Lecithin coating as universal stabilization and functionalization strategy for nanosized drug carriers to overcome the blood-brain barrier.

Lecithin coated cholesteryl oleate (ChOl) based nanoparticles (NPs) imitating natural lipoproteins represent a new and promising drug carrier strategy to cross the blood-brain barrier (BBB). In such systems lecithin serves as stabilizing as well as functionalizing agent and enables the adsorptive binding of apolipoprotein E3 (ApoE) as potential drug targeting ligand. The present work is focused on the effect of size reduction on the lecithin coating and ApoE binding. Furthermore, the transferability of this lecithin coating strategy to other NP cores, namely polylactic-co-glycolic acid (PLGA) and polylactic acid (PLA), is investigated in order to provide a universal strategy for a wide range of cores to overcome the BBB. The ChOl NPs' size was successfully reduced from 100 nm to 70 nm. Varying the core size of ChOl NPs illustrated, that the at least needed lecithin amount for sufficient stabilization could be calculated surface area dependently. However, the size reduction led to reduced dye loading per NP and increased ApoE need per NP mass. These effects turned out as huge disadvantages of smaller NPs by weakening the observed ApoE mediated effects. Nevertheless, the extended understanding of the lecithin coating could be used to transfer the concept to other core materials. PLGA and PLA NPs were investigated as alternative core materials for lecithin coating. PLGA was found to be unsuitable, whereas in the case of PLA sufficient stabilization and 100% adsorptive binding efficiency to ApoE could be achieved. The ApoE mediated effects of transcytosis at an in vitro BBB model by bypassing lysosomes were reproduced in even stronger quantities than with a ChOl core, proving lecithin coating as transferable strategy to disguise various NPs with a certain lipophilicity as lipoproteins.

Lipoprotein imitating nanoparticles: Lecithin coating binds ApoE and mediates non-lysosomal uptake leading to transcytosis over the blood-brain barrier.

Lipoproteins are naturally occurring nano sized transport vehicles in the human body. Therefore, lipoproteins could be applied as a drug carrier system. Additionally, several reports of apolipoprotein mediated blood-brain barrier (BBB) crossing suggest lipoprotein mimicking nanoparticles (NPs) as possible drug delivery vehicles to the brain. This could extend the therapy opportunities of various diseases of the central nervous system. A lipoprotein imitating NP system, consisting of a lecithin coated lipophilic cholesteryl oleate core with embedded fluorescent dye and adsorbed apolipoprotein E3 (ApoE) has been established using a two-step solvent injection method. Lecithin coating was proven to stabilize the NPs in isotonic saline solution and to bind ApoE in a highly efficient way. Fluorescent dye load (as model drug) and ApoE amount were varied, obtaining 100 nm sized, monodisperse NPs. The NPs' interaction with the BBB formed by primary porcine brain capillary endothelial cells (PBCEC) was investigated by fluorescence microscopy observing that ApoE mediated a lysosome bypassing uptake mechanism. Using this in vitro BBB model, ApoE concentration dependent permeation over the cell layer could be proven in both directions. An ApoE mediated transcytosis could be achieved, as it had been observed earlier for low-density lipoproteins. These results show that the newly developed NP system successfully mimics endogenous lipoproteins. An ApoE dependent penetration of the BBB was confirmed and provided an indication of apolipoprotein mediated transcytosis, avoiding lysosomal degradation.

Successful Simultaneous Pancreas-Kidney Re-transplantation in a Highly Human Leukocyte Antigen-Sensitized Patient.

BACKGROUND: The waiting time for re-transplantation for sensitized patients is greatly prolonged, given the lack of transplants that are available for this group and additional immunologic barriers. We report the case of a successful re-transplantation in a patient with very high levels of panel reactive antibodies ([PRA] >85%). METHODS: A 45-year-old woman had repetitive rejections after simultaneous pancreas-kidney transplantation, with consequent loss of function of both transplanted organs. Because of a symptomatic episode of kidney rejection, additional removal of the transplanted kidney was performed 6 years later. Because our patient had a very high PRA level, she was enrolled in a desensitization protocol. The regimen was based on an initial single dose of rituximab, followed by repetitive plasmapheresis/immune-absorption sessions and intravenous substitution of immunoglobulin. Eight cycles were required, until a cross-match test was negative (PRA level <50%). The protocol included prednisolone and weight-adapted thymoglobulin. The basic immunosuppressive medication consisted of prednisolone, tacrolimus, and mycophenolate mofetil. The patient's postoperative course was uneventful. RESULTS: Preoperative treatment is essential for sensitized patients. There are no prospective, randomized trials comparing all suggested desensitization protocols. The main tenets of every approach are plasmapheresis and intravenous substitution of immunoglobulin, which appear to have a strong immunomodulatory effect. In the case of re-transplantation, the clinical surgeon not only faces special technical and surgical challenges but also must confront immunologic barriers. CONCLUSIONS: Pancreas-kidney transplantation in patients with high PRA levels is feasible and can be performed successfully with novel desensitization protocols.

[Integration and utilization of physiotherapy in hospice and palliative care : A survey on clinical practice in Germany]. / Die Einbindung und Anwendung der Physiotherapie in der Hospiz- und Palliativversorgung : Ein Survey zur Praxis in Deutschland.

BACKGROUND: Palliative care is an approach that improves the quality of life of patients with incurable and progressive illnesses; therefore, in these situations physiotherapy can play an important role. AIM: This study was carried out to examine the integration and utilization of physiotherapy in palliative and hospice care services in Germany. METHODS: A cross-sectional survey including all palliative care units, specialized outpatient palliative care teams and hospices in Germany (n = 680) in 2013 was carried out. RESULTS: The response rate was 43.5 % (n = 296). Physiotherapy is predominantly applied in palliative care units (79 %) but rarely in hospices (38 %) and outpatient palliative care teams (30 %). A structured physiotherapeutic assessment is rarely carried out even on palliative care units (26 %). Positive effects of physiotherapy are especially described for symptoms, such as edema, pain, constipation and dyspnea. CONCLUSION: Despite its significant potential to relieve symptoms, physiotherapy is not systematically integrated into palliative care practice in Germany.

Corticostriatal Afferents Modulate Responsiveness to Psychostimulant Drugs and Drug-Associated Stimuli.

The medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) are both integral components of the corticobasal ganglia-thalamic circuitry that regulates addiction-related behaviors. However, the role of afferent inputs from mPFC to NAc in these behaviors is unclear. To address this, we used a Cre-recombinase-dependent viral vector approach to express G(i/o)-coupled DREADDs (designer receptors exclusively activated by designer drugs) selectively in mPFC neurons projecting to the NAc and examined the consequences of attenuating activity of these neurons on the induction of amphetamine sensitization and on drug taking and drug seeking during cocaine self-administration. Surprisingly, decreasing mPFC afferent activity to the NAc only transiently reduced locomotor sensitization and had no effect on drug taking during cocaine self-administration. However, inhibiting corticostriatal afferent activity during sensitization subsequently enhanced conditioned responding. In addition, this manipulation during drug self-administration resulted in slower rates of extinction and increased responding during drug prime-induced reinstatement-an effect that was normalized by inhibiting these corticostriatal afferents immediately before the drug prime. These results suggest that dampening cortical control over the NAc during drug exposure may lead to long-term changes in the ability of drugs and associated stimuli to drive behavior that has important implications for guiding treatments to prevent relapse.

Paternal-specific S-allele transmission in sweet cherry (Prunus avium L.): the potential for sexual selection.

Homomorphic self-incompatibility is a well-studied example of a physiological process that is thought to increase population diversity and reduce the expression of inbreeding depression. Whereas theoretical models predict the presence of a large number of S-haplotypes with equal frequencies at equilibrium, unequal allele frequencies have been repeatedly reported and attributed to sampling effects, population structure, demographic perturbation, sheltered deleterious mutations or selection pressure on linked genes. However, it is unclear to what extent unequal segregations are the results of gametophytic or sexual selection. Although these two forces are difficult to disentangle, testing S-alleles in the offspring of controlled crosses provides an opportunity to separate these two phenomena. In this work, segregation and transmission of S-alleles have been characterized in progenies of mixed donors and fully compatible pollinations under field conditions in Prunus avium. Seed set patterns and pollen performance have also been characterized. The results reveal paternal-specific distorted transmission of S-alleles in most of the crosses. Interestingly, S-allele segregation within any given paternal or maternal S-locus was random. Observations on pollen germination, pollen tube growth rate, pollen tube cohort size, seed set dynamics and transmission patterns strongly suggest post-pollination, prezygotic sexual selection, with male-male competition as the most likely mechanism. According to these results, post-pollination sexual selection takes precedence over frequency-dependent selection in explaining unequal S-haplotype frequencies.

The ins and outs of the striatum: role in drug addiction.

Addiction is a chronic relapsing disorder characterized by the loss of control over drug intake, high motivation to obtain the drug, and a persistent craving for the drug. Accumulating evidence implicates cellular and molecular alterations within cortico-basal ganglia-thalamic circuitry in the development and persistence of this disease. The striatum is a heterogeneous structure that sits at the interface of this circuit, receiving input from a variety of brain regions (e.g., prefrontal cortex, ventral tegmental area) to guide behavioral output, including motor planning, decision-making, motivation and reward. However, the vast interconnectivity of this circuit has made it difficult to isolate how individual projections and cellular subtypes within this circuit modulate each of the facets of addiction. Here, we review the use of new technologies, including optogenetics and DREADDs (Designer Receptors Exclusively Activated by Designer Drugs), in unraveling the role of the striatum in addiction. In particular, we focus on the role of striatal cell populations (i.e., direct and indirect pathway medium spiny neurons) and striatal dopaminergic and glutamatergic afferents in addiction-related plasticity and behaviors.

Predicting quality of deceased donor kidneys: the harvesting surgeon as a prognostic factor?

INTRODUCTION: The quality of donor organs is a crucial factor with regard to graft survival and function in kidney transplant recipients. The prognostic importance of surgeon-related factors during organ harvesting on graft quality has been almost unknown. Our aim was to find out whether surgical expertise as reflected by the time required for kidney retrieval influences graft survival. METHODS: In this retrospective study, we analyzed the records of 200 patients who received a cadaveric renal graft at our institution between 2000 and 2005. Graft survival and function were examined at discharge and after 1, 2, 3, and 5 years post-transplantation with the estimated glomerular filtration rate (GFR) using the Cockroft-Gault formula as a surrogate marker. We gathered the pertinent data on harvesting procedures from Eurotransplant donor reports. We correlated the length of time from cold organ perfusion to nephrectomy with graft survival. Statistical evaluation was performed using correlation analysis. RESULTS: There was no statistically significant correlation between the time the surgeon needed for kidney retrieval (starting from cold perfusion) and the outcome of transplantation. CONCLUSION: It would seem to be obvious that the longer a cadaveric donor kidney remains in the donor's body after cold perfusion, the worse the outcome will be. Our findings, however, did not prove this hypothesis even when looking at abdominal and combined abdominal and thoracic harvesting procedures separately.

Leucine 10 allelic variant in signal peptide of PCSK9 increases the LDL cholesterol-lowering effect of statins in patients with familial hypercholesterolaemia.

BACKGROUND AND AIMS: In the normal population, carriers of an additional leucine residue in a stretch of nine leucines in the signal peptide of PCSK9 (L10) have lower total (TC) and low-density lipoprotein cholesterol (LDL-C) than homozygotes for the wild-type allele (L9/L9). A similar effect was detected in familial hypercholesterolaemia (FH) patients with the p.C681X mutation of LDL-receptor (LDLR). We investigated the effect of L10 variant on basal lipid profile and response to statins in molecularly characterised FH patients. METHODS AND RESULTS: Plasma lipids were determined in 322 FH patients screened for the L9/L10/L11 polymorphism and in a subgroup of 54 patients carrying the same LDLR mutation (p.Q474HfsX63). Plasma lipids were also determined in 42 FH patients carrying the L10 variant and in a parallel group of 42 FH patients, L9/L9 homozygotes, matched for gender, age, type of LDLR gene mutation, as well as for type, dose and duration of statin treatment. In FH patients, no difference in the basal plasma TC and LDL-C levels was observed between carriers of L10 variant (L9/L10+L10/L10) and L9/L9 homozygotes. The same was true in FH patients carrying the p.Q474HfsX63 LDLR mutation. In the subgroups of statin-treated patients, the reduction of TC and LDL-C was greater in carriers of L10 (-34.0% and -42.5%, respectively) than in L9/L9 homozygotes (-27.5% and -34.3%, respectively) (P<0.001). CONCLUSION: The variant L10 of the leucine repeats in PCSK9 signal peptide is to be considered as a factor capable of modulating the lipid-lowering effects of statins in FH.

Expressing acid-sensing ion channel 3 in the brain alters acid-evoked currents and impairs fear conditioning.

Previous studies on mice with a disruption of the gene encoding acid-sensing ion channel 1a (ASIC1a) suggest that ASIC1a is required for normal fear behavior. To investigate the effects of altering the subunit composition of brain ASICs on behavior, we developed transgenic mice expressing ASIC3 via the pan-neuronal synapsin I promoter. These mice express ASIC3 in the brain, where the endogenous ASIC3 protein is not detected. We found that in ASIC3 transgenic mice, ASIC3 co-immunoprecipitated with the endogenous ASIC1a protein and distributed in the same subcellular brain fractions as ASIC1a. In addition, ASIC3 significantly increased the rate of desensitization of acid-evoked currents in cultured cortical neurons. Importantly, ASIC3 reduced Pavlovian fear conditioning to both context and auditory cues. These observations suggest that ASIC3 can heteromultimerize with ASIC1a in the brain and alter the biophysical properties of the endogenous channel complex. Moreover, these data suggest that ASIC subunit composition and channel desensitization may be critical determinants for ASIC-dependent behavior.

What do our patients understand about their trial participation? Assessing patients' understanding of their informed consent consultation about randomised clinical trials.

BACKGROUND: Ethically, informed consent regarding randomised controlled trials (RCTs) should be understandable to patients. The patients can then give free consent or decline to participate in a RCT. Little is known about what patients really understand in consultations about RCTs. METHODS: Cancer patients who were asked to participate in a randomised trial were surveyed using a semi-standardised interview developed by the authors. The interview addresses understanding, satisfaction and needs of the patients. The sample included eight patients who participated in a trial and two who declined. The data were analysed on the basis of Mayring's qualitative analysis. RESULTS: Patients' understanding of informed consent was less developed than anticipated, especially concerning key elements such as randomisation, content and procedure of RCTs. Analysing the result about satisfaction of the patients, most of the patients described their consultations as hectic and without advance notice. Health limitations due to cancer played a decisive role. However, most of the patients perceived their physician to be sympathetic. Analysing the needs of patients, they ask for a clear informed consent consultation with enough time and adequate advance notice. CONCLUSION: This study fills an important empirical research gap of what is ethically demanded in an RCT consultation and what is really understood by patients. The qualitative approach enabled us to obtain new results about cancer patients' understanding of informed consent, to clarify patients' needs and to develop new ideas to optimise the informed consent.

Characterization and mapping of non-S gametophytic self-compatibility in sweet cherry (Prunus avium L.).

Self-incompatibility in Prunus (Rosaceae) species, such as sweet cherry, is controlled by a multiallelic locus (S), in which two tightly linked genes, S-RNase and SFB (S haplotype-specific F-box), determine the specificity of the pollen and the style. Fertilization in these species occurs only if the S-specificities expressed in the pollen and the pistils are different. However, modifier genes have been proposed to be necessary for a full manifestation of the self-incompatibility response. 'Cristobalina' is a spontaneous self-compatible sweet cherry cultivar that originated in Eastern Spain. Previous studies with this genotype suggested that pollen modifier gene(s), not linked to the S-locus, may be the cause of self-incompatibility breakdown. In this work, an F(1) population from 'Cristobalina' that segregates for this trait was used to identify molecular markers linked to self-compatibility by bulked segregant analysis. One simple sequence repeat (SSR) locus (EMPaS02) was found to be linked to self-compatibility in this population at 3.2 cM. Two additional populations derived from 'Cristobalina' were used to confirm the linkage of this marker to self-compatibility. Since EMPaS02 has been mapped to the sweet cherry linkage group 3, other markers located on the same linkage group were analysed in these populations to confirm the location of the self-compatibility locus.

Self-compatibility in 'Cristobalina' sweet cherry is not associated with duplications or modified transcription levels of S-locus genes.

Sweet cherry shows S-RNase-based gametophytic self-incompatibility, which prevents self- and cross-fertilization between genetically related individuals. The specificity of the self-incompatible reaction is determined by two genes located in the S-locus. These encode a pistil-expressed ribonuclease (S-RNase) that inhibits self pollen tube growth, and a pollen-expressed F-box protein (SFB) that may be involved in the cytotoxicity of self-S-RNases. Initial genetic and pollination studies in a self-compatible sweet cherry cultivar, 'Cristobalina' (S (3) S (6)), showed that self-compatibility was caused by the loss of pollen function of both haplotypes (S (3) and S (6)). In this study, we further characterize self-compatibility in this genotype by molecular analysis of the S-locus. DNA blot analyses using S-RNase and SFB probes show no duplications of 'Cristobalina' S-locus genes or differences in the restriction patterns when compared with self-incompatible cultivars with the same S-genotype. Furthermore, reverse transcriptase-PCR of S-locus genes and quantitative reverse transcription-PCR of SFBs revealed no differences at the transcription level when compared with a self-incompatible genotype. The results of this study show that no differences at the S-locus can be correlated with self-compatibility, indicating the possible involvement of non-S-locus modifiers in self-incompatibility breakdown in this cultivar.

Preprocurement pancreas allocation suitability score does not correlate with long-term pancreas graft survival.

BACKGROUND: Within recent years, more marginal donors have been offered to Eurotransplant. To help identify suitable pancreas donors, the Eurotransplant Pancreas Advisory Committee introduced a donor score system (P-PASS). Little is known about the influence of P-PASS on long-term pancreas graft survival. METHODS: From June 1994 to September 2009, we performed 405 pancreas transplantations. In a retrospective study we analyzed P-PASS in 318 cases. Pancreas grafts from donors with P-PASS < 17 (n = 146) analyzed for graft and patient survival as well as for surgical complications were compared with donors of a PASS > or = 17 (n = 172). The mean follow-up was 7.2 +/- 4.3 years. RESULTS: Recipient characteristics were comparable in both groups. Mean P-PASS was 16.7 +/- 2.7 for both groups: 14.3 +/- 1.5 for P-PASS < 17 and 18.8 +/- 1.6 for P-PASS > or = 17. Pancreas graft survival rates for 1, 5, and 10 years were 85%, 77%, and 73% among P-PASS < 17 and 81%, 73%, and 64% among P-PASS > or = 17 groups (P = .12). There were 12 (8.2%) cases of venous thrombosis in the <17 group and 22 (12.7%) in the > or =17 group (P < .05). The relaparotomy rate was significant higher (38.7% vs 28.7%) and duration of hospital treatment longer (40.2 vs 32 days) in the P-PASS > or = 17 group (P < .05). There was no significant difference in patient or kidney graft survival between groups. CONCLUSIONS: The data demonstrated that utilization of pancreas grafts from donors with a P-PASS > or = 17 resulted in good overall outcomes and could expand the organ donor pool. There was no correlation between P-PASS and long-term patient or graft outcome. Complications requiring relaparotomy were more frequent among patients after transplantation from donors with higher P-PASS.

Modified release tacrolimus in de novo immunosuppression after simultaneous pancreas-kidney transplantation--a first single-center experience.

BACKGROUND: Modified release tacrolimus is a new, once-daily oral formulation of the established immunosuppressive agent tacrolimus. Little is known about de novo immunosuppression after simultaneous pancreas-kidney transplantation using modified release tacrolimus. METHODS: To test the feasibility of modified release tacrolimus in simultaneous pancreas-kidney transplantation (SPK), we conducted a prospective study of 14 consecutive transplants using modified release tacrolimus (Advagraf, ADV), mycophenolate mofetil, and low-dose corticosteroids as the initial immunosuppressive regimen. Patient and graft survival, the rates of acute rejection, graft function as well as ADV dosages, and trough levels (C(min)) were investigated after a mean follow-up time of 11.0 +/- 3.1 months. RESULTS: Overall patient, kidney, and pancreas graft survival were 100%, 100%, and 93%, respectively. One pancreas graft was lost owing to vascular graft thrombosis 2 days after transplantation. The incidence of rejection episodes at 11 months was 38%. ADV was well tolerated in the majority of patients. Only in 1 case tacrolimus (ADV) was stopped because of psychotic symptoms. In week 2 and 3 posttransplant, a significant adjustment in the ADV dosage was necessary to achieve sufficient tacrolimus trough levels. CONCLUSIONS: The results of this case series report demonstrate that patients after SPK can be safely treated with modified release tacrolimus. Further studies are needed to investigate pharmacokinetic profiles of modified release tacrolimus after SPK.

En bloc retroperitoneal pancreas-kidney transplantation with duodenoduodenostomy using pediatric organs.

BACKGROUND: Given the shortage of organ donors, there is a critical need to use all available pancreas grafts for transplantation. In the Eurotransplant region, only 26% of all offered pancreas grafts were transplanted during 2007. Pediatric donors are rarely used in pancreas transplantation. METHODS: In this case report, we describe a retroperitoneal en bloc pancreas-kidney transplantation (SPK) with systemic venous anastomosis and duodenoduodenostomy using grafts from an 11-year-old child. The bloc was transplanted in a 42-year-old type I diabetic patient with end-stage renal disease. The proximal end of the aortic graft was closed. Arterial anastomosis was performed end-to-end between right internal iliac artery and the aortic graft because of severe atherosclerosis. Donor portal vein and donor renal vein were anastomosed separately end-to-side to recipient inferior vena cava. Exocrine drainage was carried out with a side-to-side duodenoduodenostomy. Both grafts were in the retroperitoneal position. RESULTS: The pancreas graft functioned immediately, the kidney graft resumed function at 7 days posttransplantation. Graft function was excellent over a follow-up of 18 months. The patient had no episodes of acute rejection or graft dysfunction, no severe infections, and no additional morbidity from the modified technique of retroperitoneal pancreas transplantation using duodenoduodenostomy. CONCLUSIONS: This case indicates that pediatric donors could be used more frequently in pancreas transplantation for adult recipients and could increase the organ donor pool. En bloc SPK is a feasible and safe technique. Further studies are required to confirm the benefits of a retroperitoneal SPK using duodenoduodenostomy.

Quantification of seminal germ cells in azoospermia: correlations with testicular histology and TESE outcome.

In the treatment of male infertility by intra-cytoplasmic injection of spermatozoa (ICSI) extracted from testicular tissue (TESE), the high incidence of negative TESE outcome calls for non-invasive prognostic methods. Literature suggests that seminal haploid germ cell detection could be one. For this purpose, a multi-parametric stringent flow cytometric method was applied to 50 TESE patients for the quantification of ejaculated germ cells. Cells from 50 ejaculates were identified and quantified as spermatozoa (HC, highly condensed), round spermatids (1N), primary spermatocytes (SPC) (4N) or diploid cells (2N, including somatic and non-testicular cells) by their DNA and mitochondria staining and laser scatter characteristics, and compared with testicular biopsy histology and TESE outcome. Whereas 96% of patients displayed a diploid peak in the distribution histograms, the HC, 1N and 4N peaks were absent from the majority of samples. In 13 ejaculates, either a HC or 1N or 4N peak, or a combination of these, was discernible. Although seminal germ cell numbers bore no overall association with elongated spermatids (ES) in histology or spermatozoa retrieval in TESE outcome, 4N cells per ejaculate were correlated with the percentage of tubule sections showing SPC as the most advanced germ cells. The incidence of HC peaks was higher in patients showing some ES in histology or sperm retrieval than in the sperm-negative groups. In groups with suspected obstruction showing nearly full spermatogenesis and maximal sperm retrieval, there was no incidence of a HC peak. Germ cell peaks were associated with germ cell degeneration noted in testicular histology. In conclusion, seminal germ cells cannot provide good prognosis for TESE, although their presence could indicate the spermatogenic activity in the testis.

Long-term results after simultaneous pancreas-kidney transplantation using donors aged 45 years or older.

UNLABELLED: With the shortage of organ donors, there is a critical need to use all available pancreas grafts for transplantation. METHODS: From June 1994 to December 2006 we performed 340 pancreas transplantations (317 simultaneous pancreas-kidney 5 pancreas only, 18 pancreas after kidney) including 69 (20%) transplantations from donors aged 45 years or older. Pancreas grafts from older donors were analyzed for graft and patient survival as well as surgical complications, compared with results from younger donors. RESULTS: Recipient characteristics were comparable in both groups. The older donor group mean age was 47.8 years (+/-2.1) versus 27.9 years (+/-10.3) for the younger group. Cumulative patient survival was 96% versus 98% after 1, 82% versus 91% after 5 and 82% versus 88% after 10 years with 1-5- and 10-year kidney graft survivals of 82%, 72%, 57% versus 93%, 83%, 73%, respectively. Pancreas transplant survival after 1, 5, and 10 years were 69%, 60%, 45% in older and 88%, 76%, and 72% in younger donor cohorts. There were 14 (20%) cases of venous thrombosis in the older group and 25 (9%) in the younger group (P = .012). CONCLUSION: Our results demonstrated that utilization of pancreas grafts from donors over 45 years resulted in acceptable outcomes after simultaneous pancreas-kidney transplant and could expand the donor pool. Among the older donor group, patient survival was slightly lower than the younger group, whereas pancreas graft function was significantly inferior (P < .01). Since venous thrombosis was the main reason for pancreas graft loss in older group, anticoagulation is essential.

[Morbidity and mortality of kidney and pancreas transplantation. Analysis of 810 transplantations at one center]. / Morbidität und Letalität der Nieren- und Pankreastransplantation. Single-Center-Analyse von 810 Transplantationen.

BACKGROUND: Simultaneous pancreas kidney transplantation (SPK) is well established in the treatment of patients with type 1 diabetes and end-stage renal disease, but despite improved surgical techniques morbidity is still high. PATIENTS AND METHODS: A retrospective analysis of morbidity and mortality after first-time kidney transplantation (KTA: kidney transplant alone), pancreas transplantation (PTA: pancreas transplant alone), and SPK in a total of 810 patients was undertaken in our institution between January 1993 and December 2005. RESULTS: Of the total of 810 patients who had first-time transplantations, 524 underwent KTA, 4 underwent PTA, and 282 underwent SPK. Morbidity and mortality was significantly higher in SPK than in KTA (p < 0.05). Risk of early postoperative loss of a transplant organ was higher in SPK than in KTA, and there were more re-operations in SPK than in KTA (p < 0.05). More patients had infections infections after SPK than after KTA (p < 0.001). There were 23.0 % wound infections in SPK and 11.8 % in KTA (p < 0.05). Organ rejection occurred in 18.1 % of the patients after SPK and in 13.4 % after KTA (p = 0.07). At the time of discharge 95.0 % of KTA patients did no longer need dialysis treatment, compared with 97.1 % of SPK patients, of whom 88 % became insulin independent. One-year organ survival rate was 88 % in KTA patients and 89 % (kidney) and 86 % (pancreas) in SPK patients. CONCLUSION: Morbidity and mortality rates are still high after SPK. Excellent 1- and 5-year organ survival rates favor the use of SPK in type 1 diabetics associated with end-stage renal disease.

[Simultaneous pancreas-kidney transplantation. Influence of donor and recipient gender]. / Kombinierte Nieren-Pankreas-Transplantation. Einfluss des Spender- und Empfängergeschlechts.

BACKGROUND: Differences in graft survival due to gender have been reported after transplantation of the kidney, liver, and heart. However, little is known about the role of donor and recipient gender in simultaneous pancreas-kidney transplantation. METHODS: Single-centre analysis was performed of first simultaneous pancreas-kidney transplantations performed between 1994 and 2005 at the Bochum Transplant Center in Germany (n=218). RESULTS: Recipients of female donor organs exhibited acute organ rejections earlier and more frequently (P<0.05). Male recipients of organs from male donors had a lower risk of acute rejection than recipients of female donor organs (P<0.05). In addition to female donor gender, higher donor age and early kidney dysfunction were risk factors for perioperative rejection (P<0.05). Long-term kidney and pancreas function was best in male-donor-to-female-recipient transplants over the time periods of 7 and 3 years, respectively (P<0.05). Risk factors of long-term organ failure were: the need of revision laparotomy, organ rejection, and early postoperative organ dysfunction (P<0.05). CONCLUSION: This is the first report of graft function after simultaneous pancreas-kidney transplantation looking specifically at gender differences with respect to donor and recipient. There was an increased risk of organ rejection of female donor organs.