Eren Erken

p53 mutation in hepatocellular carcinoma after aflatoxin exposure

Mutations of the p53 gene are found in hepatocellular carcinoma (HCC), the most common form of primary liver cancer. Specific mutations might reflect exposure to specific carcinogens and we have screened HCC samples from patients in 14 different countries to determine the frequency of a hotspot mutation at codon 249 of the tumour suppressor p53 gene. We detected mutations in 17% of tumours (12/72) from four countries in south Africa and the southeast coast of Asia. There was no codon 249 mutation in 95 specimens of HCC from other geographical locations including North America, Europe, Middle East, and Japan. Worldwide, the presence of the codon 249 mutation in HCCs correlated with high risk of exposure to aflatoxins and the hepatitis B virus (HBV). Further studies were completed in two groups of HBV-infected patients at different risks of exposure to aflatoxins. 53% of patients (8/15) from Mozambique at high risk of aflatoxin exposure had a tumour with a codon 249 mutation, in contrast with 8% of patients from Transkei (1/12) who were at low risk. HCC is an endemic disease in Mozambique and accounts for up to two thirds of all tumours in men. A codon 249 mutation of the p53 gene identifies an endemic form of HCC strongly associated with dietary aflatoxin intake.

Analysis of CD28 and CTLA‐4 gene polymorphisms in Turkish patients with Behcet's disease

In this study we aimed to investigate IVS3 +17T/C single nucleotide polymorphism (SNP) of CD28 gene, +49A/G and −318C/T SNPs of CTLA‐4 gene in patients with Behçets disease (BD) and their potential association to the main clinical features of the disease. These polymorphisms were investigated in a Turkish population of 123 patients with BD and 179 healthy controls, by using PCR‐RFLP technique. HLA‐B*51 genotype was also studied in both groups by using PCR‐SSP. The frequency of IVS3 +17TC genotype of the CD28 gene was significantly increased in BD patients compared to controls (43.6% vs. 31.2%, OR = 1.663, 95% CI = 1.033–2.679, P = 0.039). CTLA‐4 +49GG genotype frequency was found to be significantly lower in patients with BD than those of healthy controls (4% vs. 10.6%, OR = 0.357, 95% CI = 0.130–0.983, P = 0.05). Genotype and allele frequencies of the CTLA‐4–318C/T polymorphism between the BD and healthy control groups were not significantly different (12.2% vs. 10.6%, OR = 1.170, 95% CI = 0.570–2.402, P = 0.713). There were no associations between the studied polymorphisms and the main clinical features of BD. The frequencies of HLA‐B*51 were 60.3% and 30.7% in BD and control groups, respectively (OR = 3.429, 95% CI = 2.115–5.559, P = 0.0001). Association between HLA‐B*51 and each studied polymorphism did not reach to significant levels (OR = 0.479, 95% CI = 0.228–1.004, P = 0.064 for CD28 IVS3 +17TT genotype; OR = 2.180, 95% CI = 1.025–4.639, P = 0.061 for TC genotype; OR = 1.570, 95% CI = 0.870–2.836, P = 0.146 for C allele). These results may suggest that CD28 IVS3 +17TC genotype may be a risk factor for the development of BD, on the contrary CTLA‐4 +49GG genotype may be protective in the studied Turkish population.

The association between cervical rib and sacralization.

Study Design. After determining the normal reference values for the length of the transverse processes of the seventh cervical vertebra, the association between the presence of cervical rib and sacralization was investigated. Objective. To determine the length of cervical rib and search for any association between cervical rib and sacralization. Summary of Background Data. Both cervical ribs and sacralization have been noted in some patients in the authors’ clinical practice. Methods. The cervical rib is a supernumerary rib arising from a cervical vertebra, or it might be simply an elongation of the transverse process of the seventh cervical vertebra. However, there is no consensus about a specified length of this process. For reference values, anteroposterior cervical radiographs of 210 normal individuals (112 male, 98 female, mean age 33.9 ± 10.1 years, range 19–61 years) were taken, and elongation of the transverse processes beyond 2 standard deviations (30 mm) was considered as cervical rib. In the guide of the reference values, 324 outpatients (165 male, 159 female, mean age 42.0 ± 14.6 years, range 17–85 years), having cervical ribs or sacralization detected by plain radiographs, were taken as the study group. As control 729 volunteers (364 male, 365 female, mean age 41.7 ± 14.3 years, range 15–76 years) were studied. Results. In 1053 patients, of 471 patients having cervical ribs, 345 (73.2%) had also sacralization; of 536 patients with sacralization, 345 (64.4%) also had cervical ribs. Significant associations were found between cervical rib with or without articulation and sacralization [&khgr;2 = 52.284, P < 0.001, odds ratio 5.097 (3.156–8.234); &khgr;2 = 139.473, P < 0.001, odds ratio 5.204 (3.922–6.905), respectively]. Conclusion. Presence of cervical rib might be a clue to the existence of sacralization or vice versa. In patients with cervical or lumbar pain, this association may be helpful for differential diagnosis before applying sophisticated diagnostic techniques.

Homozygosity for the met30 transthyretin gene in a Turkish kindred with familial amyloidotic polyneuropathy

SummaryA Turkish family is described with two members suffering from familial amyloidotic polyneuropathy. Their transthyretin genes were examined using the polymerase chain reaction, and both patients possessed the met30 mutation in both of their transthyretin genes. In this family, only individuals who are homozygous for the met30 mutation have developed symptoms.

Amyloidosis and its related factors in Turkish patients with familial Mediterranean fever: a multicentre study

OBJECTIVE The primary aim of this study was to investigate the prevalence of amyloidosis and its related factors in a large number of FMF patients. METHODS Fifteen centres from the different geographical regions of Turkey were included in the study. Detailed demographic and medical data based on a structured questionnaire and medical records were collected. The diagnosis of amyloidosis was based on histological proof of congophilic fibrillar deposits in tissue biopsy specimens. RESULTS There were 2246 FMF patients. The male/female ratio was 0.87 (1049/1197). The mean age of the patients was 34.5 years (S.D. 11.9). Peritonitis was the most frequent clinical finding and it was present in 94.6% of patients. Genetic testing was available in 1719 patients (76.5%). The most frequently observed genotype was homozygous M694V mutation, which was present in 413 (24%) patients. Amyloidosis was present in 193 patients (8.6%). Male sex, arthritis, delay in diagnosis, M694V genotype, patients with end-stage renal disease (ESRD) and family history of amyloidosis and ESRD were significantly more prevalent in patients with amyloidosis compared with the amyloidosis-negative subjects. Patients with homozygous M694V mutations had a 6-fold higher risk of amyloidosis compared with the other genotypes (95% CI 4.29, 8.7, P < 0.001). CONCLUSION In this nationwide study we found that 8.6% of our FMF patients had amyloidosis and homozygosity for M694V was the most common mutation in these patients. The latter finding confirms the association of homozygous M694V mutation with amyloidosis in Turkish FMF patients.

The Turkish version of the Bath Ankylosing Spondylitis Functional Index: reliability and validity

The purpose of this study was to investigate the reliability and validity of the Turkish version of the Bath Ankylosing Spondylitis (AS) Functional Index (BASFI). The Turkish version of the BASFI was obtained after a process of translation and back-translation. Eighty-one consecutive patients meeting the 1984 New York criteria for AS were enrolled. Patients were evaluated and requested to complete the questionnaire at days 1 and 2 and on a third occasion between days 15–90. Reliability, reproducibility, validity and sensitivity to change of the Turkish version of the index were assessed. Each score correlated closely with the index score, with coefficients between 0.727 and 0.844. Reliability analysis showed a Cronbach’s alpha score of 0.926. Correlations were found between all items of the BASFI and Schober’s test (r=−0.258 to −0.531, p<0.001–0.05), occiput-to-wall distance (r=0.284 and 0.589, p<0.001–0.05), and finger-to-floor distance (r=0.334 to 0.613, p<0.001–0.01). The total index score was correlated with the number of nocturnal awakenings (r=0.515, p<0.001), Schober’s test (r=−0.444, p<0.001), finger-to-floor distance (r=0.567, p<0.001), occiput-to-wall distance (r=0.535, p<0.001), chest expansion (r=−0.403, p<0.001), and the Dougados articular index (r=0.371, p<0.01). A good correlation was found between day 0 and 1 BASFI indices (r=0.765–0.917, p<0.001), showing good reproducibility of the index. The Turkish version of the BASFI showed reliability, reproducibility, and validity, confirming its utility in the research of AS in Turkey. However, sensitivity to changes due to drug therapy and/or rehabilitation remains to be determined.

Identification of Susceptibility Loci in IL6, RPS9/LILRB3, and an Intergenic Locus on Chromosome 21q22 in Takayasu Arteritis in a Genome-Wide Association Study

Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome‐wide association analysis of Takayasu arteritis.

FMF50: a score for assessing outcome in familial Mediterranean fever

Background Colchicine is the main treatment for familial Mediterranean fever (FMF). However, biological agents and other treatments are available for patients who are unable to receive optimal treatment. Objective To develop outcome criteria that define response to treatment. Methods Two rounds of Delphi exercise were followed by a consensus conference enabling the definition of the criteria to be employed. Data for patients with FMF responding and resistant to their treatment were obtained from the FMF Arthritis Vasculitis and Orphan disease Research in paediatric rheumatology (FAVOR) website. The suggested criteria were analysed and validated in this patient cohort. Sensitivity/specificity measures and the ability of the score to discriminate between patients with active and inactive disease via the best cut-off score were calculated by a receiver operating characteristic analysis. Results Compliance with the maximum dose of the drug was considered essential for evaluation of the patients. Seven criteria were suggested in the consensus conference. The performance of each criterion, in differentiating between resistant and responsive patients, was tested. The final set of criteria was defined as at least 50% improvement in five of six criteria, without worsening in any one defined response to treatment with a very high sensitivity and specificity. The items of this FMF50 included: 1. Percentage change in the frequency of attacks with the treatment. 2. Percentage change in the duration of attacks with the treatment. 3. Patients/parents’ global assessment of disease severity (10 cm visual analogue scale (VAS)). 4. Physicians’ global assessment of disease severity (10 cm VAS). 5. Percentage change in arthritis attacks with the treatment. 6. Percentage change in C-reactive protein, erythrocyte sedimentation rate or serum amyloid A level with the treatment. Conclusions The FMF50 produced is a user-friendly measurement tool to guide physicians and can be used in clinical trials.

Incidence of Cyclophosphamide-induced Urotoxicity and Protective Effect of Mesna in Rheumatic Diseases

Objective. To assess bladder toxicity of cyclophosphamide (CYC) and uroprotective effect of mesna in rheumatic diseases. Methods. Data of 1018 patients (725 women/293 men) treated with CYC were evaluated in this retrospective study. All of the following information was obtained: the cumulative CYC dose, route of CYC administration, duration of therapy, concomitant mesna usage, and hemorrhagic cystitis. Cox proportional hazard model was used for statistics. Results. We identified 17 patients (1.67%) with hemorrhagic cystitis and 2 patients (0.19%) with bladder cancer in 4224 patient-years. The median time for diagnosis to hemorrhagic cystitis was 10 months (4–48) and bladder cancer was 8 years (6–10.9). There were 583 patients (57.2%) who received mesna with intravenous CYC therapy. We observed similar incidence rate for hemorrhagic cystitis in both patient groups concomitantly treated with or without mesna [9/583 (1.5%) vs 8/425 (1.8%) respectively, p = 0.08]. Cumulative CYC dose (HR for 10-g increments 1.24, p < 0.001) was associated with hemorrhagic cystitis. Conclusion. Cumulative dose was the only risk factor for hemorrhagic cystitis in patients treated with CYC. No proof was obtained for the uroprotective effect of mesna in our cohort.

Serum soluble interleukin-2 receptor levels in familial Mediterranean fever.

OBJECTIVE: To investigate serum soluble interleukin-2 receptor (sIL-2R) in familial Mediterranean fever (FMF) and assess its role in acute FMF crisis. METHODS: Serum sIL-2R concentrations were measured in patients with FMF during acute crises and during inactive periods of the disease, using an immunoenzymatic assay kit. Twenty four FMF patients during acute crisis (active FMF), 17 patients with inactive FMF, 24 healthy controls, and 20 active patients with rheumatoid arthritis (as a disease control group) were studied. RESULTS: Serum sIL-2R concentrations were increased during an acute FMF crisis compared with the values in inactive FMF patients and healthy controls (P = 0.0105 and P = 0.0012 respectively), while there was no significant difference between the mean values in active FMF and rheumatoid arthritis patients (P = 0.7325). In 14 of the FMF group whose blood samples were available in both active and inactive phases, sIL-2R concentrations were significantly higher in an acute attack than in an attack-free period (P = 0.027). CONCLUSIONS: An increase in sIL-2R may be a result of hyperreactivity of IL-2R-expressing cells during an acute inflammatory attack of FMF.