Ahmet Tezel

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.

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.

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

BACKGROUND Oxidative 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. OBJECTIVE The 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. METHODS This 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. RESULTS Seventy-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). CONCLUSIONS The 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.

Inflammatory bowel disease and thrombosis.

Inflammatory Bowel Disease (IBD) is a group of chronic and relapsing inflammatory disorders of the gastrointestinalsystem. In these cases, findings are detected in extraintestinal systems also. There is a tendency for thrombotic eventsin IBD, as in the other inflammatory processes. The pathogenesis of this thrombotic tendency is multidimensional,including lack of natural anticoagulants, prothrombotic media induced via the inflammatory process, long-termsedentary life style, steroid use, surgery, and catheter placement. The aim of this review was to highlight the positiverelationship between IBD and thrombotic events, and the proper treatment of at-risk patients.

The Role of Serum Cytokines in the Pathogenesis of Hepatic Osteodystrophy in Male Cirrhotic Patients

Objective. In this study, we aimed to investigate the possible role of serum cytokines in the development of hepatic osteodystrophy. Matherial and Methods. 44 consecutive male cirrhotic patients (17 alcoholic, 20 hepatitis B, 7 hepatitis C), 15 age- and sex-matched chronic alcoholics without liver disease, and 17 age- and sex-matched healthy controls were included in the study during one year period. Bone mineral density was measured by dual X-ray absorptiometry in the lumbar vertebrate and femoral neck. Serum interleukin levels were measured by ELISA method. Results. Although osteopenia frequency between our cirrhotic patients was 20%, there was no difference in T-scores among the controls and other groups. Serum interleukin-1, interleukin-8, and tumor necrosis factor-alpha levels were not different between all groups. Serum interleukin-2 and interleukin-6 levels were higher in the cirrhotics than controls (P < 0.001). However, there were no significant difference between osteopenic and nonosteopenic cirrhotics. Conclusion. According to the results of the study in this small population of 44 male cirrhotic patients, frequency of hepatic osteopenia is small and serum interleukins 1, 2, 6, 8, and tumor necrosis factor-alpha may not play a role in the pathogenesis of hepatic osteodystrophy. Further studies in which large number of patients involved are necessary in this field.

Investigation of IL23R, JAK2, and STAT3 gene polymorphisms and gene-gene interactions in Crohn's disease and ulcerative colitis in a Turkish population.

BACKGROUND/AIMS Inflammatory bowel diseases are chronic, relapsing, inflammatory conditions. They have a genetic backround resulting in patient susceptibility. The aim of our study is to investigate the involvement of IL23R, JAK2, and STAT3 polymorphisms in inflammatory bowel diseases in a Turkish population. MATERIALS AND METHODS Polymorphisms in IL23R (rs11209026), JAK2 (rs10758669), and STAT3 (rs3816769, rs2293152, rs744166, rs957970, rs8074524) were genotyped in 69 Crohns disease patients, 157 ulcerative colitis patients, and 89 healthy controls. RESULTS The presence of (C) in rs10758669, (T) and (TT) in rs957970, and (TT) in rs744166 were found to increase the susceptibility to Crohns disease (p=0.049, p=0.016, p=0.010, p=0.035, respectively), while rs2293152 (GC), rs744166 (CT), and rs957970 (CT) provide protection against Crohns disease (p=0.007, p=0.043, p=0.043, respectively). While rs2293152 (GC) was protective, rs2293152 (CC) increased the susceptibility to ulcerative colitis (p=0.009, p=0.001). All the polymorphisms were associated with age-at-diagnosis, except rs11209026. Furthermore, rs2293152 was associated with an extension in ulcerative colitis, while rs10758669, rs3816769, rs744166, rs2293152, and rs957970 were associated with the subphenotype in Crohns disease. The presence of rs10758669 (AC) was protective against perianal Crohns disease (p=0.016). Additionally, rs10758669 and rs2293152 in Crohns disease and rs8074524, rs3816769, and rs10758669 in ulcerative colitis were associated with the requirement of immunsuppression. Finally, rs8074524 and rs10758669 in Crohns disease and rs11209026 in ulcerative colitis were associated with disease-related operation. CONCLUSION This is the first study of the single marker association of IL23R, JAK2, and STAT3 polymorphisms with ulcerative colitis and Crohns disease in a Turkish population. It was demonstrated that these polymorphisms may be effective in the etiology of inflammatory bowel disease in this Turkish population.

Dilate or wait for effective anti-inflammatory treatment for stenotic lesions associated with active inflammatory signs in Crohn's disease

We read with interest the article by Thienpont1 et al regarding the long-term outcomes of endoscopic dilatation in 133 patients with Crohns disease exhibiting ileal, ileocolonic and anastomotic strictures, on a retrospective basis. They performed multistep dilatation utilising scope balloons starting from 15–16.5 cm and widening to 18 cm at the maximal diameter. They concluded that endoscopic balloon dilatation is an effective method with long-term relief of symptomatology in 54% of patients, without a need for repeat dilatation or surgery in 76% of patients after the first dilatation. They reported the occurrence of 12 (5.1%) serious adverse events in 237 dilatations. They underlined the fact that neither active inflammation at the site of stricture, high serum C-reactive protein levels nor …

Kronik Hepatit B ve C’li Hastalarda Karaciğer Hastalığın Farklı Evrelerinde Yaşam Kalitesinin Değerlendirilmesi

Amac : Kronik hastaliklarda, hastalarin buyuk cogunlugu hastaligin getirdigi agri, yorgunluk ve depresif semptomlarla birlikte sosyal yasamlarinda kisitliliklar, fiziksel aktivitelerini gerceklestirmede guclukler yasamaktadir. Buna bagli yasam kalitesi etkilenmektedir. Kronik hepatitli hastalarda, hastaliginin erken evrelerinde hicbir semptom bulunmazken, ileri evrede siroza bagli komplikasyonlar yasam kalitesini belirgin sekilde bozabilir. Calismamizda farkli evrelerdeki kronik hepatit B (KHB) ve C (KHC)’li hastalarda yasam kalitesinin karsilastirilmasi planlanmistir. Gerec-Yontem : Hastaligin farkli evrelerindeki toplam 175 kronik hepatit (129 KHB ve 46 KHC) hastasi ve 20 saglikli gonullu calismaya alindi. Hastalara SF-36 yasam kalite indeksi anketi uygulandi. Bulgular: Her iki hastalik icin de SF-36’nin internal uyumlulugu yuksekti (Cronbach α KHB ve KHC icin:0.95, kontrol icin:0.90). KHB’de evre arttikca fiziksel ve sosyal fonksiyonlarda daha cok kisitlanma, canlilik ve enerjide daha fazla azalma ve sagliginin daha cok kotulesecegine inanma izlenmektedir. Genel olarak fiziksel ve mental saglik ile genel yasam kalitesi evre arttikca anlamli derecede azalmaktadir. KHC’de ise evre arttikca sadece fiziksel sagligin bozulmasindan dolayi iste ve gunluk etkinliklerde daha fazla kisitlama olmaktadir. Univaryant regresyon analizinde, tani ve hastalik evresinin yaninda yasadigi cevre, egitim seviyesi, sigara ve medeni durum yasam kalitesine etki eden faktorler olarak tespit edildi. Sonuc: KHC ve KHB’de, hastalik suresinin uzun olmasi, beraberinde komplikasyonlarin gelismesi ve psikolojik morbidite ile ozellikle KHC’de ve siroz hastalarinda tedavilerin yan etkileri hastalarda yasam kalitesini ciddi oranda dusurmektedir. Yasam kalitesinin arttirilmasi icin tedavi opsiyonlarinin hastaya gore olusturulmasi ve yasam kalitesini etkileyen diger faktorlerin saptanip en aza indirilmesi gerekmektedir. Anahtar Kelimeler: Kronik hepatit B; Kronik hepatit C; Yasam kalitesi

İnflamatuvar barsak hastalıklarında endoskopik izlem: Kime? Ne zaman? Nasıl?

Inflammatory bowel diseases are the chronic and relapsing pathologies of the gastrointestinal system. Endoscopic evaluation and approach models are very important tools in the diagnosis, follow-up and sometimes treatment of these cases. Endoscopic evaluation is no longer merely a screening method in inflammatory bowel diseases. Due to developments in endoscopic technology and treatment models in recent years, it is now actively used in sample collection from the targeted areas, cancer surveillance and in therapeutic processes.