bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G‐CSF (CLAG‐M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group
Authors: Wierzbowska Agnieszka , Robak Tadeusz , Pluta Agnieszka , Wawrzyniak Ewa , Cebula Barbara , Hołowiecki Jerzy , Kyrcz‐Krzemień Sławomira , Grosicki Sebastian , Giebel Sebastian , Skotnicki Aleksander B. , Piątkowska‐Jakubas Beata , Kuliczkowski Kazimierz , Kiełbiński Marek , Zawilska Krystyna , Kłoczko Janusz , Wrzesień‐Kuś Agata 
Published: July 2010

AbstractObjectives: Patients with primary refractory AML and with early relapses have unfavorable prognoses and require innovative therapeutic approaches. Purine analogs fludarabine (FA) and cladribine (2‐CdA) increase cytotoxic effect of Ara‐C in leukemic blasts and inhibit DNA repair mechanisms; therefore its association with Ara‐C and mitoxantrone (MIT) results in a synergistic effect. In the current report, we present the final results of multi‐center phase II study evaluating the efficacy and toxicity of CLAG‐M salvage regimen in poor risk refractory/relapsed AML patients.Methods: The induction chemotherapy consisted of 2‐CdA 5 mg/m2, Ara‐C 2 g/m2, MIT 10 mg/m2, and granulocyte‐colony stimulating factor. In the case of PR, a second CLAG‐M was administered. Patients in CR received consolidation courses based on high doses of Ara‐C and MIT with or without 2‐CdA.Results: One hundred and eighteen patients from 11 centers were registered; 78 primary resistant and 40 relapsed. Sixty‐six patients (58%) achieved CR after one or two courses of CLAG‐M, 49 (35%) were refractory, and 8 (7%) died early. WBC >10 g/L and age >34 yr were factors associated with increased risk of treatment failure. Hematological toxicity was the most prominent toxicity of this regimen. The probability of OS at 4 yr was 14% (95% CI 4–23%). OS was influenced by age, WBC >10 g/L and poor karyotype in both univariate and multivariate analyses. The probability of 4 yr DFS was 30% for all 66 patients in CR (95% CI 11–49%). Poor karyotype was the only factor associated with decreased probability of DFS.Conclusions: We conclude that CLAG‐M is a well‐tolerated and highly effective salvage regimen in poor risk refractory/relapsed AML.
Haematological and clinical features of β‐thalassaemia associated with Hb Dhofar
Authors: Daar Shahina , Gravell David , Hussein Hussein M. , Pathare Anil V. , Wali Yasser , Krishnamoorthy Rajagopal 
Published: July 2010

AbstractHb Dhofar is a variant haemoglobin (β29 (GGC–GGT) gly‐gly, β58 (CCT–CGT) pro‐arg) associated with a thalassaemic phenotype and unique to the Sultanate of Oman. We report clinical and haematological data on 54 subjects with Hb Dhofar (37 heterozygotes, 14 homozygotes and three compound heterozygotes with a different β‐thalassaemia mutation). In heterozygotes, the level of Hb Dhofar ranged from 8.8% to 21.5%. All heterozygotes had Hb A2 > 3.5%, consistent with β‐thalassaemia trait. Hb Dhofar in homozygotes and compound heterozygotes ranged from 26% to 59.7%, with a peripheral film consistent with homozygous β‐thalassaemia. Age at presentation in homozygotes ranged between 6 months and 8 yr, with a majority presenting before 5 yr of age. All had splenomegaly and six (43%) had undergone splenectomy. All had some degree of frontal bossing and in particular, two patients with infrequent transfusions had marked thalassaemic facies and stunting of growth. Hb Dhofar can be mistaken for Hb D as the electrophoretic mobility is similar, but differs from it by a variable and reduced quantity of variant Hb in both heterozygotes and homozygotes. Clinical and haematological data suggest that this mutation behaves like a moderately severe β+ thalassaemia allele resulting in a thalassaemia intermedia phenotype.
Quantification of progenitors capable of generating T cells in human cord blood
Authors: Kato Maiko , Masuda Kyoko , Kakugawa Kiyokazu , Kawamoto Hiroshi , Mugishima Hideo , Katsura Yoshimoto 
Published: July 2010

AbstractObjective:  For transplantation of cord blood (CB) cells, it is important to select a CB sample that can reconstitute not only myelo‐erythropoiesis but also lymphopoiesis in recipients. However, until now the reconstitution ability of CB samples has been assessed by colony forming unit‐culture (CFU‐C) assay or by simply counting CD34+ cells. The present study aims at establishing a method capable of assessing the potential of T lymphopoieses of CB samples.Methods:  CD34+CD38− cells sorted from CB were cultured on a monolayer of murine stromal cell line TSt‐4, transduced with the human Delta‐like 1 gene.Results:  Immature T cells expressing CD5 and/or CD7 were generated in the culture. As these immature T cells can easily be discriminated from mature T cells that are included in the mononuclear cell population (MNCs), we can use the MNCs as starting material for quantification of progenitors capable of generating T cells (TGP). By applying a limiting dilution analysis, we succeeded in determining the frequency of TGP in MNCs. It was found that the ratios for the number of TGP vs. that of CFU‐C differ among CB samples maximally by 3.5 times.Conclusion:  The present assay system provides a novel tool for the evaluation of CB samples, especially for their T‐cell‐generating potential.
Immunoglobulin light chain gene translocations in non‐Hodgkin’s lymphoma as assessed by fluorescence in situ hybridisation
Authors: Fujimoto Yoshiko , Nomura Kenichi , Fukada Shuji , Shimizu Daisuke , Shimura Kazuho , Matsumoto Yosuke , Horiike Shigeo , Nishida Kazuhiro , Shimazaki Chihiro , Abe Masafumi , Taniwaki Masafumi 
Published: July 2010

AbstractIn non‐Hodgkin’s lymphoma (NHL), the majority of translocations involve the immunoglobulin heavy chain gene (IGH) locus, while a few involve the immunoglobulin light chain gene (IGL) locus, consisting of the kappa light chain gene (IGκ) and the lambda light chain gene (IGλ). Although many reports have dealt with the translocation and/or amplification of IGH in NHL, only a few have identified IGL translocations. To identify cytogenetic abnormalities and the partner chromosomes of IGL translocations in NHL, we performed dual‐colour fluorescence in situ hybridisation (DC‐FISH) and spectral karyotyping (SKY) in seven NHL cell lines and 40 patients with NHL. We detected IGL translocations in two cell lines and nine patients: four patients with diffuse large B‐cell lymphoma, three with follicular lymphoma, one with extranodal marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue and one with mantle cell lymphoma. Five distinct partners of IGλ translocation were identified by SKY analysis: 3q27 in three patients, and 1p13, 6p25, 17p11.2 and 17q21 in one patient each. Three cases featured double translocations of IGH and IGL. These findings warrant the identification of novel genes 1p13, 6p25, 17p11.2 and 17q21.
GEMOX‐R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large‐cell lymphoma: a phase II study
Authors: López Andrés , Gutiérrez Antonio , Palacios Andrés , Blancas Isabel , Navarrete Maite , Morey Miguel , Perelló Antonia , Alarcón Jesús , Martínez Jordi , Rodríguez José 
Published: July 2010

AbstractObjectives: The prognosis of old or immunocompromised patients with refractory or relapsing diffuse large‐cell lymphoma (DLCL) is very poor as the current standard of salvage therapy with autologous stem cell transplantation (ASCT) is not feasible for most of them. New active regimens with an acceptable toxicity profile are needed. We aim to report the results of a phase II trial of the GEMOX‐R regimen in DLCL.Methods: A total of 32 patients received GEMOX‐R regimen in 2‐wk intervals if feasible or every 3 wk for a planned six to eight courses.Results: Median age of the population was 69 yr. Forty‐one percent of the patients were primary refractory and 59% after relapsing. At GEMOX‐R, 75% of patients had a stage III–IV and an adjusted International Prognostic Index > 1 was observed in 69%. The response rate was 43% with 34% complete response. Neutropenia and thrombopenia grade III–IV were observed in 43% of the patients and neurotoxicity grade III–IV in 7% of cases. Median follow‐up for alive patients was 13 months and the median survival was 9.1 months. At 12 months, the overall survival and progression‐free survival were 41% and 29%, respectively.Conclusions: GEMOX‐R is a new salvage regimen for DLCL with high activity and relatively safe toxicity profile, which can be offered to elderly patients not candidates of ASCT consolidation. The high efficacy of the regimen in this unfavorable population and also in immunocompromised situations warrant further investigation of this regimen in all salvage situations of this type of lymphomas.
Epidemiology and pathophysiology of immune thrombocytopenic purpura
Authors: Gernsheimer Terry 
Published: July 2010

AbstractImmune 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.
New drugs for familiar therapeutic targets: thrombopoietin receptor agonists and immune thrombocytopenic purpura
Authors: Kuter David J. 
Published: July 2010

AbstractVarious agents to treat immune thrombocytopenic purpura (ITP) have been developed on the principle that stimulating the thrombopoietin (TPO) receptor would increase platelet production. First‐generation agents—recombinant human thrombopoietin (rHuTPO) and pegylated recombinant human megakaryocyte growth and development factor (PEG rHuMGDF)—showed promise, but observations of antibody formation to PEG rHuMGDF led to the discontinuation of development of both agents. Second‐generation agents—the TPO peptide mimetics, TPO non‐peptide mimetics, and TPO agonist antibodies—have been developed to reduce or eliminate the problem of antigenicity. Clinical studies for some of these agents, such as AMG 531 (romiplosim, Nplate) and eltrombopag (Promacta), are demonstrating their relative safety and efficacy in increasing platelet counts in patients with ITP; AMG 531 and eltrombopag are in late‐stage clinical development and are able to stimulate platelet production in patients with ITP. Some differences in safety profiles have been described and are undergoing further study. There are currently seven second‐generation TPO receptor agonists that have been reported in the literature, representing the potential advantages—and continuing challenges—with this novel class of platelet‐stimulating therapies for ITP and possibly thrombocytopenia in other disease states as well.
First‐line therapies for immune thrombocytopenic purpura: re‐evaluating the need to treat
Authors: Rodeghiero Francesco 
Published: July 2010

AbstractImmune thrombocytopenic purpura (ITP) can be challenging to both diagnose and treat: despite the ability to detect anti‐platelet antibodies, the diagnosis of ITP remains one of exclusion. Management of ITP is similarly difficult as many therapies pose potential risks that may be worse than the disease. It has been generally agreed that bleeding – not platelet count – should be the rationale for treatment. Despite the absence of prospective, controlled studies, there is consensus that bleeding risks are significantly greater in patients with platelet counts <20 × 109–30 × 109/L, and therefore treatment is indicated for these patients; for those with platelet counts that are higher, but still <50 × 109/L, treatment is also indicated if accompanied by substantial mucous membrane bleeding. The standard initial treatment for ITP is oral corticosteroids to increase platelet counts. Intravenous immunoglobulin or anti‐D immunoglobulin can also increase platelet counts and are particularly useful for stimulating rapid platelet increases before planned procedures. Splenectomy, which produces a long‐lasting response in a majority of patients, is still commonly used for those who do not have long‐term responses to steroid therapy and it should remain the gold standard therapy. However, splenectomy is an invasive procedure with some patients relapsing even after several years. Very rare cases of life‐threatening or lethal infections may also occur at any time after splenectomy and thus physicians and patients are increasingly reluctant to advise or agree to this treatment approach. Other treatments have been evaluated to prevent or delay splenectomy, including high‐dose dexamethasone, intermittent anti‐D immunoglobulin infusions, and rituximab. There have been few randomized, placebo‐controlled studies of these approaches, and they cannot currently be recommended as their efficacy and safety remain unclear. Thrombopoietin receptor agonists are currently under clinical investigation for the treatment of ITP and may represent an alternative treatment option in the future. The criteria for treating ITP and the benefits and risks of therapies are discussed here. Ongoing and future studies will help define the best strategies for increasing platelet counts and reducing the risk of bleeding in ITP patients.
Emerging strategies to treat chronic immune thrombocytopenic purpura
Authors: Newland Adrian 
Published: July 2010

AbstractImmune thrombocytopenic purpura (ITP) is a fairly common hematological disorder and is a minor disease for many affected patients; most are in good health, and many can tolerate low platelet counts without the need for treatment. For the majority of patients who do undergo treatment, first‐line therapies, including corticosteroids, are effective in increasing platelet counts, although long‐term use can be associated with adverse effects. Second‐line therapies, such as immunosuppressants, have been largely untested in controlled studies of ITP patients. Like first‐line therapies, splenectomy is effective for many patients; however, it is frequently avoided by physicians who prefer the use of alternative drug therapies due to concerns about safety risks and is often declined by patients reluctant to undergo surgery. Thus, approaches to avoid or defer the use of splenectomy have been actively pursued. An anti‐CD20 antibody, rituximab, can limit the production of autoantibodies, but reactivated viral infections have been reported with its use. Agents that directly stimulate platelet production, such as thrombopoietin (TPO) receptor‐binding agents, have shown promise in clinical trials of ITP patients as well as in hepatitis C virus‐infected individuals with thrombocytopenia. Two TPO receptor agonists in advanced clinical development— eltrombopag and AMG 531—are discussed here. Both eltrombopag and AMG 531 appear to be effective in raising platelet counts and both have been well tolerated in clinical trials to date. However, potential safety issues with thrombopoietic growth factors include thrombocytosis, rebound thrombocytopenia, and increased bone marrow fibrosis. Further testing will determine which safety issues—if any—are of clinical concern.
Spontaneous rupture of the spleen as immediate complication in autologous transplantation for primary systemic amyloidosis
Authors: De Larrea Carlos Fernández , Cibeira Maria Teresa , Rovira Montserrat , Rosiñol Laura , Esteve Jordi , Bladé Joan 
Published: July 2010

AbstractAlthough splenic rupture is a recognized complication of primary amyloidosis, very few cases have been reported in the context of stem cell transplantation. A patient with systemic primary amyloidosis with renal and cardiac involvement and factor X deficiency, who developed a splenic rupture 24 h after the peripheral blood stem cells infusion during autologous transplantation, is described. This complication has been reported during stem cell mobilization and after post‐transplant hematopoietic recovery, but we have not found a previous report of splenic rupture in the immediate postinfusion period. This case illustrates that splenic rupture can occur at any time during the transplant procedure. Need for close monitoring, particularly in patients with factor X deficiency after receiving granulocyte colony stimulating factor, two recently recognized risk factors for splenic hemorrhage, is highlighted.
The heart in transfusion dependent homozygous thalassaemia today – prediction, prevention and management
Authors: Aessopos Athanassios , Berdoukas Vasilios , Tsironi Maria 
Published: July 2010

AbstractCardiac disease remains the major cause of death in thalassaemia major. This review deals with the mechanisms involved in heart failure development, the peculiar clinical presentation of congestive heart failure and provides guidelines for diagnosis and management of the acute phase of cardiac failure. It emphasizes the need for intensive medical – cardiac care and aggressive iron chelating management as, with such approaches, today, the patients outcomes can be favourable in the long term. It covers advances in the assessment of cardiac iron overload with the use of magnetic resonance imaging and makes recommendations for preventing the onset of cardiac problems by tailoring iron chelation therapy appropriate to the degree of cardiac iron loading found.
Effects of fermented soybean meal on growth performance, diarrheal incidence and immune‐response of neonatal calves
Authors: KIM Myung H. , YUN Cheol H. , KIM Hyun S. , KIM Jong H. , KANG Suk J. , LEE Chan H. , KO Jong Y. , HA Jong K. 
Published: July 2010

ABSTRACTThe effects of partial substitution of fermented soybean meal (FSBM) for soybean meal (SBM) on immune‐physiological parameters, growth performance and diarrheal incidence in neonatal calves after microbial infection were investigated. Holstein calves (n = 12) were randomly assigned to two dietary treatments: the SBM and the FSBM group. The latter group received a calf starter containing 5% FSBM instead of SBM. In order to evaluate the immunocompetence against microbial infection, all calves were challenged with porcine live vaccine by intramuscular injection at 21 days of age. The incidence and severity of diarrhea were significantly less (P < 0.05) in the FSBM group compared to those in the SBM group at 21 and 42 days of age. Feeding FSBM starter resulted in a higher (P < 0.05) relative amount of bacterial‐specific IgA than those on SBM at days 5 and 14 post‐microbial infection (DPMI). Viral‐specific IgA also increased (P < 0.05) at 5 DPMI in the FSBM group when compared to the SBM group. The average concentration of haptoglobin of calves fed FSBM was generally higher at 3 DPMI. Our results indicate that FSBM plays a role in the alleviation of diarrhea and in the production of immune‐related effector cells such as IgA and haptoglobin in calves.
Perifollicular Vascularity and Its Relationship with Oocyte Maturity and IVF Outcome
Authors: BORINI ANDREA , MACCOLINI ANDREA , TALLARINI ALESSANDRA , BONU MARIA ANTONIETTA , SCIAJNO RAFFAELLA , FLAMIGNI CARLO 
Published: July 2010

AbstractNew markers of embryo ability to implant are pursued continuously. Understanding whether an oocyte is really “mature,” that is, ready to be fertilized, would be of great help in choosing an embryo that will implant. It is usual to pay attention to the phase of meiosis, considering the extrusion of the polar body (metaphase II) to be the only sign of the maturity of the oocytes. Nevertheless, understanding more about how the cytoplasm contributes to an oocyte's competency also shows promise as a method of predicting which embryos will implant. Some studies about perifollicular vascularity have demonstrated that embryos originating from oocytes developed in well‐vascularized follicles have a higher implantation rate than those originating from oocytes developed in follicles with poor vascularization. Here, we report our results from a preliminary study in which embryos were transferred according to the degree of vascularization of the follicle. Women who received embryos originating from oocytes developed in well‐vascularized follicles had a statistically higher pregnancy rate than women who received embryos deriving from oocytes grown in more poorly vascularized follicles (34% vs. 13.7%).
PEGylation of osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF) results in decreased uptake into rats and human liver
Authors: Saito-Yabe Motoko , Kasuya Yuji , Yoshigae Yasushi , Yamamura Naotoshi , Suzuki Yukie , Fukuda Nao , Honma Masashi , Yano Kazuki , Mochizuki Shin-ichi , Okada Fumihiko , Okada Akiko , Nagayama Yuki , Tsuda Eisuke , Fischer Thomas , Höpner Ursula , Zaja Silvia , Mueller Juergen , Okada Junichi , Kurihara Atsushi , Ikeda Toshihiko , Okazaki Osamu 
Published: July 2010

Abstract

Objectives
Our aim was to investigate the effect of PEGylation on the uptake of osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF) into rat liver, kidney and spleen, and human liver.

Methods
Copolymer of polyethyleneglycol allylmethylether and maleamic acid sodium salt with OCIF (poly(PEG)-OCIF) (0.5 mg/kg) was administered to rats and the concentrations of poly(PEG)-OCIF in the liver, kidney and spleen at 15 min after administration were measured by ELISA. For human liver uptake, the liver perfusion of OCIF and 3H-labelled poly(PEG)-OCIF was conducted using fresh human liver block.

Key findings
The tissue uptake of poly(PEG)-OCIF in rats was significantly lower compared with that of OCIF. In fresh human liver perfusion, 3H-poly(PEG)-OCIF was rarely taken up into the liver. On the other hand, more than 50% of the perfused OCIF was taken up.

Conclusions
PEGylation of OCIF using poly(PEG) dramatically suppressed the uptake of OCIF into human liver as well as into rat liver and could be a promising approach for improving the pharmacokinetic and pharmacological effects of OCIF in the clinical setting.
Central nervous system activity of the proanthocyanidin-rich fraction obtained from Croton celtidifolius in rats
Authors: Moreira Eduardo L G , Rial Daniel , Duarte Filipe S , De Carvalho Cristiane Ribeiro , Horst Heros , Pizzolatti Moacir G , Prediger Rui D S , Ribeiro-do-Valle Rosa Maria 
Published: July 2010

Abstract

Objectives
The aim of the present study was to evaluate the possible neurobehavioural effects in rats of the proanthocyanidin-rich fraction (PRF) isolated from the bark of Croton celtidifolius (Euphorbiaceae).

Methods
Adult Wistar rats were treated with the PRF (0.3–30 mg/kg) and evaluated in different behavioural paradigms classically used for the screening of drugs with psychoactive effects.

Key findings
Acute intraperitoneal (i.p.) administration of PRF decreased spontaneous locomotor activity (open field arena and activity cage), enhanced the duration of ethyl ether-induced hypnosis, increased the latency to the first convulsion induced by pentylenetetrazole (60 mg/kg, i.p.) and attenuated apomorphine-induced (0.5 mg/kg, i.p.) stereotyped behaviour. In lower doses, PRF (0.3 or 3 mg/kg, i.p.) increased the frequency of open arm entries in the elevated plus-maze test.

Conclusions
The present findings suggest that the systemic administration of PRF induces a wide spectrum of behavioural alterations in rats, consistent with the putative existence of hypnosedative, anticonvulsant and anxiolytic compounds.