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Giljaca V.,Clinical Hospital Center Rijeka
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: Methotrexate has been used to treat patients with primary biliary cirrhosis as it possesses immunosuppressive properties. The previously prepared version of this review from 2005 showed that methotrexate seemed to significantly increase mortality in patients with primary biliary cirrhosis. Since that last review version, follow-up data of the included trials have been published. OBJECTIVES: To assess the beneficial and harmful effects of methotrexate for patients with primary biliary cirrhosis. SEARCH STRATEGY: Randomised clinical trials were identified by searching The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, and EMBASE (from their inception until September 2009). Reference lists were also read through. Authors of trials were contacted. SELECTION CRITERIA: We searched to include randomised clinical trials comparing methotrexate with placebo, no intervention, or another drug irrespective of blinding, language, year of publication, or publication status. DATA COLLECTION AND ANALYSIS: Our primary outcomes were mortality, and mortality or liver transplantation combined. Dichotomous outcomes were reported as relative risks (RR) and hazard ratios (HR) if applicable. Continuous outcomes were reported as mean differences (MD). MAIN RESULTS: Five trials were included. Four trials with 370 patients compared methotrexate with placebo or no intervention (three trials added an equal dose of ursodeoxycholic acid to the intervention groups). The bias risk of these trials was high. We did not find statistically significant effects of methotrexate on mortality (RR 1.32, 95% CI 0.66 to 2.64), mortality or liver transplantation combined, pruritus, fatigue, liver complications, liver biochemistry, liver histology, or adverse events. The pruritus score (MD - 0.17, 95% CI - 0.25 to - 0.09) was significantly lower in patients receiving methotrexate. The prothrombin time was significantly worsened in patients receiving methotrexate (MD 1.60 s, 95% CI 1.18 to 2.02). One trial with 85 patients compared methotrexate with colchicine. The trial had low risk of bias. Methotrexate, when compared to colchicine, did not significantly effect mortality, fatigue, liver biopsy, or adverse events. Methotrexate significantly benefited pruritus score (MD - 0.68, 95% CI - 1.11 to - 0.25), serum alkaline phosphatases (MD - 0.41 U/l, 95% CI - 0.70 to - 0.12), and plasma immunoglobulin M (MD - 0.47 mg/dl, 95% CI - 0.74 to - 0.20) compared with colchicine. Other outcomes showed no statistical difference. AUTHORS' CONCLUSIONS: Methotrexate had no statistically significant effect on mortality in patients with primary biliary cirrhosis nor the need for liver transplantation. Although methotrexate may benefit other outcomes (pruritus score, serum alkaline phosphatase, immunoglobulin M levels), there is no sufficient evidence to support methotrexate for patients with primary biliary cirrhosis.


Bralic M.,Clinical Hospital Center Rijeka | Stemberga V.,University of Rijeka | Stifter S.,University of Rijeka
Medical Hypotheses | Year: 2012

Traumatic brain injury (TBI) is a major cause of death and disability throughout the world. In recent years, researchers focused on the pathological significance of calcium accumulation in the brain after TBI. Neuronal calcium homeostasis disturbances may result in the activation of calpain a ubiquitous calcium-sensitive protease. The calpain family has a well-established causal role in neuronal cell death following acute brain injury: their activation has been observed to progressively increase after either contusive or diffuse brain trauma in animals, suggesting calpain to be a mediator of early neuronal damage.We hypothesize that pretreatment with the calpain inhibitors in population at objective risk (military soldiers' pre combat) in appropriate dose would open therapeutic time window expected to prevent and reduce extensive brain damage by providing optimal TBI neuroprotection. Additional therapeutic strategy for TBI, based on calpain modulating actions such as pretreatment with calpain inhibitors has been proposed.Since calpain overexpression has been well established in acute neuronal injury and further subsequent neurodegeneration, from a clinical viewpoint, we speculate that if this hypothesis proves correct pretreatment inhibitors introduction may become a therapeutic option for different brain pathologies to be approached and treated with. © 2012 Elsevier Ltd.


Salkic N.N.,University of Tuzla | Jovanovic P.,University of Tuzla | Hauser G.,Clinical Hospital Center Rijeka | Brcic M.,University of Tuzla
American Journal of Gastroenterology | Year: 2014

OBJECTIVES:Extent of liver fibrosis is one of the most important factors in determining prognosis and the need for active treatment in chronic hepatitis B (CHB). Noninvasive alternatives such as FibroTest/Fibrosure (FT) have been developed in order to overcome the shortcomings of liver biopsy (LB). We aimed to systematically review studies describing the diagnostic accuracy of FT for predicting CHB-related fibrosis.METHODS:MEDLINE and EMBASE searches and hand searching methods were performed to identify studies that assessed the diagnostic accuracy of FibroTest in HB patients using LB as a reference standard. We used a hierarchical summary receiver operating curves model and the bivariate model to produce summary receiver operating characteristic curves and pooled estimates of sensitivity and specificity.RESULTS:We included 16 studies (N=2494) and 13 studies (N=1754) in the heterogenous meta-analysis for liver fibrosis and cirrhosis, respectively. The area under the hierarchical summary receiver operating curve for significant liver fibrosis and for all included studies was 0.84 (95% confidence interval (CI): 0.78-0.88). At the FT threshold of 0.48, the sensitivity, specificity, and diagnostic odds ratio (DOR) of FT for significant fibrosis were 61 (48-72%), 80 (72-86%), and 6.2% (3.3-11.9), respectively. The area under the hierarchical summary receiver operating curve for liver cirrhosis and for all included studies was 0.87 (95% CI: 0.85-0.90). At the FT threshold of 0.74, the sensitivity, specificity, and DOR of FT for cirrhosis were 62 (47-75%), 91 (88-93%), and 15.7% (8.6-28.8), respectively.CONCLUSIONS:FibroTest is of value in exclusion of patients with CHB-related cirrhosis, but has suboptimal accuracy in the detection of significant fibrosis and cirrhosis. It is necessary to further improve the test or combine it with other noninvasive modalities in order to improve accuracy. © 2014 by the American College of Gastroenterology.


Atalic B.,Clinical Hospital Center Rijeka
AMHA - Acta Medico-Historica Adriatica | Year: 2015

Emanuel Edward Klein (1844 - 1925) was a British microbiologist of Croatian origin. He was born in Osijek in what is currently the Republic of Croatia and which was then part of the Habsburg Monarchy, he completed his medical studies in Vienna in 1869, and went on to spend his entire career in London. Although trained as an anatomist, embryologist and histologist, his main area of research was microbiology. Due to the fact that back then it was a new and fast developing discipline, he was able to pursue his interests in many directions and make significant discoveries, such as the identification of the ‘Bacillus enteritidis sporogenes’ as a cause of summer hospital diarrhoeas. Although the overwhelming majority of his researches dealt with bacteria which attacked humans, in 1892 he published a book entitled The Etiology and Pathology of Grouse Disease, Fowl Enteritis, and Some Other Diseases Affecting Birds, which revealed the results of his experiments on the bacteria which affected birds. In the context of the general development of the microbiology, this paper tries to give an objective evaluation of this until now widely neglected book. © 2015, Croatian Scientific Society for the History of Health. All rights reserved.


Hauser G.,Clinical Hospital Center Rijeka | Pletikosic S.,University of Rijeka | Tkalcic M.,University of Rijeka
World Journal of Gastroenterology | Year: 2014

Irritable bowel syndrome (IBS) is considered a biopsychosocial disorder, whose onset and precipitation are a consequence of interaction among multiple factors which include motility disturbances, abnormalities of gastrointestinal sensation, gut inflammation and infection, altered processing of afferent sensory information, psychological distress, and affective disturbances. Several models have been proposed in order to describe and explain IBS, each of them focusing on specific aspects or mechanisms of the disorder. This review attempts to present and discuss different determinants of IBS and its symptoms, from a cognitive behavioral therapy framework, distinguishing between the developmental predispositions and precipitants of the disorder, and its perpetuating cognitive, behavioral, affective and physiological factors. The main focus in understanding IBS will be placed on the numerous psychosocial factors, such as personality traits, early experiences, affective disturbances, altered attention and cognitions, avoidance behavior, stress, coping and social support. In conclusion, a symptom perpetuation model is proposed. © 2014 Baishideng Publishing Group Inc. All rights reserved.

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