Seasonal indoor radon concentration in Eskisehir, Turkey.

Indoor radon concentrations are subject to seasonal variation, which directly depends on weather conditions. The seasonal indoor radon concentrations were measured and the annual effective dose was estimated for the city centre of Eskisehir, Turkey. In order to reflect annual averages measurements were performed over all seasons (winter, spring, summer and autumn) including also the entire year. Measurements were carried out using Kodak-Pathe LR 115 Type II passive alpha track detectors in 220 different houses. A total of 534 measurements including measurements of different seasons were taken between 2010 and 2011. The radon concentrations for winter ranged from 34 to 531 Bq m(-3), for spring ranged from 22 to 424 Bq m(-3), for summer ranged from 25 to 320 Bq m(-3), and for autumn ranged from 19 to 412 Bq m(-3). Yearly measurements ranged from 19 to 338 Bq m(-3). In this study the average annual effective total dose from radon and its decay products was calculated to be 3.398 mSv y(-1).

Treatment of chronic delta hepatitis with lamivudine vs lamivudine + interferon vs interferon.

Chronic delta hepatitis is the most severe form of chronic viral hepatitis for which interferon (IFN) is the only available treatment. In 39 patients (25 were treatment-naïve, 14 had previously used IFN), efficacy of 1-year treatment with IFN (9 MU, t.i.w.) or lamivudine (LAM; 100 mg, q.d.) alone was compared with IFN and LAM combination (2 months of LAM to be followed by combination treatment). IFN monotherapy was given only to treatment-naïve patients. In both treatment-naïve and previous IFN users, end of treatment virological and biochemical responses were similar with IFN-LAM combination and superior to LAM monotherapy (P < 0.05). Improvement in liver histology occurred more often with IFN +/- LAM than with LAM alone (P < 0.05). In treatment-naïve patients, combination treatment was not superior to IFN monotherapy. After treatment discontinuation, virological and biochemical response rates decreased in LAM and IFN combination and IFN monotherapy. On treatment virological response at month 6 of treatment predicted sustained virological response. The results of this study suggest that addition of LAM to IFN for the treatment of delta hepatitis is of no additional value and that both treatment modalities are superior to LAM monotherapy.

Lamivudine vs lamivudine and interferon combination treatment of HBeAg(-) chronic hepatitis B.

To determine whether combination treatment of HBeAg(-) chronic hepatitis B is beneficial we studied 78 patients with HBeAg(-), HBV DNA-positive chronic hepatitis B who were randomized to lamivudine, 100 mg, qd, for 12 months or lamivudine-interferon (9 MU, t.i.w.) in combination. In the combination arm, 2 months of lamivudine treatment preceded 10 months of combination treatment. Biochemical, virologic and histologic responses were assessed at the end of treatment, after six and a median 27 months of drug-free follow-up (short- and long-term follow-up, respectively). Virologic response was defined as undetectable HBV DNA with a hybridization assay and biochemical response as normal alanine aminotransferase (ALT). Change in HBV DNA was also assessed by real-time polymerase chain reaction (PCR). Presence of YMDD mutants at the end of treatment was investigated with a line probe assay. Both treatment regimes led to a median 2 log decline in HBV DNA levels. Virologic end of treatment responses were 90 and 92% with mono- and combination treatment, respectively. Corresponding virologic responses at short- and long-term follow-up were 59 and 54%, and 27 and 25%, respectively. Patients having a baseline HBV DNA value > or =200 pg/mL were more likely to relapse within 6 months off therapy than those patients with a baseline HBV DNA level <200 pg/mL (P = 0.041). YMDD mutants were observed in 53% of patients receiving lamivudine compared with 24% of patients receiving the combination regime (P = 0.017). In conclusion, efficacy of combination treatment is similar to lamivudine monotherapy. However, combination treatment decreases the development of YMDD mutant strains compared with lamivudine monotherapy.

Risk factors for hepatocellular carcinoma in Turkey.

The contribution of hepatitis B, hepatitis C, and excess alcohol intake to the development of hepatocellular carcinoma in Turkey was assessed. The study was conducted through a questionnaire sent to seven major medical referral centers in different regions of Turkey and is based on 207 patients seen in the period 1994-1997. Of the seven centers, two were located in West Turkey (54 patients), two were in Central Turkey (85 patients), and two were in south and southeast Turkey (68 patients). In 196 of the 207 patients (94.7%), there was a history of chronic liver disease, and in 180 patients (87%) liver cirrhosis was documented. Of the 207 patients, 116 (56%) had hepatitis B, 48 (23.2%) had hepatitis C, and 33 (15.9%) had a history of excess alcohol intake. Anti-delta testing was available in 69 of 116 patients with hepatitis B, and anti-HDV was positive in 13 of these patients (13/69, 18.8%). Of the 33 patients with a history of heavy alcohol intake, 18 had concomitant chronic viral hepatitis infection, and alcohol alone was the etiology of hepatocellular carcinoma in only 15 cases (7.2%). The distribution of etiologic factors was not homogenous in different geographical regions in Turkey. In central, south, and southeastern Turkey, the predominant etiology of hepatocellular carcinoma was hepatitis B, whereas in western Turkey the impact of hepatitis B, hepatitis C, and alcohol was similar. This study indicates that hepatitis B virus infection is the leading cause of hepatocellular carcinoma in Turkey, followed by hepatitis C infection and alcoholic liver disease.

Nucleotide divergences in the core promoter and precore region of genotype D hepatitis B virus in patients with persistently elevated or normal ALT levels.

BACKGROUND: Mutation in the hepatitis B virus precore codon 28, creating a translational stop codon and double 1762-1764 T/A mutations in the core promoter region, controlling the transcription of the precore RNA and the core RNA have been suggested to correlate with the HBeAg status of patients with HBV infection. OBJECTIVES: The aim of the study was to further investigate the association of nucleotide divergences in both core promoter and precore regions with liver cell injury (reflected by ALT levels) in patients with chronic HBV infection. STUDY DESIGN: The sequences of the core promoter and the precore region of HBV isolated from 67 patients, all having genotype D and subtype ayw were analyzed. The patients were divided into two groups and four subgroups according to their HBeAg and Anti-HBe status, and ALT profile. RESULTS: It was found that the nucleotide divergences in the core promoter but not in the precore region were higher in patients having persistently elevated serum ALT than in serum ALT normal patients in both HBeAg positive and Anti-HBe positive groups (P<0.05). The number of T/A and A1896 stop codon mutations did not yield a statistically significant difference between ALT normal and elevated groups. It was also found that 1762-1764 T/A and precore A 1896 mutation existed in five and six out of 29 HBeAg positive patients, respectively. In 38 anti-HBe positive patients, 1762-1764 T/A and precore A1896 mutation were detected in three and 16 patients respectively, and coexisted in 10 patients. CONCLUSIONS: Precore A 1896 stop codon mutation seems to play an essential role in the loss of HBeAg in Turkish patients. Serum viremia levels of HBV in patients having precore stop codon and/or T/A mutation were not significantly different from the other patients carrying wild type strains. Nucleotide variability in the core promoter region may be one of the factors linked to hepatitis B disease activity.

Circulating IL-2 and IL-10 in chronic active hepatitis C with respect to the response to IFN treatment.

BACKGROUND: The importance of circulating immunoregulatory cytokines in response to IFN treatment and the change of in vivo production of these cytokines during interferon (IFN) treatment are not well known. We aimed to determine whether pretreatment serum levels of IL-2 and IL-10 are predictive of the response to IFN treatment and to investigate if treatment response or nonresponse has any effect on the circulating levels of these cytokines. PATIENTS AND METHODS: 37 patients (18 responders and 19 non-responders) with chronic hepatitis C virus (HCV) infection who received IFN-alpha2b for 6 months were studied. Responders were defined by complete alanine aminotransferase (ALT) normalization and loss of HCV RNA as detected by bDNA assay while patients who had elevated ALT levels and positive HCV RNA after 6 months were considered as nonresponders. RESULTS: Genotype distribution, ALT and HCV RNA levels were similar in responders and nonresponders. A significant number of patients with chronic hepatitis C (20/37 = 54%) had elevated IL-2 levels while IL-10 levels were not different from controls. No difference in baseline cytokine levels was observed between responders and non-responders. In the posttreatment serum samples some patients lost their detectable IL-2 or IL-10; some patients developed detectable cytokine levels after treatment irrespective of the treatment response. CONCLUSION: These results suggest that active liver injury in chronic hepatitis C is associated with increased circulating Th1 cytokine IL-2 but not with Th2 cytokine IL-10 and that circulating levels of these cytokines do not predict the response to IFN treatment. There is no constant and regular change in circulating levels of these cytokines under IFN treatment with respect to treatment response.

Vacuolating cytotoxic activity of 40 Helicobacter pylori strains isolated from Turkish patients.

In this study we examined the in vitro vacuolating cytotoxic activity of Helicobacter pylori, which is a gram-negative microaerophilic curved bacterium and a causative agent of gastritis, peptic ulcer and gastric ulcer. A vacuolating cytotoxin assay was performed to assess the vacuolating activity of 40 strains (20 gastritis, 11 gastric ulcer, and 9 duodenal ulcer), which were obtained from patients undergoing upper gastrointestinal endoscopy. The Vero cell line was used in the cytotoxic assay. Of the 40 isolates, 24 (12 gastritis, 6 gastric ulcer, 6 duodenal ulcer) were cytotoxic for the Vero cell line at 1:4 and 1:8 dilutions. Thus, vacuolating cytotoxin of H. pylori affects the Vero cell line, but it seems there is no correlation between the positivity of the strains and the risk of any particular H. pylori disease.

Influence of viral load and alanine aminotransferase on viral genetic heterogeneity in patients with chronic hepatitis C virus infection.

BACKGROUND/AIM: Hepatitis C virus (HCV) populations in vivo consist of genetically different heterogeneous mixtures defined as 'quasispecies', which vary in the hypervariable region 1 (HVR1) mostly. To further address the role of quasispecies diversity in hepatitis C infection, this study aimed to evaluate the influence of ALT, viral load and genotypes on quasispecies heterogeneity in patients with HCV infection. METHODS: Thirty-six chronic hepatitis C patients with high levels of alanine aminotransferase (ALT) were studied. None of them received any antiviral therapy. HCV RNA serum levels, genotype and genetic heterogeneity were determined by branched-chain DNA assay, restriction fragment length patterns and RT-PCR single-strand conformational polymorphism analysis of HVR1, respectively. RESULTS: Twenty-eight patients had genotype 1b (28/36; 78%), 6 patients had genotype 1a (6/36; 17%), 1 patient was 2a (1/36; 3%) and genotype could not be determined in 1 patient. The patients were categorized into two groups according to the number of bands representing the dominant strains in the circulation: group A with 2 bands having 1 strain (14/36 patients; 39%) and group B with more than 2 bands indicating more than 1 strain (22/36 patients; 61%). The serum viremia and ALT levels for these groups were 11 +/- 8.8 and 5.3 +/- 4.6 mEq/ml (p < 0.05), and 79 +/- 20, and 127 +/- 80 IU/l (p < 0.05), respectively. CONCLUSION: The results of this study suggest that hepatitis C patients having 1 dominant strain in the circulation may show a relatively weaker immune response resulting in lower ALT and higher viremia levels, whereas patients with high degrees of virus quasispecies diversity have higher ALT levels and a more active immune response causing the selection of new genome variants and depressing viral replication partly.

Circulating IL-2, IL-10 and TNF-alpha in chronic hepatitis B: their relations to HBeAg status and the activity of liver disease.

BACKGROUND/AIMS: Preferential production of immunoregulatory cytokines may play an important role in the pathogenesis of chronic hepatitis B. We aimed to determine the serum levels of IL-2, IL-10 and TNF-alpha in patients with chronic hepatitis B and to correlate these findings with the activity of liver disease, HBeAg/anti-HBe status and replication level of the virus. METHODOLOGY: Seventy-two chronic hepatitis B patients were categorized into 4 groups according to activity of liver disease and HBeAg status. Group 1 (n = 13): HBeAg and HBV DNA-positive with persistently normal ALT. Group 2 (n = 20): HBeAg and HBV DNA-positive patients with persistently elevated ALT. Group 3 (n = 19): HBeAg and HBV DNA-negative patients with persistently normal ALT. Group 4 (n = 20): HBeAg-negative patients with persistently elevated ALT and variable serum HBV DNA. IL-2, IL-10 and TNFa levels were determined in stored patient sera. RESULTS: Apart from group 1 patients, all patients groups had higher IL-2 levels compared to controls suggesting that IL-2 production is increased when liver disease becomes active in HBeAg-positive phase of HBV infection. Only group 2 patients had elevated IL-10 levels compared to controls. None of the HBeAg-negative patients had detectable TNF-alpha levels while 64% HBeAg-positive patients had elevated levels of TNF-alpha irrespective of the activity of liver disease. Except TNF-alpha, no association was found between HBV DNA status and the presence or absence of detectable cytokines in circulation. CONCLUSIONS: Our results suggest that circulating cytokine profile in chronic hepatitis B is related with the HBeAg status, replication level of the virus and the activity of liver disease.

Human MLH1 deficiency predisposes to hematological malignancy and neurofibromatosis type 1.

Heterozygous germ-line mutations in the DNA mismatch repair genes lead to hereditary nonpolyposis colorectal cancer. The disease susceptibility of individuals who constitutionally lack both wild-type alleles is unknown. We have identified three offspring in a hereditary nonpolyposis colorectal cancer family who developed hematological malignancy at a very early age, and at least two of them displayed signs of neurofibromatosis type 1 (NF1). DNA sequence analysis and allele-specific amplification in two siblings revealed a homozygous MLH1 mutation (C676T-->Arg226Stop). Thus, a homozygous germ-line MLH1 mutation and consequent mismatch repair deficiency results in a mutator phenotype characterized by leukemia and/or lymphoma associated with neurofibromatosis type 1.

Effect of postnecrotic and alcoholic hepatic cirrhosis on development of benign prostatic hyperplasia.

BACKGROUND: The object of this study was to investigate the effects of hepatic cirrhosis on the development of benign prostatic hyperplasia and consequent effects on prostatic volume, serum prostate-specific antigen (PSA), and prostatism symptoms. METHODS: Sixty patients with postnecrotic cirrhosis and alcoholic cirrhosis at age 40 and over, and 20 voluntary subjects in the same age group with normal hepatic functions, were evaluated with prostatic volume calculation by transrectal ultrasound, symptom scoring according to American Urology Association (AUA) criteria, measurement of serum prostate-specific antigen (PSA), serum total testosterone (TT), free testosterone (FT), estradiol (E2), and calculation of E2/FT ratios, and the results were analyzed statistically by the Mann-Whitney U-test. RESULTS: Serum FT and TT levels were significantly lower in the hepatic cirrhosis group compared to the control group (P = 0.0000 and P = 0000, respectively). Though mean serum E2 level was a little higher in cirrhotic patients compared to controls, the difference was not significant; however, the higher E2/FT ratio in the cirrhotic group was statistically significant (P = 0.27 and P = 0.0002, respectively). In the cirrhotic group, the decrease in FT and TT levels was greater, as the disease advanced. While E2 and E2/FT ratio increase, correlate with poor prognosis, no statistically significant differences were found. Mean prostatic volume, serum PSA level, and total symptom score were significantly higher in the control group, compared to the cirrhotic group (P = 0.0001, P = 0.0006, and P = 0.002, respectively). Prostatic volume decreased parallel to severity of disease in cirrhotic patients. CONCLUSIONS: The main reason for the decrease in mean prostatic volume in cirrhotic patients compared to subjects in the same age group with normal hepatic functions was the decrease in serum FT and TT levels, and the secondary cause was the increase in E2/FT ratio, indicating estrogenic predominance.

Hereditary pancreatitis: report of a family from Turkey.

Chronic pancreatitis is a rare disease in children and is usually secondary to underlying diseases such as hereditary pancreatitis, cystic fibrosis, hyperlipidemia, prolonged malnutrition, gallstones or anomalies of the biliary-pancreatic duct system. Hereditary pancreatitis is a common cause of chronic pancreatitis in children but is often unrecognized until months or years later. We report here a family with hereditary pancreatitis in which four members are affected.

Long-term efficacy of interferon-alpha and ursodeoxycholic acid in treatment of chronic type C hepatitis.

Interferon-alpha (IFN) and ursodeoxycholic acid (UDCA) combined have a controversial role in the treatment of chronic type C hepatitis. We studied the long-term efficacy of both drugs alone or in combination. In a three-year period, 108 patients were randomized into three treatment arms: (1) IFN alone 3 MU three times a week (N = 49), (2) IFN 3 MU three times a week + UDCA 250 mg twice a day (N = 45), and (3) UDCA alone 250 mg twice a day (N = 14). Response was defined as complete normalization of serum ALT. For the responders at the end of six months, the treatment was run to 12 months. Nonresponders (NRs) of the first group were crossed over to combination and NRs of the combination received 6 MU three times a week IFN+UDCA for the next six months. The enrollment to the UDCA alone arm was stopped early, since only 1/14 normalized serum ALT at the end of third month. However, 12/14 completed six months and 11 NRs received IFN 3 MU three times a week alone for the next six months. Twelve discontinued treatment due to side effects. Responders were followed-up untreated for 18 months. Sustained response (SR) was defined as persistence of normal serum ALT levels in this period. At the end of six months, 22/45 (48%) from the IFN-alone and 23/39 (58%) from the combination group responded. Twenty NRs from former and 15 of latter group were crossed over. While none of the 20 from the IFN-alone group responded to the combination, 1/15 NRs of the combination group responded to dose escalation. SR was achieved in 9/45 (20%) of the IFN alone and 7/39 (18%) of the combination group. The mean time form the end of the treatment to the relapse was not different between the groups. Five of 11 UDCA NRs responded to IFN with SR in 2. It was concluded that UDCA as a single agent is ineffective in achieving response in the treatment of chronic type C hepatitis. Combined with IFN, it increases response rate insignificantly although this is not sustained.