Kadim Bayan

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.

Thyroid and celiac diseases autoantibodies in patients with adult chronic idiopathic thrombocytopenic purpura

The association of chronic idiopathic thrombocytopenic purpura (cITP) and thyroid autoimmune diseases (TAD) is a known but an uncommon condition. Celiac disease (CD), which is characterized by malabsorption and villous atrophy that occur as a consequence of the ingestion of wheat gluten may also be related to other autoimmune disorders. In this study, we investigated the prevalence of thyroid anti-microsomal (TAMA) and anti-thyroglobulin (TATA) auto antibodies, anti-gliadin (AGA) IgG, IgA, anti-endomisium (EMA) IgG and IgA antibodies in 74 patients with cITP and in 162 healthy controls. TATA positivity was found in 29, and TAMA positivity in 19 out of 74 patients; and in 16 and 18 out of 162 controls respectively (p < 0.0001 and p = 0.005, respectively). TAD was diagnosed in 29 of cITP patients. AGA IgG positivity was found in 17, and IgA was present in five out of 74 patients; and AGA IgG was found in 19, and IgA was detected in 4 out of 162 controls (p = 0.032 and p = 0.143, respectively). EMA IgG positivity was found in six out of 74 patients and in nine out of 162 control subjects (p = 0.566). EMA IgA positivity was found in two out of 74 patients and in one out of 162 controls (p = 0.232). We showed that the prevalence of TAD and related autoantibodies are higher in patients with cITP. We suggest that, patients with cITP should be followed up for development of TAD. In addition, all CD related auto antibodies were found to be more frequent in patients with cITP, but only the AGA IgG reached to the clinical significance. None of the CD related auto antibody positive patients developed clinically manifested CD. Large-scale designed studies are needed to clarify the long-term impact and importance of these CD related auto antibodies in patients with cITP.

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.

Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis-B surface antigen (HBSAG) seropositive cancer patients undergoing cytotoxic chemotherapy

Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.

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.

Upper Gastrointestınal Bleeding Caused by Small-Cell Lung Cancer: A Case Report

Lung cancer is one of the most common causes of death in the world. Although small-cell lung cancer (SCLC) comprises only 20%–25% of cases, it is an aggressive and fatal cancer that is usually not diagnosed until metastatic disease is already present (1). Distant metastasis from this cancer is usually recognized in the adrenal glands, bone, liver, brain, and kidneys but is uncommon in the digestive system. Duodenal metastasis is an extremely rare condition reported in the literature (2, 3). We report the case of a patient with SCLC who was suffering from hematemesis and melena reflecting upper gastrointestinal bleeding.

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.

Kriptojenik ve HBV ilişkili sirozda HFE gen mutasyonları

Background/aims: The liver leads the list among the affected organs in hereditary hemochromatosis. We have limited knowledge about HFE gene mutations in cryptogenic cirrhosis and hepatitis B virus -related cirrhosis, which are the two important sub-titles in liver cirrhosis. We studied HFE gene mutations in these patient groups. Methods: Fiftyeight patients with cirrhosis were included in the study. The patients were divided into two equal groups. Group 1 consisted of patients with cryptogenic cirrhosis and Group 2 of patients with cirrhosis appearing on the base of hepatitis B virus . The following 12 mutations of the HFE gene were studied in both groups: V53M, V59M, H63D, H63H, S65C, Q127H, P160delC, E168Q, E168X, W169X, C282Y, and Q282P. Results: Eighteen patients were female and 40 were male. The average age in the first group was 44.35±20.6 and in the second group was 49.39±12.17; there was no statistically significant difference between the groups (p=0.230). In the cryptogenic cirrhosis patients, the total rate of allelic H63D mutation was found as 24.13% (7/29). C282Y heterozygote mutation was determined in one patient (1/29; 3.44%). In the second group, total allelic mutation rate was 20.68% (6/29). No statistically significant difference was determined between the two groups with respect to mutation rates (p=1.0). The total prevalences of H63D and C282Y mutations were found as 22.4% (13/58) and 1.72% (1/58), respectively. H63D homozygosity was found as 3.44% (2/58) and heterozygosity as 18.96% (11/58). Conclusions: The HFE gene mutation rates in cryptogenic and hepatitis B virus cirrhosis were found to be similar. C282Y mutation has been put forward in this study for the first time in our area.