Retroviral-mediated gene correction for X-linked severe combined immunodeficiency

X-linked severe combined immunodeficiency (XSCID) is a lethal disease caused by a defect in the gene encoding the common gamma chain (gamma- c) of the receptor for interleukin-2 (IL-2), IL-4, IL-7, IL-9, and IL- 15. Allogeneic bone marrow transplantation, the current therapy of choice for this defect, is often complicated by graft-versus-host disease and/or incomplete reconstitution of B-lymphocyte functions. Correction of the gene defect at the level of the autologous lymphohematopoietic progenitors could therefore represent an improvement in the medical management of these patients. To study the feasibility of a gene therapy approach for XSCID, a retroviral vector expressing gamma-c was used to transduce Epstein-Barr virus-transformed B-cell lines derived from patients with XSCID. After transduction, XSCID cells newly expressed gamma-c on the cell surface at levels comparable to those observed on B-cell lines obtained from normal donors. Moreover, the reconstituted gamma-c restored function to the IL- 2 and IL-4 receptors as shown by signal transduction mediated by phosphorylation of the JAK1 and JAK3 members of the Janus family of tyrosine kinases and by restoration of cellular proliferation in response to IL-2.     

A comparison of a Patient Enablement Instrument (PEI) against two established satisfaction scales as an outcome measure of primary care consultations

OBJECTIVES: We aimed to compare a new primary care outcome measure-the Patient Enablement Instrument (PEI)-against two established satisfaction measures [the Medical Interview Satisfaction Scale (MISS) and the Consultation Satisfaction Questionnaire (CSQ)]. Specifically, we sought (i) to test whether enablement and satisfaction are related or separate concepts; and (ii) to assess whether the internal consistency of the PEI might be enhanced by the inclusion of items from the satisfaction instruments. METHODS: Questionnaire forms containing the three instruments in a variety of combinations were distributed to a total of 818 patients attending for routine surgery consultations in three urban general practices of varying socio-economic mix. The main outcome measures were: scores on the PEI; scores on the CSQ, the MISS and their individual components; rank correlations between scores on the PEI and scores on the CSQ, the MISS and their component subscales; and Cronbach's alpha coefficient for the PEI. RESULTS: Overall mean scores, expressed as percentages of maximum scores attainable, were 44.1% for the PEI, 76.9% for the CSQ and 77.6% for the MISS. Rank correlations between PEI scores and scores for the complete CSQ and MISS instruments were 0.48 (P < 0.01) and 0.47 (P < 0.01), respectively. Correlations of PEI scores with individual component scores on the CSQ were generally lower and ranged from 0.14 to 0.53; correlations of PEI scored with MISS component scores were also generally lower and ranged from 0.21 to 0.53. Internal consistency of the PEI items (assessed by Cronbach's alpha coefficient) was lowered when items from the CSQ or MISS were added. CONCLUSIONS: The study shows that 'enablement' is a primary care outcome measure which is related to but is different from general satisfaction.