Abdullah Altintas

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.

Factor V Leiden and G20210A prothrombin mutations in patients with recurrent pregnancy loss: data from the southeast of Turkey

Factor V Leiden (FV-Leiden) and prothrombin gene mutations (FII G20210A) are well-established independent risk factors for thrombosis. In the recent years, many studies have suggested that these mutations are associated with an increased risk of recurrent pregnancy loss (RPL). We aimed to investigate the prevalence of these molecular defects in subjects with a history of early RPL. One hundred and fourteen women with three or more consecutive unexplained first-trimester miscarriages were compared to 185 parous women with uncomplicated pregnancies from the same ethnic origin. The presence of FV-Leiden and FII G20210A mutations was assessed by polymerase chain reaction analysis. Overall, 11 out of the 114 women with early RPL (9.6%) had either FV-Leiden or FII G20210A mutation, as compared with 16 out of the 185 women with normal pregnancies (8.6%; p = 0.756). The prevalence of FV-Leiden mutation was 7.9% (9/114) in patient group, compared with 7% (13/185) in control group (p = 0.780). One hundred and two patients were primary and 12 were secondary aborters. All FV-Leiden positive cases were primary aborters (8.8%; 9/102, p = 0.584). Concerning the FII G20210A, two out of 114 (1.7%) were first-trimester RPL (primary aborters) and three out of 185 (1.6%) controls were carriers of the FII G20210A mutation (1.7 vs 1.6%, p = 0.931). The results obtained from patients with first-trimester RPL and the control group have no statistical significant differences in the prevalence of FV-Leiden and FII G20210A mutations. These results suggest that mutations have no role in etiology of first-trimester recurrent abortions.

Central nervous system blastic crisis in chronic myeloid leukemia on imatinib mesylate therapy: a case report

SummaryChronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by a reciprocal translocation between chromosomes 9 and 22. Imatinib mesylate is a potent and selective inhibitory of the BCR/ABL tyrosine kinase. Imatinib is a first choice of treatment of chronic phase CML. It has also shown activity in patients with CML in accelerated or blastic phases. However, the penetration of the drug and its active metabolites into the central nervous system (CNS) is poor. Therefore, the CNS is sanctuary site for malignant cells in patients treated with imatinib. Herein, we report a patient with CML in accelerated phase that developed central nervous system disease while on imatinib mesylate therapy.

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.

Use of N-Terminal Pro-Brain Natriuretic Peptide to Assess Left Ventricular Function after Adjuvant Doxorubicin Therapy in Early Breast Cancer Patients : A Prospective Series

AbstractBackground and objective: Anthracyclines are well established and highly efficacious antineoplastic agents for various haematopoietic and solid tumours, such as breast cancer. The main adverse effect of anthracycline therapy is cardiotoxicity. The aim of this prospective study was to determine the role of plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) in assessing left ventricular function in early breast cancer patients receiving adjuvant anthracycline treatment. Methods: Thirty-three newly diagnosed breast cancer patients who received a total doxorubicin dosage of 240 mg/m2 over four treatment cycles as part of adjuvant chemotherapy after curative breast surgery were included in this study. Venous NT-proBNP levels were measured before and at the end of doxorubicin therapy. Left ventricular function was measured by echocardiography conducted 3 weeks after surgery and at the end of doxorubicin therapy. Results: NT-proBNP levels were significantly higher in patients (n = 10) with decreased left ventricular ejection fraction (LVEF) [p = 0.02]. There was no difference in LVEF (p = 0.164) or NT-proBNP levels (p = 0.844) between the patients who had high NT-proBNP levels and those who had normal NT-proBNP levels before doxorubicin chemotherapy. None of the factors studied (breast cancer grade, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, age) was found to be significantly related to NT-proBNP. Conclusion: The association between higher NT-proBNP levels and reduced LVEF in asymptomatic breast cancer patients after doxorubicin administration could be an early indication of subclinical acute anthracycline cardiotoxicity. Furthermore, breast cancer patients experiencing a progressive increase in NT-proBNP levels might be in a higher risk group for acute anthracycline cardiotoxicity.

Pulmonary hypertension in patients with essential thrombocythemia and reactive thrombocytosis

Increased incidence of pulmonary hypertension (PH) has been reported in patients with chronic myeloproliferative disorders. The exact incidence of PH in essential thrombocythemia (ET) is unknown. Most of the reported literature consists of case reports or small studies. We designed this study to asses the incidence of PH in patients with ET and reactive thrombocytosis. Previously or newly diagnosed 46 patients with ET, and 40 patients with reactive thrombocytosis secondary to iron deficiency anemia were found to be eligible for this study. Diagnosis of PH was established via transthoracic echocardiography. PH was found in 22 (47.8%) out of 46 patients with ET. Seven patients with PH were newly diagnosed ET, 5 patients with PH were in low, and the other patients with PH were in intermediate or high risk category. We found statistically significant difference in terms of platelet counts between ET patients with PH and without PH (p = 0.027). None of the patients with reactive thrombocytosis had PH. In conclusion, PH appears to be common in patients with ET. Therefore, all patients with ET should be evaluated for PH. Larger and prospective studies are required to clarify the long-term impact of PH on the survival of these patients. Future studies are also needed to determine whether cytoreductive treatment and aspirin prevent the development of PH, and to determine the effects of cytoreductive treatments and aspirin on the prognosis of PH. The effect of PH on ET prognosis should also be determined in low risk ET patients.

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.

Primary Spindle Cell Sarcoma of the Breast

Background: Primary pure breast sarcoma is a rare disease and constitutes 0.2–1.0% of all mammary malignancies. The establishment of a diagnosis of soft tissue sarcoma is difficult in adults. Immunohistochemical analysis usually proves to be helpful in indistinguishable cases. The simplistic step is to classify sarcomas on a simple descriptive basis as spindle cell sarcomas, myxoid sarcomas, pleomorphic sarcomas, and small round cell sarcomas. Case Report: Here, we present a rare case of primary spindle cell sarcoma of the breast. A 43-year-old woman was admitted to our clinic with a 2-month history of a left breast lump. Histopathological examination showed a tumor of 2.5 cm in diameter and of nuclear and histological grade 2. In the immunohistochemical examination, vimentin positivity, high nuclear overexpression of P53, high Ki-67 and S-100, desmin, leukocyte common antigen, keratin, and smooth muscle antigen, CD34, HMB45 and EMA negativity were detected. Conclusion: Most invasive breast neoplasms are epithelial tumors, and mesenchymal breast tumors are rarely seen. In primary breast sarcoma, adequate surgical tumor excision, tumor grade, and tumor diameter seem to be the most important prognostic factors.

Prevalence of antineutrophil cytoplasmic antibody positivity in patients with Hodgkin’s and non-Hodgkin lymphoma: a single center experience

Hematological malignancies are associated with the release of different autoantibodies and rheumatological manifestations. Systemic vasculitides are rare in hematological malignancies, and antineutrophil cytoplasmic antibodies (ANCA) have not been described sufficiently in hematological malignancies. In this present prospective study, we examined the prevalence of ANCA and related disease in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients in the southeast region of Turkey. We examined 119 patients with previously or newly diagnosed NHL and 60 patients with HL for the presence of ANCA and related autoimmune diseases between December 2002 and February 2007. ANCA positivity was detected in only 8 patients (4.4%); and all of these ANCA positivities were detected in patients in the HL group (13.3%); p-ANCA positivity was detected in 6 patients (3.3%); and c-ANCA positivity was detected in 2 patients (1.1%). There was statistically significant difference between patients with HL and NHL in terms of p-ANCA (p = 0.001) but none in c-ANCA (p = 0.111) positivity. None of the ANCA positive patients had vasculitides or rheumatic manifestations. In addition, we did not detect any ANCA positivity in the NHL group. In conclusion, ANCA positivities were detected only in HL patients; but we did not detect the association between ANCA positivities and rheumatic manifestations or vasculitis and also the different treatment responses in HL patients.

Thrombosis of temporal artery and renal vein in Kimura-disease-related nephrotic syndrome.

Kimura disease (KD) is an angiolymphoid proliferative disorder of unknown etiology, occurs mainly in Asian patients, presenting with subcutaneous slowly growing masses, with a predilection for preauricular and submandibular regions. The clinical course of the disease is thought to be benign. Concomitant peripheral blood eosinophilia and elevated serum immunoglobulin E levels are often observed. Main systemic manifestation of the KD is renal involvement. Renal abnormalities, notably proteinuria and nephrotic syndrome have been found to be associated with KD. We report a 42-year-old man with KD and a steroid-sensitive membraneous nephrotic syndrome with bilaterally temporal artery and renal vein thrombosis. This is the first reported case of KD associated nephrotic syndrome complicated with wide arterial and venous thrombosis from Anatolia.