Detection of FLT3 Oncogene Mutations in Acute Myeloid Leukemia Using Conformation Sensitive Gel Electrophoresis

FLT3 (fms-related tyrosine kinase 3) is a receptor tyrosine kinase class III that is expressed on by early hematopoietic progenitor cells and plays an important role in hematopoietic stem cell proliferation, differentiation and survival. FLT3 is also expressed on leukemia blasts in most cases of acute myeloid leukemia (AML). In order to determine the frequency of FLT3 oncogene mutations, we analyzed genomic DNA of adult de novo acute myeloid leukemia (AML). Polymerase chain reaction (PCR) and conformation-sensitive gel electrophoresis (CSGE) were used for FLT3 exons 11, 14, and 15, followed by direct DNA sequencing. Two different types of functionally important FLT 3 mutations have been identified. Those mutations were unique to patients with inv(16), t(15:17) or t(8;21) and comprised fifteen cases with internal tandem duplication (ITD) mutation in the juxtamembrane domain and eleven cases with point mutation (exon 20, Asp835Tyr). The high frequency of the flt3 proto-oncogene mutations in acute myeloid leukemia AML suggests a key role for the receptor function. The association of FLT3 mutations with chromosomal abnormalities invites speculation as to the link between these two changes in the pathogenesis of acute myeloid leukemiaAML. Furthermore, CSGE method has shown to be a rapid and sensitive screening method for detection of nucleotide alteration in FLT3 gene. Finally, this study reports, for the first time in Saudi Arabia, mutations in the human FLT3 gene in acute myeloid leukemia AML patients

Gastrointestinal Non-Hodgkin′s lymphoma: A clinico-pathological study

Objectives: The aim of this study is to determine the clinico-pathological features of primary gastrointestinal non-Hodgkin′s lymphoma (GI NHL) at King Abdulaziz University Hospital, Jeddah, and to compare our results to those reported in the literature. Materials and Methods: Twenty-three adult patients with primary GI NHL diagnosed over a 5-year period (2000 through 2005) were retrospectively studied clinically and histopathologically. They were classified using the REAL/WHO histopathologic classification. Results: Of the 23 patients with primary GI NHL, 14 (60.9%) were Saudis, with a male-to-female ratio of 1.3:1. The mean age of male patients was 61. 3 years, ranging from 42-83 years with an SD of ±13.09; while for females, the mean age was 64 years, ranging from 50-75 years with an SD of ±9.14. Abdominal pain was the most common presenting symptom (78.3%), and the most common primary site was the stomach (73.9%), followed by the small bowel (13%). The most frequent histologic subtype was the diffuse large B cell lymphoma, accounting for 60.9% of all cases, followed by the marginal-zone cell lymphoma (MALT type), which was Helicobacter pylori associated (39.1%). A large proportion of patients with primary GI NHL had early disease (Stage IE - 20%, Stage IIE - 58.6%). With regards to treatment, 15 patients (65.2%) had chemotherapy, while only 2 patients (8.7%) were treated by Helicobacter pylori eradication. The overall 5-year survival was 47.8%. Conclusion: The data demonstrated that primary GI NHL is more common among males, mainly in their sixth decade. Abdominal pain is the most common presenting symptom, with stomach being the most common involved site. Diffuse large B cell lymphoma is the most frequent histologic subtype, followed by extranodal marginal-zone B cell lymphoma (MALT type), which was Helicobacter-associated. A majority of cases have early disease (stage IE and IIE), mostly treated by combination chemotherapy

An explanatory mixed methods study on the validity and validation of students’ assessment results in the undergraduate surgery course

<p><b>Background/purpose:</b> There is inadequate evidence of reported validity of the results of assessment instruments used to assess clinical competence. This study aimed at combining multiple lines of quantitative and qualitative evidence to support interpretation and use of assessment results.</p> <p><b>Method:</b> This study is a mixed methods explanatory research set in two stages of data collection and analysis (QUAN : qual). Guided by Messick’s conceptual model, quantitative evidences as reliability and correlation coefficients of various validity components were calculated using students’ scores, grades and success rates of the whole population of students in 2012/2013 and 2013/2014 (<i>n</i>= 383; 326). The underlying values that scaffold validity evidences were identified via Focus Group Discussions (FGD) with faculty and students; sampling technique was purposive; and results were analyzed by content analysis.</p> <p><b>Results:</b> (1) Themes that resulted from content analysis aligned with quantitative evidences. (2) Assessment results showed: (a) content validity (table of specifications and blueprinting in another study); (b) consequential validity (positive unintended consequences resulted from new assessment approach); (c) relationships to other variables [a statistically significant correlation among various assessment methods; with combined score (0.64–0.86) and between mid and final exam results (<i>r</i> = 0.672)]; (d) internal consistency (high reliability of MCQ and OSCE: 0.81, 0.80); (3) success rates and grades distribution alone could not provide evidence to advocate an argument on validity of results.</p> <p><b>Conclusion:</b> The unified approach pursued in this study created a strong evidential basis for meaningful interpretation of assessment scores that could be applied in clinical assessments.</p

The prevalence of obstructive sleep apnea in adult patients with sickle cell disease

Purpose: Although few previous studies suggested an increased prevalence of obstructive sleep apnea (OSA) among children with sickle cell disease (SCD) compared to others, there are little data regarding this association in adults. In this study, we aimed to investigate the prevalence of OSA among the patients with SCD and its risk factors. Materials And Methods: This cross-sectional, observational study was conducted at a specialty hematology clinic. From December 2013 to July 2014, all the patients with SCD and chronic anemia were approached. Data were collected on the risk of OSA using the Berlin questionnaire, and the data on daytime sleepiness were collected using the Epworth sleepiness scale (ESS); medical history of the patients was also obtained. The objective diagnosis of OSA using polysomnography was performed in a subsample of the study population. Results: The study included 106 patients, 44.3% with SCD and 55.7% with other types of anemia being used as a comparison group. Among the patients with SCD, 14.9% were at a high risk of OSA, and 23% were confirmed to have OSA, whereas 10.1% and 16.7% of those in the comparison group did, respectively. However, there were no statistically significant differences between the two groups. Mean scores of risk factors for OSA among the patients with SCD with OSA were 28 years for age, 22.1 kg/m2for body mass index, 14.5 inches for neck circumference, 122 mmHg for systolic blood pressure, and 6.67 for ESS score. Conclusion: Although not different from chronic anemia, the OSA is a common, coexisting disease in the patients with SCD. Furthermore, it is suspected that the traditional screening tools may miss potential cases of OSA in the SCD population