摘要：The chronic myeloproliferative neoplasms (CMPN) are a group of clonal hematopoietic stem cell disorders in which large numbers of red blood cells, white blood cells, or platelets grow and spread excess in the bone marrow and the pe- ripheral blood. Cytogenetic analysis of the t (9:22) and molecular detection of BCR/ABL is the main diagnostic criteria in Philadelphia positive CMPN (CML). The identification of non-receptor tyrosine kinase JAK2 mutations (exon 14 JAK2 V617F and exon 12) have significantly contributed to our understanding of the molecular mechanisms in the pathogenesis of Philadelphia negative CMPN such as polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients. According to the revised WHO classification, JAK2 mutation is considered as a major diagnostic and clonal marker in Philadelphia negative CMPN which will play a major role in designing personal- ized treatments for the disease. JAK2 V617F mutation frequency is unknown in Saudi Arabia. Therefore, investigation of the JAK2 V617F mutation was carried out in DNA samples from 78 peripheral blood specimens corresponding to patients with polycythemia vera (PV) (n = 11), Chronic myeloid leukemia (CML) (n = 45), essential thrombocythemia (ET) (n = 10), idiopathic myelofibrosis (MF) (n = 12). We used polymerase chain reaction and direct DNA sequencing to detect the JAK2 mutation. Overall, the incidence of the JAK2 V617F mutation was 91% in PV, 40% in ET, and 25% in MF. This approach proved to be reliable and more sensitive in detecting the mutation. Two essential findings arose from our study. First, this technique could be carried out with DNA samples, even partially degraded, from routinely processed BM or peripheral blood specimens. Second, after correlation with morphological features, it turned out that the characteristics of the megakaryocytes were more specific than the mutational status of JAK2 in characterizing ET and PMF. Concerning PV, as expected, the incidence of the JAK2 mutation was higher, but the morphological criteria were misleading in some cases, strongly suggesting that the combination of both morphology and molecular data would enable the characterization of virtually all cases. JAK2 V617F mutation frequency along with accurate morphological characterization is very reliable tool in diagnosing and classifying CMPN in Saudi patients....
摘要：Haemoglobinopathies are group of diseases characterized by abnormalities both quantitative and qualitative in the synthesis of haemoglobin. Haemoglobinopathies consist of sickle cell anaemia (SCA), thalassaemia (βT) and variant haemoglobins. In India, they are responsible for the largest number of genetic disorders and hence are of great public health hazardous. In India major concerned haemoglobinopathic disorders are sickle cell anaemia and β-thalassaemia. Of the several abnormal haemoglobin molecules, four which are widely prevalent in India include: HbS, HbβT, HbE and HbD. Examination of 6463 individuals showed high incidences for haemoglobin variants, HbS and HbβT in different ethnic groups, the frequency being varies from 0% - 20% and 0% - 9% respectively. The frequency of HbS in Brahmins is 4.17%, in Kalar 5.41%, in Rajput 2.04%, in Muslims 3.73% in Maratha 2.08% in Bania 9.09% while in Teli it is 3.65%. Among the Scheduled castes and Nomadic tribal groups HbS ranges from 1% - 12%; in backward caste categories it varies from 3% - 16%; while in Scheduled tribes it ranges from 0% - 20%. The high magnitude of sickle cell trait has been noticed in the Pardhan (20.31%) followed by the Marar (16.10%), the Dhiwar (11.90%), the Gond (11.89%), the Mahar (11.81%) and the Bania (9.90%). A considerable high frequency (9.27%) of β-thalassaemia has been observed among the Sindhi population. Sporadic occurrence of HbβT and HbD among other communities suggested the gradual spread of the genes into the region. The present findings in 11 communities with the thalassaemia syndrome suggest that the β-thalassaemia is accompanied by raised level of HbA2. Unusual greater mean RBC and WBC suggest the high concentration of hypochromic microcytosis in anaemia. The mean MCV and MCH in HbβT and HbD are much lower than the normal ranges compared to HbS. The mean MCHC is much lower in HbβT, HbDD and HbS than the normal range. The cumulative gene frequency of haemoglobinopathies in India is 4.2%. With a population of over 1 billion and a birth rate of 28 per 1000, there are over 42 million carriers and over 12,000 infants are born each year with a major and clinical significant haemoglobinopathy. Out of these, clinically significant sickle cell anaemia and β-thalassaemic disorders account for almost equal numbers....
摘要：Background: The effect of repeated blood donation on some biochemical values of healthy adult male blood donors in Calabar, Nigeria was studied. Methods: One hundred and fifty three (153) healthy repeat blood donors and 90 first time blood donors constituted the study population. Samples were analyzed using colorimetric procedures. Results: The BMI values of 24.4 ± 2.4 kg/ m2 in the first time donors was significantly higher than the 21.7 ± 1.7 kg/m2 obtained in repeat donors (P < 0.001). Among all the biochemical parameters, total cholesterol showed a significant change of 2.55 ± 0.74 mmol/l after repeated donations as compared to 3.45 ± 1.47 mmol/l in the first time donors (P < 0.005). Gamma glutamyl transferase (GGT) was significantly higher in repeat donors (70.5 ± 13.5 μl) than the first time donors (62.5 ± 13.3 μl) (P < 0.05). An LDL value of 1.02 ± 0.8 mmol/l in repeat donors was significantly lower than 1.69 ± 1.0 mmol/l in first time donors (P < 0.05). A VLDL value of 0.32 ± 0.2 mmol/l in repeat donors was equally lower than 0.44 ± 0.2 mmol/l obtained in the first time donors (P < 0.05). GGT showed positive correlation with lactate dehydrogenase (LDH) and low density lipoproteins (LDL) at P < 0.05 and P < 0.01 respectively among the repeat blood donors. Triglycerides showed a positive correlation with very low density lipoprotein (VLDL) among repeat donors at P < 0.05 significant level. Pearson correlation analysis also indicates that a significant positive relationship exists between GGT and low density lipoprotein (r = 0.891, P < 0.001). The regression analysis defined the relationship as linear (y = 0.0578x + 36.87; r2 = 0.7934, P < 0.05). Conclusion: A reduction in the values of some lipid profiles and high GGT activity is associated with repeated blood donations in this study population. Repeated blood donation may play a significant role in reducing the incidence of heart disease....
摘要：We describe the effects of Darbepoietin-alfa (Darbe) administration in Multiple Myeloma (MM) after autologous he-mopoietic progenitor cell transplantation (AHPCT). 26 MM patients undergoing AHPCT entered this study. 34 hemo-globin (Hb)-matched patients who had not received recombinant human erythropoietin (Epo) or Darbe and were treated with the same protocol were retrospectively selected for comparative data. Darbe (150 micro g total dose/weekly) was initiating in four weeks after AHPCT, with the aim of achieving an Hb level of ≥11 g/dl. The time to response to Darbe therapy was longer in the patients with Hb < 10 g/dL (p = 0.05) and with endogenous Epo levels ≤ 50 mU/ml (p = 0.0098). Hb level on day 60 and 90 after AHPCT, was faster for Darbe recipients (12.5, range 9.4 - 15.4, vs 10.6, range 8.8 - 13.4 g/dL, p = 0.0001, and 13.5, range 12.3 - 14.3, vs 12, range 9.8 - 14 g/dL, respectively, p = 0.0001). The need for Red Blood Cells transfusion, included in the period of 30 - 90 days post- AHPCT was similar (p = ns). This study demonstrates the accelerating effect of Darbe on Hb increase in the setting evaluated and shows that this effect signify- cantly depends on the endogenous Epo level at the start of treatment. The strategy of giving Darbe around 1 month after high-dose melphalan (HDM) doesn't reduce RBC transfusion requirement....
摘要：Quantification of the BCR-ABL transcript is recommended to follow-up CML patients treated by imatinib mesylate (IM). Results are expressed as a normalized copy number (NCN) of BCR-ABL. We studied a cohort of 98 CML patients under IM as a first treatment and monitored by RQ-PCR after 12, 18 and 24 months according to the European LeukemiaNet recommendations. Our results support the hypothesis of an independent correlation between BCR-ABL NCN at diagnosis and major molecular response at 18 and 24 months in an inverse relationship. We also highlighted the possibility to use the NCN at diagnosis as a warning at diagnosis, and may be useful to identify patients who could benefit of a more rigorous follow-up....
摘要：The TEL/ARG oncogene is similar in structure to the TEL/ABL fusion found in human leukemia, however, we have demonstrated previously that the expression of TEL/ARG in Ba/F3 cells does not sustain strong activity of proliferation, whereas, that of TEL/ABL appeared to induce immediate cell proliferation. To study the molecular basis of the difference in the transforming activity of TEL/ARG and TEL/ABL, TEL/ARG mutants that swapped the kinase domain or C-terminus of ARG with the corresponding domain in ABL were generated, and each mutant was expressed in Ba/F3 cells. A TEL/ARG mutant containing the ABL kinase domain was similar to TEL/ARG in this study, but replacing the ARG C-terminal domain with that of ABL resulted in accelerated proliferation that was similar to that of TEL/ABL. When expressed in primary mouse bone marrow cells by retroviral transduction, spontaneous colony formation in methylcellulose culture was observed, in a fashion dependent on the C-terminal portion of ABL. These results indicate that distinct bio-phenotypes associated with these oncogenes are likely to be regulated by their C-termini, and the C-terminus of ARG contains a functional subdomain that impairs the growth signal induced by ABL family tyrosine kinase....
摘要：IgG Heavy Chain Disease (γHCD) is a rare plasma cell disorder. Hypercalcemia related to plasma cell dyscrasias is related to non-PTHrP related mechanisms. Here we describe the first case of a patient with γHCD and PTHrP related hypercalcemia. Methods: Patient case derived from chart review from 2011 to 2015. Literature review performed searching PubMed 1968-current. Results: The patient was diagnosed with hypercalcemia with elevated PTHrP and exclusion of other etiologies of hypercalcemia. She was diagnosed with (γHCD) by M-spike 0.64 g/dL, IFE showing a broad band of IgG heavy chain, without associated light chains and severe depression of the non-mono-clonal IgG. Serum immunoglobulins demonstrated elevated IgG (2110 mg/dL), normal IgA (46 mg/dL) and decreased IgM (<21 mg/dL). Bone marrow biopsy showed 5% PCs, non-clonal by kappa/lambda, but exclusive for IgG by IHC, without any staining for IgA or IgM. The patient was started on therapy with improved hypercalcemia and PTHrP levels. Conclusions: This is the first reported case of γHCD presenting with PTHrP related hypercalcemia. Given that skeletal involvement is uncommon in γHCD, hypercalcemia secondary to γHCD may at times be a PTHrP driven phenomenon and we recommend that this test be ordered in such cases....
摘要：Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course. Microarray studies allowed highlight genes differentially expressed in this pathology. In this study, we have evaluated the prognostic significance of SEPT10 expression in CLL patients. Results were correlated with immunoglobulin heavy-chain variable (IGHV) genes mutational status, genomic rearrangements and clinical parameters. SEPT10 mRNA levels were determined by quantitative real-time PCR in 70 newly diagnosed CLL patients consecutively referred to our Institution. A wide heterogeneity for SEPT10 expression was found. Gene upregulation was observed in 18.5% of cases. The univariate analysis showed a positive association between gen expression and platelet count (p < 0.0001) and a negative correlation with hemoglobin levels (p = 0.0094). Although no significant differences were observed, mean treatment free survival was shorter in patients with high expression (31 months) with respect to those with low mRNA levels (72 months). Cases with abnormal karyotypes had increased expression compared to those with normal karyotypes and no association between gene expression and FISH (fluorescence in situ hybridization) risk groups and IGHV mutational status was found. Cases using IGHV3-23 gene rearrangement had low SEPT10 expression. Our results showed an association between SEPT10 expression and features of adverse outcome but without independent prognostic value. The study of SEPT10 expression may be important for a better understanding of disease heterogeneity, adding further information to those provided by established prognostic factors....
style="font-family:Verdana;">CD40 ligation provides
signals central to chronic lymphocytic leukemia (CLL) cell survival and
proliferation. The re style="font-family:Verdana;">lease
of soluble CD40 (sCD40) may impact on both these signals and CD40 targeted
therapies. In this study we inves style="font-family:Verdana;">tigated the prognostic significance of plasma sCD40 inuntreated CLL patients (n style="font-family:Verdana;">= style="font-family:Verdana;">34). We report that 56% had levels
higher than those of normal donors and that elevated levels were associated
with significantly shorter treatment free (TFS) and overall survival. In
bivariate analysis sCD40 remained a significant marker of TFS independent of
Binet staging, CD38 positivity and lymphocyte count. RT-PCR analysis
demonstrated that CLL cells expressed transcripts encoding putative sCD40.
These results suggest sCD40 may play a role in CLL progression and that its
function, prog style="font-family:Verdana;">nostic
significance and potential impact on antibody based therapies should be further
摘要：Whole blood and its respective blood components are indispensable in today's
medical practice and their use is associated with significant costs. Blood utilization
and blood transfusion costs are generally perceived to be increasing at a time when
healthcare budgets continue being constricted. This may have far reaching consequences,
particularly in resource limited settings where healthcare spending is mainly
foreign funded. A cost-activity based blood transfusion study was carried out at a
large urban hospital in Harare, Zimbabwe on 100 patients prospectively. The inclusion
criteria took into consideration only pregnant women between the ages 15 and
50 years receiving blood transfusion. Activity based costing was achieved through
prospectively following the activities of blood transfusion from the point of collection,
storage, matching, pre-transfusion preparations, transfusion and post-transfusion,
as well as hospitalisation services costs. The average cost of blood transfusion was
found to be $540.71 from the provider's perspective. This cost was compared with
the gross domestic per capita and the poverty datum line of Zimbabwe. A continuous
review of transfusion systems to alter the supply chain system into a very economic
system was recommended....
style="font-family:Verdana;font-size:12px;">Hematopoietic stem cell transplantation(HSCT)has emerged as a curative strategy for sickle cell anemia(SCA);
it is necessary to find markers of SCA clinical severity to spare those SCA
patients whose clinical course is mild from the morbidity and mortality
associated with HSCT. Haplotypes have been correlated with the severity of
clinical manifestations in SCA patients, and fetal hemoglobin(HbF)and socioeconomic status(SeS)have also been described as negative factors. We studied these factors and
their impact on clinical manifestations in a population of Southern Brazilian
patients attending the Center for Sickle Cell Anemia at Hospital de Clínicas de
Porto Alegre/RS, Brazil. Clinical severity was defined as two or more
veno-occlusive episodes per year. The style="font-family:'} ';font-size:10pt;line-height:1.5;"> style="font-family:Verdana;font-size:12px;">β style="font-family:'} ';"> style="font-family:Verdana;font-size:12px;">S style="font-family:Verdana;font-size:12px;"> haplotypes were determined by PCR in 75 SCA patients. Among the 150 style="font-family:'} ';font-size:10pt;line-height:1.5;"> style="font-family:Verdana;font-size:12px;">β style="font-family:'} ';"> style="font-family:Verdana;font-size:12px;">S style="font-family:Verdana;font-size:12px;"> chromosomes analyzed, 99(66%)were identified as Bantu(Ban),
and 10(7%)as other haplotypes. Most
patients in our sample(62.7%)belonged
to lower SeS groups, precluding meaningful statistical analysis of SeS impact
on clinical severity. There was no correlation between haplotypes or HbF level
and SCA clinical severity. Gene polymorphisms and environmental issues have to
be taken into consideration.
摘要：Infectious mononucleosis (IM) by Epstein-Barr virus is usually a benign, self-limiting disease. Mild
to moderate immune thrombocytopenia in the setting of IM is very common and appears in approximately
half of these patients, however it rarely presents in severe form and troublesome
haemorrhage is even rarer. Rapid spontaneous resolution is possible, with the role of steroids being
controversial. Furthermore, elevation of the levels of uric acid because of immune thrombocytopenia
is observed in high frequency; however this finding is usually not mentioned. It is attributed
to a transient increase in purine turnover, it appears more often in men (with its peak
within the first 2 weeks of IM) and it is treated with intravenous fluids and bicarbonates. The
present case report describes the case of a young female patient who develops severe thrombocytopenia
and intense hyperuricemia following an Epstein-Barr infection. No severe bleeding appeared,
levels of uric acid normalised within the first two weeks of treatment and platelet levels
rise back to normal within a month under corticosteroid therapy....
摘要：The aim of this observational study was to assess the prevalence of iron-restricted erythropoiesis (IRE) in a population of elderly hospitalized anemic patients. Prevalence of IRE was found to be 41% and the most common clinical diagnoses in such patients were hematologic malignancies and solid tumors. Comparison between patients with IRE and non-IRE patients revealed that mean corpuscular volume, mean corpuscular hemoglobin, iron, and transferrin saturation were significantly lower in the IRE group, whereas no significant difference was found for Hb, transferrin, or ferritin. There was a more pronounced inflammatory response in the IRE group demonstrated by a higher C-reactive protein level....
摘要：The endothelial isoform of nitric oxide synthase (eNOS) is responsible for the physiological production of NO in endo-thelial cells and platelets. There is evidence that the G894T polymorphism of the eNOS gene is associated with this enzyme's basal activity and NO production, which could contribute to the pathogenesis of periodontal diseases (PD). Therefore, this study was designed to investigate the role of G894T polymorphism in the eNOS gene as a predisposing factor to periodontal disease. In this study we investigated the association of this polymorphism with PD in an admix-ture population (N = 119) separated into three groups: Healthy control, Moderate and Severe PD, without statistical differences among them for risk factors for PD, such as age, gender and smoking status. We observed that the GG ge-notype was associated with the progression of PD as indicated by an increase in frequency of approximately 18% in the Moderate and 26% in the Severe groups compared to the Healthy control group (p = 0.0302). This finding indicates that patients carrying the GG genotype have a greater chance of developing PD compared with those carrying the T allele, and it reinforces the notion that genetic factors contribute to the development and aggravation of PD....
Among a total of 29 blood
group systems and over 600 different blood group antigens discovered so far, ABO and Rhesus
are the most important blood group systems. The most significance rhesus
antigen is Rh-D because of its immunogenicity. The sound knowledge of ABO and
Rh-D antigens and its distribution in population is essential for the effective
management of blood transfusion services, in population genetic studies, in
resolving medico-legal issues and more importantly in compatibility test in
blood transfusion practice. Study is aimed to provide data on ABO and Rh-D
distribution in Gwalior region (Madhya Pradesh) and its comparison with related
studies in India and abroad. Total 90,000 samples in 4 years from
January 2004 to
December 2007 were grouped for ABO, Rh-D and their subgroups at Blood Bank of Gajra Raja
Medical College, along with Emergency Blood Bank, Gwalior, Madhya Pradesh, India. Blood group distribution among these
samples showed phenotypes A, B, AB and O as 22.7%, 37.5%, 9% and 30.8%
respectively. A2 and A2B were 8.0% and 8.6% respectively. The Rh-D negative phenotype was found 8.9% and DU variants/weaker D was 0.036% among the sample tested. In cord blood
samples, the incidence of
A2B were 18.6% and 20.2% respectively.