Reduced graft-versus-host disease-inducing capacity of T cells after activation, culturing, and magnetic cell sorting selection in an allogeneic bone marrow transplantation model in rats.

Graft-versus-host disease (GvHD), a major complication of allogeneic bone marrow transplantation, has been ascribed to mature T cells in the graft. Because T cells play an important role in engraftment of the bone marrow and decrease the probability of relapse of leukemia, a treatment strategy was developed to preserve the benefits of T cells in the graft and to control the severe complications of GvHD. This can be accomplished by the genetic modification of donor T cells with a suicide gene that allows their selective in vivo elimination and subsequently the abrogation of GvHD. For clinical benefit the alloreactivity of herpes simplex virus thymidine kinase (HSV-TK) gene-transduced T cells should be retained. Therefore, we investigated the influence of gene transduction and the selection procedure on T cells. We demonstrated that activation and culturing of T cells reduce their capacity to induce lethal GvHD in an allogeneic rat bone marrow transplantation model. Furthermore, positive immunomagnetic selection of gene-transduced T cells resulted in loss of the GvHD-inducing capacity of HSV-TK(+) T cells directly after MACS (magnetic cell sorting) selection; this loss could be recovered by a 1-day expansion of the selected T cells. No effect on alloreactivity was observed to be caused by the gene transduction procedure. Our study resulted in the development of an optimized culture and gene transduction protocol with preservation of T cell alloreactivity. Treatment of transplanted rats with ganciclovir resulted in a rapid reduction in the number of HSV-TK(+) T cells in the peripheral blood and in increased survival of the animals.     

Climate change, human health, and sustainable development.

Human-induced climate change threatens ecosystems and human health on a global scale. In order to withstand the worldwide threats to ecosystems, the concept of sustainable development was introduced during the 1980s. Since then, this concept has been widely applied to guide and focus policy-making. The present article reviews the health consequences of human-induced climate change on sustainable development, particularly the potential impact of such change of food supply, natural disasters, infectious diseases, ecosystems, and sea level rise. Discussed is an integrated model containing the key indicators of sustainable development. The relevance of climate change, human health, and sustainable development for international climate change policy is also examined.     

The Recognition of Hypothalamo-Neurohypophysial Functions by Developing T Cells

Neuropeptide signals and specific neuropeptide receptors have been described in the thymus supporting the concept of a close dialogue between the neuroendocrine and the immune systems at the level of early T-cell differentiation. In this paper, we review recent data about neurohypophysial (NHP)-related peptides detected in the thymus from different species. We suggest that we are dealing in fact with other member(s) of the NHP hormone family, which seems to exert its activity locally through a novel model of cell-to-cell signaling, that of cryptocrine communication. This model involves exchange of signals between thymic epithelial cells and developing thymocytes. The NHP-related peptides have been shown to trigger thymocyte proliferation and could induce immune tolerance of this highly conserved neuroendocrine family.     

Repair of large midline incisional hernias with polypropylene mesh: Comparison of three operative techniques

Polypropylene mesh is widely used for the reconstruction of incisional hernias that cannot be closed primarily. Several techniques have been advocated to implant the mesh. The objective of this study was to evaluate, retrospectively, early and late results of three different techniques, onlay, inlay, and underlay. The records of 53 consecutive patients with a large midline incisional hernia — 25 women and 28 men, mean age 60.4 (range 28–94) — were reviewed. Polypropylene mesh was implanted using the onlay technique in 13 patients, inlay in 23 patients, and underlay in 17 patients. Either the greater omentum or a polyglactin mesh was interponated between the mesh and the viscera. The records of these 53 patients were reviewed with respect to: size and cause of the hernia, pre- and postoperative mortality and morbidity, with special attention to wound complications. Patients were invited to attend the outpatient clinic at least 12 months after implantation of the mesh for physical examination of the abdominal wall. Postoperative complications occurred in 14 (26.4%) patients. The onlay technique had significantly more complications, as compared to both other techniques. Reherniation occurred in 15 (28.3%) patients. The reherniation rate of the inlay technique was significantly higher than after the underlay technique (44% vs 12%, P=0.03) and tended to be higher than the onlay technique (44% vs 23%, P=0.22). Repair of large midline incisional hernias with the use of a polypropylene mesh carries a high risk of complications and has a high reherniation rate. The underlay technique seems to be the better technique.     

Efficacy and tolerability of a topical NSAID patch (local action transcutaneous flurbiprofen) and oral diclofenac in the treatment of soft-tissue rheumatism

Summary The efficacy and safety of local action transcutaneous flurbiprofen 40 mg [flurbiprofen LAT] patches and diclofenac sodium tablets, 50 mg b.d., were compared in an open, multicentre, randomized, parallel-group study in patients with soft-tissue rheumatism. Patches were replaced at 12-hourly intervals. Clinical assessments were performed after 7 and 14 days of treatment. Fifty-six patients were treated with flurbiprofen LAT and 53 with diclofenac. Six withdrawals (three from each group) occurred during the treatment period.A statistically significant difference was observed in favour of flurbiprofen LAT for the principal measure, namely the investigator's opinion of overall change in clinical condition: 49/53 (92%) patients treated with flurbiprofen LAT had improved by day 14 compared with 36/49 (73%) patients receiving diclofenac sodium (p=0.03; eligible dataset). There were also statistically significant differences in favour of flurbiprofen LAT for the investigator's assessments of the overall severity of the clinical condition (p=0.03; eligible dataset), for the severity of pain at the region treated (p=0.04; intent-to-treat), and for the severity of tenderness (p<0.001; intent-to-treat). Supplementary analgesia (paracetamol) was required by two patients in the flurbiprofen LAT group and by eight diclofenac-treated patients. The difference in favour of flurbiprofen LAT group and by eight diclofenac-treated patients. The difference in favour of flurbiprofen LAT in the average daily consumption of paracetamol was significant (p=0.04). The patients' assessment of severity of pain on movement also favoured flurbiprofen LAT (p =0.049; eligible dataset), but there were no statistically significant differences in day or night pain or quality of sleep. For the patients' opinion of treatment there was, however, a statistically significant difference in favour of flurbiprofen LAT (p=0.02). Of the patients receiving flurbiprofen LAT, 94% regarded it as a convenient form of treatment.With respect to tolerability 8/56 (14%) patients applying flurbiprofen patches reported a total of nine adverse effects (AEs) (mainly local, mild skin irritations), vs 9/52 (17%) patients receiving diclofenac, who reported 12 AEs. Most AEs in the enteric-coated diclofenac group were of a gastrointestinal nature (one of which was severe). In terms of the proportion of patients reporting AEs related to the digestive system, there was a statistically significant difference in favour of flurbiprofen LAT (p=0.011).In conclusion, local treatment of soft-tissue rheumatism with flurbiprofen LAT was demonstrably superior to benchmark oral therapy with diclofenac sodium over a 2-week period in terms of both efficacy and gastrointestinal tolerability. Flurbiprofen LAT provided both an effective and convenient form of topical SAID treatment.