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.     

The physiological regulation of toll-like receptor expression and function in humans

Eleven mammalian toll-like receptors (TLRs 1–11) have been identified to date and are known to play a crucial role in the regulation of immune responses; however, the factors that regulate TLR expression and function in vivo are poorly understood. Therefore, in the present study, we investigated the physiological regulation of TLR expression and function in humans. To examine the influence of diurnal rhythmicity on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers ( n = 8) at time points coinciding with the peak and nadir in the endogenous circulating cortisol concentration. While no diurnal rhythmicity in the expression of TLRs 1, 2, 4 or 9 was observed, the upregulation of costimulatory (CD80 and CD86) and antigen-presenting (MHC class II) molecules on CD14⁺ monocytes following activation with specific TLR ligands was greater ( P < 0.05) in samples obtained in the evening compared with the morning. To examine the influence of physical stress on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers ( n = 11) at rest and following 1.5 h of strenuous exercise in the heat (34°C). Strenuous exercise resulted in a decrease ( P < 0.005) in the expression of TLRs 1, 2 and 4 on CD14⁺ monocytes. Furthermore, the upregulation of CD80, CD86, MHC class II and interleukin-6 by CD14⁺ monocytes following activation with specific TLR ligands was decreased ( P < 0.05) in samples obtained following exercise compared with at rest. These results demonstrate that TLR function is subject to modulation under physiological conditions in vivo and provide evidence for the role of immunomodulatory hormones in the regulation of TLR function.     

Gastric emptying of carbohydrate--medium chain triglyceride suspensions at rest.

Nine male volunteers participated in 4 gastric emptying (GE) tests of liquid equicaloric mixtures of CHO (maltodextrins) and MCT of the following composition (% CHO-% MCT): Drink (Dr) 1:70%-30%, Dr2: 80%-20%, Dr3: 90%-10%, Dr4: 100%-0%. GE was measured at rest for 90 min according to the modified double sampling technique. GE rate, expressed as t1/2 (SEM), was 23 (2.3), 24 (1.6), 27 (2.2) and 36 (2.9) min, respectively, from drink 1 to drink 4. Statistical analysis showed that all MCT containing drinks emptied faster than the 100% CHO drink. Two mechanisms may explain this observation: 1) the CHO content and osmolality increases from Dr 1 to Dr 4 (both are regulators of GE); 2) MCT may not inhibit GE as common fat does, due to a better water solubility and absorption in the small intestine, resulting in a decreased duodenal-gastric feedback.     

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.     

The effect of sweetness on the efficacy of carbohydrate supplementation during exercise in the heat.

The aim of the present study was to investigate potential mechanisms responsible for the improvement in prolonged exercise capacity in hot environments with exogenous carbohydrate. Eight endurance-trained men (VO(2)max 60.5 +/- 2.4 ml.kg(-1).min(-1), mean +/- SE) cycled to exhaustion on three occasions at 60% VO(2)max at an ambient temperature of 35 degrees C. They ingested either a sweet 6.4% carbohydrate solution (SC), a nonsweet 6.4% carbohydrate solution (NSC), or water (W). Exercise capacity was significantly increased with SC and NSC compared to W, the improvements corresponding to 15.8% and 11.8%, respectively. No difference in exercise capacity was seen between SC and NSC solutions. Plasma glucose concentrations were higher during the SC and NSC trials compared to W, significantly so at 10 min and at fatigue. Rates of carbohydrate oxidation were higher in the SC and NSC trials, although the rates never declined below 2.1 +/- 0.2 g.min(-1) in the W trial. There was no difference in the rate of rise of rectal temperature between trials, but there was a trend for subjects to fatigue at higher temperatures during the two carbohydrate trials. In conclusion, exogenous carbohydrate, independent of sweetness, improves exercise capacity in the heat compared to water alone.