Fatih Ozcelik

Allopurinol improves endothelial function and reduces oxidant-inflammatory enzyme of myeloperoxidase in metabolic syndrome

ObjectiveIn this study, we tested in patients with metabolic syndrome whether allopurinol through decreasing oxidative stress improves endothelial function, and ameliorates inflammatory state represented by markers of myeloperoxidase, C-reactive protein (CRP) and fibrinogen.MethodsIn a randomized, double-blind fashion; subjects with metabolic syndrome were treated with allopurinol (n = 28) or placebo (n = 22) for one month. Before and after treatment, blood samples were collected and the flow-mediated dilation (FMD) and isosorbide dinitrate (ISDN)-mediated dilation of the brachial artery were performed.ResultsBaseline clinical characteristics of the allopurinol and placebo groups demonstrated no differences in terms of clinical characteristics, endothelial function and inflammatory markers. After the treatment with allopurinol, FMD was increased from 8.0 ± 0.5 % to 11.8 ± 0.6% (P < 0.01), but there were no change in the placebo group. In both groups, ISDN-mediated dilation is unaffected by the treatment. As a marker of oxidative stress, allopurinol significantly reduced malondialdehyde. Moreover, myeloperoxidase levels were reduced by the treatment with allopurinol (56.1 ± 3.4 ng/ml vs. 44.4 ± 2.4 ng/ml, P < 0.05) but there were no change in the placebo group. Surprisingly, neither CRP nor fibrinogen levels were affected by the treatment in both groups.ConclusionXanthine oxidoreductase inhibition by allopurinol in patients with metabolic syndrome reduces oxidative stress, improves endothelial function, ameliorates myeloperoxidase levels and does not have any effect on CRP and fibrinogen levels.

Relationship Between Visceral Adipose Tissue and Adiponectin, Inflammatory Markers and Thyroid Hormones in Obese Males with Hepatosteatosis and Insulin Resistance

BACKGROUND AND AIMS In our detailed analysis of the recent academic publications, we have not found sufficient evidence regarding the changes of metabolism that occur in cases of insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the changes in various biomarkers of obese patients by taking into consideration the IR and NAFLD, which occur increasingly together. METHODS Obese male patients included in the study (n = 315) were divided into three groups. Group I was determined as mild pathology (n = 129; HOMA-IR ≥2.5 and grade 0 or HOMA-IR <2.5 and grade 1-2 hepatosteatosis), group II as moderate pathology (n = 145; HOMA-IR ≥2.5 and grade 1-2 or HOMA-IR <4 and grade 3 hepatosteatosis) and group III as severe pathology (n = 41; HOMA-IR ≥4 and grade 3 hepatosteatosis). Waist circumference (WC), percent body fat (%BF), visceral adipose tissue (VAT), subcutaneous abdominal fat tissue (SCAT), thyroid volume (Tvol), thyroid hormones, insulin, adiponectin, fibrinogen and ultrasensitive C-reactive protein (us-CRP) were measured in all patients. RESULTS A negative correlation between adiponectin and HOMA-IR was found (r = -0.4226; p <0.001). In addition, there were significant differences among all three groups with respect to VAT (p <0.01). Moreover total-triiodo-L-thyronine (TT3) and free-triiodo-L-thyronine (fT3) levels were observed first to decrease in group II compared to group I and then to increase in group III (p <0.001). Fibrinogen and us-CRP levels in group III were significantly higher (p <0.001). CONCLUSIONS TT3 and fT3 levels as well as adiponectin, fibrinogen and us-CRP levels may be affected by the relationship between IR and NAFLD in obese patients. Moreover, increased VAT is a more important risk factor than WC, %BF and BMI, with respect to IR and NAFLD.

A Useful Method for the Detection of Ethylenediaminetetraacetic Acid- and Cold Agglutinin-Dependent Pseudothrombocytopenia

Introduction:Pseudothrombocytopenia (PTCP), caused by platelet (PLT) aggregation, is usually associated with ethylenediaminetetraacetic acid (EDTA)-dependent antibodies and cold aggluti-nins against PLT antigens. The aim of this study was to identify the PTCP and discover the most practical method to distinguish it from real thrombocytopenia. Methods:This study included 85 patients without hemorrhagic abnormalities and suspected PTCP. Blood samples containing EDTA, citrate and EDTA-kanamycin (KN) were analyzed at room temperature and 37°C. Results:PTCP was detected in 24 of 85 patients. In 23 of 24 patients, EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) was detected; 5 of whom had also the cold agglutinin-dependent PTCP. In only 1 of 24 patients, the cold agglu-tinin-dependent PTCP was found. In this study, no significant difference was observed in leukocyte counts comparing EDTA and citrate blood samples in cases with EDTA-PTCP. Conclusion:In clinical laboratories, a significant portion of the cases with low PLT counts was attributable to EDTA-PTCP and, therefore, did not require treatment. Even if these cases can be detected by bringing the blood samples containing EDTA to 37°C or by adding KN to blood samples containing EDTA, the use of blood samples containing citrate taken for erythrocyte sedimentation rate analysis is a more practical priority method.

The relationship between serum uric acid levels and the major risk factors for the development of nonalcoholic fatty liver disease

lic services can allow a better understanding of the extent and variety of hepatobiliary diseases. We wish to report our experience in the first liver clinic ever opened in Botswana (a 2.1-million-inhabitant Southern African country) at Princess Marina Hospital, the country’s main referral hospital located in the capital, Gaborone. The liver clinic has one dedicated specialist doctor and one dedicated nurse in addition to non specialist doctors and medical students who gain experience, operates once weekly and is equipped with portable ultrasound scan and Fibroscan ; rapid tests for hepatitis B virus markers and anti-hepatitis C virus (HCV) antibodies are available. Liver biopsies are performed in the hospital where a Pathology Service is available. From 1 August 2013 (day of opening) to 31 August 2015, a considerable number of patients (347; 172 males; mean age: 38 years) presented or were referred from Primary and District Hospitals or the National Blood Transfusion Center because of either jaundice, abdominal distension, elevated liver enzymes, abnormal liver ultrasound, HBsAg or anti-HCV-positivity; 33 different types of liver diseases have been diagnosed so far. Chronic hepatitis B accounts for the highest prevalence (18.8% of the patients), and cirrhosis of different aetiologies ranks next with a prevalence of 7.8%. Other conditions include HCC (7.5%), non alcoholic steatohepatitis (7.2%), drug-induced hepatitis (7.5%), acute hepatitis B (6.1%), obstructive jaundice (largely cancer-related, 6.2%), non cirrhotic portal hypertension (5.5%), abdominal tuberculosis (3.7%), congestive hepatitis (3.6%). Patients with HCC (58% males) presented mostly at advanced stages; only 38% were HBsAg positive and no one was anti-HCV-positive. Drug-induced hepatitis was generally observed in patients on antiretroviral and/or anti-tuberculosis treatment; efavirenz and pyrazinamide were the drugs most commonly implicated. Non cirrhotic portal hypertension was more common in females (75% of cases). The vast majority of the patients were at an advanced stage of disease and would have not received an appropriate diagnosis should a liver clinic had not been opened. Patients with chronic hepatitis B are staged with Fibroscan ; pegylated interferon and oral antivirals are available for treatment. HCV infections are rare and are treated with pegylated interferon and ribavirin. Mortality rates are high largely because of late presentation (85% for HCC at 6 months, 80% for obstructive jaundice, 30% for cirrhosis, 22% for non cirrhotic portal hypertension, 14% for abdominal tuberculosis, 11% for drug-induced hepatitis). In conclusion, the establishment of a liver clinic in a public referral hospital of an African country is feasible and can considerably increase diagnosis and treatment of liver diseases. Specialised, dedicated public clinics should be established in referral hospitals in sub-Saharan African countries in order to diagnose and treat (whenever possible) the numerous cases of liver diseases observed.

The beneficial effects of allopurinol in cardiology practice: decrease in uric acid and vascular oxidative stress/ the effects of lowering uric acid levels using allopurinol on markers of metabolic syndrome in end-stage renal disease patients: a pilot study.

I read with great interest the case report presented by Emiroğlu et al. (1) for which I would like to congratulate all the authors. They described a case with Japanese type cardiomyopathy associated with pre-excitation, but without associated classical finding of deep negative precordial T waves. The authors pointed out that this case might represent a rare case of this type of cardiomyopathy and they could not give a plausible explanation for the absence of deep T wave negativity. However, I would suggest that one explanation for the absence of deep negative T waves might be pre-excitation itself. According to the surface electrocardiogram given in Figures 1 and 2 the accessory pathway seems to be located to the anteroseptal region and as it is well known that preexcitation might be responsible for abnormal repolarization vector. Hence, the normal axis of ventricular activation, namely depolarization and repolarization directions might both be changed according to the location and direction of the accessory pathway. We all are aware that residual T wave axis changes occur after ablation of accessory pathways and cardiac T wave memory are implicated for this behavior. Therefore, in this particular case deep negative T waves usually observed in patients with apical hypertrophic cardiomyopathy representing abnormal repolarization might be masked by the repolarization changes of pre-excitation. It might be interesting to see how T waves would appear after ablation of the accessory pathway. Therefore, I think that the case presented by Emiroğlu et al. (1) should not be considered as a unique entity. It might be merely related to accessory pathway mediated change of repolarization vector.

Re-determining the cut-off points of FIB-4 for patients monoinfected with chronic hepatitis B virus infection

Abstract Objective: This study aimed to determine significant liver fibrosis and cirrhosis with different FIB-4 cut-off points, and the need for liver biopsy (LB) by optimizing the initially established cut-off points of 1.45 and 3.25. Materials and methods: The study included 201 patients monoinfected with chronic HBV. METAVIR classification was used to determine the stage of fibrosis. ROC analysis and the Youden index were performed to define the optimum cut-off points. Results: A FIB-4 cut-off point of 1.45 and 1.62 generated Youden indexes of 0.51 and 0.55, the accuracy of 78.6% and 81.1% for significant liver fibrosis, respectively. The FIB-4 cut-off was set at 2.40 and 3.25 Youden indexes were 0.46 and 0.16, accuracies were 79.6% and 69.7% for significant liver fibrosis, respectively. A cut-off point of 1.45 and 1.62 for FIB-4 generated Youden indexes of 0.62 and 0.66, the accuracies of 81.6% and 84.1% for cirrhosis, while the FIB-4 cut-off point of 2.40 and 3.25 generated Youden indexes of 0.59 and 0.22, with the accuracies of 90% and 84.1% for cirrhosis, respectively. Conclusions: The FIB-4 cut-off points of 1.62 and 2.40 have higher accuracy and may decrease the need for LB 12% more than the initially established ones in HBV monoinfected patients.

Relationship between thrombocytopenia and extrahepatic metastasis of hepatocellular carcinoma: a different perspective.

To the Editor: We read the article by Lee et al., in which pretreatment platelet count was found as a reliable marker to predict extrahepatic metastasis of early stage hepatocellular carcinomas (HCC) following curative treatment, and the cirrhotic thrombocytopenia was found to contribute to relatively low metastasis incidence of HCC compared to many other cancers (1). Although this study brings a new perspective on relationship between thrombocytopenia and extrahepatic metastasis of HCC, prognostic importance of this relationship is not discussed enough. Therefore, we would like to share our thoughts and contributions to the original study in a few stages. Firstly, low platelet count was found to be highly correlated with cirrhotic processes; for that reason we think that the correlation between the low platelet count and low incidence of extrahepatic metastasis of HCC in the original study does not indicate any clinical improvement for this patient group. In a study by Nozaki et al., increased thrombopoietin level (also a result of increased platelet count) was claimed to stimulate liver regeneration and slow down the development of cirrhosis (2). Likewise, in another study, platelet-derived adenosine 50-triphosphate was found to suppress activation of human hepatic stellate cell and to provide platelets induced liver regeneration, and it was also found to reduce liver fibrosis (3). On the basis of these findings, we think that decreased platelet count probably has a negative prognostic value in patients with liver disease. Secondly, in a study evaluating risk factors for postoperative morbidity and mortality after major hepatic resection in HCC patients with underlying liver diseases, it was found that preoperative platelet count was independently associated with postoperative morbidity and mortality (4). In addition, decreased platelet level was found significantly associated with elevated alpha-foetoprotein level, increased the risk of HCC recurrence and the incidence of complications and poor survival of HCC (5). These findings bring to mind whether or not the relationship between platelet count and extrahepatic metastases of HCC is due to a cause and effect relationship. In conclusion, although low platelet count was determined to indicate a low probability for extrahepatic metastasis of HCC in the original study; but considering AFP has a negative prognostic value for HCC, this situation is not a preferable situation for the prognosis. Evaluation of possible reasons for this correlation like association between trombopoietin and hepatocellular proliferation/reduction in regeneration would increase the value of the original study.

Use of Inflammatory Cytokines and Blood PAPP-A Levels As The Laboratory Evidence of Preconditioning in Cardiac Surgery

Received: 14.05.2017 Accepted: 05.06.2017 1Erzincan University, Medical Faculty, Department of Anesthegiology and Reanimasyon, Erzincan, Turkey 2Gülhane Military Hospital, Department of Anesthegiology and Reanimasyon, Ankara, Turkey 3Göztepe Training and Research Hospital, Department of Anesthegiology and Reanimasyon, İstanbul, Turkey yazışma adresi: Didem Onk, Erzincan University, Medical Faculty, Department of Anesthegiology and Reanimasyon, Erzincan, Turkey e-mail: d.hesapdar@gmail.com INTRODUCTION

The Effect of Desflurane and Propofol Protocols on Preconditioning

BACKGROUND Preconditioning is one of the most powerful mechanisms preventing the myocardial ischemic damage that occurs during coronary artery bypass grafting. OBJECTIVES We aimed to investigate the effects of different propofol and/or desflurane administration protocols in terms of the prevention of ischaemia-reperfusion damage. MATERIAL AND METHODS Ninety patients, aged > 18 years, American Society of Anesthesiologists (ASA) category III, scheduled to undergo primary elective coronary artery bypass grafting (CABG), were included in the study. During maintenance, the patients in group 1 (n = 30) received a propofol infusion (5-6 mg/kg/h) combined with a fentanyl infusion (3-5 mcg/kg/h); the patients in group 2 (n = 30) also received a propofol infusion (5-6 mg/kg/h) combined with a fentanyl infusion (3-5 mcg/kg/h), but they were also given 6% desflurane inhalation for 15 min both before cross-clamping of the aorta and after removal of the clamp; the patients in group 3 (n = 30) received a propofol infusion (2-3 mg/kg/h) combined with a fentanyl infusion (3-5 mcg/kg/h) and received the continuous 6% desflurane inhalation. Blood samples were drawn in the preoperative period (S1), during cardiopulmonary bypass, before cross-clamping the aorta (S2), after removal of the cross-clamp (S3) and 24 h after the operation (S4). RESULTS All groups were similar in terms of age and BMI (p > 0.05). TNF-α levels were higher at S3 compared to S1, S2 and S4 (p > 0.001). The TNF-α levels at S4 were lower in group 3 than those in group 1 and group 2 (p < 0.05). In all groups, h-FABP levels showed an increase in S3 but were significantly lower at S4 (p < 0.05). In group 3, h-FABP levels at S2 and S3 were significantly lower than those in group 1 (p < 0.05). There was a moderate correlation between h-FABP and TNF-α levels (Spearmans rho = 0.472, p < 0.001). CONCLUSIONS On the basis of the measurement of h-FABP and TNF-α, low-dose propofol and continuous desflurane inhalation provide more effective preconditioning than propofol alone or a short course of desflurane in patients undergoing CABG.

Platelet reactivity in patients with atrial fibrillation

We read the article entitled ‘Gender and tachycardia: independent modulation of platelet reactivity in patients with atrial fibrillation’ with great interest. In this article Procter, et al.[1] reported that gender and heart rate are independent determinants of platelet function in patients with acute atrial fibrillation (AF). The authors pointed that female sex correlated with impaired nitric oxide (NO) responses independent of platelet aggregability and admission heart rate. However, we have some suggestions about this study: there was no control group and all patients included were > 45 years old; also, mean platelet volume (MPV) is not investigated in study group.