Current Issue : April - June Volume : 2012 Issue Number : 2 Articles : 7 Articles
In pathological conditions with concurrent neutrophilia, modifications of erythrocyte membrane proteins are reported. In chronic\r\nmyeloid leukemia (CML), amyeloproliferative disease wherein neutrophilia is accompanied by enhanced erythrophagocytosis, we\r\nreport for the first time excessive cleavage of erythrocyte band 3. Distinct fragments of band 3 serve as senescent cell antigens\r\nleading to erythrophagocytosis. Using immunoproteomics, we report the identification of immunogenic 43 kDa fragment of band\r\n3 in 68% of CML samples compared to their detection in only 38% of healthy individuals. Thus, excessive fragmentation of band\r\n3 in CML, detected in our study, corroborated with the eryptotic phenotype. We demonstrate the role of neutrophilic cathepsin\r\nG, detected as an immunogen on erythrocyte membrane, in band 3 cleavage. Cathepsin G from serum adsorbs to the erythrocyte\r\nmembrane to mediate cleavage of band 3 and therefore contribute to the eryptotic phenotype in CML....
Introduction. Patients with �Ÿ-thalassemia intermedia have a higher incidence of thromboembolic events compared to the general\r\npopulation. Previous studies have shown that patients with sickle cell disease, who are also prone to ischemic events, have higher\r\nintracranial arterial blood flow velocities measured by transcranial Doppler sonography (TCD). The aim of this study is to evaluate\r\nintracranial arterial flow velocities in patients with �Ÿ-thalassemia intermedia and compare the results with those found in healthy\r\nsubjects. Methods. Sixty-four patients with �Ÿ-thalassemia intermedia and 30 healthy subjects underwent transcranial Doppler\r\nsonography. Results. Significantly higher flow velocities were found in intracranial arteries of patients compared to controls (P =\r\n0.001). Previously splenectomized patients with thrombocytosis showed higher flow velocities than nonsplenectomized patients\r\nwithout thrombosis. Conclusion. The increased flow velocities in patients with �Ÿ-thalassemia intermedia may point to a higher risk\r\nof ischemic events. Preventive measures such as blood transfusion or antiplatelet treatment may be beneficial in these patients....
Background: The monitoring of BCR-ABL transcript levels by real-time quantitative polymerase chain reaction\r\n(RT-qPCR) has become important to assess minimal residual disease (MRD) and standard of care in the treatment\r\nof chronic myeloid leukemia (CML). In this study, we performed a prospective, sequential analysis using RT-qPCR\r\nmonitoring of BCR-ABL gene rearrangements in blood samples from 91 CML patients in chronic phase (CP) who\r\nachieved complete cytogenetic remission (CCyR) and major molecular remission (MMR) throughout imatinib\r\ntreatment.\r\nMethods: The absolute level of BCR-ABL transcript from peripheral blood was serially measured every 4 to 12\r\nweeks by RT-qPCR. Only level variations > 0.5%, according to the international scale, was considered positive.\r\nSequential cytogenetic analysis was also performed in bone marrow samples from all patients using standard\r\nprotocols.\r\nResults: Based on sequential analysis of BCR-ABL transcripts, the 91 patients were divided into three categories:\r\n(A) 57 (62.6%) had no variation on sequential analysis; (B) 30 (32.9%) had a single positive variation result obtained\r\nin a single sample; and (C) 4 (4.39%) had variations of BCR-ABL transcripts in at least two consecutive samples. Of\r\nthe 34 patients who had elevated levels of transcripts (group B and C), 19 (55.8%) had a < 1% of BCR-ABL/BCR\r\nratio, 13 (38.2%) patients had a 1% to 10% increase and 2 patients had a >10% increase of RT-qPCR. The last two\r\npatients had lost a CCyR, and none of them showed mutations in the ABL gene. Transient cytogenetic alterations\r\nin Ph-negative cells were observed in five (5.5%) patients, and none of whom lost CCyR.\r\nConclusions: Despite an increase levels of BCR-ABL/BCR ratio variations by RT-qPCR, the majority of CML patients\r\nwith MMR remained in CCyR. Thus, such single variations should neither be considered predictive of subsequent\r\nfailure and nor an indication for altering imatinib dose or switching to second generation therapy. Changing of\r\nimatinib on the basis of BCR-ABL/BCR% sustained increase and mutational studies is a prudent approach for\r\npreserving other therapeutic options in imatinib-resistant patients....
Background: Chronic Myeloid Leukemia (CML) is caused by the abnormal fusion protein BCR-ABL1, a constitutively\r\nactive tyrosine kinase and product of the Philadelphia chromosome. Gleevec (Imatinib mesylate) is a selective\r\ninhibitor of this kinase. Treatment with this agent is known to result in hematologic, cytogenetic, and molecular\r\nresponses. Patan hospital (Patan, Nepal) is one of the Gleevec International Patient Assistance Program (GIPAP)\r\ncenters for patients with CML.\r\nMethods: A total of 106 Philadelphia positive CML patients were enrolled in our center between Feb 2003 and\r\nJun 2008, and 103 of them were eligible for cytogenetic and/or hematologic response analyses.\r\nResults: Out of 103 patients, 27% patients underwent cytogenetic analysis. Imatinib induced major cytogenetic\r\nresponses in 89% and complete hematologic responses in almost 100% of the patients with confirmed CML. After\r\na mean follow up of 27 months, an estimated 90% of the patients on imatinib remained in hematologic remission\r\nand more than 90% of the patients are still alive. About 30% of patients developed some form of manageable\r\nmyelosuppression. A few patients developed non-hematologic toxic side effects such as edema and hepatotoxicity.\r\nConclusions: Our study demonstrates that imatinib is safe to use in a developing country. Furthermore, we\r\ndemonstrate that imatinib is very effective and induced long lasting responses in a high proportion of patients\r\nwith Ph chromosome/BCR-ABL1 positive CML. Imatinib is well tolerated by our patients. The lack of cytogenetic\r\nanalysis in the majority of our patients hindered our ability to detect inadequate responses to imatinib and adjust\r\ntherapy appropriately....
Background: There are many descriptions of the association of pica with iron deficiency in adults, but there are\r\nfew reports in which observations available at diagnosis of iron deficiency were analyzed using multivariable\r\ntechniques to identify significant predictors of pica. We sought to identify clinical and laboratory correlates of pica\r\nin adults with iron deficiency or depletion using univariable and stepwise forward logistic regression analyses.\r\nMethods: We reviewed charts of 262 non-pregnant adult outpatients (ages =18 y) who required treatment with\r\nintravenous iron dextran. We tabulated their sex, age, race/ethnicity, body mass index, symptoms and causes of\r\niron deficiency or depletion, serum iron and complete blood count measures, and other conditions at diagnosis\r\nbefore intravenous iron dextran was administered. We excluded patients with serum creatinine >133 �µmol/L or\r\ndisorders that could affect erythrocyte or iron measures. Iron deficiency was defined as both SF <45 pmol/L and TS\r\n<10%. Iron depletion was defined as serum ferritin (SF) <112 pmol/L. We performed univariable comparisons and\r\nstepwise forward logistic regression analyses to identify significant correlates of pica.\r\nResults: There were 230 women (184 white, 46 black; ages 19-91 y) and 32 men (31 white, 1 black; ages 24-81 y).\r\n118 patients (45.0%) reported pica; of these, 87.3% reported ice pica (pagophagia). In univariable analyses, patients\r\nwith pica had lower mean age, black race/ethnicity, and higher prevalences of cardiopulmonary and epithelial\r\nmanifestations. The prevalence of iron deficiency, with or without anemia, did not differ significantly between\r\npatients with and without pica reports. Mean hemoglobin and mean corpuscular volume (MCV) were lower and\r\nmean red blood cell distribution width (RDW) and platelet count were higher in patients with pica. Thrombocytosis\r\noccurred only in women and was more prevalent in those with pica (20.4% vs. 8.3%; p = 0.0050). Mean total ironbinding\r\ncapacity was higher and mean serum ferritin was lower in patients with pica. Nineteen patients developed\r\na second episode of iron deficiency or depletion; concordance of recurrent pica (or absence of pica) was 95%.\r\nPredictors of pica in logistic regression analyses were age and MCV (negative associations; p = 0.0250 and 0.0018,\r\nrespectively) and RDW and platelet count (positive associations; p = 0.0009 and 0.02215, respectively); the odds\r\nratios of these predictors were low.\r\nConclusions: In non-pregnant adult patients with iron deficiency or depletion, lower age is a significant predictor\r\nof pica. Patients with pica have lower MCV, higher RDW, and higher platelet counts than patients without pica....
Background: Glucose-6-Phosphate dehydrogenase (G6PD) is a key enzyme of the pentose monophosphate pathway,\r\nand its deficiency is the most common inherited enzymopathy worldwide. G6PD deficiency is common among Iraqis,\r\nincluding those of the Kurdish ethnic group, however no study of significance has ever addressed the molecular basis\r\nof this disorder in this population. The aim of this study is to determine the prevalence of this enzymopathy and its\r\nmolecular basis among Iraqi Kurds.\r\nMethods: A total of 580 healthy male Kurdish Iraqis randomly selected from a main regional premarital screening\r\ncenter in Northern Iraq were screened for G6PD deficiency using methemoglobin reduction test. The results were\r\nconfirmed by quantitative enzyme assay for the cases that showed G6PD deficiency. DNA analysis was performed on\r\n115 G6PD deficient subjects, 50 from the premarital screening group and 65 unrelated Kurdish male patients with\r\ndocumented acute hemolytic episodes due to G6PD deficiency. Analysis was performed using polymerase chain\r\nreaction/restriction fragment length polymorphism for five deficient molecular variants, namely G6PD Mediterranean\r\n(563 C?T), G6PD Chatham (1003 G?A), G6PD A- (202 G?A), G6PD Aures (143 T?C) and G6PD Cosenza (1376 G?C),\r\nas well as the silent 1311 (C?T) mutation.\r\nResults: Among 580 random Iraqi male Kurds, 63 (10.9%) had documented G6PD deficiency. Molecular studies\r\nperformed on a total of 115 G6PD deficient males revealed that 101 (87.8%) had the G6PD Mediterranean variant and\r\n10 (8.7%) had the G6PD Chatham variant. No cases of G6PD A-, G6PD Aures or G6PD Cosenza were identified, leaving 4\r\ncases (3.5%) uncharacterized. Further molecular screening revealed that the silent mutation 1311 was present in 93/95\r\nof the Mediterranean and 1/10 of the Chatham cases.\r\nConclusions: The current study revealed a high prevalence of G6PD deficiency among Iraqi Kurdish population of\r\nNorthern Iraq with most cases being due to the G6PD Mediterranean and Chatham variants. These results are similar to\r\nthose reported from neighboring Iran and Turkey and to lesser extent other Mediterranean countries....
Background: The first survey on sickle cell disease (SCD) done in Uganda in 1949, reported the district of Bundibugyo\r\nin Western Uganda to have the highest sickle cell trait (SCT) prevalence (45%). This is believed to be the highest in the\r\nwhole world. According to the same survey, the prevalence of SCT in the districts of Mbale and Sironko in the East was\r\n20-28%, whilst the districts of Mbarara and Ntungamo in the West had 1-5%. No follow-up surveys have been\r\nconducted over the past 60 years. SCA accounts for approximately 16.2% of all pediatric deaths in Uganda. The pattern\r\nof SCT inheritance, however, predicts likely changes in the prevalence and distribution of the SCT. The objective of the\r\nstudy therefore was to establish the current prevalence of the SCT in Uganda.\r\nMethods: This study was a cross sectional survey which was carried out in the districts of Mbale and Sironko in the\r\nEastern, Mbarara/Ntungamo and Bundibugyo in Western Uganda. The participants were children (6 months-5 yrs).\r\nBlood was collected from each subject and analyzed for hemoglobin S using cellulose acetate Hb electrophoresis.\r\nResults: The established prevalence of the SCT (As) in Eastern Uganda was 17.5% compared to 13.4% and 3% in\r\nBundibugyo and Mbarara/Ntungamo respectively. 1.7% of the children in Eastern Uganda tested positive for\r\nhaemoglobin ss relative to 3% in Bundibugyo, giving gene frequencies of 0.105 and 0.097 for the recessive gene\r\nrespectively. No ss was detected in Mbarara/Ntungamo.\r\nConclusions: A shift in the prevalence of the SCT and ss in Uganda is notable and may be explained by several\r\nbiological and social factors. This study offers some evidence for the possible outcome of intermarriages in reducing\r\nthe incidence of the SCT....
Loading....