Disseminated tuberculosis following reduced-intensity cord blood transplantation for adult patients with hematological diseases

Allogeneic hematopoietic stem cell transplantation (allo-SCT) recipients are prone to infections. The incidences of mycobacterial infections after allo-SCT in several case series vary from less than 0.1-5.5%. However, no study has been published on tuberculosis following unrelated cord blood transplantation (UCBT). We retrospectively reviewed medical records of 113 adult patients with a median age of 54 years who underwent reduced-intensity UCBT (RI-UCBT) at Toranomon Hospital from March 2002 to May 2004. Mycobacterium tuberculosis infections were diagnosed in three patients (2.7%), of these two patients developed primary infection and one patient developed reactivation of latent tuberculosis. The interval between RI-UCBT and the diagnosis of tuberculosis was 34, 41 and 61 days. All the patients had disseminated disease at diagnosis. Histological examination showed the lack of granuloma in caseous necrosis. Combination antituberculous treatments showed limited efficacy, and two patients died immediately after diagnosis. M. tuberculosis caused life-threatening illness, rapidly progressing in RI-UCBT recipients. The lack of granuloma in caseous necrosis suggests the impaired T-cell function in early post transplant phase of RI-UCBT. We should consider M. tuberculosis in the differential diagnoses of fever of unknown source after RI-UCBT.     

Comparison of human skeletal myoblasts and bone marrow-derived CD133+ progenitors for the repair of infarcted myocardium

OBJECTIVES: The present study was designed as a face-to-face functional comparison of human skeletal myoblasts (SMs) and CD133(+) bone marrow-derived hematopoietic progenitors in an animal model of semichronic myocardial infarction. BACKGROUND: Compared with SMs, bone marrow-derived cells have the advantage of plasticity and might more effectively regenerate ischemic cardiac tissue. However, few data exist on the comparative efficacy of these two cell types in semichronic infarcts. METHODS: A myocardial infarction was created by coronary ligation in 32 nude rats. Ten days later, rats received in-scar injections of human SMs, CD133(+) progenitors, or culture medium. Left ventricular function was assessed before and one month after transplantation by echocardiography and pressure-volume loops. Immunofluorescence, polymerase chain reaction, and in situ hybridization were used to detect cells grafted in the hearts. RESULTS: One month after transplantation, left ventricular ejection fraction decreased by 8 +/- 4% in controls, whereas it increased by 7 +/- 3% in CD133(+)-grafted hearts (p = 0.0015 vs. controls) and further by 15 +/- 5% in SM-treated hearts (p = 0.008 vs. controls). Systolic indices yielded by pressure-volume loops paralleled these data. Engrafted myotubes were identified in all SM-treated hearts by immunofluorescence, whereas in CD133(+)-grafted hearts, few human cells were only detected by polymerase chain reaction. CONCLUSIONS: In the setting of postinfarction scars, the transplantation of bone marrow-derived CD133(+) progenitors improves cardiac function, but this benefit is not superior to that afforded by myogenic cells.     

Post-partum sacral fracture associated with heparin treatment

We report the case of a 19-year-old woman who consulted for low-back pain 3 weeks after her first delivery. This young woman had a personal history of protein C deficiency and was treated daily during her pregnancy with low-molecular-weight heparin. Her body mass index was 34 and she only gained 10 kg during her pregnancy. Since the delivery - which occurred without any complication - she had suffered from a gradually increasing right-buttock pain and limp. Magnetic resonance imaging (MRI) revealed a fracture of the right sacral ala. After analgesia and 1 month of home relative bed rest, the patient recovered her functional capacities. Regarding our patient, who had no potential clinical risk factors for osteoporosis, the causal effect of heparin is thus possible but not certain. This case report illustrates the fact that clinicians should have a high suspicion of pelvic fracture in post-partum women, even in very young ones, presenting sudden onset of low back and pelvic pain, especially when they have received heparin during pregnancy. MRI seems to be the key exam because it is able to detect and stage fractures or microfractures.     

Aging and probabilistic learning in single- and multiple-cue tasks

The objective of the study was to examine some of the conditions under which elderly people are able to learn probabilistic inverse relationships and when this type of learning is no longer possible. Two kind of tasks were used: (a) two single-cue learning tasks with either direct or inverse relationships (the Single-Cue Probability Learning paradigm), and (b) three two-cue learning tasks, one with two direct relationships, one with a combination of direct and inverse relationships, and one with two inverse relationships (the Multiple-Cue Probability Learning paradigm). Four groups of participants were included in the study: young adults (18- to 25-year-olds), adults (40- to 50-year-olds), elderly people (65- to 74-year-olds), and very elderly people (75- to 90-year-olds). It was shown that (a) older adults are able to reject the direct relationship "default" hypothesis and select the inverse relationship hypothesis when outcome feedback contradicting the default hypothesis is given, and provided that the learning setting be a very simple one, involving only one cue; (b) some older adults are able to select the inverse relationship hypothesis provided that the learning setting be a simple one,involving only two inverse relationship cues; and (c) very few older adults are able to select the inverse relationship hypothesis when the learning setting is a complex one, involving two cues with both direct and inverse relationships with the criterion. These results led to the revision of the "gradual decrease of cognitive flexibility in older adults" hypothesis proposed by Chasseigne, Mullet, and Stewart (Acta Psychologicgrave;a, 103, 229-238, 1997).     

New thioredoxin targets in the unicellular photosynthetic eukaryote Chlamydomonas reinhardtii

Proteomics were used to identify the proteins from the eukaryotic unicellular green alga Chlamydomonas reinhardtii that can be reduced by thioredoxin. These proteins were retained specifically on a thioredoxin affinity column made of a monocysteinic thioredoxin mutant able to form mixed disulfides with its targets. Of a total of 55 identified targets, 29 had been found previously in higher plants or Synechocystis, but 26 were new targets. Biochemical tests were performed on three of them, showing a thioredoxin-dependent activation of isocitrate lyase and isopropylmalate dehydrogenase and a thioredoxin-dependent deactivation of catalase that is redox insensitive in Arabidopsis. In addition, we identified a Ran protein, a previously uncharacterized nuclear target in a photosynthetic organism. The metabolic and evolutionary implications of these findings are discussed.     

Mesenchymal stem cells exert differential effects on alloantigen and virus-specific T-cell responses

Mesenchymal stem cells (MSCs) suppress alloantigen-induced T-cell functions in vitro and infusion of third-party MSCs seems to be a promising therapy for graft-versus-host disease (GVHD). Little is known about the specificity of immunosuppression by MSCs, in particular the effect on immunity to pathogens. We have studied how MSCs affect T-cell responses specific to Epstein-Barr virus (EBV) and cytomegalovirus (CMV). We found that EBV- and CMV-induced proliferation and interferon- (IFN-) production from peripheral blood mononuclear cells (PBMCs) was less affected by third-party MSCs than the response to alloantigen and that MSCs had no effect on expansion of EBV and CMV pentamer-specific T cells. Established EBV-specific cytotoxic T cells (CTL) or CMV-CTL cultured with MSCs retained the ability to proliferate and produce IFN- in response to their cognate antigen and to kill virally infected targets. Finally, PBMCs from 2 patients who received MSCs for acute GVHD showed persistence of CMV-specific T cells and retained IFN- response to CMV after MSC infusion. In summary, MSCs have little effect on T-cell responses to EBV and CMV, which contrasts to their strong immunosuppressive effects on alloreactive T cells. These data have major implications for immunotherapy of GVHD with MSCs and suggest that the effector functions of virus-specific T cells may be retained after MSC infusion.     

静脉麻醉在老年患者胃肠镜检查中的应用

胃肠镜检查时易引起恶心、呕吐、腹痛,使患者产生畏惧心理,而对伴有心肺脑血管疾病的老年患者,还可引起心律失常或心肌梗死.合理的麻醉能消除患者的恐惧心理,抑制恶心、呕吐、疼痛反应,从而稳定呼吸循环功能,预防相关并发症的发生,但老年患者对麻醉药物耐受性差,且多伴有心肺脑血管疾病,故麻醉胃肠镜检查存在一定风险.     

Anxiety and depression after coronary artery bypass graft surgery: most get better, some get worse

BACKGROUND: To target interventions, patients at risk for poor outcomes after a cardiac event need to be identified. We investigated trajectories of anxiety and depression after coronary artery bypass graft surgery (CABGS) and identified patients at risk of persistent or worsening anxiety and depression. METHODS: A consecutive sample of 184 patients on the waiting list for CABGS at The Royal Melbourne Hospital completed self-report questionnaires before surgery, and at 2 and 6 months postsurgery. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale. Growth mixture modelling identified trajectories of anxiety and depression. RESULTS: Two possible trajectories emerged for anxiety, whereas three trajectories emerged for depression. Most patients (92%) followed a trajectory of minor presurgical anxiety that remitted in 6 months after CABGS, with the remainder (8%) following a trajectory of major anxiety that remitted in the same period. Minor remitted depression was also common (72% patients). Two less common depression trajectories indicated worsening or unresolved depression. One trajectory began with major presurgical depression that partially remitted by 6 months (14% patients) and the other began with minor presurgical depression that worsened by 6 months (14% patients). Unpartnered patients, smokers, those with presurgical anxiety, high cholesterol, angina, more severe disease or having repeat CABGS were at increased risk for a poor depression trajectory. CONCLUSION: Although initial anxiety and depression resolved or lessened for most patients, some patients experienced persistent or worsening depression after CABGS. Interventions can be targeted toward 'at risk' patients.