The initial detection of Toscana virus in phlebotomine sandflies from Turkey.

Toscana virus (TOSV) is a prominent arthropod-borne viral agent of human central nervous system infections occurring in the Mediterranean region. The main transmission route to susceptible individuals involves sandflies as vectors. Despite several reports revealing widespread TOSV activity in Turkey, vectors remained unidentified. A sandfly field survey was carried out in five provinces in Central, Southeast and Mediterranean Anatolia in 2017 to identify TOSV and related sandfly-borne phleboviruses and Leishmania parasites, with evidence for circulation in the region. A total of 7136 sandfly specimens, collected via standard methods, were evaluated in 163 pools. TOSV was detected in 11 pools (6.7%), comprising Phlebotomus major sensu lato, Sergentomyia dentata and Phlebotomus papatasi species. TOSV partial L and S segment sequences were characterized, that phylogenetically clustered with local and global genotype A strains. An amino acid substitution outside the conserved motifs of the viral polymerase, also present in previous TOSV sequences in endemic regions, was observed. Leishmania tropica was detected in a single pool of Ph. sergentii (0.6%). This is the first report of TOSV in sandflies from Turkey, and this study further provides evidence for additional sandfly species with the potential to transmit TOSV.

Sandfly surveillance and investigation of Leishmania spp. DNA in sandflies in Kosovo.

In the past decade, leishmaniasis seems to be re-emerging in Balkan countries. There are serious implications that Kosovo is a visceral leishmaniasis endemic region with autochthonous transmission; nevertheless, surveillance of vectors, reservoirs or the disease is not yet established. Gaining knowledge about sandfly vector species is a prerequisite for the development of a monitoring and control plan in the future. After a long gap in research of over 70 years, sandfly studies in Kosovo were resumed in 2014. During this presence/absence study, nine sandfly species were detected: Phlebotomus papatasi, Ph. perfiliewi, Ph. tobbi, Ph. neglectus, Ph. simici, Ph. balcanicus, Ph. alexandri, Ph. mascittii and Sergentomyia minuta. Three species are new with regard to the fauna of Kosovo - Ph. alexandri, Ph. balcanicus and Ph. mascittii. Besides increased diversity, changes in the number of collected specimens and distribution range of species were recorded, with Ph. neglectus being the most dominant species with the widest distribution. Testing of randomly chosen females for Leishmania spp. DNA resulted the in detection of L. tropica in a specimen of Ph. neglectus. The presence of numerous vector species in the sandfly fauna of Kosovo pose a threat for the re-emergence of vector-borne diseases. Therefore, continuous surveillance is recommended with regular updates on vector distribution and abundance.

The frequency of C609T polymorphism in the NQO1 gene and its relation to cytogenetic abnormalities in patients with myelodysplastic syndrome.

The aim of the present study is to evaluate the frequency of C609T polymorphism in the NQO1 (NAD(P)H) quinon oxydoreductase) gene and its relation to cytogenetic abnormalities in patients with Myelodysplastic Syndrome (MDS). The study group consisted of 80 patients MDS with 13 of them in the pediatric age group. The frequency of the NQO1 gene polymorphism was compared with a healthy control group involving 423 individuals. Cytogenetic abnormalities were detected in 43 patients (54%). In patients with MDS the overall frequency of the C609T polymorphism was not different than controls. Also, although the frequency of the C609T polymorphism was higher in patients with secondary MDS (sMDS) (OR: 1.893, 95% CI: 0.840-4.265, p=0.238) , 5/del(5q) (OR:1.298, 95% CI: 0.331-5.086,p=0.124), +21(OR:1.817, 95% CI:0.429-7698,p=0.124) and t(8;21) (OR:3.028, 95% CI: 0.604-15.172,p=0.137) groups, the difference did not reach statistical significiance. Our results do not support the view that the C609T polymorphism has a role in the pathogenesis of MDS. Also the frequency of the C609T allele did not seem to be associated with cytogenetic abnormalities.

Sheehan's syndrome associated with Glanzmann's Thrombasthenia: case report and literature review.

OBJECTIVES: We aimed to present a case of Sheehan's syndrome associated with Glanzmann's thrombasthenia. CASE REPORT: A 41-year-old-woman presented with hemorrhagic diathesis needed blood transfusions occasionally during her life-time. In the course of her second delivery, four units of whole blood transfusion were required to control profuse uterine bleeding and her hemodynamic status. During postpartum period, she was not able to lactate and her menstrual periods did not return. Her hormonal profile revealed gonadotropin, TSH and prolactin deficiencies. CONCLUSION: According to our knowledge, this is the first case report of hypopituitarism developed after delivery in association with Glanzmann's thromboasthenia-induced severe uterine hemorrhage.

The clinical and pharmacoeconomic analysis of invasive aspergillosis in adult patients with haematological diseases.

Invasive pulmonary aspergillosis (IPA) poses major management problems for clinicians caring for patients with haematological diseases. The clinical courses of patients with IPA who had been hospitalised in Hematology Unit, Bone Marrow Transplantation Unit and Infectious Diseases and Clinical Microbiology Unit between 1998 and 2005, the efficacy and adverse effects and costs of antifungal drugs (conventional amphotericin B deoxycholate, liposomal amphotericin B, amphotericin B lipid complex and caspofungin) used in the therapy of these patients were analysed in this study. Ninety-three patients with IPA were reviewed retrospectively. Mean age of the patients was 40.4 +/- 15.1 years (range 14-70 years). Fifty-eight male patients and 35 female patients were included in the study. Manageable hypopotassemia, nausea/vomiting and headache were the most commonly observed side-effects during antifungal (AF) therapy. While it was not found to be statistically significant with regard to the mean time to resolution of fever (P = 0.8), it was found to be statistically significant with regard to radiological regression at 30th day, and mean duration of therapy between patients who were dead or alive (P < 0.05, P < 0.001). Total cost of AF therapy for 93 patients was found to be US$4 461 824 (minimum US$387-maximum US$279 023). Of this amount, US$4 272 845 represents the payment for AF drugs, US$188 979 the payment for other expenditures. Mean cost of therapy for a patient with IPA was found to be US$49 336. Although it seemed to be difficult, investigations should primarily focus on providing standardisation of parameters relating to the duration of AF therapy. Despite the less-than-optimal safety profile of CAB, it often remains to be the preferred first line option for the treatment of fungal infections because of its broad spectrum, activity and low acquisition cost.

Factor XIII Val34Leu polymorphism does not contribute to the prevention of thrombotic complications in patients with antiphospholipid syndrome.

The effect of thrombophilic mutations in the development of thrombosis in patients with antiphospholipid syndrome (APS) has been extensively investigated. Factor XIII (FXIII) Val34Leu polymorphism is a newly described polymorphism which is located in the three amino acids away from the thrombin activation site of the FXIII-A subunit. It has been reported that the Leu allele decreases the risk of both arterial and venous thrombosis. In the present study, we examined the association between the FXIII Val34Leu polymorphism and the development of thrombosis in patients with APS. Sixty APS patients with arterial and venous thrombosis, 22 antiphospholipid antibody (aPLA) positive patients with first trimester abortus and/or thrombocytopenia, 126 healthy controls, and 60 healthy subjects who were age- and sex-matched with thrombotic APS group were included into the study. FXIII Leu allele frequencies in the APS patients with thrombosis, aPLA-positive patients without thrombosis, healthy controls, and matched controls were 13.3, 16, 19.5, and 18.3%, respectively. When we compared Leu allele frequencies between APS patients with thrombosis and aPLA-positive patients without thrombosis, healthy controls or matched controls, we could not find any difference (chi2, p = 0.43, and P = 0.09, P = 0.67, respectively). Our results showed that the FXIII Leu allele has no protective effect in the development of thrombosis in APS.

Myeloid antigen expression provides favorable outcome in patients with adult acute lymphoblastic leukemia: a single-center study.

Between July 1992 and July 2001, 81 patients with de novo adult acute lymphoblastic leukemia (ALL) treated according to the German Multicenter Study Group for Adult ALL (GMALL) 01/81 protocol were evaluated in order to analyze the effect of aberrant myeloid antigen expression on prognosis. We observed myeloid antigen aberrant expression in 21 of the adult ALL cases. We did not observe any effect of aberrant myeloid antigen expression on the time to achieve remission, relapse rate, and death rate. After 5 years of follow-up, cumulative disease-free survival of myeloid antigen (My) (+) and My (-) adult ALL patients was 67% and 43%, respectively. These data were not found to be statistically significant (P=0.29), but we did find a statistically significant difference in overall survivals between these two groups (85% vs 50%) (P=0.05). Twenty-nine patients died and the remaining 52 patients were followed for a median of 31 months. We could not find any special effect of the known prognostic factors on prediction of relapse in multivariate analysis. However, myeloid antigen expression was the most significant factor, which affected long-term survival in our patients (P=0.01). These data indicate that myeloid antigen expression is useful for predicting a favorable outcome of adult patients with ALL.

Antiphospholipid antibodies and antiphospholipid syndrome in patients presenting with immune thrombocytopenic purpura: a prospective cohort study.

The pathogenetic role and the clinical importance of the presence of antiphospholipid antibodies (APAs) in patients with immune thrombocytopenic purpura (ITP) are not clear. In this study, the prevalence and clinical significance of APAs were investigated in patients with ITP. Eighty-two newly diagnosed ITP patients were prospectively studied. They were evaluated for the presence of lupus anticoagulant (LA) and immunoglobulin G/M anticardiolipin antibodies (ACAs). Thirty-one patients (37.8%) were APA positive at diagnosis. No statistically significant differences were found between the APA-positive and APA-negative groups regarding gender, initial platelet counts, or response to methylprednisolone therapy. After 5 years of follow-up, cumulative thrombosis-free survival of APA-positive (n = 31) and APA-negative (n = 51) ITP patients was 39% and 97.7%, respectively. A significant difference was found between these groups by log-rank test (P =.0004). In addition, LA was an important risk marker for the development of thrombosis in ITP patients. After a median follow-up of 38 months, 14 ITP patients (45%) who had APA positivity developed clinical features (thrombosis or fetal losses) of antiphospholipid syndrome (APS). There were no differences between the APA-positive patients with and without APS regarding the initial platelet counts, response to the therapy, or ACA positivity. The positivity rate for LA was significantly higher in those patients with ITP who developed APS (chi(2): P =.0036; relative risk 7.15; 95% confidence interval, 1.7-47). In conclusion, this study indicates that a significant proportion of patients initially presenting with ITP and APA positivity developed APS. In patients with ITP, the persistent presence of APAs is an important risk factor for the development of APS.

Clonality of acquired primary pure red cell aplasia: effectiveness of antithymocyte globulin.

Primary pure red cell aplasia (PRCA) was diagnosed in two male patients, 65 and 69 years old respectively. In both, surface markers of peripheral blood nuclear cells revealed the presence of TCR alphabeta+ phenotype. Clonality of T cells was confirmed by the polymerase chain reaction in both patients, in whom, prednisone at a dose of 1 mg/kg/day improved the anemia and lower doses caused its renewal, resulting in the reappearance of the patient's transfusion requirement. On the other hand, the anemia seems to have been treated permanently (second case) with horse antithymocyte globulin (ATG) (20 mg/kg/day 1 to 8 +) since his hemoglobin was about 15 g/dl at the time of writing. In the first patient, the hemoglobin level was 10.5 g/dl one month after the administration of ATG (15 mg/kg/d 1 to 5 +), but unfortunately, the patient died because of a massive gastrointestinal bleeding on the fortieth day following this treatment. We, therefore, suggest that, patients with acquired primary PRCA should be screened to detect the presence of a T-cell clone and recommend that, treatment should start earlier with ATG, if the PRCA is due to a T-cell clonal disorder.

Leukemia in a patient treated with growth hormone.

It is well known that growth hormone (GH) therapy is associated with increased risk of development of malignant tumors, especially leukemia. In the case presented, growth hormone treatment was initiated in a 25-year-old patient with hypopituitarism. After 4 months of therapy with thrice a week injections of rhGH, acute myelogenous leukemia developed. It was thought that no clearcut evidence existed to establish a relationship between the growth hormone treatment and development of acute leukemia.

Antithrombin III, protein C and protein S plasma levels in patients with Behçet's disease.

The association between natural inhibitors of coagulation and thrombophilia was investigated in 35 patients with Behcet's disease. Antithrombin III and protein C levels were measured using synthetic chromogenic substrate methods, and protein S levels by quantitative enzyme-linked immunosorbent assay. There were no significant differences between patients and controls in plasma antithrombin III, protein C and free protein S concentrations. We conclude that there was no evidence of a primary coagulation inhibitor abnormality in patients with Behçet's disease.

Anemia and thrombocytopenia due to parvovirus B-19 infection in a pregnant woman.

Anemia and thrombocytopenia in a patient with parvovirus B-19 and hepatitis C infection is reported. A seven month-pregnant 20 year-old patient had been first found to be anemic and thrombocytopenic 40 days before admission to our hospital and she had been given methylprednisolone and red cell transfusions. She gave birth to a healthy baby after only eight months of pregnancy. Ten days after delivery she was admitted to our hospital because of anemia and thrombocytopenia which did not respond to treatment. On admission, the blood count showed hemoglobin 8.1 g/dL, hematocrit 23.7%, white blood cells 11,200/microL, platelets 1000/microL, and reticulocytes 0.6%. Bone marrow smear and biopsy revealed erythroblastopenia and the absence of megakaryocytes. Liver enzymes were also high (alanine aminotransferase 1469 Units/L and aspartate aminotransferase 981 Units/L). In serologic studies PVB-19 IgM was found to be positive and hepatitis C virus RNA was detected. Red cell and platelet values returned to normal levels after cessation of methylprednisolone and concomitantly PVB-19 IgG was found positive in association with IgM in repeated determinations. PVB-19 was thought to be responsible for both anemia and thrombocytopenia.