Removal selectivity of Prometheus： A new extracorporeal liver support device

AIM:To evaluate whether treatment with thePrometheus~(R)system significantly affects cytokines,coagulation factors and other plasma proteins.METHODS:We studied nine patients with acute-on-chronic liver failure and accompanying renal failure.Prometheus~(R)therapy was performed on 2 consecutivedays for up to 6 h in all patients.Several biochemicalparameters and blood counts were assessed at regulartime points during Prometheus~(R)treatment.RESULTS:We observed a significant decrease of bothprotein-bound(e.g.bile acids)and water-soluble(e.g.ammonia)substances after Prometheus~(R)therapy.Eventhough leukocytes increased during treatment(P<0.01),we found no significant changes of C-reactive protein,interleukin-6,and tumor necrosis factor-a plasma levels(all P>0.5).Further,antithrombin 3,factor Ⅱ and factorV plasma levels did not decrease during Prometheus~(R)therapy(all P>0.5),and the INR remained unchanged(P=0.4).Plasma levels of total protein,albumin,andfibrinogen were also not altered during Prometheus~(R)treatment(all P>0.5).Finally,platelet count did notchange significantly during therapy(P=0.6).CONCLUSION:Despite significant removal of protein-bound and water-soluble substances,Prometheus~(R)therapy did not affect the level of cytokines,coagulationfactors or other plasma proteins.Thus,the filters andadsorbers used in the system are highly effective andspecific for water-soluble substances and toxins bound tothe albumin fraction.     

Proteomic patterns established with capillary electrophoresis and mass spectrometry for diagnostic purposes

BACKGROUND: Proteomics applied in large scale may provide a useful diagnostic tool. METHODS: We developed an online combination of capillary electrophoresis with mass spectrometry, allowing fast and sensitive evaluation of polypeptides found in body fluids. Utilizing this technology, polypeptide patterns from urine are established within 45 minutes. About 900 to 2500 polypeptides as well as their concentrations are detected in individual urine samples without the need for specific reagents such as antibodies. To test this method for clinical application, we examined spot urine samples from 57 healthy individuals, 16 patients with minimal change disease (MCD), 18 patients with membranous glomerulonephritis (MGN), and 10 patients with focal segmental glomerulosclerosis (FSGS). RESULTS: One-hundred seventy-three polypeptides were present in more than 90% of the urine samples obtained from healthy individuals, while 690 polypeptides were present with more than 50% probability. These data permitted the establishment of a "normal" polypeptide pattern in healthy individuals. Polypeptides found in the urine of patients differed significantly from the normal controls. These differences allowed the distinction of specific protein spectra in patients with different primary renal diseases. Abnormal pattern of proteins were found even in urine from patients in clinical remission. CONCLUSION: The data indicate that capillary electrophoresis with mass spectrometry coupling provides a promising tool that permits fast and accurate identification and differentiation of protein patterns in body fluids of healthy and diseased individuals, thus enabling diagnosis based on these patterns.     

Fulminant course of leptospirosis complicated by multiple organ failure

We describe a case of a 39-year-old male, who initially presented with severe muscle pain, fever, shortness of breath and tachycardia. He was admitted to hospital with suspected myocarditis. The next days he developed a generalized icterus and acute renal failure. Suspecting leptospirosis an intravenous therapy with penicillin was started. Due to pulmonary and circulatory insufficiency intensive care was necessary. In course the patient developed all known manifestations of leptospirosis including, cardiac arrhythmia and asystolia due to AV-block III degrees, recurrent atelectases of the lungs, hyperbilirubinemia, thrombocytopenia, hepatitis, pancreatitis, very severe rhabdomyolysis and polyradiculitis with areflexia and tetraplegia. Additionally, the patient had a transient hyperthyreosis, which has not been described in the literature so far. After 33 days the patient left the intensive care unit and was discharged out of hospital a fortnight later. 4 weeks later he was able to return to work. The only residuum of this illness is a partial paresis of his right quadriceps muscle.     

Regeneration des Nierengewebes – zukünftige therapeutische Möglichkeit für Nierenerkrankungen?

The regeneration of organ tissues has been a legend in medicine since Prometheus. So far an improvement in organ regeneration by stem cells could only be demonstrated in myocardial tissue. Different organs obviously have different possibilities for regeneration. The kidneys also have the possibility to replace injured or destroyed tissue with stem cells. The reactivation of this regeneration potential can occur by various strategies which can be classified into three categories: i) multipotent adult progenitor cells regenerate kidney tissue directly or by the release of growth factors, ii) stem cells form new nephrons in the injured kidney and iii) kidney tissue is produced ex vivo by means of stem cells and then implanted as “bio-kidney tissue”. One of the medical challenges of the future is the necessary understanding of nephrogenesis and the interaction of the cell types involved in this process.     

Erythropoietin und Herzinsuffizienz

Anemia in chronic heart failure (CHF) is an independent predictor of mortality. Current clinical studies therefore explore the possibility that iron supplementation and/or therapy with recombinant, human erythropoietin (rHuEPO) improves the outcome in CHF patients. However, recent studies in patients with impaired renal function did not find any effects on cardiovascular endpoints by raising haemoglobin above 11 mg/dl. Independent of its effect on Hb levels, EPO was shown to have beneficial effects on left ventricular remodeling after infarct through direct effects on tissue-resident EPO receptors. These results have led to clinical studies testing the effect of single, high doses of rHuEPO after myocardial infarction. So far, only safety data are available. These show this approach to be safe. In summary, EPO therapy in CHF is currently experimental; data from ongoing clinical trials are eagerly awaited in order to judge the potential of this approach for patients with CHF.