Naci Tiftik

Prognostic value of matrix metalloproteinases (MMP-2 and MMP-9) in Hodgkin's and non-Hodgkin's lymphoma

Matrix metalloproteinases (MMPs) are responsible for the degradation of extracellular matrix and have an important role in tumour metastases. We investigated the role of MMP‐2 and MMP‐9 in Hodgkins disease (HD) and non‐Hodgkins lymphoma (NHL).The serum samples of patients with HD (n = 12), NHL (n = 30) and healthy control (n = 22) were analysed for MMP‐2 and MMP‐9. An immunoassay method was used for the determination of MMP‐2 and MMP‐9 levels. No statistical significance was found between HD and NHL groups for levels of MMP‐2. There were no relation between MMP‐2, MMP‐9 levels and clinical characteristics of patients. The mean MMP‐9 levels were found to be 555.6 ± 140 ng/ml, 446.6 ± 53.6 ng/ml and 111.2 ± 10.3 ng/ml in HD, NHL and control groups, respectively. Our results suggest that MMP‐9 levels are substantially increased in HD and NHL when compared with controls and may probably be used for distinguishing the benign diseases from malign lymphomas.

The importance of CD7 and CD56 antigens in acute leukaemias

The prognostic significance of immunophenotypical properties of leukaemic cells is well known. However, the biological and clinical significance of CD7 and CD56 antigen expression in acute leukaemias are not clearly established. In patients with acute leukaemias, we identified CD7 and CD56 expression and analysed their associations with markers expressed early in haemopoietic ontogeny and clinical parameters. Among 22 patients with acute leukaemia [12 acute myeloblastic leukaemia (AML), 10 acute lymphoblastic leukaemia (ALL)], we found CD7 positivity in 15 of 22 patients (68%) and CD56 positivity in four patients (18%). CD7 positivity was observed in seven patients (58%) with AML and in eight patients (80%) with ALL. CD56 positivity was observed in three patients (25%) with AML and one patient (10%) with ALL. Lymphadenopathy was present in five patients and associated with hepatosplenomegaly in three patients with ALL. Splenomegaly and hepatomegaly were present in three patients with AML. Central nervous system involvement was seen in one patient with ALL. Complete remission was achieved in nine patients (41%) (five ALL and four AML). Our data showed that CD7 and CD56 positivity at diagnosis associated with low remission rate and biological aggressiveness in a significant proportion of patients. We suggest the evaluation of CD7 and CD56 in all patients with acute leukaemias at the time of diagnosis in view of poor clinical outcome.

Valsartan-Induced Hepatotoxicity in a HBs-Ag-Positive Patient

TO THE EDITOR: Hepatotoxicity caused by angiotensin II receptor blockers is a very rare disorder. We report the first case with acute hepatic injury associated with valsartan, which is an antihypertensive agent. A 52-yr-old hypertensive woman was admitted to our hospital with complaints of weakness, nausea, jaundice, and right subcostal abdominal pain. Her past medical history was unremarkable except for primary hypertension and hepatitis B surface antigen (HBs-Ag) positivity. She had been followed as a HBs-Ag carrier for 4 yr without clinical and laboratory symptoms and signs of acute or chronic liver disease in our hospital. She had been treated for primary hypertension by valsartan for 1 month. There was no other medication. The patient had manifested pruritic erytematous skin changes 1 wk before this admission. After this complaint, moderate nausea, jaundice, and right subcostal abdominal pain developed. On admission, her physical examination revealed no abnormality except for painful mild hepatomegaly. Laboratory findings were as follows: complete blood count was normal and eosinophilia was present. Her total and direct bilirubin levels were 3.2 mg/dl and 2.8 mg/dl, respectively, on admission, and peaked 7.8 and 6.9, respectively on the 7th day of admission. Liver enzymes peaked at the 6th day as follows: ALT 780 U/L, AST 1292 U/L, -glutamyl transferase 945 U/L, and liver-specific ALP 1840 U/L. Serological tests for hepatitis virus were negative (anti-hepatitis A virus IgM, anti-hepatitis B core IgM and IgG, hepatitis B virus DNA by polymerase chain reaction, hepatitis C virus antibody hepatitis C virus RNA by polymerase chain reaction, anti-Epstein-Barr virus IgM, and anti-cytomegalovirus IgM and IgG), except for HBs-Ag positivity. Markers for toxoplasmosis, herpes simplex virus, and HIV were all negative. International Normalized Ratio (INR) and PT were mildly elevated. Hepatobiliary ultrasonography revealed mild hepatomegaly. Liver biopsy was considered, but the patient refused. Valsartan therapy was discontinued at once. Hepatic failure and related complications were not seen. The complaints of the patient were resolved within 2 wk under conservative management. Liver enzymes and bilirubin levels decreased rapidly within 2 wk and returned to normal limits within 3 months. She has been followed for 6 months asymptomatically. As far as we know, this is the first case of valsartanassociated hepatotoxicity in a patient with HBs-Ag positivity. There is just one case report of valsartan-associated hepatic injury from Spain (1). There are not a lot of cases of angiotensin II receptor antagonists associated hepatotoxicity, and in this case, presumably this association is a hypersensitivity reaction together with pruritic skin changes. Valsartan is eliminated mainly by hepatic clearance. Headache, dizziness, and fatigue were the most common adverse events in placebocontrolled studies; the incidence of these adverse events was not significantly different between placebo and valsartan recipients (2). Rash and angioedema have been reported with angiotensin II receptor antagonists very rarely (3). Drug-induced hepatic injury associated with losartan was reviewed by Tabak et al. (4). The importance of HBs-Ag positivity in this hepatotoxicity remains unknown, and the physicians who recommended these agents should be careful about this complication.

Bloodstream infections and mortality-related factors in febrile neutropenic cancer patients

Summary Background We performed a prospective observational cohort study to evaluate the causative bacteria and to identify risk factors for mortality in febrile neutropenic (FN) patients with blood stream infection (BSI). Material/Methods We conducted a prospective data collection on all patients with bacteremia or fungemia. The patients were assigned into low-risk and high-risk groups in accordance with the Multinational Association for Supportive Care in Cancer (MASCC) Risk Index. Results Throughout the study period, the patients developed 420 FN episodes. Out of 420 episodes, only 90 (21.4%) were found to have bloodstream infection. The mean age of the patients was 45.6±18.4 years and 55.6% of the patients were male. A total of 98 isolates were recovered from the cases of BSI. Coagulase-negative Staphylococcus spp (CoNS) were the most common isolates overall (33.7%). There was a significant increase in the rate of gram-negative bacteria throughout the study period (p=0.028). Overall mortality was 33%. Multivariate analyses showed that MASCC risk scores (p=0.0001, OR=15.1, CI%95 4.5–50.7), ICU wards (p=0.0002, OR= 8.6, Cl%95 1.101–68,157) and CoNS (p=0.004, OR=12.12, CI%95 2.3–64.7) were independent risk factors associated with mortality. BSI due to CoNS was associated with lower mortality; however, MASCC high risk score and ICU stay were associated with higher mortality. Conclusions The MASCC risk-index score and emergence of CoNS in positive blood cultures are valuable tools in the management of FN.

Prothrombin G20210A gene mutation with LightCycler polymerase chain reaction in venous thrombosis and healthy population in the southeast of Turkey

Venous thrombosis (VT) is a common disease, with an annual incidence in the general population of approximately 1 per 1000. The prevalence of genetic risk factors for thrombosis varies greatly in different parts of the world. Prothrombin G20210A (PT G20210A) gene mutation has been recently identified as a common risk factor in venous thrombosis. Sixty-one patients with VT, differing in age and sex, and 340 healthy subjects were consecutively enrolled into our study to determine the prevalence of PT G20210A in VT and in the healthy population of the southeast of Turkey. The mutation was identified with fluorescence resonance energy transfer (FRET) with the LightCycler polymerase chain reaction. The PT G20210A mutation was found to be 6.5% (4/61) in the VT group and 1.2% (4/340) in the healthy group (P = 0.021). Three patients with VT had a heterozygous PT G20210A mutation, and the other patient with VT had both Factor V Leiden and PT G20210A mutations. We showed that this method may be used safely for detection of the PT G20210A gene mutation, and the prevalence of PT G20210A mutation is significantly higher in patients with VT than in the healthy population in the southeast of Turkey.

Hepatitis C virus in patients with non-Hodgkin's lymphoma in southeastern Anatolia region of Turkey: A prospective case-control study of 119 patients

Hepatitis C virus (HCV) has been associated with several extrahepatic disorders including mixed cryoglobulinemia (MC), autoimmune thyroiditis, Sjogrens syndrome. Such associations have led to the suggestion that HCV may participate in the development of various immunmediated disorders. Recently, it has been hypothesised that HCV might act as a trigger for the development of monoclonal B-cell disorders such as non-Hodgkins lymphoma (NHL). Discordant data have been reported in different geographic regions of the world. The aim of this prospective case-control study was to detect the prevalence of HCV in patients with NHL in southeastern Anatolia region of Turkey. In this study, HCV antibody prevalence and cryoglobulinemia were investigated in 119 patients with histologically diagnosed NHL. The control group consisted of 117 patients who visited the outpatient clinic of internal medicine. None of the patients had HCV antibody positive (0%) with the enzyme immunoassay and reverse transcriptase polymerase chain reaction (RT-PCR). One of the control patients had positive HCV antibody (0.9%). Our data does not support the association between HCV infection and NHL in southeastern Anatolia region of Turkey.

Mean Platelet Volume and Related Factors in Patients at Different Stages of Diabetic Nephropathy A Preliminary Study

Introduction: Mean platelet volume (MPV) is an independent cardiovascular disease predictor, and characteristics of MPV in patients with diabetic nephropathy (DN) are not well known. Aim: To determine the MPV levels in patients at different stages of DN. Patients and Methods: The MPV levels were investigated in healthy participants (group 1, n = 157), patients with type 2 diabetes mellitus without complication (group 2, n = 160), diabetic patients with clinical proteinuria (group 3, n = 144), and in patients with chronic kidney disease due to DN (group 4, n = 160). Findings: The MPV level was higher in all diabetic patients than that in normal participants (P < .05). The MPV values had a positive correlation with the serum creatinine and proteinuria, and a negative correlation with the glomerular filtration rate ([GFR] P < .001 for all, r values; .72, and .82, and −.92, respectively). Conclusion: The MPV values were higher in diabetic groups than that in normal participants. Both GFR and proteinuria were the most powerful determinants of MPV.

Factor V Leiden mutation in venous thrombosis in southeast Turkey.

Venous thrombosis (VT) is a common disease, with an annual incidence in the general population of approximately 1 per 1,000. Factor V Leiden mutation (G1691A) (FVL) is the most common risk factor in venous thrombosis. The prevalence of FVL for thrombosis varies greatly in different regions of the world. FVL mutation has been identified both by conventional method and fluorescence resonance energy transfer (FRET) with the LightCycler. Sixty-one patients with VT, different in age and sex, were consecutively entered into this study to assess the prevalence of FVL in VT in southeast Turkey. FVL mutation was found in 24.6% (15/61). Fourteen individuals were heterozygous and 1 homozygous, a rate of 22.9% and 1.6%, respectively. In conclusion, the authors suggest that FVL mutation is common in patients with venous thrombosis in southeast Turkey.

Ultraviolet recall phenomenon associated with methotrexate and cytarabine.

JEADV 2006, 20, 341–362

Seasonal Association of Immune Thrombocytopenia in Adults

BACKGROUND Immune thrombocytopenia (ITP) is an autoimmune disorder. It is characterized by thrombocytopenia due to thrombocyte destruction mediated by autoantibodies; however, cytotoxic and defective regulatory T-lymphocytes play an important role in its pathogenesis. While childhood ITP is usually acute, self-limiting and generally seasonal in nature, ITP in adults is usually chronic; its relation with seasons has not been studied. AIMS We investigated whether months and/or seasons have triggering roles in adults with ITP. STUDY DESIGN Descriptive study. METHODS A retrospective case review of adult patients with primary ITP diagnosed at various University Hospitals in cities where Mediterranean climate is seen was performed. Demographic data, date of referral and treatments were recorded. Corticosteroid-resistant, chronic and refractory cases were determined. Relation between sex, corticosteroid-resistant, chronic and refractory ITP with the seasons was also investigated. RESULTS The study included 165 patients (124 female, mean age=42.8±16.6). Most cases of primary ITP were diagnosed in the spring (p=0.015). Rates of patients diagnosed according to the seasons were as follows: 35.8% in spring, 23% in summer, 20.6% in fall, and 20.6% in winter. With respect to months, the majority of cases occurred in May (18.2%). Time of diagnosis according to the seasons did not differ between genders (p=0.699). First-line treatment was corticosteroids in 97.3%, but 35% of the cases were corticosteroid-resistant. Steroid-resistant patients were mostly diagnosed in the spring (52.1%) (p=0.001). ITP was chronic in 52.7% of the patients and they were also diagnosed mostly in the spring (62.7%) (p=0.149). CONCLUSION This is the first study showing seasonal association of ITP in adults and we have observed that ITP in adults is mostly diagnosed in the spring. The reason why more patients are diagnosed in the spring may be due to the existence of atmospheric pollens reaching maximum levels in the spring in places where a Mediterranean climate is seen.