Comparison of crossmatch results obtained by ELISA, flow cytometry, and conventional methodologies.

The complement-dependent lymphocytotoxicity crossmatch (CXM) is the presently accepted standard for detection of donor-reactive alloantibodies in transplant patients. However, the newer flow cytometric (FXM) and ELISA (EXM) crossmatch technologies are increasingly used as substitutes for the CXM. We have compared the sensitivity and reproducibility of FXM vs. EXM and, in general, find them to be quite similar. However, when we compared the agreement of FXM vs. EXM in 112 donor/recipient combinations, we found that they identified different subsets of donor-specific alloantibodies in about 35% of the tests. When compared to the standard CXM method, the EXM correlated much better than did the FXM, yielding a much lower rate of false positive (2.5% vs. 8%) and false negative (7% vs. 18.5%) results. The reduction in time required to obtain a result (3 h) and the cost of materials ($25/test) was identical for the EXM and FXM. We conclude that the ELISA method for crossmatching has advantages over the flow cytometric method as a substitute for the present standard complement-dependent lymphocytotoxicity method.     

Communicating unexpected pharmacogenomic results to biobank contributors: A focus group study

ObjectivesThe goals of this study were to explore 1) the impact of returning unexpected pharmacogenomic (PGx) results to biobank contributors, and 2) participant views about improving communication.MethodsWe conducted a qualitative focus group study with biobank participants (N = 54) who were notified by mail of an individual research result indicating increased risk for adverse events associated with the common cancer drug 5-fluorouracil (5-FU). We employed a framework approach for analysis.ResultsOur results revealed three themes illustrating participants’ questions and uncertainty, especially regarding how to share results with health providers and family members, and remember them over time. Participants valued results for themselves and others, and for the future of medicine. Risk perception was framed by health identity. “Toxicity narratives,” or familiarity with another’s adverse reaction to chemotherapy, increased the sense of importance participants reported.ConclusionThese focus group results highlight research participant remaining questions and high valuation of PGx results, even when unexpected.Practice implicationsWe identify PGx research participants’ needs for clear clinical translation messaging that attends to health identity, pragmatics of sharing information with family members, and patient perceptions of barriers to transferring research results to a clinical context.     

The relationship between psychosocial factors and breast cancer: some unexpected results

A growing body of research suggests a link between psychosocial factors and breast cancer. Research in this area often contains methodological problems, however, such as small sample size, inadequate comparison groups, omission of important control variables, inclusion of only a few psychosocial variables, and failure to analyze moderating effects. To overcome these problems, the present study examined the link between breast cancer and multiple psychosocial variables (life events, coping, Type A behavior pattern, availability of social support) among 1,052 women with and without breast cancer. After controlling for history of breast cancer and age, we found very few significant relationships between psychosocial variables and breast cancer. Furthermore, the relationship between life events and breast cancer was not moderated by coping, Type A, or availability of social support. Methodological and substantive reasons for these findings are discussed.     

Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications

Familial hyperparathyroidism is not uncommon in clinical endocrine practice. It encompasses a spectrum of disorders including multiple endocrine neoplasia types 1 (MEN1) and 2A, hyperparathyroidism-jaw tumour syndrome (HPT-JT), familial hypocalciuric hypercalcaemia (FHH), and familial isolated hyperparathyroidism (FIHP). Distinguishing among the five syndromes is often difficult but has profound implications for the management of patient and family. The availability of specific genetic testing for four of the syndromes has improved diagnostic accuracy and simplified family monitoring in many cases but its current cost and limited accessibility require rationalisation of its use. No gene has yet been associated exclusively with FIHP. FIHP phenotypes have been associated with mutant MEN1 and calcium-sensing receptor (CASR) genotypes and, very recently, with mutation in the newly identified HRPT2 gene. The relative proportions of these are not yet clear. We report results of MEN1, CASR, and HRPT2 genotyping of 22 unrelated subjects with FIHP phenotypes. We found 5 (23%) with MEN1 mutations, four (18%) with CASR mutations, and none with an HRPT2 mutation. All those with mutations had multiglandular hyperparathyroidism. Of the subjects with CASR mutations, none were of the typical FHH phenotype. These findings strongly favour a recommendation for MEN1 and CASR genotyping of patients with multiglandular FIHP, irrespective of urinary calcium excretion. However, it appears that HRPT2 genotyping should be reserved for cases in which other features of the HPT-JT phenotype have occurred in the kindred. Also apparent is the need for further investigation to identify additional genes associated with FIHP.