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This pre-specified analysis of DAPA-CKD assessed the impact of sodium-glucose cotransporter 2 inhibition on abrupt declines in kidney function in high-risk patients based on having chronic kidney disease (CKD) and substantial albuminuria. DAPA-CKD was a randomized, double-blind, placebo-controlled trial that had a median follow-up of 2.4 years. Adults with CKD (urinary albumin-to-creatinine ratio 200-5000 mg/g and estimated glomerular filtration rate 25-75 mL/min/1.73m2) were randomized to dapagliflozin 10 mg/day matched to placebo (2152 individuals each). An abrupt decline in kidney function was defined as a pre-specified endpoint of doubling of serum creatinine between two subsequent study visits. We also assessed a post-hoc analysis of investigator-reported acute kidney injury-related serious adverse events. Doubling of serum creatinine between two subsequent visits (median time-interval 100 days) occurred in 63 (2.9%) and 91 (4.2%) participants in the dapagliflozin and placebo groups, respectively (hazard ratio 0.68 [95% confidence interval 0.49, 0.94]). Accounting for the competing risk of mortality did not alter our findings. There was no heterogeneity in the effect of dapagliflozin on abrupt declines in kidney function based on baseline subgroups. Acute kidney injury-related serious adverse events were not significantly different and occurred in 52 (2.5%) and 69 (3.2%) participants in the dapagliflozin and placebo groups, respectively (0.77 [0.54, 1.10]). Thus, in patients with CKD and substantial albuminuria, dapagliflozin reduced the risk of abrupt declines in kidney function. HJLH and DC are co-primary authors. The DAPA-CKD Trial Committees and Investigators are listed in the Appendix.

Terminal niereninsuffiziente Patienten konnen in Deutschland bei entsprechender Gesundheit auf die Warteliste bei Eurotransplant aufgenommen werden, um ein Nierentransplantat zu erhalten. Eurotransplant mit Sitz in Holland ubernimmt dabei fur die beteiligten Lander die Organisation der Verteilung. Hintergrund dieses Zusammenschlusses ist die Bereitstellung eines moglichst grosen Spender- und Empfangerpools, um gerade fur die Nierenallokation Organe mit bestmoglicher Ubereinstimmung und damit einem zu erwartenden besseren Transplantatuberleben zu ermoglichen. Aktuell gibt es neben der Standardallokation, die auch Regeln fur Patienten mit hochster Dringlichkeit und fur Kinder enthalt, sowie Sonderprogramme fur hochimmunisierte Patienten, fur Patienten uber 65 Jahre und fur Nieren, die uber eine Standardallokation nicht vermittelbar sind. In diesem Artikel sollen 50 Jahre nach Grundung von Eurotransplant die geltenden Allokationsregeln reflektiert und mogliche Weiterentwicklungen diskutiert werden.

Mit der Plasmaseparation und der Immunadsorption stehen den Nephrologen zwei effektive Methoden zur Entfernung von Plasmabestandteilen fur derzeit etwa 80 ganz unterschiedliche Erkrankungen in der stationaren Betreuung zu Verfugung. Ziel dieser Arbeit ist es, einen kurzen Uberblick uber Historie und Gegenwart des therapeutischen Plasmaaustauschs unter Berucksichtigung der Rolle der Nephrologie aufzuzeigen und die aktuellen pathophysiologischen Vorstellungen eines therapeutischen Plasmaersatzes zu klaren. Zusatzlich wird auf den Einsatz auf Intensivstationen sowie auf Besonderheiten bezuglich der Medikamentenelimination hingewiesen. Als Grundlage der Ubersicht werden die aktuellen Guidelines des therapeutischen Plasmaersatzes bzw. der Immunadsorption sowie die Literatur bezuglich der medikamentosen Therapie und dem Einsatz der Verfahren auf der Intensivstation unter Berucksichtigung eigener Erkenntnisse diskutiert. Bei der Plasmaseparation wird das Patientenplasma entfernt und durch fremde Bestandteile ersetzt, wodurch neben dem Plasmavolumen und dem kolloidosmotischen Druck auch die Bestandteile der Gerinnung und die plasmatische Immunabwehr erhalten bleiben. Bei der Immunadsorption wird das Patientenplasma uber eine zweite Saule gefuhrt, und es erfolgt je nach Sauleneigenschaft eine mehr oder weniger spezifische Adsorption von Bestandteilen des Plasmas, wie z. B. Antikorpern mit Ruckfuhrung des „gereinigten“ Patientenplasmas; hier verarmt entsprechend das Plasma an Immunglobulinen. Die Evidenzgrade fur eine Therapie unterscheiden sich in den 2013 neu uberarbeiteten Guidelines je nach Krankheitsbild ganz erheblich. Die Entscheidung fur das eine oder andere Verfahren hangt dabei von publizierten und lokalen Erfahrungswerten, den technischen Moglichkeiten, der wahrscheinlichen Therapiedauer, aber auch von den verhandelten Abrechnungsmodalitaten ab. Das Nebenwirkungsprofil der unterschiedlichen Methoden unterscheidet sich, ist aber insgesamt in geschulten Handen als gering ausgepragt einzuschatzen. Der Einfluss der Methoden auf eine Medikamentenelimination ist nicht immer einfach vorhersehbar und muss im Einzelfall besprochen werden. Viele Indikationen zur Plasmaseparation/Immunadsorbtion sowie die Einschatzung von Risiken und Chancen der Methoden sind den Kollegen aus anderen Disziplinen nicht immer vertraut, sodass auf die Nephrologie hier Aufklarungsarbeit zukommt, um bei korrekter Indikation eine Therapie durchfuhren zu konnen.

Die Immunsuppression, welche die Abstosung der transplantierten Nieren verhindert, geht mit einem erhohten Risiko fur die Tumorentwicklung einher. Andere Langzeitkomplikationen nach Transplantation, wie die des kardiovaskularen Systems oder Infektionen, nehmen an Bedeutung ab, sodass Tumoren sich zur fuhrenden Ursache der hohen Mortalitat in dieser Bevolkerungsgruppe entwickeln werden. Eine Reihe von Faktoren ist neben der Menge an Immunsuppression fur die Tumorentwicklung von Bedeutung, so u. a. die die genetische Disposition, Viren und maligne Vorerkrankungen. Die Reduktion der Immunsuppression sowie eine konsequente und dem spezifischen Risiko angepasste Tumorvorsorge sind gegenwartig die wichtigsten Masnahmen zur Reduktion des Risikos, solange neue Formen der Immunsuppression bzw. die Induktion immunologischer Toleranz gegenuber dem Transplantat noch nicht zur Verfugung stehen.

Einleitung: Ein Nierenstein in einer Transplantatniere stellt eine seltene Komplikation dar und kann zu einer massiven Beeintrachtigung der Organfunktion fuhren. Verschiedene interventionelle Techniken sind in der Steintherapie bekannt. In diesem Fall wird die perkutane Nephrolitholapaxie erfolgreich eingesetzt. Kasuistik: Bei einem 65-jahrigen Patienten wird zwei Monate nach einer erfolgreichen Nierentransplantation eine Harnstauung II diagnostiziert und als Ursache ein Konkrement in der oberen Kelchgruppe gefunden. Dieses wird mittels perkutaner Nephrolitholapaxie mithilfe eines 15 Charr Storz-Mini-Endoskops zunachst desintegriert und mit einer Fasszange entfernt. Danach lasst sich eine Steinfreiheit nachweisen. Schlussfolgerung: Im Vergleich zu anderen Verfahren in der Steintherapie stellt die perkutane Nephrolitholapaxie bei transplantierten Nieren ein sicheres und einzeitiges Therapieverfahren dar. Die Verwendung des 15 Charr Storz-Mini-Endoskops ist auserdem weniger invasiv als die bisher in der Therapie verwendeten groserlumigen Endoskope. Introduction: Nephrolithiasis in a transplanted kidney is an uncommon complication and may lead to an acute deterioration in renal function. Different techniques for stone treatment are known. In this case, we were successful by using percutaneous nephrolithotomy for the removal of the stone. Case Report: A 65-year-old male patient was found with urinary retention II° two months after renal transplantation. A stone in the upper pole calix was found as the probable cause. Percutaneous nephrolithotomy with a 15-Charr Storz mininephroscope was used successfully to disintegrate and remove the stone. Conclusion: In comparison to other techniques for the removal of stones, percutaneous nephrolithotomy is a secure method in the treatment of nephrolithiasis in a transplanted kidney. This technique treats the renal stone in one session. We used a 15-Charr Storz mininephroscope which is less invasive than the usually used nephroscopes with a bigger lumen.

Die Option der Nierentransplantation muss bei allen Patienten mit einer terminalen Niereninsuffizienz gepruft werden, da die Nierentransplantation im Vergleich mit allen Dialyseverfahren dem Patienten nicht nur mehr Lebensqualitat bietet, sondern auch das Patientenuberleben signifikant verlangert. Fur den Patienten ist die Transplantation durch eine Lebendnierenspende optimal, da hierdurch die Wartezeit minimiert wird und Transplantatfunktionsdauer und Lebenserwartung am besten sind. Fur den Spender verbleibt jedoch ein vornehmlich operationsbedingtes Restrisiko. Nach der Transplantation bedarf es einer sehr sorgfaltigen Betreuung besonders in den ersten 6 Monaten, in denen das Rejektions- und das Infektionsrisiko am hochsten sind. Langerfristig bedarf es einer sorgsamen Tumorvorsorge und einer konsequenten Behandlung der kardiovaskularen Risikofaktoren. Voraussetzung fur eine optimale Betreuung dieser Patienten ist eine enge Zusammenarbeit zwischen einem Transplantationszentrum und niedergelassenen Arzten.

Mit den Calcineurininhibitoren Ciclosporin A und Tacrolimus, den DNA-Synthesehemmern Mycophenolsaure und Azathioprin und nicht zuletzt den TOR-Inhibitoren Everolimus und Sirolimus stehen derzeit eine Vielzahl von Medikamenten fur die Immunsuppression nach Nierentransplantation zu Verfugung. Diese werden noch durch Antikorper und Steroide erganzt. In dem vorliegenden Artikel werden neben den grundlegenden Daten zur Pharmakokinetik, dem Nebenwirkungsprofil und dem Interaktionspotenzial der Immunsuppressiva die Moglichkeiten und Grenzen verschiedener derzeit eingesetzter Medikamentenkombinationen einschlieslich aktueller Richtlinien der Rejektionstherapie diskutiert.

Background andobjectivesThecalcimimeticcinacalcet reduced therisk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients. Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified. ResultsOlderpatients hadhigher baselineprevalenceof diabetesmellitusandCV comorbidity. Annualizedrates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. Conclusions In the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone. Clin J Am Soc Nephrol 10: ccc–ccc, 2015. doi: 10.2215/CJN.07730814

We report the case of a patient who experienced anuric renal transplant failure for 44 days after living related kidney transplantation. Immunosuppressive and other therapies were carefully adapted to the findings of frequent renal transplant biopsies, which ultimately led to excellent graft function.

Organ transplantation offers the potential to improve quality of life and prolong survival for increasing numbers of patients with organ failure, and bone marrow or peripheral stem cell transplantation may constitute the only curative approach for patients with select haematological diseases. Since the early sixties, heterologous polyclonal sera against human thymocytes or lymphocytes (ATG or ALG) are employed for immunosuppression, but significant progress in transplantation medicine was achieved with the introduction of novel oral immunosuppressive agents like calcineurin inhibitors, mycophenolate mofetil and – more recently – sirolimus. However, acute rejection episodes or high risk clinical situations, e.g. in pretransplanted patients may require even more pronounced immunosuppression. In these situations, several monoclonal antibodies against defined antigens broaden the therapeutic armentarium today [1]. Among these are antibodies against the IL-2 receptor (CD25) or CD3, and antibodies against other antigens are expected to follow along this line [2].

Short- and long-term rates of success after cadaveric kidney transplantation are significantly inferior to those from living related or unrelated donors. The major difference between cadaveric and living donation is brain death. In the present study we analyzed the influence of duration of brain death on short- and long-term graft function after cadaveric kidney transplantation. The interval between declaration of donor brain death and the beginning of the cold ischemia time before graft explantation was defined as duration of brain death (DBD). The influence of DBD on incidence of primary graft function and on duration of delayed kidney graft function as well as on kidney graft survival was analyzed in 1106 patients transplanted in one center and confirmed in a validation study of a second series of 752 kidney graft recipients from another transplant center. Kidney grafts harvested from donors with longer DBD (>470 min) exhibited a significantly higher incidence of primary graft function and a significantly better graft survival rate in comparison to kidneys from donors with a shorter DBD (

This article provides an overview of the literary prose written in Dutch about the Congo, the former Belgian colony. The Congo was ruled over by king Leopold II as his private property from 1885 to 1908. From 1908 to 1960 it was governed by the Belgian state. The Congo gained its independence on 30 June 1960. During the colonial period and after the Congolese independence a substantial number of Flemish literary works have been written about the Congo. During the colonial period most of them were written in the colonialist vein. They reflect a Eurocentric perspective and a colonialist attitude. However, there are also a number of writers who are critical of the colonial project. Some of them criticize the way in which the colonization is carried out; others reject the colonial enterprise out of hand. After the Congolese independence Flemish authors engaged in some serious soul searching. The universality of western values is examined and the problems regarding acculturation are addressed. In the last two decades authors such as Guido Tireliren and Lieve Joris have tried to understand the Congo from within. Most Flemish literature on the Congo is not of a high literary quality but from a historical-cultural perspective it is a very important domain of study. Keywords: Flemish prose on the Congo, Congo literature, postcolonialism, Eurocentrism. Tydskrif vir Letterkunde Vol. 46 (1) 2009: pp. 109-122

Nephrolithiasis in a transplanted kidney is an uncommon complication and may lead to an acute deterioration in renal function. Different techniques for stone treatment are known. In this case, we were successful by using percutaneous nephrolithotomy for the removal of the stone.A 65-year-old male patient was found with urinary retention II degrees two months after renal transplantation. A stone in the upper pole calix was found as the probable cause. Percutaneous nephrolithotomy with a 15-Charr Storz mininephroscope was used successfully to disintegrate and remove the stone.In comparison to other techniques for the removal of stones, percutaneous nephrolithotomy is a secure method in the treatment of nephrolithiasis in a transplanted kidney. This technique treats the renal stone in one session. We used a 15-Charr Storz mininephroscope which is less invasive than the usually used nephroscopes with a bigger lumen.

Kidney transplantation is the best option for all patients with terminal renal failure. Kidney transplantation is not only associated with an improved quality of life in comparison to all other renal replacement therapies, this method also offers a significantly extended lifespan. Therefore, the option for transplantation has to be verified for every patient with renal failure. Graft and patient survival is best when transplantation is carried out just before starting dialysis treatment. Realistically, only living donor transplantation offers the option of sparing the recipient a long waiting period on dialysis. Although transplantation from living donors is superior to cadaveric kidney transplantation, a small risk remains for the donor. Kidney transplantation and the immunosuppressive therapy are associated with an increased risk for certain types of infection, an increased tumour risk and an increased risk for cardiovascular complications. To address these problems, specific recommendations for patient surveillance have been provided by different transplantation societies.

Despite the lack of nephrotoxicity, adverse effects of the new antiproliferative immunosuppressant everolimus have been reported. By varying time point and dose of everolimus treatment as well as the degree of glomerular injury, the specific conditions and potential mechanisms leading to adverse actions in the anti-Thy1 model have been determined. Only the combination of early and high-dose everolimus treatment (1-3 mg/kg bw) with a severe glomerular lesion ('full-dose' anti-Thy1 model) caused adverse effects with a high mortality rate, progressive apoptosis, crescent formation and glomerulosclerosis. In contrast, either later start or low-dose (0.3 mg/kg bw) therapy or treatment of a less severe lesion ('reduced dose' anti-Thy1 model) appeared to be relatively safe for the glomerular architecture. The adverse effects of everolimus were linked to its marked inhibition of endothelial cell, but not necessarily mesangial cell proliferation. In addition, everolimus markedly inhibited the angiogenic cytokine vascular endothelial growth factor in nephritic glomeruli in vivo. These experimental results suggest special caution regarding the use of everolimus in all situations of severe glomerular cell injury requiring extensive capillary repair, where at least adaption to a low dose needs to be considered.

Die HCV Reinfektion nach LTx stellt aufgrund ihres haufig aggressiven Verlaufs ein groses klinisches Problem dar. Die Therapie mit Interferon (IFN) und Ribavirin ist aufgrund der in der Regel bestehenden Niereninsuffizienz der Patienten und damit potentiellen Akkumulation von Ribavirin erschwert. Methoden: 34 Patienten mit HCV Reinfektion nach LTx erhielten entweder eine Therapie mit IFN alpha–2a (Roferon 3–6 MU 3 x Wo) und Ribavirin (800–1000mg/die) (Gruppe 1; n=12) oder peg-IFN alpha–2b (Pegintron 1–1,5mg/kg KG) (Gruppe 2; n=22) und Ribavirin (800–1000mg/die) fur 1 Jahr. Eine Reduktion der Ribavirindosis im Verlauf der Therapie wurde in Gruppe 1 bei Anamie vorgenommen, in Gruppe 2 entsprechend des Talspiegelmonitorings mittels HPLC (Zielspiegel: 8–12 microMol/L). Zusatzlich wurde bei schwerer Anamie Erythropoetin eingesetzt. Ergebnisse: Bei 9/12 (75%) der Patienten in Gruppe 1 und 10/22 (45%) der Patienten in Gruppe 2 musste die Therapie aufgrund starker AZ-Verschlechterung (n=6), Panzytopenie (n=3), Verschlechterung der Leberfunktion (n=3) bzw. anderen Ursachen (n=7) vorzeitig abgebrochen werden. Eine histologisch gesicherte Abstosungsreaktion fand sich in keinem Fall. Die Ribavirindosis wurde in der Gruppe 2 starker reduziert (Adaptation nach Drugmonitoring) als in der Gruppe 1. Erythropoetin wurde bei 2/11 (18%) der Patienten in Gruppe 1 und 6/22 (27%) in Gruppe 2 gegeben. Eine Normalisierung der GPT fand sich bei 9/12 (75%) der Patienten in Gruppe 1 und bei 10/22 (45%) in Gruppe 2 unter Therapie, persistierte aber 6 Monate Therapieende nur bei Patienten in Gruppe 2 (0% versus 35%). Ein virologisches Ansprechen war in Gruppe 1 und 2 unter Therapie gleich haufig (36% und 36%), ein bleibendes Ansprechen 6 Monate nach Therapieende haufiger in Gruppe 2 (9% versus 25%). Genotyp 2/3 Patienten wiesen in Gruppe 2 ein sehr gutes bleibendes virologisches Ansprechen auf (3/4 (75%)), nicht aber in Gruppe 1 (0/2). Schlussfolgerung: Die hohe Therapieabbruchrate konnte durch Ribavirin Spiegelmonitoring und Einsatz von peg-IFN gesenkt werden. Trotz geringerer Ribavirindosisfand sich tendenziell ein besseres bleibendes Therapieansprechen in Kombination mit Peg-IFN im Vergleich zur IFN Gruppe. Insbesondere Genotyp 2/3 Patienten profitierten von der Therapie. Keywords: HCV, Interferon, Lebertransplantation, Ribavirin

Die medikamentose Immunsuppression nach Organtransplantation ist mit einem erhohten Risiko verbunden, an opportunistischen Infektionen zu erkranken. Durch die Modulation des Immunsystems sind die klinische Symptomatik, der Verlauf und typische diagnostische Zeichen wie Rontgenbildveranderung, Fieber oder Blutbildveranderungen modifiziert. Trotzdem bedurfen gerade diese Patienten einer schnellen Diagnosestellung und der fruhzeitigen Einleitung der Therapie. Dies gelingt nur, wenn selbst primar blande erscheinende Symptome bei dieser Patientengruppe richtig interpretiert werden und eine konsequente Diagnostik zur Folge hat. Hierfur bedarf es einer verbreiteten Kenntnis dieser Erkrankungen und einer engen Zusammenarbeit zwischen niedergelassenen Internisten und dem Transplantationszentrum.

The risk to acquire opportunistic infections is clearly increased in patients receiving immunosuppressive therapeutic regimens following organ transplantation or during treatment of autoimmune disorders. The modulation of the immune system can alter the clinical symptoms and the course of infectious diseases, including diagnostic signs such as fever or pathological changes in radiographs or blood cell counts. However, a rapid diagnosis and start of treatment is essential in these patients. Thus, a correct interpretation of even mild symptoms in the initial phase of an infectious disease is essential for establishing a diagnosis and initiation of a therapy at an early stage. Therefore, it is necessary that the clinical hallmarks of these diseases are widely known and that physicians treating these patients cooperate closely with transplant centers.

Objective: Therapy of elevated cholesterol serum concentrations is often necessary in patients with kidney transplants. However, the pharmacokinetics of HMG-CoA reductase inhibitors when administered in combination with sirolimus and cyclosporin A (CsA) have not been determined. The aim of this study was to investigate the pharmacokinetics of cerivastatin when administered in combination with sirolimus in patients with kidney transplants, and to review the literature with regard to the differences in pharmacological behavior between sirolimus, CsA and tacrolimus. Methods: Patients (n = 7) with a stable and functioning kidney transplant and elevated LDL cholesterol serum concentrations were included in the study. After an observation period of 3 months, and whilst receiving sirolimus and CsA, cerivastatin (0.2 mg daily) was administered for a period of 3 months. Pharmacokinetic parameters were calculated on Day 1 and 3 months after initiation of cerivastatin therapy. Routine laboratory parameters and clinical adverse events were monitored throughout the study period. Results: Single-dose cerivastatin AUC was 2 to 3-fold higher in comparison to published values obtained in healthy subjects. The accumulation ratio of cerivastatin (after 3 months/ Day 1) was 1.6. Sirolimus and CsA trough levels, and the sirolimus AUC did not differ after single dose and multiple doses of cerivastatin. Conclusions: The combination therapy of cerivastatin with sirolimus and CsA leads to a significant increase in cerivastatin exposure. Additional drug monitoring of sirolimus and CsA is not necessary.

Background Hyperlipidaemia is an important risk factor for cardiovascular disease in renal transplant recipients. The aim of this study was to test the efficacy and possible drug-drug interactions of the new HMG-CoA reductase inhibitors (statins) atorvastatin and cerivastatin in cyclosporin A (CsA)-treated renal transplant patients. Subjects and methods. Thirty patients with stable graft function and LDL cholesterol of 130 mg/dl were randomly assigned to active treatment groups (10 mg atorvastatin or 0.2 mg cerivastatin), or a control group. CsA blood trough levels were controlled on a weekly basis and adapted if they changed more than 25% from baseline values (100-150 ng/ml). Lipid levels and routine laboratory parameters before and after a treatment period of 3 months were compared. Results In the group treated with cerivastatin no significant changes in CsA blood trough levels occurred (CsA 116+/-21 ng/ml vs 110+/-20 ng/ml). In contrast, in the group treated with atorvastatin, four of 10 patients had a rise in CsA blood trough levels of more than 25% within 7-14 days of starting therapy. In the remaining patients no significant changes in CsA drug levels occurred. After therapy with atorvastatin or cerivastatin, total cholesterol, LDL cholesterol, and triglycerides were significantly lower compared with baseline conditions. No changes of CsA or lipoprotein levels were present in the control group. Conclusion In our study population both statins were very effective in lowering elevated LDL cholesterol levels. Cerivastatin did not influence CsA blood trough levels, whereas atorvastatin increased CsA levels in four of 10 patients. Further research in a larger study is necessary in order to confirm these results and to investigate the possible reasons for this drug interaction.

Background. Mycophenolate mofetil (MMF) is used for immunosuppression after renal transplantation because it reduces lymphocyte proliferation by inhibiting inosine monophosphate dehydrogenase (IMPDH) in lymphocytes and GTP biosynthesis. In the present study we asked if therapeutic concentrations of MMF might interfere with mesangial cell (MC) proliferation which is involved in inflammatory proliferative glomerular diseases. Methods. Rat and human MCs were growth-arrested by withdrawal of fetal calf serum ( FCS ) and stimulated by addition of FCS, platelet-derived growth factor (PDGF) or lysophosphatidic acid (LPA). Different concentrations of MMF (0.019--10 μM) were added concomitantly in the presence or absence of guanosine. MC proliferation was determined by [ 3 H]thymidine incorporation. Cell viability was assessed by trypan blue exclusion. Apoptotic nuclei were stained using the Hoechst dye H33258. Cytosolic free Ca 2+ concentrations were determined with the fluorescent calcium chelator fura-2-AM. Results. MMF inhibited mitogen-induced rat MC proliferation with an IC 50 of 0.45±0.13 μM. Human MCs proved to be even more sensitive (IC 50 0.19 ± 0.06 μM). Inhibition of MC proliferation was reversible and not accompanied by cellular necrosis or apoptosis. Addition of guanosine prevented the antiproliferative effect of MMF, indicating that inhibition of IMPDH is responsible for decreased MC proliferation. Early signalling events of GTP-binding-protein-coupled receptors, such as changes in intracellular Ca 2+ levels were not affected by MMF. Conclusions. The results show that MMF has a concentration-dependent antiproliferative effect on cultured MCs in the therapeutic range, which might be a rationale for the use of this drug in the treatment of mesangial proliferative glomerulonephritis.

An alternative approximation for the high frequency MIS capacitance as a function of surface potential and/or biasing potential is proposed. Its main advantage over the existing ones lies in the fact that the correct inversion potential barrier shape in the semiconductor is taken into account. The proposed procedure accounts more accurately for the experimentally observed leveling off of the capacitance at the onset of inversion. As compared with the exact solution as proposed by Sah et al. [4], the present method is much simpler and requires less computation time. Es wird eine Alternativ-Naherung fur die hochfrequente MIS-Kapazitanz als Funktion des Oberflachenpotentials und/oder der Vorspannung vorgeschlagen. Ihre hauptsachlichen Vorteile gegenuber den bereits existierenden bestehen in der Tatsache, das die korrekte Form der Inversionspotentialbarriere berucksichtigt wird. Die vorgeschlagene Methode gibt das beobachtete Nivellieren der Kapazitanz beim Einsetzen der Inversion genauer wieder. Im Vergleich zu der von Sah [4] vorgeschlagenen exakten Losung, ist die Methode viel einfacher und benotigt weniger Rechenzeit.

Anaesthesia for laryngoscopies and bronchoscopies is confronted with a double problem. In fact, both anaesthesiologist and surgeon are sharing the same working area. The anaesthesiologist has to provide not only an adequate oxygenation and elimination of CO2, but also enough working-space for the surgeon and a good view of the larynx. Moreover, the larynx should not be irritated and the vocal cords must be in a complete relaxation state.

The head-down position is a current practice in gynaecological surgery. Indeed, this method permits a better exposition of the organs of the pelvis and presents an easier way to operate on them. Many graduations are possible in this position and often the surgeon asks for an extreme declivity even sometimes exagerated.

This case report analyses the anesthetic technique and early postoperative treatment of a five months old baby with congenital aortic stenosis. Administration of cardiotonics and diuretics was necessary before surgery because of severe heart failure. The patient was anesthetized with halothane in pure oxygen and ventilated by means of an Engström ventilator. Surgical treatment consisted of valvulotomy under extracorporeal circulation and normothermia. Recovery was uneventful.

Renders L. La date de naissance de Caton d'Utique et l'âge légal de la questure au dernier siècle de la république. In: L'antiquité classique, Tome 8, fasc. 1, 1939. pp. 111-125.

The head-down position is a current practice in gynaecological surgery. Indeed, this method permits a better exposition of the organs of the pelvis and presents an easier way to operate on them. Many graduations are possible in this position and often the surgeon asks for an extreme declivity even sometimes exagerated.