Retention of "safe" blood donors. The Retrovirus Epidemiology Donor Study

BACKGROUND: There are obvious advantages to increasing donor retention. However, for reasons of blood safety, certain donors may, in fact, be more desirable to retain than others. “Safe” donors are defined as those who provided a blood donation that was negative on all laboratory screening tests and who subsequently reported no behavioral risks in response to an anonymous survey. This study identifies the most important factors affecting the intention of “safe” donors to provide another donation. STUDY DESIGN AND METHODS: An anonymous survey asking about donation history, sexual history, injecting drug use, and recent donation experience was mailed to 50,162 randomly selected allogeneic donors (including directed donors) who gave blood from April through July or from October through December 1993 at one of the five United States blood centers participating in the Retrovirus Epidemiology Donor Study. Before mailing, questionnaires were coded to designate donors with nonreactive laboratory screening tests at their most recent donation. RESULTS: A total of 34,726 donors (69%) responded, with substantially higher response among repeat donors. According to reported intentions only, the vast majority of “safe” donors indicated a high likelihood of donating again within the next 12 months. Only 3.4 percent reported a low likelihood of donating again. A comparison of those likely to return and those unlikely to return reveals significant differences in demographics and in ratings of the donation experience. A higher proportion of those unlikely to return were first-time donors, minority-group donors, and donors with less education. The highest projected loss among “safe” donors was seen for those who gave a fair to poor assessment of their treatment by blood center staff or of their physical well-being during or after donating. CONCLUSION: These data suggest that efforts to improve donors' perceptions of their donation experience, as well as attention to the physical effects of blood donation, may aid in the retention of both repeat and first-time donors.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Indomethacin increases the effect of isosorbide dinitrate on cerebral hemodynamic in migraine patients: pathogenetic and therapeutic implications

Intracerebral vascular reactivity induced by the nitric oxide (NO) donor isosorbide dinitrate (IDN, 5 mg sublingually) is more major and longer-lasting in migraine patients who develop delayed headache in response to the drug. The headache is purportedly due to neuronally-mediated vascular mechanisms. Indomethacin inhibits prostaglandin synthesis, which is involved in NO generation. Indomethacin also decreases cerebral blood flow by constricting precapillary resistance vessels. In the present study, the hemodynamic effects of indomethacin were evaluated in migraine patients and healthy controls by means of transcranial Doppler monitoring. Indomethacin caused a significant decrease in mean flow velocity in the middle cerebral artery. This was an additional effect to the mean velocity decrease induced by IDN. The interactions between the two drugs suggest that their effects on cerebral hemodynamics (and pain) may be of relevance both in understanding the role of NO in migraine pathogenesis and in evaluating symptomatic treatments for migraine attacks.     

Endotracheal suctioning causes right upper lobe collapse in intubated children

Objective: Right upper lobe collapse is a common radiographic finding in intubated children. We hypothesized that deep suctioning and uncontrolled negative pressures during endotracheal tube suctioning were significant contributory factors. Methods : The incidence of right upper lobe (RUL) collapse in intubated, ventilated children on a paediatric cardiac intensive care unit was determined over a 3-month period ( n = 102). Graduated suction catheters and suction vacuums of < 165 cm H₂O were then introduced. Another prospective audit was carried out 3 months later ( n = 60). Results : We found that 24% developed RUL collapse and 4 developed an apical pneumothorax. Following the introduction of graduated catheters and controlled vacuums pressures, a significant reduction in the incidence of RUL collapse, to 7%, was observed ( p < 0.05). Conclusions : We conclude that high negative pressure and deep-suctioning causes RUL collapse in children. Any lobar collapse not only prolongs the child's stay in intensive care, but can be associated with further morbidity which may have a serious implication. By improving suctioning technique this morbidity can be significantly reduced.     

Automated Sequence Preprocessing in a Large-Scale Sequencing Environment

A software system for transforming fragments from four-color fluorescence-based gel electrophoresis experiments into assembled sequence is described. It has been developed for large-scale processing of all trace data, including shotgun and finishing reads, regardless of clone origin. Design considerations are discussed in detail, as are programming implementation and graphic tools. The importance of input validation, record tracking, and use of base quality values is emphasized. Several quality analysis metrics are proposed and applied to sample results from recently sequenced clones. Such quantities prove to be a valuable aid in evaluating modifications of sequencing protocol. The system is in full production use at both the Genome Sequencing Center and the Sanger Centre, for which combined weekly production is ~100,000 sequencing reads per week.     

Sensitive PCR-restriction fragment length polymorphism assay for detection and genotyping of Giardia duodenalis in human feces

An assay that uses heminested PCR-restriction fragment length polymorphism analysis for the detection and genotyping of Giardia duodenalis on the basis of polymorphism in the triose phosphate isomerase (tpi) gene was developed. This assay was evaluated with DNA extracted from purified parasite material, bacterial cultures, whole human feces containing G. duodenalis and other parasites, and their corresponding immunofluorescence-stained fecal smears on glass microscope slides. The assay was specific and discriminated between G. duodenalis assemblages A and B. RFLP analysis further distinguished two groups (designated groups I and II) within assemblage A. Among 35 DNA samples extracted from whole feces from patients with confirmed sporadic giardiasis, the tpi gene was amplified from 33 (94%). Of these, nine (27%) samples contained assemblage A group II, 21 (64%) contained assemblage B, and 3 (9%) contained a mixture of assemblage A group II and assemblage B. The tpi gene of G. duodenalis assemblage B was amplified from 21 of 24 (88%) DNA samples extracted from whole feces from patients with confirmed cases of infection in a nursery outbreak. No amplification was detected from the remaining three DNA samples. Overall, analysis of DNA extracted from material recovered from stained microscope slides identified identical G. duodenalis genotypes in 35 (65%) of the 54 samples for which a genotype was established with DNA from whole feces. The heminested PCR method developed is sensitive, simple, and rapid to perform and is applicable for the analysis of other intestinal pathogens.     

Age group differences in psychological distress: the role of psychosocial risk factors that vary with age

BACKGROUND: There is continuing controversy about how age affects depression and anxiety, with a lack of consistent results across studies. Two reasons for this inconsistency are age bias in measures and different patterns of exposure to risk factors across age groups in various studies. METHOD: Data on anxiety and depression symptoms were collected in a community survey of 7485 persons aged 20-24, 40-44 or 60-64 years. These measures were investigated for factorial invariance across age groups. Data were also collected on a wide range of potential risk factors, including social, physical health and personal factors, with the aim of determining whether these factors might partly or wholly account for age group differences. RESULTS: The invariance of correlated latent factors representing anxiety and depression was examined across age groups, and a generalized measure of psychological distress was computed. Depression, anxiety and psychological distress showed a decline across age groups for females and a decline from 40-44 to 60-64 years for males. Some of these age differences were accounted for by other risk factors, with the most important being recent crises at work and negative social relationships with family and friends. CONCLUSION: Psychological distress generally declined across the age range 20-64 years and this was not attributable to measurement bias. Differential exposure to risk factors explained some, but not all, of the age group difference. Therefore other mechanisms that explain the lower level of distress in older age groups remain to be identified.     

Autoimmunity and inflammation due to a gain-of-function mutation in phospholipase C gamma 2 that specifically increases external Ca2+ entry

The identification of specific genetic loci that contribute to inflammatory and autoimmune diseases has proved difficult due to the contribution of multiple interacting genes, the inherent genetic heterogeneity present in human populations, and a lack of new mouse mutants. By using N-ethyl-N-nitrosourea (ENU) mutagenesis to discover new immune regulators, we identified a point mutation in the murine phospholipase Cg2 (Plcg2) gene that leads to severe spontaneous inflammation and autoimmunity. The disease is composed of an autoimmune component mediated by autoantibody immune complexes and B and T cell independent inflammation. The underlying mechanism is a gain-of-function mutation in Plcg2, which leads to hyperreactive external calcium entry in B cells and expansion of innate inflammatory cells. This mutant identifies Plcg2 as a key regulator in an autoimmune and inflammatory disease mediated by B cells and non-B, non-T haematopoietic cells and emphasizes that by distinct genetic modulation, a single point mutation can lead to a complex immunological phenotype.