Patterns of use of group O, Rh-negative red cells in a large metropolitan area and an action plan to control utilization

BACKGROUND: In southeastern Michigan, the group O, Rh-negative (O-) red cell supply was below emergency levels during one-sixth of 1994, despite 43-percent overcollection of O- red cell units relative to the size of the O- patient population. O- red cell units are overutilized because of their universal ABO and Rh compatibility. This study evaluated how hospitals in a large metropolitan area utilized O- red cell units, so that strategies could be devised to reduce O- usage. STUDY DESIGN AND METHODS: Through an O- red cell utilization survey, 56 hospitals were encouraged to collect three months' worth of transfusion data, either prospectively or retrospectively. O- usage was compared to total red cell usage and categorized into transfusions to O- patients, those to non-O- patients, and the number of O- units that outdated. RESULTS: Of 40,616 units transfused in 38 hospitals, 3,535 (8.7%) were O-; 71 percent of the O- units were transfused to O- patients, 28 percent were transfused to non-O- patients, and 1 percent outdated. Hospital transfusions to O- patients appeared to correlate with the racial makeup of the patient population, while hospital transfusions to non-O- patients appeared to correlate with hospital size and the hospital's transfusion practices. CONCLUSION: O- red cell usage in a hospital is dependent on the racial and ethnic mix of the hospital's patient population, the amount of transfusion activity, and the hospital's transfusion practices. An understanding of the dynamics of O- usage allowed the development of strategies to decrease O- utilization.     

New N-terminal modified proctolin analogues

Five proctolin analogues modified in position 1 of the peptide chain by Cit (I), Lys (II), His (III), Phe(p-NH₂) (IV) and γ-Abu (V) were synthesized by conventional liquid phase method. Biological activity of the obtained peptides was investigated by the cardioexcitatory test on two insect species, cockroach, Periplaneta americana L. and yellow mealworm, Tenebrio molitor L.     

Dendritic cell biology and the application of dendritic cells to immunotherapy of multiple myeloma

Dendritic cells (DCs) are extremely efficient antigen-presenting cells that are potent stimulators of both B and T cell immune responses. Although DCs are normally present in extremely small numbers in the circulation, recent advances in DC biology have made it possible to generate DCs in culture. DCs can be generatedin vitro from various cellular sources including bone marrow, cord blood and peripheral blood. Although culture conditions are extremely diverse, the majority of protocols grow DCs in GM-CSF and either TNF-alpha and/or IL-4. The addition of other growth factors such as SCF and Flt-3 ligand can dramatically enhance DC recovery. It is important to appreciate that DC subsets have been identified. Thus, DC at different stages of maturation, based on phenotype and capacity to capture antigen, can be obtained depending on culture conditions. For clinical applications, DCs can be generated in serum-free media and cryopreserved for future clinical applications. The ability to obtain DCs in numbers suitable for manipulating immune responses has pushed DC-based immunotherapies into the spotlight for treatment of various malignancies, including multiple myeloma, a B cell malignancy that is presently incurable. Although high-dose chemotherapy and transplantation have improved complete remission rates and overall survival in myeloma, immunotherapeutic strategies are needed for the additional cytoreduction needed to achieve a cure. Because DCs specialize in antigen capture and are extremely potent at stimulating T cell responses, they are ideally suited for generating anti-myeloma T cell responsesin vivo. Several studies have demonstrated that myeloma protein, also called idiotype (Id), is sufficiently immunogenic and can be used to generatein vivo T cell responses in myeloma patients. Clinical trials using Id-pulsed DCs as a vaccine to treat minimal residual disease or relapsed myeloma are currently underway. Feasibility studies indicate that antigen-pulsed autologous DCs can be used to elicitin vivo Id-specific T cell responses. Additional studies are needed to optimize current DC vaccination protocols and determine clinical benefits associated with this approach. It is hoped that, following conventional therapies, a combination of adoptive immunotherapeutic modalities such as DCs together with myeloma-specific T cells may lead to improved clinical responses in multiple myeloma, and ultimately lead to complete remission and cure.     

Limitations of flow cytometry in the analysis of CDIalHLADR+ human oral mucosal Langerhans cells

Suspensions of human oral epithetial cells were stained with antibodies to CD la and HLADR conjugated with fluorochromes and analysed by flow cytometry with the aim of purifying double-labetled Langerhans cells, a population comprising approximatety 2% of the cell total. Whole suspensions had high levets of autofluorescence and a wide range of forward and right angle scatter properties. The mean percentage of CDIalHLADR+ cells was 2.I%, though the double-labetled cells did not form a discrete group and the percentages of positive cells using control antibodies were similar. Density gradient centrifugation prior to flow cytometry did not facilitate Langerhanr cell identification within the suspension. The results indicate flow cytometric analysis of minority cell populations (such as Langerhans cells) within oral epithetium is limited by the autofluorescence of physically heterogeneous keratinocytes, and emphasise the importance of controls in studies of oral epithetium which use this method.     

A novel isotonic-balanced electrolyte solution with 1% glucose for intraoperative fluid therapy in children: results of a prospective multicentre observational post-authorization safety study (PASS)

Background: The recommendations for intraoperative fluid therapy in children have been adapted from hypotonic to isotonic electrolyte solutions with lower glucose concentrations (1–2.5% instead of 5%) to avoid hyponatremia and hyperglycemia. Objective: The objective of this prospective multicentre observational post‐authorization safety study was to evaluate the intraoperative use of a novel isotonic‐balanced electrolyte solution with 1% glucose (BS‐G1) with a particular focus on changes in acid–base status, electrolyte and glucose concentrations. Methods: Following local ethics committee approval, pediatric patients aged up to 4 years with an ASA risk score of I–III undergoing intraoperative administration of BS‐G1 were enrolled. Patient demographics, the performed procedure, adverse drug reactions, hemodynamic data, and the results of blood gas analysis before and after infusion were documented with a focus on changes in acid–base status, electrolyte and glucose concentrations. Results: In 107 patients (ASA I–III; age 16.2 ± 15.4, range day of birth to 47.7 months; body weight 8.8 ± 4.8, range 1.6–18.8 kg), the mean volume infused was 20 ± 12.6 (range 3.6–83.3) ml·kg^?1 BS‐G1. During the infusion, hemoglobin, hematocrit, anion gap, strong ion difference, and calcium decreased and chloride and glucose increased significantly within the physiologic range. All other measured parameters including sodium, bicarbonate, base excess, and lactate remained stable. Neither hypoglycemia (glucose <2.5 mmol·l^?1) nor hyperglycemia (glucose >10 mmol·l^?1) was documented after BS‐G1 infusion. No adverse drug reactions were reported. Conclusion: The studied isotonic‐balanced electrolyte solution with 1% glucose helps to avoid perioperative acid–base imbalance, hyponatremia, hyperglycemia, and ketoacidosis in infants and toddlers and may therefore enhance patient safety.     

Efficacy and safety of tonabersat, a gap-junction modulator, in the acute treatment of migraine: a double-blind, parallel-group, randomized study

The ability of tonabersat to relieve the symptoms of migraine attacks with or without aura was evaluated in a randomized, double-blind, placebo-controlled, multicentre, parallel-group study. Patients received 20 or 40 mg of tonabersat, or 50 mg of sumatriptan (positive control), or placebo at the onset of a moderate or severe attack. Headache intensity, relief and recurrence were recorded for 24 h after dosing. On the basis of primary or secondary efficacy measures, tonabersat did not provide a clinically or statistically significant advantage over placebo. Tonabersat generally was well tolerated and had no effect on vital signs, electrocardiogram recordings or laboratory values. The lack of efficacy may be a function of the slow absorption of tonabersat. As a consequence of slow absorption, daily administration of tonabersat as prophylaxis for migraine attacks is under investigation in ongoing studies.