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M Tarek Elghetany

Publications and source records attributed to M Tarek Elghetany.

At least 19 recordsLinked to original sources
PubMed2007

Paraplegia as the presenting manifestation of extramedullary megakaryoblastic transformation of previously undiagnosed chronic myelogenous leukemia.

Extramedullary tumors, also known as granulocytic sarcomas (GS), occur most frequently in acute myelogenous leukemia (AML). They may signal the onset of the accelerated phase of chronic myelogenous leukemia (CML) or the blastic transformation of a myeloproliferative disorder. Occasionally, a GS may be the presenting sign of undiagnosed AML, and rarely the presenting sign of undiagnosed CML or aleukemic leukemia. Paraplegia due to a spinal cord GS is an extremely rare presentation of undiagnosed leukemia. This is the first case report of paraplegia as the presenting manifestation of extramedullary megakaryoblastic transformation of previously undiagnosed CML. A 53-year-old woman reported back pain for 6 days, rapidly progressing to paraplegia. Physical examination noted a large abdominal mass and flaccid paralysis in both lower extremities. Spinal MRI revealed a T4-T6 vertebral mass causing spinal stenosis and cord compression. Tumor debulking and laminectomy were performed emergently. The tumor consisted of noncohesive blast cells. The CBC revealed a leukocyte count of 238,300/microl and a differential consistent with CML. Reexamination of the patient found that the abdominal mass was a giant spleen. Further immunohistochemical studies of the tumor were consistent with extramedullary acute megakaryoblastic blast transformation of CML. Although extramedullary blast crises herald the accelerated phases in approximately 10% of CML cases, megakaryoblastic blast transformation of CML accounts for less than 3% of these cases. The combination of acute paraplegia and megakaryoblastic transformation in a previously undiagnosed patient with CML is extremely rare and may pose a diagnostic dilemma.

Combined Modality Therapy↗
PubMed2005

Impact of preanalytical variables on granulocytic surface antigen expression: a review.

BACKGROUND: There is a gradual but steady increase in the use of granulocytic surface marker studies to diagnose several inherited and acquired blood and bone marrow disorders. Diagnosis and follow-up of patients with inflammation and infection are other areas of quantitative flow cytometric application. Despite the increased use of flow cytometry to study granulocytes, there seems to be no well-established standards regarding specimen handling for these studies. METHODS: This review summarizes the effect of preanalytical variables on granulocytic surface markers. RESULTS AND CONCLUSIONS: Storing specimens in sodium heparin at room temperature for up to 72 h seems satisfactory. Other anticoagulants, although acceptable, may have a shorter storage time. Storage time could be prolonged further with the use of some preservation media. Lysed whole blood is the preferred technique. Techniques should avoid major temperature change and excessive manipulation and should maintain storage and methodologic temperature with minimal fluctuation. Fixation before staining with the antibody may result in decreased expression of some surface antigens.

Animals↗
PubMed2005

Catastrophic antiphospholipid syndrome: a rare cause of disseminated microvascular thrombotic injury - a case report with pathological and molecular correlative studies.

Catastrophic antiphospholipid syndrome (CAPS) is a severe and rare variant of antiphospholipid syndrome (APS) characterized by acute multiorgan failure due to small vessel thrombi in patients with positive antiphospholipid antibodies. We report a fatal case of catastrophic antiphospholipid syndrome in a young woman with a history of polymyositis and Hodgkin lymphoma. The patient was admitted to hospital because of severe foot pain following several weeks of skin ulcerations. Doppler ultrasonography showed evidence of arterial ischemia of the both lower extremities. Despite anticoagulation, immunosuppression, plasmapheresis and antibiotic therapy, she developed cutaneous gangrene, retroperitoneal hematoma, ileus, and acute respiratory and renal failure that resulted in death. Autopsy showed multifocal vascular injury and microthrombi with associated hemorrhages and infarcts in multiple organs. The patient had normal levels of functional protein C and protein S and a normal level of plasma homocysteine. Tests for common thromophilic gene mutations including prothrombin 20210, factor V Leiden 1691, and methylene tetrahydrofolate reductase 677 were negative. To our knowledge, this is the first CAPS patient with molecular studies for genetic prothrombotic mutations. Our report showed that there was no association between the development of CAPS and inherited thromophilia.

Adult↗
PubMed2005

CD36: a multiligand molecule.

CD36 is a multiligand receptor associated with a broad array of physiological processes and involved in markedly diverse disorders, including atherosclerosis, insulin resistance and diabetes, dyslipidemia, tumor angiogenesis, and host defense against Plasmodium falciparum. CD36 deficiency has proved to be common, particularly in ethnic groups such as African Americans and Asians. CD36 is commonly expressed on blasts in acute monocytic leukemia, megakaryoblastic leukemia, and erythroleukemia. The role of CD36 in sickle cell crises and cerebral malaria is debatable. As a receptor for thrombospondin 1, CD36 plays a role in the regulation of angiogenesis, which may be a therapeutic strategy for controlling the dissemination of malignant neoplasms. The future challenge will be to further understand the mechanisms by which CD36 affects these diverse functions and to design therapeutic strategies that can alter the course of the diseases.

Antigens, CD↗
PubMed2004

Flow cytometric study of neutrophilic granulopoiesis in normal bone marrow using an expanded panel of antibodies: correlation with morphologic assessments.

Flow cytometry studies of surface markers of neutrophils have been performed mostly on peripheral blood, and for a limited spectrum of diseases. Studying maturation defects on developing neutrophils in the bone marrow (BM) may be helpful in BM diseases, such as myelodysplastic syndromes and Shwachman-Diamond syndrome. We applied an expanded panel of antibodies to examine normal maturation patterns in 26 control samples of BM together with microscopic correlation. Promyelocytes correlated well with the CD24(-) and CD11b(-) populations, and metamyelocytes correlated well with the CD16(+) population (intermediate positivity). An excellent correlation was also identified between the sum of bands and segmented neutrophils and each of the following: CD16(++) (strong positivity), CD35(+), CD87(+), and CD64(-). Although visually identified segmented neutrophils paralleled CD10 positivity, there was an appreciable difference between both methods. We conclude that neutrophilic granulocyte maturation in the BM is accompanied by a change in surface antigens that reflects certain stages of development. A successful strategy for detecting maturation defects is to include several antibodies that are known to be expressed or absent at the same stage of maturation, such as CD16, CD35, CD64, and CD87.

Adolescent↗
PubMed2003

Physiologic variations in granulocytic surface antigen expression: impact of age, gender, pregnancy, race, and stress.

There is a growing interest in the use of granulocytic surface markers for the diagnosis of some inherited and acquired disorders, such as Shwachman-Diamond syndrome and myelodysplastic syndromes. Understanding the impact of physiologic factors, such as age, gender, pregnancy, race, and stress on granulocytic surface markers is essential for appropriate interpretation of results. Some surface markers show marked variations at the very early and the very late stages in life. Fetal granulocytes tend to have a lower expression of CD11b, CD11c, CD18, and CD32. Term neonatal granulocytes are frequently associated with a lower expression of CD10, CD11b, CD13, CD33, and CD62L and a higher expression of CD55 and CD64. Elderly individuals have shown a higher expression of CD64. Pregnancy is associated with temporary changes in granulocytic surface markers, such as a lower expression of CD16 and a higher CD64, partially mimicking an inflammatory response. Stress also has an impact on some surface markers, particularly adhesion molecules, such as CD62L and CD54. These factors need to be taken in consideration for the optimal interpretation of granulocytic surface marker studies.

Age Factors↗
PubMed2003

CD87 as a marker for terminal granulocytic maturation: assessment of its expression during granulopoiesis.

BACKGROUND: Understanding the normal surface maturation pattern of granulocytes is essential for the recognition of abnormal patterns, which in turn may be of diagnostic or pathogenetic significance in disorders such as myelodysplastic syndromes and inherited bone marrow failure disorders. CD87 plays a role in cellular interaction, cell migration, and inflammatory response. Surface expression of this antigen has not been adequately studied on bone marrow granulocytes, and the small number of previous studies has provided conflicting data. METHODS: Bone marrow aspirates from 11 control subjects were studied by flow cytometry and a lysed whole blood technique to compare surface expression of CD87 on marrow granulocytes with those of CD11b, CD16, CD35, and CD10, which are expressed at the myelocyte, metamyelocyte, band, and segmented stage of neutrophilic development, respectively. Four sorting experiments of CD87(+) granulocytes were also performed. RESULTS: Our study showed no statistical difference between surface expression of CD35 and CD87 (P > 0.3), whereas significant differences existed between CD87 and the other antibodies (P < 0.004). Sorting experiments showed that more than 80% of CD87(+) cells were bands and segmented neutrophils. Dual staining for CD87 and CD35 showed that most CD87(+) granulocytes coexpress CD35. CONCLUSIONS: CD87 is expressed on granulocytes at the band and segmented neutrophil stage of development and can be used to study normal and abnormal granulopoiesis.

Adolescent↗
PubMed2003

Urokinase plasminogen activator receptor (CD87): something old, something new.

CD87 is a widely expressed receptor for urokinase plasminogen activator (uPA) and plays a critical role in regulation of cell-surface plasminogen activation. An expanding body of evidence suggests that CD87 is involved in regulation of diverse physiological and pathological processes, including cellular adhesion, cell motility, angiogenesis, tumor invasion, and tumor metastasis. These data characterize CD87 as a pleiotropic molecule that mediates a wide range of events beyond plasminogen activation through extensive and complex interactions with other cell-surface molecules, such as integrins and L-selectin. The association of CD87 overexpression in tumor cells with tumor invasion has attracted many researchers to exploration of the potential therapeutic utility of CD87 by targeting binding of CD87 to uPA, the interactions between CD87 and other surface and matrix molecules, CD87 gene expression, and posttranscriptional modification. Therapeutic strategies targeting CD87 as a key molecule of tumor invasion and metastasis have great potential for becoming valuable assets in therapy for malignant tumors.

Cell Movement↗
PubMed2002

Expression of CD4 on peripheral blood granulocytes. a novel finding in a case of myelodysplastic syndrome in association with t(5;12).

Myelodysplastic syndromes (MDS) are associated with cell maturation defects that can manifest as abnormal surface antigen expression. We describe a patient with refractory anemia with excess blasts, who presented with infection and extensive dysplastic features in peripheral blood granulocytes. The granulocytes expressed CD11b, CD13, CD15, CD33, and CD43. The granulocytes also expressed CD4 antigen. Cytogenetic analysis showed a clonal t(5;12)(q33;p13). The patient improved on antibiotics with partial improvement in the dysplastic features. However, shortly after, the patient experienced paravertebral extramedullary blast transformation followed by a leukemia phase of acute monoblastic leukemia. The patient died a few days later. This is the first report describing anomalous expression of CD4 on granulocytes in MDS. Since the breakpoint on chromosome 12 is near the CD4 gene, which is mapped to 12p12, we hypothesize that dysregulation of the CD4 gene may have occurred resulting in its persistent expression on mature and maturing granulocytes.

CD4 Antigens↗
PubMed2002

Assessment of CD24 expression on bone marrow neutrophilic granulocytes: CD24 is a marker for the myelocytic stage of development.

The understanding of normal surface maturation pattern of granulocytes plays an essential role in identifying abnormal patterns, which may be of diagnostic or pathogenetic significance in some disorders, such as myclodysplastic syndromes. CD24, which is expressed only on granulocytes and not on monocytes, has not been adequately studied. Surface marker studies on eight control marrows indicate that CD24 is expressed on bone marrow granulocytes in a pattern that is similar to CD11b while much different than the more mature markers, CD16b and CD35. Three sorting experiments show that the majority of CD24(-) cells are promyelocytes. We conclude that CD24 is expressed on the neutrophilic granulocytes at the stage of myelocytes, and hence it could potentially be used to study normal and abnormal maturation of granulocytes.

Antigens, CD↗
PubMed2002

p53 protein overexpression in bone marrow biopsies of patients with Shwachman-Diamond syndrome has a prevalence similar to that of patients with refractory anemia.

CONTEXT: Shwachman-Diamond syndrome (SDS) is a rare inherited disorder characterized by pancreatic insufficiency, neutropenia, and in some patients, metaphyseal dysostosis. Patients with SDS are at a high risk for development of bone marrow failure, myelodysplastic syndrome, and acute leukemia. The p53 gene plays a major role in cell-cycle regulation, particularly in the presence of a genetic alteration in DNA, a critical step for the initiation of leukemogenesis. p53 gene up-regulation and p53 protein overexpression may occur as a cellular reaction to significant DNA damage. Shwachman-Diamond syndrome and refractory anemia patients have close similarities in the prevalence of acute leukemia and in cell-cycle changes in bone marrow cells. This similarity was further investigated for p53 protein overexpression using archived tissue from patients with hematologic diseases having various leukemic propensities, including SDS and refractory anemia. METHODS: Immunohistochemical staining for p53 protein overexpression was performed on bone marrow biopsies from 9 patients with SDS. These specimens were compared with biopsies from 71 patients with acquired hematologic disorders with variable risk levels for leukemia, including acquired aplastic anemia (n = 14), refractory anemia (n = 46), and various acquired cytopenias (n = 11), as well as 37 control subjects. RESULTS: p53 protein overexpression was identified only in patients with SDS and in patients with refractory anemia; these groups exhibited comparable prevalences of 78% and 72%, respectively. None of the patients with acquired aplastic anemia, acquired cytopenias, or in the control group showed overexpression of p53 protein. CONCLUSION: The prevalence of p53 protein overexpression in SDS is significantly different from that in acquired aplastic anemia and acquired cytopenias, but it is similar to the prevalence in refractory anemia. We speculate that p53 protein overexpression in this bone marrow failure syndrome may represent an early indicator of significant DNA genetic alteration, which is a crucial step in the process of leukemogenesis.

Adolescent↗
PubMed2001

Ionized magnesium in the homeostasis of cells: intracellular threshold for Mg(2+) in human platelets.

The role of extracellular magnesium ions in the homeostasis of intracellular ionized magnesium ([Mg(2+)](i)) in human platelets was studied. For media containing 0.00 to 0.60 mmol/l of extracellular ionized magnesium ([Mg(2+)](o)), the mean [Mg(2+)](i) fluctuated between 533 and 760 micromol/l. As the [Mg(2+)](o) was increased to 1.5 mmol/l, the [Mg(2+)](i) increased proportionately and peaked at 1470.1 micromol/l. Additional increase in the [Mg(2+)](o) from 1.50 to 6.00 mmol/l resulted in decreased [Mg(2+)](i) until it equilibrated between 739 and 776 micromol/l. The influx of Mg(2+) at [Mg(2+)](o) of 0.60 and 1.50 mmol/l was studied using verapamil, a calcium channel inhibitor, and ouabain, an inhibitor of the Na/K pump, respectively. The verapamil (25 mmol/l) blocking experiments resulted in a 92.4% inhibition of the Mg(2+) influx into the platelet at a [Mg(2+)](o) of 1.50 mmol/l. Ouabain (0.5 and 2.5 mmol/l) showed an enhancement effect on the influx of Mg(2+) at [Mg(2+)](o) of 0.60 mmol/l and no effect at 1.50 mmol/l. The effect of verapamil indicates that ion channels that are homologous to calcium ion channels may be involved in the influx of Mg(2+) into the platelets. The inhibition of Mg(2+) influx for [Mg(2+)](o) greater than 1.50 mmol/l may illustrate a protective mechanism that attempts to maintain the viability of platelets at abnormally high [Mg(2+)](o). These results suggest that there is an intracellular Mg(2+) threshold of 1500 micromol/l, above which an active mechanism prevents further influx of Mg(2+).

Blood Platelets↗
PubMed2001

Accuracy and precision of point-of-care testing for glucose and prothrombin time at the critical care units.

The use of point-of-care testing (POCT) in critical care patient units has continued to increase since the 1980s. This increase is due to the need for prompt therapeutic interventions that may impact mortality and morbidity, and reduce the overall cost of healthcare for critically ill patients. The diagnostic manufacturing industry has risen to this challenge by introducing portable and/or handheld analyzers for use at the point-of-care. In order to ensure the public safety in the USA, the Food and Drug Administration (FDA) must approve the use of each POCT analyzer. The FDA approval is based on established performance criteria that includes relative accuracy and precision documentation. This study evaluated the precision and accuracy of the POCT prothrombin time and glucose analyzers relative to the manufacturers' specifications, to the internal QC in the main laboratory, and to the results of the external proficiency-testing program. The QC for the prothrombin time had a precision that ranged from 2.84% to 3.45% (POCT) and from 1.27-1.66% (main laboratory). The precision for the glucose QC ranged from 5% to 5.2% (POCT) and 0.9-2.7% (main laboratory). Using the results of the external proficiency testing, the inter-laboratory CV% for the POCT prothrombin time ranged from 3.5% to 5.0% and the main laboratory had a range of 2.5-2.9%. The inter-laboratory CV% ranges for glucose POCT and the main laboratory were 4.9-10.6% and 1.8-3.5%, respectively. The main laboratory analyzers proved to be more accurate than the POCT analyzers as indicated by comparison to the mean prothrombin time and glucose results of all participating laboratories in the proficiency testing program.

Blood Glucose↗