Identification of peripheral CD154+ T cells and HLA-DRB1 as biomarkers of acute cellular rejection in adult liver transplant recipients.

Decreasing graft rejection and increasing graft and patient survival are great challenges facing liver transplantation (LT). Different T cell subsets participate in the acute cellular rejection (ACR) of the allograft. Cell-mediated immunity markers of the recipient could help to understand the mechanisms underlying acute rejection. This study aimed to analyse different surface antigens on T cells in a cohort of adult liver patients undergoing LT to determine the influence on ACR using multi-parametric flow cytometry functional assay. Thirty patients were monitored at baseline and during 1 year post-transplant. Two groups were established, with (ACR) and without (NACR) acute cellular rejection. Leukocyte, total lymphocyte, percentages of CD4+ CD154+ and CD8+ CD154+ T cells, human leukocyte antigen (HLA) mismatch between recipient-donor and their relation with ACR as well as the acute rejection frequencies were analysed. T cells were stimulated with concanavalin A (Con-A) and surface antigens were analysed by fluorescence activated cell sorter (FACS) analysis. A high percentage of CD4+ CD154+ T cells (P = 0·001) and a low percentage of CD8+ CD154+ T cells (P = 0·002) at baseline were statistically significant in ACR. A receiver operating characteristic analysis determined the cut-off values capable to stratify patients at high risk of ACR with high sensitivity and specificity for CD4+ CD154+ (P = 0·001) and CD8+ CD154+ T cells (P = 0·002). In logistic regression analysis, CD4+ CD154+ , CD8+ CD154+ and HLA mismatch were confirmed as independent risk factors to ACR. Post-transplant percentages of both T cell subsets were significantly higher in ACR, despite variations compared to pretransplant. These findings support the selection of candidates for LT based on the pretransplant percentages of CD4+ CD154+ and CD8+ CD154+ T cells in parallel with other transplant factors.

Patients' perceived health status following primary surgery for oral and oropharyngeal cancer.

How oral and oropharyngeal cancer patients view their 'quality of life' is of fundamental importance. Any differences seen in their health state compared with normative data and with other disease conditions allows a wider perspective on their outcome after surgery. A cross-sectional postal survey was undertaken of patients treated for oral/oropharyngeal squamous cell carcinoma by primary surgery using the University of Washington Quality of Life Questionnaire Version 4 (UW-QOL v4) and the EuroQol EQ-5D. Of 348 patients surveyed, 224 returned analysable forms, (response rate 64%). In the EQ-5D items, 40% of the group reported a problem in walking, 23% with self-care, 44% in performing usual activities, 50% with pain or discomfort and 33% with anxiety or depression. The mean overall health visual analogue scale (VAS) score was 74 (SE 1) minimum 30 and maximum 100. The mean utility (health index) score was 0.75 (SE 0.02) minimum -0.18 and maximum 1.0. Compared to national reference data, patients in our cohort of under 60 years of age fared significantly worse than expected for their age but this was not so for older patients. There were strong correlations between appropriate domains of the EQ-5D and UW-QOLv4 and between UW-QOL global measures and EQ-5D VAS.

Spinal cord compression in renal osteodystrophy.

A patient undergoing regular haemodialysis for chronic renal insufficiency developed neck pain followed by progressive spinal cord compression due to subluxation at the level C3-4. Decompression, laminectomy and osteosynthesis led to an almost complete recovery. A review of all the histological specimens suggested that hyperparathyroidism and not amyloidosis caused the vertebral destruction.

Capsaicin-induced ion fluxes increase cyclic GMP but not cyclic AMP levels in rat sensory neurones in culture.

Capsaicin, which induces fluxes of sodium, calcium, and potassium ions in a subset of both neonatal and adult rat dorsal root ganglion neurones, increased cyclic GMP (cGMP) levels by a factor of 20 (EC50 0.07 microM) to 10-20 pmol cGMP/mg protein in these cells. Cyclic AMP (cAMP) levels were unaffected. Nonneuronal cells derived from rat ganglia, and both neurones and nonneuronal cells from chick were unresponsive to capsaicin. Capsaicin-induced cGMP elevation in rat dorsal root ganglion (DRG) neurones was unaffected by pertussis toxin, lowered by compounds that block voltage-sensitive calcium channels, and was abolished by the removal of extracellular calcium. Calcium, guanidine, and rubidium fluxes were unaffected by treatment of DRG cells with sodium nitroprusside or dibutyryl cGMP. The cGMP response to capsaicin is thus a function of capsaicin-evoked calcium uptake through voltage-sensitive calcium channels. Elevated cGMP levels do not, however, contribute to capsaicin-evoked ion fluxes or to their desensitisation.

Activation of guanylate cyclase by bradykinin in rat sensory neurones is mediated by calcium influx: possible role of the increase in cyclic GMP.

Bradykinin, which activates polymodal nociceptors, increased cyclic GMP (cGMP) in a capsaicin-sensitive population of cultured sensory neurones from rat dorsal root ganglia (DRG) by stimulating guanylate cyclase, but had no effect on cyclic AMP (cAMP). In nonneuronal cells from DRG, bradykinin increased cAMP, but not cGMP. The bradykinin-induced increase in cGMP in the neurones was completely blocked by removal of extracellular Ca2+, or by incubation of the cells with the calcium channel blockers nifedipine and verapamil. Pretreatment of the neurones with either dibutyryl cGMP or sodium nitroprusside (which elevates cGMP) inhibited bradykinin-induced formation of inositol phosphates. It is possible that cGMP could be involved in the regulation of polyphosphoinositide turnover in DRG neurones.