Interleukin-28 gene polymorphisms may contribute to HBsAg persistence and the development of HBeAg-negative chronic hepatitis B.

BACKGROUND & AIMS: Aim of this study was to investigate whether a potential association exists between several single nucleotide polymorphisms (SNPs) of the IL-28B gene (rs12979860, rs1188122, rs8099917, rs8105790, rs12980275) and HBsAg persistence. Further, a potential effect on the development of HBeAg-negative CHB vs. inactive HBsAg carrier state was assessed in a genotype D HBV cohort. A cohort of chronic HDV patients was also used to see if they behave differently compared to chronic HBV patients. METHODS: This study was conducted in three main patient cohorts: Group 1 consisted of 482 patients with HBsAg persistence. Of them 143 were inactive carriers, 94 had HBeAg-positive chronic hepatitis B (CHB) and 245 had anti-HBe-positive CHB. Group 2 represents spontaneously recovered HBV patients; they were anti-HBs and anti-HBc positive. Group 3 consisted of 176 chronic hepatitis delta (CHD) patients with antidelta and HDV-RNA positivity. DNA sequencing was performed for genotyping. RESULTS: When patients with HBsAg persistence were compared with spontaneously recovered patients, a significant difference was observed for rs8105790 (P < 0.0001), rs12980275 (P < 0.02). Patients who had the CC/TC genotype for rs8105790 (P < 0.0001) and AA genotype for 1188122 (P < 0.02) were more likely to be inactive HBsAg carriers, when inactive HBsAg carriers were compared with HBeAg-negative CHB patients. Comparison of CHD patients vs. recovered HBV patients was parallel to that of HBV persistence vs. recovered HBV with similar significant differences in same SNPs. CONCLUSION: These results suggest that IL-28B polymorphisms may contribute to HBsAg persistence and the development of the inactive HBsAg carrier state.

Potential proteomic biomarkers in assessing liver fibrosis using SELDI-TOF MS.

BACKGROUND/AIMS: The accurate assessment of the severity of liver fibrosis is of paramount importance in determining treatment strategies, response to treatment and prognosis in patients with chronic liver disease. The aim of this study was to investigate potential proteomic biomarkers for assessing stages of hepatic fibrosis. METHODS: Serum samples of 83 patients with chronic liver disease (using METAVIR index, 17 F0, 30 F1, 6 F2, 9 F3, and 21 F4 patients) and 29 healthy controls were analyzed using surface-enhanced laser desorption/ionization time-of- flight mass spectrometry on IMAC30 ProteinChip arrays. Discriminatory peaks between groups were identified using Mann-Whitney U non-parametric test. Comparison of mild (F0, F1) and severe fibrosis (F2, F3, F4) was performed using tree classification (cross-validation) with the Biomarker Patterns Software, version 5.0 (Ciphergen Biosystems, US). RESULTS: No statistically significant discriminatory peak was evident between F0, F1 and F2 fibrosis. More than 30 peaks were found to be discriminatory between patients with cirrhosis (F4) and all other stages of liver fibrosis, including F2 and F3. Six surface-enhanced laser desorption/ionization proteomic features were found to be discriminative for mild (F0, F1) vs. advanced (F2, F3, F4) fibrosis (AUROC ≥0.8, p<0.05, Mann-Whitney test). The decision tree (m/z 4280, 10453 and 6376) yielded a sensitivity of 83.3% (30/36), a specificity of 85.1% (40/47), a positive predictive value of 81.1%, and a negative predictive value of 86.9%, with an AUROC of 0.94. CONCLUSIONS: The results of this study revealed discriminatory peaks between the protein profiles of patients with cirrhosis and other stages of liver fibrosis. Potential proteomic biomarkers can be notably determined for discriminating mild and advanced fibrosis using surface-enhanced laser desorption/ionization time-of- flight mass spectrometry.

Evaluation of Scheimpflug imaging parameters in subclinical keratoconus, keratoconus, and normal eyes.

PURPOSE: To determine the efficacy of different Scheimpflug-imaging parameters in discriminating between subclinical keratoconus, keratoconus eyes, and normal eyes. SETTING: Department of Ophthalmology, Ankara University Faculty of Medicine, Ankara, Turkey. DESIGN: Comparative case series. METHODS: Pentacam Scheimpflug measurements were taken in eyes with mild to moderate keratoconus, subclinical keratoconus, or with myopic astigmatism (normal eyes). Several parameters provided by the software or derived from the elevation maps were evaluated and compared between the groups. The Mann-Whitney test, receiver-operating-characteristic (ROC) curves, and logistic regression analysis were used to compare the mean measurements and to evaluate the sensitivity and specificity of the parameters or constructed models. RESULTS: The corneal power and elevation measurements were statistically significantly higher and the cornea was significantly thinner in eyes with subclinical or clinical keratoconus than in normal eyes (P < .05). The ROC curve analysis showed high overall predictive accuracy of various elevation and thickness indices in discriminating ectatic corneas from normal corneas. Logistic regression analysis showed that the goodness of fit of a model using a combination of corneal power, thickness, and anterior elevation parameters was best in discriminating keratoconus eyes from normal eyes, whereas that of a model using a combination of corneal power, thickness, and posterior elevation was best in discriminating subclinical keratoconus eyes from normal eyes. CONCLUSION: Combined analysis of anterior and posterior corneal power, elevation, and thickness data provided by the Scheimpflug device effectively discriminated between ectatic corneas and normal corneas. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Antiepileptic activity of melatonin in guinea pigs with pentylenetetrazol-induced seizures.

BACKGROUND: Antiepileptic and neuroprotective effects of melatonin (N-acetyl-5-methoxytryptamine) have been shown at higher doses (50-160 mg/kg). We aimed to investigate the antiepileptic effects of low-dose melatonin (10 mg/kg) on pentylenetetrazol (PTZ)-induced experimental epilepsy model. MATERIALS AND METHODS: Twelve male albino guinea pigs weighing 500-800 g were used in our work. Initially, latent period, seizure intensity and mortality parameters were evaluated during the epileptic seizure induced by PTZ. After a recovery period of 7 days, effects of the neuroprotective agent, melatonin (which is dissolved in 2.5% ethanol-saline solution), on epileptic seizures induced by PTZ were evaluated. Effects of 2.5% ethanol, which is an anticonvulsant agent when administered acutely in high concentrations, on PTZ-induced seizures were also evaluated. RESULTS: Data obtained from the study groups (PTZ, PTZ + melatonin and PTZ + ethanol) were evaluated by paired t-test, and p<0.005 was considered statistically significant. The differences of latent periods between the PTZ and PTZ + melatonin groups were found to be statistically significant (p<0.001). CONCLUSION: Although melatonin does not have a primary anticonvulsant effect at low doses (10 mg/kg), it lowers the mortality rates and attenuates seizure severity while increasing the latent period.

Anterior chamber parameters measured by the Pentacam CES after uneventful phacoemulsification in normotensive eyes.

PURPOSE: We set out to quantify changes in the anterior chamber volume (ACV), anterior chamber depth (ACD) and anterior chamber angle (ACA) measurements obtained by the Pentacam rotating Scheimpflug camera following uneventful phacoemulsification surgery in normotensive eyes with open iridocorneal angles. METHODS: We enrolled 44 eyes of 44 consecutive patients undergoing cataract extraction in this prospective study. Patients with a history of glaucoma, angle-closure glaucoma or any other concurrent ocular disease were excluded. A detailed eye examination including intraocular pressure (IOP) measurement was performed and ACV, ACD and inferior, superior, temporal and nasal ACA measurements were obtained in each patient eye using the Pentacam Comprehensive Eye Scanner (Pentacam CES) before and 3 months after phacoemulsification and intraocular lens (IOL) implantation with temporal clear corneal incision. Data were compared using paired t-test and one-way anova. RESULTS: Mean preoperative ACV, ACD, ACA and IOP measurements were 164.7 +/- 49.8 mm(3), 3.0 +/- 0.8 mm, 35.7 +/- 10.2 degrees and 15.8 +/- 3.7 mmHg, respectively. Three months postoperatively, mean ACV, ACD, ACA and IOP measurements were 200.9 +/- 33.3 mm(3), 3.9 +/- 0.9 mm, 41.5 +/- 6.5 degrees and 13.2 +/- 3.9 mmHg, respectively. Postoperative mean ACV, ACD and ACA values in all four quadrants were significantly increased (p < 0.0001, p < 0.0001, p < 0.0001, respectively), whereas IOP was significantly reduced (p < 0.0001). CONCLUSIONS: The Pentacam CES allowed very easy, fast, automatic and non-contact quantification of the anterior chamber parameters pre- and postoperatively in all patient eyes. Measurements obtained confirm that in normotensive eyes with open iridocorneal angles, the ACV and ACD increase and the ACA widens in all quadrants 3 months after uneventful phacoemulsification and IOL implantation. These changes are accompanied by a significant fall in IOP in the short term.

Effects of polymorphism in G2677T/A triallelic region of MDR1 gene in Turkish patients with inflammatory bowel disease.

BACKGROUND/AIMS: Crohn's disease and ulcerative colitis are both chronic inflammatory disorders of the gastrointestinal tract, the main causes of which remain unknown. Crohn's disease and ulcerative colitis are characterized by cell-mediated immune response against the luminal bacteria. It is suggested that expression levels and function of P-glycoprotein, encoded by the MDR1 gene, are important for protection of the gut against xenobiotics and bacterial toxins. Therefore, the mutations of the MDR1 gene are thought to be related with the pathogenesis of inflammatory bowel disease. The aim of this study was to investigate the G2677T/A polymorphism in the MDR1 gene in Turkish patients with inflammatory bowel disease and a healthy control group. METHODS: In our study, the genotypes of endoscopically or histopathologically diagnosed Crohn's disease (n: 35; 14 F, 21 M) and ulcerative colitis (n: 82; 36 F, 46 M) patients and of 70 healthy individuals (39 F, 31 M) were compared. In the patient and control groups, polymerase chain reaction restriction fragment length polymorphism analysis was performed for two polymorphisms (G2677T and G2677A) of the MDR1 gene. RESULTS: In this study, the frequency of alleles at position 2677 of the MDR1 gene, which has a triallelic polymorphism, was not found to be significantly different between the patient and the healthy control groups. Moreover, the 2677A allele was not detected in either the patient group or the healthy control group. CONCLUSIONS: In this study, the G2677T/A polymorphism observed in the MDR1 gene was not found to be a risk factor for Crohn's disease or ulcerative colitis.

Corneal elevation and thickness in relation to the refractive status measured with the Pentacam Scheimpflug system.

PURPOSE: To prospectively evaluate the elevation and thickness data in patients with different types of refractive errors. SETTING: Department of Ophthalmology, Ankara University Faculty of Medicine, Ankara, Turkey. METHODS: After the refractive errors in 215 consecutive patients were determined, corneal topography measurements with the Pentacam Scheimpflug system were taken in the right eye of all patients and the right eye of 31 healthy emmetropic volunteers. The eyes with refractive errors were assigned to 1 of the following 4 groups: myopia, myopic astigmatism, high myopia, and hyperopia. The means of the parameters of 3 Pentacam measurements were evaluated and compared. RESULTS: Eyes with high myopia had significantly lower mean corneal thickness and volume measurements and higher mean anterior chamber depth (ACD) and anterior chamber volume (ACV) measurements than eyes in the other groups. The mean ACD, ACV, and anterior chamber angle were significantly lower in hyperopic eyes than in the other groups. The mean keratometry readings were statistically significantly flatter in the hyperopia group than in the other 4 groups. CONCLUSIONS: Eyes with high myopia had thinner corneas and deeper anterior chambers than emmetropic eyes and eyes in the other ametropic groups. Excluding eyes with hyperopia, which had significantly flat anterior and posterior elevation measurements, the elevation measurements in eyes with myopic refractive errors did not differ from each other or from those in emmetropic eyes. These findings may help clinicians and refractive surgeons using the Pentacam to better define normal from abnormal in the clinical setting.

Clarithromycin resistance prevalence and Icea gene status in Helicobacter Pylori clinical isolates in Turkish patients with duodenal ulcer and functional dyspepsia.

Clarithromycin resistance in Helicobacter pylori is a principal cause of failure of eradication therapies, and its prevalence varies geographically. The IceA gene is a virulence factor associated with clinical outcomes. The objective of this study was to determine the current state of clarithromycin resistance prevalence, and to investigate the role of iceA genotypes in 87 Turkish adult patients (65 with functional dyspepsia and 22 with duodenal ulcer). A2143G and A2144G point mutations were tested by PCR-RFLP for clarithromycin resistance. Among the patients in the study, 28 patients were tested by agar dilution as well. Allelic variants of the iceA gene were identified by PCR. A total of 24 (27.6%) strains evidenced one of the mutations, either A2143G or A2144G. IceA1 was found to be positive in 28 of the strains (32.2%), iceA2 was positive in 12 (13.8%) and, both iceA1 and iceA2 were positive in 22 (25.3%) strains. In conclusion, we discovered no relationships between iceA genotypes and functional dyspepsia or duodenal ulcer, nor between clarithromycin resistance and iceA genotypes. Clarithromycin resistance appears to be more prevalent in Turkish patients.

Corneal thickness measurements in normal and keratoconic eyes: Pentacam comprehensive eye scanner versus noncontact specular microscopy and ultrasound pachymetry.

PURPOSE: To compare central corneal thickness (CCT) measurements taken with the Pentacam comprehensive eye scanner (CES), noncontact specular microscopy (SM), and ultrasound pachymetry (UP) in normal and keratoconic corneas. SETTING: Department of Ophthalmology, Ankara University School of Medicine, Ankara, Turkey. METHODS: In a prospective study, 3 CCT measurements were taken with the Pentacam CES, SM, and UP in that sequence from 1 eye of 45 consecutive patients with myopia (group A) and 62 consecutive patients with keratoconus (group B). Eyes with keratoconus were further divided into 3 subgroups, mild, moderate, and severe, according to the mean keratometry readings. RESULTS: Pentacam CES (r = 0.994) and UP (r = 0.993) demonstrated very high and comparable reproducibility in group A. In group B, Pentacam CES displayed better reproducibility (r = 0.988) than UP (r = 0.969) and SM (r = 0.901). The mean CCT measurements of Pentacam CES and UP were not significantly different in group A (P = .37) and in eyes with mild keratoconus (P = .29), whereas significant differences between all instrument pairs were evident in group B and in moderate and severely keratoconic eyes (P<.05). Noncontact SM measurements were significantly smaller than those of Pentacam CES and UP in all groups (P<.05) when a measurement could be obtained. There were significant linear correlations between CCT measurements of Pentacam CES, UP, and noncontact SM in groups A, B, and mildly keratoconic eyes (P<.001). CONCLUSIONS: Results suggest that whereas Pentacam CES and UP may be used interchangeably in normal eyes in the clinical setting for the measurement of CCT, one should be cautious interpreting corneal thickness data from Pentacam CES, UP, and particularly SM in eyes with keratoconus. Whereas, in normal and mildly keratoconic eyes, Pentacam CES and UP demonstrated very high and comparable reproducibility, in moderately keratoconic eyes, Pentacam CES readings showed better reproducibility than UP.

In vivo confocal microscopy findings in keratoconus.

PURPOSE: : To evaluate corneal structure in eyes with keratoconus by using in vivo confocal microscopy. METHODS: : In a prospective institutional study, 48 eyes of 24 consecutive patients with keratoconus were examined by in vivo confocal microscopy. Forty-four eyes of 22 healthy subjects served as the control. The main outcome measures were qualitative and quantitative changes encountered at confocal microscopy examination. RESULTS: : In the keratoconus group, in vivo confocal microscopy findings included elongated, exfoliating superficial epithelial cells; brightly reflective material deposition within the basal epithelial cells; prominent, thickened subbasal nerves; structural changes in subbasal nerve fibers; pronounced reflectivity and irregular arrangement of stromal keratocytes; structurally abnormal anterior stromal keratocyte nuclei; folds in the anterior, mid, and posterior stroma; folds in Descemet's membrane; pleomorphism and enlargement of endothelial cells; and endothelial guttata. No such abnormal findings were present in the control group. There were significant differences between the two groups in terms of the mean basal epithelial, anterior and posterior stromal keratocyte densities, the mean basal epithelial cell area, and the mean endothelial cell hexagonality percentages. CONCLUSIONS: : Quantitative and qualitative structural changes were observed in all corneal layers in eyes with keratoconus by using slit-scanning confocal microscopy. The changes at all levels were more prominent in eyes with severe keratoconus. This noninvasive in vivo technique may prove to be useful in the diagnosis and follow-up of keratoconus and in the understanding of its pathophysiology.

NOD2/CARD15, NOD1/CARD4, and ICAM-1 gene polymorphisms in Turkish patients with inflammatory bowel disease.

PURPOSE: The genetic susceptibility of people with certain NOD2/CARD15, NOD1/CARD4, and ICAM-1 gene variants to inflammatory bowel disease is still under investigation. The aim of this study was to investigate polymorphisms in the NOD2/CARD15 (R702W, G908R, and 3020insC), NOD1/CARD4 (E266K, D372N), and ICAM-1 (G241R, K469E) genes, which are known to be associated with inflammation, in Turkish patients with inflammatory bowel disease and healthy control groups. METHODS: The genotypes of 70 patients with endoscopically and histopathologically diagnosed Crohn's disease (38 men, 32 women; mean age, 38.8 +/- 1.3), 120 patients with ulcerative colitis (67 men, 53 women; mean age, 41.7 +/- 1.3) and 106 healthy control subjects (37 men, 69 women; mean age, 35.7 +/- 1.4), who stated that they had never had any prior bowel disease history, were compared. A polymerase chain reaction-restriction fragment length polymorphism analysis was performed for two variants of the ICAM-1 gene, the three main variants of the NOD2/CARD15 gene, and the E266K variant of the NOD1/CARD4 gene, and DNA sequencing was used for the D372N polymorphism of the NOD1/CARD4 gene. RESULTS: In this study, the three previously described Crohn's disease-predisposing variants of the NOD2/CARD15 gene and the polymorphisms examined in the NOD1/CARD4 and ICAM-1 genes were not found to be associated with ulcerative colitis or Crohn's disease. CONCLUSIONS: These findings suggest that the polymorphisms observed in the NOD2/CARD15, NOD1/CARD4, and ICAM-1 genes are not genetic susceptibility factors for Crohn's disease or ulcerative colitis in Turkey.

Cytokine gene polymorphisms in Turkish patients with inflammatory bowel disease.

OBJECTIVE: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the bowel, the causes of which are not fully known. Ethnic differences in disease prevalence, familial aggregation of the disease and studies of twins provide the most important evidence to suggest that genetic factors play a role in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to examine the allelic polymorphisms that can determine the immune response levels in tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1B), interleukin-1 receptor antagonist ( IL-1RN) and interleukin-10 (IL-10) genes and to investigate their roles in the inflammatory pathway in IBD. MATERIAL AND METHODS: The study included 120 patients with UC and 70 patients with CD who were diagnosed either endoscopically or histopathologically. The control group comprised 105 healthy individuals who stated that they had never had any bowel disease during their life span. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method for polymorphisms in the TNFalpha gene at positions -308 and -238, the IL-10 gene at positions -1082 and -627, the IL-1B gene at -511 regions and the variable number of tandem repeat (VNTR) method for polymorphism in the intron 2 of the IL-1RN gene were performed. The results were analyzed on agarose gel electrophoresis. RESULTS: No significant differences were found in the allele and genotype frequencies of the polymorphisms in the IL-1B, IL10, TNFalpha and IL-1RN genes between the patients with UC and CD and controls. CONCLUSIONS: The results suggest that these polymorphisms were not important risk factors in the susceptibility to IBD in Turkish patients.

Peritumoral brain edema in intracranial meningiomas.

OBJECTIVE: The goal of this study was to determine the relationship between patient age and gender and meningioma location, histological subtype, size, lobulation and peritumoral brain edema (PTBE). PATIENTS AND METHODS: In a series of 55 patients with intracranial meningiomas, factors possibly related to the development of PTBE were analyzed. We used an EI (edema index) as the indicator of PTBE. EI was calculated by dividing the area of PTBE by that of the tumor. Thus if EI = 1, there is no PTBE. Univariate analysis was used to evaluate the relationship between EI and related factors. The MEI (mean edema index) difference between age groups was calculated using the Duncan Test. RESULTS: We found that none of the factors analyzed influenced PTBE except patient age 61-70 years, which correlated with PTBE (p = 0.022). The difference between MEI in the 41-50 years and 61-70 years age groups was significant, with that in the 61-70 years age group being significantly higher. CONCLUSION: We conclude that these findings in the 61-70 years age group may constitute an increased risk of perioperative mortality and morbidity.

Amiodarone keratopathy: an in vivo confocal microscopy study.

PURPOSE: To evaluate the characteristics and evolution of corneal morphologic changes induced by systemic amiodarone treatment by using in vivo slit scanning confocal microscopy in an attempt to understand the pathogenesis of corneal and other systemic side effects of this drug. METHODS: Forty-nine eyes of 25 consecutive subjects receiving amiodarone therapy (group A) and 26 eyes of 13 age- and sex-matched healthy control subjects (group B) were enrolled in the study. RESULTS: In group A, the mean dosage of amiodarone was 224.0 +/- 71.3 mg, and the mean duration of treatment was 21.3 +/- 20.9 months. In eight (8 of 49,16.3) eyes of four patients, no deposition was observed, neither by slitlamp nor by confocal microscopy. The deposition could be detected as early as 2 months after the onset of treatment in 41 (41 of 49, 83.7%) eyes, by slitlamp and confocal microscopy. Deposition was significantly correlated with the duration of treatment and, therefore, the cumulative dose of the drug ingested. Deposits were observed as bright, hyper-reflective spots that were localized intracellularly and were present at the level of basal lamina of all 41 (100%) corneas in which deposition could be observed at confocal microscopy. Deposits were also observed in the superficial epithelium, anterior stroma, mid stroma, and subepithelial nerves in eyes with grade 2 to 4 keratopathy. Additionally, morphologic abnormalities were observed in anterior stromal keratocytes, subepithelial and stromal nerves, and endothelium. The mean anterior and posterior keratocyte densities were statistically significantly higher than those in group B. CONCLUSIONS: In addition to showing drug deposition does not seem to occur before 2 months of treatment and does not seem to be correlated with tear function. Although the clinical significance of morphologic changes induced by the drug is known and although deposition could not be detected before it was evident with slitlamp biomicroscopy, with some improvement in instrumentation, the authors believe that confocal microscopy will also prove to be useful in early diagnosis and in understanding the pathophysiology of amiodarone keratopathy. This may help grow insight to the mechanism of other, sometimes lethal, systemic side effects of this drug.

Changes in the seroepidemiological pattern of Helicobacter pylori infection over the last 10 years.

BACKGROUND/AIMS: This study was undertaken to evaluate changes in the seroepidemiological pattern of Helicobacter pylori in a group of Turkish children over a span of 10 years. METHODS: A total of 403 (219+184) serum samples were obtained from a primary school located in the urban part of Ankara in 1990 and 2000. All of the samples were from healthy students aged 7-14 (in 1990, n= 219, 109 females; and in 2000, n= 184, 90 females). RESULTS: All serum samples were assayed for Helicobacter pylori IgG by means of enzyme-linked immunosorbent assay. The overall prevalence of Helicobacter pylori antibodies was 78.5% in 1990 and 66.3% in 2000. The prevalence of Helicobacter pylori was found to be decreasing over a time span of 10 years (p<0.01). While the most susceptible age group to Helicobacter pylori in 1990 was 10 years (89.5%), in 2000 the susceptible age group was 8 years (85.0%). CONCLUSIONS: Our data suggest that the seroprevalence of Helicobacter pylori infection seems to have decreased during the last 10 years in Turkey. This change may be attributable to the changes in environmental condition and socioeconomic development that have taken place in the country.