Identification of clinical and simple laboratory variables predicting responsible gastrointestinal lesions in patients with iron deficiency anemia

Iron deficiency anemia (IDA) is a frequent disorder. Also, it may be a sign of underlying serious diseases. Iron deficiency points to an occult or frank bleeding lesion when occurred in men or postmenopausal women. In this study, we aimed to evaluate the diagnostic yield of endoscopy in patients with IDA and to define predictive factors of gastrointestinal (GI) lesions causing IDA. Ninety-one patients (77 women, 14 men; mean age: 43 years) who were decided to have esophago-duodenoscopy and/or colonoscopy for iron deficiency anemia were interviewed and responded to a questionnaire that included clinical and biochemical variables. The endoscopic findings were recorded as GI lesions causing IDA or not causing IDA. Endoscopy revealed a source of IDA in 18.6 % of cases. The risk factors for finding GI lesions causing IDA were as follows: male gender (p= 0.004), advanced age (> 50 years) (p= 0.010), weight loss (over 20% of total body weight lost in last 6 month) (p= 0.020), chronic diarrhea (p= 0.006), change of bowel habits (p= 0.043), epigastric tenderness (p= 0.037), raised carcinoembryonic antigen (CEA) level (normal range: 0-7 ng/mL) (p= 0.039), < 10 gr/dl hemoglobin (Hb) level (p=0.054). None of these risk factors had been present in 21 (23%) women younger than 51 years. In this group, no patient had any GI lesion likely to cause IDA (negative predictive value= 100%). In multivariate analysis, advanced age (p=0.017), male gender (p< 0.01) and weight lost (p=0.012) found that associated with GI lesions in all patients. It may be an appropriate clinical approach to consider these risk factors when deciding for gastrointestinal endoscopic evaluation in iron deficiency anemia

DOWNREGULATION OF STEAROYL-COA DESATURASE 1 (SCD-1) PROMOTES RESISTANCE TO IMATINIB IN CHRONIC MYELOID LEUKEMIA

Chronic myeloid leukemia (CML) is a malignant hematopoietic stem cell disease resulting in the fusion of BCR and ABL genes and characterized by the presence of the reciprocal translocation t(9;22)(q34;q11). BCR-ABL, a product of the BCR-ABL fusion gene, is a structurally active tyrosine kinase and plays an important role in CML disease pathogenesis. Imatinib mesylate (IMA) is a strong and selective BCR-ABL tyrosine kinase inhibitor. Although IMA therapy is an effective treatment, patients may develop resistance to IMA therapy over time. This study investigated the possible genetic resistance mechanisms in patients developing resistance to IMA. We did DNA sequencing in order to detect BCR-ABL mutations, which are responsible for IMA resistance. Moreover, we analyzed the mRNA expression levels of genes responsible for apoptosis, such as BCL-2, P53, and other genes (SCD-1, PTEN). In a group of CML patients resistant to IMA, when compared with IMA-sensitive CML patients, a decrease in SCD-1 gene expression levels and an increase in BCL-2 gene expression levels was observed. In this case, the SCD-1 gene was thought to act as a tumor suppressor. The present study aimed to investigate the mechanisms involved in IMA resistance in CML patients and determine new targets that can be beneficial in choosing the effective treatment. Finally, the study suggests that the SCD-1 and BCL-2 genes may be mechanisms responsible for resistance. Keywords  CML; Imatinib resistance; BCR-ABL mutations; SCD-

Chronic Liver Diseases And Iron: A Concise Review With Emphasis On Hypotransferrinemia And Hypohepcidinemia

Iron studies in chronic liver diseases (CLDs) have a long history. Currently we can mention certainties, uncertainties, and hopes related to this topic. It is certain that iron metabolism problems and hepatic siderosis are frequent in CLDs and they get more frequent as CLD progresses, but true iron overload is rare. There are conflicting literature data on the mechanism of siderosis, the role of iron in CLD pathogenesis, and the potential benefits of iron removal. We may hope that pharmacological approaches targeting iron metabolism disorders of CLD will be actively evaluated in the future. In this review, we aimed to present a general outlook of this extensively studied topic.WoSScopu

Use Of Second Generation Tyrosine Kinase Inhibitors For Second-Line Treatment Of Chronic Myeloid Leukemia After Imatinib Failure

Invention of imatinib was a great step for much more successful clinical management of chronic myeloid leukemia (CML). Now, two other tyrosine kinase inhibitors (TKIs) are available both for first-line and later treatments of CML. In Turkey, currently 2nd line TKIs are indicated only for imatinib failure. This review will evaluate indications for changing imatinib with dasatinib or nilotinib, success of the 2nd line agents in the second-line treatment and some important properties of these agents.WoSScopu

Clinical Investigation Of Oral Findings In Inherited Disorders Of Platelet Function

Objective: Bleeding disorders are a very important health problem due to the associated high risk of hemorrhage during dental procedures. The present study aimed to investigate oral manifestations of inherited disorders of platelet function (IDPF). Materials and Methods: The study included 20 IDPF patients (mean age: 31.90 +/- 10.71 years) and 40 healthy controls (mean age: 31.63 +/- 9.07 years). Tooth brushing habits, level of education, and clinical index scores (Simplified Oral Hygiene Index [OHI-S], Decayed Missing Filled Teeth Index [DMFT] index, probing depth [PD] index, Gingival Bleeding Index [GB!], and Community Periodontal Index [CPI]) were recorded. Results: There weren't any significant differences between the 2 groups with respect to tooth brushing habit, level of education level, OHI-S, DMFT index, or CPI (p>0.05), whereas significant differences in PD index and GBI were observed between the groups (p<0.05). Conclusion: The present study's findings show that IDPF has a negative effect on periodontal tissues. (Turk J Hematol 2011; 28: 294-8)WoSScopu

Real-life outcomes of unselected acute promyelocytic leukemia patients: a single-center 14-year experience

Background. After the inclusion of all-trans retinoic acid (ATRA) into the treatment of Acute Promyelocytic leukemia (APL), a notable improvement concerning the survival rates of patients with APL has been observed. However, the population-based studies demonstrated that there was no marked improvement in the survival of patients after the 2000s. We aim to describe the clinical response and prognosis of adult patients diagnosed with APL and examine the change in these outcomes by the time period of diagnosis

Free Protein S Reference Ranges In Gravidas Without Hereditary And Acquired Thrombophilia

We carried out a retrospective cohort study to construct reference ranges for free protein S (FPS) levels during pregnancy and identify any conditions or factors that may affect FPS levels. Patients that were ordered thrombophilia screening tests during gestational period were identified. Patients demonstrated to have hereditary or acquired thrombophilia were excluded. Reference ranges were constructed using regression analysis. Outcome of the index pregnancy and pregnancy complications was used to identify any confounding factors. A total of 455 pregnant women were included. The quadratic equation for FPS according to gestational age (GA) was [75.497 + (-1.516*GA) + 0.018*GA*GA]. FPS level and GA were negatively correlated (Spearmans rho statistic [r(s)] = -0.436, p = 0.001). FPS level and fetal growth restriction (FGR) were negatively correlated ([r(s)] = -0.093, p = 0.049). FPS level and placental abruption were positively correlated ([r(s)] = 0.098, p = 0.039). Stepwise linear regression model constructed to predict FPS level with gestational age, placental abruption and FGR as the predictor variables. Gestational age was the only variable retaining statistically significant relation with FPS level (chi(2) = 0.216, df = 3, p = 0.001). FPS levels decrease significantly throughout gestation in gravidas without hereditary and/or acquired thrombophilias. In patients without thrombophilia FPS levels are not associated with pregnancy complications. The obtained reference intervals may be useful for the clinicians ordering FPS during pregnancy

Does Endothelium Agree With the Concept of Idiopathic Hepatic Vessel Thrombosis?

AIM: To investigate the major steps of thrombogenesis and to identify the differences in these steps between idiopathic patient group and control group. METHODS: Fibrinogenesis was studied by measuring the activated factor VII, total and free levels of tissue factor pathway inhibitor (TFPI). The fibrinolysis step was investigated by determining the global fibrinolytic capacity. The endothelial function was assessed by measuring the levels of soluble adhesion molecules, namely soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1) and soluble E-selectin molecule. The exclusion criteria from "idiopathic" patient group were abdominal surgery, pregnancy, use of oral contraceptives, anti-phospholipid syndrome, Behcet's disease, cancer, myeloproliferative diseases. The congenital factors like mutations of factor-V Leiden and prothrombin, deficiencies of proteins C and S, antithrombin, hyperhomocysteinernia and hyperfibrinogenemia were ruled out. The total number of patients was reduced from 96 to 9 (7 with portal vein thrombosis, 2 Budd Chiari syndrome) by exclusion criteria. RESULTS: The levels of adhesion molecules sICAM-1, sVCAM-1, free TFPI levels and global fibrinolytic capacity were significantly different (P < 0.05) in the patient group indicating an endothelial dysfunction and a lower fibrinolytic activity. CONCLUSION: These results show that this patient group should be tested by means of enclothelial dysfunction and managed differently. (c) 2006 The WIG Press. All rights reserved.Wo

Functional Exhaustion Of Cd4(+) T Cells Induced By Co-Stimulatory Signals From Myeloid Leukaemia Cells

To cope with immune responses, tumour cells implement elaborate strategies such as adaptive resistance and induction of T-cell exhaustion. T-cell exhaustion has been identified as a state of hyporesponsiveness that arises under continuous antigenic stimulus. Nevertheless, contribution of co-stimulatory molecules to T-cell exhaustion in cancer remains to be better defined. This study explores the role of myeloid leukaemia-derived co-stimulatory signals on CD4(+) T helper (Th) cell exhaustion, which may limit anti-tumour immunity. Here, CD86 and inducible T-cell co-stimulator ligand (ICOS-LG) co-stimulatory molecules that are found on myeloid leukaemia cells supported Th cell activation and proliferation. However, under continuous stimulation, T cells co-cultured with leukaemia cells, but not with peripheral blood monocytes, became functionally exhausted. These in vitro-generated exhausted Th cells were defined by up-regulation of programmed cell death 1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte activation gene 3 (LAG3) and T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) inhibitory receptors. They were reluctant to proliferate upon re-stimulation and produced reduced amounts of interleukin-2 (IL-2), tumour necrosis factor- (TNF-) and interferon- (IFN-). Nonetheless, IL-2 supplementation restored the proliferation capacity of the exhausted Th cells. When the co-stimulation supplied by the myeloid leukaemia cells were blocked, the amount of exhausted Th cells was significantly decreased. Moreover, in the bone marrow aspirates from patients with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS), a subpopulation of Th cells expressing PD-1, TIM-3 and/or LAG3 was identified together with CD86(+) and/or ICOS-LG(+) myeloid blasts. Collectively, co-stimulatory signals derived from myeloid leukaemia cells possess the capacity to facilitate functional exhaustion in Th cells.Wo