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Biomedical subjects

S Panzer

Publications and source records attributed to S Panzer.

At least 37 records · Page 2Linked to original sources
PubMed2001

RHD sequencing: a new tool for decision making on transfusion therapy and provision of Rh prophylaxis.

The serological differentiation of weak D from partial D, D-negative and D-positive is not always unequivocal. Therefore, sequencing of the RHD gene is required in some cases. Very recently, several new differences between RHD and RHCE have been identified which permitted us to design primers close to the exon/intron boundaries of the RHD-exons. We evaluated these primers in 83 D-positive and 18 D-negative blood donors and applied the new method for the characterization of the RHD gene in six individuals with weak D phenotype. The amplification reactions were concordant with serological findings in 100 of 101 donors (99.0%). In one D-positive donor the PCR for exons 2 and 5 gave a negative result, while the sequence of the remaining eight exons was unchanged. By sequencing samples with very weak D serological reactions, we identified weak D type 4.2.2 and weak D type 15, both previously reported to be associated with anti-D-alloimmunization. Consequently, we recommended the selection of D-negative blood in the weak D type 4.2.2 patient, and the provision of Rh prophylaxis for pregnant women with weak D type 15. In summary, a new RHD sequencing method was developed which can be applied if serological reactions are inconclusive.

Blood Donors↗
PubMed2001

Report on the Tenth International Platelet Genotyping and Serology Workshop on behalf of the International Society of Blood Transfusion.

BACKGROUND AND OBJECTIVES: The aims of the 10th International Platelet Serology and Genotyping Workshop were to evaluate the proficiency of platelet immunology determinations. MATERIALS AND METHODS: There were 40 participants from 25 countries of four continents. Thirty-eight institutions reported results for genotyping, and 38 institutions reported their serological results. For genotyping, EDTA-anticoagulated whole-blood samples were provided (to allow the inclusion of DNA-separation methodology in the analysis) as well as separated DNA of a and b alleles for human platelet antigen (HPA)-1 to -6. For serological evaluations, sera contained allo- and autoantibodies, and for sensitivity testing a standard freeze-dried sample of HPA-5 antibody. RESULTS: All participants reported HPA-1, -2, -3 and -5 genotyping results; HPA-4 was determined in 29 laboratories and HPA-6 in 21. Results from 16 laboratories were concordant with the majority vote for all allotypes, eight institutions reported one deviation, five laboratories two, and nine laboratories three or more deviations. Twelve institutions had no deviation from the majority vote for HPA antibodies, nine had one, three had two, and 14 had three or more deviations. Most laboratories reported a reactivity of the standard anti-HPA-5b sample with HPA-5b platelets at a dilution of 1:4-1:8. Four laboratories detected anti-Gova in one sample. Seventeen laboratories reported no deviation from the majority vote for pan-reactive platelet antibodies, 12 had one deviation, two had two, and seven had three or more deviations. In addition, seven participants reported antibodies against glycoprotein IV (GPIV), three against glycoprotein V (GPV) and three against CD 109. These results were discussed at a meeting organized jointly with the International Society of Blood Transfusion (ISBT) 2000 Congress. CONCLUSION: The results for pan-reactive antibodies were heterogeneous with most discrepancies from the majority vote. The provision of sufficient samples for many participants is difficult. Based on the results and discussion it is clear that frequent workshops are needed in the future. Therefore, workshops shall be organized regionally, and each region shall participate with one institution in international workshops. The latter are needed to assure international exchange of experience and quality.

Antibody Specificity↗
PubMed2001

Platelet-reactive HLA antibodies associated with low posttransfusion platelet increments:a comparison between the monoclonal antibody-specific immobilization of platelet antigens assay and the lymphocytotoxicity test.

BACKGROUND: Platelet-reactive HLA antibodies are a major reason for low posttransfusion platelet increments. The clinical importance and value of the test systems for their in vitro determination is still controversial. STUDY DESIGN AND METHODS: A prospective analysis of HLA antibodies was performed in sera obtained once a week for at least 4 consecutive weeks from 55 patients (female/male, 28/27; age: median, 49 years; range, 18-69) undergoing intensive chemotherapy and in need of prophylactic platelet transfusions. All sera (n = 330) were analyzed by the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay and by the standard lymphocytotoxicity test (LCT). RESULTS: In the MAIPA, 24.5 percent of sera (81/330) obtained from 22 patients contained HLA antibodies. These were detected significantly more often by the MAIPA assay than by the LCT (24.5% vs. 8.2%). Fifty-five sera (20 patients) were positive in the MAIPA assay only. In 15 patients, HLA antibodies were transient. In 3 patients, HLA antibodies were detected earlier by the MAIPA assay than by the LCT. Significantly more sera obtained at the time of low posttransfusion platelet increments were positive in MAIPA alone, rather than in both MAIPA and the LCT (44% vs. 17%). CONCLUSION: The MAIPA assay is more sensitive than the standard LCT in detecting platelet-reactive HLA antibodies. These MAIPA-positive/LCT-negative HLA antibodies affect the posttransfusion platelet increment.

Adolescent↗
PubMed2001

Relationship of intestinal parasites to the environment and to behavioral factors in children in the Bolikhamxay Province of Lao PDR.

From March to July 1998 the infection rates of 732 children aged below 15 years were assessed. The investigation was conducted in selected villages of the Bolikhamxai Province in Lao PDR. Socio-economic conditions and behavioral pattern were studied. The three soil-transmitted helminths, Ascaris lumbricoides, Trichuris trichiura and hookworm were found with prevalence rates of 67.14, 17.49 and 12.83%, respectively. Infection rates with other intestinal parasites were negligible. Of the children investigated, 56.7% harbored one and 20.45% more than one parasite. Except for hookworms, no statistically significant differences were found between genders. The probability of being infected with A. lumbricoides is associated with living in mountainous areas. For hookworms, infection is associated with staying in the plains. A river in the vicinity of the village is linked with the probability of being infested with Trichuris trichiura. Not to belong to a family with the ability to own expensive items increases the probability by almost two times of getting infested with A. lumbricoides. Unhygienic behavioral factors were important in increasing the probability of suffering from A. lumbricoides and T trichiura infection. Behavioral factors did not seem to be related to hookworm infections. It was concluded that after mass treatment, besides promoting the construction of toilets, it is also important to improve personal hygiene so that a lasting impact on the infection rate of the most prevalent parasites in Lao PDR could be achieved. Measures to control parasitic infections do not have to be postponed until a marked improvement of the economic situation has occurred.

Adolescent↗
PubMed2001

Impaired platelet function among platelet donors.

BACKGROUND: Platelet transfusions are effective for the prevention and treatment of bleeding in patients with disorders of platelet number and/or function. In recent years plateletpheresis concentrates have outnumbered pooled platelet concentrates, albeit with significant differences between nations. Thus, the platelet quality of individual donors has become increasingly important. The aim of this study was to gain an estimate for the prevalence of impaired platelet function among platelet donors. STUDY DESIGN AND METHODS: We determined the inter-donor variability in platelet plug formation with a PFA-100 analyzer, the prevalence of impaired thromboxane formation, and effects of the density in alpha2 integrin polymorphism and density. RESULTS: (i) Collagen-epinephrine induced closure time (CEPI-CT) showed a great inter-subject variability in platelet donors and was higher than in healthy controls (p = 0.008). One-fifth of donors had abnormal CEPI-CT values and 11% exceeded >300 s (max measurable value). (ii) Decreased serum thromboxane B2 levels were found in 9% of all donors, compatible with surreptitious intake of cyclooxygenase inhibitors or with an aspirin-like defect. CEPI-CT correlated inversely with TxB2-levels in donors and controls. (iii) The density of the alpha2-integrin correlated negatively with CEPI-CT and CADP-CT values in controls, but was not responsible for the observed impaired platelet function in donors. (iv) Finally, the ABO blood group system modulates closure times. CONCLUSION: In sum, a large number of platelet donors present with prolonged closure times. Decreased thromboxane formation and frequent platelet donation partly account for this observation.

Adenosine Diphosphate↗
PubMed2000

Inhibitory activity of aspirin on von Willebrand factor-induced platelet aggregation.

The effect of aspirin (ASA) on vWF induced platelet - platelet interaction is unknown. We therefore tested the response of platelets to von Willebrand factor (vWF) coated beads induced platelet aggregation before and after i.v. and oral ASA. 1000 mg ASA was infused to 10 healthy individuals and after a wash-out period 7 volunteers received 100 mg ASA orally over a period of 11 days. Prior to ASA and in regular intervals thereafter we tested the reactivity to vWF-coated beads to assess platelet adhesion/aggregation and the fade-out time of ASA effects on platelets. Considerable interindividual variability in response to vWF-coated beads was observed, both before ASA and after treatment with ASA. The maximal response to vWF-coated beads (Tmax), the time lag, and the slope of the curve were significantly affected by i.v. ASA, whereas 100 mg of ASA had only inconstant effect on Tmax and slope. The absolute reduction of Tmax after ASA depended on the pre-ASA level, while the percentage of the reduction was similar in all individuals. Thus, platelet aggregation induced by vWF-coated beads is impaired by ASA. Furthermore, our data indicate a large interindividual variability of the response to ASA shortly after treatment induction, which becomes more constant after prolonged treatment.

Adult↗
PubMed2000

Platelet glycoprotein Ia gene dimorphism alpha2-807 in malignant arrhythmia in coronary artery disease.

It has been shown recently that the variable expression of the platelet collagen receptor integrin alpha2beta1 predisposes to thrombotic risk on the one hand and hemorrhagic risk on the other hand. The level of expression of the integrin alpha2beta1 is genetically controlled and associated with the alpha2-807 dimorphism. The expression level of this platelet collagen receptor may play a central role in the rapidly evolving coronary artery lesions that lead to malignant arrhythmia and sudden cardiac death. We studied allelic frequencies of the alpha2-807 dimorphism for their relation as a risk factor for malignant arrhythmia in a well-defined subgroup of patients with coronary artery disease. We compared allelic frequencies (by sequence specific primer polymerase chain reaction) of the dimorphism that is associated with integrin alpha2beta1 levels in 94 Caucasoid survivors of sudden cardiac death with a matched group of 106 patients with coronary artery disease without sudden cardiac death. Gene frequencies in the patient groups did not differ and were similar to those in the general population represented by 217 healthy individuals. There was no overrepresentation of an allele in any group. The inherited dimorphism that is associated with the levels of platelet integrin alpha2beta1 is not associated with malignant arrhythmia in coronary artery disease patients.

Adult↗
PubMed2000

Presence of clone-specific antigen receptor gene rearrangements at birth indicates an in utero origin of diverse types of early childhood acute lymphoblastic leukemia.

There is strong evidence that infant leukemias with a t(4;11) translocation originate in utero. To test whether other subtypes of childhood leukemias are also initiated during fetal life, we used clone-specific genetic markers for the analysis of neonatal blood spots from 5 children aged 6 months to 4 years 8 months at diagnosis of pro-B, common acute lymphoblastic leukemia (ALL), and T-ALL. In all children, the clonotypic antigen receptor gene rearrangements were already present at birth. The estimated amount of clonotypic cells was in the range of 10 to 100 cells per blood spot. In 2 infants with a t(4;11) positive ALL, we detected similar amounts of the fusion gene sequences compared with the clonal antigen receptor gene rearrangements, suggesting the presence of both markers in the same cells. Our data indicate that the first leukemogenic event of diverse types of childhood ALL may already occur in utero. (Blood. 2000;95:2722-2724)

B-Lymphocytes↗
PubMed2000

Rapid molecular response during early induction chemotherapy predicts a good outcome in childhood acute lymphoblastic leukemia.

Early response to therapy is an independent prognostic factor in childhood acute lymphoblastic leukemia. Although most patients have rapid early responses, as detected by morphology, 15% to 20% of patients have relapses. The authors evaluated residual disease by molecular methods on day 15 of minimal residual disease (MRD) therapy and compared these data with their recently established MRD-based risk stratification, defined by MRD levels 5 weeks after induction treatment and before consolidation. All 68 children treated according to current Berlin-Frankfurt-Münster (BFM) protocols went into morphologically complete remission after induction. There was a significant difference in outcome between children with rapid disease clearance and those with high levels of day-15 MRD (P =.035). Among patients with high levels of day-15 MRD, only the MRD-based risk stratification was predictive of the outcome. All patients with negative or low day-15 MRD had excellent prognoses and were in the MRD-based low-risk group. Thus, after only 2 weeks of treatment, the authors were able to identify a patient population of 20% who may benefit from the least intensive treatment.

Adolescent↗
PubMed2000

Thrombopoietin induces rapid resolution of thrombocytopenia after orthotopic liver transplantation through increased platelet production.

Thrombopoietin (TPO) deficiency has been proposed as an important etiologic factor for thrombocytopenia in advanced-stage liver disease. To clarify the contributions of platelet production, platelet consumption, coagulation activation, and splenic sequestration to thrombocytopenia in liver disease, we studied TPO serum levels and markers of platelet production, platelet activation, and coagulation activation before and 14 days after orthotopic liver transplantation (OLT) in 18 patients with advanced liver cirrhosis. Thrombocytopenia before transplantation occurred with low-normal serum levels of TPO, normal levels of platelet and coagulation activation markers, and no increase in bone marrow production of platelets. TPO serum levels increased significantly on the first day after OLT, preceding the increase of reticulated platelets by 3 days and peripheral platelets by 5 days. Normalization of the peripheral platelet count occurred in most patients within 14 days of OLT, irrespective of the change in spleen size assessed by computed tomography volumetry. Normalization of platelet counts was not hampered by a certain degree of platelet activation observed during the steepest increase in the peripheral platelet count. Bone marrow production of platelets increased significantly within 2 weeks of transplantation. Low TPO serum levels with low platelet counts and without platelet consumption suggests low TPO production in end-stage liver disease. The rapid increase in TPO serum levels after transplantation induces an increase in the bone marrow production of platelets. Decreased TPO production in the cirrhotic liver is an important etiologic factor for thrombocytopenia in liver disease that is rapidly reversed by transplantation.

Adult↗
PubMed2000

The platelet alpha2-integrin (GPIa) nucleotide-807 polymorphism is not associated with a risk for maternal-fetal human platelet antigen-5 incompatibility.

Alloimmunization against human platelet antigen (HPA)-5 may lead to neonatal alloimmune thrombocytopenia. The HPA-5 dimorphism is expressed on the platelet alpha2beta1 integrin. The density of this receptor is associated with another dimorphism of the 2beta1 integrin (nucleotide-807C/T). We hypothesized that anti-HPA-5b-induced neonatal thrombocytopenia is more likely to occur if the receptor is expressed at high than at low levels. Among 933 mother-child pairs, we identified 79 HPA-5aa mothers giving birth to a HPA-Sab offspring. Seventeen mothers had HPA-5b antibodies, but the offspring had a normal platelet count. We genotyped the offspring and mothers for the alpha2-807C/T dimorphism to evaluate its relationship to antibody formation. There was no difference between the frequency of the 807C/T dimorphism among children delivered from alloimmunized mothers and those from mothers without antibodies (P>0.3). The frequency of the 807C/T dimorphism was not different in the two maternal groups. In three maternal-fetal incompatibilities, we observed at delivery normal platelet counts of platelets typed HPA-5b-alpha2807T, despite increasing maternal antibody titers during the pregnancy. Our data do not support the hypothesis that the 807C/T dimorphism in the HPA-5ab children is a predisposing factor to either elicit alloimmunization against HPA-5b or for neonatal alloimmune thrombocytopenia.

Adult↗
PubMed2000

Calcaneal ultrasound attenuation and vitamin-D-receptor genotypes in celiac disease.

BACKGROUND: Osteopenia is common in patients with celiac disease and is believed to result from malnutrition. Osteoporosis in otherwise healthy individuals is related to genetically determined polymorphisms within the vitamin-D-receptor (VDR) gene. We hypothesized that in celiac patients particular genes of the VDR enhance the susceptibility for malnutrition-associated low-bone density. METHODS: We determined allelic frequencies within the VDR gene by restriction fragment length polymorphism analysis in 92 patients with celiac disease (age, 15-83 years). Thirty-eight patients were on a gluten-free diet; 54 patients did not adhere to a diet. The determined VDR polymorphisms in 111 unrelated newborns served as controls. Osteopenia was determined by means of ultrasound measurements of the calcaneus (n = 78). Bone turnover was estimated by osteocalcin determination (n = 60). RESULTS: There was no difference in the frequency of the VDR gene polymorphisms in patients with celiac disease compared with controls. Adjusted ultrasound measures of the calcaneus were low in 47% of patients, but there was no difference of the VDR gene frequencies in these patients compared with those with normal ultrasound results or controls. Bone turnover was higher in patients without a gluten-free diet (P = 0.02). Again, there was no association with any particular VDR gene. CONCLUSIONS: Patients with celiac disease frequently have osteopenia, which is not related to any of the determined genes within the VDR.

Adolescent↗
PubMed2000

Monitoring of aspirin (ASA) pharmacodynamics with the platelet function analyzer PFA-100.

BACKGROUND: Anti-platelet drug therapy is currently performed without monitoring, because the established method of platelet aggregometry is cumbersome. The recently developed platelet function analyzer PFA-100 measures shear stress dependent, collagen epinephrine (CEPI) and collagen adenosine diphosphate (CADP) induced platelet plug formation. As the PFA-100 provides a valuable tool to detect patients with platelet dysfunction more efficiently and cost-effectively than aggregometry, we investigated its potential to monitor the efficacy of aspirin treatment. METHODS: All healthy volunteers (n = 10) received a fractionated infusion of L-aspirin to establish individual dose-response curves. Further, in a randomized, double-blind, placebo controlled two-way cross over study the same volunteers received either 50 or 100 mg aspirin/day p.o. for a period of 11 days to determine the day-to-day variability CEPI induced closure time (CT) under constant intake of low dose aspirin, and to compare the efficacy of those two doses. RESULTS: Intra- and intersubject variability of CEPI-CT averaged 9% and 22%, respectively. Seven volunteers exceeded the maximum of CEPI-CT (>300 s) already after infusion of 100 mg L-aspirin. Intake of 100 mg of aspirin elicited a more rapid onset of effect than 50 mg, which was only significant on days 3 and 4 of aspirin intake. The aspirin induced CEPI-CT prolongation correlated positively with basal CEPI-CT values (r = 0.86; p = 0.001) and were strongly dependent on von Willebrand Factor levels (r = -0.9; p = 0.001). CONCLUSION: Thus, the PFA-100 system appears suitable to demonstrate an aspirin-induced platelet effect in a longitudinal study, and may be adequate to monitor a patient's compliance. However, prospective trials have to be conducted to demonstrate whether the EPI-CT achieved under ASA-intake has predictive value for cardiovascular outcome.

Adenosine Diphosphate↗
PubMed1999

The role of the anterior prefrontal cortex in human cognition.

Complex problem-solving and planning involve the most anterior part of the frontal lobes including the fronto-polar prefrontal cortex (FPPC), which is especially well developed in humans compared with other primates. The specific role of this region in human cognition, however, is poorly understood. Here we show, using functional magnetic resonance imaging, that bilateral regions in the FPPC alone are selectively activated when subjects have to keep in mind a main goal while performing concurrent (sub)goals. Neither keeping in mind a goal over time (working memory) nor successively allocating attentional resources between alternative goals (dual-task performance) could by themselves activate these regions. Our results indicate that the FPPC selectively mediates the human ability to hold in mind goals while exploring and processing secondary goals, a process generally required in planning and reasoning.

Brain Mapping↗
PubMed1999

The rise of reticulated platelets after intensive chemotherapy for AML reduces the need for platelet transfusions.

We assumed that a recovery of thrombopoiesis after intensive chemotherapy for acute myelogenous leukemia (AML) could reduce the need for prophylactic platelet transfusions. We therefore assessed the start of platelet production by means of daily determination of reticulated platelets (RP). The increase in RP occurred on day 20 (median) after the start of chemotherapy and was followed by a rise of peripheral platelet counts 2-3 days thereafter. Consequently, a rise of RP during the period of recovery can be regarded as representing the reconstitution of the peripheral platelet count and may reduce or eliminate the need for prophylactic platelet transfusions.

Adult↗
PubMed1999

Heterogeneous TCR delta Vdelta2-Ddelta3 rearrangements and their relation to IgH and TCR gamma gene status in childhood B cell precursor leukaemias.

In this study we aimed to test the hypothesis that leukaemias with oligoclonal Vdelta2-Ddelta3 rearrangements are clonal at the IgH and TCRG gene status and that the oligoclonality is a poor prognostic marker. In ten leukaemias the individual Vdelta2-Ddelta3 rearrangements characterised different populations as deduced from single cell analysis and/or from densitometric differences of PCR products. Five of these leukaemias were clonal by the IgH and/or TCRG gene status. We therefore conclude that ALL is a clonal disease despite the presence of heterogeneous TCRD rearrangements. Our clinical data show that oligoclonality at the TCRD level does not represent an adverse prognostic factor.

Aneuploidy↗
PubMed1999

Identification of women with early breast cancer by analysis of p43-positive lymphocytes.

Regular screening mammographies and increasing knowledge of high-risk groups have resulted in an improvement in the rate of detection of smaller malignant lesions. However, uncertain minimal mammographic features frequently require further costly and often uncomfortable investigation, including repeat radiological controls or surgical procedures, before cancerous lesions can be identified. Placental isoferritin (p43), a protein with immunosuppressive effects, has been detected on the surface of lymphocytes taken from peripheral blood in patients with breast cancer. In this study we evaluated the sensitivity and specificity of the expression of p43-positive lymphocytes as a marker in early stage breast cancer and also investigated its expression on T-cell subpopulations. The presence of p43-positive lymphocytes was investigated using the monoclonal antibody CM-H-9 and flow cytometry in 76 women with controversial, non-palpable mammographic findings who were undergoing surgical biopsy. Patients with early breast cancer (n = 48) had significantly higher p43-positive cell values (median 3.83%, range 0.98-19.4) than patients with benign lumps (n = 28, median 1.43%, range 0.17-3.7) or controls (n = 22, median 1.3%, range 0.4-1.87) (P < 0.0001). At a cut-off level of 2% p43-positive cells a sensitivity of 91.7% and a specificity of 89.3% for detection of breast cancer could be reached. While the median ratio of total CD4+/CD8+ cells was 2.6, a ratio of 1.3 was found for the p43-positive subpopulation (P < 0.001), thus indicating a significant link between p43 and CD8+ cells. The determination of p43-positive lymphocytes in peripheral blood could serve as an additional diagnostic tool in patients with controversial mammographic findings and could also reduce the need for cost-intensive and often uncomfortable management of these patients.

Antigens, Neoplasm↗