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Background: Metformin is the first-choice drug for patients with Type 2 diabetes, and this therapy is characterized by being weight neutral. However, in the elderly an additional unintentional weight loss could be considered as an adverse effect of the treatment., Objectives: We aimed to perform a meta-analysis of placebo-controlled studies investigating the body weight changes upon metformin treatment in participants older than 60 years., Materials and Methods: PubMed, EMBASE and the Cochrane Library were searched. We included at least 12 week-long studies with placebo control where the mean age of the metformin-treated patients was 60 years or older and the body weight changes of the patients were reported. We registered our protocol on PROSPERO (CRD42017055287)., Results: From the 971 articles identified by the search, 6 randomized placebo-controlled studies (RCTs) were included in the meta-analysis (n = 1541 participants). A raw difference of -2.23 kg (95% CI: -2.84 --1.62 kg) body weight change was detected in the metformin-treated groups as compared with that of the placebo groups (p<0.001). Both total cholesterol (-0.184 mmol/L, p<0.001) and LDL cholesterol levels (-0.182 mmol/L, p<0.001) decreased upon metformin-treatment., Conclusions: Our meta-analysis of RCTs showed a small reduction of body weight together with slight improvement of the blood lipid profile in patients over 60 years. With regard to the risk of unintentional weight loss, metformin seems to be a safe agent in the population of over 60 years. Our results also suggest that metformin treatment may reduce the risk of major coronary events (-4-5%) and all-cause mortality (-2%) in elderly diabetic populations., Competing Interests: The authors have declared that no competing interests exist.

: The diagnosis of thrombophilia is a cost-consuming and time-consuming process, as each defect should be separately investigated. The Coagulation Inhibitor Potential (CIP) assay is a promising new global test, sensitive for most of the hereditary thrombophilias, developed for manual methodology. We adapt the original method to an optical coagulation analyser. By this automation, the test will be easier, faster and more precise, and it also allows carrying out 18 measurements simultaneously. The CIP assay was performed in 126 healthy subjects and 193 patients with different types of hereditary thrombophilia conditions. Detected with conventional laboratory tests high-risk thrombophilia was present in 70 patients: deficiencies of antithrombin (AT) (n = 12), protein C (PC) (n = 14), protein S (PS) (n = 6), homozygous factor V Leiden (FVL) mutation (n = 9) and combined types (n = 29). Low-risk thrombophilia was present in 123 patients: heterozygous FVL (n = 115) and FII G2010A mutation (n = 8). Significantly lower median CIP values were found for AT-,PC-, PS deficiencies, homozygous and heterozygous FVL mutations and combined thrombophilias (P < 0.01) as compared with healthy controls. There was no significant difference between the heterozygous FIIG20210A (P = 0.669) thrombophilia group and the healthy controls. The best performance of the test was achieved at the cut-off value of 90.0 U (area: 0.981) with 96% sensitivity and 92% specificity in the high-risk thrombophilia group estimated by receiver operating characteristic analysis. The new method seems to be appropriate and reliable for the detection of AT-, PC- and PS deficiencies, homozygous FVL mutation and also for combined deficiencies. The automated CIP test is insensitive to FII G2010A mutation.

Background: Aging sarcopenia characterized by low muscle mass with low muscle strength affects men and women differently. The contribution of interleukin-6 (IL-6) to sarcopenia has been suggested based on a negative correlation between plasma IL-6 and muscle function described by some studies. However, no consensus regarding clinically relevant cut-off criteria has been reached. Another question arises whether pooling male and female data is an accurate way to determine the predictive value of IL-6 in sarcopenia. The present meta-analysis was designed to assess: (1) whether plasma IL-6 in aged populations in fact correlates negatively to muscle strength; (2) whether such a correlation exists both in men and in women; and (3) whether plasma IL-6 shows a gender difference in old age., Methods: We applied the preferred reporting items for systematic review and meta-analysis protocols (PRISMA). We searched PubMed and Embase for papers that reported data on individuals over 65 without inflammatory diseases. We extracted either separate male and female data on plasma IL-6 along with at least one muscle parameter or correlation coefficient between plasma IL-6 and these parameters. Random effect models calculated with DerSimonian and Laird weighting methods were applied to analyze correlation coefficients and gender difference in plasma IL-6. Egger's test was used to assess the small study effect., Results: Twenty articles out of 468 records identified were suitable for analyses. Plasma IL-6 correlates negatively with grip strength in mixed populations and also separately in men [- 0.25 with 95% confidence interval (CI): - 0.48, - 0.02] and in women (- 0.14 with 95% CI: - 0.24, - 0.03). However, contrary to expectations, men with better muscle condition have higher plasma IL-6 than women of similar age with worse muscle condition (plasma IL-6 male-female difference: 0.25 pg/mL with 95% CI: 0.15, 0.35)., Conclusion: This is the first study to demonstrate that a higher predictive IL-6 cut-off level should be determined for aging sarcopenia in men than in women.

Introduction: Laparoscopy is more beneficial than the conventional open technique, however the pneumoperitoneum created may have an ischemic side effect., Objective: Our aim was to evaluate the protective effects of preconditioning during laparoscopic cholecystectomies (LC)., Methods: 30 patients were randomized into 2 groups: I. PreC (preconditioning: 5 min. inflation, 5 min. deflation, followed by conventional LC), II: LC (conventional LC). Blood samples were taken before hospitalization (C = control), before surgery, after anaesthesia (B.S.), after surgery (A.S.) and 24 hours after the procedure (24 h). Measured parameters were: malondialdehyde (MDA), reduced glutathione (GSH), sulfhydril groups (-SH), superoxide-dismutase (SOD), catalase (CAT), myeloperoxidase (MPO), length of hospitalization and pain (VAS = visual analogue scale)., Results: Compared to the BS levels, no significant changes were detected in SOD's activity and MDA levels. GSH concentrations were significantly increased in the PreC group after operation. SH-, MPO, CAT and liver function enzymes were not significantly different. Hospitalization was shorter in the PreC group. Based on the VAS score patients had less pain in the PreC group., Conclusion: Significant differences concerning PreC group were found in GSH values. In the PreC group pain decreased by 2-2.5 units following the procedure, 24 h after surgery, and hospitalisation was also significantly shorter. In our pilot study the potential protective effect of preconditioning could be defined.

Background: Leptin is one of the major adipokines in obesity that indicates the severity of fat accumulation. It is also an important etiological factor of consequent cardiometabolic and autoimmune disorders. Aging has been demonstrated to aggravate obesity and to induce leptin resistance and hyperleptinemia. Hyperleptinemia, on the other hand, may promote the development of age-related abnormalities. While major weight loss has been demonstrated to ameliorate hyperleptinemia, obese people show a poor tendency to achieve lasting success in this field. The question arises whether training intervention per se is able to reduce the level of this adipokine., Objectives: We aimed to review the literature on the effects of training intervention on peripheral leptin level in obesity during aging, in order to evaluate the independent efficacy of this method. In the studies that were included in our analysis, changes of adiponectin levels (when present) were also evaluated., Data Sources: 3481 records were identified through searching of PubMed, Embase and Cochrane Library Database. Altogether 19 articles were suitable for analyses., Study Eligibility Criteria: Empirical research papers were eligible provided that they reported data of middle-aged or older (above 45 years of age) overweight or obese (body mass index above 25) individuals and included physical training intervention or at least fitness status of groups together with corresponding blood leptin values., Statistical Methods: We used random effect models in each of the meta-analyses calculating with the DerSimonian and Laird weighting methods. I-squared indicator and Q test were performed to assess heterogeneity. To assess publication bias Egger's test was applied. In case of significant publication bias, the Duval and Tweedie's trim and fill algorithm was used., Results: Training intervention leads to a decrease in leptin level of middle-aged or older, overweight or obese male and female groups, even without major weight loss, indicated by unchanged serum adiponectin levels. Resistance training appears to be more efficient in reducing blood leptin level than aerobic training alone., Conclusions: Physical training, especially resistance training successfully reduces hyperleptinemia even without diet or major weight loss.

Background: High hyperdiploid (HeH) pre-B pediatric acute lymphoblastic leukemia (B-pALL) is known to be heterogeneous by prognosis, but the stratification principals according to conventional cytogenetic analysis (CCA) are equivocal., Procedure: Untreated bone marrow samples of 214 B-pALL patients were previously classified according to the modal numbers (iMN 8 ) based on the gains of the chromosomes 4, 6, 10, 14, 17, 18, 21, and X as revealed by consecutive and correlated 2×4 color interphase fluorescence in situ hybridization, and at least five years of follow up data were analyzed., Results: Data from 48 of the 53 HeH (iMN 8 >50) B-pALL patients indicated that among the age, gender, WBC, and iMN 8 parameters, only the last was significantly associated with overall survival (pOS), which allowed the cases to be classified as iMN 8 51-54 (75%) and iMN 8 ≥ 55 (95%). Among the specific chromosomal gains of +4, +4/+6, +4/+17 and +4/+18, the first exhibited the most significance in terms of beneficial outcomes. The better prognostic group according to the iMN 8 was associated with a significantly reduced complexity of the subclonal landscape. However, iMN 8 did not prove to be an independent variable but was instead overridden by isolated trisomy of chromosome 4., Conclusions: These data indicate that the better outcomes in the HeH B-pALL group arose from the gain of a specific chromosome that always ranks at the same position in the sequential acquisition of the affected chromosomes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Pathogenesis of the non-random accumulation of extra chromosomes in the low and high hyperdiploid (HeL, HeH) pre-B pediatric acute lymphoblastic leukemia (B-pALL) is largely unknown, and has been clarified with respect only to tetrasomic chromosomes. We analyzed the hierarchy of changes in chromosome number and chromosomal instability, as well as clonal heterogeneity and evolution, in the untreated bone marrow cell samples from 214 B-pALL patients., Procedure: Applying relocation, 2 × 4 color interphase fluorescence in situ hybridization was used to detect copy number alterations (CNAs) of the most commonly involved chromosomes, 4, 6, 10, 14, 17, 18, 21, and X. This approach allowed us to acquire a dataset correlated for all eight parameters., Results: Based on chromosome number, an average of 6.9 and 10.2, whereas according to unique constellation 15.3 and 26.7 subclones could be identified in the HeL and HeH subgroups, respectively. Cluster analysis revealed the order of CNAs to chromosomes was highly conserved, and network analysis indicated changes in chromosome number were sequential for 80-90% of all numerical aberrations. Significant chromosome instability was revealed in both subgroups of leukemia., Conclusions: Data generated using this new approach indicate that chromosomal instability, which causes heterogeneity in the subclonal landscape, and the sequential changes to chromosome numbers, are both determining factors in the pathomechanism of the hyperdiploid B-pALL. These new observations could prompt research into the mitotic machinery of leukemic cells to identify new therapeutic targets for treating this disease., (© 2014 Wiley Periodicals, Inc.)

Introduction: Normal pregnancy is associated with hypercoagulable state. Elevated markers of coagulation and fibrinolytic system activation indicate increased thrombin activity and increased fibrinolysis following fibrin formation throughout pregnancy. These changes exceed the biological variability in most cases. Haemostatic reference intervals are generally based on samples from non-pregnant women. Thus, they may not be relevant to pregnant women, a problem that may hinder accurate diagnosis and treatment of haemostatic disorders during pregnancy. The aim of the study was to follow the changes of haemostatic parameters and to establish gestational age-specific reference intervals during normal pregnancy., Materials and Methods: Blood samples of 83 pregnant women were collected at gestational weeks 16, 26 and 36. Fibrinogen, D-dimer, and C-Reactive Protein (CRP) were examined. Reference intervals were calculated for fibrinogen, D-dimer tests with two different methods (mean±2 SD or median and 2.5th and 97.5th percentiles with 90% confidence intervals)., Results: fibrinogen and D-dimer increased progressively throughout pregnancy. Mean fibrinogen levels were higher than the maximum of the conventional reference interval, already in the 16th week of pregnancy. D-dimer levels were at or above the conventional cutoff point (250ng/mL) throughout the pregnancy in 42% of pregnant women, while in the 36th week 98% of them displayed elevated D-dimer levels. CRP did not increase in normal pregnancy., Conclusions: There seems to be an emerging need to reconsider fibrinogen and D-dimer values from a different aspect in pregnancy compared to non-pregnant reference intervals. New reference ranges are suggested to be established in pregnancy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: There are contradictory data on chronic lung injury caused by marijuana, which is partially due to insufficient basic research. Anecdotic reports draw attention to an increased rate of primary spontaneous pneumothorax (PSP) among young marijuana smokers, suggesting a causative link., Methods: A retrospective analysis of 20 patients treated for PSP in our department in the last two years was performed. Demographics, treatment modality and outcome data were analysed. Chi-square, Mann-Whitney and Fisher tests were applied for statistical evaluation. Gender distribution: 16 male, 4 female, age 23.95 ± 4,57 years: min: 18, max: 32. 13/20 patients admitted to be regular cannabis users (CU), among them 11 male, 2 female, age 24.54 ± 4.77 years. Altogether 7/20 patients had a history of previous pneumo-thorax, with a higher recurrence rate among CU (odds ratio 1.56)., Results: In the non-cannabis user group (NCU) 3/7 patients were managed with thoracic drainage alone. 4/7 NCH patients needed major surgery, VATS was performed on all 4 patients. 4/13 CU patients were managed with thoracic drainage, 9/13 patients needed thoracotomy (8 VATS, 1 open thoracotomy). We found a shorter drainage time among NCU patients (4.00 ± 1.00 days NCU vs 4.5 ± 1.73 days CU, p = 0.651). Operative treatment was needed more frequently among cannabis users (69.23% vs NCU 57.14%, p = 0.651) due to impaired lung expansion. Recurrence was detected in 2 patients after drainage, 1 CU, 1 NCU patients, respectively, both of them were managed with VATS. On histological examination there were no major differences between the two groups, 11/13 of operative cases had pulmonary emphysaema . Based on county demographical and clinical data, there's a higher risk for PSP among cannabis users (odds ratio 3.86)., Conclusions: Despite the small sample size, there seems to be a connection between marijuana use and PSP prevalence. It's unclear if marijuana directly contributes to the development of pneumothorax, or just aggravates a fundamentally fragile lung parenchyma condition. In this group of young patients a more aggressive surgical approach is recommended, considering underlying parenchymal impairment and higher recurrence rate.

Migraine and multiple sclerosis (MS) can both cause white matter lesions that appear similar on conventional MRI. This study aimed to compare these abnormalities, and to find anatomical biomarkers specific for migraine. Supratentorial white matter hyperintensities (WMH) of 17 migraineurs and 15 patients with MS were counted, volumetrically analyzed, and their lobar distribution assessed on fluid-attenuated inversion recovery MRI. We found that migraine WMH affected mainly the deep white matter and subcortical U-fibers, belonged to the anterior circulation, appeared more frequently in the frontal and parietal lobes, showed no difference in average size between lobes, and were smaller and fewer than in MS. Most of the MS WMH were in the frontal lobe and were the smallest average size, while the fewest WMH with the largest size were in the occipital lobe. The pattern of supratentorial WMH appearance differs between the two groups; however, accurate differential diagnosis of WMH by conventional MRI is probably not possible in individual patients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Local delivery of antibiotics via PMMA (polymethyl-methacrylate) has been widely used in the treatment of chronic osteomyelitis for over 40 years. Unfortunately, PMMA is water insoluble, which seriously limits antibiotic delivery. In addition, the polymerization temperature of PMMA is high, and consequently, only heat-stable antibiotics can be used. Therefore our aim has been to develop an effective antibiotic delivery system, which can be loaded with a wide variety of drugs and deliver the molecules in a predictable manner. Capsules with wall thicknesses of 0.3-0.6 mm from PMMA mixtures containing 40-70 w/w% (weight percent) of sorbitol were prepared and their permeability tested with BPB (Bromophenol Blue). Sorbitol content and wall thickness correlated with the BPB release. SEM (scanning electron microscopy) showed that the canalization of capsules also was well correlated with both sorbitol content and wall thickness. The PMMA-sorbitol-based capsule can potentially be a versatile tool in assuring effective delivery of antibiotics and other substances.

The aim of our prospective study was to assess the concordance between postvoid residual volumes (PVR) of the urinary bladder obtained by two different three-dimensional (3-D) ultrasound (US) volumetric methods (VOCAL and XI VOCAL) and with measurement by the catheter in postoperative patients who have undergone radical hysterectomy. The 3-D sonographic volume-determination of PVR with both methods correlated significantly with the actual amount of PVR by the catheter. The accuracy of both 3-D US volumetric methods was significantly higher under 300 mL of PVR. Bland-Altman plots were generated to examine limits of agreement. Both noninvasive 3-D sonographic methods are appropriate for the correct volume-determination of PVR following radical hysterectomy. Thus, we may avoid routine, albeit often unnecessary, catheterization to measure postoperative residual bladder volumes and subsequently the incidence of lower urinary tract infection may be reduced and better postoperative comfort for patients may be permitted., (Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Brain white matter hyperintensities are more prevalent in migraine patients than in the general population, but the pathogenesis and the risk factors of these hyperintensities are not fully elucidated. The authors analyzed the routine clinical data of 186 migraine patients who were referred to the Outpatient Headache Department of the Department of Neurology, Medical School, University of Pécs, Hungary between 2007 and 2009: 58 patients with white matter hyperintensities and 128 patients without white matter hyperintensities on 3 T MRI. Significant associations between the presence of white matter hyperintensities and longer disease duration (14.4 vs. 19.9 years, p = 0.004), higher headache frequency (4.1 vs. 5.5 attacks/month, p = 0.017), hyperhomocysteinemia (incidence of hyperintensity is 9/9 = 100%, p = 0.009) and thyroid gland dysfunction (incidence of hyperintensity is 8/14 = 57.1%, p = 0.038) were found. These data support the theory that both the disease duration and the attack frequency have a key role in the formation of migraine-related brain white matter hyperintensities, but the effects of comorbid diseases may also contribute to the development of the hyperintensities.

Background: Morphea is an inflammatory autoimmune skin sclerosis of unknown etiology. A causative role of Borrelia burgdorferi infection has been controversially discussed, but no conclusive solution has yet been achieved., Objective: Intrigued by 3 young patients with severe Borrelia-associated morphea and high-titer antinuclear antibodies, we retrospectively examined the relationship between Borrelia exposure, serologic autoimmune phenomena and age at disease onset in morphea patients., Methods: In 90 morphea patients the presence of Borrelia-specific serum antibodies was correlated to the age at disease onset and the presence and titers of antinuclear antibodies. Patients with active Borrelia infection or high-titer antinuclear antibodies due to systemic sclerosis or lupus erythematosus served as controls., Results: We observed a statistically highly significant association between morphea, serologic evidence of Borrelia infection, and high-titer antinuclear antibodies when disease onset was in childhood or adolescence., Limitations: Because pathogenic Borrelia species may vary in different geographic regions the relevance of Borrelia infection in morphea induction may show regional variations., Conclusion: B burgdorferi infection may be relevant for the induction of a distinct autoimmune type of scleroderma; it may be called "Borrelia-associated early onset morphea" and is characterized by the combination of disease onset at younger age, infection with B burgdorferi, and evident autoimmune phenomena as reflected by high-titer antinuclear antibodies. As exemplified by the case reports, it may take a particularly severe course and require treatment of both infection and skin inflammation.

Unlabelled: Hospitalization attributable to gastrointestinal and other major bleeding is frequently associated with acenocoumarol treatment., Aims: To assess the level of knowledge among patients in respect to harmful adverse effects, interactions with medication and nutrition regarding acenocoumarol treatment., Methods: Questionnaires consisting of 66 questions were completed in offices of family doctors (77), and during consultations at the 3rd Department of Internal Medicine (80)., Results: 157 patients (male:female=45:55; age=65.5 years) were involved. In the group informed by the whole team (doctors, nurses and dietitians) everyone heard about the possible adverse effects. In the group where family doctors or other specialists provided information, 14.5% or 31.1% did not hear about any side-effect. The importance of diet was unknown by 71.4% of the patients. The knowledge of interactions between acenocoumarol and other medications is low: aspirin was known by 24.4%, analgetics by 23.0% and vitamin K by 18.6% of the patient., Conclusions: Regarding acenocoumarol treatment, patients' knowledge should be enlarged. However, it can be significantly improved by the contribution of other team members such as nurses and dietitians.

Detecting balanced translocations using tissue sections plays an important diagnostic role in cases of hematological malignancies. Manual scoring is often problematic due to truncation and overlapping of nuclei. Reports have described automated analysis using primarily tile sampling. The aim of this study was to investigate an automated fluorescent in situ hybridization analysis method using grid sampling on tissue sections, and compare the performance of dual-fusion (DF) and break-apart (BA) probes in this setting. Ten follicular, 10 mantle cell lymphoma, and 10 translocation-negative samples were used to set the threshold of false positivity using IGH/CCND1, IGH/BCL-2 DF, and IGH BA probes. The cut-off distances of red and green signals to define fusion signals were 0.5, 1.0, and 1.2 mum for the IGH/CCND1, IGH/BCL-2 DF, and IGH BA probes, respectively. The mean false positivity of grid units was 5.3, 11.4, and 28.1%, respectively. Ten to 14 additional samples analyzed blindly and were correctly classified using each probe. Discriminating positive and negative samples using automated analysis and grid sampling was possible with each probe, although different definitions of fusion signals were required due to the different physical distances between the DNA probes. Using the DF probes resulted in lower false positivity, which was less affected by signal numbers per grid units.

Introduction: New prognostic factors discovered in chronic lymphocytic leukemia have recently got into the center of clinical interest. While the predictive value of cytogenetical abnormalities, immunoglobulin heavy chain gene mutation status, CD38 and ZAP70 expression is already well known, the significance of multi-drug resistance in chronic lymphocytic leukemia is not well characterized., Aims: The goal of this study was to characterize the multidrug resistance features in 82 patients with chronic lymphocytic leukemia at the genetical, expression- and functional level and to compare it with the patient's clinical behavior (survival and response to therapy)., Methods: Light Cycler Real Time PCR based "Single Nucleotide Polymorphism" analysis of the MDR1 gene, as a biological predictor of the expression level of P-glycoprotein was tested in 66 patients with chronic lymphocytic leukemia. P-glycoprotein expression and MDR-function was detected in 82 cases by flow cytometry (by use of anti-P-glycoprotein monoclonal antibody and calcein-verapamil functional test). Response to therapy was analyzed by statistical Fisher-test in the treated 35 patients. The survival analysis (Log-rank test) was performed on the whole population ( n = 82)., Results: No significant correlation was found between the three levels of multidrug resistance (genetics, phenotype, function) in our patients with chronic lymphocytic leukemia. P-glycoprotein positive cases (n = 9) were predominantly non-responders (8/9, 89%). There must be, however, other mechanisms causing non-response (total non-responders: 13/35 treated cases). Most of P-glycoprotein negative CLL patients (n = 26) responded well (21/26, 80%) to chemotherapy (responders: 22/35 treated CLL) (p < 0,001). The tendency was the same in the average expected survival rate between P-glycoprotein positive and negative patients (84 vs 203 months) but the difference was not significant (p = 0,106)., Conclusions: This study proved the clinical prognostic significance of P-glycoprotein expression of leukaemic cells predicting the chemotherapy response and partially estimating the general survival of patients suffering from chronic lymphocytic leukemia.

Aim: The aim of this study was to compare the efficiency of the preoperative combined chemo-radiotherapy in the treatment of locally advanced squamous cell carcinoma in different locations of the oesophagus., Methods: Between 1997 and 2005, 102 patients with locally advanced (T3-4) squamous cell oesophageal cancer received preoperative chemo-radiotherapy. In 40 cases, the tumour was localised in the upper-third (Group I), while in 62 cases, in the middle-third of the oesophagus (Group II). Survival rates of patients receiving neoadjuvant therapy were compared with a historical control group. In addition, Group I and Group II were compared to each other, as well., Results: survival rate was significantly better after neoadjuvant therapy (p:0.0042) Resection was performed in 70% of the patients from Group I, and in 50% of those complete pathological remission (pCR) was observed. The perioperative morbidity and mortality rates were 43% and 14%, respectively. As far as Group II, 69% of the patients underwent oesophageal resection, with a perioperative mortality of 18% and morbidity rate of 62%. pCR was observed only in 7% of the cases. The median survivals (21 and 22 months) and the R0 resection rates (82 and 84%) were similar in the two groups. The pCR subgroup showed a significantly better survival rate., Conclusion: In this study, we demonstrated that preoperative chemo-radiotherapy increases survival in locally advanced oesophageal cancer. A significantly higher rate of complete response was observed in patients with upper-third oesophageal cancer. It seems that this group has superior sensitivity to multimodal treatment; therefore, our results support a new prognostic factor in oesophageal cancer treatment.

Introduction: Results of a retrospective study of patients who underwent pulmonary metastasectomies after colorectal surgery in the last five years are reported here. Prognostic factors are evaluated and analyzed in the context of current literature., Material and Methods: 37 lung resections were performed in 33 patients between 2001 and 2006, the male:female ratio was 19:14. The average age was 61.3 years (49-76). We analyzed the extent of lung resections, disease free intervals (DFI), laterality of the tumours, number and locations of metastases, lymph node involvements and the incidence of resection of hepatic metastases. Altogether, 20 solitary lung metastases were removed and 17 multiple resections were performed. 25 sublobar resections, 11 lobectomies and one pneumonectomy were carried out. 18 patients had right sided, eight patients had left sided and six patients had bilateral disease. 6 of the 33 patients underwent either synchronous or metachronous liver resection for hepatic metastases., Results: Survivals were calculated by the Kaplan-Meier method. The average DFI was 27.6 months. When all patients were considered, the average survival was 28 months. 52% of the patients had a 3-year postoperative survival, if lung metastases were present only., Conclusions: Patients benefit from surgical removal of lung metastases of colorectal cancer. There were no differences in survival rates between patients who underwent resection of solitary or multiple lung metastases up to seven deposits. However, the average survival was 12 months shorter if hilar/mediastinal lymph nodes were involved. Furthermore, the average survival of six patients with hepatic metastases was 10 months shorter than the rest of the group. There was no benefit of DFI over 24 months. None of the other prognostic factors showed significant difference.

Background/aims: Experimental and clinical studies demonstrated that probiotics containing lactobacilli significantly improve the outcome of acute pancreatitis. In a prospective, randomized, double-blinded study the role of "Synbiotic 2000", a new synbiotic composition with high colony forming unit (CFU) was evaluated in the treatment of severe acute pancreatitis., Methodology: Patients with severe acute pancreatitis were randomized into two groups. Nasojejunal feeding was commenced within 24 hours after admission in both groups and continued for at least seven days. The first group of patients received four different lactobacilli preparations with 1010 CFU, respectively, and prebiotics containing four bioactive fibers (inulin, beta-glucan, resistant starch and pectin) in addition. Patients in the second (control) group received only prebiotics., Results: 62 patients with severe acute pancreatitis completed the study. Altogether 8 patients died. Lower incidence of multiorgan failure (MOF), septic complications and mortality were detected in the first group compared to the control, but the differences were not significant statistically. The total incidence of systemic inflammatory response syndrome (SIRS) and MOF were significantly different between the two groups (8 vs. 14; p < 0.05). Furthermore, the number patients recovering with complications were significantly less in the first group receiving modern synbiotic therapy compared to the control (p < 0.05). Finally, lower rate of late (over 48 hours) organ failure was detected in the first versus the control group (3.0% vs. 17.2%)., Conclusions: The results suggest that early nasojejunal feeding with synbiotics may prevent organ dysfunctions in the late phase of severe acute pancreatitis. In addition, the data also indicate that the infection of pancreatic necrosis may be associated with early phase organ failure.

The authors estimated the onset, incidence and treatment of pseudophakic retinal detachment after phacoemulsification and intraocular lens implantation in 11,098 consecutive patients over a 10-year period. About 40 eyes in 37 patients were diagnosed with pseudophakic retinal detachment (risk = 0.36%). Significant risk factors included: axial length > 25.0 mm, age < 65 years and intraoperative complications. The final best corrected visual acuity improved by 2 or more Snellen E lines in 52.5% of cases.

It has been shown that PARP inhibition is protective in several models of ischemia-reperfusion injury including cardiac, cerebral and renal ones. Due to their ability to reduce myocardial necrosis and to improve myocardial function PARP inhibitors emerged as candidates for treating various cardiovascular diseases including acute myocardial ischemia. Since the pathophysiology of acute ischemic cardiac diseases involves haemostatic impairment and the therapeutic regimen includes antithrombotic drugs, we investigated the effect of the potent poly(ADP-ribose) polymerase (PARP) inhibitor INO-1001 alone and in combination with platelet aggregation inhibitors (aspirin, eptifibatide and tirofiban), unfractionated heparin, low molecular weight heparin (enoxaparin) or the recombinant fibrinolytic drug (alteplase), on various haemostatic parameters in vitro. ADP- and epinephrine-induced platelet aggregation was evaluated by optical aggregometry in the presence or absence of different concentrations of INO-1001, in combination with aspirin, tirofiban, eptifibatide or saline on ten healthy volunteers' platelet rich plasma (PRP). Activated partial thromboplastin time, Anti-Xa activity and euglobulin lysis time were determined in the presence or absence of different concentrations of INO-1001, in combination with sodium heparin, enoxaparin or alteplase, respectively. INO-1001, on its own does not affect the measured platelet, and haemostatic functions, i.e. does not reduce the respective anti-platelet, anti-coagulant and thrombolytic activity of therapeutically relevant concentrations of aspirin, tirofiban, eptifibatide, enoxaparin and alteplase in vitro. INO-1001 enhanced the effects of heparins above therapeutic ranges; the magnitude of this effect was negligible. Consequently, the PARP inhibitor INO-1001 can be safely applied together with the drugs tested.

Introduction: Preload-independent pulsed tissue Doppler echocardiography (TDI) and conventional pulsed Doppler echocardiography were used to assess the global left ventricular diastolic function in patients with hypertrophic cardiomyopathy (HCM). Levels of B-type natriuretic peptide (BNP) could be elevated in patients with isolated left ventricular diastolic dysfunction., Aim: The study was to investigate the correlation between BNP levels and the parameters measured by conventional echocardiography and TDI in patients with HCM., Patients: 32 consecutive patients with HCM (21 male, 11 female, mean age 47 +/- 14 years) were studied. Inclusion criteria were: normal sinus rhythm; ejection fraction > or = 50%; absence of moderate to severe mitral regurgitation or prosthetic mitral valve., Methods: In addition to the conventional transmitral flow patterns (E, A, E/A, DT, IVRT) myocardial early (Ea) and late diastolic (Aa) velocities were measured at the lateral and septal border of the mitral annulus by ATL HDI 5000 ultrasound system. Ea/Aa and E/Ea ratios were calculated. NT-proBNP levels were measured by Roche-Elecsys test (immunoassay). Because the distribution of BNP values did not appear to be normal, the values were transformed into a natural logarithm (InBNP)., Results: Mean BNP level was 543 +/- 845 pg/ml. BNP levels negatively correlated with lateral Aa values (r = -0.59, p < 0.001). No significant relationship was observed between BNP levels and other echocardiographic parameters. By stepwise multiple linear regression analysis the only significant predictor of InBNP was lateral Aa value, too (r = -0.467, p < 0.05)., Conclusion: Significant correlation was found between BNP levels and a single TDI parameter characterizing left atrial systolic function, but there was no significant correlation between BNP levels and global left ventricular diastolic function characterized by either conventional echocardiographic or TDI parameters.

Our knowledge of Gastrointestinal Stromal Tumours (GIST) has been broadened in the last few years by the discovery of the key function of c-kit tyrosine kinase mutation in their pathogenesis. A single institution database is presented and a hypothesis is examined regarding probable connection between GIST and other gastrointestinal malignancies. Between 2000 and 2004 20 patients were admitted to our department with GIS tumour. With the addition of three cases detected between 1991 and 2000, and proved to be GIST retrospectively, 23 cases are followed. Mean age was 64.52 years, male to female ratio 11:12. Ten tumours originated from the stomach, ten from small bowel, one from rectum and two from mesenterium. All patients underwent surgery, 16 operations were completed with R0 radicality, one R1 and four R2 resections were performed. Follow-up ranged from 1 to 157 months. Five out of 23 patients died (21.7%), six patients live with metastatic disease, twelve are disease free. Amongst patient-, tumour- and treatment-related factors the prognostic significance of Fletcher's risk and radicality of resection was demonstrated (p<0.05). Significantly more synchronous or metachronous gastrointestinal malignancies were found is this population of GIST patients, when compared to the prevalence of malignancies in normal Hungarian population (p<0.001).

Background: The diagnosis of analgesic nephropathy has improved significantly with modern imaging techniques. We reviewed a large portion of the Hungarian dialysis population to obtain additional insight into the problem., Methods: Twenty-two participating dialysis units enrolled 1400 patients on renal replacement therapy between 1 January 1995 and 1 January 1998. Patients with no known aetiology (n = 284) were interviewed and studied with renal imaging. We assessed the presence of decreased renal mass combined with either bumpy contours, papillary calcification, or both. The subjects studied were interrogated extensively., Results: Our survey suggested analgesic nephropathy in 47 of 1400 patients (3.3%), 3-fold higher than the EDTA database estimate for Hungary. The analgesics most commonly abused were phenacetin-containing mixtures. The driving symptoms were mainly headache and joint pain. Cardiovascular complications were more common than in the rest of the dialysis population, independent of smoking and lipid values (P<0.01)., Conclusions: Phenacetin should be banned. Our study results support the need for longitudinal cohort and case-control studies in Hungary.

Cisapride is a potent third generation prokinetic agent acting on postganglionic receptors by increasing the release of acetylcholine. In a prospective, self-controlled study the prokinetic action of cisapride was tested on pedicled stomach, jejunum and colon grafts used for substitute after esophageal resection. Between 1995 and 1998 15 patients with gastric pull up, 10 patients with colon replacement or bypass and eight patients with free jejunum transplant or jejunum replacement were evaluated. Esophageal transit scintigraphy was performed before and after cisapride administration. From the time-activity curves, the half-life of radiolabeled bolus in the esophagus was calculated and preadministration and postadministration half-lives were compared. Cisapride significantly reduced the half-life of radiolabeled bolus in the substitute in the case of stomach and jejunum replacement, while for colon replacement the results were dispersed too widely to yield significant difference. Cisapride exerts prokinetic effect on pedicled stomach and jejunum substitutes after esophageal resection.

Diabetes mellitus is characterized by increased methylglyoxal (MG) production. The aim of the present study was to investigate the role of iron in the cellular and molecular effects of MG. A red blood cell (RBC) model and L-arginine were used to study the effects of MG in the absence and presence of iron. Intracellular free radical formation and calcium concentration were measured using dichlorofluorescein and Fura-2-AM, respectively. Effects of MG were compared to the effect of ferrous iron. Reaction of L-arginine with MG was investigated by electron spin resonance (ESR) spectroscopy and by a spectrophotometric method. MG caused an iron dependent oxidative stress in RBCs and an elevation of the intracellular calcium concentration due to formation of reactive oxygen species. Results of co-incubation of MG with ferrous iron in the RBC model suggested an interaction of MG and iron; one interaction was a reduction of ferric iron by MG. A role of iron in the MG-L-arginine reaction was also verified by ESR spectroscopy and by spectrophotometry. Ferric iron increased free radical formation as detected by ESR in the MG-L-arginine reaction; however, ferrous iron decreased it. The reaction of MG with L-arginine yielded a brown product as detected spectrophotometrically and this reaction was catalyzed at a lower rate with ferric iron but at a higher rate with ferrous iron. These data suggest that MG causes oxidative stress in cells, which is due at least in part to ferric iron reduction by MG and to the modification of amino acids e.g. L-arginine by MG, which is catalyzed by iron redox cycling.

Aims: The aboral pouch, a new type of gastric substitute, has been introduced after total gastrectomy and compared to simple Roux-en-Y reconstruction in a prospective, randomized study. Anthropometric data, serum nutritional parameters, small intestinal passage, lipid and carbohydrate absorption and quality of life were measured 6 and 12 months after total gastrectomy., Patients and Methods: Between September 1997 and April 2000 46 patients entered the study, 24 to the aboral pouch group and 22 to the control, simple Roux-en-Y group., Results: Interim analysis of the data revealed significantly higher serum cholesterol levels, better lipid absorption and quality of life in patients who underwent aboral pouch construction., Conclusion: Aboral pouch construction is a feasible reconstruction method after total gastrectomy providing better lipid absorption and quality of life for patients after total gastrectomy., (Copyright 2001 Harcourt Publishers Limited.)

In recent years elaboration of the diagnosis of analgesic-nephropathy (ANP) with the help of imaging techniques significantly increased the possibility of diagnosing the disease. Therefore, evaluating the prevalence of ANP has become more accurate in our country as well. The prevalence of ANP has been investigated in patients who have newly been taken into the dialysis program due to renal disease of unknown aetiology in 22 dialysis centers between December 1994-December 1997. The diagnosis of ANP has been based on revealing chronic drug abuse in the history and positive results of renal imaging (decrease in length of both kidneys combined with either bumpy contours and/or papillary calcification). Among 284 patients dialysed with unknown diagnosis 42 (14.8% of all cases) proved to have ANP. All patients except 2 took analgesic mixtures containing phenacetin/paracetamol, phenason derivatives, acetilsalysilic acid, caffeine and/or codeine. According to their investigations, ANP is a common disease resulting in end-stage renal failure in Hungary as well.

Advanced glycation end products play an important role in the development of tissue damage in diabetes mellitus. The aim of the present study was the investigation of the excretion of different glycation end products in the urine. Methylglyoxal, an intermediate product of the glycation, formed with L-arginine in an in vitro model two fluorescent peaks. These peaks can be characteristic for imidazolone-like product(s) which are produced also in the reaction of methylglyoxal with proteins described in the literature, suggesting modification of proteins with methylglyoxal at the guanidino group of the L-arginine amino acid. Using the fluorescent characteristics of these (excitation/emission: 320/400 nm and 340/425 nm) and the generally accepted wavelength of the so called non-specific advanced glycation end product (370/440 nm) could be identified these glycation end products in the urine of 98 patients with diabetes mellitus (21 type I., 77 type II., 51 female and 47 male, mean age: 56.6 years). These three particular glycation end products showed significant intercorrelations in the urine (p < 0.001). Concentrations of these glycation end products in the urine correlated negatively with the serum creatinine in the range between 120-240 mumol/l (p < 0.001). Data presented here verify that non-specific glycation end product and imidazolone-like glycation end products can be detected in the urine of diabetic patients. Elimination of these products by the urine is markedly decreased in the stage of early renal insufficiency. These decrease in the secretion can cause an elevation of the advanced glycation end products in the circulation leading progression of diabetic complication.

Carbonyl stress-induced tissue damage is caused by reactive aldehydes produced by non-enzymatic glycation, oxidative stress and metabolic processes. The aim of this study was the detection of the major markers of carbonyl stress in the urine of diabetic patients (21 type 1, 77 type 2, 51 female, 47 male, 56.6 +/- 13.7 year of age; mean +/- SD). Oxidative stress was detected by using the reaction of malondialdehyde, the end product of free radical damage of the tissues, with L-arginine. This reaction produced a fluorescent compound, pyrimidinyl-L-ornithine. Thus, pyrimidinyl-L-ornithine, as well as pentosidine, an advanced glycation end product, and the non-specific advanced glycation end product, which is thought to be partially as a result of lipid peroxidation, could be detected simultaneously by using the fluorescent method. Correlation coefficients among the concentrations of these products in the urine of 98 diabetic patients were as follows: pyrimidinyl-L-ornithine vs. non-specific advanced glycation end product: r = 0.72, p < 0.001; pentosidine vs. non-specific advanced glycation end product: r = 0.68, p < 0.001; pentosidine vs. pyrimidinyl-L-ornithine: r = 0.60, p < 0.001. Strong negative correlations were found between the serum creatinine levels of these patients, between 120-240 mumol/l, and the urinary concentration of these products: r = -0.88 for non-specific advanced glycation end products, r = -0.86 for pentosidine and r = -0.89 for pyrimidinyl-L-ornithine (p < 0.001 for all three). These data support a closer relation of the so-called non-specific glycation end product to oxidative stress than to non-enzymatic glycation. Results presented here suggest an early retention of the products of carbonyl stress in the patients with moderate renal insufficiency, which can play a role in the development of diabetic complications.

During a 5-year period from 1993 to 1998, 22 cases of caustic esophageal injuries were referred to our clinic, caused by acid consumption as suicidal intentions or as an accident. Four out of 10 cases where acute exploration was performed the corrosion was so extended that no further intervention could be done, and all of them died within 24 hours. In the remaining 6 cases acute esophagogastrectomy, or total gastrectomy with esophageal exclusion was performed. Three out of 6 patients survived primary surgery, who later underwent esophageal reconstruction with a colon substitute. In 12 patients no indication for acute surgery arose, but later during the follow-up in 5 of them dysphagia and corrosive stricture developed. All underwent successful esophageal reconstruction with colon substitute. Case reports, acute management, indications for surgery and prognostic factors are also discussed.

Rotational dynamics and ordering of myosin heads in glycerinated skeletal muscle fibres were studied using an isothiocyanate-based spin label attached to the fast-reacting thiol sites of myosin and were compared with data obtained for maleimide and iodoacetamide spin labels attached to the same sites. The ordering of probe molecules on the millisecond time scale in the rigor state, at sarcomere length 2.2-2.3 +/- 0.1 microns, was static. Isothiocyanate probe molecules showed greater mobility; the segment holding the label rotated in the microsecond time range. In the saturation transfer EPR time domain, MgADP did not produce a significant change in the mobility of spin labels. The spectra of isothiocyanate spin-labelled fibres were analyzed in terms of two narrow distributions with mean angles of 75 degrees and 56 degrees. In the rigor state, the fractions represented approximately 76% and 24% of the total EPR absorbance. In the presence of MgADP, the conventional EPR spectra showed large changes in the ordering of isothiocyanate probe molecules towards a new distribution, the population with a theta value of 56% increased from 24% to 71% at the expense of the 75% population with no change in the mean angles of the distributions. In the case of maleimide and iodoacetamide spin-labelled fibres, however, the effect of MgADP on the probe angular distribution was small.

The effect of 6,6'-methylene-bis-2,2,4-trimethyl-1,2-dihydroquinoline (MTDQ) and its water soluble species (MTDQ-DA) was studied in biological membrane and model systems using EPR spectroscopy for detecting molecular motion and radical formation. Both compounds influenced the rotational mobility of maleimide spin labels attached to proteins of the nerve membrane: the addition of MTDQ or MTDQ-DA induced an increase of the rigidity of the membrane in the environment of the attaching sites. The reaction of MTDQ-DA with hydroxyl and superoxide free radicals showed that this compound was also a competitive OH and superoxide free radical scavenger. The reaction rate constant of the formation of MTDQ-DA free radical was k = (4.0 +/- 0.5) x 10(9) M-1 s-1 in the hydroxyl free radical generating system. Simulation of EPR spectra supported that MTDQ-DA free radical was very likely a stable nitroxide free radical.

Low-power He-Ne laser irradiation causes a well-defined and energy dependent cell destruction of in vitro cultured cell lines sensitized by hematoporphyrin derivative (HPD). The mechanism of this photosensitization was studied by measuring with polarization microscopic, scanning electron microscopic, and electron-spin-resonance (ESR) spectroscopic parameters. The cell damage caused by photosensitization and laser irradiation seems to be a complex process, however the biological membranes seem to be one of the primary targets. The energy of laser light causes rotation and resonance changes of macromolecules and the water molecules, resulting in an increased structural order of the submembraneous components in the living cells, detectable microscopically. During the photosensitization process, the red (630 nm) He-Ne laser light, during a one-photon energy activation, causes excitation of hematoporphyrin molecules to their triplet state. The excitation of HPD molecules results in a multi-step, free-radical generating effect, measured by ESR spectroscopy and studied by the ultrastructural changes of membrane organization and cell shape. Similar effects could be observed on in vitro lipid-water liposome membranes.

Thermal behavior of intact and LC-2 deficient myosin obtained from bovine heart was studied using EPR and DSC techniques. The reactive thiol sites (Cys 704) of myosin was labelled with 4-maleimidopiperidine-nitroxyl, and the measurements were taken in X-band in the conventional and saturation transfer EPR time domains. DSC scans were made from 5 degrees up to 60 degrees C with 0.25 degree C/min scan rate. Bovine heart myosin was isolated by standard methods. The LC-2 deficient myosin was prepared by cleaving myosin with alpha-chymotrypsin (400:1 molar ratio) for 1.5 min at 25 degrees. Our basic finding was a conformational change in LC-2 deficient myosin detected at 18 degrees C. It was not observed in intact myosin suggesting that the dissociation of the regulatory light chain resulted in a local structural change in the neighbourhood of the attached label in the 20 kD domain. The rotational correlation time of the label and the microwave saturation behavior of myosin at 25 degrees C exhibited no significant differences after removal of the LC-2 light chain. However, the mobility of the same label was significantly diminished in skeletal muscle. Studying the melting behavior of myosin, six endothermic peaks were detected at 19; 41.3; 43.3; 45.5; 48.5; and 54.3 degrees C (enthalpies: 708.4; 399; 773.8; 1089; 1612.8; and 3304.8 kJ/mol). They were assigned to the segment containing the essential thiols: HMM S-2, HMM S-1 (50kD and 20kD plus 27kD) and LMM. Removal of the LC-2 light chain was associated with the disappearance of the 18 degrees transition showing again a structural change in LC-2 deficient myosin which extended to a larger region.

The nitroxide spin label (iodoacetamido)proxyl (IPSL) was specifically and rigidly attached to sulfhydryl 1 (SH1) on myosin subfragment 1 (S1). The specificity of this label for SH1 was demonstrated by using a technique where the spin label is localized on the electrophoresis-isolated proteolytic fragments of myosin using electron paramagnetic resonance (EPR). Studies of the rigidity of the probe on SH1 indicate that the IPSL is immobilized on the surface of S1 in the presence and absence of the nucleotides MgADP or MgATP. The EPR spectrum of muscle fibers decorated with IPSL-S1 shows that the IPSL-S1 rotates from its orientation in rigor upon binding MgADP. The angular displacement due to nucleotide binding is larger than that detected with the (maleimido)tempo spin label [Ajtai, K., French, A. R., & Burghardt, T. P. (1989) Biophys. J. 56, 535-541], demonstrating that the IPSL is oriented on the myosin cross-bridge in a manner that is favorable for detecting cross-bridge rotation during the rigor to MgADP state transition.

The effect of MTDQ, a dihydroquinoline type free radical scavenger was studied in biological membranes, and model systems. Using spin-labelling and spin-trapping methods, it was that MTDQ induced a decrease of the mobility of spin labels attached to the thiol sites of membrane proteins, and it was a strong free radical scavenger in hydroxyl and superoxide anion free radical generating systems. The experimental results suggest that the presence of MTDQ in the cell membranes may improve the protection of membrane components against free radical attacks.

Direct evidence was given concerning the free radical production of hematoporphyrin (HP) and its derivative, during illumination, by ESR spectroscopy. A spin trapping measurement was carried out using PBN spin trap for determination of this radical(s). Three different spin-adducts were found. Two of them are likely to be connected to the reactive free radical production of HP.