[Blockade of B7:CD28 costimulatory pathway reduces the vascular damage in an experimental model of chronic rejection]. / Riduzione del danno vascolare in un modello sperimentale de rigetto cronico mediante blocco selettivo della via di costimolazione B7:CD28.

AIM: Costimulatory blockade and donor specific transfusion (DST) can catalyze tolerance of transplanted organs through a multistep adaptation between the recipient and donor immune systems. Such an in vivo process may prolong graft survival. Aim of this study was to evaluate the outcome of aortic transplantation under CTLA4Ig and DST in a mismatched model in rats. METHODS: Orthotopic aortic transplantation was performed in recipients Lewis from Wistar-Furth rats. The animals were stratified into 3 groups, according to the postoperative treatment. Group 1 had aortic transplantation only (controls, n=6), while group 2 (n=7) had a load of donor splenocytes (DST). Group 3 was treated with DST and CTLA4Ig. All the animals were sacrificed at the 60th postoperative day and the aortic specimens were prepared for histology. Intimal cells, muscular cells and lymphocyte cell infiltration were evaluated by serial counts. RESULTS: In Group 1 there was a severe chronic rejection, while group 2 showed a slower onset of chronic rejection with less inflammatory infiltrate than group 1 (P<0.05). Group 3 had the best overall outcome with lower infiltration and minimal alterations compared with groups 1 and 2. CONCLUSIONS: Costimulatory blockade and DST load can prevent the onset of chronic rejection in this experimental setting. Despite the wide availability of immunosuppressors, which makes transplantation a today's clinical routine, the solution to chronic rejection is still elusive. The synergistic role of splenocytes and costimulatory blockade raises interesting perspectives about the immunomodulatory role of spleen in tolerance induction.

Long-term follow-up in children treated for retroperitoneal malignant tumours.

Thirty-two long-term survivors after treatment with surgery, radiotherapy and chemotherapy for neuroblastoma (NRB) and Wilms' tumour (WT) were re-evaluated after a period of more than 10 years (mean 16 yr 1 mo, range 27 yr 2 mo/10 yr 5 mo). In addition to routine clinical and laboratory studies, all patients underwent auxometry, echocardiography, spinal X-ray, abdominal US and kidney radionuclide scans. Neither obvious physical signs nor cutaneous toxicity were noted at inspection. No dysmenorrhoea or sexual disorders were mentioned. Haematological data turned out to be all in the normal range, except for TIBC/UIBC ratio (out of range in 70 % of cases); gammaGt (62.5 %); A/G ratio (12.5 %); ALT (37.5 %). Auxometrical data were all in the normal range; in particular, results of mean weight and height were just slightly over the 50 degrees centile. Spinal X-rays revealed mild kyphotic deformities (68.9 %), pelvic obliquity and tilting (62.5 %), rotation of the vertebral bodies (34.3 %) and compensatory curves of the spine (21.8 %). No impairment of cardiac functions was noted at echocardiography. No alteration of the hepatic structure was detectable at US scans. Marked impairment of the renal function (20 % and 1.5 % residual function) was detected at radionuclide imaging in 2 NRB patients who had not undergone nephrectomy, with the kidney having almost disappeared in one. In conclusion, the study emphasises the need for careful and prolonged follow-up for the detection of sequelae than can appear even many years after the initial treatment, and the wisdom and the need for a continued search for less aggressive protocols; as long as the cure rate is not compromised, less aggressive protocols should aim for a satisfactory overall survival with a reduced incidence of sequelae and hence a better quality of life.

Symptomatic unilateral renal angiomyolipoma in a child with tuberous sclerosis.

We report a case of unilateral renal angiomyolipoma in a 10-year-old boy with tuberous sclerosis. The case is worthy of attention because the symptoms occurred at an early age and because the lesion was unilateral, the latter confirmed at 11-year follow-up. The presentation and treatment are discussed, and the pertinent literature is reviewed. The case demonstrates that it is of clinical importance to monitor renal involvement in children with tuberous sclerosis.

[Whole pancreatic transplantation and islet transplantation. Experiment notes]. / Trapianto di pancreas intero e trapianto di isole. Note sperimentali.

BACKGROUND: The results of pancreas transplantation have greatly improved in recent years. The path to further improvements goes through extensive experimental researches. METHODS: This study describes the effects of different procedures as hemodynamic asset and postoperative outcome. Twenty-nine swine underwent a total pancreatectomy, and were stratified into five groups. Group one (n = 5) served as control. Group two (n = 7) was autotransplanted. Group three (n = 6) and group four (n = 6) underwent allotransplantation; the first without immunosuppression and the second treated with cyclosporine and steroids. In group five (n = 5) Langerhans Islets transplantation was performed. RESULTS: Survival was different depending on which methodology was applied. The postoperative survival was 7 +/- 2 days in group one, 24 +/- 16 days in group two, 17 +/- 7 days in group three, 27 +/- 8 days in group four and 12 +/- 6 days in group five. CONCLUSIONS: The postoperative glucose control was normal in group two and group four while a severe diabetes appeared in group one (group 1 vs group 2: p < 0.05) and in group three during acute graft rejection after the 12th postoperative day (group 3 vs group 4: p < 0.05). Glycemia was slightly controlled in group five. The intraoperative hemodynamic status was evaluated at the time of pancreatectomy, harvesting, revascularization, and when surgery was over. Among the different parameters studied (mean arterial and pulmonary pressure, pulmonary wedge pressure, central venous pressure, cardiac output, oxygen extraction ratio, systemic vascular resistance, oxygen delivery and oxygen consumption), a statistically significant difference between group one and group five (p < 0.05) was observed.

[Treatment of the nephrotoxicity of immunosuppressive drugs with insulin-like growth factor-I]. / Trattamento della nefrotossicità da farmaci immunosoppressori con insulin-like growth factor-I.

BACKGROUND: Delayed graft function is a common and severe complication after cadaveric kidney transplantation. Besides a more complicated postoperative course, DGF can worsen the overall graft survival. In particular, DGF enhances the nephrotoxicity of mainstream immunosuppressants cyclosporine and FK506. This study evaluates a new therapeutical approach to the treatment of DGF related nephrotoxicity, based on the administration of IGF-I. METHODS: Sixty inbred Lewis rats underwent a bilateral clamping of the renal pedicles (20') as standard damage. The animals were stratified in six groups, according to the postoperative treatment. Group 1 served as control and received only the standard ischemic injury. Cyclosporine and FK506 were added in groups 3 and 5. Groups 2, 4 and 6 had the same treatment of groups 1, 3, 5 respectively, plus the administration of IGF-I. Blood samples were drawn daily to evaluate creatinine and BUN for 7 days. RESULTS: The rats treated with IGF-I had significantly better values compared to the respective controls (2-way ANOVA, p < 0.05). CONCLUSIONS: In conclusion, IGF-I improves the nephrotoxicity of mainstream immunosuppressants in this model. Its use is potentially beneficial for transplantation.