Auto Group Research Articles

Cytokine profiles in stem cell transplantation: Possible use as a predictor of graft-versus-host disease

Graft-versus-host disease (GvHD) complicates many allogeneic stem cell transplants (alloSCT), and several factors are known to be associated with the development of GvHD besides human leucocyte antigen (HLA) incompatibility. We investigated whether changes in serum levels of soluble IL-2 receptor (sIL-2Ra), tumour necrosis factor-alpha (TNF-a), transforming growth factor-beta (TGF-ß), vascular endothelial growth factor (VEGF) and soluble Fas (sFas) correlated with the development of GvHD in patients undergoing SCT, and might thus be potentially of use to anticipate the development of GvHD, allowing early modification of immunosuppressive therapy. sIL2Ra and sFas levels were significantly raised in allograft, autograft (allo and auto) and non-graft groups compared to the normal controls (HC), but there was no statistical difference between the three patient groups. TNF-a was raised in the auto and allo groups and the non-graft patients compared to the HC group (median 4.37?pg/ml), but only reached significance in the allo group (median 6.02?pg/ml; p=0.008) when this was compared with the non-graft patients. There was no significant difference in TGF-ß levels between any of the groups. The median serum VEGF levels were decreased in allo and auto patients compared to HC, (31 and 62?pg/ml versus 90?pg/ml, respectively), with a significant difference in the auto group (p=0.007). VEGF levels were significantly lower in the auto versus the allo group (p=0.008) and also in the auto versus the non-graft group (median 104?pg/ml; p=0.011). When the allo group was divided into patients who developed GvHD and those who did not, serum VEGF levels were significantly higher in those with GvHD (p=0.028).

Immunologic Effects of Allogeneic versus Autologous Blood Transfusion in Patients Undergoing Radical Oesophagectomy

Blood transfusion is often required in patients undergoing radical oesophagectomy, and is associated with immunosuppression that may worsen postoperative and long-term outcomes. However, the immunologic effects of allogeneic versus autologous transfusion have not been studied in this group of patients. We analyzed 103 patients who underwent radical oesophagectomy for oesophageal cancer, including 45 patients who received allogeneic transfusions (Allo), 16 patients who donated autologous blood but were not transfused (Auto-1) and 42 patients who received autologous transfusions (Auto-2). Peripheral blood lymphocyte subsets and natural killer (NK) cell activity were analyzed for 2 weeks postoperatively. Furthermore, the rate of infectious complications such as pneumonia and wound infection was compared. Patients receiving blood transfusion had decreased CD4+ lymphocyte counts and NK cell activity postoperatively, compared to Auto-1 patients. However, these abnormalities were corrected by day 14 in the Auto-2 group, but not in the Allo group. CD8+ lymphocyte counts were decreased in all groups postoperatively, returning to normal by 14 days in the Auto-1 group only. The rate of infectious complications was significantly higher in the Allo than in the Auto group. Blood transfusion is associated with adverse immunologic effects in patients undergoing radical oesophagectomy. However, autologous blood transfusion is favourable compared to allogeneic transfusion. Autologous transfusion programs should be employed when possible in this group of patients.

Effect of a platelet-activating factor (PAF) receptor antagonist on hyperacute xenograft rejection; evaluation in a pig kidney-human blood xenoperfusion model.

In pig to human discordant xenotransplantation, PAF may contribute to the pathogenesis of hyperacute xenograft rejection (HXR). We examined the release of PAF and the effect of a PAF receptor antagonist (BN 52021) on HXR in a pig kidney-human blood xenoperfusion model. Pig kidneys were perfused with porcine blood (AUTO group, n = 5), human blood (HETER group, n = 6) or human blood plus BN 52021 (BN group, n = 4), respectively. In contrast to HETER kidneys that never produced urine and were rejected in 15-30 min, the administration of BN 52021 induced a partial recovery of glomerular filtration rate and allowed kidneys to function until the end of the study. The release of PAF and soluble P-selectin, as well as endothelial P-selectin expression and tissue myeloperoxidase (MPO), were much higher in the HETER than in the AUTO group. HETER and BN kidneys displayed similar natural xenoantibody titres, CH50, PAF, soluble P-selectin as well as renal immunoglobulin (IgM, IgG, IgA) and complement (C3, C1q) deposition. However, HETER kidneys displayed a full histologic picture of HXR (mainly interstitial haemorrhage and vascular microthrombi) and BN kidneys had only endothelial cell swelling. Also, BN 52021 administration attenuated glomerular and vascular P-selectin expression and renal tissue MPO activity. We conclude that in the pig kidney-human blood xenoperfusion model, PAF is produced in higher amounts than in the pig kidney-pig blood autologous combination. The administration of BN 52021 exerts a protective effect by means of attenuating the acute inflammatory response and blocking vascular microthrombi formation.

Effect of Human Natural Xenoantibody Depletion and Complement Inactivation on Early Pig Kidney Function

Preformed xenoreactive natural antibodies (XNA) and complement mediate hyperacute xenograft rejection (HXR) in pig-to-human discordant xenotransplantation. In a pig kidney-human blood xenoperfusion model, we investigated whether XNA depletion and/or human complement inactivation preserved early pig kidney function. Pig kidneys were perfused for 180 min with pig blood (AUTO group, n = 8), human blood (HETER group, n = 6), complement-inactivated human blood (COMi group, n = 5), XNA-depleted human blood (ABd group, n = 5) or complement-inactivated and XNA-depleted human blood (ABd&COMi group, n = 5). HETER kidneys were rejected after 15–30 min and showed vascular microthrombi and interstitial hemorrhages. XNA depletion and/or complement inactivation prevented HXR. The glomerular filtration rate in ABd, COMi and ABd&COMi groups was significantly lower than in the AUTO group. Also, beyond 60 min, the COMi group showed a significantly lower glomerular filtration rate than that observed in ABd and ABd&COMi groups. Kidneys from ABd, COMi and ABd&COMi groups displayed endothelial cell edema, as well as higher soluble P-selectin levels and a higher renal myeloperoxidase content than the AUTO group kidneys. COMi and ABd&COMi groups had a significantly lower renal myeloperoxidase level than the HETER group. Also, in contrast to HETER and ABd groups, these complement-inactivated groups failed to show a positive correlation between P-selectin and renal myeloperoxidase. We also investigated platelet-activating factor (PAF) as possible mediator for these functional and pathologic changes. We found that blood PAF levels were similar in HETER, ABd, COMi and ABd&COMi groups and significantly higher than in the AUTO group. Also, when PAF was added to porcine endothelial cell monolayers, morphological changes due to cytoskeleton contraction were observed, and these changes were prevented by preincubation with a PAF receptor antagonist. In conclusion, although depletion of XNA and/or complement inactivation prevent HXR, the pig kidney function is not preserved at the level of the autologous combination. The PAF overproduction observed in the xenogenic combination, which is independent of the presence of XNA and complement, may be, at least in part, responsible for early endothelial cell morphological changes still present when HXR is prevented.

160a Interstitial pneumonitis incidence during a fractionated total body irradiation: Results of an original digitized image processing

Interstitial pneumonitis (IP) is a major toxicity problem after Total Body Irradiation (TBI). The aim of this retrospective study was to evaluate the irradiated lung volumes (ILV) despite shielded blocks to try to correlate the effective ILV with IP incidence. From 1984 to 1994, 146 patients with acute leukemia (AML or ALL) or chronic myeloid leukemia, received TBI prior to Bone Marrow Transplantation (120 Allo, 26 Auto). The IP incidence was 27% in Allo group and 6% in the Auto group. Two groups were comprised: “IP” group (n = 35) versus “non-IP” group (n = 111). The median follow-up was 32 months. It was given a fractionated TBI (12 Gy/3 fractions/3 days) with customized shielded lung blocks in order to reduce the pulmonary dose to 8 Gy. To calculate the ILV, we used an original digitized image processing with 3D mathematical model applied from the portal films. For every patient, each daily portal film was digitized with 3CCD-camera and improved with image processing. ILV and protected lung volumes were determined from the digitized portal films. The 3D calculations was automatically computed from their measurements to calculate the ILV. The median ILV in both groups was 466 cm3. In the “IP” group, the ILV was 484 cm3 versus 407 cm3 in the “non-IP” group (P = NS). The median dose-rate was similar between the two groups (0.045 Gy/mn). Although the difference was not significant, ours findings suggest a higher incidence of IP when the ILV increased. This hypothesis needs to be confinued by a prospective study.

Automatic External Defibrillators Used by Emergency Medical Technicians

In a randomized controlled clinical trial, the effectiveness of emergency medical technician (EMT) use of automatic external defibrillators (AEDs) was compared with EMT use of standard defibrillators for patients in cardiac arrest. A total of 321 cardiac arrest patients were treated during the study: 116 were treated by EMTs using the AED (AUTO group), 158 were treated by EMTs using the standard defibrillators (standard group), and 47 were treated by EMTs using the standard defibrillator when they were assigned to use the AED. There was no significant differences in hospital admission or discharge rates between the AUTO group (54% admitted, 28% discharged) and the standard group (52% admitted, 23% discharged) for patients in ventricular fibrillation (VF), for patients in non-VF rhythms, or for all patients combined. The only significant difference observed was in the time from power ON to first shock: 1.1 minutes average AUTO group and 2.0 minutes average standard group. The treatment groups did not differ significantly in sensitivity for VF (78% AED, 76% standard), specificity for non-VF rhythms (100% AED, 95% standard), or rates of defibrillation to a non-VF rhythm (62% AED, 57% standard). We conclude that in clinical outcomes and device performance, AEDs are comparable with standard defibrillators and should be considered an acceptable alternative. Automatic external defibrillators appear to have advantages over standard defibrillators in training, skill retention, and faster operation. Such devices can make early defibrillation available for a much larger portion of the population. They are a major innovation for the prehospital care of cardiac arrest patients.

Kinetics of interaction of m-chlorophenyl isocyanate with n-decanol in oligobutadiene

The authors have studied the kinetics of the interaction of m-chlorophenyl isocyanate with n-decanol modelling the terminal fragment of the macromolecule of hydroxyoligobutadiene in oligobutadiene. Information has been obtained on the reactivity of the auto associated and π-bound OH groups which is compared with the data on the reactivity of the OH groups of the hydroxyoligobutadienes of different M.