ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background.Reactive oxygen species (ROS) and glutathione (GSH) depletion contribute to organ injury after bone marrow transplantation (BMT). Keratinocyte growth factor (KGF) ameliorates graft-versus-host disease (GVHD)-associated organ injury in murine BMT models.Methods.B10.BR mice received total body irradiation (TBI; day −1) ± cyclophosphamide (Cy; 120 mg/kg/day i.p., days −3 and −2), then were transplanted on day 0 with C57BL/6 bone marrow + spleen cells as a source of GVHD-causing T cells. KGF (5 mg/kg/day subcutaneously [s.c.]) or saline was given on days −6, −5, and −4. Lung and liver GSH and oxidized GSH disulfide (GSSG) levels were measured on days 0 and 5 and glutathione redox potential (Eh) calculated. Organ malondialdehyde (MDA) was determined on day 5 as an index of ROS-mediated lipid peroxidation.Results.In lung, TBI+BMT oxidized GSH Ehand increased MDA. Cy further oxidized lung GSH Eh. In liver, neither BMT regimen altered GSH redox status or MDA. KGF prevented the decrease in lung GSH after TBI+Cy and decreased lung MDA after both TBI and TBI+Cy. KGF increased liver GSH levels and GSH Ehafter TBI and GSH Ehafter TBI+Cy.Conclusions.In murine allogeneic BMT, TBI oxidizes the lung GSH redox pool and Cy exacerbates this response by 5 days post-BMT. In contrast, liver GSH redox status is maintained under these experimental conditions. KGF treatment attenuates the Cy-induced decrease in lung GSH, decreases post-BMT lung lipid peroxidation, and improves liver GSH redox indices. KGF may have a therapeutic role to prevent or attenuate GSH depletion and ROS-mediated organ injury in BMT.

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background.Pulmonary edema, owing to an impairment of microvascular barrier function, is an important feature in lung ischemia/reperfusion (IR) injury. Inhalation of nitric oxide (NO) during the period of reperfusion has previously been shown to reduce this leakage response.Methods.We investigated the impact of short-term (30 min) low-dose (10 ppm) pre-ischemic NO inhalation on IR injury in buffer-perfused rabbit lungs, subsequently undergoing 210 min of warm, anoxic-ventilated ischemia.Results.Far-reaching suppression of the leakage response, reflected by manifold increased capillary filtration coefficients and edema formation, was noted in lungs with pre-ischemic NO administration, corresponding to the beneficial effect of NO inhalation during reperfusion. The effect of NO pre-exposure was not related to vasodilation, because microvascular pressures were unchanged, and was mimicked by pre-ischemic intravascular administration of sodium nitroprusside with subsequent washout of this agent. NO inhalation during reperfusion, but not pre-ischemic, short-term NO administration, provoked a manifold increase in the accumulation of guanosine 3′,5′-cyclic monophosphate (cGMP) in the perfusate. The cGMP-analogue, 8-Br-cGMP, mimicked the anti-edematous effect of NO when present during reperfusion, but pre-ischemic, short-term administration of 8-Br-cGMP provided only limited protection. The guanylate cyclase-inhibitor, 1H-[1, 2, 4]-Oxadiazolo-[4,3-a]-quinoxalin-1-one (ODQ), largely antagonized the beneficial effects of NO inhalation during reperfusion but had only minor influence on the effect of NO pre-exposure.Conclusions.“Preconditioning” of the lung vasculature with short-term NO administration maintains endothelial integrity in a subsequent ischemia/reperfusion maneuver, with nonvasodilatory and non-cGMP-related mechanisms suggested to be largely responsible. This finding may offer interesting perspectives for donor management in clinical lung transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background.Pancreatic islet transplantation in diabetes, by restoring euglycemia, should in time correct the abnormal accumulation of advanced glycation end products (AGEs) over target tissues, thus delaying the development of late diabetic complications.Methods.Homologous islet transplantation was performed in inbred Lewis rats 15 days (TA), 4 months (TB), and 8 months (TC) after streptozotocin diabetes. Group TA was studied for 12 months and groups TB and TC were studied for 4 months after transplantation. Normal (N) and diabetic (D) rats formed the control groups. Metabolic control in the transplant (T) groups was evaluated by oral glucose tolerance test. Blood glucose, glycated hemoglobin, and body weight were determined in all groups. AGE levels were determined by spectrofluorometry in eye lens proteins and by ELISA in aortic and tail tendon collagen.Results.T groups showed normal oral glucose tolerance tests and metabolic parameters. The latter were altered in all D groups (P<0.005 toP<0.0001 versus N and T groups). AGEs were increased in the D groups (P<0.05 toP<0.001) versus the N groups. AGEs in the TA and TB groups were not different from those of the N groups but were significantly reduced (P<0.05 toP<0.001) when compared with those of the D groups. In the TC group, eye lens AGEs were significantly elevated (P<0.001) or significantly reduced (P<0.01) when compared with those of the N or D groups, respectively. Aortic collagen AGEs were elevated (P<0.01) by comparison with those of the N groups and not statistically different from those of the D groups. Tail tendon collagen AGE levels lay between those of the N and D groups, without reaching a statistical significance.Conclusions.These results indicate that primary and early secondary (groups TA and TB) but not late secondary (group TC) islet transplantations are capable of blocking or reducing an abnormal accumulation of AGEs, thus confirming the importance of preventive transplantation therapies.

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background.The severe shortage of cadaver donor kidneys for transplantation has prompted many centers to utilize older donor kidneys, which have been associated with lower graft survival rates. The aim of the present study was to examine the availability and feasibility of considering kidneys from donors over the age of 60.Method.We studied 252 cadaveric renal transplant recipients (156 males, 96 females) who received kidneys from uncontrolled non-heart-beating donors between 1987 and 1997. We performed in situ cooling with especially designed double-balloon catheters to minimize warm ischemic kidney damage. Recipients were classified according to donor age (<age 60 and >age 60), and we examined graft survival rates. All patients were followed for a minimum of 1 year after transplantation.Results.Graft survival rates for recipients of kidneys from the older donor group at 1, 5, and 10 years after transplantation were 77%, 37%, and 30%, respectively. Corresponding values for the younger donor kidney recipients were 87%, 64%, and 47%, respectively (P=0.0011). Improved survival rates were noted when older kidneys were used for lighter weight recipients (<54 kg). No other significant factors impacted on older donor graft survival rates.Conclusion.Older donor kidneys are associated with poorer graft survival rates. However, kidney transplants from older donors can be quite effective in lighter weight recipients (<54 kg).

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background.Despite passive immunoprophylaxis a significant number of patients, especially if hepatitis B virus (HBV) DNA is positive prior to transplantation, develop HBV recurrence. This number might be reduced by lowering viral replication pretransplant with antiviral agents and by postoperative combination of antiviral agents and passive immunoprophylaxis.Patients and methods.A total of 74 HBV-DNA positive patients who underwent liver transplantation between 9/88 and 4/00 were analyzed retrospectively. Before lamivudine or famciclovir were available, in total 40 patients did not receive any preoperative antiviral therapy. Since 11/93, 17 patients were treated with famciclovir 1500 mg daily, after 4/96 17 patients with lamivudine 150 mg daily prior liver transplantation. Posttransplant all patients received passive immunoprophylaxis aiming at a titer of more than 100 U/liter. In the 34 patients with preoperative antiviral therapy an additional prophylaxis with the respective antiviral agent was applied.Results.Under preoperative famciclovir and lamivudine 30 and 71% of patients became HBV-DNA negative, respectively. Actuarial reinfection rate 2 years after liver transplantation was 48% without antiviral prophylaxis, which was not statistically different from 55% under perioperative famciclovir therapy. In contrast only 18% developed HBV recurrence under perioperative lamivudine treatment. During both antiviral regimens neither pre nor posttransplant severe side effects were observed.Conclusion.Perioperative application of famciclovir is not recommendable, whereas lamivudine seems to lower recurrence rates significantly. Whether the observed effect is due to pre- or postoperative application remains to be addressed in further studies. In addition the long-term course has to be awaited.

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background.Endothelial dysfunction is an early key event in the development of arteriosclerotic cardiovascular disease (ASCVD), thus an early marker of subclinical ASCVD. Endothelial function is impaired in renal transplant recipients (RTR) treated with cyclosporine (CyA). Tacrolimus is associated with less hyperlipidemia and hypertension than CyA, however, there are no data on endothelial function in tacrolimus-treated RTR.Methods.High-resolution brachial ultrasonography was used to assess endothelium-dependent dilatation (EDD), and endothelium-independent dilatation (EID) in 20 stable RTR and a control group of 10 healthy subjects without clinical evidence of ASCVD. The RTR group included patients receiving CyA (n=10) and tacrolimus (n=10). EDD and EID were measured as percent increase in brachial artery diameter in response to reactive hyperemia and nitroglycerin, respectively.Results and Conclusions.EDD was significantly lower in RTR versus controls (1.7±0.7 vs. 7.3±0.7%,P<0.0001), whereas EID was similar in the two groups. No significant differences were found in EDD or in EID between CyA- and tacrolimus-treated RTR. Glomerular filtration rate, plasma homocysteine, blood pressure, and lipid profiles were similar in CyA- and tacrolimus-treated RTR.

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background.We first introduced the orthotopic liver transplantation utilizing cavaplasty technique in 1994. This paper describes the surgical technique and assesses the outcome of the cavaplasty OLT.Methods.The cavaplasty procedure was used in 115 consecutive orthotopic liver transplantations, including six left lateral and two right lobe transplantations, between November 1994 and September 2000. Fifty-three (66.3%) transplantations required femoro-axillary veno-venous bypass in the initial 4 years, whereas only eight (22.9%) needed VB in the subsequent 2 years. Conversion to piggyback or standard technique was not necessary in any patient.Results.Median results are as follows: operative time 4.5 hr, warm ischemia time 25 min, and blood transfused (packed red blood cells) 6 units. These findings did not differ between first transplantation and retransplantation. There were no perioperative deaths related to the cavaplasty technique. No hepatic venous outflow obstruction was observed, including living-related OLTs. No patient required postoperative hemodialysis for acute renal failure. The median intensive care and hospital stays were 2 days and 10 days, respectively.Conclusions.The cavaplasty technique requires no retrocaval, hepatic vein, or short hepatic vein dissection, and the inferior vena cava can be preserved, which provides advantages for hepatectomy and easy hemostasis, especially during retransplantation. The wide-open triangular caval anastomosis is easy to perform, allowing short implantation time and size matching and avoiding outflow obstruction. The short implantation time reduces the need for veno-venous bypass. Our experience indicates that the cavaplasty technique can be applied to all patients and is justified by minimal technical complications.

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID