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Biomedical subjects

U Frei

Publications and source records attributed to U Frei.

At least 19 recordsLinked to original sources
PubMed2007

[Analysis of personnel costs after reorganization of intensive care using calculated diagnosis-related groups comparative data. An investigation at the Charité Berlin].

BACKGROUND: In an extensive project intensive care units (ICUs) of the Charité University Hospital were reorganized. The aim of this investigation was to determine if staff costs after this reorganization are financed by modular profits of diagnosis-related groups (DRGs). METHODS: Staff costs of all non-pediatric intensive care units, including ICUs, intermediate care units and post-anaesthesia care units (PACUs) in the Charité University Hospital were compared with the modular profits of all DRGs of patients older than 14 years in 2005. These DRGs were converted into the German refined DRG (GDRG) system 4.0 from 2006 with calculations based on actual income for medical doctors and nurses in 2006. Due to changed wage agreements for the incomes of physicians in 2006 there was an increase of costs. For the other professional groups an increase in income is expected, which cannot be estimated at present. RESULTS: The calculation revealed that staff costs of the ICUs at the Charité University Hospital based on a current German mean base rate of 2,836 EUR were 4.2% above the modular profits of the DRGs. As a result of a structural reorganization of the ICUs, the costs of staff could be adapted to the modular profits. Under the conditions of the actual reduced base rate of Berlin of 2,955 EUR the costs and profits were nearly equal. As the financial impact of the reorganization of the ICUs will take full effect in the coming years, it can be anticipated that with an expected base rate of 2,949 EUR in 2010 the intensive care medicine of a University hospital in Germany can become profitable. DISCUSSION: The spectrum of intensive care medicine at the Charité University Hospital covers the maximum range of operative and non-operative medicine. After an extensive reorganization of the ICUs under the aspect of staff costs, intensive care medicine can become profitable under the 4.0 G-DRG system. With consequent reorganization the cost efficiency of staff can be optimized, particularly in the setting of high-end intensive care medicine.

Adolescent↗
PubMed2006

Hypoxia-inducible factors and tubular cell survival in isolated perfused kidneys.

Adaptation to hypoxic environment is conferred through hypoxia-inducible transcription factors (HIFs). We have previously shown that the HIF system is transiently activated in vivo in radiocontrast-induced acute renal failure, associated with profound hypoxia in the renal medulla. Medullary thick ascending limbs (mTALs), the most affected nephron segments in this model, were virtually unable to mount an adaptive HIF response. Here, we study correlations between oxygenation, HIF activation, and cell viability in a related ex vivo model, the isolated perfused rat kidney (IPK). In IPKs perfused with cell-free oxygenated medium, severe medullary hypoxic damage developed, affecting 42+/-9% of mTALs in the mid-inner stripe. HIF-1alpha tubular immunostaining was noted with a zonal and tubular pattern largely similar to our findings in vivo: in 34+/-3% of collecting ducts (CDs) within the mid-inner stripe and extensively in the papillary tip, whereas mTALs were all HIF-negative. In IPKs supplemented with RBCs (improved oxygen supply), mTAL damage was totally prevented and CDs' HIF expression was attenuated (22+/-4%). By contrast, although measures designed to reduce medullary hypoxia by decreasing tubular reabsorptive activity (furosemide, ouabain, or high-albumin-non-filtering system) reduced mTAL damage, all paradoxically resulted in increased HIF expression in CDs (51+/-4%), and 17+/-3% of mTALs became immunostained as well. Our data confirm that CDs and mTALs have markedly different HIF responses, which correlate with their viability under hypoxic stress. mTALs transcriptional adaptation occurs within a narrow hypoxic range, and it appears that workload reduction can shift mTALs into this window of opportunity for HIF activation and survival.

Animals↗
PubMed2006

Acute renal failure after liver transplantation: incidence, etiology, therapy, and outcome.

Acute renal failure (ARF) was a frequent complication after orthotopic liver transplantation (OLT) when ARF was defined by a calculated glomerular filtration rate decrease of >50% or by a doubled serum creatinine above 2.5 mg/dL within the first week after OLT. We analyzed 1352 liver transplant recipients in retrospective fashion with regard to the incidence, etiology, therapy, and outcome of ARF; 162 patients developed ARF within the first week after OLT (12%), among whom 157 patients (97%) were recompensated by postoperative day 28. Altogether 52 patients (32%) received an average of 6 hemodialysis treatments, excluding the 5 patients (3%) who developed end-stage renal failure. Risk factors for this complication included hepatorenal syndrome type II, a glomerular filtration rate of <50 mL/min, and a diagnosis of hepatitis C.

Acute Kidney Injury↗
PubMed2006

Expression of hypoxia-inducible transcription factors in developing human and rat kidneys.

Early kidney development is associated with the coordinated branching of the renal tubular and vascular system and hypoxia has been proposed to be a major regulatory factor in this process. Under low oxygen levels, the hypoxia-inducible transcription factor (HIF) regulates the expression of genes involved in angiogenesis, erythropoiesis and glycolysis. To investigate the role of HIF in kidney development, we analyzed the temporal and spatial expression of the oxygen regulated HIF-1alpha and -2alpha subunits at different stages of rat and human kidney development. Using double-staining procedures, localization of the HIF target geneproducts vascular endothelial growth factor (VEGF) and endoglin was studied in relation to HIFalpha. In both species, we found marked nuclear expression of HIF-1alpha in medullary and cortical collecting ducts and in glomerular cells. In contrast, HIF-2alpha was expressed in interstitial and peritubular cells podocytes of the more mature glomeruli. After completion of glomerulogenesis and nephrogenesis, HIF-1alpha and -2alpha were no longer detectable. The HIF-target gene VEGF colocalized with HIF-1alpha protein in glomeruli and medullary collecting ducts. HIF-2alpha colocalized with the endothelium-associated angiogenic factor, endoglin. Both HIFalpha isoforms are activated in the developing kidney in a cell-specific and temporally controlled manner, indicating a regulatory role of oxygen tension in nephrogenesis. HIF-1alpha seems to be primarily involved in tubulogenesis and HIF-2alpha in renal vasculogenesis. Both isoforms are found in glomerulogenesis, potentially having synergistic effects.

Animals↗
PubMed2006

'Low-dose' dopamine worsens renal perfusion in patients with acute renal failure.

'Low-dose' dopamine is frequently used in intensive care units (ICU) for its presumed renoprotective effects, but prospective and retrospective studies have so far not proven prevention or amelioration of renal injury. Data on renal perfusion following dopamine infusion are limited. In order to circumvent the problem of patient heterogeneity in the ICU setting, we used a crossover design in a prospective, double-blind randomized controlled study to investigate the effect of 'low-dose' dopamine on renal resistance indices, as determined by Doppler ultrasound. Forty patients, 10 without and 30 with acute renal failure (ARF, defined as doubling of baseline creatinine or an increase above 2 mg/dl), were included. Dopamine (2 mug/kg min) or placebo was given intravenously in alternating sequence for four subsequent periods of 60 min, starting randomly with either dopamine or placebo. Resistive (RI) and pulsatility index (PI) were closely correlated, positively related to serum creatinine values at baseline and highly reproducible during the two paired infusion periods. Dopamine reduced renal vascular resistance in patients without ARF (median RI/PI from 0.70 to 0.65/1.20 to 1.07, P<0.01) but increased resistance indices in patients with ARF (median RI/PI from 0.77 to 0.81/1.64 to 1.79, P<0.01) in the absence of effects on systemic hemodynamics. Subgroup analysis of patients with ARF revealed that dopamine induced renal vasoconstriction above 55 years (n=22) and in patients not receiving norepinephrine (n=20). In conclusion 'low-dose' dopamine can worsen renal perfusion in patients with ARF, which adds to the rationale for abandoning the routine use of 'low-dose' dopamine in critically ill patients.

Acute Kidney Injury↗
PubMed2006

Amelioration of anemia after kidney transplantation in severe secondary oxalosis.

INTRODUCTION: In small bowel disease such as M. Crohn, the intestinal absorption of oxalate is increased. Severe calcium oxalate deposition in multiple organs as consequence of enteric hyperoxaluria may lead to severe organ dysfunction and chronic renal failure. The management of hemodialyzed patients with short bowel syndrome may be associated with vascular access problems and oxalate infiltration of the bone marrow leading to pancytopenia. Although the risk of recurrence of the disease is very high after renal transplantation, it may be the ultimate therapeutic alternative in secondary hyperoxaluria. CASE: Here, we report a patient with enteric oxalosis due to Crohn's disease. He developed end-stage renal disease, erythropoietin-resistant anemia, oxalate infiltration of the bone marrow and severe vascular access problems. Following high-urgency kidney transplantation, daily hemodiafiltration of 3 hours was performed for 2 weeks to increase oxalate clearance. Despite tubular and interstitial deposition of oxalate in the renal transplant, the patient did not require further hemodialysis and the hematocrit levels normalized. DISCUSSION: Early treatment of hyperoxaluria due to short bowel syndrome is essential to prevent renal impairment. Declining renal function leads to a further increase in oxalate accumulation and consecutive oxalate deposition in the bone marrow or in the vascular wall. If alternative treatments such as special diet or daily hemodialysis are insufficient, kidney transplantation may be a therapeutic alternative in severe cases of enteric oxalosis despite a possible recurrence of the disease.

Adult↗
PubMed2005

[60 year old patient with soft tissue infection of the right leg].

Group A streptococcal necrotizing fasciitis is a rare disease associated with high mortality. Since severe toxic shock syndrome is a common complication, only immediate and aggressive surgical intervention, adequate antimicrobial therapy and supportive intensive care can be life-saving. We report about successful treatment of a 60-year old patient with necrotizing fasciitis and multiple organ failure.

Anti-Bacterial Agents↗
PubMed2005

Cyclosporine-based immunosuppressive strategies for kidney recipients: interim analysis of German data from the Multinational Observational Study (MOST).

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.

Adult↗
PubMed2005

Accurate prediction of kidney allograft outcome based on creatinine course in the first 6 months posttransplant.

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.

Creatinine↗
PubMed2005

Comparable kidney graft survival of type 1 diabetics treated with simultaneous pancreas-kidney transplantation and nondiabetic patients treated with cadaveric renal transplantation.

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 <19 hours, there was no difference in graft or patient survival. These data suggest that donor and recipient age as well cold ischemic time have a greater impact on early outcome and postoperative complications of renal transplants than HLA matching.

Cadaver↗
PubMed2005

Policy principles and implementation guidelines for private sector participation in the water sector--a step towards better results.

To achieve the Millennium Development Goals, all partners (public, private, NGOs) must be engaged for improving and expanding the water supply and sanitation services. Yet, high transaction costs, unclear role allocation and lack of trust and commitment put Private Sector Participation (PSP) at risk. The initiative "Policy Principles and Implementation Guidelines for Private Sector Participation in Sustainable Water Supply and Sanitation" contributes to equitable, effective, ecological and efficient PSP projects. Based on a multi stakeholder process, the Policy Principles are offering an open and transparent framework for the negotiation of valid, widely accepted and action-oriented solutions, while the Implementation Guidelines focus on success factors for building partnerships on the operational level.

Ecology↗
PubMed2004

Bilirubin-adsorption in 23 critically ill patients with liver failure.

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 (p<0.001). Levels of bile acid were reduced from 41.8+/-6 to 33.5+/-5 mg/dL. The 30-day mortality was 50%. BA was able to halt and stabilize the progressive increase in bilirubin levels in all patients. In contrast to survivors, non-survivors were characterized by a repeated rapid rise in bilirubin levels after cessation of BA treatment. CONCLUSIONS: 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.

Adsorption↗
PubMed2003

[Anemia and erythropoietin in critically ill patients].

The transfusion of red blood cells is still associated with possible adverse effects and a residual risk of transmission of viral and nonviral diseases. In addition, there is an increasing shortage of blood supply worldwide. These two facts together with the success experienced in the treatment of various types of anemia with recombinant human EPO, have recently led to an increasing interest in the anemia of critically ill patients. As in the anemia of chronic diseases there are several reasons that contribute to the development of anemia in patients on intensive care units: pre-existing anemia, blood loss, reduced red cell life span, impaired iron availability and a direct inhibition of erythropoiesis by inflammatory cytokines. The implications of anemia for the progression and prognosis of critical illness are still unclear and the optimal treatment, including optimal "transfusion triggers" remains controversial. Recombinant human EPO has been proven to be effective in ameliorating the anemia of critical illness in several pilot studies and is currently being tested in larger trials.

Adult↗
PubMed2003

Differences in the permeability of high-flux dialyzer membranes for bacterial pyrogens.

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.

Escherichia coli Proteins↗