Donor-derived transmission events in 2013: a report of the Organ Procurement Transplant Network Ad Hoc Disease Transmission Advisory Committee.

BACKGROUND: The Organ Procurement Transplant Network Disease Transmission Advisory Committee (DTAC), a multidisciplinary committee, evaluates potential donor-derived transmission events (PDDTE), including infections and malignancies, to assess for donor transmitted events. METHODS: Reports of unexpected PDDTE to Organ Procurement Transplant Network in 2013 were fully reviewed by DTAC. A standardized algorithm was used to assess each PDDTE from a given donor and to classify each individual recipient from that donor. RESULTS: Of 443 total PDDTE submitted, 159 were triaged and not sent out to the full DTAC. Of 284 fully evaluated reports, 32 (11.3%) resulted in a proven/probable (P/P) transmission of infection, malignancy or other conditions to 42 recipients. Of 204 infection events, 24 were classified as P/P affecting 30 recipients, with four deaths. Bacteria were the most frequently reported type of infection, accounting for 99 reports but only 12 recipients from 11 donors experienced P/P transmission. There were 65 donors reported with potential malignancy events and 5 were classified as P/P transmissions with 8 affected recipients and 2 deaths. Additionally, there were 16 noninfection, nonmalignancy reports resulting in 3 P/P transmissions to 4 recipients and 1 death. CONCLUSIONS: There was a 43% increase in the number of PDDTE reported and reviewed in 2013 over 2012. However, the percent with P/P transmission remains low, affecting recipients from 32 donors especially when compared with the more than 14,000 donors recovered annually in the United States. The continued use of the new standard algorithm and triaging process will enhance the reproducibility of DTAC assessments and allow more robust analysis of our aggregate DTAC experience.

HLA class II linkage disequilibrium and haplotype evolution in the Cayapa Indians of Ecuador.

DNA-based typing of the HLA class II loci in a sample of the Cayapa Indians of Ecuador reveals several lines of evidence that selection has operated to maintain and to diversify the existing level of polymorphism in the class II region. As has been noticed for other Native American groups, the overall level of polymorphism at the DRB1, DQA1, DQB1, and DPB1 loci is reduced relative to that found in other human populations. Nonetheless, the relative evenness in the distribution of allele frequencies at each of the four loci points to the role of balancing selection in the maintenance of the polymorphism. The DQA1 and DQB1 loci, in particular, have near-maximum departures from the neutrality model, which suggests that balancing selection has been especially strong in these cases. Several novel DQA1-DQB1 haplotypes and the discovery of a new DRB1 allele demonstrate an evolutionary tendency favoring the diversification of class II alleles and haplotypes. The recombination interval between the centromeric DPB1 locus and the other class II loci will, in the absence of other forces such as selection, reduce disequilibrium across this region. However, nearly all common alleles were found to be part of DR-DP haplotypes in strong disequilibrium, consistent with the recent action of selection acting on these haplotypes in the Cayapa.

Issues surrounding MDI formulation development with non-CFC propellants.

Reformulation of metered-dose inhalers (MDIs) without the use of chlorofluorocarbon (CFC) propellants presents numerous obstacles because there are no alternative propellants that can serve as immediate replacements for pharmaceutical use. Hydrofluorocarbons (HFCs), hydrochlorofluorocarbons (HCFCs) and hydrocarbons (HCs) are all under consideration as possible alternatives for CFC propellants. However, no single propellant or combination of propellants has been identified with all of the physical-chemical properties of CFCs. Based on their zero ozone depletion potentials, relatively low global warming potentials, non-flammabilities, densities, and vapor pressures, HFA-134a and HFA-227 are the most attractive replacement propellants identified to date. Yet, their use in MDIs will still require: (1) identification of a metering valve with propellant and formulation-compatible gaskets, (2) use of current suspending agents at levels much lower than in present MDIs or identification (and characterization) of new suspending agents, and (3) modification of existing manufacturing technologies. Demonstration of acceptable final product stability, safety and efficacy will be necessary prior to submission to worldwide registration authorities.

Additive effect of albuterol and ipratropium bromide in the treatment of bronchospasm in children.

Inhaled albuterol (A) (salbutamol) alone and albuterol plus ipratropium bromide (IB) were administered to 12 asthmatic children. Following administration of A alone or in combination with IB, there was a significant increase in FEV1 and FEF. Significant statistical difference in favor of the association A plus IB was observed at 120 and 240 minutes for FEV1 and in the period 120, 180, and 240 minutes for FEF. The additive effect was present both in the large and small airways. The short-lived additive effect of A plus IB suggests the opportunity to increase the frequency of drug administration in patients with severe bronchial obstruction.