The importance of angiotensin II type 1 receptor gene polymorphism to losartan treatment in improving glomerulopathy in type 1 diabetic patients.

OBJECTIVE: Diabetic nephropathy (DN) is a clinical syndrome characterized by persistent albuminuria, increasing arterial blood pressure and progressive decline in glomerular filtration rate (GFR). When persistent albuminuria is established, antihypertensive treatment becomes most important factor in slowing the progression of diabetic glomerulopathy. Aim of this study was to examine if renoprotective response to losartan therapy, in patients with diabetic nephropathy, depends on 1166 A/C gene polymorphism for its target receptor, angiotensin II type 1 receptor (AT1R). SUBJECTS AND METHODS: The study included 35 patients with diabetes mellitus type 1 and high urinary albumin excretion rate (>30mg/24h) genotyped for the 1166 A/C gene polymorphism for the AT1R. The participants were segregated into three genotype groups according to combinations of A or C allele: AA-16, AC-15 and CC-4 patients. The patients received losartan 50mg daily for 4 weeks, following 100mg daily for 8 weeks. At baseline and after losartan therapy period, blood pressure, GFR (Gates method) and filtration fraction (FF) were calculated. FF was calculated by dividing GFR by ERPF (Schlegels method). RESULTS: GFR remained unchanged in all genotype groups. FF was significantly reduced from baseline by 0.018±0.024 (P=0.012) only in the AC group. In the AA genotype FF was reduced from baseline by 0.017±0.03 (P=0.052) and in the CC group by 0.01±0.008 (P=0.092). In the AA group, systolic blood pressure declined from 136±24mmHg at baseline, to an average of 121±18mmHg at the end of the study (P=0.001). The AC group achieved reduction from 131±10mmHg at baseline to 115±7mmHg (P=0.001) during the investigation period. In the AA genotype group losartan reduced diastolic blood pressure from 86±13mmHg at baseline to 78±8mmHg (P=0.004), and in the AC genotype from 88±5mmHg at baseline to 11.7±5.6mmHg during the investigation period (P=0.001). In the CC genotype diastolic blood pressure reduction remained nonsignificant (P=0.066). CONCLUSION: The results of our small sample size study provide the evidence that 1166 A/C AT1R polymorphism could be associated with the renoprotective response to losartan therapy.

Simple risk algorithm to predict serious bleeding in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: RISK-PCI bleeding score.

BACKGROUND: Bleeding is a potentially catastrophic complication after primary percutaneous coronary intervention (PPCI). It occurs most frequently within the first 30 days following the intervention. The aim of this study was to generate a simple and accurate risk model for the prediction of bleeding after PPCI. METHODS AND RESULTS: The training set included 2,096 patients enrolled in the RISK-PCI trial. The model was validated using a database of 961 patients enrolled in the ART-PCI trial. Bleeding was defined as type ≥3a bleeding according to the Bleeding Academic Research Consortium definition. Multivariate logistic regression was used to evaluate the predictors of outcome. A sum of weighted points for specific predictors was calculated to determine the final score. The model included 5 independent predictors of 30-day bleeding: gender (female); history of peptic ulcer; creatinine clearance at admission (<60 ml/min); hemoglobin at presentation (<125 g/dl); and Killip class >1 heart failure at admission. The model showed good discrimination and calibration for the prediction of bleeding in the derivation set (C-statistic, 0.79; goodness of fit, P=0.12) and in the validation set (C-statistic, 0.76; goodness of fit, P=0.37). Patients were classified into 3 risk classes and the observed incidence of 30-day bleeding of 1.0%, 3.5% and 10.7% corresponded to the low-, intermediate- and high-risk classes, respectively. CONCLUSIONS: A simple risk model was developed that has a reasonably good capacity for the prediction of 30-day bleeding after PPCI.

L-FABP can be an early marker of acute kidney injury in children.

BACKGROUND: Acute kidney injury (AKI) is a common postoperative complication following cardiopulmonary bypass (CPB) surgery. New biomarkers to identify patients with early AKI (before increases in serum creatinine) are needed to facilitate appropriate treatment. This study aimed to test the role of urinary liver fatty-acid-binding protein (L-FABP) as an early biomarker for AKI in children undergoing CPB surgery. METHODS: This is a case-control study of children undergoing CPB. AKI was defined as 50 % increase in serum creatinine at 48 h after surgery. For each patient, five serum and urine samples were obtained corresponding to time 0 h (presurgery) and 2, 6, 24, and 48 h after surgery. RESULTS: Twenty-seven patients, median age 360 days, were enrolled. AKI developed in 11 patients (41 %); three needed renal replacement therapy (peritoneal dialysis); there were two deaths. There were significant differences between patients with and without AKI in L-FABP levels at 2, 6, and 48 h after surgery, length of hospital stay, and CPB time; there were no differences in gender, patient age, and body weight. L-FABP was normalized to urinary creatinine concentration at all time points, with area under the receiver operator curve (AUC ROC) 0.867 at 2 and 6 h postoperatively. Correlation coefficient between L-FABP and length of hospital stay after surgery was statistically significant (r = 0.722, p value = 0.000). CONCLUSIONS: Our results suggest that urinary L-FABP can be used to diagnose AKI earlier than rise in serum creatinine in children undergoing CPB.

Health-related quality of life among patients with symptomatic carotid disease.

OBJECTIVES: To evaluate health-related quality of life (HRQoL) in patients with symptomatic carotid disease (amaurosis fugax, transient ischaemic attack, stroke); to compare it with that of the general population; to explore whether HRQoL depends on the severity of the disease and to investigate the possible association between some demographic and clinical characteristics of patients and HRQoL. METHODS: This cross-sectional study involved 175 patients with symptomatic carotid atherosclerotic disease who were referred for endarterectomy between January 2011 and December 2011. HRQoL was measured using Medical Outcome Survey Short Form 36 (SF-36). RESULTS: In comparison to both referent populations, patients with carotid disease had significantly lower mean SF-36 scores for role-physical (41.6 vs. 61.5 and 67.8), social functioning (65.4 vs. 73.8 and 80.0), role-emotional (48.2 vs. 68.6 and 80.5) and mental health (51.5 vs. 61.9 and 66.0). The SF-36 scores were significantly lower in female patients with carotid disease than in men (for role-physical 32.3 vs. 46.5; for bodily pain 57.0 vs. 73.0; for general health 55.6 vs. 61.5; for vitality 55.4 vs. 60.1; for social functioning 57.1 vs. 69.8 and for role-emotional 37.2 vs. 54.1). Significantly lower SF-36 scores were also found in patient with comorbidity (for physical functioning 68.1 vs. 77.7; for role-physical 35.1 vs. 52.3; for bodily pain 62.6 vs. 75.4; for general health 56.8 vs. 63.8; for social functioning 61.9 vs. 71.0, for role-emotional 41.6 vs. 59.1and for mental health 52.5 vs 49.8). In a multivariable analysis, education, occupation, body mass index, metabolic syndrome and severity of the disease had a weak influence on patients' HRQoL, while age, marital status, smoking, alcohol consumption, physical activity and the degree of carotid stenosis had no effect on patients' HRQoL. The SF-36 scores did not substantially change after adjustment for confounding variables. CONCLUSIONS: Patients with symptomatic carotid disease had poorer HRQoL, especially its mental components, than the general population. The severity of the disease was significantly associated only with the SF-36 role-physical subscale. HRQoL in patients with symptomatic carotid disease was poorer in women than in men, and was not affected by age and other demographic and clinical characteristics of patients.

The influence of maternal smoking and exposure to residential ETS on pregnancy outcomes: a retrospective national study.

In a nationwide study of Serbian births, in 2008, we estimated the influence of maternal prenatal smoking and environmental tobacco smoke (ETS) exposure on birth outcomes. Using stratified two-stage random cluster sampling, 2,721 women were interviewed in-person (response rates 98.1 %), and 2,613 singleton live births were included. Date of birth, gender, birthweight, birth height and head circumference were copied from the official hospital Birth Certificate. Six exposure categories were defined according to mother's smoking history and exposure to ETS. We calculated adjusted mean values and group differences by analysis of covariance, and adjusted odds ratios for the low birthweight (LBW < 2,500 g). Compared to the reference category (non-smoking, non-exposed to ETS) we observed birthweight reductions in infants whose mothers smoked continuously during the pregnancy and were exposed to ETS (-162.6 g) and whose mothers were not exposed to ETS (-173 g) (p = 0.000, and p = 0.003, respectively), as well as reduction in birth length (-1.01 and -1.06 cm; p = 0.003 and p = 0.000, respectively). Reduction in birthweight and birth length related to exposure categories was not linear. Adjusted OR for LBW was almost tripled for mothers who smoked over the entire pregnancy and were non-exposed to ETS (aOR 2.85; 95 % CI 1.46-5.08), and who were exposed to ETS (aOR 2.68; 95 % CI 1.15-6.25). Our results showed strong effects of smoking throughout the pregnancy on reduced birthweight, birth length and head circumference, and increased risk for LBW. We were not able to detect an effect for ETS exposure alone.

Feasibility of applying data mining techniques for predicting technical difficulties during laparoscopic cholecystectomy based on routine patient work-up in a small community hospital.

BACKGROUND/AIMS: Predicting technical difficulties in laparoscopic cholecystectomy (LC) in a small regional hospital increases efficacy, cost-benefit and safety of the procedure. The aim of the study was to assess whether it is possible to accurately predict a difficult LC (DLC) in a small regional hospital based only on the routine available clinical work-up parameters (patient history, ultrasound examination and blood chemistry) and their combinations. METHODOLOGY: A prospective, cohort, of 369 consecutive patients operated by the same surgeon was analyzed. Conversion rate was 10 (2.7%). DLC was registered in 55 (14.90%). Various data mining techniques were applied and assessed. RESULTS: Seven significant predictors of DLC were identified: i) shrunken (fibrotic) gallbladder (GB); ii) ultrasound (US) GB wall thickness >4 mm; iii) >5 attacks of pain lasting >5 hours; iv) WBC >10x109 g/L; v) pericholecystic fluid; vi) urine amylase >380 IU/L, and vii) BMI >30kg/m2. Bayesian network was selected as the best classifier with accuracy of 94.57, specificity 0.98, sensitivity 0.77, AUC 0.96 and F-measure 0.81. CONCLUSION: It is possible to predict a DLC with high accuracy using data mining techniques, based on routine preoperative clinical parameters and their combinations. Use of sophisticated diagnostic equipment is not necessary.

Pancreatic cancer mortality in Serbia from 1991-2010 - a joinpoint analysis.

AIM: To analyze the trends of pancreatic cancer mortality in Serbia. METHODS: The study covered the population of Serbia in the period 1991 to 2010. Mortality trends were assessed by the joinpoint regression analysis by age and sex. RESULTS: Age-standardized mortality rates ranged from 5.93 to 8.57 per 100 000 in men and from 3.51 to 5.79 per 100 000 in women. Pancreatic cancer mortality in all age groups was higher among men than among women. It was continuously increasing since 1991 by 1.6% (95% confidence interval [CI] 1.1 to 2.0) yearly in men and by 2.2% (95% CI 1.7 to 2.7) yearly in women. Changes in mortality were not significant in younger age groups for both sexes. In older men (≥55 years), mortality was increasing, although in age groups 70-74 and 80-84 the increase was not significant. In 65-69 years old men, the increase in mortality was significant only in the period 2004 to 2010. In ≥50 years old women, mortality significantly increased from 1991 onward. In 75-79 years old women, a non-significant decrease in the period 1991 to 2000 was followed by a significant increase from 2000 to 2010. CONCLUSION: Serbia is one of the countries with the highest pancreatic cancer mortality in the world, with increasing mortality trend in both sexes and in most age groups.

New-Onset Paroxysmal Atrial Fibrillation in the Setting of Acute Pulmonary Embolism Is Associated with All-Cause Hospital Mortality in Women but Not in Men.

BACKGROUND: Patients with acute pulmonary embolism (PE) may have various types of atrial fibrillation (AF). The role of AF in hemodynamic states and outcomes may differ between men and women. METHODS: In total, 1600 patients (743 males and 857 females) with acute PE were enrolled in this study. The severity of PE was assessed using the European Society of Cardiology (ESC) mortality risk model. Patients were allocated into three groups according to their electrocardiography recordings taken during hospitalization: sinus rhythm, new-onset paroxysmal AF, and persistent/permanent AF. The association between the types of AF and all-cause hospital mortality was tested using regression models and net reclassification index (NRI) and integrated discrimination index (IDI) statistics with respect to sex. RESULTS: There were no differences between the frequencies of the types of AF between men and women: 8.1% vs. 9.1% and 7.5% vs. 7.5% (p = 0.766) for paroxysmal and persistent/permanent AF, respectively. We found that the rates of paroxysmal AF significantly increased across the mortality risk strata in both sexes. Among the types of AF, the presence of paroxysmal AF had a predictive value for all-cause hospital mortality independent of mortality risk and age in women only (adjusted HR, 2.072; 95% CI, 1.274-3.371; p = 0.003). Adding paroxysmal AF to the ESC risk model did not improve the reclassification of patient risk for the prediction of all-cause mortality, but instead enhanced the discriminative power of the existing model in women only (NRI, not significant; IDI, 0.022 (95% CI, 0.004-0.063); p = 0.013). CONCLUSION: The occurrence of paroxysmal AF in female patients with acute PE has predictive value for all-cause hospital mortality independent of age and mortality risk.

Epidemiology of chronic kidney disease in children in Serbia.

BACKGROUND: The epidemiological information from well-defined populations regarding childhood chronic kidney disease (CKD), particularly those concerning non-terminal stages, are scanty. The epidemiology of CKD in children is often based on renal replacement therapy (RRT) data, which means that a considerable number of children in earlier stages of CKD are missed as they will reach end-stage renal disease (ESRD) in adulthood. Here, we report the basic epidemiological data on childhood CKD in Serbia, gathered over the 10-year period of activity of the Serbian Pediatric Registry of Chronic Kidney Disease. METHODS: Since 2000-09, data on incidence, prevalence, aetiology, treatment modalities and outcome of children aged 0-18 years, with CKD Stages 2-4 and CKD Stage 5, were collected by reporting index cases from paediatric centres. RESULTS: Three hundred and thirty-six children were registered (211 boys, 125 girls, male/female ratio 1.7). The median age at registration was 9.0 years [interquartile range (IQR) 3-13]. Median follow-up was 4.0 years (IQR, 1-9). The median glomerular filtration rate (GFR) at the time of the registration was 39.6 mL/min/1.73m(2) (IQR, 13.8-65.4). Median annual incidence of CKD 2-5 stages was 14.3 per million age-related population (p.m.a.r.p.), while those of CKD 2-4 or CKD 5 were 9.1 and 5.7 p.m.a.r.p., respectively. The median prevalence of CKD 2-5 was 96.1 p.m.a.r.p., 52.8 p.m.a.r.p. in CKD 2-4 and 62.2 p.m.a.r.p. in CKD 5. The main causes of CKD were congenital anomalies of kidney and urinary tract and hereditary nephropathies. Kidney survival was the worst in children with glomerular diseases and in those with advanced CKD. Haemodialysis was the most common first modality of RRT. Mortality rate was 4.5%, mainly due to cardiovascular and infectious complications. CONCLUSIONS: Epidemiology of paediatric CKD in Serbia is similar to that reported from developed European countries. The knowledge of the epidemiology of earlier stages of CKD is essential for both institution of renoprotective therapy and planning of RRT, a fact of paramount importance in countries with limited resources.

Acute patellar dislocation in adolescents: operative versus nonoperative treatment.

PURPOSE: The purpose of this prospective non-randomised study was to compare the efficacy of two opposed methods, operative and conservative. Our hypothesis was that if the method was selected correctly, on an individual basis, the results should be approximately equal. METHODS: The study included 37 adolescents aged between 12 and 16 years, with a mean follow up of 6.1 years. The presence of a significant loose body, confirmed by precise imaging, was the key for selecting operative or arthroscopic treatment. In both groups of patients, we evaluated functional knee scores and the incidence of residual patellofemoral disorders. RESULTS: We confirmed our hypothesis using the t-test to compare functional results and a test for comparison of proportions for incidence of residual disorders. There was no statistically significant difference (p=0.091) between operatively and conservatively treated groups with regard to functional results. The same statistical outcome emerged when comparing incidences of re-dislocation (p=0.854), or other major patellar instabilities (p=0.856), between the groups. CONCLUSIONS: The results obtained should not promote a non-operative method on the basis of lower risk, but do support an individual approach based on precise diagnosis and defined criteria.

Increasing incidence of childhood type 1 diabetes in Montenegro from 1997 to 2006.

OBJECTIVE: To determine and analyze the incidence of type 1 diabetes mellitus (T1DM) in 0- to 14-yr-old children in Montenegro from 1997 to 2006. RESEARCH DESIGN AND METHODS: This was a prospective study. Primary case ascertainment came from a diabetes register and secondary independent data source was from prescription data. Age and sex-standardized incidence rates were calculated using direct method, assuming an equal distribution in each age/sex group. The 95% confidence interval (CI) were estimated assuming the Poisson distribution. The independent effects of calendar year, two 5-yr time periods, sex and age groups were estimated with Poisson regression modeling. RESULTS: During the 10-yr period, 184 new cases of type 1 diabetes were identified. Case ascertainment was 100% complete using the capture-recapture method. The mean annual standardized incidence rate over the 10-yr period was 13.4/100 000/yr (95% CI: 11.5-15.5). It increased on average by 4.6% per year (95% CI: -0.4 to -9.6%, p = 0.07). The time-period specific incidence rate from year 1997 to 2001 was significantly lower (10.8; 8.5-13.5) compared with the second period from 2002 to 2006 (16.3; 13.3-19.7), (p < 0.0001). The age-specific incidence for the 0-4-yr age group was significantly lower (8.9; 6.3-12.3) than in 5- to 9-yr age group (14.1; 10.8-18.1); and in the 10-14 yr group (17.2; 13.7-21.3) per 100,000 children. CONCLUSIONS: The incidence rate in last 5 yr places Montenegro in the group of countries with moderate risk for development of type 1 diabetes in children. The average annual increase in incidence is 4.6%.

A prospective cohort study for prediction of difficult laparoscopic cholecystectomy.

INTRODUCTION: Difficult laparoscopic cholecystectomy (DLC) is a stressful condition for surgeon which is followed by greater risk for various injuries (biliary, vascular etc.) Preoperative factors that are related to DLC are landmarks for surgeon to assess the possibilities for overcoming difficulties and making early decision about conversion to an open surgery. In prospective cohort study we evaluated and defined the importance and impact of preoperative parameters on difficulties encountered during surgery, defined DLC, predictors of DLC and index of DLC. MATERIALS AND METHODS: All patients in the study were operated by the same surgeon. We defined the total duration of the operation as the time from insertion of Veress needle to the extraction of gallbladder (GB) and DLC as a laparoscopic cholecystectomy (LC) that lasted longer than the average duration of LC and the value of one standard deviation. RESULTS: Multivariate logistic regression analysis identified five predictors significantly related to DLC: GB wall thickness > 4 mm, GB fibrosis, leukocytosis ˃10 × 109 g/L, ˃ 5 pain attacks that lasted longer than 4 h and diabetes mellitus. The sensitivity of the generated index of DLC in our series is 81.8% and specificity 97.2%. CONCLUSION: Preoperative prediction of DLC is important for the surgeon, for his operating strategy, better organization of work in operating room, reduction of treatment expenses, as well as for the patient, for his timely information, giving a consent for an operation and a better psychological preparation for possible open cholecystectomy (OC).

Serbia within the European context: An analysis of premature mortality.

BACKGROUND: Based on the global predictions majority of deaths will be collectively caused by cancer, cardiovascular diseases, and traffic accidents over the coming 25 years. In planning future national health policy actions, inter - regional assessments play an important role. The purpose of the study was to analyze similarities and differences in premature mortality between Serbia, EURO A, EURO B, and EURO C regions in 2000. METHODS: Mortality and premature mortality patterns were analysed according to cause of death, by gender and seven age intervals. The study results are presented in relative (%) and absolute terms (age-specific and age-standardized death rates per 100,000 population, and age-standardized rates of years of life lost - YLL per 1,000). Direct standardization of rates was undertaken using the standard population of Europe. The inter-regional comparison was based on a calculation of differences in YLL structures and with a ratio of age-standardized YLL rates per 1,000. A multivariate generalized linear model was used to explore mortality of Serbia and Europe sub-regions with ln age-specific death rates. The dissimilarity was achieved with a p

Biomarkers for the prediction of early pulmonary embolism related mortality in spontaneous and provoked thrombotic disease.

Factors associated with provoked PE may influence a biomarker's predictive value for the primary outcome. The aim of this study was to investigate the value of BNP, cTnI, CRP and D-Dimer measurements taken soon after hospital admission for the prediction of 30-day PE-caused death in patients with spontaneous versus provoked PE.Data were extracted from a pool of 726 consecutive PE patients enrolled in the multicenter Serbian PE registry. Blood concentrations of BNP, cTnI, CRP and D-dimer were measured during the first 24 h of hospitalization. BNP blood level had strong predictive value for the primary outcome in spontaneous PE (c-statistics 0.943, 95% CI 0.882-1.000, p = .001) and a slightly lower predictive outcome in provoked PE (c-statistics 0.824, 95% CI 0.745-0.902, p < .001). NRI and IDI showed that none of the markers, when added to BNP, could improve Cox regression prediction models for 30-day PE-related mortality in either the spontaneous or provoked PE group. Blood levels of BNP measured during the first 24 h of hospital admission had an excellent predictive value for 30-day PE-related mortality in spontaneous PE and slightly lower predictive value in provoked PE, whereas CRP, cTnI and D-Dimer did not contribute significantly to the predictive value of BNP in either group.

Impact on long-term mortality of access and non-access site bleeding after primary percutaneous coronary intervention.

OBJECTIVES: The influence of the bleeding site on long-term survival after the primary percutaneous coronary intervention (PCI) is poorly understood. This study sought to investigate the relationship between in-hospital access site versus non-access site bleeding and very late mortality in unselected patients treated with primary PCI. METHODS: Data of the 2715 consecutive patients with ST-segment elevation myocardial infarction treated with primary PCI, enrolled in a prospective registry of a high volume tertiary centre, were analysed. Bleeding events were assessed according to the Bleeding Academic Research Consortium (BARC) criteria. The primary outcome was 4-year mortality. RESULTS: The BARC type ≥2 bleeding occurred in 171 patients (6.3%). Access site bleeding occurred in 3.8%, and non-access site bleeding in 2.5% of patients. Four-year mortality was significantly higher for patients with bleeding (BARC type ≥2) than in patients without bleeding (BARC type 0+1), (36.3% vs 16.2%, p<0.001). Patients with non-access site bleeding had higher 4 year mortality (50.7% vs 26.5%, p=0.001). After multivariable adjustment, BARC type ≥2 bleeding was the independent predictor of 4 year mortality (HR 2.01; 95% CI 1.49 to 2.71, p<0.001). Patients with a non-access site bleeding were at 2-fold higher risk of very late mortality than patients with an access site bleeding (HR 2.62; 1.78 to 3.86, p<0.001 vs HR 1.57; 1.03 to 2.38, p=0.034). CONCLUSIONS: Both access and non-access site BARC type ≥2 bleeding is independently associated with a high risk of 4-year mortality after primary PCI. Patients with non-access site bleeding were at higher risk of late mortality than patients with access site bleeding.

The assessment of health-related quality of life in relation to the body mass index value in the urban population of Belgrade.

BACKGROUND: The association between excess body weight, impairment of health and different co-morbidities is well recognized; however, little is known on how excess body weight may affect the quality of life in the general population. Our study investigates the relationship between perceived health-related quality of life (HRQL) and body mass index (BMI) in the urban population of Belgrade. METHODS: The research was conducted during 2005 on a sample of 5,000 subjects, with a response of 63.38%. The study sample was randomly selected and included men and women over 18 years of age, who resided at the same address over a period of 10 years. Data were collected by means of a questionnaire and nutritional status was categorized using the WHO classification. HRQL was measured using the SF-36 generic score. Logistic regression analysis was used to compare HRQL between subjects with normal weight and those with different BMI values; we monitored subject characteristics and potential co-morbidity. RESULTS: The prevalence of overweight males and females was 46.6% and 22.1%, respectively. The prevalence of obesity was 7.5% in males and 8.5% in females.All aspects of health, except mental, were impaired in males who were obese. The physical and mental wellbeing of overweight males was not significantly affected; all score values were similar to those in subjects with normal weight.By contrast, obese and overweight females had lower HRQL in all aspects of physical functioning, as well as in vitality, social functioning and role-emotional. CONCLUSION: The results of our study show that, in the urban population of Belgrade, increased BMI has a much greater impact on physical rather than on mental health, irrespective of subject gender; the effects were particularly pronounced in obese individuals.

GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia.

BACKGROUND/AIMS: The purpose of this study was to investigate the involvement of GABAergic mechanisms in the antihyperalgesic effect of carbamazepine and oxcarbazepine by examining the effect of bicuculline (GABA(A) receptor antagonist) on these effects of antiepileptic drugs. METHODS: Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: (1) the development of hyperalgesia induced by Con A; (2) the effects of carbamazepine/oxcarbazepine on Con A-induced hyperalgesia, and (3) the effects of bicuculline on the carbamazepine/oxcarbazepine antihyperalgesia. RESULTS: Intraperitoneally injected bicuculline (0.5-1 mg/kg, i.p.) exhibited significant suppression of the systemic antihyperalgesic effects of carbamazepine (27 mg/kg, i.p.) and oxcarbazepine (80 mg/kg, i.p.). When applied intraplantarly, bicuculline (0.14 mg/paw, i.pl.) did not produce any change in the peripheral antihyperalgesic effects of carbamazepine (0.14 mg/paw, i.pl.) and oxcarbazepine (0.5 mg/paw, i.pl.). Bicuculline alone did not produce an intrinsic effect in the paw-pressure test. CONCLUSION: These results indicate that the antihyperalgesic effects of carbamazepine and oxcarbazepine against inflammatory hyperalgesia involve in part the GABAergic inhibitory modulation of pain transmission at central, but not at peripheral sites, which is mediated via GABA(A) receptor activation.

Stressful life events and psychological dysfunctions before the onset of type 1 diabetes mellitus.

AIM: To test the hypothesis that stressful life events and psychological dysfunction increase the risk for development of type 1 diabetes mellitus (DM1). METHOD: A case-control study comprising 105 children with DM1 and 210 controls matched by age +/- 1 year), sex and place of residence. Conditional univariate and multivariate logistic regressions were used to analyze the data. RESULTS: After adjustment for possible confounders, the following factors were positively related to DM1: parents' job-related issues changed or lost job (odds ratio [OR] 11.5, 95% confidence interval [CI] 1.6-81.8); other severe life events--severe accident, hospitalization or death of close friend, quarrels between parents, war in republics of former Yugoslavia, near-drowning in a pool, falling down, unhurt participant of an accident (OR 68.5, 95% CI 13.5-349.0); other minor life events--conflicts with parents/teacher/neighbors, lost in town, physical attack, failure in competition, penalty, examination, death of pet, presence at lightning strike, thrown out of dwelling (OR 32.7, 95% CI 6.3-169.6); and learning problems (OR 17.5, 95% CI 4.3-71.6). CONCLUSION: These results support the hypothesis that stressful life events and psychological dysfunctions are associated with DM1.

Time trends in cancer mortality in central Serbia.

OBJECTIVE: To examine cancer mortality trends in Central Serbia (1985-2002). METHODS: Cancer mortality rates were based on the official death certificates (n=192849). They were standardized for age and sex. RESULTS: In the observed period, mortality rates showed a tendency to increase in both males (y = 118.54 + 2.27x, p = 0.0001) and females (y = 83.32 + 1.02x, p = 0.0001). Mortality of lung cancer increased in both sexes (y = 32.38 + 0.86x, p < 0.001 for males, y = 6.25 + 0.25y, p < 0.001 for females), as did colorectal cancer (y = 10.87 + 033x, p < 0.001 for males, y = 8.51 + 0.09x, p < 0.05 for females). Breast cancer mortality rates increased (y = 14.48 + 0.35x, p = 0.0001), and so did cervical cancer (y = 5.14 + 0.14x, p < 0.01). Mortality of gastric cancer in males has been moderately decreasing after 1990s (y(19902002) = 13.67-0.20x, p < 0.01), while prostate cancer mortality remained relatively stable. CONCLUSIONS: Increasing cancer mortality trends in the last 18 years in Central Serbia indicate the extremely urgent needs for health authorities to adopt measures of cancer prevention that proved effective in other countries.

Burden of cancer in Serbia.

AIM: To provide a comprehensive assessment of burden of selected cancers in Serbia. METHOD: We calculated disability adjusted life years (DALY)-- the sum of the years of life lost (YLL) from premature mortality and the years lived with disability (YLD)--for cancers of stomach, colon and rectum, lung, breast, and cervical cancer for central Serbia and Vojvodina, Serbia and Montenegro. The obtained values were compared with the corresponding values for European region as estimated by the World Health Organization. The study was conducted between October 2002 and September 2003. The cancer burden was estimated for the year 2000. RESULTS: Observed cancers were responsible for 133,689 DALYs (73,197 for men and 60,482 for women). There were significantly more losses because of premature death than disease disability (95.2% vs 4.8% in men P<0.001, and 93.2% vs 6.8% in females, P<0.001). The cancer burden was dominated by lung cancer in men and breast cancer in women. The cancer burden was very small before the age of 35. CONCLUSION: DALYs per 1000 population were higher in Serbia than in the European region for all observed cancers except for stomach cancer. The participation of a burden caused by disability in the total burden of selected cancers was lower in Serbia than in other European countries, with the greatest differences in colorectal, breast, and cervical cancers.