Busulfan and total body irradiation as antihematopoietic stem cell agents in the preparation of patients with congenital bone marrow disorders for allogenic bone marrow transplantation

The capacity of busulfan and total body irradiation to ablate hematopoietic stem cells as preparation for the allogeneic bone marrow transplantation of patients with congenital bone marrow disorders was studied. Fourteen patients received 18 transplants; busulfan was used in the preparatory regimen of eight transplants and total body irradiation in the regimens of six transplants. Sustained hematopoietic ablation was achieved in six of eight patients prepared with busulfan and in all six patients prepared with total body irradiation. Three patients prepared with total body irradiation died with idiopathic interstitial pneumonitis, whereas no patients receiving busulfan developed interstitial pneumonitis. The optimal antihematopoietic stem cell agent to be used for the preparation of patients with congenital bone marrow disorder for bone marrow transplantation is not certain.     

Demonstration of burst-promoting activity of recombinant human GM-CSF on circulating erythroid progenitors using an assay involving the delayed addition of erythropoietin

We demonstrate through the use of an in vitro assay involving the delayed addition of erythropoietin that human recombinant GM-CSF, cloned from a mature T cell line, Mo, clearly has burst-promoting activity (BPA) on peripheral blood erythroid progenitors at picomolar concentrations. Delay for up to 72 hours of the addition of erythropoietin to semi-solid methylcellulose cultures of concentrated peripheral blood progenitors minimizes or eliminates BPA-independent erythroid colony formation with little loss of BPA-dependent erythroid colony formation. This assay will prove useful in accurately detecting sources of BPA.     

Beta-thalassemia due to two novel nucleotide substitutions in consensus acceptor splice sequences of the beta-globin gene

We have identified two novel RNA-splicing mutations affecting a critical nucleotide (nt) in the acceptor consensus sequences at both the IVS-1/exon 2 and IVS-2/exon 3 junctions of the human beta-globin gene. Both mutations are single nt substitutions, T to G and C to A, at position -3 adjacent to the invariant AG dinucleotide. For the IVS- 2/exon 3 mutation abnormal splicing into the cryptic splice site at IVS- 2 nt 579 is documented. Identification of these two mutations provides further support for the importance of the location of specific nucleotides within the consensus sequences in splice site selection and RNA processing.     

Alteration in bone marrow adherent layer growth factor expression: a novel mechanism of chronic myelogenous leukemia progression

Philadelphia chromosome1 positive (Ph1) chronic myelogenous leukemia (CML) is characterized by metamorphosis of the chronic phase to blastic crisis. However, cellular events associated with this transition are poorly understood. To examine the possible participation of hematopoietic growth factors in this process, we studied growth factor expression in adherent layers of bone marrows derived from CML Ph1 patients in various stages of the disease. Interleukin-1 beta (IL-1 beta) and IL-6 mRNA were expressed in five of six patients, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in one of six patients with myeloid/undifferentiated blast crisis. In addition, leukemia inhibitory factor (LIF) expression was increased in four of six patients with myeloid/undifferentiated blast crisis phase of the disease. IL-1 beta was also detected in bone marrow adherent layer conditioned medium from two of these patients. These results were in sharp contrast to the lack of detectable levels of uninduced IL-1 beta, IL-6, and GM-CSF mRNA, in samples derived from 4 patients in lymphoid blastic crisis, 3 in accelerated, and 11 in chronic phases of the disease, or from normal controls. The possibility of a paracrine loop formation, whereby the adherent layers representing the bone marrow stroma are induced to express hematopoietic growth factors, was supported by our finding IL-1 beta mRNA expression in the leukemic blast cells in three of four studied patients in blast crisis and IL-1 beta protein production in seven of eight patients studied. Finally, coculturing CML blast crisis cells onto pre-established adherent layers induced the expression of both IL-1 beta and IL-6 genes. From this preliminary study, it appears that abnormal expression of growth factors is a common event with CML Ph1 progression. We hypothesize that IL-1 beta generated by the transformed malignant clone stimulates the marrow stroma to produce various growth factors, and that this process may play a role in disease progression.     

Measurement of ploidy distribution in megakaryocyte colonies obtained from culture: with studies of the effects of thrombocytopenia

Microdensitometric measurement of the DNA content of individual megakaryocytes was performed using megakaryocyte colonies obtained following culture, in soft agar, of hematopoietic cells from C57BL/6J mice. Two types of colonies were detected. After 7 days of culture, the big cell type contained 16 /+- 2.3 acetylcholinesterase (AChE) positive cells/colony, with a mean ploidy level of 16.8 /+- 0.8/cell and the ploidy distribution characteristic of recognizable megakaryocytes in bone marrow. The heterogeneous type contained 44 /+- 9.6 cells/colony (some of which were AChE negative), with a mean ploidy level of 6.8 /+- 0.7/cell. The ploidy distribution of heterogeneous colonies differed markedly from big cell colonies, with preponderance of 2N and 4N cells. Colony-forming cells, obtained 4-5 days after induction of acute thrombocytopenia, gave big cell colonies with a marked increase in DNA content. Mean ploidy level increased to 21.5 /%- 1.8/cell; the frequency of 32N cells increased from 17% to 30% and 64N cells from 0% to 6%. This is the pattern of change observed in bone marrow, in vivo, 24 to 48 hr after induction of acute thrombocytopenia. The number of cells/colony did not increase. In contrast, acute thrombocytopenia did not alter the ploidy of heterogeneous colonies. The different responses to the stimulus of acute thrombocytopenia suggest that there are at least two types of Meg-CFC. The delayed appearance of altered Meg-CFC that produced big cell colonies indicates that the pool of stem cells, from which committed megakaryocyte precursors are derived, may respond indirectly to the stimulus of platelet depletion.     

Neutrophil mediated smooth muscle cell loss precedes allograft vasculopathy

Background  

Cardiac allograft vasculopathy (AV) is a pathological process of vascular remodeling leading to late graft loss following cardiac transplantation. While there is consensus that AV is alloimmune mediated, and evidence that the most important alloimmune target is medial smooth muscle cells (SMC), the role of the innate immune response in the initiation of this disease is still being elucidated. As ischemia reperfusion (IR) injury plays a pivotal role in the initiation of AV, we hypothesize that IR enhances the early innate response to cardiac allografts.     

新生儿呼吸窘迫综合征的管理——欧洲共识指南2010版

一、简介 2010版指南包含了2007年后循证医学的最新证据,如现在有更多的证据支持以前推荐的早期使用肺表面活性物质及持续气道正压通气(CPAP);对产房稳定进行了扩充,并有一些新的推荐,如延迟脐带结扎;增加了避免和减少使用机械通气及通气时间,以及咖啡因、鼻腔通气、允许性高碳酸血症、新式呼吸机通气模式的使用等内容;还增加了其他情况下发生的新生儿呼吸窘迫综合征(RDS)的管理.该指南得到欧洲围产医学会的认同.     

Staplerh?morrhoidopexie im Vergleich zur Milligan-Morgan- und Ferguson-H?morrhoidektomie: ein systematisches Review

Zusammenfassung Fragestellung:   Ziel dieser Studie war, ein systematisches Review und eine Metaanalyse der Kurz- und Langzeitergebnisse der Staplerh?morrhoidopexie durchzuführen. Patienten und Methodik:   Mit einer Literatursuche wurden randomisierte, kontrollierte Studien zum Vergleich von Staplerh?morrhoidopexie und Milligan-Morgan-/Ferguson-H?morrhoidektomie abgefragt. Die Daten wurden für jede Studie einzeln entnommen und die Unterschiede mit Fixed- und Random-Effects-Modellen analysiert. Ergebnisse:   Es wurden 34 randomisierte Studien und zwei systematische Reviews gefunden; hiervon wurden 29 Studien eingeschlossen. Die Staplerh?morrhoidopexie erwies sich in Bezug auf den Klinikaufenthalt (p < 0,001) als statistisch signifikant überlegen und hinsichtlich der postoperativen Schmerzen (perioperativ und früh-postoperativ), der Operationsdauer sowie der Blutungen (postoperativ und sp?t-postoperativ) als numerisch überlegen. Nach der Staplerh?morrhoidopexie waren Prolapsrezidive und wiederholte Eingriffe aufgrund von Rezidiven h?ufiger. Bei den Komplikationsraten wurden keine Unterschiede beobachtet. Schlussfolgerung:   Die Staplerh?morrhoidopexie reduziert die Dauer des Krankenhausaufenthalts und k?nnte einen Vorteil im Sinne einer kürzeren Operationsdauer, weniger postoperativer Schmerzen und geringerer Blutungen bieten, ist jedoch mit einer erh?hten Rate von Prolapsrezidiven assoziiert. übersetzter Nachdruck aus Int J Colorectal Dis 2009;24:335–44; DOI 10.1007/s00384-008-0611-0.