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Primary malignant tumors of the aorta are only rarely reported. We describe here our findings in a 55-year-old patient who was referred to us with progressive renal insufficiency. At angiography, right renal artery occlusion and high-grade stenosis of the left renal artery was found in this patient, who had undergone aortobiliacal reconstruction for acute Leriche syndrome 5 months previously. Histological evaluation of thrombotic material revealed an intraluminal malignant tumor to be the underlying cause. This diagnosis was then confirmed in samples harvested during angiography. CT scan showed an extension beginning 2 cm proximal to the celiac trunk. The patient was treated by thoracoabdominal resection of the aorta, including the paraaortal tissue, left side nephrectomy, and adrenalectomy. A thoracoabdominal aortic prosthesis was inserted up to the iliacal bifurcations and the celiac and superior mesenteric arteries reimplanted. Right nephrectomy followed 3 weeks later. The postoperative course was uneventful.

Recently, highly sensitive molecular assays to detect HCMV, HHV-6 and HHV-7 have been developed but their ability to detect patients at high risk for disease is unclear.The positive predictive values (PPV) of pp65-antigenemia, quantitative plasma DNA and pp67-mRNA for CMV-disease were prospectively compared in 82 transplant recipients (72 renal, 10 pancreas-kidney) without CMV-prophylaxis. In addition, the prevalence of HHV-6 and HHV-7 infection were assessed using qualitative PCR. The assays were performed weekly.Three patients (3,7%) developed CMV-disease and were effectively treated. They were positive in all three CMV-assays. The PPVs of pp65-Ag, DNA viral load and pp67-mRNA were 33%, 20% and 25% in CMV-positive and 100%, 67% and 50% in seronegative recipients. Sensitivity and negative predictive value were 100% for all assays. Using cut-offs, PPVs were 75% (pp65-Agor = 20/200.000 cells) and 100% (PCRor =30.000 copies/ml). Transfusion of2 packed red cells, rejection and non-functioning graft were risk factors for CMV Five patients and one patient were positive for HHV-6 and HHV-7 resp.; both were symptomless and did not have a HCMV infection.Therefore, pp65-antigenemia and plasma PCR with a cut-off could be useful for monitoring preemptive therapy.

The association between renal hyperparathyroidism (HPT) and differentiated thyroid carcinoma is discussed. To determine the prevalence and potential risk factors, we performed a retrospective analysis of our patients (1998–2004) and compared the data with the data from other surgical and autopsy studies. At our hospital, a total of 347 parathyroidectomies in 339 patients with renal HPT were performed. Most patients underwent preoperative ultrasound investigation of the thyroid gland and, if indicate, thyroid scintigraphy. Intraoperatively, both thyroid lobes were mobilized and palpated. Detected thyroid nodules were adequately resected and investigated histologically. A systematic analysis of the international literature was performed using the PubMed/MEDLINE system to identify publications on the prevalence of papillary thyroid carcinoma (PTC) in patients with renal HPT and in the overall population. Altogether, 133 patients (39.2%) underwent simultaneous thyroid surgery. The initial operation was hemithyroidectomy in 55 (16.2%), Dunhill operation in 36 (10.6%), unilateral subtotal resection in 17 (5.0%), bilateral subtotal resection in 5 (1.5%), and enucleation of a thyroid nodule in 18 (5.3%). A PTC was found in 8 of 339 patients (2.4%) and a follicular thyroid carcinoma in 1. Among 311 patients with primary cervical operation, 6 (1.9%) had a papillary thyroid carcinoma. All papillary tumors were classified as pT1 with a diameter of 1 to 12 mm; three were bifocal, and only one patient had positive lymph nodes. None of the analyzed factors showed a significant correlation with the occurrence of thyroid carcinoma. Depending on the screening method, the prevalence of occult PTC in European autopsy studies ranged from 5% to 9% and was markedly higher in almost all studies than in the present one. The prevalence of PTC in the present study makes an etiologic association between renal HPT and PTC unlikely. The clinical significance of these tumors remains unclear becauses all incidental tumors were small. However, if easily and safely feasible, relevant thyroid nodules should be removed during parathyroid surgery.

The aim of this study is to investigate reasons for the large reported differences in renal replacement therapy (RRT) incidence between Germany and England and Wales (EW).Age- and sex-standardized incidence rates were calculated at day 0, day 90, and day 180 by using registry data, and early RRT mortality was studied as an indicator of ascertainment differences. Nationally representative health survey data were analyzed to provide general population prevalence data for major chronic kidney disease risk factors: hypertension, diabetes, vascular disease, obesity, and smoking. Resource data were collected from routine sources and national surveys, and literature searches were performed to explore variation in chronic kidney disease prevalence, late referral, early start, and nondialytic therapy.The gap in RRT incidence between Germany and EW increased after adjusting for differences in early mortality. The standardized day-90 incidence rate ratio was 1.79 (193.0 per million of the adult population [pmap] in Germany and 107.5 pmap in EW) diabetes and vascular disease explained 79% of this difference. Diabetes, ischemic heart disease, and hypertension were 1.85-, 1.24-, and 1.18-fold more prevalent in Germany, whereas rates of hypertension control were 0.54-fold lower (20% versus 37% in England). Ischemic heart disease mortality rates were lower in Germany.Much of the difference in RRT incidence between Germany and EW is explained by a greater prevalence of diabetes, hypertension, and vascular disease in the German general population, particularly those older than 65 years, and lower competing mortality risk.

Introduction We collected data from kidney recipients with a functioning graft at German kidney transplant centers in order to analyze the efficacy of various cyclosporine (CsA)-based immunosuppressive strategies, the effects of different perioperative and maintenance regimens, and the impact of donor source on clinical outcome. Methods As part of the ongoing prospective Multinational Observational Study in Transplantation (MOST), data for both prospective and retrospective analysis were collected from kidney recipients over 18 years bearing a functioning graft that was transplanted at 21 German kidney transplant centers between 1987 and 2002. Results Data from 1223 renal graft recipients, including their CsA-based immunosuppressive regimens, were stratified as: 402 de novo patients (median 6.8 months posttransplant) and 821 patients on maintenance therapy (median 71 months posttransplant). Triple regimens with CsA + mycophenolate mofetil (MMF) + steroids (Ste) currently comprise the major perioperative immunosuppressive strategies in Germany (de novo 65%). IL-2 receptor antagonist (IL-2Ra) use is increasing (de novo 18%, maintenance 4%), while mono and dual regimen use de novo is declining (de novo 4%, maintenance 20%). Among 689 patients transplanted between 1987 and 2002 with outcome data, the mean incidence of acute rejection during the first posttransplant year was 21.6%. Rejection rates on initial therapy with CsA + MMF + Ste ± antibodies ( n = 517) averaged 17.8%. Conclusions Between 1987 and 2002, CsA-based immunosuppression combined with MMF and Ste became the most commonly used strategy for both initial and maintenance therapy after kidney transplantation in Germany, yielding the low acute rejection rates particularly when combined with IL-2Ra.

Most attempts to predict early kidney allograft loss are based on the patient and donor characteristics at baseline. We investigated how the early posttransplant creatinine course compares to baseline information in the prediction of kidney graft failure within the first 4 years after transplantation. Two approaches to create a prediction rule for early graft failure were evaluated. First, the whole data set was analysed using a decision-tree building software. The software, rpart, builds classification or regression models; the resulting models can be represented as binary trees. In the second approach, a Hill-Climbing algorithm was applied to define cut-off values for the median creatinine level and creatinine slope in the period between day 60 and 180 after transplantation. Of the 497 patients available for analysis, 52 (10.5%) experienced an early graft loss (graft loss within the first 4 years after transplantation). From the rpart algorithm, a single decision criterion emerged: Median creatinine value on days 60 to 180 higher than 3.1 mg/dL predicts early graft failure (accuracy 95.2% but sensitivity = 42.3%). In contrast, the Hill-Climbing algorithm delivered a cut-off of 1.8 mg/dL for the median creatinine level and a cut-off of 0.3 mg/dL per month for the creatinine slope (sensitivity = 69.5% and specificity 79.0%). Prediction rules based on median and slope of creatinine levels in the first half year after transplantation allow early identification of patients who are at risk of loosing their graft early after transplantation. These patients may benefit from therapeutic measures tailored for this high-risk setting.

The immune system undergoes a complex and continuous remodeling as the result of aging. These changes have a major impact on allorecognition and alloresponse. In addition, immunosuppression in the elderly is challenging as a consequence of an increased incidence of associated comorbidities and altered pharmacokinetics. Both advanced donor and recipient age should be considered independent risk factors for poor patient and graft survival rates, albeit acting in a synergistic manner. Consequently, modifications of the immune system because of aging may request an age-adapted allocation and immunosuppression in parallel with close patient monitoring. Interventions to selectively target changes associated with the senescence process seem to be promising therapeutic strategies to improve transplantation outcome. Here, we are going to review the immunologic changes associated with the aging process relevant for transplantation and their impact on immunosuppressive protocols, organ allocation policies, and transplantation outcome.

Objectives To analyze the predictive values of selective venous sampling (SVS) in our own experience and in a systematic meta-analysis of the international literature and to compare them with the results of noninvasive localization studies before reoperative parathyroid surgery. Data Sources Twenty-one consecutive patients with persistent or recurrent renal hyperparathyroidism underwent preoperative SVS and noninvasive imaging. These data were added to a systematic review of the literature on localization studies before reoperative surgery. The literature search included localization studies, recurrent hyperparathyroidism, and reoperation. Study Selection Prospective and retrospective studies that provided at least the true-positive rate of 1 procedure were included. Data from initial surgery, hyperfunctioning autografts, and case reports were excluded. Data Extraction Thirty-one publications reported on SVS (n = 22), technetium Tc 99m sestamibi scintigraphy (n = 17), thallium-technetium scintigraphy (n = 11), ultrasonography (n = 18), magnetic resonance imaging (n = 12), and computed tomography (n = 13). The overall analysis was performed by dividing the overall number of true- and false-positive results by the total number of patients. Data Synthesis Localization by SVS was correct in 20 of 21 patients. In 1 patient with 2 localizations, only 1 was predicted correctly. Therefore, the sensitivity of SVS was at least 90%, with no false-positive results. Overall true- and false-positive rates, respectively, in 31 studies were 71% and 9% for SVS, 69% and 7% for technetium Tc 99m sestamibi scintigraphy, 54% and 16% for magnetic resonance imaging, 55% and 15% for thallium-technetium scintigraphy, 50% and 18% for ultrasonography, and 45% and 14% for computed tomography. Conclusions With its high sensitivity, SVS is the gold standard in patients with persistent or recurrent renal hyperparathyroidism and negative results of noninvasive localization procedures. The noninvasive procedure of choice is now technetium Tc 99m sestamibi scintigraphy, with high sensitivity and a low rate of false-positive results.

A number of bacterial cytokine-inducing substances (CIS) such as lipopolysaccharides (LPS) and exotoxins have been detected in dialysate and may contribute to inflammation in hemodialysis patients. Short DNA fragments, oligodeoxynucleotides (ODN) of 6 to 20 nucleotides, are able to bind to Toll-like receptors and are stimulatory on immune cells. ODN induce natural killer cell activity and induce IFN-gamma, TNF-alpha, and IL-6 from mononuclear cells. The presence of ODN in dialysate samples and bacterial cultures was investigated. ODN were extracted from fluids by adsorption to reverse-phase columns. ODN were detected in 18 of 20 investigated dialysate samples, in eight of 10 reverse-osmosis water samples, and in all cultures from various bacterial strains. The presence of bacterial DNA in dialysate was confirmed by PCR specific for bacterial tRNA gene sequences. Saline for intravenous use contained 0.02 +/- 0.01 microg/ml DNA, dialysate samples contained 0.28 +/- 0.02 microg/ml, and Pseudomonas cultures contained 1.0 +/- 0.03 microg/ml DNA. ODN from bacterial cultures were only partially removed by ultrafiltration and were able to diffuse through regular high-flux dialyzer membranes. Synthetic cytosine-guanosine dinucleotide-containing ODN were able to induce IL-6 in human mononuclear cells. It is concluded that short bacterial-derived DNA fragments are present in clinically used fluids, e.g., dialysate. These fragments are of sufficient small size to pass through dialyzer membranes. Bacterial DNA fragments may be an overlooked factor contributing to inflammation in hemodialysis patients.

Introduction. The goal of the Eurotransplant renal allocation scheme is to provide every patient on the waiting list with a reasonably balanced opportunity for a donor offer. New initiatives were taken in order to maximize donor usage while maintaining a successful transplant outcome. Methods. Two Eurotransplant projects were launched in order to accommodate changes in donor and recipient profiles. A re-addressing of the non-heart-beating donor pool was undertaken and an allocation scheme in which organs from donors aged >65 are allocated to recipients aged >65 [the Eurotransplant Senior Programme (ESP)] was introduced. Results. Especially in The Netherlands, an enormous increase in the number of non-heart-beating donor kidneys has been observed, however with a pace-keeping reduction in heart-beating donors. The organization-wide implementation of the ESP has been successful. The 3 year graft survival rates for these age-matched transplants were as good as the human leukocyte antigen (HLA)-matched transplants (64 vs 67%) (P=0.4). Conclusion. Within the framework of sound research, the utmost flexibility and creativity is needed to keep or even increase the number of renal transplants when faced with a quantitatively stagnating but qualitatively deteriorating donor pool. Both the non-heart-beating donor protocol and the ESP have proven to be quite successful in achieving this goal without compromising the outcome for the individual end-stage renal disease patient.

Purpose Previous studies suggest that high levels of bilirubin exert cytotoxic, neurotoxic and encephalopathic effects that themselves may lead to further deterioration of liver function and multiorgan failure. Although extracorporeal BA is not a causal therapy, there are case reports of clinical benefits of BA. The present retrospective study investigated the clinical utility and effectiveness of BA in 23 patients with liver failure. Methods Twenty-three patients (61±11 years) with excessive hyperbilirubinemia (>25 mg/dL) after liver transplantation (n=7), partial liver resection (n=12) and others (n=4) were treated with BA (3.6 liters plasma per BA, BR350, Asahi) and followed for 45±8 days. Results A mean of 6.6 treatments (3–16) were performed per patient. On average, a single BA treatment reduced bilirubin-levels from 31±12 to 23.7±9 mg/dL (pConclusions BA is able to stabilize or decrease bilirubin levels in patients with liver failure. Our experience suggests that BA is a safe and promising short-term treatment option for patients with acute deterioration of hepatic function.

Cyclosporine (CsA) is a critical-dose drug for which a minor change in absorption can have important clinical implications. Generic formulations of CsA are becoming more widely available, but standard criteria for bioequivalence require only that a single study in healthy volunteers demonstrate that mean pharmacokinetic parameters fall within 80-125% of the mean values for Neoral, the reference formulation of CsA. However, CsA absorption is known to differ between healthy volunteers and transplant patients and between different types of transplant patients, such that standard bioequivalence testing may be inadequate to ensure interchangeability of CsA formulations in all patients. The limited available clinical evidence has shown that stable renal transplant patients receiving Neoral have a significant reduction in mean CsA trough level after transfer to the Cicloral formulation. Mean pharmacokinetic values have been reported as equivalent following transfer to Gengraft in one study, but mean CsA trough fell and mean serum creatinine rose significantly in a separate trial. The only clinical outcomes data available are from a retrospective study of de novo renal transplant patients, which reported a significantly higher incidence of biopsy-proven acute rejection in patents receiving Gengraf versus Neoral (39% versus 25%, P

In contrast to that in patients with primary hyperparathyroidism, the value of intraoperative intact parathyroid hormone (iPTH) measurement is still unclear in patients with renal hyperparathyroidism and was, therefore, evaluated in a large cohort of patients.Intraoperative iPTH measurement was performed in 153 patients with renal hyperparathyroidism (129 with terminal renal failure and 24 with functioning kidney graft). Subtotal and total parathyroidectomy were performed in 123 and 13 patients, respectively, during initial surgery. In patients with recurrent disease (17), the respective hyperfunctioning tissue was removed. Intraoperative blood samples were obtained by puncture of the internal jugular vein before preparation of the parathyroids (PTH0) and 15 min after parathyroidectomy (PTH15). iPTH was measured with the Elecsys 2010 system. Postoperative iPTH levels (PTH(post)) were determined at postoperative days 1 to 3 and at week 2. Patients were arbitrarily divided in four groups according to the postoperative iPTH values: 0-25 pg/ml (group 1), 26-65 pg/ml (group 2), 66-150 pg/ml (group 3) and more than 150 pg/ml (group 4).The mean PTH0 value was 869+/-57 pg/ml, which decreased to 167+/-15 pg/ml at PTH15. The mean relative PTH15 value was 21.6+/-1.7%. Postoperatively, iPTH decreased to 42+/-9 pg/ml. The postoperative iPTH value of the 129 patients with terminal renal failure was 25 pg/ml or less in 99 patients, 26-65 pg/ml in 11 patients, 66-150 pg/ml in eight patients and higher than 150 pg/ml in 11 patients. Two successive criteria of iPTH decrease were used: first, a PTH15 ofor =150 pg/ml or, second, a relative PTH15 ofor =30% less was used. Fifteen patients did not fulfil both criteria. In 13 of them (86.7%) iPTH(post) was higher than 65 pg (true failure to decline). Of 114 patients who fulfilled the criteria, 108 (94.7%) had normal postoperative iPTH values (true decline). Absolute PTH15 values of less than 150 pg/ml predicted normal postoperative iPTH levels in 77 of 78 patients.A PTH15 value of 150 pg/ml or less predicts operative success in patients with renal failure in 98.7% of cases, independently of the relative decay. In contrast, if the relative PTH15 is higher than 30%, high postoperative PTH values are predicted with a probability of 86.7%. Although there remain some borderline cases, intraoperative iPTH measurement is accurate and also can be useful in patients with renal hyperparathyroidism.

Patienten mit akutem Myokardinfarkt und einer Fibrinolysetherapie unterliegen auserhalb randomisierter Studien trotz verbesserter pharmakologischer und invasiver Strategien einer hospitalen Letalitat von uber 10%. Der prognostische Wert der hamostatischen Marker Thrombin-Antithrombin-III-Komplex (TAT), Prothrombinfragment F1.2 (F1.2) und Plasmin-α2-Antiplasmin-Komplex (PAP) fur das Erreichen des kombinierten primaren Endpunktes Tod, Re-Myokardinfarkt oder Notwendigkeit zur ungeplanten Revaskularisierung innerhalb von 30 Tagen wurde an 34 konsekutiven Patienten (62,4 ± 11,9 Jahre, 79% Manner) bei Aufnahme sowie nach 4, 8, 12 und 24 h mittels ELISA-Technik untersucht. Die multivariate Analyse hinsichtlich des kombinierten primaren Endpunktes wurde fur die Variablen Alter und Geschlecht kontrolliert. 15 Patienten erhielten eine Streptokinaselyse, 19 Patienten wurden mit rt-PA behandelt. Eine Reperfusion wurde bei 56% der Patienten erreicht. Die TAT-Spiegel der Ereignisgruppe betrugen im Median (25/75%-Perzentilen) nach 4 h 21,3 (9,5/41,0) μg/l und in der Gruppe ohne Ereignis 8,2 (5,2/ 15,6) μg/l (p = 0,012), zum Zeitpunkt 12 h 12,2 (7,1/40,3) μg/l und 6,0 (4,6/15,3) μg/l (p = 0,036). Fur die anderen TAT-Abnahmezeitpunkte sowie die F 1.2- und PAP-Werte wurden keine signifikanten Unterschiede festgestellt. Die Odds Ratio hinsichtlich des primaren Endpunktes betrug fur Patienten mit TAT-Werten uber 20,1 μg/l nach 4 h 7,16 (95%-Konfidenzintervall (KI): 1,25–41,16; p = 0,027) sowie mit TAT-Spiegeln uber 6,0 μg/l nach 12 h 18,15 (95-KI: 1,88– 175,47; p = 0,012). Die fruhe Bestimmung erhohter TAT-Werte nach 4 und 12 h bei Patienten mit akutem Myokardinfarkt und Fibrinolysetherapie ermoglicht die Identifizierung von Hochrisikopatienten fur den weiteren klinischen Verlauf. Diese Patienten profitieren moglicherweise von einer aggressiveren antithrombotischen Therapie und sollten einer fruhen Koronarangiographie zugefuhrt werden.

In March 1996, a new allocation point system for cadaver kidneys, the Eurotransplant (ET) Kidney Allocation System (KAS), was introduced in ET, the first multinational organ exchange organization. The aims of ETKAS were to reduce average and maximum waiting time, to allow patients with rare human leukocyte antigen (HLA) phenotypes or combinations to receive an "optimal" offer, to keep the exchange rates between the participating countries balanced, and finally to keep optimal graft survival, by means of HLA matching. Elderly patients and highly sensitized patients profit in addition from special programs, the ET Senior Program and the Acceptable Mismatch Program, respectively. All kidneys are offered to the pool and are allocated according to the degree of HLA matching, mismatch probability, waiting time, distance from the donor center, and balance between the countries participating in ET. A summary of 6 years' experience with the ETKAS is presented in this article.

Clinically, an increasing number of older recipients are listed for transplantation. We examined recipient age-associated alterations of the immune response and their effects on graft function.Three- and 18-month-old Lewis (LEW) rats received kidneys from 3- and 18-month-old Fischer 344 (F344) rats (1.5 mg/kg/d cyclosporine A for 10 days; n=6/group) and were observed for 180 days. In additional groups, double kidney transplantations were performed to determine the impact of nephron mass and recipient age on graft outcome.All young recipients but only 66% of old recipients survived the observation period. Increasing recipient age resulted in a significant decrease in renal allograft function (P0.001), more advanced morphologic evidence of chronic allograft damage (P0.001), and greater cellular infiltration (P0.05) and major histocompatibility complex expression (P0.01) within grafts. Additional in vitro studies examined age-related changes in the cellular immune response by enzyme-linked immunosorbent assay, fluorescence-activated cell sorter analysis, and alloreactive enzyme-linked immunospot: splenocytes from old LEW rats produced significantly more interleukin (IL)-2 (P0.0001), IL-4 (P0.05), interferon (IFN)-gamma (P0.0001), and tumor necrosis factor-alpha (P0.05). IFN-gamma-producing memory-type T cells were significantly elevated in older rats (P0.0001). Moreover, they revealed significantly more alloreactive T cells directed against F344 (146 +/- 64.2 and 512 +/- 277/10(6) T cells; P0.05). Double renal allografts from young donors into old recipients confirmed an independent effect of recipient age on the acceleration of chronic graft deterioration.The enhanced cellular immune responsiveness in elderly recipients was associated with advanced chronic graft injury. Clinically, older recipients may need a modified immunosuppression.

The diagnosis of phaeochromocytoma may be delayed due to episodic and short-lasting forms of a phaeochromocytoma crisis and the otherwise presence of rather unspecific symptoms. We present an unusual case of a 28-year-old female with a history of thyroidectomy for familial medullary thyroid carcinoma who repeatedly presented to hospital with a normal heart rate and normal blood pressure after an anxiety attack, intermittent palpitations and hyperthermia. Two hours after admission to hospital for diagnostic clarification the patient was found in asystole and a successful resuscitation was performed. Massive pulmonary oedema, rhabdomyolysis and acute renal failure characterised the further clinical course. An adult respiratory distress syndrome developed. On the third day after admission a hypertensive crisis led to the diagnosis of phaeochromocytoma and multiple endocrine neoplasia (MEN) type IIA. After continuous haemofiltration, renal function was restored and the patient underwent removal of a tumour of...

There is increasing need to make accurate early diagnosis and rule out acute coronary syndromes (ACS) in patients who present to the emergency department (ED) with chest pain. Accurate diagnosis will reduce the number of inappropriate management decisions, and the number of malpractice lawsuits relating to these decisions. Early diagnosis will facilitate faster entry to treatment protocols such as anticoagulant and antiplatelet therapies resulting in reduced morbidity, mortality, and hospital length of stay. Rapid rule-out of ischemia will facilitate discharge of patients at no or low risk for cardiovascular complications and alleviate the diminishing resources available to EDs. Although the presence of ST-segment depressions on the electrocardiogram (ECG) is evidence of ischemia, the ECG is nondiagnostic in the majority of unstable angina patients. Radionuclide imaging is a sensitive marker for ischemia, but is expensive and requires a high degree of technical expertise.

Allocation of kidneys from donors older than 64 years to recipients older than 64 years was started in 1999 to improve use of older donor kidneys. Kidneys are allocated locally without HLA-matching to keep cold ischemia short. We compared survival and rejection rates in elderly patients allocated in the old-for-old program (ESP) to patients aged 60 years and older based on HLA-matching, expected ischemia and waiting time (ETKAS). The 69 ESP patients were older (67.9 +/- 2.5 vs. 63.9 +/- 2.9 years), had older donors (71.2 +/- 3.9 vs. 44.6 +/- 14.5 years) and more HLA-mismatches (4.2 +/- 1.2 vs. 1.6 +/- 1.7) than the 71 ETKAS patients, while ischemia was shorter (7.8 +/- 3.4 vs. 14.2 +/- 5.5 h). ESP and ETKAS had similar graft (1-year: 83.6% vs. 86.9%) and patient survival (85.2% vs. 89.5%). With the introduction of ESP, use of older recipients and donors rose from less than 2% to 16% and 11%, respectively. Incidence of acute rejections was significantly higher in the ESP group (1 year: 43.2% vs. 27.4%) and significantly correlated with the degree of HLA-matching. Introduction of old-for-old allocation allows successful expansion of the donor and recipient pool without affecting patient and graft survival. HLA-matching should not be ignored, as the risk of acute rejection in elderly patients is substantial.

Since the sixties kidneys have been transplanted successfully at the 2 predecessors of today's transplant center at the Charité. So far, 1,290 kidneys were transplanted resulting in 89.8% overall graft survival at one year and 78.6% at 5 years. Several factors were associated with these results. Ischemia times were very short (11.9 +/- 7.3 hours). Patients with diabetic nephropathy were rarely transplanted without combined pancreas transplantation. Combined with a pancreas transplantation, kidney grafts fared even better than those of non-diabetic patients. The share of living donation is still rising and is associated with a better outcome than cadaveric grafts. In contrast, the effect of HLA mismatches was not very pronounced. Zero- and one-mismatch transplantations had a clear benefit over those with 2-3 mismatches, but higher numbers of mismatches did not lead to worse results. To expand the donor pool with kidneys from old donors (64 years) we participate in the Eurotransplant Senior Program (ESP) where these kidneys are allocated locally to recipients aged 65 years and older without HLA matching. The ischemia times for ESP kidneys were shorter (7.3 +/- 3.0 hours) but transplants were less well matched (4.2 +/- 2.1 mismatches). Graft survival was not different from controls aged 60 years and older who received a kidney from a donor under age 65. The ESP patients do not require prolonged hospitalization for transplantation (30.6 +/- 14.6 days versus 35.3 +/- 26.0 days in patients below 60 years). With the introduction of the ESP the number of transplantations in recipients aged 60 years and above have risen considerably.

AIMS: The increasing use of high-flux membranes for hemodialysis has raised concerns that patients dialyzed with these membranes may be at higher risk of being exposed to cytokine-inducing bacterial substances in the dialysate than patients dialyzed with low-flux membranes. We investigated the permeability of various high-flux membranes for both purified E. coli lipopolysaccharide (LPS) as well as for LPS derived from Stenotrophomonas (Sten.) maltophilia. MATERIALS AND METHODS: An in vitro dialysis circuit with saline in the blood compartment of 3 dialyzers containing different membranes (polysulfone, helixone and Diapes) was employed. The dialysate was challenged with increasing doses of sterile filtrates derived from Sten. maltophilia cultures or with purified LPS from E. coli. Samples from the blood compartment were tested for cytokine induction (IL-1beta, IL-6 and TNF) in mononuclear cells as well as for LPS by limulus amebocyte lysate test (LAL). RESULTS: IL-6 induction above sterile controls (< 0.02 ng/ml IL-6) was observed by samples from the blood side of DIAPES dialyzers (1.2 +/- 0.7 ng/ml IL-6) after challenging the dialysate with 4.1 +/- 3.6 U/ml E. coli LPS (9.9 +/- 4.5 ng/ml IL-6). In contrast, at the same challenge dose no significant IL-6 induction above sterile controls was observed by blood side samples of polysulfone (0.15 +/- 0.07 ng/ml) and helixone (0.09 +/- 0.05 ng/ml) dialyzers. Increasing the amount of E. coli LPS in the dialysate further augmented IL-6 induction by blood side samples of Diapes but not of polysulfone and helixone dialyzers. Similar results were obtained for IL-1beta and TNF. After challenging the dialysate with E. coli LPS as well as with cultures of Sten. maltophilia, significantly more LAL reactivity was observed in the blood compartment of Diapes compared to polysulfone and helixone. CONCLUSIONS: There are considerable differences between high-flux membranes regarding their permeability for cytokine-inducing substances from E. coli as well as for LPS derived from E. coli and Sten. maltophilia. Dialyzers that leak CIS under aqueous conditions in vivo should not be used unless the dialysate has passed through an ultrafilter.

Troponins I and T represent the current biomarker standard for diagnosis of myocardial infarction. Even small increases of cardiac troponins have prognostic implications, but not all patients at risk are correctly classified, particularly at admission. We identified elevated whole-blood choline as a promising marker and performed a prospective study of 327 patients with a suspected acute coronary syndrome that focused on the analysis of troponin-negative patients. Diagnostic classification of patients and the definition of troponin cutoffs were performed according to the new European Society of Cardiology/American College of Cardiology criteria. Blood was sampled serially and choline was measured using high-performance liquid chromatography mass spectrometry in whole blood. Patients were followed for 30 days. In patients with negative troponin I test results at admission (n = 250), choline was a predictor of cardiac death and nonfatal cardiac arrest (hazard ratio 6.0, p = 0.003), life-threatening arrhythmias (hazard ratio 3.75, p = 0.004), heart failure (hazard ratio 2.87, p = 0.002), and coronary angioplasty (hazard ratio 2.57, p = 0.001). In multivariate analysis of troponin-negative patients, choline was the strongest predictor of cardiac death or arrest (odds ratio 6.05, p = 0.01). Choline was not a marker for myocardial necrosis but indicated high-risk unstable angina in patients without acute myocardial infarction (sensitivity 86.4%, specificity 86.2%). Thus, an increased concentration of choline at hospital admission is a predictor of adverse cardiac events in patients with suspected acute coronary syndromes. Whole blood choline may be useful for early risk stratification of these patients, particularly if troponin results are negative on admission.

A possible diagnostic role of procalcitonin (PCT) as a marker for ventilator associated pneumonia (VAP) in patients with an already triggered acute phase response after successful cardiopulmonary resuscitation (CPR) was investigated. In 28 patients with return of spontaneous circulation (ROSC) after out of hospital CPR, measurements of PCT, C-reactive protein (CrP), white blood cell count (WBC) and body temperature were compared with the clinical course of the patients. In this setting, PCT was the only marker to differentiate between patients with and without VAP (median value on day 1, 6.0 vs. 0.5 ng/ml; P

Bioincompatibility of peritoneal dialysis fluids (PDF) has been linked to the presence of glucose degradation products (GDP). Previous experiments have shown that short-term exposure to several GDP at concentrations found in commercially available PDF had no significant effect on human peritoneal mesothelial cells (HPMC). During continuous ambulatory peritoneal dialysis, however, cells are continually exposed to GDP for extended periods of time. Thus, the impact of GDP on HPMC during long-term exposure was assessed. HPMC were cultured for up to 36 d in the presence of 6 identified GDP (acetaldehyde, formaldehyde, furaldehyde, glyoxal, methylglyoxal, and 5-HMF) at doses that reflect their concentrations in conventional PDF. At regular time intervals, the ability of HPMC to secrete cytokines (interleukin-6 [IL-6]) and extracellular matrix molecules (fibronectin) was evaluated. In addition, cell viability, morphology, and proliferative potential were assessed. Exposure to GDP resulted in a significant reduction in mesothelial IL-6 and fibronectin release. Approximately 80% of this decrease occurred during the first 12 d of the exposure and was paralleled by a gradual loss of cell viability and development of morphologic alterations. After 36 d of exposure, the number of cells in GDP-treated cultures was reduced by nearly 60%. However, GDP-treated cells were able to resume normal proliferation when transferred to a normal GDP-free medium. HPMC viability and function may be impaired during long-term exposure to clinically relevant concentrations of GDP, which suggests a potential role of GDP in the pathogenesis of peritoneal membrane dysfunction during chronic peritoneal dialysis.

While some studies clearly demonstrated transfer of cytokine-inducing substances (CIS) through dialysis membranes, other authors were unable to reproduce such a transfer. This inconsistency may have been caused by marked differences in experimental design. We performed a systematic evaluation of cytokine induction in whole blood and from separated peripheral blood mononuclear cells (PBMC) using either purified lipopolysaccharide (LPS) or culture supernatants from various bacterial strains. An in vitro hemodialysis circuit with whole blood in the blood compartment was employed; the dialysate was contaminated with sterile filtrates from Pseudomonas aeruginosa cultures. Addition of plasma samples from the blood side to PBMC readily induced interleukin (IL)-1β and IL-6 after contamination of the dialysate, while the same samples failed to induce cytokine production in whole blood. In experiments using direct incubation, purified P. aeruginosa LPS induced more IL-1β and IL-6 in whole blood compared to PBMC. In contrast, bacterial filtrates from Escherichia coli, Enterobacter cloacae and especially P. aeruginosa induced significantly less cytokines in whole blood compared to PBMC. Addition of erythrocytes but not granulocytes decreased cytokine induction by bacterial filtrates as well as by LPS, probably by adsorption of these substances. The addition of 30% plasma increased cytokine induction by LPS but decreased cytokine induction by P. aeruginosas filtrates. Our results suggest that cellular and plasmatic components of whole blood interact with bacterial CIS altering their pyrogenic activity. The detection of CIS depends on the test system used; whole blood cultures are not as sensitive for the detection of CIS from bacterial filtrates as PBMC cultures.

The aims of this study were to evaluate whether platelets are activated during strenuous exercise in healthy athletes. Also, to determine the impact of plasmin and thrombin activity and catecholamine release. Previous studies have shown activation of the hemostatic system after competitive exercise, but platelet activation was thought to be absent in trained athletes. The impact of thrombin and other potent platelet activators is still a matter for debate. We examined 30 healthy triathletes during a triathlon competition. Flow cytometric detection of CD62p (P-selectin) was used to measure in vivo activation of platelets. Platelet-leukocyte aggregates were also determined. Thrombin concentration was assessed by the thrombin-antithrombin III complex (TAT) and the fibrinolytic state was characterised by the plasmin-alpha2-antiplasmin complex (PAP). Catecholamines were measured by means of high-pressure liquid chromatography. CD62p rose from baseline (2.3%) to 3.4% and was still elevated after 2 hours (3.1%, p = 0.0133). Platelet-leukocyte aggregates were elevated 30 min after exercise (4.3 % vs 3.6%) and decreased significantly after 60 min (2.9 %, p = 0.008). TAT increased from 3.9 microg/l to 8.3 microg/l after competition and to 5.4 microg/l 2 hours later (p < 0.001). PAP increased 10-fold from 350 microg/l to 3,267 microg/l after the triathlon and was still elevated after 2 hours (1,074 microg/l, p

Background : International guidelines have been established for the use of cardiac markers in the early diagnosis and risk assessment of patients with acute coronary syndromes. Methods: A single center, prospective observational study was conducted in a tertiary care university hospital on 200 consecutive patients with suspected acute myocardial infarction (AMI). Blood was drawn on admission and after 2, 4, 8, 12 and 24 h for the measurement of CK-MB/CK activity, myoglobin, CK-MB mass and troponin I. A 6-week follow-up was undertaken for the combined end point of acute coronary syndrome and death. Results: Myoglobin showed an early diagnostic sensitivity of 0.65 on admission, 0.90 after 2 h and 0.92 after 4 h compared with 0.46, 0.74 and 0.88 for CK-MB/CK activity. The combination of myoglobin and cTnI increased the diagnostic value compared with myoglobin alone on admission, 2 and 4 h later. In multivariate analysis, cTnI and CK-MB/CK mass, but not myoglobin and CK-MB/CK activity, were shown to be independent predictors on the 6-week follow-up. Conclusions : Repetitive myoglobin measurements within 4 h of admission, combined with at least one early troponin test, was shown to be the strategy of choice in early AMI diagnosis and prognosis assessment.

IL-17 is a newly discovered cytokine implicated in the regulation of hemopoiesis and inflammation. Because IL-17 production is restricted to activated T lymphocytes, the effects exerted by IL-17 may help one to understand the contribution of T cells to the inflammatory response. We investigated the role of IL-17 in leukocyte recruitment into the peritoneal cavity. Leukocyte infiltration in vivo was assessed in BALB/Cj mice. Effects of IL-17 on chemokine generation in vitro were examined in human peritoneal mesothelial cells (HPMC). Administration of IL-17 i.p. resulted in a selective recruitment of neutrophils into the peritoneum and increased levels of KC chemokine (murine homologue of human growth-related oncogene α (GROα). Pretreatment with anti-KC Ab significantly reduced the IL-17-driven neutrophil accumulation. Primary cultures of HPMC expressed IL-17 receptor mRNA. Exposure of HPMC to IL-17 led to a dose- and time-dependent induction of GROα mRNA and protein. Combination of IL-17 together with TNF-α resulted in an increased stability of GROα mRNA and synergistic release of GROα protein. Anti-IL-17 Ab blocked the effects of IL-17 in vitro and in vivo. IL-17 is capable of selectively recruiting neutrophils into the peritoneal cavity via the release of neutrophil-specific chemokines from the peritoneal mesothelium.

The hepatorenal syndrome (HRS) is characterized by renal vasoconstriction leading to deterioration of renal function in patients with liver disease. A possible role of endothelin-1 (ET-1) in the pathogenesis of HRS has been suggested, but a correlation between ET-1 plasma levels and the development of HRS as well as the recovery from HRS following OLT has not been shown yet. We performed longitudinal measurements of ET-1 plasma levels in four groups of patients, 5 patients with HRS before and after orthotopic liver transplantation (OLT), 10 patients without HRS undergoing OLT, 20 patients with chronic renal failure but without liver disease, and 12 healthy controls. Before OLT, plasma levels of ET-1 were higher in patients with HRS (19.5 +/- 8.6 ng/l, P < 0.001; n = 5) compared to patients without HRS (4.9 +/- 1.1 ng/l; n = 10), normals (1.2 +/- 0.18 ng/l; n = 12), and patients with chronic renal failure (2.4 +/- 0.4 ng/l; n = 20). Patients with HRS compared to patients without HRS had higher levels for creatinine (2.42 +/- 0.6 vs. 0.89 +/- 0.05 mg/dl, P < 0.05), creatinine clearance (107 +/- 9 ml/min vs. 44.6 +/- 5.5 ml/ min, P < 0.001), and bilirubin (11.4 +/- 3.8 vs. 3.7 +/- 1 mg/dl, P < 0.05) before OLT. Within one week after OLT, there was a rapid decrease in ET-1 levels in patients with HRS while creatinine and bilirubin levels decreased slower. Regression analysis revealed a weak correlation between serum creatinine and ET-1 (r = 0.192, P = 0.04) and a significant correlation between serum bilirubin and ET-1 (r = 0.395, P < 0.001). The means of the ET-1 levels decreases rapidly with improvement of liver function after OLT. Levels of ET-1 correlate with excretory liver function assessed by bilirubin. The fall in ET-1 levels preceding improvement of renal function further strengthens the concept of ET-1 being a causative factor in HRS.

Abstract —The tyrosine kinase receptor Tie2 (also known as Tek) plays an important role in the development of the embryonic vasculature and persists in adult endothelial cells (ECs). Tie2 was shown to be upregulated in tumors and skin wounds, and its ligands angiopoietin-1 and -2, although they are not directly mitogenic, modulate neovascularization. To gain further insight into the regulation of Tie2, we have studied the effect of hypoxia and inflammatory cytokines, two conditions frequently associated with neoangiogenic processes, on Tie2 expression in human ECs. Exposure to 1% O 2 led to a time-dependent significant rise of Tie2 protein levels in human coronary microvascular endothelial cells (HCMECs) and dermal microvascular ECs (HMEC-1) (3.2- and 2.5-fold within 24 hours), which was reversible after reoxygenation, and induced a less marked increase in human umbilical vein ECs (HUVECs; 1.7-fold). Hypoxia-conditioned medium and d -deoxyglucose did not change Tie2 expression, but desferrioxamine and cobalt, which are known to mimic hypoxia-sensing mechanisms, induced Tie2 at ambient oxygen tensions. Tumor necrosis factor-α induced Tie2 in a time- and dose-dependent fashion in all 3 EC types (HUVEC, 2.3-fold; HMEC-1, 2.8-fold; and HCMEC, 3.0-fold; 10 ng/mL, 24 hours). Enhanced expression was also found after exposure to interleukin-1β (1 ng/mL). Changes in Tie2 protein levels were paralleled by changes in mRNA expression. In accordance with these in vitro findings, immunohistochemistry revealed focal upregulation of Tie2 in capillaries at the border of infarcted human and rat myocardium. In conclusion, the data show that hypoxia and inflammatory cytokines upregulate Tie2, which may contribute to the angiogenic response in ischemic tissues.

Objective: Inflammation and hypoxia are frequently associated, but their interaction is poorly understood. In vitro studies have shown that hypoxia stimulates the genes of acute phase proteins (APP) and cytokines known to induce APP. We decided to determine kinetics and potential determinants of an acute phase response after cardiac arrest and to assess whether isolated moderate hypoxia can induce APP in humans in vivo. Design: Prospective, observational study in patients and human experiment. Setting: Tertiary care university hospital. Patients and participants: 22 patients after primarily successful cardiopulmonary resuscitation (CPR) and 7 healthy volunteers. Interventions: None in patients; exposure of volunteers to simulated altitude (460 torr/6 h). Results: Following CPR, type-1 APP (C-reactive protein, α1-acidglycoprotein, serum amyloid A) and type-2 APP (haptoglobin, α1-antitrypsin) increased consistently within 1–2 days and the ’negative' APP transferrin was downregulated. This APP response occurred irrespective of the cause of arrest, the estimated time of anoxia, clinical course or patient outcome and was not different in patients with and without infectious complications. Exposure of healthy volunteers to less severe but more prolonged hypoxia did not induce APP, although a time dependent increase of serum erythropoietin (EPO) was measurable under these conditions, indicating the activation of oxygen dependent gene expression. Conclusions: (i) A marked acute phase response occurs regularly after cardiac arrest, but within the complexity of this situation the severity of hypoxia is not a predominant determinant of this response. (ii) Despite in vitro evidence for similarities in the oxygen dependent regulation of APP and EPO production, the oxygen sensitivity of these proteins in vivo is different. (iii) Measurements of APP are not revealing regarding infectious complications in the early phase after CPR.

To determine incidence, severity, characteristics, and causes of anemia and transfusion requirements in medical intensive care patients.Open prospective clinical study in a 24-bed medical intensive care unit in a tertiary-care university hospital.Patients (N = 96) treated in the intensive care unit for3 days.None.Parameters of erythropoiesis and red blood cell metabolism, including hemoglobin, reticulocyte counts, serum iron, transferrin, ferritin, haptoglobin, vitamin B12, folic acid, and erythropoietin concentrations were determined serially. Diagnostic blood loss and red blood cell transfusions were recorded, and the total blood loss was estimated from changes in hemoglobin concentrations and the amount of hemoglobin transfused.The median hemoglobin concentration was 12.1 g/dL at admission and 11.2 g/dL at the end of the intensive care unit stay. A total of 74 patients (77%) suffered from anemia and received 257 red blood cell units, approximately half of which were given within the first 5 days. Three patients who received 19 red blood cell units were admitted with acute gastrointestinal bleeding, but in the remainder, a median total blood loss of 128 mL/d was not (n = 60) or not solely (n = 11) a result of overt bleeding. Diagnostic blood loss declined from a median of 41 mL on day 1 to20 mL after 3 wks and contributed 17% (median) to total blood loss. Acute renal failure, fatal outcome, and simplified acute physiology score38 on admission were associated with a 5.8-, 7.0-, and 2.8-fold increase in total blood loss. Reticulocyte counts and erythropoietin concentrations were inappropriately low for the degree of anemia, and plasma transferrin saturation was mostly20%.Anemia is frequent and results in a high requirement for red blood cell transfusions in the medical intensive care setting. A major proportion of blood loss is not caused by overt bleeding or diagnostic blood sampling but, rather, may result from various other reasons, e.g., occult gastrointestinal bleeding and renal replacement therapy. The erythropoietic response to anemia is blunted, probably as a consequence of an inappropriate increase in erythropoietin production and diminished iron availability. (Crit Care Med 1999; 27:2630-2639)

Leukocyte infiltration plays a major role in ischemia-associated organ dysfunction and damage. A crucial step for extravasation of white blood cells is binding of leukocyte β-integrins to endothelial adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). To test for direct effects of oxygen on this process we studied ICAM-1 and VCAM-1 expression in human dermal microvascular and umbilical vein endothelial cells (EC) exposed to different oxygen tensions in the absence or presence of tumor necrosis factor-α (TNF-α). Hypoxia (95% N2-5% CO2) resulted in a downregulation of basal but not TNF-α-induced expression of ICAM-1 and VCAM-1. Subsequent rises in oxygen (21, 40, or 95% O2) led to marked increase of ICAM-1 and VCAM-1 cell surface and mRNA expression in both EC types, which after 16 h amounted to about one-third to one-half of maximal TNF-α-induced expression. This increase was greatest after 0.5-h hypoxia and was blunted with prolonged hypoxic preincubation. Exposure of cells preincubated under “normoxic” (21% O2) conditions to hyperoxia (40 or 95% O2) also enhanced expression of both adhesion molecules, but the increase was lower than in cells preexposed to hypoxia. The nitric oxide synthesis inhibitor NG-nitro-l-arginine methyl ester (l-NAME) enhanced ICAM-1 and VCAM-1 expression under basal and hypoxic conditions, but in the presence of l-NAME, levels in reoxygenated cells were not higher than basal levels. Moreover, the oxygen-induced rise could be mimicked by addition of H2O2to normoxic cells, and the oxygen-induced expression of VCAM-1 but not of ICAM-1 was inhibited by addition of the free radical scavengers superoxide dismutase, N-acetyl-l-cysteine, and pyrrolidinedithiocarbamate. These data indicate that an increase in oxygen availability stimulates ICAM-1 and VCAM-1 expression on micro- and macrovascular EC, which may contribute to adhesion and transmigration of different leukocyte populations in ischemia-reperfusion injuries.

Emphysematous pyelonephritis is a rare, often severe infection of one or both kidneys that is most often caused by bacterial infection. Surgical intervention is often necessary. We describe a case of a diabetic patient with bilateral emphysematous pyelonephritis caused by Candida infection that was treated conservatively. Renal function recovered almost completely in spite of giving a potential nephrotoxic drug for 6 weeks.

A case of panarteritis with purpura fulminans, mononeuritis multiplex, gastrointestinal manifestation and presumably cardiac involvement in a previously healthy 22-year-old man with a history of drug abuse including cocaine, cannabinoids and methamphetamines is described. Histopathological examination of the gut led to the diagnosis of panarteritis without immune deposits. Antineutrophil antibodies were negative. Besides the drugs, no other possible cause of vasculitis was found. The patient recovered completely after 1 year. Drug abuse is a thus possible cause of severe extracerebral disabling vasculitis.

Wahrend sich die Transplantation des gesamten Pankreas mit anhangendem Duodenalsegment gegenuber der Pankreassegmenttransplantation weltweit durchgesetzt hat, wird die Drainagetechnik des exokrinen Pankreas noch kontrovers diskutiert. Die vesikale Drainage des exokrinen Pankreas geht einher mit chronischem Bikarbonatverlust, moglicher Dehydrierung, Cystitis und Harnwegsinfekten und erfordert in bis zu 32% der Falle eine Konversion zu enteraler Drainage [6]. Demgegenuber ist die immunologische Uberwachungsmoglichkeit des enteral drainierten Pankreastransplantats durch fehlende Urinamylaseausscheidung eingeschrankt.

Simultaneous pancreas kidney transplantation is currently the state of the art therapy for patients with type 1 diabetes mellitus and diabetic nephropathy. Up to 30% of patients loose the pancreas with a kidney graft that continues to function. Under those conditions, isolated pancreas retransplantation can be indicated. We compared the outcome of these patients with the outcome of patients undergoing primary pancreas after kidney transplantation. From 1998 to 2005, we performed 205 pancreas transplantations. Three patients were considered for isolated pancreas retransplantation; to date, two have received a new organ. One was retransplanted twice. In two cases, the reasons for the initial graft loss in the retransplantation group were pancreatitis with hemorrhagic bleeding and in the third case severe rejection. After retransplantation two of three patients lost their graft owing to bleeding and venous thrombosis. One of three organs was successfully transplanted and the patient does not require insulin. During the same time, three pancreas after kidney transplantations were performed; all are doing well und are free of insulin. The study despite the small number of cases shows a high complication rate after pancreas retransplantation. Nevertheless, pancreatic retransplantation should be considered in selected patients.

Background Peritoneal catheter exit-site infections cause a relevant morbidity in peritoneal dialysis patients and are frequently caused by Staphylococcus aureus. We tested the hypothesis that adherence of exit-site-derived S. aureus to epithelial cells and peritoneal catheter silicone tubes discriminates virulent and less virulent strains. Methods The binding of isolated S. aureus to an epithelial cell line (HEp-2) and to silicone tubes was analyzed using light-microscopy or radioactive labeling of bacteria. Results Of 378 exit-site swabs, 99 (26%) were positive for microbial growth. S. aureus was cultured in 25 of 99 positive swabs; three of 13 swabs taken in exit-site infections grade 3 and 4 that had tested positive for S. aureus. Adherence of S. aureus from exit-site infections grade 2, 3 and 4 to Hep-2 cells did not differ from adherence of bacteria isolated from asymptomatic or moderately inflamed catheter exit sites (grade 0-2). However, binding of S. aureus to silicone tubes was enhanced in grade 0/1 compared with grade 2-4 exit-site isolates. Conclusions Staphylococcus aureus is an important pathogen in CAPD-related exit-site infection being isolated in about 6.6% of all exit-site swabs (and in 25% of all positive swabs). Silicone-adhesive strains may be of more clinical significance in peritoneal dialysis patients since adhesion to silicone was increased in S. aureus strains isolated in more severe exit-site infections.

INSULIN resistance and hyperinsulinism after pancreas transplantation are well known consequences due to immunosuppressive therapy and systemic insulin delivery. Impaired glycemic control may develop. The differentiation from pancreas rejection may be difficult; pancreas biopsy is still a diagnostic tool not widely used. Glucose tolerance tests provide information on the secretory function of the b cell. Fasting insulin levels are often variable and interpretation can be difficult. To assess insulin resistance in recipients of a pancreas–kidney transplant we employ the euglycemic hyperinsulinemic clamp (EHC) as developed by De Fronzo in 1979. The following case report illustrates the use of EHC to investigate the impact of immunosuppressant drugs in a patient with progressively deteriorating glycemic control within the first 6 months after transplantation.

The OKT3 monoclonal antibody (mAb) recognizing the CD3 complex on human T-cells has been shown to be an effective immunosuppressive agent for the treatment and the prevention of acute rejection episodes in allograft recipients [1]. Following the initial doses of OKT3 mAb, activation of T lymphocytes and monocytes is observed. This is accompanied by a massive cytokine release, particularly following the first injection. The mAb opsonizes the circulating T-cells and the coated cells disappear quickly from circulation. OKT3 mAb is commonly administered for 5-10 days. The manifestation of side effects weeks (cytomegalovirus infection/disease, bacterial and fungal infections) or even months (Epstein-Barr-Virus related lymphoproliferative disease) after therapy as well as the good long-term effects on graft function suggest long-lasting immunosuppressive effects. Since peripheral T-cells reappear in the circulation already during therapy (with modulated CD3/T-cell receptor complex) and T-cell counts reach commonly pretreatment levels within 2-3 days after cessation of OKT3 mAb, the long-lasting immunosuppressive effects are not simply explainable by T-cell depletion. We wondered whether T-cells reappearing in the circulation after cessation of therapy, were functionally different from those before OKT3 mAb therapy. Our data suggest a selective depletion of activated T-cells particularly of type 1-like T-cells by OKT3 mAb resulting in long-lasting immune deviation that may explain the long-term effects of OKT3 mAb treatment.

Simultaneous pancreas-kidney transplantation (SPK) is now a common treatment for insulin-dependent diabetic patients with end-stage renal disease. This study analyzed the patient and graft survival rates of 231 kidney transplantations (KTX) in nondiabetic patients and of 95 SPK in diabetic patients between January 1, 1998 and December 31, 2001. The SPK group showed significantly better patient and graft survival rates after 5 years than the KTX group (96% and 90% vs 85% and 75%, respectively; P < .05). Even the serum creatinine level during the first 2 years showed significantly lower levels in the SPK group (P < .01). The patients in the SPK group were significantly younger. They received organs from younger donors than the patients in the KTX group (P < .01). The cold ischemia time and the time on previous dialysis were also shorter in the SPK group (P < .01). However, the number of HLA mismatches was higher in the SPK patients (P < .01). Limiting the analysis to recipients younger than 60 years, donors younger than 58 years, and cold ischemia time to