compared with those who survived (controls). For each case, two controls (matched for age, gender, and year of hospitalization) were randomly chosen.ResultsSignificant differences between cases and controls were found for serum potassium levels (p < 0.001), the number of hospitalizations (p < 0.001), and duration of hospitalization (p < 0.001). A significant association with lethal outcome was found for serum potassium levels even in the normal range (adjusted odds ratio 40.52; 95% CI 1.20, >1,000.00; p = 0.004).ConclusionsEven though the number and duration of psychiatric hospitalizations were identified as factors determining survival after admission for DT, only serum potassium levels were found to be significant. Patients with an increase in potassium (or absence of hypokalemia) may require more intensive treatment. Monitoring of serum levels of potassium is important not only as an indicator for replacement but also as an indicator of maladaptation.

Clinical and laboratory parameters associated with death in acute pancreatitis

Introduction. Acute pancreatitis is an inflammatory condition having the significant mortality rate in the case of severe forms of disease. The aim of this study was to investigate putative factors of increased mortality with contradictory prior evidence, and to reveal factors that were insufficiently explored previously. Methods. A prospective cohort study with nested case/control design included all adult patients treated for acute pancreatitis in Clinical Center of Kragujevac, Serbia, during the 3-year period (from October 2011 to December 2014). The cases (n=19) were patients who died, while the controls (n=113) were patients who survived. The associations between putative risk factors and the study outcomes were tested by univariate and multivariate logistic regressions, and expressed as crude and adjusted odds ratios (OR) with corresponding 95% confidence intervals (CI). Results. Significant association with the lethal outcome in acute pancreatitis was found for advanced age (adjusted OR 1.12, 95%CI 1.02-1.23), presence of significant comorbidities (adjusted OR 10.62, 95%CI 1.01-111.39), higher interleukin-8 (IL-8) value on third day from onset of symptoms (adjusted OR 1.05, 95%CI 1.02-1.08), use of tramadol and/or morphine (adjusted OR 47.34, 95%CI 3.21-699.08), BISAP score ≥ 3 in the first 24 hours (adjusted OR 48.11, 95%CI 3.14-736.29), and prophylactic use of antibiotics (adjusted OR 0.07, 95%CI 0.01-0.85). Conclusion. Advanced age, significant comorbidities, use of tramadol and/or morphine and more severe disease as assessed by BISAP score can increase the risk for death in acute pancreatitis, while prophylactic use of antibiotics may have a protective role. [Projekat Ministarstva nauke Republike Srbije, br. 175007]

Factors associated with the rate of COPD exacerbations that require hospitalization

BACKGROUND/AIM Exacerbations are key events in chronic obstructive pulmonary disease (COPD). Frequent exacerbations occurring during the natural course of COPD lead to deterioration of health-related quality of life and are major causes of morbidity and mortality. The aim of this study was to identify factors independently associated with frequent severe exacerbations of COPD that require hospitalization. MATERIALS AND METHODS A case-control study was performed to analyze risk factors and frequency of severe exacerbations, which were defined by the GOLD guideline criteria. Stepwise multivariate regression was used to determine the significant predictors of frequent exacerbations. RESULTS Results revealed five independent predictors of frequent exacerbations: age, length of hospital stay, FEV1/FVC ratio, CRP level above 10 mg/L, and respiratory comorbidities. CONCLUSION COPD patients should be more carefully assessed in terms of age, length of hospital stay, FEV1/FVC ratio, CRP level, and respiratory comorbidities. Patients under 65 years of age with respiratory comorbidities, longer hospital stay, lower FEV1/FVC ratio and CRP of <10 mg/L are more prone to experiencing a minimum of one additional hospitalization in the following year. Patients could spend less time in the hospital environment and increase their quality of life by adjusting these risk factors for hospitalization due to COPD.

Non-Opioid Analgesics Consumption At The Surgery Departments Of A Secondary Care Hospital In General Hospital In Kraljevo, Serbia

Abstract The aim of this study was to determine the amount of non-opioid analgesics consumed at the surgical departments of a secondary care hospital in Serbia, a developing country undergoing a socioeconomic transition that thus lacks sufficient funds to finance and invest in the healthcare system. At the departments of gynaecology, urology, otolaryngology, general surgery and orthopaedics with traumatology at the General Hospital, Kraljevo from 2010 to 2012, six different non-opioid analgesics were used: diclofenac, ketorolac, ibuprofen, metamizole sodium, paracetamol (for per os and parenteral use), and meloxicam (for parenteral use only). Drugs in the M01 Anatomical Therapeutic Chemical classification group were consumed statistically significantly more than drugs in the N02 group (U=0.000; p<0.001). With regard to the average consumption amounts of all monitored drugs, diclofenac was consumed the most, followed by ketorolac. Meloxicam was the least used drug. There were significant differences in the average annual consumption of ibuprofen between surgical departments, but this was not the case for the other non-opioid analgesics. The differences in the average consumption between the individual drugs were significant for each year of observation. Due to the incongruity of the results of previous studies related to non-steroidal anti-inflammatory drug consumption at different surgery wards, additional research in different geographical areas of our country is necessary to enhance the quality of prescription patterns on a national level and adjust them based on the latest scientific data and European trends.

Risk Factors For Development Of Acute Necrotizing Pancreatitis

Abstract Acute necrotizing pancreatitis (ANP) is a severe form of acute pancreatitis that is associated with high morbidity and mortality. Thus, an adequate initial treatment of patients who present with acute pancreatitis (AP) based on correct interpretation of early detected laboratory and clinical abnormalities may have a significant positive impact on the disease course. The aim of the study was to determine patient- and initial treatment-related risk factors for the development of acute necrotizing pancreatitis. For the purpose of this study a case-control design was chosen, including adult patients treated for AP in the surgical Intensive Care Unit (sICU) of Clinical Center of Kragujevac, from January 2006 to January 2011. The cases (n=63) were patients who developed ANP, while the controls (n=63) were patients with AP without the presence of pancreatic necrosis. The controls were randomly selected from a study sample after matching with the cases by age and sex. Significant association with the development of ANP was found for the presence of comorbidity (adjusted OR 6.614 95%CI 1.185-36.963), and the use of somatostatin (adjusted OR 7.460, 95%CI 1.162-47.833) and furosemide (adjusted OR 2710.57, 95%CI 1.996-56.035) started immediately upon admission to the sICU. This study suggests that comorbidities, particularly the presence of serious cardio-vascular disease, can increase the risk for development of acute necrotizing pancreatitis. The probability for the development of ANP could be reduced by the avoidance of the initial use of loop diuretics and somatostatin.