Perioperative Minimal Induction Therapy: A Further Step toward More Effective Immunosuppression in Transplantation

Dual induction with low doses of rabbit anti-human thymoglobulin (RATG) and basiliximab effectively and safely prevented allograft rejection in high-risk renal transplant recipients. To assess whether treatment timing affects efficacy and tolerability, in this single-center, matched-cohort study, we compared posttransplant outcomes in 25 patients and 50 gender-, age-, and treatment-matched reference patients induced with the same course of 7 daily RATG infusions (0.5 mg/kg/day) started before or after engraftment, respectively. All subjects received basiliximab (20 mg) before and 4 days after transplantation, withdrew steroids within 6 days after surgery, and were maintained on steroid-free immunosuppression with cyclosporine and mycophenolate mofetil or azathioprine. Over 12 months after transplant, 1 patient (4%) and 13 reference patients (26%) had acute rejection episodes. One patient and 5 reference-patients required dialysis therapy because of delayed graft function. In all patients circulating CD4+ and CD8+ T lymphocytes were fully depleted before engraftment. Both treatments were well tolerated. In kidney transplantation, perioperative RATG infusion enhances the protective effect of low-dose RATG and basiliximab induction against graft rejection and delayed function, possibly because of more effective inhibition of early interactions between circulating T cells and graft antigens

TNF-alpha, IL-4R-alpha and IL-4 polymorphisms in mild to severe asthma from Italian Caucasians.

Asthma is a chronic airway inflammatory disease associated with airway hyperresponsiveness which affects subjects with genetic predisposition. An association has been reported between some polymorphisms in various cytokine genes and asthma. Most of them are single nucleotide polymorphisms (SNPs). These polymorphisms are detected in the protein coding sequence or in the promoter region thus influencing cytokine production. We investigated the involvement of SNP mapping in 5 cytokine genes in mild to severe asthmatics of Italian Caucasians. The frequency of alleles and genotypes, relatively to 10 allelic specificities of the cytokine genes, was defined in 57 asthmatics and in 124 control subjects by a Polymerase Chain Reaction-Sequence Specific Primer method. TNF-alpha -308A and TNF-alpha -238A allele frequencies were higher in asthmatics than in controls (p less than 0.001). Significant differences in the frequency of IL-4 -590T allele and of IL-4Ralpha +1902A allele were also detected in asthmatics in comparison with controls (pless than 0.001 and p=0.005, respectively). Similarly, IL-1alpha -889C allele was present in 84.1 percent of asthmatics and in 70.2 percent of controls (p=0.013). Furthermore, the IL-4Ralpha +1902A/A and IL-1alpha -889C/C homozygous conditions and the TNF-alpha -308G/A, TNF-alpha -238G/A, IL-4 -590T/C and IL-10 -1082G/A heterozygous conditions were significantly associated with asthma (p less than 0.05). ACA haplotype of IL-10 was observed only in asthmatic patients. This study reports, for the first time, the frequency of 10 different single nucleotide polymorphisms in 5 cytokine genes in the Italian Caucasians. Furthermore, we also indicate that in our population some single nucleotide polymorphisms are associated with mild to severe bronchial asthma

NONOSTANTE TUTTO ... I COLORI! SAGGIO SU HENRI BARBUSSE

Un saggio sulla straordinaria opposizione di colori nel buio della I Guerra Mondiale. Henri Barbusse, memore della spiritualità del colori, vede in essi la possibilità della fuga dall'atroce contingenza

Time course of cytokines, hemodynamic and metabolic parameters during hyperthermic intraperitoneal chemotherapy

Background: Systemic response to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) causes the activation of endocrine, metabolic, hemodynamic and inflammatory processes. The aim of this work is to describe and analyze the time course of the inflammatory markers concentration during CRS+HIPEC in plasma and peritoneal fluids and the association with hemodynamic and metabolic parameters. Methods: Pre-, intra- and postoperative data were collected. Tumor necrosis factor (TNF), interleukine 6 (IL-6), pro-calcitonin (PCT), cancer antigen 125 (CA-125) in blood and in peritoneal fluids were evaluated. Results: Thirty-eight patients were included, 29 (76.3%) of them were female. Mean/median PCI was 9.2/5, primary malignancy was 5 colorectal cancer (13.2%), 5 gastric cancer (13.2%), 23 ovarian cancer (60.5%) and 5 other malignancies (13.2%). Combined clinical risk 0-1 was reached in all patients. Cardiac index, heart rate and central venous pressure increased during the procedure, while stroke volume variation showed a decrease. Mean arterial pressure and superior vena cava oxygenation were stable throughout the whole procedure. TNF and CA-125 were steady during the whole procedure; IL-6 had a relevant increase from baseline to start of perfusion (P<0.01); PCT had a steady increase at every time point. Peritoneal sampling showed a statistically significant increase (P<0.01) between start and end of the perfusion phase for all markers but TNF. Serum and peritoneal marker concentration were similar for TNF, PCT and CA-125. IL-6 showed a sharp difference. Conclusions: The most significant variations were in IL-6 and PCT levels. The cytokines level parallels the hemodynamic derangements. Treatment during HIPEC should mimic the established treatment during sepsis and septic shock

Time course of cytokines, hemodynamic and metabolic parameters during hyperthermic intraperitoneal chemotherapy

Systemic response to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) causes the activation of endocrine, metabolic, hemodynamic and inflammatory processes. The aim of this work is to describe and analyze the time course of the inflammatory markers concentration during CRS+HIPEC in plasma and peritoneal fluids and the association with hemodynamic and metabolic parameters

Time course of cytokines, hemodynamic and metabolic parameters during hyperthermic intraperitoneal chemotherapy

Systemic response to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) causes the activation of endocrine, metabolic, hemodynamic and inflammatory processes. The aim of this work is to describe and analyze the time course of the inflammatory markers concentration during CRS+HIPEC in plasma and peritoneal fluids and the association with hemodynamic and metabolic parameters