e‐Learning and transfusion medicine

Audits of clinical transfusion practice have consistently demonstrated deficiencies in knowledge and practice that impact on patient safety and in some cases result in death. These deficiencies include transfusion being prescribed inappropriately, administration of blood components using poor processes, documentation deficiencies and inadequate identification of potential transfusion recipients. Improvement needs to be driven by a multifaceted approach that includes robust systems and mechanisms to ensure compliance combined with education of staff. However, education of medical, nursing and other staff involved in the transfusion chain can be difficult. Large numbers of staff, shiftwork, varying levels of background knowledge and limited resources create significant challenges. Consideration of these problems and informal needs analysis defined a web‐based or on‐line learning tool (e‐learning) as being a suitable mechanism to assist hospitals to increase knowledge of staff. An effective e‐learning tool must be engaging, replicate an authentic learning environment, cater for various learning styles and engage the learner in the learning process. This requires knowledge of on‐line learning best‐practice, learner profiles, learning styles and the learning environment, as well as consideration of interface design, motivational tools and knowledge retention strategies. Funding was provided by the South Australian Department of Health, under the BloodSafe programme, to develop an e‐learning tool. This has resulted in a multimedia‐rich programme utilizing video, audio, animations, and case studies and didactic instruction in order to create an authentic learning environment. Learning content includes expert and peer education, case studies, interactive games and puzzles and modelling of best‐practice processes. A flexible learning pathway gives learners control over learning sequence, content viewed and assessment. Learner demographics, progress and assessment tools and records are stored in an SQL database. This tool is available for use by hospitals and healthcare institutions and professionals. Initial use has demonstrated a high degree of acceptance with participants providing strong feedback on the content, learning pathway and ease of use. Further development is being undertaken to add additional modules offering advanced content and/or a broader audience base. The initial implementation of this e‐learning tool is directed at an Australian audience, however, the content is relevant to the wider transfusion scene in the Asia‐Pacific region (and beyond) as a mechanism for educating staff involved in all steps of the transfusion chain.     

Extended long-term culture reveals a highly quiescent and primitive human hematopoietic progenitor population

Long-term culture-initiating cells (LTC-IC) are hematopoietic progenitors able to generate colony-forming unit-cells (CFU) after 5 to 8 weeks (35 to 60 days) of culture on bone marrow (BM) stroma and represent the most primitive progenitors currently detectable in vitro. We have recently reported that long-term cultures initiated with CD34+CD38- cells from BM or cord blood are able to continue generating CFU for at least 100 days, ie, beyond the standard LTC-IC period. In this report, single-cell cultures from cord blood and retroviral marking of cord blood and BM were used to study whether the subpopulation of CD34+CD38- cells able to generate CFU beyond 60 days ("extended long-term culture-initiating cells" or ELTC-IC) are functionally distinct from LTC-IC in terms of timing of initial clonal proliferation and generative capacity. All cord blood LTC-IC formed clones of greater than 50 cells by day 30. In contrast, cord blood ELTC- IC proliferated later in culture, 50% forming clones after day 30. Although efficient retroviral marking of LTC-IC was seen (25% to 45%), marking of ELTC-IC was inefficient (< 1%), consistent with a more quiescent progenitor population. There was a positive correlation between time of clonal proliferation and generative capacity. ELTC-IC generated threefold to fourfold more progeny than did LTC-IC (P < .002). These studies show that there is a functional hierarchy of progenitors in long-term culture which correlates with their level of quiescence. By extending the LTC-IC assay, a more primitive progenitor may be studied that may be functionally closer to the human long-term repopulation stem cell in vivo.     

The spectrum of MR detectable cortical microinfarcts: a classification study with 7-tesla postmortem MRI and histopathology

Cerebral microinfarcts (CMIs) are common neuropathologic findings in aging and dementia. We explored the spectrum of cortical CMIs that can be visualized with 7T magnetic resonance imaging (MRI). Thirty-three coronal brain slices of 11 individuals with neuropathologically confirmed dementia were subjected to a high-resolution postmortem 7T MRI protocol. First, we identified all visible small (⩽5 mm) intracortical and juxtacortical lesions on postmortem MRI. Lesions were classified as CMI or nonCMI based on histology, and their MR features were recorded. Thirty lesions were identified on the initial MRI evaluation, of which twenty-three could be matched with histology. Histopathology classified 12 lesions as CMIs, all of which were located intracortically. On the basis of their MR features, they could be classified as chronic gliotic CMIs—with or without cavitation or hemorrhagic components—and acute CMIs. Eleven MRI identified lesions were not of ischemic nature and most commonly enlarged or atypically shaped perivascular spaces. Their MRI features were similar to gliotic CMIs with or without cavitation, but these ‘CMI mimics'' were always located juxtacortically. 7T postmortem MRI distinguishes different histopathologic types of cortical CMIs, with distinctive MR characteristics. On the basis of our findings, we propose in vivo rating criteria for the detection of intracortical CMIs.     

The effect of the Fanconi anemia polypeptide, FAC, upon p53 induction and G2 checkpoint regulation

Fanconi anemia (FA) is an autosomal recessive disease marked by developmental defects, bone marrow failure, and cancer susceptibility. FA cells are hypersensitive to DNA cross-linking and alkylating agents and accumulate in the G2 phase of the cell cycle in response to these agents. FA cells also display genomic instability, suggesting a possible defect in the p53 pathway. To test the effect of heterologous expression of FAC cDNA on drug-induced cytotoxicity, G2 accumulation, and p53 induction in FA cells, we compared two isogenic FA cell lines: HSC536N (mock), a FA type C cell line sensitive to mitomycin C (MMC), and the same cell line transfected (corrected) with wild-type FAC cDNA (HSC536N [+FAC]). HSC536N (+FAC) cells showed a 30-fold increase in resistance to MMC concentration. Similarly, increases in resistance were observed following exposure to cisplatin, carboplatin, and cyclophosphamide. In addition, HSC536N (+FAC) cells showed a twofold lower G2 accumulation following MMC treatment. To analyze the possible interaction of FAC with the p53 pathway, we analyzed p53 induction in mock and corrected cell lines following exposure to MMC. HSC536N (mock) cells induced p53 at lower MMC concentrations than HSC536N (corrected). Caffeine, a known G2 checkpoint inhibitor, not only inhibited G2 accumulation seen in both cell lines but also caused the resistant HSC536N (+FAC) to become as sensitive to MMC as HSC536N (mock) cell line. We conclude that the FAC protein has a specific cytoprotective effect and may function as a cell cycle regulator of the G2 phase of the cell cycle.     

Effects of pain and fatigue on physical functioning and depression in persons with muscular dystrophy

BackgroundPain and fatigue are common symptoms experienced by persons with muscular dystrophy (MD). However, it is unclear from previous studies whether pain and fatigue have independent effects on physical functioning and depression, and whether age moderates the relationship of pain and fatigue with physical functioning and depression.ObjectiveThis cross-sectional study aimed to describe the relationship of pain and fatigue to physical functioning and depression in persons 20–89 years old with MD.MethodA convenience sample of 332 individuals with MD completed a questionnaire that included measures of physical functioning (PROMIS item bank items), depression (PHQ-9), pain intensity (0–10 NRS), and fatigue (0–10 NRS).ResultsPain and fatigue were each independently associated with physical functioning and depression. Depressive symptoms were most severe among middle-aged participants (45–64 years old) relative to older and younger participants. Physical functioning had a negative relationship with chronological age.ConclusionsSymptoms of pain and fatigue are significantly and independently related to physical functioning and depression in persons with MD. Research is needed to determine if treatments that target both pain and fatigue in patients with MD have more beneficial effects than treatments that target only one of these symptoms.     

Mapping social processes at work in nursing knowledge development

In this paper, we suggest a blueprint for combining bibliometrics and critical analysis as a way to review published scientific works in nursing. This new approach is neither a systematic review nor meta‐analysis. Instead, it is a way for researchers and clinicians to understand how and why current nursing knowledge developed as it did. Our approach will enable consumers and producers of nursing knowledge to recognize and take into account the social processes involved in the development, evaluation, and utilization of new nursing knowledge. We offer a rationale and a strategy for examining the socially‐sanctioned actions by which nurse scientists signal to readers the boundaries of their thinking about a problem, the roots of their ideas, and the significance of their work. These actions – based on social processes of authority, credibility, and prestige – have bearing on the careers of nurse scientists and on the ways the knowledge they create enters into the everyday world of nurse clinicians and determines their actions at the bedside, as well as their opportunities for advancement.     

二尖瓣疾病左心室充盈压的多普勒评估

由于在瓣膜区域、左心室松弛性和僵直性等方面易于发生混淆．传统多普勒测量对二尖瓣疾病病人左心房压的预测上受到限制。然而，在犬和临床研究中，组织多普勒成像所测定的充盈早期二尖瓣血流速率起始段和房室环的充盈早期速率之间的时间窗（time interval between the onset of early diastolic mitral inflow velocity and annular early diastolic velocity，TE-Ea）与左心室舒张时间常数（time constant of left ventricular relaxation，t）良好相关，并且不受上述瓣膜区域、左心室舒张和僵直等变量的影响。因此在病人人群中开展这项研究，检验其用途。     

The significance of HLA-DRB1 matching on clinical outcome after HLA-A, B, DR identical unrelated donor marrow transplantation

Despite matching for serologically defined HLA-A, B, DR antigens, acute graft-versus-host disease (GVHD) is a major complication contributing to increased morbidity and mortality in patients who undergo marrow transplantation from unrelated donors. The extent to which unrecognized mismatching for alleles that encode DR1-DR18 contribute to the increased risk of acute GVHD and overall survival is unknown. We analyzed 364 patients and their HLA-A, B, DR serologically matched donors to determine whether molecular typing of DRB1 alleles can allow more accurate donor/recipient matching and thereby improve clinical outcome after marrow transplantation. DRB1 alleles were typed by sequence-specific oligonucleotide probe hybridization methods. Selected alleles were confirmed by DNA sequencing. Of the 364 pairs, 305 were matched and 59 were mismatched for DRB1. The probability of moderate to severe acute GVHD was .48 for the matched and .70 for the mismatched patients. Compared with mismatched patients, the estimated relative risk (RR) of GVHD for matched patients was .58 (95% confidence interval [CI], .40 to .85). DRB1 matching decreased the risk of transplant- related mortality (RR, .66; 95% CI, .44 to .97) and was associated with decreased overall mortality (RR, .71; 95% CI, .51 to 1.0). Therefore, matching DRB1 alleles of the donor and recipient decreases the risk of acute GVHD and improves survival after unrelated marrow transplantation. These results indicate that prospective matching of patients and donors for DRB1 alleles is warranted.     

Detection of platelet-directed immunoglobin G in sera using the peroxidase-anti-peroxidase (PAP) slide technique

An immunohistochemical procedure for the detection of immunoglobulin G adherent to platelets is described. The peroxidase anti-peroxidase method is used to detect antibody activity directed against platelets from normal donors in the sera from 305 individuals. These subjects were divided into three groups: group 1, patients referred for tissue typing; group 2, healthy normal females; group 3, healthy normal males. In group 1, 28% of the sera were found to be positive; in most of these a history of prior transfusions was obtained. In group 2, 7.4% were found to be positive, most having previous pregnancies. Only 1% were found to be positive in group 3, and no reason for presensitization was found. Results from the indirect immunofluorescence technique served as a control and as a means to compare the sensitivity. Under the conditions chosen, the peroxidase anti-peroxidase test was two to eight times more sensitive than the immunofluorescence technique. Specificity of the peroxidase anti-peroxidase technique was demonstrated using a monospecific anti-PLA1 antiserum. It is concluded that the peroxidase anti-peroxidase slide technique may be a useful tool in the study of platelet-related immunophenomena.