["Do-not-rescuscitate"--Results of introducing a standardized order sheet on documentation quality]. / "Do not rescuscitate"--Auswirkungen der Einführung eines standardisierten Formulars auf Therapiebegrenzungen in der klinischen Praxis.

INTRODUCTION: DNR orders have been used internationally since the 1970 s. Despite the growing importance of patient preference in German law, there is little data on DNR orders in Germany Methods: The prevalence of DNR orders was assessed on the hospital wards. Healthcare were asked about their experiences and opinions in two polls. The charts of all deceased patients were reviewed for DNR notes for 9 month before and after introduction of the new DNR order sheets. RESULTS: The prevalence of DNR orders remained constant at 8% of patients. In 12,4% of these DNR status was not known by the nursing staff. After introduction of the order sheet, the percentage of orders with comprehensive documentation increased from 5.9 to 65.4% of orders (p < 0.001). In the polls the healthcare workers saw a significant improvement in information content of DNR orders after introduction of the new order sheets. The chart review documented an improved documentation of DNR status going up from 28.8 to 40.8% of deceased patients (p < 0.001). The fraction of comprehensive orders increased from 32% to 84.6% (p < 0.001). CONCLUSION: INTRODUCTION of DNR order sheets in a German hospital lead to objective improvements in the quality of end-of life care documentation while the prevalence of DNR orders remained unchanged.

Acute renal failure and liver dysfunction after subcutaneous injection of 3-sn-phosphatidylcholine (Lipostabil®)-case report.

INTRODUCTION: Drug-induced tubulointerstitial nephritis and acute tubular necrosis are common, and are often caused by drugs especially antibiotics or non-steroidal anti-inflammatory drugs. Drug-induced liver dysfunction and renal failure after subcutaneous injection of phosphatidylcholine was not reported so far. 3-sn-Phosphatidylcholine has been described as a cell lysis reaction-inducing drug. Its in vitro data indicated a relevant toxicity potential. In particular human cell types such as fibroblast-like preadipocytes, vascular and skeletal muscle cells, or renal epithelial cells react more sensitive than other human cell types. CASE REPORT: We present a 28-year-old woman who received 3.5 g (70 mL) of 3-sn-phosphatidylcholine (Lipostabil®) at once subcutaneously (s. c.) in both gluteal regions. The drug was originally introduced to prevent fat embolism. Nevertheless, its off-label use in aesthetic therapy for treatment of localized fat deposits through subcutaneous administration is becoming increasingly common. Three hours after injection the patient suffered from severe nausea and emesis. Within 24 hours a dramatic increase of liver enzymes and a beginning liver dysfunction were observed. Subsequently, renal function deteriorated two days later making a temporary haemodialysis necessary. Hepatic improvement was observed after three days of treatment. Renal function was fully recovered after two weeks. CONCLUSION: To the best of our knowledge, this is the first reported patient presenting with acute liver dysfunction and renal failure after subcutaneous injection of 3-sn-phosphatidyl-choline (Lipostabil®) indicating the risk of an off-label use of this drug.

The programmed death (PD)-1/PD-ligand 1 pathway regulates graft-versus-host-reactive CD8 T cells after liver transplantation.

Acute graft-versus-host disease (aGVHD) is a life-threatening complication after solid-organ transplantation, which is mediated by host-reactive donor T cells emigrating from the allograft. We report on two liver transplant recipients who developed an almost complete donor chimerism in peripheral blood and bone marrow-infiltrating T cells during aGVHD. By analyzing these T cells directly ex vivo, we found that they died by apoptosis over time without evidence of rejection by host T cells. The host-versus-donor reactivity was selectively impaired, as anti-third-party and antiviral T cells were still detectable in the host repertoire. These findings support the acquired donor-specific allotolerance concept previously established in animal transplantation studies. We also observed that the resolution of aGVHD was not accompanied by an expansion of circulating immunosuppressive CD4/CD25/FoxP3-positive T cells. In fact, graft-versus-host-reactive T cells were controlled by an alternative negative regulatory pathway, executed by the programmed death (PD)-1 receptor and its ligand PD-L1. We found high PD-1 expression on donor CD4 and CD8 T cells. In addition, blocking PD-L1 on host-derived cells significantly enhanced alloreactivity by CD8 T cells in vitro. We suggest the interference with the PD-1/PD-L1 pathway as a therapeutic strategy to control graft-versus-host-reactive T cells in allograft recipients.

Reduced secretion of proinflammatory cytokines of monosodium urate crystal-stimulated monocytes in chronic renal failure: an explanation for infrequent gout episodes in chronic renal failure patients?

BACKGROUND: In gouty arthritis, monosodium urate (MSU) crystals interact with monocytes and neutrophils to produce inflammatory reactions associated with acute synovitis. In patients with end-stage renal disease (ESRD), gouty arthritis is a rare condition despite often severe hyperuricaemia. We wondered whether differences in the secretion of proinflammatory cytokines by MSU crystal-stimulated monocytes might be one explanation for the low incidence of gouty arthritis in patients with ESRD compared with healthy controls. METHODS: Thirteen patients with ESRD on intermittent haemodialysis treatment, six patients with chronic renal failure not yet on dialysis, and 15 age- and sex-matched healthy controls were examined. Monocytes, purified from peripheral blood mononuclear cells (PBMC) by immunomagnetic bead separation, were incubated for 18 h in the presence of MSU crystals, Escherichia coli lipopolysaccharide (LPS) or medium alone. The supernatants were studied for the presence of interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) using cytokine-specific enzyme-linked immunosorbent assays. RESULTS: Monocytes from patients with ESRD produced significantly lower amounts of IL-1beta, IL-6 and TNF-alpha after stimulation with MSU crystals or LPS than did monocytes from healthy subjects. Cytokine production was not significantly different between ESRD patients on haemodialysis and chronic renal failure patients not yet on dialysis. Artificial MSU crystals were stronger stimuli than tophus-derived 'natural' MSU crystals. CONCLUSION: We demonstrate that monocyte-associated immunosuppression in ESRD leads to reduced secretion of proinflammatory cytokines in response to stimuli such as MSU crystals. This may be one of the factors preventing many ESRD patients from the manifestation of acute gout despite often severe hyperuricaemia.

Purification of a derepressible arylsulfatase from Chlamydomonas reinhardti. Properties of the enzyme in intact cells and in purified state.

Arylsulfatase (aryl-sulfate sulfohdydrolase, EC 3.1.6.1) has been purified from SO4-2-minus-starved cells of Chlamydomonas reinhardti. The enzyme was isolated from acetone-powder extract by (NH4)2SO4 precipitation, Sephadex G-200 filtration and ion-exchange chromatography. Only one fraction of aryl-sulfatase was found. The final preparation was homogenous by the criteria of sedimentation, diffusion and polyacrylamide gel electrophoresis. The purified enzyme had a molecular weight of about 150 000, estimated by ultracentrifugation and gel filtration, and an isoelectric point of 9.0. The properties of the enzyme as investigated in intact cells and in the purified state were found to be very similar except for the temperature optimum. Imidazole strongly increased the enzyme by increasing the V, but reduced the affinity for the substrate. The enzyme activity was competitively inhibited by borate with a greater affinity for borate than for the substrate. The Chlamydomonas enzyme is a Type I arylsulfatase since it was inhibited by CN-minus, but not SO4-2-minus and phosphate.

The capacity for arylsulfatase synthesis in synchronous and synchronized cultures of Chlamydomonas reinhardti.

The green algae Chlamydomonas reinhardti synthesizes arylsulfatase (arylsulfate sulfohydrolase EC 3.1.6.1) by derepression when the concentration of SO4-2-minus in the growth medium is less than about 5-10-minus 5 M. The following observations indicate that the arylsulfatase enzyme is stable while its mRNA was unstable: (1) The increase in enzyme activity stopped and remained constant after addition of cycloheximide to derepressed cells. (2) After readdition of SO4-2-minus the increase in enzyme activity continued at a lower rate whereafter it remained constant. (3) No decay of radioactivity was observed after readdition of SO4 2-minus in labelled enzyme protein isolated from pulse-labelled --S cells. The maximum rate of arylsulfatase synthesis. Measurements of this capacity in cells taken at different developmental stages from a selection synchronous and from a light-dark synchronized culture showed that: (1) Arylsulfatase was derepressible at all stages of the life cycle. (2) The same periodic capacity patterns were found, both with the synchronized and the synchronous cells. Furthermore, the rate of accummulation of RNA and protein changed in the same periodic manner during the life cycle as did the enzyme capacity.