Establishment and operation of a Good Manufacturing Practice-compliant allogeneic Epstein-Barr virus (EBV)-specific cytotoxic cell bank for the treatment of EBV-associated lymphoproliferative disease.

Epstein-Barr virus (EBV) is associated with several malignancies, including post-transplant lymphoproliferative disorder (PTLD). Conventional treatments for PTLD are often successful, but risk organ rejection and cause significant side effects. EBV-specific cytotoxic T lymphocytes (CTLs) generated in vitro from peripheral blood lymphocytes provide an alternative treatment modality with few side effects, but autologous CTLs are difficult to use in clinical practice. Here we report the establishment and operation of a bank of EBV-specific CTLs derived from 25 blood donors with human leucocyte antigen (HLA) types found at high frequency in European populations. Since licensure, there have been enquiries about 37 patients, who shared a median of three class I and two class II HLA types with these donors. Cells have been infused into ten patients with lymphoproliferative disease, eight of whom achieved complete remission. Neither patient with refractory disease was matched for HLA class II. Both cases of EBV-associated non-haematopoietic sarcoma receiving cells failed to achieve complete remission. Thirteen patients died before any cells could be issued, emphasizing that the bank should be contacted before patients become pre-terminal. Thus, this third party donor-derived EBV-specific CTL cell bank can supply most patients with appropriately matched cells and most recipients have good outcomes.

Cold ischemia time, surgeon, time of day, and surgical complications.

BACKGROUND: Surgical factors are an important cause of early renal allograft loss and contribute to patient morbidity and mortality. The United Kingdom National Confidential Enquiry into Peri-operative Deaths has reported that operating out of normal working hours was associated with higher patient mortality because of inexperienced surgeons. In this study, we looked into whether operating outside normal working hours or the grade of the surgeon affected the incidence of surgical complications. We also examined the relationship between cold ischemic time (CIT) and likelihood of surgical complications. PATIENTS AND METHODS: We performed a retrospective review of 322 adult recipients who received their first cadaver kidney transplant in our center between January 1, 1998 and June 30, 2001. Information on surgical complications were collected from patients' records. CIT, time of surgery, and grade of the operating surgeons was obtained from a local audit database (www.nwkta.org.) and the database held by UK Transplant. RESULTS: Surgical complication(s) were less likely to occur if one of the surgeons was a consultant (P =0.002). We found no association between cold storage and incidence of surgical complication(s). The median CIT was 21.30 (range 3.3-43.5) hours, n=229, in the group without complications compared with 21.80 (8.8-47.9) hours, n=77, for those with complications. The incidence of surgical complications was the same regardless of whether the operation took place during the day, evening, or night. CONCLUSIONS: Prolonged CIT and operating out of normal working hours did not increase the incidence of surgical complications. Presence of a consultant did, however, reduce the likelihood of a surgical complication occurring.

Just enough measurement: a proposed paradigm for designing medical instrumentation.

Our research group hypothesizes that one way to provide low-cost healthcare delivery efficiently is through the use of a large number of inexpensive sensors that can provide meaningful medical data. Typical development of medical instrumentation pursues increased resolution and higher accuracy - accompanied by a corresponding increase in cost; it is no secret that high costs impose a heavy burden on healthcare. We seek to invert the adage that quality is more important than quantity by extracting high quality biomedical information from a large quantity of low-cost measurements, and to demonstrate this using measurement instrumentation developed in our lab for extra-clinical assessment and rehabilitation tools. This will be discussed in terms of our initial experiments in evaluating balance and postural stability. This is an area of critical clinical importance: 2.6 million non-fatal fall injuries in persons over age 65 resulted in direct health care costs of $19 billion (in 2000) in the U.S., and the number of persons over age 65 in the U.S. is projected to more than double between 2000 and 2030.