الدكتور جمال السهيلي

Coombstest

In immunologicalhemolyticanemiasantibodiestargetinga RBC antigenbindtothe membrane. Iftheydo notactivatecomplement(calledincomplete antibodies), no RBC lysisoccurs.
However, antibody-coatedRBCsare capturedin the spleen and destroyed.

Coombstest: todetectincomplete antierythrocyteantibodies

Direct AntiglobulinTest (DAT): TodetectantibodiesboundtoRBC surface.
Ifcellsare coatedwithIgG, ananti-IgGantiserumwillgenerate bridgesamongcells, thuscausingredcellagglutination.
Patient’s blood.
ObtainwashedRBCs(toeliminate allplasma IgG).
Addantiglobulinantiserum.
Incubate 15 min37°C.
Look foragglutination(visual, microscope).

IndirectAntiglobulinTest (IAT): Todetect
antierythrocyteantibodiesfr

المزيد

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التصنيفات : غير مصنف |

دوّن الإدراج

Reticulocyte Count

Objectives:

1.       To perform, within 20% accuracy of intructor’s values, reticulocyte counts on whole blood specimens.

2.      To perform reticulocyte counts with and without a Miller ocular.

3.      List reference ranges for reticulocytes.

4.      Correlate the reticulocyte count results with normal and disease states.

5.      List sources of error in the reticulocyte count.

6.      Calculate the reticulocyte count and corrected reticulocyte count.

7.      Calculate the Reticulocyte Production Index (RPI).

8.      List 2 common supravital stains.

Principle:

Reticulocytes are immature RBCs that contain remnant cytoplasmic ribonucleic acid (RNA) and organelles such as mitochondria and ribosomes.  Reticulocytes are visualized by staining with supravital stains (methylene blue or brilliant cresyl blue) that precipitate the RNA and organelles.  These stains cause the ribosomal and residual RNA to coprecipitate with the few remaining mitochondria and ferritin masses in living young erythrocytes to form microscopically visible dark-blue clusters and filaments (reticulum).  The reticulocyte count is a means of assessing the erythropoietic activity of the bone marrow.  The number of reticulocytes is expressed as a percentage of the total number of erythrocytes counted.

The reticulocyte count is elevated in patients with hemolytic anemia, hemorrhage, and following the treatment of iron deficiency anemia.  The reticulocyte count is decreased in cases of aplastic anemia and disorders resulting in ineffective erythropoiesis.

Specimen:

Whole blood that is anticoagulated with either EDTA or heparin is suitable. Capillary blood drawn into heparinized tubes or immediately mixed with stain may also be used.   RBCs must still be living when the test is performed; therefore, it is best to perform it promptly after blood collection.  Blood may be used up to 8 hours after collection.  Stained smears retain their color for a prolonged amount of time.

Quality Control:   

Three slides should be made for each retic count performed.  The final calculated retic% from the first two slides should agree within 15% of each other.  If this criterion is not met, count the third slide.

Reagents, Supplies, and Equipment:

1.       Commercially prepared liquid new methylene blue solution.  It should be stored in a brown bottle.  If precipitate is a problem on the smear, the stain should be filtered prior to use.

2.      Microscope slides

3.      Microscope

4.      10 x 75 test tubes

5.      Pasteur pipets (with bulb if pipets are glass)

6.      Capillary tubes

7.      Miller ocular (if available)

Procedure:

            Preparation of Smears

1.        Label a 10 x 75 mm test tube with patient name and ID

2.      Add 5 drops of new methylene blue solution to the labeled test tube

3.      Add 5 drops of well mixed EDTA anticoagulated blood to the labeled test tube.

4.      Mix the contents by gently shaking.

5.      Incubate at room temperature (20-24°C) for 10 minutes.

6.      After the 10 minute incubation, gently mix the stain/blood solution.

7.      Using the wedge smear technique, make two additional smears (not to thick or thin.

8.      Allow to AIR dry. (Do not blow to hasten drying)

9.      Label the slides with patient name, ID# and date.

Manual Method of Counting (WITHOUT Miller disc)

1.        Place the first slide on the microscope stage and, using the 10x (low power) objective, find an area in the thin portion of the smear in which the red cells are evenly distributed and NOT touching each other. 

2.      Without moving the slide, change to 100x (oil immersion objective), add oil, and find an area of the smear in which there are approximately 100 red cells visible per field.  A method for finding a field with around 100 RBCs is to mentally divide the field into 4 quadrants and count one of those 4 quadrants.  If you count 22-28 RBCs in one quadrant, then the area is acceptable.  In other words, there should be around 25 RBCS in ¼ of the oil immersion field visible.

3.      Begin counting both the RBCs and the retics.  Be sure to count all cells that contain a blue-staining filament or at least 2 or more discrete blue aggregates of reticulum in the erythrocyte as retics and RBCs. (See procedure notes for inclusions that may be confused with reticulum.) 

4.      Continue counting consecutive oil immersion fields until you have reached 1000 total red cells (RBCs + Retics).  You may count 500 cells on two slides, as an alternate method.

5.      Record the number or Retics counted on each smear on the data sheet.

6.      If the two slides do not agree within ±15% roughly two units), perform a retic count on the third slide.

7.      Calculate the percent of reticulocytes as follows:

% Retics=   # of reticulocytes counted in 1000 total red cells

        10

                     Example:

Slide 1= 46 in 1000 erythrocytes

Slide 2= 48 in 1000 erythrocyte

Average= 47

                                    Retics counted = 47 in 1000 erythrocytes

                                    % Retics = 47/10 =4.7%

                                                                                                               Field of View

            Method using the Miller disk:                            k

                                                            Retic counting sq.

                                                         RBC counting sq.

1.       Use a 100x objective and a 10x ocular secured with a Miller disc.  The Miller disc imposes two squares onto the field of view of the oil immersion objective. The retic counting square is 9x the area of the RBC counting square. 

2.      Find a suitable area of the smear that shows 3-10 RBCs in the Retic counting square.

3.      Count the retics within the large retic counting square including the cells touching the top and right sides of the small square.

4.      Count all cells in the RBC counting square.  Count retics in this square as both a retic and an RBC.  Cells touching the lines should only be counted on the bottom and left sides.

5.         Continue counting in other acceptable fields.

6.         Stop counting when you have reached 111 total RBCs (RBCs +Retics) from the RBC counting square.  This number of cells should be reached in 15-20 fields and corresponds to 999 RBCs counted with the standard manual procedure.

7.      Calculate the % Reticulocytes  using the Miller disc method by the following formula:

              % Retics = Total Retics counted (both squares)

                                                               10

                        Example:

                        Retics counted in retic counting sq. (large sq.)=20

                        RBCs counted in RBC counting sq. (small sq)=111

                                          %retics= 20/10 = 2%

            Calculation of corrected reticulocyte for Low Hematocrit

The reticulocyte count is most often expressed as a percentage of total red cells. 

المزيد

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التصنيفات : غير مصنف |

دوّن الإدراج

المزيد

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التصنيفات : غير مصنف |

دوّن الإدراج

 The World Health Organization (WHO) classification of the myeloid neoplasms

1. James W. Vardiman,
2. Nancy Lee Harris, and
3. Richard D. Brunning

Abstract

A World Health Organization (WHO) classification of hematopoietic and lymphoid neoplasms has recently been published. This classification was developed through the collaborative efforts of the Society for Hematopathology, the European Association of Hematopathologists, and more than 100 clinical hematologists and scientists who are internationally recognized for their expertise in hematopoietic neoplasms. For the lymphoid neoplasms, this classification provides a refinement of the entities described in the Revised European-American Lymphoma (REAL) Classification—a system that is now used worldwide. To date, however, there has been no published explanation or rationale given for the WHO classification of the myeloid neoplasms. The purpose of this communication is to outline briefly the WHO classification of malignant myeloid diseases, to draw attention to major differences between it and antecedent classification schemes, and to provide the rationale for those differences.

Introduction

Recently, the World Health Organization (WHO), in conjunction with the Society for Hematopathology and the European Association of Hematopathology, published a new classification for hematopoietic and lymphoid neoplasms.1 The concepts that underlie this classification were derived from numerous published clinical and scientific studies and from the experience of more than 100 pathologists, clinicians, and scientists from around the world who collaborated to develop this consensus classification.2 A basic principle of the WHO system is that the classification of hematopoietic and lymphoid neoplasms should utilize not only morphologic findings but also all available information, including genetic, immunophenotypic, biologic, and clinical features to define specific disease entities. Essentially, the WHO classification attempts to incorporate those disease characteristics that have proved to have clinical and biologic relevance into a useful, working nomenclature.

For the lymphoid neoplasms, the WHO classification provides refinement of the entities defined in the Revised European-American Lymphoma (REAL) Classification—a system that is now widely used by pathologists and clinicians.3 The WHO classification of myeloid neoplasms includes many of the criteria of the French-American-British (FAB) Cooperative Group classifications of acute myeloid leukemia (AML)4 and myelodysplastic syndromes (MDS)5 as well as guidelines of the Polycythemia Vera Study Group (PVSG) for the chronic myeloproliferative diseases (CMPDs),6 7 but there are some significant differences. The purpose of this communication is to outline briefly the WHO classification of the myeloid neoplasms, to draw attention to major differences between the WHO and previous classifications of these disorders, and to provide the rationale for these differences. In addition, we wish to address and clarify specific issues concerning the classification that have appeared both prior and subsequent to the publication of the WHO monograph. The WHO classification of the myeloid neoplasms is outlined in Tables 1 to 7. The detailed criteria for each subtype can be found in the WHO monograph.1

Table 1.

WHO classification of acute myeloid leukemia

Prerequisites for the diagnosis of myeloid neoplasms by the WHO classification

The WHO classification is similar to the FAB and PVSG schemes in that it relies on morphologic, cytochemical, and immunophenotypic features of the neoplastic cells to establish their lineage and degree of maturation. As was true for antecedent classifications, the WHO recognizes the practical importance of the “blast count” in categorizing myeloid diseases and in predicting prognosis. Therefore, the WHO attempts to clearly define “blasts” and to clarify specific issues regarding their accurate and reproducible enumeration. Some of the criteria for blast morphology differ from those in previous classifications.

The blast percentage and assessment of degree of maturation and dysplastic abnormalities in the neoplastic cells should be determined, if possible, from a 200-cell leukocyte differential performed on a peripheral blood smear and a 500-cell differential performed on marrow aspirate smears stained with Wright Giemsa or May-Grünwald Giemsa. The blast percentage should be correlated with an estimate of the blast count from the marrow biopsy section. In addition to myeloblasts, the monoblasts and promonocytes in acute monoblastic/monocytic and acute and chronic myelomonocytic leukemia and the megakaryoblasts in acute megakaryoblastic leukemia are considered as “blast equivalents” when the requisite percentage of blasts is calculated for the diagnosis of AML. In acute promyelocytic leukemia (APL), the blast equivalent is the abnormal promyelocyte. This latter cell is usually characterized by a reniform or bilobed nucleus, but its cytoplasm may vary from heavily granulated with bundles of Auer rods to virtually agranular. A recent, detailed morphologic analysis of the abnormal promyelocytes in APL has led to a better appreciation of the cytologic variability of the leukemic cells in this disorder.8 Erythroid precursors (erythroblasts) are not included in the blast count except in the rare instance of “pure” erythroleukemia. Dysplastic micromegakaryocytes are also excluded from the blast percentage. Although assessment of the number of cells that express the antigen CD34 provides valuable data for diagnostic and prognostic purposes, the percentage of CD34⁺ cells should not be considered a substitute for a blast count from the smears or an estimate from the bone marrow biopsy. Although CD34⁺hematopoietic cells generally are blasts, not all blasts express CD34.9

The percentage of blasts proposed by the WHO to categorize a specific case is the percent blasts as a component of all nucleated marrow cells, with the exception of acute erythroleukemia (see below). If a myeloid neoplasm is found concomitantly with another hematologic neoplasm—for example, therapy-related AML and plasma cell myeloma—the cells of the nonmyeloid neoplasm should be excluded when blasts are enumerated. Cytochemical studies (myeloperoxidase, nonspecific esterase) and/or immunophenotyping studies (detection of myeloid-related antigens, such as CD117, CD13, CD33) must provide evidence that the neoplastic cells belong to one or more of the myeloid lineages10 11 unless this is obvious from specific morphologic findings, such as Auer rods. (Note: The term “myeloid” refers, in this paper, to bone marrow–derived cells, including granulocytes, monocytes, erythroid, and megakaryocytic lineages.)

The WHO classification for AML, MDS, and MPD includes specific genetic subcategories; thus, determination of genetic features of the neoplastic cells must be performed if possible. Many recurring genetic abnormalities in the myeloid neoplasms can be identified by reverse transcriptase–polymerase chain reaction (RT-PCR) or fluorescent in situ hybridization (FISH), but cytogenetic studies should be performed initially and at regular intervals throughout the course of the disease for establishing a complete genetic profile and for detecting genetic evolution. Although it has been suggested that the lack of immediate availability of genetic information is an obstacle to the utilization of the WHO classification,12 currently available technology should allow assimilation of genetic data in a time frame that will allow appropriate categorization and therapy. It is anticipated that future advances in technology will result in more rapid availability of genetic information.

Acute myeloid leukemia

During the nearly 3 decades that the FAB system was used for classifying AML, it was discovered that many cases of AML are associated with recurring genetic abnormalities that affect cellular pathways of myeloid maturation and proliferation. The FAB classification, initially proposed in 1976,4 provided a consistent morphologic and cytochemical framework in which the significance of the genetic lesions could be appreciated. In some instances, such as APL and acute myelomonocytic leukemia with abnormal eosinophils (M4Eo), the morphologic characteristics predict the genetic abnormalities. However, morphologic-genetic correlations are not always perfect, and the genetic findings may predict the prognosis and biologic properties of the leukemia more consistently than does morphology. Furthermore, in many cases either there is no correlation between morphology and genetic defects or the underlying genetic and molecular defects cannot be identified. Thus, although the FAB classification recognizes the morphologic heterogeneity of AML, it does not always reflect the genetic or clinical diversity of the disease.

Some investigators suggest that a more relevant classification of AML can be achieved if 2 distinctive subgroups with different biologic features are recognized: (1) AML that evolves from MDS or has features similar to those found in MDS and (2) AML that arises de novo without significant myelodysplastic features.13 14 The characteristics associated with these 2 groups indicate that they have fundamentally different mechanisms of leukemogenesis. MDS-related leukemia is associated with multilineage dysplasia, poor-risk cytogenetic findings that often include loss of genetic material, and a poor response to therapy. The incidence of this type increases with age, consistent with the hypothesis that MDS and MDS-related leukemia arise through multiple insults to the genetic constitution of the hematopoietic stem cell that occur over time. In contrast, de novo AML usually lacks significant multilineage dysplasia, is often associated with good-risk cytogenetic abnormalities, particularly certain recurring chromosomal translocations and inversions, and often has a favorable response to appropriate therapy, with good failure-free and overall survival times.15 16 This type of leukemia has a relatively constant incidence throughout life and is the type most likely to be observed in children and young adults.13 It is probable that specific genetic events associated with these leukemias, which often involve transcription factors, are a major, rate-limiting step in their pathogenesis.17

The concept that these and other subgroups of AML can be recognized and classified as unique diseases through correlation of morphologic, genetic, and clinical data is a major theme of the WHO classification and serves as the basis for the 2 most significant differences between it and the FAB classification: (1) a lower blast threshold for the diagnosis of AML in the WHO classification and (2) the categorization of cases of AML into unique clinical and biologic subgroups in the WHO classification.

In the WHO classification, the blast threshold for the diagnosis of AML is reduced from 30% to 20% blasts in the blood or marrow. In addition, patients with the clonal, recurring cytogenetic abnormalities t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22), and t(15;17)(q22;q12) should be considered to have AML regardless of the blast percentage (Table 1).

A number of studies indicate that patients with 20% to 29% blasts in their blood or bone marrow often have similar clinical features—including response to therapy and survival times—as those with 30% or more blasts. According to the FAB criteria for MDS, patients with 20% to 29% blasts in the blood or marrow are classified in the MDS subgroup of refractory anemia with excess of blasts in transformation (RAEBT).5 In the WHO proposal, most patients with 20% to 29% blasts and myelodysplasia will be classified as AML with multilineage dysplasia—a subgroup that includes patients with a prior history of MDS as well as patients who present initially with AML and dysplasia in multiple cell lines. AML with multilineage dysplasia can be considered the most advanced manifestation of MDS.

Numerous reports indicate that a significant number of patients with RAEBT and AML with myelodysplastic-related features share several important biologic and clinical features. According to some studies, myeloid cells from patients with RAEBT and MDS-related AML have nearly identical profiles of proliferation and apoptosis that differ from those in refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), and refractory anemia with excess blasts (RAEB).18 Poor-risk cytogenetic abnormalities, including abnormalities of chromosome 7 and complex abnormalities, increased expression of multidrug-resistance glycoproteins, and poor response to chemotherapy, are also common in RAEBT and in MDS-related AML.14 19 Some investigators have also reported that, when matched for similar disease features, such as white blood cell count or cytogenetic abnormalities, patients with RAEBT and AML have similar survival times if treated with identical therapy.20-22 In addition, data from the International MDS Risk Analysis Workshop indicate that RAEBT is not an indolent disease. In that study, 25% of patients with 20% to 30% blasts evolved to AML in 2 to 3 months, 50% in 3 months, and more than 60% developed AML within 1 year. The median survival time for patients with RAEBT was less than 1 year.23

We suggest that the sum of these data indicates that patients with 20% to 29% blasts in the blood and/or bone marrow accompanied by multilineage myelodysplasia have essentially the same disease as do those with AML with multilineage dysplasia and 30% or more blasts and should be classified in the same category. It is important to emphasize that therapeutic decisions for patients with MDS-related AML should be based not only on the percentage of blasts but also on clinical findings, the rate of disease progression, and genetic data. The effect on the blast percentage of any previous therapy, such as growth factor therapy, must also be taken into account. These cautionary notes apply regardless of whether the blast count is 20%, 30%, or more in a patient with myelodysplastic-related disease.

The lower blast percentage required for a diagnosis of AML also addresses another issue: the classification of patients who have no evidence of multilineage myelodysplasia—that is, patients with true de novo AML—as RAEBT because their blood or bone marrow specimens have fewer than 30% blasts on the initial evaluation. If the leukemia manifests no evidence that it is myelodysplastic related, it does not seem justified to categorize it as a myelodysplastic syndrome. Such a designation could result in inappropriate stratification for risk-determined therapy. Patients with the specific recurring cytogenetic abnormalities t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22), and t(15;17)(q22;q12) should be classified as having AML regardless of the blast percentage.

Three unique subgroups of acute myeloid leukemia are recognized by the WHO classification (Table 1): (1) AML with recurrent genetic abnormalities, (2) AML with multilineage dysplasia, and (3) AML and MDS, therapy related. Cases that do not satisfy the criteria for any of these subgroups, or for which no genetic data can be obtained, should be classified as one of the entities in a fourth subgroup: AML, not otherwise categorized.

Acute myeloid leukemia with recurrent genetic abnormalities

In the subgroup “AML with recurrent genetic abnormalities,” the WHO recognizes 4 well-defined recurring genetic abnormalities (Table 1) that are usually associated with de novo AML. They are commonly encountered: nearly 30% of patients with AML will have one of these genetic abnormalities.24-26 In cases of AML with t(15;17), t(8;21), and inv(16) or t(16;16), there is such a strong correlation between the genetic findings and the morphology that the genetic abnormality can usually be predicted from the microscopic evaluation of the blood and marrow specimens. Furthermore, because AMLs associated with these abnormalities have distinctive clinical findings and a favorable response to appropriate therapy, they can be considered as truly distinct clinicopathologicgenetic entities.15 16 25 26 Although abnormalities of 11q23 are often associated with myelomonocytic or monocytic differentiation, AML associated with this abnormality cannot always be predicted with any degree of confidence from the morphology alone.

As noted above, the leukemias associated with these recurrent genetic abnormalities generally have the features of de novo AML. However, all of the genes affected in this group are apparently vulnerable to damage caused by certain types of chemotherapy, specifically with topoisomerase II inhibitors, and can be involved in some cases of therapy-related leukemia.27 28 In these instances, the unique clinical background indicates that the case should be classified as therapy-related AML.

It is anticipated that the list of entities included in this subgroup will expand in the future. Some members of the WHO committees suggested that other recurring genetic abnormalities, such as t(8;16), t(6;9), or t(3;3), should be included in the current listing. Although these latter genetic abnormalities are often associated with unique morphologic and/or clinical features, it is not yet clear whether they define a unique disease or are mainly of prognostic significance within other subgroups. Furthermore, at least some of the recurring genetic abnormalities—for example, t(3;3)—are more frequently associated with myelodysplastic-related disease than with de novo AML and would be better incorporated into the subgroup of AML with multilineage dysplasia.

It has been suggested that the WHO classification cannot realistically be used for AML because genetic information is not always available in a timely manner.12 Alternatively, a “realistic” classification has been proposed that permits cases to be classified if the morphologic findings are “suggestive” of a specific genetic abnormality even without adequate knowledge that such a genetic defect is actually present.12 We agree that the lack of complete information is a problem, but because the genetic data often predict response to treatment and prognosis and often drive treatment decisions, hematologists and pathologists are appropriately under pressure to obtain this information in a timely manner. Furthermore, although the recurring genetic abnormalities are often associated with distinctive morphologic findings, identification of the genetic defect provides a more objective, reproducible means of identifying a specific lesion. For example, the detection of the CBFβ/MYH11(inv(16) or t(16;16)) by molecular and/or cytogenetic techniques is reported to correlate with the morphologic diagnosis of M4Eo in 30% to 100% of cases.29-31 Although the reason for this reported variability is unclear, what is clear is that if the inv(16) is present, the “real” classification is AML with inv(16). In daily practice one often cannot put a given specimen into a precise disease category without more information than is available at the time—a problem that is by no means confined to the diagnosis of a particular category of AML. We believe that in a case of AML with morphologic features suggestive of a specific genetic abnormality, but for which complete information is not yet available, the pathologist should issue a report that indicates the case may belong to a particular genetic category but that more data are required to prove it. The report should indicate what data are needed and whether the studies are in progress or if a new specimen is necessary. However, we strongly believe that a classification that includes categories that are suggestive of a specific genetic entity for cases that are “not-quite-yet-classifiable” is not what is necessary to solve the problem of the lack of timely information. What is needed instead is a carefully worded report that informs the clinician of what more needs to be done to accurately complete the diagnosis.

Acute myeloid leukemia with multilineage dysplasia

The WHO classification “AML with multilineage dysplasia” recognizes the biologic and clinical importance of MDS-related AML. The diagnosis of this subtype is readily established in patients in whom there is a well-documented history of MDS or a myelodysplastic/myeloproliferative disease (MDS/MPD) that has been present for at least 6 months prior to the onset of overt AML (Table1). However, the definition of MDS-related AML is more difficult for those cases that present initially as acute leukemia. Whether morphologic, genetic, biologic, clinical features, or some combination of these should be used as defining characteristics was a point of controversy among members of the WHO committees. For practical purposes and worldwide usage, however, it was agreed that morphologic evidence of multilineage dysplasia would be the most universally available marker for its recognition. In the WHO classification, the diagnosis of AML with multilineage dysplasia without antecedent MDS or MDS/MPD is made when blasts constitute at least 20% of the blood or marrow cells and when 50% or more of the cells in 2 or more myeloid lineages are dysplastic in a pretreatment sample. Although the 50% figure may appear high, it is derived from a number of studies that indicate that a lower threshold of dysplasia may not consistently identify AML with MDS-like features.32-35 In some studies, multilineage dysplasia is an independent prognostic factor only in patients who have favorable cytogenetics but has no additional adverse impact in patients with poor-risk genetics.35 We suggest that a combination of genetic and morphologic studies may ultimately be used to further characterize this type of leukemia.

Acute myeloid leukemias and myelodysplastic syndromes, therapy related (t-AML and t-MDS)

Two types of t-AML and t-MDS are recognized in the WHO classification, depending on the causative therapy: an alkylating agent/radiation–related type and a topoisomerase II inhibitor–related type.

Alkylating agent/radiation–related t-AML and t-MDS.

This disorder usually appears 4 to 7 years after exposure to the mutagenic agent. Approximately two thirds of cases present with MDS and the remainder as AML with myelodysplastic features.36-40It could be disputed whether a distinct category is needed for alkylating agent–related AML, because it is similar to AML with multilineage dysplasia and could be placed in that category.12 However, the identification of a known, predisposing etiologic agent is but one major difference between these 2 groups; there is also a higher incidence of abnormalities involving chromosomes 5 and/or 7 and a worse clinical outcome in the therapy-related group.36-39

Topoisomerase II inhibitor–related AML.

In contrast to alkylating agent–related t-AML and t-MDS, acute leukemia secondary to topoisomerase II inhibitors often does not have a preceding myelodysplastic phase, and it most frequently presents as overt acute leukemia, often with a prominent monocytic component.27 28 41-44 The latency period between the initiation of treatment with topoisomerase II inhibitors and the onset of leukemia is short, ranging from 6 months to 5 years, with median times of 2 to 3 years usually reported.27 28 41-43 Most often, this type of t-AML is associated with balanced translocations involving chromosome bands 11q23 or 21q22.27 28 42-44However, other translocations including inv(16)(p13q22) or t(15;17)(q22;q12) have been reported, and in these latter instances, as with 11q23 and 21q22 abnormalities, the morphologic and clinical findings are similar to those observed in patients with these translocations and no history of prior cytotoxic therapy.27 28 The initial response to therapy of topoisomerase II inhibitor–related AML as well as the overall survival are reported to be similar to cases of

المزيد

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التصنيفات : غير مصنف |

دوّن الإدراج

 التهاب الكبد الفيروسي أ  ( إلتهاب الكبد الوبائي )     Hepatitis A

تعتبر الاصابة بفيروس التهاب الكبد من النوع (ا) من أهم مسببات التهاب الكبد الحاد، وفي أكثر من 80% من الحالات تمر الإصابة على شكل نزلة انفلونزا حادة (حمى و قشعريرة)، ولا يعرف المصاب بإصابته بإلتهاب الكبد .

 كيفية انتقال العدوى في التهاب الكبد الفيروسي ا :-

تنتقل عدوى التهاب الكبد الوبائي عن طريق التماس مع البراز محمل بالفيروسات المعدية، ويكون التماس بعدة طرق منها :

-          اللمس المباشر للفضلات (البراز) الملوثة، وذلك يحصل مثلآ عند تغيير الحفاظة لطفل مصاب بالفيروس دون الإنتباه إلى غسل اليدين جيدآ بعد ذلك

-          أكل الفاكهة والخضراوات الملوثة، أو تناول الطعام المعد بواسطة شخص لامس الفضلات الملوثة ولم يغسل يديه جيدآ

-          شرب الماء الملوث بالفيروس المسبب

-          الممارسة الجنسية المحرمة (اللواط) مع شخص مصاب

 فترة الحضانة :-

نقصد بفترة الحضانة، الفترة الزمنية الفاصلة بين دخول الفيروس إلى الجسم وبدء الاعراض، وهي في حالة التهاب الكبد الفيروسي "أ" ما بين 15-50 يومآ بمعدل 28 يوم

 فترة العدوى :-

ويقصد بها الفترة الزمنية التي لا يكون فيها المصاب ناقلآ للعدوى وهي تمتد من اسبوعين قبل بدء الاعراض، وأهمها اليرقان وتستمر لمدة اسبوع بعد ظهوره

 الاعراض :-

يمكن أن تمر الاصابة بالتهاب الكبد الفيروس (ا) دون حدوث أية أعراض تذكر، ويمكن أن يشتكي المصاب من أعراض مختلفة بالحدة حسب شدة المرض، وهي كالتالي :

-          الاحساس بالتعب والارهاق

-          ارتفاع في درجة الحرارة

-          فقد الشهية

-          آلام في البطن

-          اسهال أو قيء

-          اليرقان ويشمل: اصفرار البول، وتغير لون البراز (يصير لون البراز فاتحآ)، واصفرار الجلد وملتحمة العين.

-     اختلال في وظيفة الكبد يظهر على شكل ارتفاع في مستوى الانزيمات الكبدية في الدم

تحتفي الاعراض تمامآ بعد مرور أربعة اسابيع على بدايتها، وتحدث مناعة جائمة ضد الفيروس، ولا يتطور المرض إلى التهاب مزمن أو تليف الكبد

 التشخيص :-

يعتمد الطبيب في تشخيص التهاب الكبد الفيروسي أ على التاريخ المرضي والفحص السريري، واجراء تحليل مخبري للدم للبحث عن الاجسام المضادة للفيروس (أ)

المزيد

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التصنيفات : غير مصنف |

دوّن الإدراج

قال علماء في بريطانيا الجمعة إن الإجهاد في العمل والضغوط المصاحبة له تزيد احتمالات الإصابة بأمراض القلب والسكري.

وكشف باحثون في كلية لندن أن ضغوط العمل تؤثر سلبا على الأيض (التغييرات الكيميائية في الخلايا الحية التي تؤمن الطاقة)، ما يؤدي إلى أعراض تشمل ارتفاع ضغط الدم ومستويات الكولستيرول والسكر في الدم إضافة إلى الوزن الزائد.

وقال الباحث بالكلية تاراني تشاندولا إن دراسة أجريت على أكثر من 10 آلاف موظف مدني بريطاني أظهرت أنه كلما زاد الإجهاد في العمل كلما زادت احتمالات الإصابة بالأعراض المؤدية إلى الإصابة بأمراض القلب والسكري.

ودرس العلماء معدلات الإجهاد لدى الموظفين

المزيد

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التصنيفات : غير مصنف |

دوّن الإدراج

مع توالي التقارير التي تشير إلى أن معدل ازدياد مرض السكري في الدول العربية يتجه نحو الارتفاع، تبقى التوعية هى حجر الأساس في وقف انتشار هذا المرض، لذلك يحتفل العالم يوم 14 نوفمبر من كل عام باليوم العالمي لمرض السكري، ويوافق هذا التاريخ ذكرى ميلاد العالم (فردريك بانتنج) مكتشف الإنسولين.

توصل فريق بحثي بالمركز الق

المزيد

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التصنيفات : غير مصنف |

دوّن الإدراج

علكة لأخذ الأنسولين بدل الحقن والحبوب     

أعلن صيدلي أميركي اكتشافه طريقة جديدة لإدخال مادة الأنسولين إلى الجسم عن طريق مضغ علكة بدل الأدوية الأخرى كالحقن والحبوب التي تؤخذ عن طريق الفم.

وقال روبرت دويلي من جامعة سايروكوس في نيويورك إن لديه حلا محتملا لمشكلة أن الجسم لديه آلية معينة لحماية وامتصاص الجزيئات القيمة لما تتعرض له من تلف عند وصولها إلى الأمعاء، مضيفا أن العلكة التي اخترعها تساعد الجسم على امتصاص الأنسولين بالشكل المطلوب.

وأضاف

المزيد

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التصنيفات : غير مصنف |

دوّن الإدراج

المزيد

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التصنيفات : غير مصنف |

دوّن الإدراج

A). Distribution

B). Regulation

C). Protection

 

A). Plasma

1). 90% water

2). 2% 100’s of solute.

3). 8% Plasma proteins

B). Formed elements:

all formed elements originate with the stem cell

1). Erythrocytes:

2). Leukocytes

a). Granulocytes b). Agranulocytes i). Neutrophils ii). Eosinophils iii). Basophils i). Lymphocytes ii). Monocytes

3). Platelets

A). Function

Respiratory gas transport

i).    great affinity

ii).   a large surface area

 iii). not use the oxygen

iv).  small size

B). Structure

1). Biconcave

2). No nucleus

3). Few organelles

4). Small

5). hemoglobin molecules

C). Hemoglobin proteins

O2 binding

 

D). Production of Erythrocytes:   Erythropoiesis

1). Hemocytoblast stem cell

2).Stem cell becomes committed

3).

4). Erythroblasts accumulate iron and hemoglobin

5).

6). Released as erythrocyte

 

Normoblasts eject organelles

Early erythroblasts have ribosomes

E). Controls of RBC concentration

 

1). Hormonal

i). Erythropoietin released by the kidneys

ii). Testosterone enhances erythropoietin

 

2). Erythrocyte destruction

i). Macrophages engulf old RBCs

ii). Iron is salvaged

iii). Heme degrades into bilirubin

 

 

SUMMARY of Development and Destruction Erythrocytes

 

Low O2

↓

Kidney releases erythropoietin

↓

 erythropoiesis in the red bone marrow

↓

RBCs are released

↓

Old, damaged RBCs engulfed by macrophages

                                  ↓                                                                 ↓

Remaining heme                                                       Iron recycled

↓

Become bilirubin

↓

Goes to the liver

↓

secreted in bile

↓

Bile enters the intestine

↓

Converts to urobilinogen

↓

Excreted in feces

Bilirubin

F). ABO Blood Types

Red blood cells have proteins called antigens on the membranes

1). Antigens & Antibodies

 

These can be A or B (or Rh) or all 3 or none of them.

If there are no A/B antigens the type is O.

If there are no Rh antigens it is Rh-.

 

Another set of proteins in the plasma are called antibodies or agglutinogens

An individual does not contain antibodies to the antigens on their red blood cells.

 

i.e.  A person with an A antigen would not have an A antibody

(anti-A) in their plasma because it would clump their red blood cells.

 

They would however have an antibody to antigens that are not normally present (anti-B)

 

ABO blood types cannot receive any blood that contains antigens that will clump in the presence of their natural antibodies.

2). Typing

   

Type O does not react  to anti A or anti B

Type A reacts to Anti A but not Anti B

Type B reacts to Anti B but not Anti A

Type AB reacts to both Anti A & B

 

Rh+ reacts to Anti Rh.

Rh- does not react Anti Rh.

http://orion.ramapo.edu/~spetro/labsyllabus/lbsys05.html

المزيد

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التصنيفات : غير مصنف |

دوّن الإدراج