The relevance of donor T cell-directed immunoglobulin G in historic sera in the age of flow cytometry

BACKGROUND: Renal transplant recipients with a positive historic cross-match due to donor T cell-directed IgG antibodies are considered to have decreased graft survival, even if their current serum is negative prior to transplantation. With the use of flow cytometric cross-match for testing current sera, false-negative results could be eliminated and the outcome of transplantation in this group of patients could be improved, assuming that immunological memory is effectively controlled with immunosuppression. METHODS: We reviewed our records to identify those patients who underwent cadaveric renal transplant, with a historic IgG positive cytotoxic T cell cross-match and a current negative flow cytometric T cell cross-match. RESULTS: Eighteen patients underwent cadaveric renal transplant in the face of a historic IgG positive T cell cross-match and a current negative flow cytometric T cell cross-match. In 14 patients treated with cyclosporine-based immunosuppression the 1-, 2-, and 3-year cumulative graft survival rates were 57, 50, and 43%, respectively. Ten of the 14 patients (71%) ultimately lost their grafts. CONCLUSIONS: Even with negative flow cytometric cross-match in current serum, a positive historic conventional cross-match suggests a high risk of graft failure.     

The trouble with kidneys derived from the non heart-beating donor: a single center 10-year experience

BACKGROUND: The demand for renal transplantation has increasingly outstripped the supply of donor organs especially over the past 10 years. Although related and unrelated live donation is being promoted as one option for increasing the donor pool, it is unlikely that this will in itself be able to bridge the gap. Non-heart beating donors (NHBD) can provide an alternative supply of organs, which should substantially increase the donor pool. METHODS: In Newcastle, NHBD kidneys have been used for transplantation for a period of 10 years. In the early period (1988-1993) excellent results were obtained (90.5% success); however, these donors were controlled NHBD, Maastricht category III. In the second phase (1994-1998) increasing numbers of donors were obtained from the Accident and Emergency Department unit. These were failed resuscitation for cardiac arrest (category II). The rates of success in this period were poor (45.5% success) and the program was halted. The third phase of the program used machine perfusion of the kidneys and glutathione S transferase enzyme analysis to assess viability. RESULTS: Using such approaches renal transplants from largely category II donors produced a success rate of 92.3% which was significantly better than the phase II period of the program (P=0.023, Fisher two-tail test). CONCLUSION: Machine perfusion and viability assessment of NHB kidneys in phase III of the program has increased our donor pool as well as improved the graft survival. This is particularly relevant for the use of the category II NHB donor where the incidence of primary nonfunction was high, illustrated by phase II where machine perfusion/viability assessment was not used.     

Renal allograft rejection: beta-chemokine involvement in the development of tubulitis

BACKGROUND: Tubulitis is a defining feature of renal allograft rejection. Graft dysfunction may result from damage inflicted on tubular epithelial cells by intratubular cytotoxic T lymphocytes. Graft cells are known to produce chemokines during acute rejection, but it is not known whether changes in expression of specific chemokines can influence the composition of the intratubular lymphocyte population. We examined expression of individual chemokines in biopsy sections showing different pathological rejection grades. METHODS: Sections from Banff-graded transplant biopsies were examined for the presence of beta-chemokines (MCP-1, MIP-1alpha, MIP-1beta, and RANTES) by immunofluorescence and semiquantitative confocal laser scanning microscopy. RESULTS: Beta-chemokines were expressed predominantly at the basolateral surface of tubular epithelial cells. Expression of MCP-1 and MIP-1beta was significantly higher in sections showing grade 2 rather than grade 1 acute rejection. RANTES and MIP-1alpha showed no significant variation in level of expression between rejection grades. CONCLUSIONS: Beta-chemokines are expressed by tubular epithelial cells during acute rejection. Consistent expression of RANTES and MIP-1alpha suggests a general role in recruiting T lymphocytes. However, MCP-1 and MIP-1beta may play a more subtle role in recruitment of specific T-cell subsets, such as Th1 cells, during acute cellular rejection.     

Human Herpesvirus Type 8 and Kaposi's Sarcoma

Kaposi's sarcoma-associated herpesvirus or human herpesvirus type8 (HHV-8) is present in all forms of Kaposi's sarcoma (KS) aswell as in primary effusion lymphomas and some cases of Castleman'sdisease. In KS tissues, HHV-8 is present in endothelial andspindle cells. Current serologic tests suggest that HHV-8 ispredominantly found in those at risk of KS and is not as widespreadas most other human herpesviruses. HHV-8 encodes various proteinsthat may play a role in promotion of cellular growth, includingcyclin- and G-coupled protein receptor homologues, and anti-apoptoticproteins, including Bcl-2, IL-6 (i.e., interleukin 6), and FLIP(i.e., FLICE inhibitory protein) homologues. In addition, HHV-8encodes two macrophage inflammatory-like proteins with anti-humanimmunodeficiency virus and angiogenic potential.     

14. FDG CDET (2D Dual-Head Coincidence Gamma Camera) in the Primary Staging of Oesophageal Cancer. Histopathological Correlation

Purpose: The aim of this study was to evaluate the role of FDG-CDET for the detection of primary oesophageal tumour, lymph node involvement and distant extension before surgery.Methods and patients: In patients fasting for 6h or more, 150-250 MBq of 18F-FDG were injected i.v. and 2D imaging (whole-body scan and at least a tomoscintigram) was started 45 min. later, using a PICKER gamma camera. We studied 14 patients (pts). All of them were operated on (mean time between FDG and surgery: 5.4 +/- 3.8 days) and staging results were correlated with post surgical histology.Results: The primary lesion took up FDG in all cases but one (FN in a 5 mm lesion). The primary NM staging of these 14 pts was negative with FDG-CDET in 7 cases (4 TN and 3 FN corresponding to an invasion of satellite lymph nodes in 2 cases and to a metastatic infracentimetric subdiaphragmatic lymph node in one case) and positive in 7 cases (7 TP corresponding to 10 foci), revealing in 4 cases a sub-diaphragmatic lymph node extension unknown prior to FDG-CDET. One pt referred for characterisation of an oesophageal lesion (failure of multiple biopsies) had an intense focus of FDG uptake in this area (TP confirmed by surgery). The overall sensitivity was 13/14 = 93% on a per patient basis and 21/25 = 84% on a per lesion basis. Specificity on a per lesion basis was 5/5 = 100%.Conclusion: These first results, obtained in an indication of FDG not frequently evaluated even with dedicated PET systems, seem very promising, the oesophageal neoplastic lesions appearing to take up FDG with a high intensity.     

Seasonality and trend in blood lead levels of New York State children

Background  

Environmental exposure to lead remains a significant health problem for children. The costs of lead exposure in children are estimated to be considerably more than other childhood diseases of environmental origin. While long-term trends in blood lead levels (BLLs) among children are declining, seasonal variation persists. Cross-sectional studies have found a peak in summer months. Part of this variation may be due to increased exposure to lead paint on window sills and through increased contact with soils containing lead during the summer. The current study represents the largest published population-based study on seasonality and trends in the BLLs of children to date. In addition, the results offer a comparison of recent data on seasonality of BLLs in New York State children, to studies conducted over the past three decades.