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ITP
Kinds of ITP Terms modified by ITP Selected AbstractsReticulated platelet counts correlate with treatment response in patients with idiopathic thrombocytopenic purpura and help identify the complex causes of thrombocytopenia in patients after allogeneic hematopoietic stem cell transplantationCYTOMETRY, Issue 4 2007Anna-Katharina Thomas-Kaskel Abstract Background: In thrombocytopenic conditions of unknown origin, quantification of reticulated platelets (RP) in the peripheral blood by flow cytometry has been shown to differentiate increased platelet (Plt) turnover from insufficient Plt production. Methods: We used a whole blood flow cytometry method combining thiazole orange and anti-CD41a-staining to assess RP in 71 healthy subjects, six with thrombocytopenic myelodysplastic syndrome (MDS), nine with liver cirrhosis, 14 patients with idiopathic thrombocytopenic purpura (ITP), and 12 patients who had undergone hematopoietic stem cell transplantation (HSCT). Results: Patients with MDS had normal, patients with liver cirrhosis had slightly elevated RP counts compared to healthy subjects. ITP patients had elevated RP counts, and RP >15% were associated with treatment response (P = 0.015). In 7/10 patients after HSCT, an increase of RP preceded Plt recovery, whereas in patients with secondary thrombocytopenia after normal regeneration, the assessment of RP allowed the differentiation between conditions with high Plt turnover, such as GvHD and microangiopathy, indicated by high RP counts, and graft failure, indicated by low RP counts. Conclusions: Our data provide the rationale for prospective studies on the diagnostic and prognostic value of RP counts in larger patient populations with ITP and after HSCT. © 2007 Clinical Cytometry Society [source] Recent advances in enhancing the sensitivity of electrophoresis and electrochromatography in capillaries and microchips (2006,2008)ELECTROPHORESIS, Issue 1 2009Michael C. Breadmore Abstract Poor sensitivity is still considered to be one of the major limitations of electrophoresis, which is surprising given the power, flexibility and versatility of many of the approaches to on-line concentration that have developed over the last 20 years. This is still a very active area of interest and this review will cover developments in the field over the last two years since the last review (Electrophoresis 2007, 28, 254,281) through to June 2008. It includes developments in the fields of stacking, covering all methods from field-amplified sample stacking and large volume sample stacking, through to ITP, dynamic pH junction and sweeping. Attention is also given to on-line or in-line extraction methods that have been used for electrophoresis. [source] Determination of ethyl glucuronide in human serum by hyphenation of capillary isotachophoresis and zone electrophoresisELECTROPHORESIS, Issue 8 2008Michaela Nováková Abstract The determination of ethyl glucuronide (EtG), a marker of recent alcohol consumption, in human serum by hyphenation of capillary ITP (CITP) and CZE is reported. For CITP step, 1×10,2,M hydrochloric acid adjusted with ,-aminocaproic acid (EACA) to pH,4.4 was used as the leading electrolyte, and 1×10,2,M nicotinic acid with EACA, pH,4.4, was used as the terminating electrolyte (TE). All electrolytes contained 0.2% hydroxypropylcellulose to suppress electroosmosis. In CITP, EtG was separated from fast serum macrocomponents chloride, phosphate, lactate, and acetate. Zones of microcomponents including EtG that migrated between acetate and nicotinate were forwarded to the second capillary filled with a BGE identical with the TE. Conductivity detection was used in the CITP step. Sensitive detection in the CZE step was performed using indirect spectrophotometric detection at 254,nm. The assay is based on a 1:5 dilution of serum with deionized water and has a concentration LOD for EtG in diluted sample of 9.8×10,9,M. The method was used for the determination of EtG in sera of volunteers consuming alcohol. [source] Recent developments in CE and CEC of peptidesELECTROPHORESIS, Issue 1 2008Václav Ka, ka Dr. Abstract The article brings a comprehensive survey of recent developments and applications of high-performance capillary electromigration methods, zone electrophoresis, ITP, IEF, affinity electrophoresis, EKC, and electrochromatography, to analysis, preparation, and physicochemical characterization of peptides. New approaches to the theoretical description and experimental verification of electromigration behavior of peptides and to methodology of their separations, such as sample preparation, adsorption suppression, and detection, are presented. Novel developments in individual CE and CEC modes are shown and several types of their applications to peptide analysis are presented: conventional qualitative and quantitative analysis, purity control, determination in biomatrices, monitoring of chemical and enzymatical reactions and physical changes, amino acid and sequence analysis, and peptide mapping of proteins. Some examples of micropreparative peptide separations are given and capabilities of CE and CEC techniques to provide important physicochemical characteristics of peptides are demonstrated. [source] Analysis of sub-ppb levels of Fe(II), Co(II), and Ni(II) by electrokinetic supercharging preconcentration, CZE separation, and in-capillary derivatizationELECTROPHORESIS, Issue 20 2007Marek Urbanek Abstract The analysis of sub-ppb levels of Fe(II), Co(II), and Ni(II) in heat exchanger fluids of nuclear power plants is needed to monitor corrosion. A method involving preconcentration with electrokinetic supercharging (electrokinetic injection with transient ITP), CZE separation, and in-capillary derivatization with ortho -phenanthroline (o -Phe) for direct UV detection was thus developed. First, a multizone BGE was loaded into the capillary by successive hydrodynamic introduction of zones of (i) o -Phe-containing BGE, (ii) BGE for the zonal separation, and (iii) ammonium-based leading electrolyte. Metal cations were electrokinetically injected and stacked at the capillary inlet behind this last leading zone. Finally, a terminating electrolyte zone was hydrodynamically introduced. When a constant voltage was applied, metal ions kept on concentrating isotachophoretically, then separated in CZE mode, were complexed by migrating through an o -Phe zone, and finally detected by direct absorbance. To detect extremely thin peaks, it was attempted for the first time to focus the derivatization reagent by inducing a second transient ITP, before labeling analytes, already separated in CZE mode. With this arrangement, LODs were about 30,ppt in pure water. In heat exchanger fluid matrices containing 1000,ppm bore and 2,ppm lithium, only Fe(II) cation was detected among the three cations of interest at the 1,ppb level using the present method, and its LOD was about ten times higher, due to the lower loading rate during electrokinetic injection. [source] Determination of iodide in samples with complex matrices by hyphenation of capillary isotachophoresis and zone electrophoresisELECTROPHORESIS, Issue 20 2007Pavla Pant Abstract A method has been developed for the determination of iodide in mineral water, seawater, cooking salt, serum, and urine based on hyphenation of capillary ITP and zone electrophoresis. A commercially available instrumentation for capillary ITP with column-switching system was used. ITP served for removal of chloride present in the analyzed samples in a ratio of 106,107:1 to iodide, zone electrophoresis was used for evaluation. Isotachophoretic separation proceeded in a capillary made of fluorinated ethylene,propylene copolymer of 0.8,mm id and 90,mm total length to the bifurcation point filled with a leading electrolyte (LE) composed of 8,mM HCl,+,16,mM ,-alanine (,-Ala),+,10% PVP,+,2.86,mM N2H4×2HCl, pH,3.2; and a terminating electrolyte composed of 8,mM H3PO4,+,16,mM ,-Ala,+,10% PVP,+,5,mM N2H4, pH,3.85 for all the matrices except seawater. For ITP of seawater the LE consisted of 50,mM HCl,+,100,mM ,-Ala,+,10% PVP +,2.86,mM N2H4×2HCl, pH,3.52. Distance of conductivity detector from the injection point and bifurcation point was 52 and 38,mm, respectively. Zone electrophoresis was performed in a capillary made of fused silica of 0.3,mm id and 160,mm total length filled with LE from isotachophoretic step. LODs reached for all matrices were 2,3×10,8,M concentration (2.5,4,,g/L) enabled monitoring of iodide in all analyzed samples with RSD 0.4,9.3%. Estimated concentrations of iodide in individual matrices were 10,6,10,8,M. [source] Enantioselective analysis of pheniramine in urine by charged CD-mediated CZE provided with a fiber-based DAD and an on-line sample pretreatment by capillary ITPELECTROPHORESIS, Issue 15 2007Jozef Marák Abstract Application potentialities of CZE on-line coupled with capillary ITP and DAD to the identification and determination of trace concentration levels (,g/L) of pheniramine (PHM) enantiomers and their metabolites present in complex ionic matrices of biological origin (urine) are shown. An enhanced (enantio)selectivity of the CZE separation system obtained by the addition of carboxyethyl-,-CD (CE-,-CD) to the carrier electrolyte provided CZE conditions for a reliable identification of similar/identical DAD spectra of structurally related compounds (PHM enantiomers and their metabolites) in clinical urine samples differing in qualitative and quantitative composition of sample matrix constituents. A high sample loadability (a 30,,L sample injection volume), partial sample clean-up (removing macroconstituents from the sample), and preconcentration of the analytes in ITP stage resulted in the decrease of concentration LOD for PHM enantiomers in urine to 5.2 and 6.8,,g/L (2.2×10,8 and 2.8×10,8,mol/L), without using any sample pretreatment technique. The background correction and smoothing procedure applied to the raw DAD spectra provided analytically relevant DAD spectra of PHM enantiomers and their metabolites also when they were present in urine sample (30,,L injection volumes of ten-times diluted urine sample) at a 9×10,8,mol/L concentration. DAD spectra of PHM enantiomers present in urine samples matched their reference spectra with reasonable certainties. DAD spectra of PHM metabolites were compared with the reference spectra of PHM enantiomers and a good match was found which indicates the similarities in the structures of enantiomers and their metabolites detected in the urine samples. This fact allows performing the quantitative analyses of PHM metabolites in the urine samples by applying the calibration parameters of PHM enantiomers also for PHM metabolites and the results show the possibilities of using the ITP,CZE,DAD combination for the direct analysis of PHM enantiomers and/or their metabolites in urine without any sample pretreatment. ITP,CZE,DAD method with oppositely charged selector is suggested to use in clinical research as it provides favorable performance parameters including sensitivity, linearity, precision, recovery, and robustness with minimal demands on sample preparation. [source] Determination of trace cationic impurities in butylmethylimidazolium-based ionic liquids: From transient to comprehensive single-capillary counterflow isotachophoresis-zone electrophoresisELECTROPHORESIS, Issue 23 2006Marek Urbánek Abstract Determination of impurities in ionic liquids (ILs) remains a difficult task. In this work, the hyphenation of isotachophoretic,(ITP) preconcentration to zone electrophoresis,(ZE) has been explored for the trace analysis of the cationic impurities Na+, Li+, and methylimidazolium (MI+) in butylmethylimidazolium (BMI+)-based ILs. Simultaneous detection of UV-transparent and UV-absorbing impurities was ensured by a BGE composed of creatinine-acetate buffer. To induce ITP, three different strategies were evaluated: (i),Sample self-stacking ensured by the addition of ammonium acetate (NH4Ac) to 25,50-fold diluted IL solution (transient ITP). (ii),Complete ITP-ZE separation performed in a single capillary: ITP was realized in discontinuous electrolytes comprising an 80,mM NH4Ac, 40,mM acetic acid, 30,mM ,-CD, pH,5.05, leading electrolyte,(LE) and a 10,mM creatinine, 10,mM acetic acid, pH,4.9, terminating electrolyte,(TE). To create the ZE stage, the ITP stack of analytes was moved back toward the capillary inlet by pressure and simultaneously the capillary was filled with the BGE. This protocol made it possible to accommodate a 2.5-times diluted IL sample. (iii),Complete counterflow ITP-ZE with continuous electrokinetic sample supply: the ITP stage was performed in a capillary filled with a 150,mM NH4Ac, 75,mM acetic acid, 30,mM ,-CD, pH,5.0 LE, with 40-times diluted IL at the capillary inlet. BMI+ from IL acts as the terminating ion. The LODs reached in this latter case were at the 10 and 1,ppb levels for MI+ and Li+ in diluted IL matrix, respectively. [source] Sensitive chiral analysis by capillary electrophoresisELECTROPHORESIS, Issue 1 2006Carmen García-Ruiz Abstract In this review, an updated view of the different strategies used up to now to enhance the sensitivity of detection in chiral analysis by CE will be provided to the readers. With this aim, it will include a brief description of the fundamentals and most of the recent applications performed in sensitive chiral analysis by CE using offline and online sample treatment techniques (SPE, liquid,liquid extraction, microdialysis, etc.), on-column preconcentration techniques based on electrophoretic principles (ITP, stacking, and sweeping), and alternative detection systems (spectroscopic, spectrometric, and electrochemical) to the widely used UV-Vis absorption detection. [source] Corticosteroid side-effects and risk for bleeding in immune thrombocytopenic purpura: patient and hematologist perspectivesEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2009Jacqueline A. Guidry Abstract Objectives:, The purpose of this study was to examine hematologist and patient perspectives about the side-effects of the corticosteroid treatment of immune thrombocytopenic purpura (ITP) and their perspectives about the patient's risk for bleeding. The specific aim was to compare patient and hematologist perspectives and, if a difference was documented, the implications of that difference. We hypothesized that patients with ITP may have more concern about corticosteroid side-effects and less concern about serious bleeding than hematologists. Methods:, We surveyed 80 patients in the Oklahoma ITP Registry and all 83 hematologists in Oklahoma about the occurrence and severity of 18 corticosteroid side-effects and risks for serious bleeding. Results:, Response rates were 80% (patients) and 71% (hematologists). Responses of patients and hematologists were significantly different from each other regarding both the frequency of severe corticosteroid side-effects and the risk of serious bleeding. For 13 of the 18 corticosteroid side-effects, patients reported more frequent occurrence of severe symptoms than hematologists (P < 0.05); physicians reported more frequent occurrence for one side-effect (P < 0.05). Conversely, 69% and 93% of hematologists reported being very worried about serious bleeding when responding to two case scenarios describing patients with platelet counts of 10 000/,L and 5000/,L (P < 0.05), compared with only 16 (31%) of 51 patients whose lowest platelet count had been <10 000/,L. Conclusion:, Awareness of the different opinions about corticosteroid side-effects and risk for bleeding between ITP patients and hematologists may improve management decisions. [source] Immune thrombocytopenic purpura: epidemiology and implications for patientsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2009Marc Michel Abstract The age-adjusted prevalence of immune thrombocytopenic purpura (ITP) is estimated to be 9.5 per 100 000 persons in the USA while its annual incidence is estimated to be 2.68 per 100 000 in Northern Europe (at a cut-off platelet count of <100 × 109/L). The mean age of adults at diagnosis in Europe is 50 yrs and the incidence of ITP increases with age. Both the treatments used to treat patients with ITP and the disease itself can impact on patient health-related quality of life (HRQoL). As the incidence of ITP in Europe rises, especially in the elderly, the number of patients with a decreased HRQoL is increasing. Literature searches and focus groups have aided the development of a conceptual model to assess HRQoL. In this model, low platelet counts and the associated symptoms of ITP in addition to the side effects of treatment are proposed as the main determinants of a negatively impacted HRQoL. Primary conceptual domains of HRQoL, affected in patients with ITP, include emotional health, functional health, work, social and leisure activities and reproductive health. As treatment benefits are likely to improve these domains, the conceptual model could be used for better management of patients, taking into account HRQoL. The short-form 36-item questionnaire (SF-36) and the ITP Patient Assessment Questionnaire (ITP-PAQ) are validated measures of HRQoL which can provide a comprehensive assessment of numerous factors to help evaluate decisions about patient management. Future clinical trials investigating treatment options for ITP should assess HRQoL using these validated questionnaires. [source] Aberrant increase in the immature platelet fraction in patients with myelodysplastic syndrome: a marker of karyotypic abnormalities associated with poor prognosisEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2009Naomi Sugimori Abstract Objectives:, Some patients with myelodysplastic syndrome (MDS) show a marked increase in the percentage of immature platelet fraction (IPF%) despite the absence of severe thrombocytopenia. To determine the significance of such an unbalanced increase in the IPF%, we investigated the IPF% and other laboratory findings of 51 patients recently diagnosed with MDS. Method:, Subjects consisted of 80 healthy males, 90 healthy females, and 51 patients with MDS and 20 patients with idiopathic thrombocytopenic purpura (ITP). The IPF and IPF% were determined using a Sysmex XE-2100 system loaded with IPF Master software (XE IPF Master, Sysmex). Platelet counts were measured simultaneously. Results:, IPF% and platelet counts of these patients ranged from 1.1% to 25.1% (median, 5.3%) and from 6 to 260 × 109/L (median, 71 × 109/L), respectively. Twelve patients showed platelet counts more than 50 × 109/L with 10% or more IPF%. All of the 12 patients had chromosome abnormalities including monosomy 7 and complex abnormalities involving 7 or 5q. In the other 39 patients who did not show the aberrant IPF% increase, chromosomal abnormalities were seen only in seven patients and none of them had chromosome 7 abnormalities. The IPF% of two patients increased to more than 10% in association with the appearance of monosomy 7. Conclusions:, These findings suggest that a high IPF% in MDS patient may be a marker for karyotypic abnormalities with a poor prognosis, including chromosome 7 abnormalities. [source] Rituximab therapy in adult patients with relapsed or refractory immune thrombocytopenic purpura: long-term follow-up resultsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2008Marta Medeot Abstract Objective:, To evaluate the long-term activity and toxicity profile of rituximab in adult patients with idiopathic immune thrombocytopenic purpura (ITP). Patients and methods:, Twenty-six patients with active and symptomatic ITP relapsed or refractory received weekly infusions of rituximab 375 mg/m2 for 4 wk. Median time from diagnosis to rituximab was 34.5 months. The following parameters of efficacy and toxicity were considered: complete response (CR) and partial response (PR), relapse rate, relapse-free survival (RFS), therapy-free survival (TFS), short- and long-term toxicity. Results:, CR and PR were 14/26 (54%) and 4/26 (15%), respectively. Median time of observation was 56.5 months (range 39,77). Nine of the 18 responding patients relapsed after a median of 21 months (range 8,66); 9/26 patients (35%) maintained the response, with a median follow-up of 57 months (range 39,69), and 11/26 (42%) did not necessitate further therapy; estimated 5 yr RFS and TFS were 61% and 72%, respectively. Younger age and shorter interval from diagnosis to rituximab appeared indicators of better outcome. Rituximab administration was associated with two episodes of short-term toxicity, with one case of serum sickness syndrome; no infectious or other significant long-term complications were documented. Conclusion:, Rituximab therapy may achieve long-lasting remission in nearly one-third of patients with relapsed or refractory ITP, with a good safety profile. [source] Epidemiology and pathophysiology of immune thrombocytopenic purpuraEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2008Terry Gernsheimer Abstract Immune thrombocytopenic purpura (ITP) is characterized by the presence of antiplatelet antibodies and immune platelet destruction. The disorder has been described as having a predilection for young women over men. Bone marrow megakaryocytes appear morphologically and quantitatively normal, and early platelet kinetic studies were consistent with reduced platelet survival as the primary abnormality in ITP. During the last 10,20 yr, understanding of the kinetics of this disorder has evolved with evidence that platelet survival is not as abbreviated as previously thought. Thrombopoietin levels are only minimally elevated, if at all, suggesting marrow stimulation and platelet production may not be maximized. Megakaryocyte physiology appears to be altered in ITP, also suggestive of diminished platelet production. It appears both platelet survival and production are impaired in ITP. The epidemiology of ITP is reviewed here and the pathophysiology of ITP is reconsidered. [source] ITP: A new regulatory issue!EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2007John W. SempleArticle first published online: 4 AUG 200 No abstract is available for this article. [source] Interferon-, +874A/T and interleukin-4 intron3 VNTR gene polymorphisms in Chinese patients with idiopathic thrombocytopenic purpuraEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2007Xiaoli Chen Abstract Objectives:, The polarization of Th1/Th2 towards Th1 contributes to the pathogenesis of idiopathic thrombocytopenic purpura (ITP). Cytokines may play crucial roles in the pathogenesis of ITP. The purpose of this study was to investigate whether the interferon (IFN)-, +874(A/T) and interleukin-4 (IL-4) variable number of tandem repeats (VNTR) in intron3 polymorphisms may be responsible in part for genetic susceptibility to ITP. Methods:, Genotyping of IFN-, +874A/T and IL-4 intron3 VNTR was performed in 196 patients with ITP and 128 healthy individuals by polymerase chain reaction sequence-specific primers and direct PCR respectively. Results:, There was no association between IFN-, +874A/T and IL-4 intron3 VNTR polymorphism and ITP risk when all patients, as a group, were analyzed. When the patients were subdivided into two groups: childhood ITP and adult ITP, no statistical differences were found in the genotype and allele frequencies of IFN-, +874A/T and IL-4 intron3 VNTR between the two groups and the controls. Similar results were observed between acute childhood ITP, chronic childhood ITP, acute adult ITP or chronic adult ITP and the controls. Conclusion:, These polymorphisms were distributed similarly between the patients with ITP and the controls, demonstrating that these two candidate gene polymorphisms are not attributed to ITP susceptibility. [source] Ursodeoxycholic acid treatment of idiopathic thrombocytopenic purpura with liver dysfunctionEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2003Michiaki Koike Abstract: Ursodeoxycholic acid (UDCA) is known to reduce immunoglobulin from B cells and cytokine production from T cells. We found that UDCA increased the platelet count in two idiopathic thrombocytopenic purpura (ITP) patients who have liver dysfunction. UDCA was tolerated and did not cause diarrhea in the amounts used. Further investigation is needed to evaluate the effectiveness of UDCA in ITP patients. [source] Plasma-soluble Fas (APO-1, CD95) and soluble Fas ligand in immune thrombocytopenic purpuraEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2000Chie Yoshimura Abstract: We investigated the levels of various cytokines and soluble factors in ITP patients, in order to determine the influence of these factors on the pathogenesis of ITP. We found increases in IL-2, IL-6, IFN-,, and M-CSF levels in ITP patients compared with those in healthy individuals. On lymphocyte phenotype analysis, we found no clear difference in total T cell population (CD2+ CD19, cells) or cytotoxic T cell frequency (CD8+ CD11b, cells) between these two groups. The frequency of helper/inducer T cells (CD4+ CD8, cells) was decreased in ITP patients. There was a significant increase in activated T cells (CD3+ HLA-DR+ cells) in ITP patients. Furthermore, frequencies of NK cells of potent activity (CD16+ CD56+ cells) were significantly elevated in ITP patients. Seventeen of the 54 ITP patients (31.5%) had elevated levels of sFas, and 11 of the 54 patients (20.4%) of sFasL. In addition, a significant increase of sFasL was observed in sFas-positive ITP patients, and in these patients the sFasL level was correlated with that of sFas (r=0.687, p<0.01). We found significant increases in IL-2 and sIL-2R levels in sFas-positive ITP patients. For other factors examined, however, there were no differences in level between sFas-positive and-negative ITP patients. Percentages of activated T cells (CD3+ and HLA-DR+ cells) and NK cells (CD16+ and CD56+ cells) were significantly higher in sFas-positive ITP patients than in sFas-negative ITP patients. These findings suggests that the pathogenesis of ITP includes alteration of the Fas/FasL pathway. [source] Indirect study of thrombopoiesis(TPO, reticulated platelets, glycocalicin)in patients with hereditary macrothrombocytopeniaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2000F. Fabris To better understand the pathogenesis of thrombopoiesis in this hereditary thrombocytopenic disorder, we determined the percentage of reticulated platelets (RP), plasma glycocalicin (GC) and thrombopoietin (TPO) levels in 29 patients with CHMT, 23 patients with immune thrombocytopenic purpura (ITP), and 17 patients with thrombocytopenia secondary to decreased bone marrow megakaryocytes (hypoplasia). The % RP was similar in CHMT (2.27±1.33) and hypoplasia (1.98±1.35) patients and markedly lower than that in ITP patients (8.80±7.97; p<0.001), suggesting that the production of new platelets is reduced in CHMT. Plasma GC was within the normal range (0.84±0.16 ,g/mL) both in patients with CHMT (0.63±0.20 ,g/mL) and ITP (0.82±0.90 ,g/mL), while it was significantly decreased in patients with hypoplasia (0.16±0.04 ,g/mL; p<0.001). When the GC value was normalized for platelet count, the GC index was normal in CHMT patients (2.05±1.1) and in patients with hypoplasia (0.85±0.10) while it was significantly increased in ITP patients (10.88±18.00; p<0.001); thus, patients with CHMT seem to have a normal platelet turnover. TPO was significantly increased in CHMT (195±72 pg/ml) as compared with normal (80±53 pg/ml; p<0.002); however, the mean level was not as high as in ITP patients (345±167 pg/mL; p<0.001). This finding suggests that CHMT syndrome is not secondary to a defective production of TPO and that megakaryocyte mass is nearly normal. [source] Mouse RS21-C6 is a mammalian 2,-deoxycytidine 5,-triphosphate pyrophosphohydrolase that prefers 5-iodocytosineFEBS JOURNAL, Issue 6 2009Mari Nonaka Free nucleotides in living cells play important roles in a variety of biological reactions, and often undergo chemical modifications of their base moieties. As modified nucleotides may have deleterious effects on cells, they must be eliminated from intracellular nucleotide pools. We have performed a screen for ITP-binding proteins because ITP is a deaminated product of ATP, the most abundant nucleotide, and identified RS21-C6 protein, which bound not only ITP but also ATP. Purified, recombinant RS21-C6 hydrolyzed several canonical nucleoside triphosphates to the corresponding nucleoside monophosphates. The pyrophosphohydrolase activity of RS21-C6 showed a preference for deoxynucleoside triphosphates and cytosine bases. The kcat/Km (s,1·m,1) values were 3.11 × 104, 4.49 × 103 and 1.87 × 103 for dCTP, dATP and dTTP, respectively, and RS21-C6 did not hydrolyze dGTP. Of the base-modified nucleotides analyzed, 5-I-dCTP showed an eightfold higher kcat/Km value compared with that of its corresponding unmodified nucleotide, dCTP. RS21-C6 is expressed in both proliferating and non-proliferating cells, and is localized to the cytoplasm. These results show that RS21-C6 produces dCMP, an upstream precursor for the de novo synthesis of dTTP, by hydrolyzing canonical dCTP. Moreover, RS21-C6 may also prevent inappropriate DNA methylation, DNA replication blocking or mutagenesis by hydrolyzing modified dCTP. [source] Proof of an Association between Helicobacter pylori and Idiopathic Thrombocytopenic Purpura in Latin AmericaHELICOBACTER, Issue 3 2007Germán Campuzano-Maya Abstract Background:, Association between Helicobacter pylori and idiopathic thrombocytopenic purpura (ITP) has been found in Japan and in some European countries. It has also been shown that eradication of H. pylori can increase platelet counts in patients with ITP. The aims of this study were to determine the prevalence of H. pylori infection in patients with ITP in Colombia, and the effect of bacterial eradication on their platelet counts. Materials and methods:, Between December 1998 and April 2006, a total of 32 patients diagnosed with ITP were included in the study. Controls were age and sex matched. Results:,H. pylori infection in patients with ITP was significantly higher (p = .00006) than in control individuals (90.6% and 43.8%, respectively), as determined by 13C-urea breath test. A significant association between H. pylori infection and ITP was found (p < .0003), with an odds ratio (OR) of 13.15 (95%CI: 3.24,53.29). Multivariate analysis for the association between H. pylori and ITP showed an OR of 20.44 (95%CI: 3.88,107.49) for women and 19.28 (95%CI: 2.03,183.42) for individuals over 50 years. All 29 H. pylori -positive patients with ITP received eradication treatment. After a median follow up of 12.2 months, 80.8% had a recovery in platelet counts. Conclusions:, According to these results and others from different countries where H. pylori infection rates are high, patients with ITP should be initially tested for H. pylori status, and if present, infection should be eradicated before initiating a drastic conventional ITP treatment. An algorithm for the study and management of patients with ITP in the post- Helicobacter era is presented. [source] Current management of adult idiopathic thrombocytopenic purpura in practice: a cohort study of 201 patients from a single center,INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2004J. Zimmer Summary To define usefulness and response to therapy and outcome in adults with idiopathic thrombocytopenic purpura (ITP) in clinical practice. We retrospectively reviewed a cohort of 201 consecutive patients with ITP, diagnosed between 1985 and 1994. In particular, we analyzed the therapies used, their response rates, prognostic indicators of response and outcome. In 62 patients, with minor bleeding episodes and a mean (±SD) platelet count of 88 ± 23 × 109/l, no treatment was used and chronic ITP was diagnosed in 59%. A total of 139 patients, with bleeding episodes in 71.2% cases and a mean platelet count of 20 ± 13 × 109/l, received at least one treatment. Three patients died (1.5% of the series). Corticosteroids were used in 118 patients, with an initial response rate of 82.2% and a long-term complete response (CR) of only 22.9%. Intravenous immunoglobulin was used in 26 patients, with an initial transient response in more than 60%. A splenectomy was performed in 55 patients, with an initial response rate of 92.5% and a long-term CR in 60%. Young age and prior response to corticosteroids were significant predictors of a durable response to splenectomy. Danazol was given in 37 patients, with a favorable response in 73% of cases. Our results illustrate the guidelines of the American Society of Hematology. Patients with moderate thrombocytopenia do not require treatment. In severe cases, splenectomy is the only treatment giving durable cures in a significant proportion of patients. Despite frequent chronicity, ITP is life-threatening only in a minor subset of patients. [source] An aging Interventions Testing Program: study design and interim reportAGING CELL, Issue 4 2007Richard A. Miller Summary The National Institute on Aging's Interventions Testing Program (ITP) has developed a plan to evaluate agents that are considered plausible candidates for delaying rates of aging. Key features include: (i) use of genetically heterogeneous mice (a standardized four-way cross), (ii) replication at three test sites (the Jackson Laboratory, TJL; University of Michigan, UM; and University of Texas, UT), (iii) sufficient statistical power to detect 10% changes in lifespan, (iv) tests for age-dependent changes in T cell subsets and physical activity, and (v) an annual solicitation for collaborators who wish to suggest new interventions for evaluation. Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen (NFP), 4-OH-,-phenyl-N-tert-butyl nitrone (4-OH-PBN), or nordihydroguiaretic acid (NDGA). An interim analysis was conducted using survival data available on the date at which at least 50% of the male control mice had died at each test site. Survival of control males was significantly higher, at the interim time-point, at UM than at UT or TJL; all three sites had similar survival of control females. Males in the NDGA group had significantly improved survival (P = 0.0004), with significant effects noted at TJL (P < 0.01) and UT (P < 0.04). None of the other agents altered survival, although there was a suggestion (P = 0.07) of a beneficial effect of aspirin in males. More data will be needed to determine if any of these compounds can extend maximal lifespan, but the current data show that NDGA reduces early life mortality risks in genetically heterogeneous mice at multiple test sites. [source] The long-term efficacy of Helicobacter pylori eradication therapy in patients with idiopathic thrombocytopenic purpuraJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2007Masaaki Satake Abstract Background and Aim:, A beneficial effect of Helicobacter pylori (H. pylori) eradication in patients with H. pylori -positive idiopathic thrombocytopenic purpura (ITP) has been reported by several investigators; however, it was not clear whether the recovered platelet count after H. pylori eradication was maintained for a long period. Method:, Thirty-eight ITP patients who were examined for H. pylori infection were assessed. H. pylori -positive patients received a standard antibiotic therapy for H. pylori eradication. We investigated the long-term effect of H. pylori eradication on platelet recovery in patients with H. pylori -positive ITP. Results:, Of the 38 ITP patients, 26 (68.4%) were positive for H. pylori. The response rate of platelet recovery was 56.5% (13/23 patients). Twelve patients showed complete response (CR) and one showed partial response (PR). The mean platelet counts 6 months after eradication significantly increased from 31 × 109/L to 129 × 109/L in 23 H. pylori -eradicated patients (P < 0.001). The median platelet counts of responders 1, 2, 3, and 4 years after eradication were 168 × 109/L (n = 10), 193 × 109/L (n = 9), 168 × 109/L (n = 7), and 243 × 109/L (n = 4) after a mean follow-up of 25.8 months. Conclusion:, Eradication therapy for H. pylori -positive patients with ITP was effective and a favorable effect was maintained for long periods. [source] Evaluation of platelet kinetics in patients with liver cirrhosis: Similarity to idiopathic thrombocytopenic purpuraJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2007Mikio Kajihara Abstract Background:, Thrombocytopenia is a common manifestation of liver cirrhosis (LC), but its underlying mechanism is not fully understood. The purpose of the present paper was to evaluate the platelet kinetics in LC patients by examining several non-invasive convenient markers. Methods:, Fifty-seven LC patients, 32 patients with idiopathic thrombocytopenic purpura (ITP), 12 with aplastic anemia (AA), and 29 healthy individuals were studied. Plasma thrombopoietin was measured by enzyme-linked immunosorbent assay. Absolute reticulated platelet (RP) count and plasma glycocalicin were used as indices for thrombopoiesis, and the indices for platelet turnover were the RP proportion and the plasma glycocalicin normalized to the individual platelet count (GCI). Results:, There was no difference in thrombopoietin levels between LC patients and healthy controls. The RP proportion and GCI were significantly higher and the absolute RP count and glycocalicin significantly lower in LC patients than in healthy controls. These markers in ITP and LC patients were comparable, but significantly different from those in AA patients. The bone marrow megakaryocyte density in LC and ITP patients was similar, and significantly higher than in AA patients. Conclusions:, Cirrhotic thrombocytopenia is a multifactorial condition involving accelerated platelet turnover and moderately impaired thrombopoiesis. Thrombopoietin deficiency is unlikely to be the primary contributor to cirrhotic thrombocytopenia. [source] Intended management of children with acute idiopathic thrombocytopenic purpura: A national surveyJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 1-2 2005MK Marks Objective: In Australia acute idiopathic thrombocytopenic purpura (ITP) is mainly treated by paediatricians (either general paediatricians or paediatric haematologists/oncologists). A survey was conducted to gauge the current practice of treating children with acute ITP in Australia. Methods: All practising Australian paediatricians registered by the Royal Australasian College of Physicians were surveyed regarding their intended management of children with acute ITP. The questionnaire, adapted from a study of paediatric haematologists/oncologists in North America, presented four clinical scenarios of children with acute ITP with a platelet count of 3000 × 109/L, with and without mucosal bleeding (wet and dry purpura, respectively). Questionnaires were returned by mail or filled in online at a dedicated webpage. Results: Five hundred and sixty-three of 1097 (51%) paediatricians responded to the survey. Data from 140 who had treated at least one child with ITP in the previous 12 months were analysed. Respondents indicated that children with acute ITP are usually or always hospitalised (58,92%) and that 48% would be given active treatment, even with dry purpura. Various regimens of i.v. immunoglobulin or corticosteroids are used when treatment is administered. In comparing Australian and North American management of acute ITP there were many similarities, although Australian paediatricians were less likely to arrange a bone marrow aspirate if corticosteroids were prescribed. Conclusions: There is great variation in the intended management of children with acute ITP in Australia. Previously published management recommendations regarding investigation and treatment have had little impact on intended practice. Prospective studies are required to evaluate hypotheses so as to produce evidence-based recommendations for treatment of patients with acute ITP. [source] Influence of crystal structure on the tableting properties of n -alkyl 4-hydroxybenzoate esters (parabens)JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2007Yushi Feng Abstract Certain crystallographic features, such as the existence of slip planes, can greatly facilitate the ability of crystals to deform plastically. An investigation of the relationship between the slip planes and the tableting performance of the crystals of methyl, ethyl, n -propyl, and n -butyl 4-hydroxybenzoate (parabens) was conducted. The absence of slip planes in methyl paraben crystal structure results in significantly poorer tableting performance than the other three parabens. While slip planes are present in the crystal structures of ethyl, propyl, and butyl parabens, they exhibited different plasticity as confirmed by crystal free volume analysis, crystal nano-indentation hardness, and Heckel analysis. Sieved fraction, 150,250 µm, of each paraben powder was compressed into tablets under different conditions. Tablet tensile strength, porosity, and Indices of tableting performance (ITP) were obtained. Under the same compaction pressure, tablet tensile strength was higher for crystals with higher plasticity. Tableting performance, assessed using the ITP, also improved with increasing crystal plasticity. The results confirm that high levels of plasticity, which can result from the presence of slip planes in crystal lattice, plays a critical role in the formation of strong and intact tablets by means of powder compaction. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 3324,3333, 2007 [source] Synthesis of hydrophilic/CO2 -philic poly(ethylene oxide)- b -poly(1,1,2,2-tetrahydroperfluorodecyl acrylate) block copolymers via controlled/living radical polymerizations and their properties in liquid and supercritical CO2JOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 10 2004Zhi Ma Abstract Hydrophilic/CO2 -philic poly(ethylene oxide)- b -poly(1,1,2,2-tetrahydroperfluorodecyl acrylate) block copolymers were synthesized via reversible addition,fragmentation chain transfer (RAFT) polymerization, iodine transfer polymerization (ITP), and atom transfer radical polymerization (ATRP) in the presence of either degenerative transfer agents or a macroinitiator based on poly(ethylene oxide). In this work, both RAFT and ATRP showed higher efficiency than ITP for the preparation of the expected copolymers. More detailed research was carried out on RAFT, and the living character of the polymerization was confirmed by an ultraviolet (UV) analysis of the SC(S)Ph or SC(S)SC12H25 end groups in the polymer chains. The quantitative UV analysis of the copolymers indicated a number-average molecular weight in good agreement with the value determined by 1H NMR analysis. The properties of the macromolecular surfactants were investigated through the determination of the cloud points in neat liquid and supercritical CO2 and through the formation of water-in-CO2 emulsions. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2405,2415, 2004 [source] Prediction of the location of stationary steady-state zone positions in counterflow isotachophoresis performed under constant voltage in a vortex-stabilized annular columnJOURNAL OF SEPARATION SCIENCE, JSS, Issue 18 2007Schurie L. M. Harrison Abstract A theoretical model is presented and an analytical expression derived to predict the locations of stationary steady-state zone positions in ITP as a function of current for a straight channel under a constant applied voltage. Stationary zones may form in the presence of a countercurrent flow whose average velocity falls between that of a pure leader zone and of a pure trailer zone. A comparison of model predictions with experimental data from an anionic system shows that the model is able to predict the location of protein zones with reasonable accuracy once the ITP stack has formed. This result implies that an ITP stack can be precisely directed by the operator to specific positions in a channel whence portions of the stack can be removed or redirected for further processing or analysis. [source] An acquired inhibitor to the GPVI platelet collagen receptor in a patient with lupus nephritisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2009P. NURDEN Summary.,Background: GPVI is a major platelet collagen signaling receptor. In rare cases of immune thrombocytopenic purpura (ITP), autoantibodies to GPVI result in receptor shedding. Objectives: To investigate a possible pathogenic role of plasma anti-GPVI antibody located in a woman with lupus nephritis. Methods: Measured were (i) platelet aggregation to collagen and convulxin, (ii) platelet GPVI expression (flow cytometry and western blotting), (iii) plasma soluble GPVI (sGPVI, dual antibody ELISA), and (iv) plasma anti-GPVI antibody (ELISA using recombinant sGPVI). Results: In 2006 and early 2007, the patient had a normal platelet count but a virtual absence of platelet aggregation to collagen and convulxin. Her platelets responded normally to other agonists including cross-linking ITAM-dependent Fc,RIIA by monoclonal antibody, IV.3. Flow cytometry and western blotting showed a platelet deficiency of GPVI. Plasma sGPVI levels were undetectable whereas ELISA confirmed the presence of anti-GPVI antibody. Sequencing revealed a normal GPVI cDNA structure. The patient's plasma and the isolated IgG3 fraction activated and induced GPVI shedding from normal platelets. A deteriorating clinical condition led to increasingly strict immunosuppressive therapy. This was globally associated with a fall in plasma anti-GPVI titres, the restoration of platelet GPVI and the convulxin response, and the loss of her nephrotic syndrome. Conclusions: Our results show that this patient acquired a potent anti-GPVI IgG3 antibody with loss of GPVI and collagen-related platelet function. Further studies are required to determine whether anti-GPVI antibodies occur in other lupus patients with nephritis. [source] | |||||||||||||||||||||||||||||||||||||