We aimed to evaluate levels of amino-terminal pro-brain natriuretic peptid (NT-proBNP) in prediction of left ventricular ejection fraction (LVEF) in heart failure patients. Prospective study on 60 consecutive patients with symptoms and signs of heart failure was performed. Blood samples for NT-proBNP analysis was taken from all test subjects and echocardiography was also done in all of them. According to LVEF value, patients were divided into four groups; those with <or=30%, 31 to 39%, 40 to 49% and >or=50%. NT-proBNP values correlated with LVEF value. Regression analysis was used to evaluate how well NT-proBNP values predict LVEF. We used Receiver Operating Characteristic Curve calculation to evaluate diagnostic performance of NT-proBNP in estimation of LVEF. Average value of NT-proBNP in test group was 3191.69+/-642.89 pg/ml (p<0.001). Average value of NT-proBNP decreased with higher LVEF categories with significant (p<0.001) and high negative correlation (r= -0,75). Stepwise multivariate linear regression analysis showed that logarithmic value of NT-proBNP was excellent predictor of LVEF value (p<0.05). Model equation based on regression analysis was LVEF=88.645-15.311 x log (NT-proBNP). Predictive model for LVEF yielded from regression analysis had sensitivities of 98% and 81%, specificities of 20% and 90%, positive predictive values of 86% and 78% and negative predictive values of 67% and 92% for predicting patients with LVEF<50% and LVEF<40%, respectively. There was negative linear correlation between NT-proBNP and LVEF. NT-proBNP was excellent predictor of LVEF value (p<0.05).

Diagnosis and management of patients with SLE (Systemic Lupus Eritematosus), autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), involves specific diagnostic tests, such as IFA-AMA, IFA anti-dsDNA and immunoblotting for the detection of autoantibodies for specific autoantigens (mitochondria, dsDNA, M2, LKM-1, LC-1, SLA/LP). We established specific correlation between the detected autoantibodies and corresponding clinical findings. The total of 813 serum specimens were probed with IFA-anti-dsDNA, 98 of which tested positive. We also performed dilution analysis to the end point for all the positive specimens. Numerous specimens were tested by IFA, AMA and immunoblotting.

Since its foundation in 1992, the Croatian Medical Journal (CMJ) has followed the strict standards of quality in the scientific publishing. However, the Journal has been aware that its specific position demands more than just following the already established rules. From the very beginning, the Journal declared an “author-helpful policy,” stating that “journal editors should have a major role in training authors in science communication, especially in smaller and developing scientific communities. Journal authors usually send scientifically acceptable but poorly prepared articles and it is a pity to lose valid data because of their poor presentation.” (1,2). In brief, the editors and editorial staff of the CMJ have been well aware that the skills of scientific reporting and publishing in our academic community are not developed and that valuable research results and valid data are being lost because of poor presentation. To be perfectly honest, ten years ago this statement looked like a nice promise, one of the many we in academic medicine learnt not to take too seriously.

UNLABELLED The gallbladder cancer is the most common primary cancer of the hepatobiliary system, and ranks fifth of the cancers of the gastrointestinal system. It is accidentaly found in 1-3 % of patients with gallstone disease, and in 0,5-2,4% on postmortem exam. GOAL Show the incidence, clinical state, and suplement the diagnostic procedure of the patients with the risk factors for gallbladder cancer. Find proper surgical treatment in every stage of the disease according to Nevin-Moran system and the hystological type of the cancer. METHODS Retrospectively we evaluated all cholecystectomies in our hospital in a three year period. We established the incidence of gallbladder cancer and we tried to discover the common characteristics of this group of patients. We analized the histological type of the cancer, and the stage of the disease in correlation with clinical presentation, results of the surgical treatment , and the survival and the quality of life. RESULTS In three years we performed 2553 cholecystectomies, and in 1,7 % of patients -43 patient we discovered the cancer of gallbladder. It is 5 times more common in females. The mean age of the patients with gallbladder cancer is 65 years (55 - 82 years). The etiology of this disease is unknown. In 5 (11,6 %) patients cancer is discovered preoperatively. In 38 (88,4 %) patients it was adenocarcinoma of the gallbladder. Other morphologic types are analplastic cancer, carcinosarcoma, and "squamous cell carcinoma". In 30 patients (69,8 %) we performed cholecystectomy, and in 8 (18,6%) patients extended cholecystectomy with its components. Radical resective procedures on liver were performed in 5 (11,6%) patients. According to the localisation in 60% of cases the cancer was located in fundus, in 30% of cases in corpus,and 10% of cases in the neck of the gallbladder. No patient with stage V survived 1 year after the procedure. CONCLUSION The incidence of the gallbladder cancer in our series is in the slight increase. The quality of life and the survival are inversely correlated with the depth of the invasion and the extent of the spread of the cancer. The extensive surgical procedures in advanced stage of the disease, because of the grim prognosis, does not justify the risk of the operative treatment.

The retrospective study included 250 patients, treated at Clinic for cardiovascular diseases of Tuzla Clinical center, between 30.08.2003. and 15.11.2004. In the coronary disease group there were 145 men, 55 women, with diagnosed coronary artery stenosis of 50% or more. The control group had 150 patients, 35 men and 15 women, medium age of 58.2. The control group had coronary artery stenosis of 50% or less. Coronarography was done using AXIOM ARTIS DFC (SIEMENS). Lipoproteins were determined on the Clinic for biochemistry of Tuzla Clinical Center using automatic analyser DIMENSION LxR (DADE BOEHRING). In the coronary artery disease (CAD) group elevated triglycerides were found in 38.5%, total cholesterol in 88% and LDL 55.5% of patients. The concentration of HDL cholesterol was elevated in 52.5% of patients. In the control group elevated values of triglycerides were found in 28%, total cholesterol 46%, LDL cholesterol 16%, and lower values of HDL in 10% of patients. Statistically significant differences of lipide profile of CAD patients in relation to the control group was defined. Using regresional analysis it was established that decide elevated values of total and LDL cholesterol, low values of HDL were also significant.

UNLABELLED The news in understanding intrahepatal anatomy, such as radiology contemporary technology making easier segmental and bisegmental access to hepatal resection. This access comprises resection of isolated anatomical segments or a sector of liver which is depends of magnitude of intrahepatal pathological process. After segmental or bisegmental resection of liver, patients were analysed in the period from 15 and 30 days after the operation. Analysis of patients from this period comprise: localisation of tumour in relation on segments, liver test and follow up, technique of resection, intraoperative stream, the period of operation, blood follow up through v. portae, blood loss and quantitative and qualitative analysis of postoperative complications. RESULTS between January 2000 and March 2005, sixty two subject were analysed that have been operated on our clinic (segmental or bisegmental resection), because of the metastatic process of liver and hepatocellular carcinoma of liver (HCC). Hospital mortality was 2.1%, with most often mortality in patients with HCC and cirrhosis of liver. High of morbidity from this period were 19,8%. Need for transfusion of blood (fresh erythrocytes) were 1,2 +/- 0,5 U. Patients with HCC had more needs from blood transfusions contrary patients without HCC; 2,9 +/- 1,4 contrary 0,7 +/- 0,28 U (p<0,05). Recidivism of malignant process in hepatal margin were 2,7%. CONCLUSION Segmental hepatal resection is very accurate technique which makes possible complete resection of tumour and in the same time preservation of healthy liver parenchyma. Segmental hepatal resection is especially useful for patients with HCC and patients with recidivism or progress of primary process.

INTRODUCTION Spinal muscular atrophies (SMA) are group of neuromuscular disorders characterized by degeneration of motorneurons in anterior column of medulla spinalis, and sometimes in motoneurons of cranial nerves and the brain. Causes of SMAs are mutations in genes encoding for SMN, SIP and NAIP that are very low in motorneurons of these patients. Ribonucleases (RNases) are enzymes that depolimerize RNA and may destabilize DNA. AIM The objective of this study was to determine ribonuclease activity in serum and urine of SMA patients. METHODS RNases were purified by anion-kation-exchange chromatographies, and HPLC, and their activity was measured by immunodetection using specific antibodies against rinonucleases in presence of RNA as a substrate. RESULTS Eosinophil-derived neurotoxin (EDN) activity iin serum of SMA patients was 5.6, 3.8 and 2.6 higher in type I, II and III comparing with control group. RNase inhibitor activity in serum of the same patients was 3.0 and 2.4 lower in type I and II vs. Control group, but in type III was unchanged. Similar results are found in urine of the same patients. CONCLUSION Increased serum and urin EDN activities in SMA patients could be used as a new additional clinical marker in their diagnosis.

Liver resections, because of its complexity, present a big challenge for every surgeon. A malignant diseases, which are the most frequent indications for this type of operations, additionally complicate job of the surgeons. Because the flag immunological system, in this type of patients, with reduced reserves of the liver, can have unforeseen postoperative consequence. The bleeding during and after operations presents one of the most difficult problems with liver resections. Introduction of the Pringle maneuver, reduce the risks for this operations to the minimum. The aim of this work at first is to analyze and compare functional parameters of the liver with or without intermittent hepatic pedicle clamping (HPC), for the purpose of the establishing invasivity and justification of its application. A statistical pattern was 30 patients with performed liver resections using intermittent HPC and 30 patients without using intermittent HPC, during liver resections. Results showed that performing liver resections with Pringle manuever do not have negative repercussions on the liver functions with less postoperative complications and postoperative hospital duration.

We have reported that norepinephrine (NE) and angiotensin II (Ang II) increase CaM kinase II activity, which, in turn, activates cytosolic phospholipase A2 (PLA2) and releases arachidonic acid. The products of arachidonic acid generated via cytochrome P-450 and lipoxygenase contribute to the development of hypertension and vascular smooth muscle cell (VSMC) hyperplasia. The purpose of this study was to investigate whether CaM kinase II contributes to VSMC proliferation elicited by NE and Ang II and to hypertension induced by Ang II. NE (1 &mgr;mol/L) and Ang II (1 &mgr;mol/L) increased proliferation of rabbit aortic VSMC as measured by increased [3H]-thymidine incorporation; this effect of NE and Ang II was attenuated 88±10% and 64±11% by the CaM kinase II inhibitor KN-93, respectively. Infusion of Ang II with miniosmotic pumps (350 ng/min for 6 days) in rats elevated mean arterial pressure (MABP), which was reduced by simultaneous infusion of KN-93 (578 ng/min, for 6 days) (Ang II alone: MABP =174±3 mm Hg, n=12 versus Ang II + KN-93: MABP 123±5 mm Hg, n=4, P <0.05). Administration of KN-93 as a single bolus injection (16 mg/Kg), but not its vehicle, in Ang II–infused hypertensive animals also decreased MABP from 179±9 mm Hg to 109±6 mm Hg (n=5, P <0.05). CaM kinase II activity was increased in the kidney of Ang II–infused hypertensive animals compared with normotensive controls. Treatment with KN-93 reduced CaM kinase II activity and ameliorated the intravascular injury in the kidneys of Ang II–infused hypertensive rats. Our data indicate that CaM kinase activation represents an important component of the mechanism(s) initiating VSMC proliferation and the development and maintenance of Ang II–induced hypertension in rat.

In this review we used the published data on depleted uranium (experimental and epidemiological) from the current literature. Depleted uranium is a toxic heavy metal that in high dose may cause poisoning and health effects as those caused by lead, mercury, and chromium. It is slightly radioactive. The aim of this review was to select, to arrange, to present references of scientific papers, and to summarise the data in order to give a comprehensive image of the results of toxicological studies on depleted uranium that have been done on animals (including carcinogenic activity). We have also used epidemiological posted study results related to occupational and environmental exposure to depleted uranium. The toxicity of uranium has been studied extensively. The results of the studies indicated primarily its chemical toxicity, particularly renal effects, but depleted uranium is not radiological hazard. Uranium is not metal determined to be carcinogenic (the International Agency of Research on Cancer). The military use of depleted uranium will give additional insight into the toxicology of depleted uranium. The present controversy over the radiological and chemical toxicity of depleted uranium used in the Gulf War requests further experimental and clinical investigations of its effects on the biosphere and human beings.

We have reported that norepinephrine (NE) and angiotensin II (Ang II) increase CaM kinase II activity, which, in turn, activates cytosolic phospholipase A2 (PLA2) and releases arachidonic acid. The products of arachidonic acid generated via cytochrome P-450 and lipoxygenase contribute to the development of hypertension and vascular smooth muscle cell (VSMC) hyperplasia. The purpose of this study was to investigate whether CaM kinase II contributes to VSMC proliferation elicited by NE and Ang II and to hypertension induced by Ang II. NE (1 mol/L) and Ang II (1 mol/L) increased proliferation of rabbit aortic VSMC as measured by increased [H]-thymidine incorporation; this effect of NE and Ang II was attenuated 88 10% and 64 11% by the CaM kinase II inhibitor KN-93, respectively. Infusion of Ang II with miniosmotic pumps (350 ng/min for 6 days) in rats elevated mean arterial pressure (MABP), which was reduced by simultaneous infusion of KN-93 (578 ng/min, for 6 days) (Ang II alone: MABP 174 3 mm Hg, n 12 versus Ang II KN-93: MABP 123 5 mm Hg, n 4, P 0.05). Administration of KN-93 as a single bolus injection (16 mg/Kg), but not its vehicle, in Ang II–infused hypertensive animals also decreased MABP from 179 9 mm Hg to 109 6 mm Hg (n 5, P 0.05). CaM kinase II activity was increased in the kidney of Ang II–infused hypertensive animals compared with normotensive controls. Treatment with KN-93 reduced CaM kinase II activity and ameliorated the intravascular injury in the kidneys of Ang II–infused hypertensive rats. Our data indicate that CaM kinase activation represents an important component of the mechanism(s) initiating VSMC proliferation and the development and maintenance of Ang II–induced hypertension in rat. (Hypertension. 2002;39[part 2]:704-709.)

The signaling mechanisms downstream of growth factor-stimulated proliferation in myeloid leukemia cells have not yet been fully elucidated. Recent evidence suggests that alternate pathways to the mitogen-activated protein kinase cascade are required. We have previously shown that Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) activates cytosolic phospholipase A2 (cPLA2), which is involved in the proliferation of vascular smooth muscle cells. In the present study, the contribution of this pathway was investigated in the proliferation of U-937 myeloid leukemia cells. In U-937 cells, fetal bovine serum (FBS)-induced proliferation was attenuated by CaM kinase II inhibitor KN-93 but not by its inactive analog KN-92. Inhibitors of cPLA2 (methyl arachidonyl fluorophosphonate and arachidonyl trifluoromethyl ketone) also reduced proliferation of U-937 cells. FBS-induced proliferation was also attenuated by cotransfection with cPLA2 antisense oligonucleotides. These results suggest a role for CaM kinase II and cPLA2 in the proliferation of U-937 cells. FBS stimulated CaM kinase II and cPLA2 activities in a time-dependent manner. Moreover, FBS-stimulated phosphorylation and activation of cPLA2 activation was inhibited by KN-93. FBS-stimulated phosphorylation of CaM kinase II was blocked by KN-93 but not by cPLA2 inhibitors, suggesting that CaM kinase II activates cPLA2. The products of phospholipid hydrolysis produced by cPLA2, lysophosphatidylcholine but not arachidonic acid, increased [3H]thymidine incorporation in U-937 cells. These data suggest that exposure of U-937 cells to FBS promotes phosphorylation and activation of CaM kinase II, leading to stimulation of cPLA2 and generation of lysophosphatidylcholine and resultant proliferation of these cells.

INTRODUCTION Impaired cardiac function is frequently present in patients on maintenance haemodialysis. AIM To assess the left ventricular diastolic function in patients on haemodialysis. MATERIAL AND METHODS We used 2D and pulsed wave Doppler echocardiography to evaluate the left ventricular diastolic function in 40 patients on haemodialysis and compared those to healthy controls. RESULTS Majority of Doppler parameters were changed in patients on haemodialysis. Diastolic dysfunction was present in 77.5% patients. In comparison to the healthy controls haemodialysis patients showed significant increase in peak velocity of late diastolic filling, (A wave, 76.82 +/- 23.76 cm/s vs. 58.46 +/- 9.65 cm/s p < 0.001) and reduction in the E/A ratio (1.00 +/- 0.26 vs. 1.26 +/- 0.31 p < 0.001). CONCLUSION There was significant impairment in left ventricular diastolic function in patients on haemodialysis.

INTRODUCTION The activation of PI-3 kinase/AKT/PKB signal transduction pathway has implicated in the cell growth regulation and proliferation. AIM To determine a role of PI-3 kinase/AKT/PKB signal transduction pathway in the kidney of Angiotensin II-induced hypertensive rats. METHODS NZW (New Zealand White) rats have been infused by Angiotensin II using osmotic minipump for six days (n = 8). Control group was untreated rats (n = 6). PI-3 inase and AKT/PKB activities were measured in the presence or absence of different inhibitors. RESULTS Angiotensin II elevated mean arterial blood pressure (MABP) to 182 +/- 2 mm Hg (p < 0.001) vs untreated control rats (95 +/- 3 mm Hg). Ras-GTPase and PI-3 Kinase activities were elevated in angiotensin II-treated group. Ras inhibitors FPT III and BMS/191563 attenuated MABP to 122 +/- 2 and 127 +/- 4 mm Hg (p < 0.05) and abolished Ras-GTPase and PI-3 Kinase activities. AKT/PKB activity followed the PI-3 kinase activity. CONCLUSION PI-3 kinase/AKT/PKB signal transduction pathway in the kidney is activated and mediates Angiotesin II-induced hypertension.

Precancerous and early cancerous lesions of the cervix uteri (ASCUS, AGUS, LSIL and HSIL) are precursors of invasive cancer of the cervix uteri. By Papanicolaou test they are graded as Pap III and Pap IV. Different factors may increase a risk for those lesions as well as converting low stage lesion into higher one. Oral contraceptive use is one of the most potential risk factor for those lesions. The goal of this study was to examine a relationship between oral contraceptive use and precancerous and early cancerous lesion of the cervix lesion of the cervix uteri by using Papanicolaou test. After adjustment for other potential risk factors our results have shown: 1) there is high significant positive relationship between oral contraceptives use and precancerous and early cancerous lesions of the cervix uteri; 2) the users of oral contraceptives have shown Pap III and Pap IV smear grade five to ten years earlier than non-users; 3) long-term users have shown Pap III and Pap IV five years earlier than short-term users for middle age group (35-44 years); 4) the border between Pap III and Pap IV is shifted for five years toward earlier age.