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Biomedical subjects

Abdulgabar Salama

Publications and source records attributed to Abdulgabar Salama.

At least 19 recordsLinked to original sources

High-level serum B-cell activating factor and promoter polymorphisms in patients with idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which platelets are opsonised by autoantibodies and destroyed by macrophages. Therefore, ITP represents a prototype of a B-cell-mediated autoimmune disorder. B-cell activating factor (BAFF) is a member of the tumour necrosis factor family and an important regulator of B-cell development. BAFF levels were determined in serum samples from 53 patients with ITP. Serum BAFF levels in patients with an active ITP were increased when compared with the healthy control group (median 1620 pg/ml vs. 977 pg/ml; P < 0.001). Moreover, immunosuppressive treatment was associated with strongly suppressed BAFF levels (median 629 pg/ml; P < 0.01). In addition, a polymorphic site was detected in the BAFF promoter region (-871) that appeared to occur more frequently in ITP patients than in healthy persons. This promoter variant was associated with very high BAFF levels in ITP patients. Our data suggest that BAFF is an important pathogenetic factor in the development of ITP.

Adult↗

A novel agglutination test for antigen-specific detection of platelet antibodies.

A simple and rapid antigen-specific assay for the identification antibodies to platelets is lacking, yet. Red-dyed polystyrene microbeads were coated with monoclonal antibodies to various platelet glycoprotein complexes, and used for the detection of platelet autoantibodies and alloantibodies. The results were largely identical with those obtained by monoclonal antibody-specific immobilization of platelet antigen assay (MAIPA). The new test is reliable yet less complex and time-consuming than the currently available assays, and it can be implemented in any routine laboratory.

Agglutination Tests↗

Detailed analysis of the variability of peptidylarginine deiminase type 4 in German patients with rheumatoid arthritis: a case-control study.

Peptidylarginine deiminase type 4 (PADI4) genotypes were shown to influence susceptibility to rheumatoid arthritis (RA) in the Japanese population. Such an association could not previously be confirmed in different European populations. In the present study, we analysed exons 2-4 of PADI4 in 102 German RA patients and 102 healthy individuals to study the influence of PADI4 variability on RA susceptibility by means of haplotype-specific DNA sequencing. Analyses of the influence of PADI4 and HLA-DRB1 genotypes on disease activity and on levels of anti-cyclic citrullinated peptide antibodies were performed. Comparing the frequencies of PADI4 haplotype 4 (padi4_89*G, padi4_90*T, padi4_92*G, padi4_94*T, padi4_104*C, padi4_95*G, padi4_96*T) (patients, 14.7%; controls, 7.8%; odds ratio = 2.0, 95% confidence interval = 1.1-3.8) and carriers of this haplotype (patients, 27.5%; controls, 13.7%; odds ratio = 2.4, 95% confidence interval = 1.2-4.8), a significant positive association of PADI4 haplotype 4 with RA could be demonstrated. Other PADI4 haplotypes did not differ significantly between patients and controls. Regarding the individual PADI4 variants, padi4_89 (A-->G), padi4_90 (C-->T), and padi4_94 (C-->T) were significantly associated with RA (patients, 49.5%; controls, 38.7%; odds ratio = 1.6, 95% confidence interval = 1.1-2.3). Considering novel PADI4 variants located in or near to exons 2, 3, and 4, no quantitative or qualitative differences between RA patients (8.8%) and healthy controls (10.8%) could be demonstrated. While the PADI4 genotype did not influence disease activity and the anti-cyclic citrullinated peptide antibody level, the presence of the HLA-DRB1 shared epitope was significantly associated with higher anti-cyclic citrullinated peptide antibody levels (P = 0.033). The results of this small case-control study support the hypothesis that variability of the PADI4 gene may influence susceptibility to RA in the German population. Quantitative or qualitative differences in previously undefined PADI4 variants between patients and controls could not be demonstrated.

Adolescent↗

Misdiagnosis in patients with diclofenac-induced hemolysis: new cases and a concise review.

Diclofenac has been implicated in many cases of life-threatening immune hemolytic anemia (IHA). Nevertheless, confusion still occurs at the bedside and in the laboratory. Herein we report nine new patients and summarize all published cases (total, n = 61). Direct and indirect antiglobulin tests were performed according to standard procedures. Tests for drug-dependent antibodies were performed in the presence and absence of the target drugs and their ex vivo antigens (in the urine of patients treated with the drug). Diclofenac- and/or ex-vivo-antigen-dependent red cell antibodies were detected in all new cases. We identified nine new cases with diclofenac-dependent IHA. All cases were initially suspected to have an abdominal illness and/or autoimmune hemolytic anemia of warm type. Acute renal failure was present in three of the 9 new patients and in 20 of 37 published patients. Seven of the 46 patients died (15%), and clinical information is lacking in 15 other published cases. Diclofenac-dependent and/or ex-vivo-antigen-dependent IHA should always be considered when a patient on diclofenac develops acute renal failure and/or IHA.

Acute Kidney Injury↗

Differences in the transmigration of different dendritic cells.

OBJECTIVE: Although several methods for the generation of dendritic cells (DCs) exist, little is known about the transmigration capacities of the cells developed. Their ability to migrate to the adjacent lymphatic system is relevant since their efficacy does also rely on their potential to interact with lymphocytes. METHODS: We studied the transmigration of DCs derived from hematopoietic progenitor cells (HPC), from peripheral blood monocytes, and from leukemic cells. DCs from monocytes and leukemic cells could be generated within 1 week, whereas DCs from HPC needed 2 weeks for maturation. RESULTS: While DCs from all sources showed similar morphologic features and allostimulatory capacities, their transmigration capacities varied: HPC-derived DCs showed the highest migratory response to macrophage inflammatory protein (MIP)-3alpha and beta. Monocyte-derived DCs were equally attracted to MIP-3beta and stroma-derived factor (SDF)-1alpha. Only few leukemic DCs migrated in response to SDF-1. Other chemoattractants tested included MIP-1alpha and RANTES. Replacement of fetal bovine by human serum did not change the DC's overall migratory capacities. It did, however, influence the responsiveness to certain chemokines. CONCLUSION: Although DCs from all three sources are immunocompetent antigen-presenting cells, our findings suggest that HPC and monocyte-derived DCs can be administered subcutaneously and intravenously, but that leukemic DCs should be injected into the lymph node.

Cell Communication↗

Implant-related inflammatory arthritis.

BACKGROUND: A 54-year-old woman presented with myalgia and arthralgia predominantly in the knees and small joints of the hands and feet with morning stiffness lasting for at least 2 h. The patient had received a wrought titanium 6-aluminium 4-vanadium alloy C cage implant 1.5 years previously, following a severe disc prolapse. No signs of rheumatic disease were evident before the C cage was implanted. INVESTIGATIONS: Physical examination, radiography, skin and muscle biopsies, serology tests, white blood cell count, HLA genotyping, tumor necrosis factor release assay, skin patch test, lymphocyte transformation test. DIAGNOSIS: Implant-related inflammatory arthritis. MANAGEMENT: Combination therapy with corticosteroids, disease-modifying antirheumatic drugs and nonsteroidal anti-inflammatory drugs, and replacement of the titanium cage with a polyetherketone cage.

Arthralgia↗

A simple and practical assay for the antigen-specific detection of platelet antibodies.

BACKGROUND: The antigen-specific assays currently used for characterization of platelet (PLT)-reactive auto- and alloantibodies are too technically complex and impracticable for most routine laboratories. Here, a novel antigen-specific particle assay (ASPA) for PLTs similar to that of red blood cells is described. STUDY DESIGN AND METHODS: PLTs were solubilized and then incubated with red-dyed polystyrene particles coated with monoclonal antibodies (MoAbs) to various PLT glycoprotein complexes. These particles were directly tested for coating with autoantibodies (n = 8) or indirectly tested for serum autoantibodies (n = 33) or alloantibodies against HPA-1a (n = 4) or HPA-5b (n = 5). Serum samples from healthy blood donors (n = 100) served as negative controls. RESULTS: Negative reactions were clearly distinguishable from positive reactions, and the results of the particle assay were in concordance with those obtained by the standard MoAb-specific immobilization of PLT antigen assay (MAIPA) in all cases with alloanti-bodies. In three patients, only the ASPA was able to detect autoantibodies that were completely undetectable by the MAIPA. In contrast, in only one patient, the MAIPA detected autoantibodies that the ASPA failed to detect. CONCLUSION: In our opinion, the new ASPA is reliable, yet less complex and time-consuming than the currently available assays, and it can be implemented in any routine laboratory.

Antibodies, Monoclonal↗

Thawing procedures and the time course of clotting factor activity in fresh-frozen plasma: a controlled laboratory investigation.

BACKGROUND: In this study, we evaluated the effects of the thawing process of 2 commercially available devices on the activity of clotting factors, inhibitors and activation markers of the hemostatic system in fresh-frozen plasma (FFP). In an experimental procedure, FFP was thawed under running warm water at 42 degrees C. METHODS: Plasma of 20 healthy donors was sampled, separated, and distributed in 3 plasma bags. Within 2 h after sampling plasma bags was frozen at a temperature of -30 degrees C to -40 degrees C and stored for at least 8 wk. After sampling (baseline) as well as immediately and 1, 2, 4, and 6 h after thawing, the activity of FV, FVII, FVIII, fibrinogen, fibrin monomers (FM), d-dimers (DD), alpha2-antiplasmin (alpha2-AP), and protein S (PS) was determined from each plasma bag. RESULTS: From 1 h to 6 h after thawing, no significant differences in the activity of the investigated coagulation markers dependent on the thawing procedure were found. However, immediately after thawing and independent of the thawing procedure, the activity of FVII was significantly decreased (P < 0.01), whereas FM were significantly increased (P = 0.001). CONCLUSION: The thawing procedures studied exhibited no significant influence on activity and stability of the investigated markers of coagulation over the study period. The decreased activity of FVII and the clinical significance of the increase in FM require further research.

Adult↗

Gene polymorphisms implicated in influencing susceptibility to venous and arterial thromboembolism: frequency distribution in a healthy German population.

Evolvement and progression of cardiovascular diseases affecting the venous and arterial system are influenced by a multitude of environmental and hereditary factors. Many of these hereditary factors consist of defined gene polymorphisms, such as single nucleotide polymorphisms (SNPs) or insertion-deletion polymorphisms, which directly or indirectly affect the hemostatic system. The frequencies of individual hemostatic gene polymorphisms in different normal populations are well defined. However, descriptions of patterns of genetic variability of a larger extent of different factors of hereditary hypercoagulability in single populations are scarce. The aim of this study was i) to give a detailed description of the frequencies of factors of hereditary thrombophilia and their combinations in a German population (n = 282) and ii) to compare their distributions with those reported for other regions. Variants of coagulation factors [factor V 1691G>A (factor V Leiden), factor V 4070A>G (factor V HR2 haplotype), factor VII Arg353Gln, factor XIII Val34Leu, beta-fibrinogen -455G>A, prothrombin 20210G>A], coagulation inhibitors [tissue factor pathway inhibitor 536C>T, thrombomodulin 127G>A], fibrinolytic factors [angiotensin converting enzyme intron 16 insertion/deletion, factor VII-activating protease 1601G>A (FSAP Marburg I), plasminogen activator inhibitor 1-675 insertion/deletion (5G/4G), tissue plasminogen activator intron h deletion/insertion], and other factors implicated in influencing susceptibility to thromboembolic diseases [apolipoprotein E2/E3/E4, glycoprotein Ia 807C>T, methylenetetrahydrofolate reductase 677C>T] were included. The distribution of glycoprotein Ia 807C>T deviated significantly from the Hardy-Weinberg equilibrium, and a comparison with previously published data indicates marked region and ethnicity dependent differences in the genotype distributions of some other factors.

Arterial Occlusive Diseases↗

Hemoglobin screening in prospective blood donors: comparison of different blood samples and different quantitative methods.

Portable photometers are increasingly used for hemoglobin screening in blood centers. In a total of 500 unselected prospective blood donors, venous hemoglobin concentrations were measured using a hematology analyzer, and fingerstick hemoglobin concentrations were measured on both a HemoCue B and a Biotest hemoglobin photometer. In 100 of the donors, earstick hemoglobin levels were also measured on the HemoCue system. The mean hemoglobin levels in the fingerstick samples were slightly higher than those in the venous samples. The deviation exceeded the limit of +/-10g l(-1) in 9% of samples tested by HemoCue and in 20% of those investigated by Biotest. The use of earstick samples led to considerable overestimation of the actual hemoglobin concentration.

Blood Donors↗

Failure of bedside ABO testing is still the most common cause of incorrect blood transfusion in the Barcode era.

BACKGROUND AND OBJECTIVES: ABO-incompatible red blood cell (RBC) transfusions are a major risk in transfusion medicine. Identification of factors leading to this hazard is important to improve transfusion safety. MATERIAL AND METHODS: All consecutive erroneous ABO-incompatible transfusions occurring from January 1997 to December 2004 at the Charité University Hospital in Berlin, Germany were analysed. RESULTS: A total of 343,432 RBC units were transfused, and eight patients erroneously received 13 ABO-incompatible RBC concentrates. The most frequent error was incorrect bedside testing (n=7). Intensive care treatment was required in two cases, but there were no fatal mistransfusions. Four patients had no or only mild reactions. CONCLUSION: Mistransfusions are still a considerable risk in transfusion medicine despite quality control systems and electronic data processing. An increase in transfusion safety may require the introduction of further systems, e.g. radio-frequency identification (RFID) tags.

ABO Blood-Group System↗

The alpha4beta1 and alpha5beta1 integrins mediate engraftment of granulocyte-colony-stimulating factor-mobilized human hematopoietic progenitor cells.

BACKGROUND: The alpha4beta1 and alpha5beta1 integrins are major adhesion molecules of murine and human hematopoietic progenitor cells. Granulocyte-colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPCs) are the most important source for clinical hematopoietic cell transplantation today. The contribution of alpha4beta1 and alpha5beta1 integrins to homing of PBPCs has not been studied yet. STUDY DESIGN AND METHODS: The expression of alpha4beta1 and alpha5beta1 integrins on purified human PBPCs was analyzed. Integrin function in adhesion to recombinant fibronectin and migration on fibronectin-coated transwells was assessed with fragments combining different adhesion domains and function-blocking antibodies. Finally, the function of those integrins in a transplantation model was investigated with repopulating cells of nonobese diabetic/severe combined immune-deficient (NOD/SCID) mice. RESULTS: More than 90 percent of all purified peripheral blood CD34+ cells express alpha4beta1 integrins, whereas only 10 to 15 percent express alpha5beta1. The alpha4beta1 integrin alone influences adhesion whereas alpha4beta1 and alpha5beta1 both mediate chemotaxis of clonogenic CD34+ progenitor cells on recombinant fibronectin. Importantly, antibodies against the integrins alpha4beta1 and alpha5beta1 independently reduce the repopulation of NOD/SCID mouse marrow after transplantation of human peripheral blood CD34+ cells. CONCLUSIONS: Alpha4beta1 and alpha5beta1 integrins are functional and critical adhesion receptors expressed on G-CSF-mobilized CD34+ hematopoietic blood progenitor cells with repopulating capacity mediating engraftment after transplantation.

Animals↗

Rapid identification of iron deficiency in blood donors with red cell indexes provided by Advia 120.

BACKGROUND: A new generation of automated hematology analyzers allows the rapid determination of various red cell (RBC) indexes, including the percentage of hypochromic mature RBCs (HYPOm) and the hemoglobin (Hb) content of reticulocytes (CHr). These indexes have not yet been validated as measures for the detection of iron deficiency in blood donors. STUDY DESIGN AND METHODS: Iron status was evaluated in a total of 1142 unselected prospective blood donors based on measurement of serum ferritin, soluble transferrin receptor, and Hb compared to RBC indexes provided by an automated hematology analyzer (Advia 120, Bayer HealthCare) including HYPOm and CHr. RESULTS: Assuming that the most precise measure for body iron storage is related to the logarithm of the ratio of soluble transferrin receptor to ferritin, the sensitivity of ferritin for the diagnosis of iron depletion was 89 percent compared to 57 percent for HYPOm and CHr, respectively, to 69 percent for the combination of both RBC indexes, and to 26 percent for Hb concentration. CONCLUSION: The RBC indexes HYPOm und CHr are significantly better screening measures for identification of iron depletion in blood donors than Hb.

Adolescent↗

After major ABO-mismatched allogeneic hematopoietic progenitor cell transplantation, erythroid engraftment occurs later in patients with donor blood group A than donor blood group B.

BACKGROUND: Isohemagglutinins directed against the donor blood group frequently delay erythroid engraftment after major ABO-mismatched allogeneic hematopoietic progenitor cell transplantation (HPCT). Graft-versus-host reactions are capable of accelerating the clearance of isohemagglutinins. Whether immunogenicity of the A- and B-antigen is important in this process is unknown. PATIENTS AND METHODS: Data of 807 patients from three centers were screened for patients with major or bidirectionally ABO-mismatched donors. Clinical data and red blood cell (RBC) transfusion support were analyzed retrospectively. RESULTS: A total of 158 patients with major or bidirectionally mismatched donors were identified. After major mismatched HPCT, patients with anti-A directed against the donor blood group required RBC transfusion support for a median of 109 days (range, 0-324 days) compared to 21 days (range, 2-98 days) for patients with anti-B directed against donor blood group (log-rank test, p = 0.0001). Other risk factors associated with prolonged RBC transfusion support in univariate analysis were age (p = 0.024), cytomegalovirus infection (p = 0.016), hemolytic anemia (p = 0.027), and chronic bleeding disorders (p = 0.038). The independent influence of donor blood group and recipient age were confirmed in a multivariate analysis. CONCLUSION: These results indicate that the immunogenicity of the ABO antigen plays an important role for the kinetics of erythroid engraftment after ABO-mismatched HPCT.

ABO Blood-Group System↗

Oxaliplatin-induced immune pancytopenia.

BACKGROUND: Oxaliplatin, a third-generation platinum compound, has been implicated in isolated cases of immune hemolytic anemia and/or immune thrombocytopenia. The first case of severe immune pancytopenia related to oxaliplatin is described. PATIENT AND METHODS: A 79-year-old woman with colorectal cancer was initially treated with 5-fluorouracil and she later received oxaliplatin and leucovorin every 2 to 4 weeks. During the 15th and 17th cycles of chemotherapy she developed thrombocytopenia, hemolysis, and neutropenia. No problems occurred during the 16th cycle without oxaliplatin. Serologic testing including detection of drug-dependent antibodies and autoantibodies was performed with standard techniques. RESULTS: Serologic findings included a positive immunoglobulin G direct antiglobulin test; nonreactive red blood cell (RBC) eluates; platelet (PLT)-bound antibodies to glycophorin (GP) IIb-IIIa, GPIb-IX, and GPIa-IIa; and oxaliplatin-dependent antibodies to PLTs, RBCs, and neutrophils. CONCLUSION: Oxaliplatin may lead to the production of ddabs to RBCs, PLTs, and neutrophils. Thus the risk of immune cytopenias should always be considered in patients treated with oxaliplatin.

Aged↗