Biodegradable polymeric stents for vascular application in a porcine carotid artery model: English version.

Over the past years the development of biodegradable polymeric stents has made great progress; nevertheless, essential problems must still be solved. Modifications in design and chemical composition should optimize the quality of biodegradable stents and remove the weaknesses. New biodegradable poly-L-lactide/poly-4-hydroxybutyrate (PLLA/P4HB) stents and permanent 316L stents were implantedendovascularly into both common carotid arteries of 10 domestic pigs. At 4 weeks following implantation, computed tomography (CT) angiography was carried out to identify the distal degree of stenosis. The PLLA/P4HB group showed a considerably lower distal degree of stenosis by additional oral application of atorvastatin (mean 39.81 ± 8.57 %) compared to the untreated PLLA/P4HB group without atorvastatin (mean 52.05 ± 5.80 %). The 316L stents showed no differences in the degree of distal stenosis between the group treated with atorvastatin (mean 44.21 ± 2.34 %) and the untreated group (mean 35.65 ± 3.72 %). Biodegradable PLLA/P4HB stents generally represent a promising approach to resolving the existing problems in the use of permanent stents. Restitutio ad integrum is only achievable if a stent is completely degraded.

Up-regulation of ICAM-1 during cold ischemia triggers early neutrophil infiltration in human pancreas allograft reperfusion.

BACKGROUND: Graft pancreatitis is induced by ischemia/reperfusion injury in which neutrophil infiltration is believed to be a crucial early event. This observation suggests the presence of adhesion molecules already at the time of reperfusion. Therefore, this study was performed to evaluate the pattern of ICAM-1 and P-Selectin expression on human pancreas allografts following cold ischemia and reperfusion. PATIENTS AND METHODS: We performed an analysis of pancreas biopsy specimens taken from 13 patients undergoing pancreas transplantation compared with pancreas specimens from 10 patients following resection. Cryostat sections were stained with monoclonal antibodies against CD11b, a neutrophil marker, and the adhesion molecules ICAM-1 and P-Selectin. RESULTS: Extensive infiltration of CD11b-positive cells was detected in venules and capillaries of pancreas allografts after reperfusion (18.38 +/- 0.87) compared with controls (T1 4.22 +/- 0.55) or with tissue specimens at about 10 hours of cold ischemia (2.60 +/- 0.35; P < .001). Similarly, the pattern of P-Selectin showed a moderate expression before organ harvest (1.54 +/- 0.21) and in samples during cold ischemia (1.46 +/- 0.24) followed by a significantly greater number of P-Selectin-positive cells after reperfusion (2.54 +/- 0.18; P = .005). ICAM-1 was only weakly expressed on the surface of the venular endothelium in all controls (0.77 +/- 0.12). In contrast to P-Selectin, ICAM-1 showed prominent up-regulation during cold ischemia (2.23 +/- 0.23; P < .001) with no further increase after reperfusion (2.23 +/- 0.17). CONCLUSION: The data suggested that ICAM-1 was already up-regulated during cold ischemia, possibly representing the mechanism of early neutrophil infiltration observed in human pancreatic ischemia/reperfusion injury.

How to recognize a suitable pancreas donor: a Eurotransplant study of preprocurement factors.

INTRODUCTION: Because of the increasing demand for pancreas transplantation, more marginal donors are offered to Eurotransplant. The aim of this study was to validate a donor quality score that would facilitate recognition of a suitable pancreas donor among all reported donors. MATERIALS AND METHODS: We analyzed all 3180 consecutively reported pancreas donors for the period between January 1, 2002 and June 30, 2005 and determined the influence of the preprocurement pancreas suitability score (P-PASS) on the acceptance of a pancreas. We defined a range and point weight for each variable based on clinical expertise and known literature. RESULTS: Multiple regression analysis using pancreas acceptance as an outcome variable identified P-PASS > or = 17 as a significant cutoff point (P < .001). Pancreata from donors with P-PASS > or = 17 were three times more likely to be refused. CONCLUSION: The donor score can help in screening for potential pancreas donors, where an ideal donor has a P-PASS < 17. Our data demonstrate that consideration of a combination of preprocurement factors can help identify a suitable pancreas donor. Therefore, we recommend that a pancreas donor score be calculated for each potential pancreas donor, and all donors with a P-PASS < 17 should be considered for pancreas donation.

Pharmacokinetics and penetration of linezolid into inflamed soft tissue in diabetic foot infections.

OBJECTIVE: Physiological changes and local and systemic inflammation may affect plasma and tissue pharmacokinetics of antimicrobial agents in diabetics. The aim of the study was to investigate the penetration of linezolid into inflamed areas of infected diabetic foot wounds and the pharmacokinetics in the risk population of diabetics. METHODS: Pharmacokinetics and tissue penetration of linezolid into inflamed diabetic foot infection (DFI) tissue were determined at steady state in 15 patients with diabetes type 2 and DFI following administration of multiple oral doses of 600 mg given every 12 h. Second debridement was performed on days 4-6, 3 h after linezolid administration. Linezolid concentrations were determined in perinecrotic wound tissue of inflamed diabetic foot by high-performance liquid chromatography (HPLC). RESULTS: A mean maximum plasma concentration (C(max)) in plasma of 14.3 mg/L was attained at a median of 2.0 h [time to reach C(max) (T(max)) range 0.5-6.0 h). Area under the concentration time curve from zero to 12 h (AUC(0-12 h)) with a mean of 114.1 mgh/L and C(min) of 5.4 mg/L were achieved in patients with diabetes mellitus type 2. Penetration of linezolid into inflamed areas of DFI with tissue/plasma ratios of mean 101.7% [95% confidence interval (CI) 56; 148%] produced a mean concentration of 9.6 microg/g (95% CI 7.4; 11.8 microg/g) greater than those predicted to be effective against methicillin-resistant staphylococci [minimum concentration that inhibits 90% of organisms (MIC(90)) of 4 mg/L]. Tissue/plasma ratios correlated positive with systemic inflammation. CONCLUSION: Plasma pharmacokinetics of linezolid in diabetics and adequate levels in inflamed areas of diabetic foot wound suggest that an oral dose of 600 mg bd of linezolid provides effective concentrations for treating methicillin-resistant Staphylococcus aureus (MRSA) in DFI.

Involvement of dendritic cells in allograft rejection new implications of dendritic cell-endothelial cell interactions.

For almost half a century immunologists have tried to tear down the MHC barrier, which separates two unrelated individuals during transplantation. Latest experimental data suggest that a breakthrough in vitro is imminent. Dendritic cells (DCs), which activate naïve allo-reactive T-cells (TCs), play a central role in the establishment of allo-antigen-specific immunity. Allograft solid organ rejection is initiated at the foreign endothelial cell (EC) layer, which forms an immunogenic barrier for migrating DCs. Thus, DC/EC interactions might play a crucial role in antigen-specific allograft rejection. Organ rejection is mediated by host allo-reactive TCs, which are activated by donor DCs (direct activation) or host DCs (indirect activation). Direct allo-antigen presentation by regulatory dendritic cells (DCreg) can play an instructive role towards tolerance induction. Several groups established that, DCregs, if transplanted beforehand, enter host thymus, spleen, or bone marrow where they might eventually establish allo-antigen-specific tolerance. A fundamental aspect of DC function is migration throughout the entire organism. After solid organ transplantation, host DCs bind to ECs, invade allograft tissues, and finally transmigrate into lymphoid vessels and secondary lymphoid organs, where they present allo-antigens to naïve host TCs. Recent data suggest that in vitro manipulated DCregs may mediate allo-transplantation tolerance induction. However, the fundamental mechanisms on how such DCregs cause host TCs in the periphery towards tolerance remain unclear. One very promising experimental concept is the simultaneous manipulation of DC direct and indirect TC activation/suppression, towards donor antigen-specific allo-transplantation tolerance. The allo-antigen-specific long-term tolerance induction mediated by DCreg pre-transplantation (with simultaneous short-term immunosuppression) has become reproducible in the laboratory animal setting. Despite the shortcomings of laboratory animal studies, strong promises are deriving from these studies for clinical kidney, heart, and liver transplantation.

Anastomotic stenting in a porcine aortoiliac graft model.

The purpose of the study was to evaluate the feasibility of anastomotic stent application in a porcine aortoiliac graft model. In a total of 10 pigs, a polytetrafluoroethylene aortobi-iliac graft was implanted through a midline abdominal incision. The lower edge of the iliac vessel was graft-inverted about 1 mm to produce irregularities at the downstream anastomosis. After transverse graft incision, six stainless-steel stents, six poly-L-lactic acid (PLLA) stents and four PLLA stents with 10% polycaprolactone (PCL) were implanted at the iliac anastomotic site using a 6 mm balloon dilatation catheter. Four anastomotic sites were left untreated. After two weeks, the patency of graft limbs was evaluated by contrast-enhanced computed tomography (CT). Both metal and polymeric stent designs provided adequate flexibility to manoeuvre across the anastomotic site for expansion in the chosen position. After deployment, the stent-arterial wall contact was complete on a macroscopic view. On CT scan, all metal and PLLA-stented graft limbs were free of stenosis, whereas all PLLA/PCL stents were occluded. The non-stented graft limbs showed a stenosis of 50-70%. In summary, this model is feasible to assess preclinically the deployment and patency rate of an anastomotic stent and to test future stent developments.

Renal ischemia-reperfusion injury: new implications of dendritic cell-endothelial cell interactions.

In renal ischemia/reperfusion (I/R) injury endothelial cells are a main target. The disturbance of endothelial cell physiology leads to endothelial swelling and narrowing of the blood vessel lumen. We attribute this effect to impairment of endothelial cell nitric oxide synthase (NOS). NO is significantly reduced in the course of hypoxia causing dysfunction of the vascular smooth muscle tone. Subsequently to an I/R injury, the inflammatory response results in endothelial activation with enhanced dendritic cell (DC) adhesion and migration. Thus, alloreactive leukocytes are recruited to the inflammatory site. Finally, dendritic cell-endothelial cell interactions may play a crucial role in antigen-specific allograft rejection in I/R renal injury. DCs, which activate naïve alloreactive T cells, play a central role in the establishment of alloantigen-specific immunity. In the course of hypoxia rejection is initiated at the activated layer of foreign endothelial cells (EC), which forms an immunogenic barrier for migrating DCs and T cells. Host DCs that bind to postischemic activated ECs invade the allografted tissues, or remain stationary in the subendothelial layer, or transmigrate into lymphoid vessels and secondary lymphoid organs, where they present alloantigens to naïve host T cells. Organ rejection is mediated by host alloreactive T cells, which are activated by donor DCs (direct activation) or host DCs (indirect activation). We hypothesized that DC-EC binding and migration is the first step in the renal I/R injury that mediates allotransplant rejection. We sought to better understand the downstream events of a renal I/R injury by understanding DC binding and migration, thereby seeking new strategies for more specific immunomodulatory interventions. Herein we developed a new allotransplant-rejection model after renal I/R injury.

Pharmacokinetic profiling of cyclosporine microemulsion during the first 3 weeks after simultaneous pancreas-kidney transplantation.

The optimal effect of therapy with cyclosporine (CsA) seeks to minimize undesirable side effects while maximizing immunosuppression. This balance, depends on CsA exposure, which may be characterized by the area under the concentration-time-curve (AUC). Therefore, we tested the pharmacokinetic profile of microemulsion CsA as a superior approach to guide clinical immunosuppression after de novo simultaneous pancreas-kidney transplantations. We examined 10 consecutive pancreas-kidney recipients with type 1 diabetes and end-stage renal disease. All patients were treated with a regimen consisting of CsA, mycophenolate mofetil (MMF), and prednisone. Full (9-point) pharmacokinetic studies (C0, C1, C2, C3, C4, C6, C8, C10, C12) were performed on week 1 and during week 3 to examine CsA pharmacokinetic profiles. Mean AUC0-12 of 4431 +/- 2400 microg x h/L at week 1 remained stable at week 3 (5119 +/- 1190 microg x h/L). The C6 sampling time displayed the best correlation with AUC0-12 (r2 = 0.881), followed by C3 (r2 = 0.758). Our preliminary data after simultaneous pancreas-kidney transplantation support the hypothesis that C3 or C6 sampling is a more accurate predictor of the AUC0-12 than C0. The combination of two samplings, namely C3 + C6 (r2 = 0.938) or C2 + C6 (r2 = 0.955) proved excellent prediction of exposure after simultaneous pancreas-kidney transplantation.

Dendritic cells as pharmacological targets for the generation of regulatory immunosuppressive effectors. New implications for allo-transplantation.

Dendritic cells (DCs) play a central role in the establishment of tolerance/immunity, because they activate naïve T cells (TCs). Therefore, the pharmacological modulation of DCs has become a major field of interest in immunology. A large body of literature has arisen from the studies of DC biology during immunosuppressive drug treatment. Immunosuppressive drugs have improved the therapeutic management of allograft organ transplantation and autoimmune diseases, significantly. There is now strong evidence that, DCs might be the key for antigen specific tolerance induction. Recently, the existence of a population of DCs that migrate to the regional lymph node in the steady state has been identified. Such steady state immature migrating DCs are loaded with tissue antigens and deliver self-antigens towards secondary lymphatic organs and might educate TCs towards self-tolerance. Latest experimental data from rodent solid organ allo-transplantation supports the idea, that DCs might even become regulatory DCs towards foreign antigen specific tolerance induction. Apparently, regulatory donor DCs invade host secondary lymphatic organs where they might eventually educate host TCs towards foreign antigen specific tolerance. Seemingly, it depends on the DC maturation state whether pharmacologically modulated DCs induce antigen specific long-term tolerance in allo-transplantation solid organ transplantation. Several authors reported a positive self-limiting feedback loop between tolerogenic DCs and allo-specific regulatory TCs. Thus, the DC-TC network appears as an exceptionally good target for pharmacological manipulations. Here we review how immunosuppressive agents interfere with DC maturation, migration and homeostasis. We are developing a rational to select different drugs for the generation of regulatory DCs, for allo-transplantation clinical settings.

Deletion of the tissue response against alginate-pll capsules by temporary release of co-encapsulated steroids.

Transplantation of encapsulated living cells is a promising approach for the treatment of a wide variety of diseases. Large-scale application of the technique, however, is hampered by inflammatory responses against the capsules. In the present study, we investigate whether tissue responses against alginate-PLL-alginate capsules can be modulated by co-encapsulation and temporary release of immunomodulating factors such as dexamethasone. Such an approach may be mandatory in order to increase the function and survival of encapsulated tissue since it has been shown that the tissue response can be caused by many, insurmountable factors. In an in vitro assay, we demonstrated an antiproliferative effect of dexamethasone-containing capsules on L929-mouse-fibroblasts. Subsequently, capsules prepared of purified alginate with or without solved dexamethasone were implanted in the peritoneal cavity of rats and retrieved one month later for histological evaluation. Most of the capsules without dexamethasone proved to be overgrown and adherent to the abdominal organs whereas with co-encapsulated dexamethasone the majority of the capsules were found freely floating in the peritoneal cavity without overgrowth. We conclude that co-encapsulation of dexamethasone has a profound effect on fibroblasts and macrophages adherence to immunoisolating capsules.

Exogenous and endogenous nitric oxide donors improve post-ischemic tissue oxygenation in early pancreatic ischemia/reperfusion injury in the rat.

INTRODUCTION: In pancreatic ischemia/reperfusion (IR) injury (IRI) the role of nitric oxide (NO) is not completely understood. Using a rat model of normothermic in situ IRI, the effect of endogenous and exogenous NO donors on post-ischemic tissue oxygenation and tissue damage was investigated. METHODS: IR was induced by 2-hour normothermic in situ ischemia of a pancreatic tail segment pedunculated on the splenic vessels with 2 h of reperfusion in an untreated, an L-arginine- and a sodium-nitroprusside-treated group (Wistar rats, n = 7/group). Animals without ischemia served as controls. Tissue oxygenation (pO(2ti)) was monitored using a pO2-sensitive Clark-type electrode. Histological investigation was performed following a semiquantitative score (edema, vacuolization, PMN infiltration, necrosis). Plasma lipase was another marker of organ damage. RESULTS: The administration of L-arginine and sodium nitroprusside caused a significant amelioration of the decrease in pO2i) after reperfusion compared to IR animals (p < 0.05). Histological damage was also reduced in the NO donor groups (p < 0.05). After reperfusion, plasma lipase in the L-arginine-treated animals was significantly lower compared to IR and sodium nitroprusside (p < 0.05). CONCLUSIONS: The administration of both endogenous and exogenous NO donors is protective in IRI of the rat pancreas which can be seen by an improvement in post-ischemic tissue oxygenation which indicates better nutritive tissue perfusion, amelioration of the histological tissue injury and, in L-arginine animals, lower lipase levels. NO donors could be useful in the prevention and reduction of the pancreatic IRI.

Islet autotransplantation combined with pancreatectomy for treatment of pancreatic adenocarcinoma: a case report.

Extensive pancreatectomy (EP) may increase the resection rate of pancreatic adenocarcinoma (PA). Unfortunately, EP often results in unstable diabetes. Recently, islet autotransplantation (auto-Tx) has offered the potential to prevent this metabolic disorder. Because of the fear of contamination of prepared islets by malignant cells, this procedure has so far not been used as a treatment for PA. We herein report a case of a 63-year-old nondiabetic patient who underwent EP combined with islet auto-Tx in an emergency operation following histologically proved R(0)-resection for PA (pT(3)pN(1)G(2)). Islets were isolated from the excised pancreas using a continuous digestion filtration device. The resultant preparation was injected into the portal vein. Owing to the moderate fasting hyperglycemia, postoperative exogenous insulin therapy was necessary (26 U/d). After discharge, the patient's daily insulin dose was gradually reduced. At 1-year follow-up the fasting C-peptide level was 0.66 ng/mL, and an oral glucose tolerance test (oGTT) and an intravenous (IV) glucagon stimulation (GS) showed functioning engrafted islets. The K-ras mutations were detected in the paraffin-embedded PA, but not in the prepared islets or in the peripheral blood. Computed tomographic (CT) imaging revealed neither local tumor recurrence nor liver metastases. At 2-year follow-up, the patient was on a balanced food regimen and gaining weight. Although he remains insulin-dependent (16 U/d), he is metabolically stable (HbA(1)(c) 5.9%). The fasting C-peptide level is 0.68 ng/mL. The peak value of C-peptide in response to oGTT was 0.92 ng/mL and to GS 0.89 ng/mL. At this time Ca19-9 and CEA are increased to 35.3 U/mL and 19.2 ng/mL, respectively. The patient died 2.5 years after operation owing to tumor recurrence. There was no evidence for liver metastases. We postulate that histologic evaluation (R(0)-resection) and detection of K-ras mutations may be useful techniques. However, islet auto-Tx after EP for adenocarcinoma should only be regarded for rescue therapy. Studies on strategies to exclude possible contamination of islet tissue with carcinoma cells are critically important.

Influence of nitric oxide on microcirculation in pancreatic ischemia/reperfusion injury: an intravital microscopic study.

Recently, protective effects of nitric oxide donors in pancreatic ischemia/reperfusion (IRI) injury have been described. Their role in post-ischemic microcirculation was previously not investigated. Ischemia reperfusion was induced in an isolated pancreatic tail segment in situ. Animals were randomized to four experimental groups (n=7 animals/group), the control group (CO) received saline as placebo. Treatment groups received either sodium nitroprusside (SN) 5 min before until 2 h after reperfusion, L-arginine (LA) 30 min before reperfusion until 2 h after reperfusion or sodium nitroprusside and L-arginine (SNLA) together. After induction of ischemia (2 h) post-ischemic microcirculation was observed for 2 h by intravital-fluorescence microscopy. Functional-capillary density (FCD), leukocyte adherence in post-capillary venules (LAV) and histological damage were analysed. After reperfusion FCD decreased in all groups (P<0.05). FCD was significantly restored in all groups with administration of nitric oxide donors after reperfusion (P<0.05) as compared to CO without significant difference between the individual nitric oxide donor groups. Leukocyte adherence was significantly increased 1 h and 2 h after reperfusion (P<0.001) as compared to baseline, which was lower in all nitric oxide donor groups. Histological damage in the pancreatic tail-segment was significantly reduced in nitric oxide donor groups (P<0.01). Administration of nitric oxide donors might be useful in ischemia-reperfusion injury of the pancreas by its protective effect on microcirculation and inflammatory reaction.

Dendritic cell endothelium interaction in autoimmunity.

Monocyte derived dendritic cells play a central role in controlling immunity by activating naïve T lymphocytes. Monocytes can leave the blood stream by endothelial cell transmigration and differentiation into dendritic cells. A fundamental aspect of dendritic cell biology is their capacity to engulf tissue antigens and revers-migrate into lymph nodes. In lymph nodes dendritic cells can traffic to T-cell areas where they activate naïve T-cells. Throughout this review we are developing a model of in vivo activation of auto-reactive T-cells by activated dendritic cells.

High levels of C-reactive protein after simultaneous pancreas-kidney transplantation predict pancreas graft-related complications and graft survival.

BACKGROUND: Although pancreas graft-related complications are frequent after simultaneous pancreas-kidney transplantation (SPK), there are no parameters predicting the risk for these complications. METHOD: A two-center retrospective study was performed in 97 patients who underwent SPK to investigate the peak serum value of c-reactive protein (CRP) during the first 72 hr after SPK in view of graft-related complications and graft survival. RESULTS: Mean peak CRP was 115.6 +/- 71.5 mg/L. Mean peak CRP was higher in patients needing relaparotomy (n=31) (136.4 vs. 105.8 mg/L, P=0.048), especially when postoperative bleeding was excluded (P=0.015); in patients with graft pancreatitis (P=0.03); and in patients with graft loss (n=19; P<0.001) compared with patients without these complications. With a cut-off of peak CRP at the level of mean plus 1 SD (187.05 mg/L), there was a significantly higher incidence of relaparotomies (P=0.01; bleedings excluded: P=0.003), graft pancreatitis (P=0.03), and pancreas graft loss (P<0.0001) in patients with high peak CRP compared with patients with low peak CRP. No differences were noticed with regard to rejection rate, mortality, and kidney graft loss. CONCLUSION: Our findings suggest that peak CRP is a helpful parameter in predicting pancreas graft-related complications and pancreas graft survival after SPK. Our results also stress the importance of early graft damage in pancreas transplantation.

Vascular heme oxygenase-1 induction suppresses microvascular thrombus formation in vivo.

OBJECTIVE: By heme degradation, heme oxygenase-1 (HO-1) provides endogenous carbon monoxide and bilirubin, both of which play major roles in vascular biology. The current study aimed to examine whether induction of HO-1 and its byproducts modulate the process of microvascular thrombus formation in vivo. METHODS AND RESULTS: In individual microvessels of mouse cremaster muscle preparations, ferric chloride-induced thrombus formation was analyzed using intravital fluorescence microscopy. When mice were pretreated with an intraperitoneal injection of hemin, a HO-1 inducer, immunohistochemistry and Western blot protein analysis of cremaster muscle tissue displayed a marked induction of HO-1. In these animals, superfusion with ferric chloride solution induced arteriolar and venular thrombus formation, which, however, was significantly delayed when compared with thrombus formation in animals without HO-1 induction. The delay in thrombus formation in hemin-treated mice was completely blunted by tin protoporphyrin-IX, a HO-1 inhibitor, but not by copper protoporphyrin-IX, which does not inhibit the enzyme. Coadministration of the vitamin E analogue Trolox in HO-1-blocked animals almost completely restored the delay in thrombus formation, implying that, besides CO, the antioxidant HO pathway metabolite bilirubin mainly contributes to the antithrombotic property of HO-1. This was further supported by the fact that bilirubin was found as effective as hemin in delay of ferric chloride-induced thrombus formation. Animals with HO-1 induction revealed reduced P-selectin protein expression in cremaster muscle tissue, which most probably presented the molecular basis for delayed thrombus growth. CONCLUSIONS: Local induction of HO-1 activity may be of preventive and therapeutic value for clinical disorders with increased risk of thrombotic events.

[Pancreas transplant pathology: clinicopathologic and experimental findings]. / Pathologie der Pankreastransplantation: Klinisch-pathologische und experimentelle Befunde.

134 pancreas transplantations (113 simultaneous pancreas-kidney, 5 pancreas after kidney, 16 pancreas transplants alone) done in Rostock from VI/95 to III/04 were evaluated in respect to pancreas transplant lesions. Additionally, 36 pancreas specimen of Brown Norway rats experimentally transplanted into diabetic Lewis rats were examined. From 55 out of the 134 pancreas transplant patients, 122 partly repeated pancreas graft specimen examinations were carried out morphologically. The principal lesions in the human pancreas transplants were acute (enzymatic) necrotizing transplant pancreatitis (41 samples), acute (13) and chronic (14) transplant rejection specimen as well as primary or secondary graft thrombosis (12 probes). 23 probes were zero-hour biopsies and 2 showed normal tissue. From 69 out of the 118 pancreas transplant patients with an additional kidney graft, a total of 159 renal transplant probes were examined. They showed the following lesions: acute tubular damage or acute renal failure (23), acute (56) or chronic (22) kidney graft rejection, acute tubular cyclosporine or FK 506 toxicity (53), and histologically normal graft tissue (8 cases). As in other grafted organs, the changes occurring in the transplanted pancreas consist of varying lesions related and/or not related to pancreas transplant rejection. A concise classification and a reproduceable grading schedule are suggested for diagnostic, differential diagnostic, therapeutic, and prognostic purposes. Pancreatic rejection lesions can be classified according to a proposed Rostock '04 working classification of pancreas allograft rejection into three grades (I: mild, II: moderate, III: severe) both for acute and chronic pancreas rejection. There was no direct correlation of the findings in 21 patients with simultaneously studied pancreas and renal transplant biopsies. In contrast to renal grafts, pancreatic rejection signs were often superimposed by acute transplantation pancreatitis with or without secondary graft thrombosis, nonenzymatic necroses or infection. Experimental acute pancreas transplant rejection in rats showed quite similar findings to human grafts and was also graded into three different acute rejection stages.

Prilocaine plasma levels and methemoglobinemia in patients undergoing tumescent liposuction involving less than 2,000 ml.

BACKGROUND: As a reaction to reported adverse outcomes after lidocaine infiltration in tumescent liposuction, prilocaine has gained increasing popularity. Previous studies investigating large-volume liposuction procedures found maximum prilocaine levels and methemoglobinemia up to 12 h postoperatively, suggesting that liposuction should be performed as a hospital procedure only. The aim of this study was to determine prilocaine plasma levels and methemoglobinemia in patients after low- to average-volume liposuction for the purpose of defining the required postoperative surveillance period. METHODS: In 25 patients undergoing liposuction involving less than 2,000 ml prilocaine levels and methemoglobinemia were measured over 4 h postoperatively. Liposuction was conducted after the tumescent technique using a 0.05% hypotonic prilocaine solution with epinephrine. RESULTS: The average prilocaine dose was 6.8 + 0.8 mg/kg, with a maximum dose of 15 mg/kg. The peak prilocaine plasma level of 0.34 mug/ml occurred 3 h after the infiltration. The mean methemoglobinemia at this time point was 0.65%. Only one patient demonstrated a slightly elevated methemoglobin level of 1.4%, but lacked any clinical signs of methemoglobinemia. The prilocaine recovery in the aspirate averaged 36 +/- 4%, indicating that a large amount is removed by suctioning. CONCLUSIONS: The patients did not experience high plasma levels of prilocaine or methemoglobinemia undergoing liposuction involving less than 2,000 ml using a 0.05% hypotonic prilocaine solution. The authors therefore conclude that this procedure can be performed safely with a monitoring period of 12 h.