Onur Ural

Streptococcus zooepidemicus meningitis and bacteraemia.

Group C streptococci are common causative agents of epidemic infections in animals and a rare cause of meningitis in humans. The case is reported of a 75-y-old man with meningitis caused by a group C streptococcus (Streptococcus zooepidemicus). He had frequent contact with horses, which were a possible source of infection. In spite of treatment with a third generation cephalosporin, the outcome was fatal.

Correlation between intrahepatic hepatitis B virus cccDNA levels and other activity markers in patients with HBeAg-negative chronic hepatitis B infection.

Objective The aim of this study was to demonstrate the relation between intrahepatic (IH) hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) levels and the other HBV replicative intermediates and hepatocyte expression of HBV antigens. Patients and methods Patients with hepatitis B surface antigen (HBsAg) positivity, hepatitis B early antigen negativity, serum HBV DNA levels 104 copies/ml or more, and constantly or intermittently increased alanine aminotransferase levels were included. Results Fifty-nine patients were included. There was a good correlation between the levels of IH HBV cccDNA and serum HBV DNA (P<0.001). Serum HBsAg levels were weakly correlated with IH HBV cccDNA levels and moderately correlated with serum HBV DNA (r=0.322, P=0.017; r=0.489, P=0.001, respectively). There were no significant correlation between serum HBsAg level and histologic activity index groups (P=0.691), but stage 0, 1, and greater than 2 fibrosis groups were positively correlated with serum HBsAg levels (P=0.019). IH cccDNA and serum HBV DNA were significantly different in hepatitis B core antigen staining groups (P=0.008 and <0.001, respectively) but there was no significant correlation between HBsAg staining groups and HBV replication markers. There was a weak correlation between serum HBsAg levels and IH HBsAg and hepatitis B core antigen levels (r=0.333, P=0.012; r=0.366, P=0.006, respectively). In multivariate analysis, alanine aminotransferase, age, fibrosis stage, and serum HBsAg quantitation were the most important factors predicting IH HBV cccDNA level. Conclusion Histopathologic damage, serum HBV DNA levels, and IH HBV replication markers have a more complex and dynamic process. However, both serum and IH HBV replication markers provide important knowledge about the activity of the disease.

The Clinical Significance of Serum Apoptotic Cytokeratin 18 Neoepitope M30 (CK-18 M30) and Matrix Metalloproteinase 2 (MMP-2) Levels in Chronic Hepatitis B Patients with Cirrhosis.

Background Serum apoptotic cytokeratine 18 neoepitope M30 (CK-18 M30) and matrix metalloproteinase 2 (MMP-2) have been popular markers for detecting liver fibrosis in recent years. CK-18 is a major intermediate filament protein in liver cells and one of the most prominent substrates of caspases during hepatocyte apoptosis. MMP-2 plays an important role in tissue remodeling and repairing processes during physiological and pathological states. Objectives The objective of this study was to investigate the significance of CK-18 M30 and MMP-2 levels for clinical use in patients with chronic hepatitis B (CHB), as well as their sensitivity in determining cirrhotic patients. Patients and Methods This study included 189 CHB patients and 51 healthy controls. A modified Knodell scoring system was used to determine the fibrosis level in chronic hepatitis B patients. CK-18 M30 levels were determined with an M30-Apoptosense ELISA assay. MMP-2 levels were determined with the ELISA assay. Results The study group consisted of 132 (69.8%) males and 57 (30.2%) females, and the control group consisted of 25 males (49.0%) and 26 females (51%). Patients’ CK-18 M30 levels were higher than values of the control group (308 [1–762] vs. 168 [67–287], P=0.001). Serum MMP-2 levels were found to be statistically higher in the patient group with respect to the controls (3.0 [1.1–6.8] vs. 2.0 [1.2–3.4], P=0.001). The highest serum CK-18 M30 and MMP-2 levels were measured in patients with cirrhosis. Serum apoptotic CK-18 M30 levels positively correlated with advanced age, fibrosis stage, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (P= 0.001, 0.033, 0.001, and 0.001, respectively). Serum MMP-2 levels positively correlated with fibrosis stage, serum ALT, and AST levels (P= 0.001, 0.001, and 0.001, respectively). Conclusions Our study indicated that CK-18 M30 and MMP-2 levels were higher in CHB patients compared to healthy controls and they were in association with significant hepatic fibrosis, especially cirrhosis.

Two outbreaks of ESBL‐producing Klebsiella pneumoniae in a neonatal intensive care unit

In the present study, two epidemic episodes of extended spectrum beta‐lactamase (ESBL)‐producing Klebsiella pneumoniae in the neonatal intensive care unit (NICU) were evaluated.

Retreatment of Chronic Hepatitis C Infection with Telaprevir: Preliminary Results in Turkey

BACKGROUND The use of pegylated interferon alpha and ribavirin (PegIFN/RBV) for the retreatment of chronic hepatitis C virus (HCV) infection without a sustained virological response (SVR) prior to PegIFN/RBV treatment has resulted in low success rates. AIMS To investigate the efficacy and safety of telaprevir (TVR) in combination with PegIFN/RBV in patients infected with HCV genotypes 1 and 4 who were previously treated with PegIFN/RBV and failed to achieve SVR. STUDY DESIGN Multi-center, retrospective, cross-sectional study. METHODS The study included 111 patients: 80 prior relapsers, 25 prior null responders, and six prior partial responders to PegIFN/RBV treatment. The patients were given TVR/PegIFN/RBV for 12 weeks, followed by a 12-week PegIFN/RBV treatment; virological response results were assessed at weeks 4, 12, and 24. Treatment was discontinued in patients with HCV RNA >1000 IU/mL at week 4 or with negative RNA results at week 4 but >1000 IU/mL at week 12. Rapid virological response (RVR), early virological response (EVR), extended rapid virological response (eRVR), and virological response at 24th week of treatment were evaluated. The side effects of combination therapy and the rates of treatment discontinuation were investigated. RESULTS The mean age of the patients was 56.02±9.96 years and 45.9% were male. Ninety-one percent of the patients were infected with viral genotype 1, 69.6% with the interleukin (IL) 28B genotype CT and 20.2% were cirrhotic. The RVR rate was 86.3% in prior relapsers, 56% in prior null responders, and 50% in prior partial responders (p=0.002). EVR rates in those groups were 91.3%, 56%, and 83.3%, respectively (p<0.001). eRVR rates were 83.8% in prior relapsers, 48% in prior null responders, and 50% in prior partial responders (<0.001). The virological response at the 24th week of treatment was found to be the highest in prior relapsers (88.8%); it was 56% in prior null responders and 66.7% in prior partial responders (p<0.001). Common side effects were fatigue, headache, anorexia, malaise, anemia, pruritus, dry skin, rash, dyspepsia, nausea, pyrexia, stomachache, and anorectal discomfort. All treatments were discontinued due to side effects in 9.9% of patients. CONCLUSION High virological response rates were obtained with TVR/PegIFN/RBV treatment. Although side effects were frequently observed, the discontinuation rate of combination therapy was low.

Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C

BACKGROUND Drug resistance development is an expected problem during treatment with protease inhibitors (PIs), this is largely due to the fact that Pls are low-genetic barrier drugs. Resistance-associated variants (RAVs) however may also occur naturally, and prior to treatment with Pls, the clinical impact of this basal resistance remains unknown. In Turkey, there is yet to be an investigation into the hepatitis C (HCV) drug associated resistance to oral antivirals. MATERIALS AND METHODS 178 antiviral-naïve patients infected with HCV genotype 1 were selected from 27 clinical centers of various geographical regions in Turkey and included in the current study. The basal NS3 Pls resistance mutations of these patients were analyzed. RESULTS In 33 (18.5%) of the patients included in the study, at least one mutation pattern that can cause drug resistance was identified. The most frequently detected mutation pattern was T54S while R109K was the second most frequently detected. Following a more general examination of the patients studied, telaprevir (TVR) resistance in 27 patients (15.2%), boceprevir (BOC) resistance in 26 (14.6%) patients, simeprevir (SMV) resistance in 11 (6.2%) patients and faldaprevir resistance in 13 (7.3%) patients were detected. Our investigation also revealed that rebound developed in the presence of a Q80K mutation and amongst two V55A mutations following treatment with TVR, while no response to treatment was detected in a patient with a R55K mutation. CONCLUSION We are of the opinion that drug resistance analyses can be beneficial and necessary in revealing which variants are responsible for pre-treatment natural resistance and which mutations are responsible for the viral breakthrough that may develop during the treatment.

Ocular effects of pegylated interferon-α in patients with chronic hepatitis B

Abstract Purpose: To evaluate the early retinal changes and its reflection on the visual field examination in chronic hepatitis B (CHB) patients using pegylated interferon-α (PEGIFN-α) monotherapy. Patients and methods: Thirty eyes of fifteen patients with CHB were examined prospectively for changes in the fundus examination and visual field examination (both Humphrey Perimetry and Frequency Doubling Perimetry). The patients were examined before and in 3 months intervals after starting the PEGIFN-α treatment. The changes in the fundus examination were noted and the visual field examinations, retinal nerve fiber thickness, Schirmer scores and color vision before and at 3 months of the treatment were compared. The statistical evaluation was performed with paired-t test, using SPSS 16.0 Inc. (Chicago, IL). Results: The mean age of the 15 patients (seven male, eight female) was 52.5 ± 12.4 years. There was no significant retinal change in none of the patients. Neither the visual field examination with Humphrey Field Analyzer nor the Frequency Doubling Perimetry results has demonstrated any significant change during 3 months follow-up. There was a statistically significant increase in the retinal nerve fiber layer (RNFL) thickness; while Schirmer test scores for dry eye assessment was significantly decreased. Conclusion: PEGIFN-α monotherapy, which is used for treatment of CHB, may cause some changes in the thickness of RNFL that may necessitate the close follow-up for further morphological changes of the optic disc in these patients.

Neuro-Behçet's syndrome presenting with features mimicking acute tuberculous meningitis

Behçets disease is an inflammatory disease that can involve multiple systems. Here, we describe a case of neuro-Behçets syndrome presenting with features mimicking acute tuberculous meningitis. Behçets disease should be considered in the differential diagnosis of a meningeal syndrome unless a viral or bacterial agent is demonstrated.

Is serum high-mobility group box 1 (HMGB-1) level correlated with liver fibrosis in chronic hepatitis B?

Background: High-mobility group box 1 (HMGB1), identified as an alarmin molecule, was shown to have a role in virus-triggered liver injury. We aimed to evaluate the association between serum levels of HMGB1 and liver fibrosis. Method: This cross-sectional case-control study included 189 chronic hepatitis B (CHB) patients and 51 healthy controls. All patients underwent liver biopsy and modified Knodell scoring system used to determine the fibrosis level in CHB patients. Serum HMGB1 levels were determined with enzyme-linked immunosorbent assay (ELISA). Results: Mean serum HMGB1 levels of patients (58.1 ± 54.7) were found to be higher than those of the control group (7.1 ± 4.3) (P = .001). HMGB1 levels of patients with advanced-stage fibrosis (stage 4 and 5) were detected to be higher than those of patients with early-stage fibrosis (stage 1–3). However, this difference was not statistically significant (P > .05). Albumin levels of fibrosis 3 and 4 patients were lower than fibrosis 1 and 2 patients. ALT, HBV DNA, and AFP levels of fibrosis 5 patients were significantly higher than fibrosis 1 and 2 patients, and their platelet and albumin levels are lower than fibrosis 1 and 2 patients (P < .001). In a logistic regression model, fibrosis levels were correlated with ALT values and inversely correlated with albumin levels. Conclusion: In this study, we demonstrated that serum HMGB1 levels increase in the early course of liver injury and this increase is not correlated with severity of the liver damage.

Primary hydatid disease of brachialis and biceps brachii muscles: a case report

Primary hydatid cyst of the skeletal muscle is very rare and accounts for less than 1% of all cases. It is often asymptomatic and can pose diagnostic problems. Accurate diagnosis should be made using ultrasonography and magnetic resonance imaging. Proper treatment should be a wide surgical resection of the localized muscle with the aid of antihelmintic chemotherapy pre- and postoperatively. We report a case of primary hydatic cyst located simultaneously in both the biceps brachii and brachialis muscles, treated with wide resection surgery and pre- and postoperative anthelmintic chemotherapy.