Hasan Umit

The relationship between virulence factors of Helicobacter pylori and severity of gastritis in infected patients.

The outcome of Helicobacter pylori infection has been related to specific virulence-associated bacterial genotypes. The best known genotypic virulence factors of H. pylori are cytotoxin-associated gene A (cagA) and vacuolating cytotoxin gene A (vacA). The objective of this study was to assess the relationship between H. pylori cagA and vacA status and histopathological findings. Esophagogastrodoedonoscopy was performed in 80 dyspeptic patients. Antrum and corpus biopsies were obtained for isolation of H. pylori and for histopathological assessment. The polymerase chain reaction was used to detect cagA and vacA genes of H. pylori using specific primers. Biopsy samples were stained with hematoxylin and eosin, and histopathological findings were graded using the “updated Sydney system”. H. pylori from 57 of the 80 patients was incubated. Of the 57 patients, 44 were cagA positive. In the corpus biopsy specimens there was a significant relationship between the density of H. pylori colonization (Pxa0=xa00.02) and chronic inflammation (Pxa0=xa00.02) and cagA-positive genotypes. In the antrum specimens there was a significant relationship between cagA positivity and neutrophil activity (Pxa0=xa00.003) and glandular atrophy (Pxa0=xa00.002), but not with H. pylori density, chronic inflammation, and intestinal metaplasia. The odds ratio of cagA-positive vs. cagA-negative strains for the presence of glandular atrophy, irrespective of grading and of gastric localization, was 4.62 (95% CI, 1.18–18.08, Pxa0=xa00.041). No significant relationships were observed between vacA s1 and s2 genotypes and histopathological parameters. Corpus neutrophil infiltration was found to be more severe in the m1 group than in the m2 group (Pxa0=xa00.004). Other histopathological features showed no difference between m1 and m2 genotypes. In conclusion H. pylori strains showing cagA positivity are associated with more severe gastritis in some histological features but virulence factors of H. pylori do not appear to determine the overall pattern of gastritis.

Effects of methylene blue in reducing cholestatic oxidative stress and hepatic damage after bile-duct ligation in rats

The aim of this study was to evaluate the effects of methylene blue against cholestatic oxidative stress and liver damage after ligation of the common bile duct in male Wistar rats. Eight animals were included in each of the following five groups: untreated control, methylene blue control, sham-operated, bile-duct ligation, and bile-duct ligation plus methylene blue. Methylene blue was administered intraperitoneally for 14 days at a daily dose of 2mg/kg per day. All rats were sacrificed 2 weeks following the experimental treatment and the livers of all groups were examined biochemically and histopathologically. The severity of cholestasis and hepatic injury were determined by changes in the plasma, including enzymatic activities: aspartate aminotransferase, alanine aminotransferase, gamma glutamine transferase, and also bilirubin levels. Malondialdehyde, nitric oxide and superoxide dismutase were measured to indicate the oxidative status in the liver tissue. Myeloperoxidase activity and levels of tissue hydroxyproline were determined as measures of neutrophil activation and collagen accumulation, respectively. Liver damage was significantly prevented in the bile-duct ligated rats treated with methylene blue compared with the control bile-duct ligated rats without methylene blue. Treatment with methylene blue markedly reduced activities of serum transaminase, gamma glutamine transferase and bilirubin levels as compared to bile-duct ligated rats without methylene blue. Positive immunolabelling for alpha-smooth muscle actin (alpha-SMA) was increased, especially in vascular smooth muscle cells, fibrotic septa and also around the proliferated bile ducts, after bile-duct ligation. Only weak alpha-SMA immunolabelling was seen in livers of rats treated with methylene blue. These results indicate that methylene blue can attenuate hepatic damage in extrahepatic cholestasis by reducing oxidative stress and inflammatory processes.

Prevalence and MDCT characteristics of asymptomatic Bochdalek hernia in adult population.

PURPOSEnTo determine the frequency of asymptomatic incidental Bochdalek hernias in adults, using multidetector computed tomography (MDCT), and to ascertain any possible relationship between Bochdalek hernia and age, gender, or body mass index (BMI).nnnMATERIALS AND METHODSnSeven hundred and forty-eight abdominal, and 602 chest MDCT scans, which had been performed for a variety of reasons on 1350 adults, were investigated retrospectively. Location and size of Bochdalek hernias seen on these scans were correlated with age, gender, and BMI. On the basis of BMI, patients with Bochdalek hernia were classified as group A (BMI < 25) and group B (BMI > or =25).nnnRESULTSnA total of 171 Bochdalek hernias were identified in 142 of 1350 patients, ranging in age from 25 to 90 years (median age, 57.2), representing a prevalence of 10.5%. Sixty leftsided unilateral Bochdalek hernias (42.2%), 53 (37.4%) rightsided unilateral Bochdalek hernias, and 29 (20.4%) bilateral Bochdalek hernias were detected. Forty-five (31.6%) were categorized as small, 82 (57.8%) were medium-sized, and 15 (10.5%) were large. BMI was < 25 in 62 patients (43.7%), and > or =25 in 80 patients (56.3%). Fourteen patients (9.9%) were young adults, while 86 (60.6%) were middle aged, and 42 (29.6%) were elderly. No statistically significant relationship was found between dimensions or hernia locations and age, gender, or BMI of patients with Bochdalek hernia.nnnCONCLUSIONnIn view of the high prevalence of Bochdalek hernia in our study (10.5%), the multiplanar and reconstruction features of MDCT seem to facilitate the diagnosis of asymptomatic incidental Bochdalek hernia. No relationship was found between asymptomatic incidental Bochdalek hernia and age, gender, or BMI in adults.

Epidemiological Features of Ulcerative Colitis in Trakya, Turkey

To determine the epidemiological features of ulcerative colitis in the Trakya region of Turkey, southeast Europe, we conducted a descriptive, cross-sectional, hospital-based study. All subjects were followed, and age, sex, place of residence, family history, educational status, tobacco consumption and use of oral contraceptives were recorded. The study included 49 cases of ulcerative colitis. The incidence of the disease was 0.59 per 100 000 in 1998, 0.89 per 100 000 in 1999, 0.89 per 100 000 in 2000 and 0.69 per 100 000 in 2001. The overall prevalence of the disease was 4.9 per 100 000; it was 2.18 per 100 000 in rural areas and 5.87 per 100000 in urban areas. As in the Mediterranean countries, both the incidence and the prevalence of ulcerative colitis were found to be low. The incidence was significantly higher in urban areas than in rural areas.

Effects of sphingosylphosphorylcholine against cholestatic oxidative stress and liver damage in the common bile duct ligated rats.

The goal of this study was to evaluate the possible protective effects of sphingosylphosphorylcholine (SPC) against cholestatic oxidative stress and liver damage in the common bile duct ligated rats. Fifty-six animals were included in each of the following 7 groups: control, SPC control, phosphate-buffered solution control, sham operated, bile duct ligation (BDL), BDL plus phosphate-buffered solution, and BDL plus SPC. Sphingosylphosphorylcholine was administered 14 days at a daily dose of 2 microm/mL intraperitoneally. The severity of cholestasis and hepatic injury was determined by changes in the plasma enzyme activities of aspartate aminotransferase, alanine aminotransferase, gama glutamin transferase, and levels of total bilirubin and direct bilirubin. Malondialdehyde, nitric oxide, and superoxide dismutase were determined to evaluate the oxidative status in the liver tissue. Myeloperoxidase activity and levels of tissue hydroxyproline were determined to assess neutrophil activation and collagen accumulation, respectively. Treatment with SPC markedly reduced serum transaminase activities as compared to BDL rats. Sphingosylphosphorylcholine also inhibited the increase in liver malondialdehyde; nitric oxide levels significantly and also attenuated the depletion of superoxide dismutase in the liver after BDL. Similarly, the increase in tissue myeloperoxidase activity and hydroxyproline owing to BDL was also attenuated by the SPC treatment. These data were supported by histopathologic findings. The alpha-smooth muscle actin-positive cells in the BDL were observed to be reduced with the SPC treatment. In conclusion, these findings suggested that SPC can attenuate hepatic damage in extrahepatic cholestasis by prevention of oxidative stress, and inflammatory process. All these findings suggest that SPC may be a promising new therapeutic agent for cholestatic liver injury.

Lamivudine-induced acute pancreatitis in a patient with decompensated Hbv-related chronic liver disease

To The Editor: Studies on fialuridine, a nucleoside analogue had been stopped due to deaths attributed to toxic events including acute pancreatitis. Another nucleoside anologue, lamivudine which is used widely in the treatment of chronic hepatitis B is considered a safe drug. A patient with precore mutant HBV-related decompensated liver cirrhosis, who died, is reported because of lamivudine-induced acute pancretitis. A 75-year-old man with HBVrelated chronic liver disease was hospitalized for treatment of tense ascites. He was complaining of pruritis, jaundice, abdominal swelling, and leg edema. No alcohol consumption history was present. He had a past history of hypertension and heart failure for during a10-year period. He was using digoxine and furosemide on an irregular basis. Physical examination revealed spider angiomata on face and upper trunk, scleral subicterus, white nails, thenar and hypothenar atrophy and erythema, loss of body hair, pretibial edema, and tense abdominal ascites. Platelet count was 83,000/mm, hemoglobin; 8.5 g/dL, white blood cell (WBC) count; 2800/mm, prothrombin time (PT); 21 seconds, alanine aminotransferase; 146 U/L, aspartate aminotransferase; 208 U/L, total bilirubin; 3.2 mg/dL, total protein; 6.9 gr/dL, albumin; 2.3 gr/dL. HBs Ag and anti-HBe were positive. Serum protein electrophoresis revealed gamma globulines as 49%. Albumin to globulin ratio was 0.47. At the admission, C-reactive protein (CRP) and renal function were normal. Ascitic fluid total protein was 0.5 gr/dL, serum-ascites albumin gradient was 2.2 and was compatible with cirrhotic ascites but not with a cardiac source of portal hypertension. Ascitic fluid gram smear and cultures were normal. Upper endoscopy revealed large esophageal varices and severe portal hypertensive gastropathy in the fundus. The patient was treated with furosemide 40 mg/d and spironolactone 100 mg/d by mouth, bed rest, fluid restriction, and low salt diet. After an uneventfull hospital course of 19 days, lamivudine 100-mg/day treatment was started due to a clinical course with significantly elevated liver enzymes and active viral replication (HBV DNA: 3564 pg/mL by hybridization). Liver biopsy was not performed because of the low platelet count and prolonged PT. Lamivudine was stopped 3 days later due to asymptomatic rise in serum amylase up to 1400 U/L (repeat value was 1057 U/L). Four days later after return of amylase to normal, rechallange of lamivudine resulted in severe epigastric pain radiating to back, nausea, vomiting, and ileus accompanied hyperamylasemia (1375-1075 U/L). White blood count was elevated to 24000/mm. CRP was 43 mg/dL. Lowgrade fever, diffuse abdominal tenderness and diminished bowel sounds were determined by physical examination. Air-fluid levels and dilated small and large bowels were obvious on upright plain abdominal X-rays. Tomography revealed focal acute pancreatitis along with the radiologic findings of cirrhosis. The patient died in progressive multiorgan dysfunction syndrome within the following 7 days. Although mild symptoms such as malaise, irritability, headaches, nausea, and vague abdominal pain attributed to lamivudine have been reported, it is not believed that these side-effects are more prevalent than that observed in the placebo group. Lamivudine seems to be less well-tolerated in patients with advanced human immunodeficiency virus infection, but data are insufficient to clarify its tolerability in this patient population. Acute pancreatitis has been reported in children with HIV infection during lamivudine treatment but was not directly attributable to lamivudine therapy. However, no case has been reported in the English literature citing lamivudine-induced acute pancreatitis in any chronic hepatitis B patient with active viral replication except for only asymptomatic hyperamylasemia, lipasemia, and elevated creatine phosphokinase serum levels. Although furosemide which has a well-known pancreatoxic potential and/or spironolactone may also play a role on development of acute pancreatitis in this patient, this is the first case report of a patient who develops acute pancreatitis while using lamivudine for the purpose of treatment of chronic active hepatitis B. Probably, chronic heart failure and diuretic use facilitated the development of acute pancreatitis easily. In conclusion, serum amylase elevations in patients with chronic liver disease using lamivudine may not be innocent. Patients taking this drug should be followed closely for the clinical signs and symptoms of acute pancreatitis.

Increased Frequency of Gastrointestinal Symptoms in Patients with Fibromyalgia and Associated Factors: A Comparative Study

Objective. To determine the frequency and severity of gastrointestinal (GI) symptoms in patients with fibromyalgia (FM). Methods. We included 152 women with FM (mean age 45.4 ± 12.2 yrs), 98 women with rheumatoid arthritis (RA; mean age 45.5 ± 12.3 yrs), and 60 healthy female controls (mean age 44 ± 11.3 yrs). All patients were questioned about the severity of their chronic widespread pain, symptoms of FM, symptoms of dyspepsia, using a visual analog scale (VAS), and anxiety-depression scale. Patients were asked self-reported (yes/no), symptom-based (≥ 2 criteria) constipation and severity of constipation questions, and about the severity of quality of life (QOL) disturbance secondary to dyspepsia and constipation. Results. Patients with FM had higher symptom severities for belching, reflux, bloating, sour taste, and vomiting than patients with RA and controls (all p values < 0.01). Patients with FM had significantly more dyspepsia-related QOL disturbances than the other 2 groups (p < 0.01). FM and RA patients had more frequent self-reported constipation than controls (respectively, 42.1%, 48%, 21.7%; p < 0.01). The frequency of symptom-based constipation was significantly higher in the RA group (49%) than in FM (29.6%) and control groups (23.3%) (p < 0.01). Constipation-related QOL disturbance was significantly higher in patients with FM than in controls (p < 0.01). Conclusion. In patients with FM, the severity scores of dyspepsia symptoms, constipation, and dyspepsia-related QOL disturbance were higher than in patients with RA and controls. The higher GI symptom severity in patients with FM might have negative effects on their QOL.

Effects of vitamins E and C supplementation on hepatic glutathione peroxidase activity and tissue injury associated with ethanol ingestion in malnourished rats

BACKGROUNDnOxidative stress has been associated with tissue injury in alcoholic liver disease. Although this close association is well known, whether prevention of oxidative stress retards tissue injury has not been thoroughly investigated.nnnOBJECTIVEnThe aim of this study was to determine the effects of supplementation with vitamins E and C on antioxidant enzyme status and histologic changes in hepatic tissue in a rat model of alcoholic liver disease.nnnMETHODSnThis 8-week, blinded, controlled study was conducted at the Department of Internal Medicine, Trakya University, Edirne, Turkey. Weanling albino female protein-deficient Wistar rats weighing ∼200 g were randomly assigned to 1 of 6 groups: (1) liquid diet+ethanol+vitamin E 15 mg/kg PO (LDetvitE); (2) liquid diet+ethanol+vitamin C 10 mg/kg PO (LDetvitC); (3) liquid diet+ethanol+vitamin E 15 mg/kg+vitamin C 10 mg/kg PO (LDetvitEC); (4) liquid diet+ethanol (LDet); (5) liquid diet+isocaloric sucrose (LDS); and (6) normal diet (control). The primary end point of the study was to determine whether antioxidant vitamin E/C combination therapy prevents development of hepatic fibrosis (ie, cirrhosis in a period of 1 year). After being euthanized at week 8, the rats were weighed, and their livers and spleens were weighed. Hepatic tissue specimens were histopathologically assessed according to the Brunt system. Hepatic tissue glutathione peroxidase, superoxide dismutase, and catalase activities were determined. Biochemical tissue collagen concentrations were measured to determine the presence of hepatic fibrosis.nnnRESULTSnSeventy-two rats were included in the study (mean [SE] weight, 205 [21] g) (12 rats per group). Initially planned to last 48 weeks, the study was terminated at 8 weeks due to the death of 3 rats in each group (except the LDS group and control group). The relative liver weight was significantly lower in the LDetvitEC group compared with that in the LDet group (mean [SE], 3.7% [0.5%] vs 4.8% [0.9%]; P<0.01). Mean (SE) hepatic tissue glutathione peroxidase activity was significantly reduced in the LDet-treated rats compared with controls (1.2 [0.2] vs 2.6 [0.3] U/mg protein; P<0.001). The groups that received supplementation with vitamin E, vitamin C, and vitamins E and C combined had significantly more hepatic glutathione peroxidase activity (mean [SE], 2.1 [0.5], 2.5 [0.2], and 2.6 [0.7] U/mg protein, respectively) compared with the LDet group (1.2 [0.2] U/mg protein) (all, P<0.001). No significant between-group differences in hepatic superoxide dismutase or catalase activities were found. Compared with controls (14.5 [1.9] μg collagen/mg protein), the mean (SE) histologic hepatic collagen concentration was significantly higher in all groups (19.2 [1.2], 19.5 [3.3], 18.5 [3.0], 25.9 [3.3], and 21.6 [1.5] μg collagen/mg protein in the LDetvitE, LDetvitC, LDetvitEC, LDet, and LDS groups, respectively; P<0.01, P<0.01, P<0.05, P<0.001, and P<0.001, respectively). Compared with the LDet group, the mean hepatic collagen concentration was significantly lower in the LDetvitE, LDetvitC, and LDetvitEC groups (P<0.01, P<0.05, and P<0.01, respectively). The LDetvitEC group had a significantly lower mean (SE) hepatic inflammatory score compared with the LDet group (0.8 [0.1] vs 1.3 [0.2]; P<0.05). The LDetvitEC group had a significantly lower mean (SE) hepatic necrosis score compared with that in the LDet group (1.5 [0.2] vs 2.4 [0.3]; P<0.05).nnnCONCLUSIONSnThe results of this study in protein-deficient rats fed with a high-fat liquid diet suggest that supplementation with vitamin E, vitamin C, and a combination of vitamins E and C was associated with decreased ethanol-induced hepatic glutathione peroxidase activity and hepatic fibrosis, and that supplementation with vitamins E and C might have attenuated the development of hepatomegaly and hepatic necroinflammation, whereas this result was not found in the group given a liquid diet and ethanol in this 8-week study. (Curr Ther Res Clin Exp. 2006;67:118-137) Copyright

PREDICTORS OF SHORT‐TERM OUTCOME OF SPONTANEOUS BACTERIAL PERITONITIS IN TURKISH CIRRHOTIC PATIENTS

To the Editor, Several studies have shown an increased incidence of malignancy in patients with celiac disease (CD). Such a trend is detectable both in Europe, where CD has a high prevalence, and in the USA, where CD was considered uncommon until recently. We report some data taken from an Italian group of patients affected by CD that show that there was a higher risk, with respect to the general population, of developing intestinal nonHodgkin’s lymphoma. In the present study, 1968 patients diagnosed with CD over a 20-year period (between January 1982 and December 2002) in 20 Italian clinical centers specializing in gastrointestinal diseases were observed. The diagnosis of CD was made according to revised ESPGHAN criteria as follows: (i) histological evidence of atrophy of duodenal or jejunum mucosa; (ii) recovery at control biopsy after a glutenfree diet; and (iii) serological positivity for AGA IgG or IgA and EMA IgG. For each patient, demographic data and symptoms, and concomitant pathology results at the time of the diagnosis of CD were collected. Each patient gave their informed consent to take part in the study and the protocol was approved by the ethics committee of each participating center. Of the 1968 patients, 20 patients had already been diagnosed with gastrointestinal non-Hodgkin’s lymphoma at diagnosis of CD (17 cases of intestinal non-Hodgkin’s lymphoma and three cases of gastric non-Hodgkin’s lymphoma). We found CD predominantly affected men (2:1). The standardized morbidity ratio (95% CI) for the malignancy results was 6.25 (3.8–9.6). In addition, we noticed that the risk of developing gastrointestinal non-Hodgkin’s lymphoma correlates with the age at diagnosis. The mean age of the patients with a non-Hodgkin’s lymphoma at diagnosis of CD is 46.1 ± 13.8 years, whereas the mean age of the control group, represented by the patients with no neoplasm at diagnosis, is equal to 36.6 ± 13.7. Therefore, the delayed diagnosis of CD is likely to be a risk factor for developing a lymphoma, probably because of the prolonged exposure to gluten. These data are consistent with those of other studies, indicating a relationship between CD and the development of gastrointestinal non-Hodgkin’s lymphoma. It is noteworthy that most of these cases occur before the diagnosis of CD. Celiac disease is often an asymptmonatic condition, with a high rate of associated pathologies and malignancies, often diagnosed before CD is diagnosed. Non-Hodgkin’s lymphomas are very frequent and can develop in sites other than the gastrointestinal tract, such as the skin, spleen, liver and central nervous system. The mechanism for the development of nonHodgkin’s lymphoma in patients with CD is not known. However, chronic inflammation and antigenic stimulation, increased intestinal permeability and the release of inflammatory cytokines have been suggested. In our group of patients, we found only one case of extra-intestinal non-Hodgkin’s lymphoma, a lymphoma of the spleen. Sometimes the concomitant pathologies suggest the diagnosis of CD. Our results stress the importance of implementing programs aimed at making an early diagnosis of CD in order to prevent its complications, even if the best method of screening has yet to be determined.

Patients with iron deficiency anemia have an increased prevalence of gallstones

We determined the frequency of gallstones (GS) in iron deficiency anemia (IDA) patients and evaluated factors that could affect GS formation—like lipid levels and gallbladder (GB) motilities of the patients. One hundred and eleven IDA patients (88 females, 23 males; median age, 42) and 81 healthy controls (68 females, 13 males; median age, 42) were included into our study. The clinical findings of all IDA patients were recorded down; biochemical values and body mass index (BMI) were determined; and abdominal ultrasonography was performed. In addition, GB emptying was monitored by ultrasound at 30-min intervals for 2xa0h after a mixed meal in randomly chosen, age-matched 25 IDA patients and 26 controls. Fasting volume (FV), residual volume (RV), and ejection fraction (EF) for all GBs were determined. The frequency of GS plus cholecystectomy was significantly higher in IDA patients (15 cases, 13.5%) than in the control group (five cases, 6.2%, pu2009=u20090.048). IDA patients with GS plus cholecystectomy were older than those without GS plus cholecystectomy (pu2009<u20090.001). FV and EF did not differ between IDA and control groups (pu2009>u20090.05). On the other hand, RV was significantly higher in IDA group than in controls (pu2009=u20090.035). The frequency of GS in IDA patients was significantly higher than in controls. The increased prevalence of GS in IDA might be explained with impaired GB motility.