Yekta Tüzün

Familial Mediterranean fever gene mutations in the Southeastern region of Turkey and their phenotypical features

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent inflammatory attacks of serosal membranes. Several studies have focused on the differences between frequency of the mutations and their phenotypical manifestations. The aim of this study was to evaluate whether or not this phenotypical variation is associated with the existence of particular mutations. Twelve MEFV (Mediterranean fever) gene mutations were investigated in 119 patients suffering from FMF. Heterozygote M694V (21/119), heterozygote E148Q (21/119), homozygote M694V (17/119) and heterozygote V726A (12/119) mutations were the most common mutations. Patients were grouped according to the presence of the M694V mutation: group I was M694V/M694V, group II was M694V/others, and group III was other/other. Mean severity scores for the groups were 13.94 ± 4.10, 10.79 ± 3.01 and 8.31 ± 2.26, respectively. There were statistically significant differences between the mean severity scores of groups I and II (p = 0.029), groups I and III (p < 0.0001), and groups II and III (p < 0.0001). Diagnosis of amyloidosis was established in four (23%) patients of group I, and three (8%) patients of group II, but in none of the patients in group III. There was also a statistically significant difference between groups I and III (p = 0.046), but not between groups II and III (p = 0.083) and groups I and II (p = 0.317) in terms of amyloidosis development. In conclusion, we found a higher disease severity score and higher prevalence of amyloidosis in FMF patients who were M694V mutation carriers. Many ethnic groups live in Anatolia and more ethnic origin-based studies are needed to determine the real effect of these mutations on disease severity and amyloidosis.

Serum c-reactive protein (CRP) levels and insulin resistance in non-obese women with polycystic ovarian syndrome, and effect of bicalutamide on hirsutism, CRP levels and insulin resistance

Background/Aims: Insulin resistance is associated with serum C-reactive protein (CRP) levels. We aimed to evaluate the effect of bicalutamide on insulin resistance and serum CRP levels in non-obese polycystic ovarian syndrome (PCOS) patients. Methods: 40 non-obese patients (BMI ≤25 kg/m2) with PCOS and, 40 age- and BMI-matched healthy women were studied. Patients received bicalutamide orally at the dose of 25 mg/day. Serum CRP levels were measured with immunometric assay. Homeostasis model assessment (HOMA-IR) index was used for insulin resistance. Results: Mean Ferriman-Gallwey score (FGS) (p = 0.001), insulin (p = 0.001), serum glucose (p = 0.001), prolactin (p < 0.003), total (p < 0.04) and free testosterone (p = 0.001) and free androgen index (FAI) levels (p = 0.001) of PCOS subjects were higher than in the control group. Mean HOMA-IR of PCOS patients was higher than in control subjects (2.43 ± 1.2 and 0.94 ± 0.37, p = 0.001). CRP levels in subjects with PCOS was also higher than in control subjects (4.27 ± 1.33 and 0.98 ± 0.19, p = 0.001). After bicalutamide treatment, FGS, free and total testosterone and FAI decreased (p = 0.001). HOMA-IR, prolactin and CRP levels did not show any statistical difference with bicalutamide treatment. Conclusions: PCOS patients had insulin resistance and a high CRP level. Bicalutamide treatment did not influence insulin resistance and CRP level in PCOS, and this ineffectiveness of bicalutamide on CRP levels may be the result of insulin resistance and/or high prolactin levels at this time.

A comprehensive analysis of 12 thrombophilic mutations and related parameters in patients with inflammatory bowel disease: data from Turkey

BackgroundPossible association of inflammatory bowel disease (IBD) with the most common inherited prothrombotic conditions has been the focus of many investigations. Advance in modern molecular biology is expanding the thrombophilia evaluation steadily. We tried to put forward a comprehensive thrombophilic profile in IBD and to see the probable role of this profile in pathogenesis.MethodsA total of 60 adults (33 patients and 27 healthy controls) were included. We used the CVD-StripAssay which is based on the reverse-hybridization principle to identify a total of 12 thrombophilic gene mutations: Factor V R506Q, Factor V H1299R, prothrombin G20210A, Factor XIII V34L, beta-Fibrinogen-455 G-A, PAI-1 4G/5G, platelet GPIIIa L33P, MTHFR C677T, MTHFR A1298C, ACE I/D, Apo B R3500Q and Apo E2/E3/E4, respectively. Besides, we evaluated many related blood parameters such as protein C, protein S, AT-III, IL-6, TNF-alpha, Apo-A1, Apo-B100, homocysteine (tHcy) etc. using commercially available assays.ResultsThe frequencies of genetic polymorphisms were found to be statistically insignificant among patients and controls, except for three: Beta-Fibrinogen-455G-A, MTHFR A1298C and ACE-I/D. Two patients with a history of deep venous thrombosis had more than one polymorphism. Patients with MTHFR C677T and MTHFR A1298C gene mutations had a similar mean tHcy levels with controls. Patients with Apolipoprotein B R3500Q and Apolipoprotein E4 gene mutations had similar mean LDL-cholesterol levels. Mean total cholesterol and triglyceride levels were similar in patients and controls of Apo E2, E3, E4 alleles.ConclusionPredominantly, the presence of genetic mutations that predispose to hypercoagulable states does not appear to be in correlation with IBD. There was a statistical difference between the proportions of the mutated allele frequencies of Beta-Fibrinogen-455G-A, MTHFR A1298C and ACE-I/D in IBD.

How to Increase the Diagnostic Value of Malignancy-Related Ascites: Discriminative Ability of the Ascitic Tumour Markers

Making a differential diagnosis between malignant and non-malignant ascites is an important clinical issue, but cytological examination has a relatively low diagnostic sensitivity. This study aimed to find a discriminative model that distinguished between malignancy-related and non-malignant ascites. The study included 107 patients: 50 with non-malignant and 57 with malignant ascites. Ascites was analysed using a range of tumour markers and standard cytology. Standardized canonical discriminant function coefficients were used to distinguish between ascites types. The combination of carbohydrate antigen (CA) 15-3, carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA-21.1) discriminated between malignancy-related ascites and non-malignant ascites with an accuracy of 98.8% compared with an accuracy of 77.8% for cytological examination. In conclusion, the use of a discriminant function constructed from a combination of CA15-3, CEA and CYFRA-21.1 could distinguish malignant from non-malignant ascites with greater accuracy than cytological examination. Further studies in larger population groups are warranted.

Correlation of Tumour Markers in Ascitic Fluid and Serum: Are Measurements of Ascitic Tumour Markers a Futile Attempt?

Correlations between tumour markers in ascitic fluid and serum were investigated to determine whether ascitic fluid analysis had any diagnostic advantage over serum in 91 adults with ascites (55 malign; 36 benign). Serum and ascitic fluid were analysed for carcinoembryonic antigen (CEA), cancer antigen (CA) 125, CA19.9, CA72.4, CA15.3, α-fetoprotein (AFP) and cytokeratin-19 fragment (CYFRA). The tumour markers were skewed between the groups so were logarithmically transformed. Correlations between serum and ascitic fluid were tested using Pearsons correlation coefficient. Serum and ascitic fluid levels of CEA, CA125, CYFRA and AFP in the malign group were statistically different and CEA, CA19.9, CA5.3, CYFRA and AFP were statistically different in the benign group. For both groups, all tumour markers were highly correlated in serum and ascitic fluid, with the exception of CYFRA in the malign group. These results indicate that, where malignant ascites is suspected, analysing tumour markers in ascitic fluid does not have any advantage over serum analysis.

Replacement of hystological findings: serum hyaluronic acid for fibrosis, high-sensitive C-reactive protein for necroinflamation in chronic viral hepatitis

Because of limitations in biopsy procedure, several non‐invasive tests have been developed for predicting the histological findings in chronic hepatitis. A fibrosis (F) score 1 or above and necroinflammation [histological activity index (HAI)] score 4 or above are required to initiate the treatment in chronic viral hepatitis. Literature includes many studies on hyaluronic acid (HA) as a non‐invasive procedure in predicting histological findings but lacks on high‐sensitive‐C‐reactive protein (hsCRP). We evaluated the diagnostic value of HA and hsCRP in patients with chronic viral hepatitis.

Hepatitis B virus reactivation induced by Yttrium-90-ibritumomab-tiuxetan.

Non-Hodgkin’s lymphoma (NHL) is a heterogeneous group of lymphoproliferative disorders with differing patterns of behavior and treatment responses. The majority of NHL cases (85%) are of B-cell origin [1]. In the last decade, important advances have been made on the treatment modalities in patients with NHL. Targeted therapies have been in use in NHL patients for nearly 5 years. The chimeric anti-CD20 monoclonal antibody (MoAb) rituximab was first studied in recurrent indolent NHL, and resulted in an objective response rate of 48% with a median time to progression of over 1 year only [2]; degree of activity can be quite significant and unfortunately, a substantial number of patients do not respond to therapy. These cases of refractory or relapsed low grade, follicular or transformed NHL, including patients with rituximab-refractory disease, can be effectively treated with radioimmunotherapy (RIT). RIT has been used to target radiation to tumor tissue with radio-labeled MoAb in NHL patients in an attempt to limit toxicity to normal cells, including the B cells. To date, there are only two commercially available RITs approved by the Food and Drug Administration, namely ibritumomab tiuxetan (Zevalin) and tositumomab (Bexxar). RIT-associated side effects due to radiation effects observed on the bone marrow are relatively limited and occur approximately 4 – 8 weeks after treatment. Chemotherapeutic-associated hepatitis HBV flare up is rarely seen and most cases are detected in HBsAg(þ) carrier patients. Herein, we reported a patient with HBV reactivation induced by ibritumomab tiuxetan therapy, who had been HBsAg carrier. Administration of antiviral agents appears warranted in HBsAg carrier patients receiving treatment with ibritumomab tiuxetan. A 56-year-old male patient admitted to our clinic in January 2006 with a history of fatigue, night sweats, fever, and left supraclavicular masses. On physical examination, 2-cm diameter left supraclavicular and 3-cm bilateral axillar lymphadenopathies were detected. After excisional biopsy of supraclavicular mass, histopathologic examination showed low grade, CD20(þ) follicular NHL. Before administration of systemic chemotherapy, performance status was ECOG 1. Baseline biochemical analyses were as follows: LDH: 88 U/l(100 – 190 U/l), ALT: 14 U/l (10 – 35 U/l), AST 24 U/l (10 – 40 U/l) and bilurubin levels were normal. Hepatitis B virus markers were as follows: HBsAg(þ), anti-HBsAg(7), HBeAg(7), anti-HBeAg(7), anti-HBcAg IgM(7), and antiHBcAg IgG(þ) were detected. HBV DNA(7), HDV IgM(7), HDV IgG(7), and HDV RNA were negative before administration of systemic chemotherapy. Erythrocyte sedimentation rate was 12 per hour. On radiological examination, 2-cm diameter left supraclavicular, bilateral multiple axillar, and abdominal lymphadenopathies were detected on thoraco-abdominal computerized tomography. Bilateral iliac crest biopsy was normocellular and atypical cells were not detected. Stage of disease was PIB according to Ann Arbor staging system. R-CVP (cyclophosphamide, vincristine, prednisone,

The effects of nonsteroidal anti-inflammatory drugs on platelet function and severity of upper gastrointestinal haemorrhage

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal (GI) damage primarily due to the inhibition of prostaglandin synthesis in gastric mucosa, which is an important factor in mucosa protection. Platelets are a cardinal feature of vascular repair. A variety of angiogenic stimulators are stored in platelets and are released during clotting at the wound. When there is a defect in any of these functions and/or platelet number, haemostasis is usually impaired and there may be an associated increased risk and severity of bleeding. While the mechanism of mucosal injury and bleeding are well documented with the use of NSAIDs, very little is known about the platelet function abnormalities and their effects on severity of upper GI bleedings. We performed a prospective analysis of 49 patients who had a history of NSAIDs use to investigate the association between the platelet function impairment associated with NSAIDs and severity of upper GI haemorrhages. Thirty-six of 49 patients (73.5%) had deteriorated platelet function. Mean severity score of patients with deteriorated platelet functions was 3.39, and that of patients with normal platelet functions was 2.46. Mean severity score was statistically significantly higher in patients with deteriorated platelet functions. In conclusion, impaired platelet functions associated with NSAIDs may cause more severe upper GI bleeding. Clinicians should be alert for GI complications especially in older patients and in those with a history of ulcer bleeding.

Two cases of bacterial meningitis accompanied by thalidomide therapy in patients with multiple myeloma: is thalidomide associated with bacterial meningitis?

Morbidity and mortality in multiple myeloma is often attributed to life-threatening infections. A defect in humoral immunity has been proposed for the predisposition to bacterial infections. Most of the infections are of bacterial origin, and the most serious are septicemia, meningitis, and pneumonia. Thalidomide is a drug with pleiotropic effects. The immunomodulatory effects of thalidomide are at least partially mediated through its ability to down-regulate the pathogenic over-production of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is a cytokine that plays a central role in the regulation of the host immune and inflammatory response to infection. In the central nervous system, TNF-alpha is involved in induction of a fever response and triggers the release of other cytokines, and may also influence transport of compounds into the brain, leading to cerebrospinal fluid leukocytosis, increased protein influx, and lactate accumulation. Thalidomide has been shown to down-regulate the production of TNF-alpha. On the other hand, knowledge of the effects of thalidomide on granulocyte functions is limited. Thalidomide has been shown to attenuate neutrophil adhesion and chemotaxis. We present herein two cases of Streptococcus pneumoniae bacterial meningitis that developed soon after the initiation of thalidomide treatment, and discuss the effect of thalidomide on the immune system. Although, it is not clear whether thalidomide caused the development of the bacterial infections and meningitis, or what its pathogenetic mechanisms are, physicians should be alert for signs and symptoms of meningitis in patients with multiple myeloma who are treated with thalidomide, especially those in neutropenic states.

Dubin-Johnson Sendromu Tanılı Bir Olgu Nedeniyle Konjuge Hiperbilirubinemiler

Ectopic neurohypophysis is an anomaly of the Pituitary gland which may be associated with short stature due to Growth hormone deficiency. MRI is the modality of choice in diagnosing this condition. We present a case of pituitary dwarfism and ectopic neurohypophysis with clinical and radiological findings. 21 year-old male admitted with short stature. All hormones, except prolactin, of anterior hypophysis were low. Bright spot was ectopically located at level of median eminence on enhanced MRI of hypophysis and stalk of hypophysis was not observed. Ectopic neurohypophysis may be present with pituitary dwarfism. Cranial MRI may be useful to investigate related pathologies in such cases.