Effect of the switch status of Helicobacter pylori outer inflammatory protein A on gastric diseases.

Helicobacter pylori OipA (Outer Inflammatory Protein A) is an outer membrane protein that takes role in the adherence and colonization to the stomach. oipA gene expression is regulated by the slipped-strand mispairing mechanism through a hypermutable CT dinucleotide repeat motif in the 5΄ region. Alterations in the CT number repeats cause frame-shift mutations to result in phase variation of oipA expression. While a functional "On" status has been recognized as a risk factor for peptic ulcer diseases and gastric cancer in many studies, some controversial findings still exist. To this end, this study compiled the sequence data of oipA from 10 different studies between 2000-2019 and 50 oipA DNA sequences from our own research that examined the relationship between the phase On/Off status of oipA and gastric diseases based on CT repeat number. Overall, we have reached 536 oipA DNA sequences from patients. This large collection of oipA sequences first clarified the absolute conservation of the peptide-pentamer of FWLHA for phase ''On'' status, suggesting this pentamer as a superior marker for the determination of oipA status than counting the number of CT repeats. Combining the sequence and patient data, we have re-analyzed the association between the ''On'' status of oipA and gastric diseases. Our results showed a strong association between oipA ''On'' status and gastric cancer supporting previous findings. We also investigated the AlphaFold2 computed structure of OipA that adopts a beta-barrel fold closely resembling to the autotransporter family of H. pylori. Altogether, this study confirms a strong association between oipA ''On'' statuses and severe gastrointestinal diseases like cancer and provides useful insights into the FWLHA pentamer as an indicator of "On" status of oipA putative autotransporter function rather than CT repeats number.

The crosstalk between H. pylori virulence factors and the PD1:PD-L1 immune checkpoint inhibitors in progression to gastric cancer.

BACKGROUND: The progression to gastric cancer has been linked to chronic infection with Helicobacter pylori (H. pylori). Immune checkpoint inhibitors (programmed cell death -1, PD-1; programmed cell death -ligand 1, PD-L1) have a role in cancer immune escape. The relationship between H. pylori virulence factors with PD-1, PD-L1 T helper 1 (Th1), T helper 17 (Th17), and regulatory T cell (Treg) response genes, has not been thoroughly investigated in the development of gastric cancer. Therefore, we evaluated how H. pylori virulence factors influence the expression levels of immune-related genes in the development of gastric immunopathology. METHODS: A total of 92 gastric tissues of normal controls and patients with gastritis, gastric ulcer, and gastric cancer were examined for the expression of immune-checkpoint inhibitor genes (PD-1 PD-L1), Th1 (interferon- γ, IFN-γ), Th17 (interleukin- 17, IL-17, Retinoic-acid-receptor- related orphan nuclear receptor gamma t, RORγ-t), and Treg (Forkhead box P3, FOXP3) response genes with quantitative real-time PCR (qRT-PCR). Furthermore, correlation of H. pylori virulence factors' (cytotoxin-associated gene A, cagA; vacuolating cytotoxin gene A, vacA (s1,s2,m1,m2); blood group antigen-binding adhesin gene A, babA, duodenal ulcer promoting gene A, dupA; the putative neuraminyllactose-binding hemagglutinin homolog, hpaA; neutrophil-activating protein A napA; outer inflammatory protein A, oipA; urease A, ureA; and urease B, ureB) genotypes with a degree of inflammation and density of H. pylori were investigated. Next, the relationship between H. pylori virulence factors and immune-checkpoint inhibitor genes, and T-cell response genes was evaluated. Eventually, a decision tree model was developed to determine the clinical outcome of patients using expression data. RESULTS: The intensity of PD-1 and PD-L1 mRNA expression was increased significantly in gastric tissue of patients with gastric ulcer (PD-1: 2.3 fold, p=0.01; PD-L1: 2.1 fold, p=0.004), and gastric cancer (PD-1: 2 fold, p= 0.04; PD-L1: 1.8 fold, p=0.05) compared with control subjects. Also, PD-1: PD-L1 expression was significantly higher in patients with gastritis, who were infected with a marked density of H. pylori compared with its mildly infected counterparts. Furthermore, a novel negative correlation was found between PD-1 (r= -0.43) and PD-L1 (r= -0.42) with FOXP3 in patients with gastritis. CagA-positive H. pylori strain's negative association with PD-L1 expression (r=-0.34) was detected in patients with gastritis. Interestingly, PD-1 mRNA expression correlated positively with vacA s2/m2, in gastritis (r=0.43) and ulcer (r=0.43) patients. Furthermore, PD-1: PDL1 expression negatively correlated with vacA m1/m2 (r=-0.43 for PD-1; r=-0.38 for PD-L1) in gastritis patients. Moreover, an inverse correlation of PDL1 was present with vacA m1 (r=0.52) and vacA s1/m1 (r=0.46) versus vacA m2 (r=-0.44) and vacA m1 (r=0.52) and vacA s1/m2 (r=-0.14) in ulcer patients, respectively. Also, a correlation of vacA m2 (r=-0.47) and vacA s1/s2 (r= 0.45) with PD-1 was detected in ulcer patients. In addition, a novel negative correlation between FOXP3 mRNA levels and napA was shown in patients with gastritis and ulcer (r=-0.59). Finally, a computer-based model that was developed showed that knowing the expression levels of PD-L1, RORγ-t, and vacA s1/m2 would be useful to detect the clinical outcome of a patient. CONCLUSION: Our results suggested that PD-1:PD-L1 immune checkpoint inhibitors were increased in gastric pre-cancerous lesions that progress to gastric cancer. Herein, we report the relationship between H. pylori virulence factors and expression of host immune checkpoint inhibitors for diagnostic prediction of gastric malignancies using computer-based models.

Analyzing esophageal squamous cell papillomas for the presence of human papilloma virüs.

BACKGROUND/AIMS: Human Papilloma Virus (HPV) infection can be a predisposing condition for the development of squamous cell papilloma (SCP) of the esophagus, which can progress to dysplasia and to carcinoma as a result of chronic infection. The aim of the present study was to search for the presence of HPV in the esophageal SCP, and to genotype the detected HPV. MATERIALS AND METHODS: Data from patients with definite diagnosis of SCP of the esophagus were identified from pathology records for two years period at different Hospitals. Slides from each patient were reviewed and samples with satisfactory papilloma tissues were submitted to molecular analysis. DNA has been isolated. DNA sequencing has been performed for genotyping HPV for all types. RESULTS: Our study group consisted of 21 women and 17 men (a total of 38 patients), mean age was 41 years (range 17-67 years). Most of the papillomas were located at mid-esophagus (68%). Eight out of 38 patients (21%) had associated erosive esophagitis, and fourteen patients (36.8%) had Helicobacter Pylori (H. pylori). Of the 38 SCP analyzed, seven (19%) were positive for HPV DNA. Three of them were of genotype 6, whereas four were of genotype 16, 18, 31, 81 that are known as highly oncogenic. There were no correlations between the presence of HPV and the patient's age, the presence of reflux esophagitis or H. pylori, smoking habit and the location of the papillomas. CONCLUSION: The presence of high-risk type HPV in esophageal SCP may implicate a role of the virus in the pathogenesis of the esophageal tumor.

Ki67 as a prognostic factor for long-term outcome following surgery in gastrointestinal stromal tumors.

OBJECTIVE: This study aimed to examine the value of Ki67 expression along with other potential prognostic factors for predicting overall survival and disease-free survival in patients with gastrointestinal stromal tumors who underwent curative resection. PATIENTS AND METHODS: Sixty-eight histologically confirmed and operated patients with gastrointestinal stromal tumors were included. Clinical and follow-up data were retrieved from medical records and patients were contacted at the end of the study. The effects of certain clinical and histopathological parameters on survival outcomes were examined. RESULTS: Sixty-eight patients were followed for a mean duration of follow-up of 2923.3 patient-months. Twelve deaths (17.6%), seven metastasis (10.3%), and two local recurrences (2.9%) occurred. Overall survival was 102.5 months [95% confidence interval (CI), 88.3-116.8] and disease-free survival was 91.8 months (95% CI, 76.5-107.2). Multivariate analyses identified a high Ki67 index (≥ 10%) as an independent predictor of both poor overall survival (hazard ratio, 4.8; 95% CI 1.2-19.2; P=0.027) and poor disease-free survival (hazard ratio, 15.3; 95% CI, 4.7-50.2). CONCLUSION: A high Ki67 expression seems to be a useful prognostic factor that would aid in predicting disease course in gastrointestinal stromal tumors. These findings deserve further investigation in larger studies.

Multiplex-PCR-Based Screening and Computational Modeling of Virulence Factors and T-Cell Mediated Immunity in Helicobacter pylori Infections for Accurate Clinical Diagnosis.

The outcome of H. pylori infection is closely related with bacteria's virulence factors and host immune response. The association between T cells and H. pylori infection has been identified, but the effects of the nine major H. pylori specific virulence factors; cagA, vacA, oipA, babA, hpaA, napA, dupA, ureA, ureB on T cell response in H. pylori infected patients have not been fully elucidated. We developed a multiplex- PCR assay to detect nine H. pylori virulence genes with in a three PCR reactions. Also, the expression levels of Th1, Th17 and Treg cell specific cytokines and transcription factors were detected by using qRT-PCR assays. Furthermore, a novel expert derived model is developed to identify set of factors and rules that can distinguish the ulcer patients from gastritis patients. Within all virulence factors that we tested, we identified a correlation between the presence of napA virulence gene and ulcer disease as a first data. Additionally, a positive correlation between the H. pylori dupA virulence factor and IFN-γ, and H. pylori babA virulence factor and IL-17 was detected in gastritis and ulcer patients respectively. By using computer-based models, clinical outcomes of a patients infected with H. pylori can be predicted by screening the patient's H. pylori vacA m1/m2, ureA and cagA status and IFN-γ (Th1), IL-17 (Th17), and FOXP3 (Treg) expression levels. Herein, we report, for the first time, the relationship between H. pylori virulence factors and host immune responses for diagnostic prediction of gastric diseases using computer-based models.

A multicenter, randomized, prospective study of 14-day ranitidine bismuth citrate- vs. lansoprazole-based triple therapy for the eradication of Helicobacter pylori in dyspeptic patients.

BACKGROUND/AIMS: Proton-pump inhibitor and ranitidine bismuth citrate-based triple regimens are the two recommended first line treatments for the eradication of Helicobacter pylori. We aimed to compare the effectiveness and tolerability of these two treatments in a prospective, multicentric, randomized study. MATERIALS AND METHODS: Patients with dyspeptic complaints were recruited from 15 study centers. Presence of Helicobacter pylori was investigated by both histology and rapid urease test. The patients were randomized to either ranitidine bismuth citrate 400 mg bid plus amoxicillin 1 g bid plus clarithromycin 500 mg bid (n=149) or lansoprazole 30 mg bid plus amoxicillin 1 g bid plus clarithromycin 500 mg bid (n=130) treatment arm for 14 days. Adverse events have been recorded during the treatment phase. A 13 C urea breath test was performed 6 weeks after termination of treatment to assess the efficacy of the therapy. Eradication rate was calculated by intention-to-treat and per-protocol analysis. RESULTS: Two hundred seventy-nine patients (123 male, 156 female) were eligible for randomization. In per-protocol analysis (n=247), Helicobacter pylori was eradicated with ranitidine bismuth citrate- and lansoprazole-based regimens in 74,6% and 69,2% of cases, respectively (p>0,05). Intention-to-treat analysis (n=279) revealed that eradication rates were 65,1% and 63,6% in ranitidine bismuth citrate and in lansoprazole-based regimens, respectively (p>0,05). Both regimes were well-tolerated, and no serious adverse event was observed during the study. CONCLUSION: Ranitidine bismuth citrate-based regimen is at least as effective and tolerable as the classical proton-pump inhibitor-based regimen, but none of the therapies could achieve the recommendable eradication rate.

Groove (paraduodenal) pancreatitis: Report of two cases.

"Groove" pancreatitis is a rare segmental form of chronic pancreatitis that involves the area located between the common bile duct, head of the pancreas and duodenum. It is more common in middle-aged males who have a history of alcohol abuse. The differential diagnosis varies from anatomic variants to malignancies. The most relevant differential diagnosis of groove pancreatitis is adenocarcinoma of the head of the pancreas. Most of the cases were diagnosed after pancreatic resection. Thus, the correct diagnosis of this rarely seen disease is very important to avoid unnecessary tests or procedures and to determine the definitive treatment.

IgG-based elimination diet in migraine plus irritable bowel syndrome.

OBJECTIVES: To evaluate therapeutic potential of the immunoglobulin G (IgG)-based elimination diet among migraine patients with irritable bowel syndrome (IBS). BACKGROUND: Food elimination has been suggested as an effective and inexpensive therapeutic strategy in patients with migraine and concomitant IBS in the past studies. METHODS: A total of 21 patients (mean [standard deviation] age: 38.0 [11.2] years; 85.7% females) diagnosed with migraine and IBS were included in this double-blind, randomized, controlled, cross-over clinical trial composed of baseline (usual diet), first diet (elimination or provocation diets), and second diet (interchange of elimination or provocations diets) phases and 4 visits. RESULTS: IgG antibody tests against 270 food allergens revealed mean (standard deviation) reaction count to be 23.1 (14.1). Compared with baseline levels, elimination diet per se was associated with significant reductions in attack count (4.8 [2.1] vs 2.7 [2.0]; P < .001), maximum attack duration (2.6 [0.6] vs. 1.4 [1.1] days; P < .001), mean attack duration (1.8 [0.5] vs. 1.1 [0.8] days; P < .01), maximum attack severity (visual analog scale 8.5 [1.4] vs. visual analog scale 6.6 [3.3]; P < .001), and number of attacks with acute medication (4.0 [1.5] vs. 1.9 [1.8]; P < .001). There was a significant reduction in pain-bloating severity (1.8 [1.3] vs. 3.2 [0.8]; P < .05), pain-bloating within the last 10 days (3.2 [2.8] vs. 5.5 [3.1]; P < .05), and improvement obtained in quality of life (3.6 [1.4] vs. 2.9 [1.0]; P < .05) by the elimination diet as compared with provocation diet. CONCLUSIONS: Our findings indicate that food elimination based on IgG antibodies in migraine patients who suffer from concomitant IBS may effectively reduce symptoms from both disorders with possible positive impact on the quality of life of the patients as well as potential savings to the health-care system.

Can an immunohistochemistry method differentiate intestinal tuberculosis from Crohn's disease in biopsy specimens?

BACKGROUND: It is sometimes difficult to diagnose whether a patient has intestinal tuberculosis or Crohn's disease because both have similar clinical, pathologic, and endoscopic features. However, their therapies are completely different and a mistake in diagnosis can result with deterioration. Many laboratory methods for the diagnosis of tuberculosis require considerable time to receive a diagnostic result. We wanted to evaluate whether an immunohistochemical tuberculosis staining method can be helpful for faster differentiation of biopsy materials. METHODS: We used formalin-fixed paraffin-embedded histologically diagnosed small intestine (n=1), colon (n=7), skin (n=8), lung (n=5), lymph node (n=24) tuberculosis and Crohn's disease (n = 28) biopsy materials only with granulomas. Demographic characteristics like age and gender were also obtained. Pathology specimens were stained immunohistochemically with an antibody to VP-M660, targeting the 38-kDa antigen of Mycobacterium tuberculosis. RESULTS: In the M. tuberculosis group, 33/45 of patients have positive immunohistochemistry (IHC) staining (73% sensitivity, 93% specificity), whereas only two of 28 patients have positive staining in the Crohn's group (p<0.001). The positive staining with IHC was detected as 85.7, 75, 75, and 60% in colon, lymph node, skin, and lung granulomas, respectively, in M. tuberculosis patients. CONCLUSIONS: Immunohistochemical staining of biopsy specimens with anti-VP-M660 seems to be a simple and fast technique with 73% sensitivity and 93% specificity for establishing an earlier differentiation of M. tuberculosis from Crohn's disease.

The prevalence of the mutation in codon 249 of the P53 gene in patients with hepatocellular carcinoma (HCC) in Turkey.

UNLABELLED: Hepatocellular carcinoma (HCC) is one of the most common cancers in the worldwide. Aflotoxins, products of Aspergillus Flavus found in the high humidity environments induce HCC in humans by causing mutations in oncogenes such as codon 249 mutation of p53 in hepatocytes. In turkey, aflatoxins are found to be increased in some foods in certain areas, such as Istanbul which have high humidity. In present study we aimed to look for the prevalence of codon 249 mutation of p53 in patients with HCC, cirrhosis and chronic hepatitis B (CHB). METHODS: DNA was extracted from plasma and mutation was detected by PCR-RFLP method. RESULTS: the codon 249 mutation of p53 is found one out of 50 HCC (2%) patients. In conclusion, although codon 249 mutation of p53 gene has been found very rare but it exists showing the effect of aflatoxins in HCC patients in Turkey.

Oxidative stress in Helicobacter pylori infection: does supplementation with vitamins C and E increase the eradication rate?

AIM: This study aims to assess the antioxidant property of vitamins E and C in Helicobacter pylori infection, and to determine if adding them to standard triple therapy plus bismuth subcitrate increases the H. pylori eradication rate. METHODS: This study included 160 patients infected with H. pylori, who were randomized into one of two groups. Patients in group A (n = 80) received lansoprazole (30 mg, b.i.d.), amoxicillin (1000 mg, b.i.d.), clarithromycin (500 mg, b.i.d.), and bismuth subcitrate (300 mg, q.i.d.) for 14 days, while patients in group B (n = 80) received vitamin C (500 mg, b.i.d.) and vitamin E (200 IU, b.i.d.) for 30 days, in addition to lansoprazole (30 mg, b.i.d.), amoxicillin (1000 mg, b.i.d.), clarithromycin (500 mg, b.i.d.), and bismuth subcitrate (300 mg, q.i.d.) for 14 days. Total antioxidant capacity (TAC) was evaluated with a Randox kit. Success rate was calculated using both intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS: One hundred and sixty patients were analyzed using ITT analysis. One hundred and fifty-three patients completed the study. In group A, H. pylori eradication was achieved in 48 (60%) of the 80 patients included in the ITT analysis, and in 48 (64%) of the 75 patients included in the PP analysis. In group B, H. pylori eradication was achieved in 73 (91.25%) of the 80 included in the ITT analysis and in 73 (93.5%) of the 78 patients included in the PP analysis. The eradication rate was significantly higher in group B than in group A (p < .005). TAC was at the lower limit of normal in both groups and the difference between them was not statistically significant (p > .05). CONCLUSION: In group B, H. pylori eradication rate was 91.25%, which is higher than the ideal 80% eradication rate. The results of the present study show that adding the prescribed doses of vitamins E and C to antimicrobial therapy is effective in eradicating H. pylori infection.

Serum levels of adipokines in patients with chronic HCV infection: relationship with steatosis and fibrosis.

BACKGROUND AND AIMS: Hepatic steatosis and fibrosis are common histological findings in patients with chronic hepatitis C virus (HCV) infection. In this study we sought to determine whether serum levels of three adipokines (leptin, adiponectin and resistin) show any biochemical correlation with hepatic steatosis and fibrosis in patients with chronic HCV infection. METHODS: We examined a total of 51 patients with chronic HCV infection (22 males and 29 females, mean BMI: 27.4+/-5kg/m(2)) and 24 healthy control subjects (10 males and 14 females, mean BMI: 23.2+/-3kg/m(2)). Liver steatosis and fibrosis were scored on biopsies. Serum levels of leptin, adiponectin and resistin were determined by ELISA. RESULTS: HCV genotypes were 1b in 41 patients (80.4%), 3a in three patients (5.9%), 2a in two patients (3.9%), 1a in two patients (3.9%), 1c in one patient (2%), and 2b in one patient (2%). Serum levels of leptin, resistin, and the leptin-to-adiponectin ratio were significantly higher in patients with chronic HCV infection than in controls. Steatosis and fibrosis were detected in 33.3% and 70.5% of chronic HCV patients, respectively. No significant association with serum adipokine levels and degree of steatosis was evident. Low serum levels of resistin were associated with the presence of fibrosis independently of potential confounders. CONCLUSIONS: Patients with chronic HCV infection display elevated levels of adipokines in their sera. Reduced concentrations of resistin may be a biochemical marker of fibrosis in this patient group.

Awareness of hepatitis C virus transmission routes among patients, their household contacts and health care staff: does perception match the reality?

BACKGROUND/AIMS: The worldwide seroprevalence of hepatitis C virus infection is around 3%. Since there is no effective vaccine, a major effort should be given to counselling both HCV-infected patients and those at risk of infection. Our aim was to determine the awareness of the transmission routes of hepatitis C virus in health care staff (HC staff), HCV-infected patients and their household contacts. METHODS: A reliable and valid self-report inquiry consisting of 14 questions was completed by 397 HC staff (75 first-year, 75 last-year medical students, 89 dentists, 71 pharmacists, 87 nurses), 68 HCV-infected patients and 62 household contacts. All subjects were asked about the various modes of transmission of hepatitis C virus. RESULTS: Ninety-seven percent of the HC staff, 85% of hepatitis C virus patients and 90% of household contacts were aware of the parenteral transmission of hepatitis C virus. Ninety percent of HC staff, 54% of hepatitis C virus patients and 66% of household contacts admitted the role of sexual transmission, with significant difference between the subgroups of HC staff (p<0.05). Fifteen percent of the first-year medical students did not consider sexual contact as a mode of transmission. Sharing personal items such as toothbrushes, razors and nail scissors were considered as risk factors for transmission by 94% of HC staff, 44% of hepatitis C virus patients and 71% of their household contacts. Skin contact, sharing clothes and using the same toilet were considered hazardous by 18%, 14% and 26% of the HC staff, respectively. Skin contact and using the same toilet were considered as risk factors (and/or were unknown) by 30% and 44% of the hepatitis C virus patients and by 36% and 51% of the household contacts, respectively. CONCLUSIONS: Transmission of hepatitis C virus by blood and blood products was better recognized in all groups tested, but the other means of infection were either overestimated (skin contact, sharing toilet and clothes) or under-recognized (blood-contaminated objects). More vigorous education programs are needed to increase awareness of hepatitis C virus in various risk groups in our country.

Clinical characteristics of inflammatory bowel disease in Turkey: a multicenter epidemiologic survey.

AIM: To investigate the epidemiologic and clinical characteristics of inflammatory bowel disease (IBD) patients in a large multicenter, countrywide, hospital-based study in Turkey. MATERIALS AND METHODS: Twelve centers uniformly distributed throughout Turkey reported through a questionnaire the new IBD cases between 2001 and 2003. The incidence of ulcerative colitis (UC) and Crohn's disease (CD) has been reported per 100,000 people. Epidemiologic features and clinical characteristics of both diseases were analyzed. RESULTS: During the study period, 661 patients of UC and 216 patients of CD were identified. The incidence in the referral population was 4.4/100,000 and 2.2/100,000 for UC and CD, respectively. The age of the patients showed the characteristic biphasic distribution with 2 peaks between 20 and 30 and 50 and 70 years. A male predominance was observed in both diseases. A history of smoking was detected in 15.5% of UC patients and 49.3% of patients with CD. Family history was positive in 4.4% in UC and 8.3% in CD patients. Concomitant amebiasis was observed in 17.3% of patients with UC and 1.3% of patients with CD. A history of appendectomy was reported in 15% of patients with CD and only 3% of patients with UC. Both extraintestinal and local complications were more frequent in CD patients, whereas arthritis was most common in both diseases. CONCLUSIONS: IBDs are frequently encountered in Turkey. IBD incidence is lower than North and West Europe but close to Middle East in our country. The majority of IBD cases are diagnosed in young people (20 to 40 y) with predominance in males. The rate of both intestinal and extraintestinal complications in our population was low when compared with the data reported in the literature. IBD and especially UC, can coexist with amebiasis or become manifest with amebic infestation. The presence of concomitant ameba may create confusion and cause dilemmas in the diagnosis and treatment of UC.

Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-gamma (PPARgamma) gene in inflammatory bowel disease.

BACKGROUND & AIMS: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has recently been implicated as an endogenous regulator of cellular proliferation and inflammation. Impaired expression of PPAR-gamma in colonic epithelial cells in ulcerative colitis (UC) and increased expression in hypertrophic mesenteric adipose tissue in Crohn's disease (CD) have been reported. Furthermore, PPAR-gamma ligands have been shown to inhibit tissue injury associated with immune activation in UC. Any mutation in PPAR-gamma gene may be responsible for the increase in inflammatory mediators and hence the perpetuation of inflammation in inflammatory bowel disease (IBD) patients. One common polymorphism in PPAR-gamma gene is proline to alanine substitution (Pro12Ala) which results from a CCA to GCA missense substitution in codon 12 of exon 2 of the PPAR-gamma gene. In this study, we aimed to explore Pro12Ala polymorphism in PPAR-gamma gene in IBD in Turkish patients. METHODS: 69 patients with CD, 45 with UC and 100 controls of similar age and sex were studied. Genomic DNA was isolated from peripheral blood leucocytes and mutagenically separated-polymerase chain reaction (PCR) analyses were performed to determine the Pro12Ala polymorphism of the PPAR-gamma gene. RESULTS: We observed no significant differences in the frequency of the Pro12Ala polymorphism in the PPAR-gamma gene among subjects with CD, UC and controls (15.9%, 15.5% and 13%, respectively, p>0.05). CONCLUSION: These results suggest that Pro12Ala polymorphism in the PPAR-gamma gene relates neither to the risk of the development of inflammatory bowel disease nor to the clinical subtypes of CD in the Turkish population.

Actinomycotic hepatic abscess.

Actinomycotic hepatic abscess was diagnosed in a 46-year-old male driver from Ukraine presenting with the symptoms of malaise, loss of appetite, upper right quadrant pain, weight loss, and night sweats which had been present for last 2 months. Computed tomography (CT) of the abdomen revealed a hypodense mass in the left liver lobe which was suspected as hepatocellular carcinoma. Histopathological examination of the CT guided biopsy specimen yielded a diagnosis of actinomycotic abscess of the liver. Treatment with intravenous penicillin for 6 weeks followed by a course of oral penicillin for 14 weeks resulted in complete cure as evidenced by clinical improvement and radiological disappearance of the lesion.

Serum leptin is not a diagnostic marker for familial Mediterranean fever attacks.

The aim of our study is to determine whether there is a relationship between familial Mediterranean fever (FMF) attacks and serum leptin levels. We enrolled 25 patients (22 males and 3 females) and 25 healthy controls (21 males and 4 females) with a mean age of 24.42 +/- 1.22 (Mean +/- SEM) years and 24.30 +/- 1.19 years (Mean +/- SEM), respectively. We investigated serum levels of leptin, interleukin-6 (IL-6) erythrocyte sedimentation rate (ESR), C-reactive protein (CRP),fibrinogen, and leukocyte counts before the attack and 8-12 hours after the attack started. The same parameters have been investigated in the control subjects. The mean serum leptin levels before the attacks were 6.45 +/- 1.05 (Mean +/- SEM) and during the attacks were 7.59 +/- 1.3 (Mean +/- SEM) in FMF group,respectively. There was a slight increase in serum leptin levels during the attacks but it was not statistically significant (P > .05). The mean serum leptin levels were 16.12 +/- 2.81 in the control group which were not different from the mean serum leptin levels before and during the attack periods in the study group (P > .05). However, there were statistical differences in the serum levels of IL-6, ESR, CRP, fibrinogen, and leukocyte counts before and during the attack periods (P > .05). No correlation was found between serum leptin levels and IL-6, ESR, CRP, fibrinogen, and leukocyte counts (P > .05). Serum leptin levels do not increase during FMF attacks and therefore it is not useful for diagnostic purposes and follow-up during treatment.

Influence of serum folic acid levels on plasma homocysteine concentrations in patients with rheumatoid arthritis.

The purpose of this study was to investigate whether negative effects of methotrexate (mtx) on blood homocysteine (hmc) levels can be prevented with the replacement of folic acid. 42 female patients with rheumatoid arthritis (RA) were studied. Patients were separated into two groups according to their treatment status with mtx (group I: 27 patients taking mtx and folic acid; group II: 15 patients not using mtx). The level of hmc was found to be 6.3+/-2.4 micromol/l in group I and 7.87+/-3.2 micromol/l in group II (p>0.05). Folic acid levels of group I and II were found to be 21.3+/-15.9 ng/ml and 8.41+/-2.86 ng/ml respectively (p<0.001). There was a statistically-significant correlation between age and hmc levels (r=0.386, p=0.012). Negative statistically-significant correlations were observed between folic acid and hmc levels. The effects of mtx on hmc can be prevented with the replacement of folic acid.

Mid-esophageal ulceration and candidiasis-associated distal esophagitis as two distinct clinical patterns of tetracycline or doxycycline-induced esophageal injury.

BACKGROUND: Tetracyclines may cause esophageal injury. GOALS: The aims of this study are to describe 2 distinct clinical patterns of esophageal injury induced by tetracycline or its derivate doxycycline and to compare these patterns with respect to demographic, endoscopic, and clinical characteristics of the patients. STUDY: Forty-eight patients with the diagnosis of doxycycline- or tetracycline-induced esophageal injury by endoscopy were analyzed retrospectively. The patients were considered in 2 groups according to the type and the location of esophageal lesions (Group A: mid-esophageal ulceration, n = 18; Group B: distal esophagitis, n = 30). RESULTS: Patients in Group A were significantly younger than in Group B (P = 0.0014). In Group A, 15 patients (83%) had single ulceration, 2 (11%) double, and 1 (6%) circumferential at the mid-esophagus. In Group B, all patients had multiple micro-ulcerations in the distal esophagus. Development of mid-esophageal ulceration was induced predominantly by doxycycline, whereas distal esophagitis was induced by tetracycline. The description of drug ingestion with little or no water by patients in Group A was significantly more frequent than in Group B (94% vs. 10%, P < 0.001). Associated medical and benign gastric diseases and esophageal candidiasis were significantly more frequent in Group B (P = 0.006, P < 0.001, P < 0.001, respectively). Prompt response to medical therapy was observed in both groups with no significant difference (P = 0.093). CONCLUSIONS: The type of tetracyclines used by patients may give some clues to physicians on the pattern of esophageal injury because mid-esophageal ulceration seems to be more frequently associated with doxycycline and distal esophagitis with or without candidiasis with tetracycline.