Elisabeth Marion Schneider

Modern management of children with haemophagocytic lymphohistiocytosis.

Haemophagocytic lymphohistiocytosis (HLH) is characterized by fever, hepatosplenomegaly, central nervous system symptoms, cytopenias, coagulopathy and lipid changes because of hypercytokinaemia and organ infiltration by phagocytosing histiocytes. Most cases are triggered by an infection. The common basis seems to be an inherited or acquired defect of immune effector cells. Diagnostic work-up should include the search for an infectious agent, especially viruses, and the measurement of disease markers such as fibrinogen, ferritin, triglycerides, sCD25, inflammatory cytokines and natural killer cell function. Initial therapy aims to suppress hyperinflammation, which can be achieved by immunosuppressive and cytostatic treatment with corticosteroids and cyclosporin A, and by etoposide. A combination of all three drugs is recommended for patients with severe symptoms, and cyclosporin A and corticosteroids are the treatment of choice for children with rheumatic diseases and HLH. Bone marrow transplantation, which offers a cure for nearly two-thirds of patients, should be performed in all children with primary genetic HLH.

Granulocyte colony-stimulating factor (G-CSF) serum levels in surgical intensive care patients

SummaryThe granulocyte colony-stimulating factor (G-CSF) regulates neutrophil differentiation and function. Serum levels of G-CSF increase during acute infectious processes. The levels of G-CSF were measured in 59 surgical intensive care unit (ICU) patients. In general, G-CSF was only elevated during the first 2 days after admission to the ICU. Higher G-CSF levels were more frequently observed in patients without infectious complications and in patients who survived. Later on, G-CSF levels were below 100 pg/ml in almost all patients studied. The highest G-CSF level (20,000 pg/ml) was observed in one patient with septic shock 36 h after leukopenia. The patient recovered from septic shock and multiple organ failure and was discharged. It is proposed that surgical ICU patients with low or undetectable G-CSF serum levels may benefit from exogenous G-CSF substitution protocols.

Tin-mesoporphyrin for inhibition of heme oxygenase during long-term hyperdynamic porcine endotoxemia.

Heme oxygenase (HO) has both deleterious and protective effects in various shock models. Most of these data have been derived from experiments with hypodynamic shock states associated with depressed cardiac output. Therefore we studied the role of HO during long-term porcine hyperdynamic endotoxemia characterized by a sustained increase in cardiac output resulting from colloid resuscitation to maintain mean arterial pressure > 60 mmHg. Systemic, pulmonary, and hepatosplanchnic hemodynamic and metabolic effects of the HO-inhibitor tin–mesoporphyrin (SnMP) were assessed in anesthetized and mechanically ventilated animals. After 12 h of continuous intravenous lipopolysaccharide (LPS), animals received either vehicle (n = 6) or SnMP (n = 8; 6 &mgr;mol kg−1 i.v. over 30 min at 12 and 18 h of LPS). Measurements were performed before LPS, before SnMP infusion, and at 24 h of LPS. SnMP did not influence systemic hemodynamics but significantly increased mean pulmonary artery pressure. Although liver blood flow was not affected, SnMP markedly impaired liver lactate clearance. HO inhibition was associated with increased plasma nitrate levels likely the result of increased NO production. Our results suggest a protective role of HO activation during hyperdynamic porcine endotoxemia possibly as a result of an interaction with the LPS-induced increase in NO formation.

BK viremia in critically ill surgical patients with hemorrhagic or septic shock.

BackgroundInfections with polyomavirus BK virus (BKV) are a common cause of renal dysfunction after renal transplantation and may also be harmful in surgical patients with shock. The aim of the present study was to determine the frequency of BKV viremia in critically ill surgical patients with septic or hemorrhagic shock, and, if viremia is detectable, whether viremia may be associated with renal dysfunction.FindingsA total of 125 plasma samples from 44 critically ill surgical patients with septic or hemorrhagic shock were tested by real-time polymerase chain reaction (PCR) for BKV DNA during their stay on the intensive care unit (ICU). BKV viremia occurred in four patients, i.e. in three of the septic and in one of the hemorrhagic shock group. There was no association between viremia and renal dysfunction. All positive samples contained a low viral load (< 500 copies/ml).ConclusionsSince BK viremia was rarely found and with low viral load only in critically ill surgical patients with shock, it is very unlikely that BK viremia results in BK nephropathy later on.

Vermindert die prophylaktische Gabe von Filgrastim (r-metHuG-CSF) lnfektionskomplikationen bei chirurgischen lntensivpatienten?

Bei chirurgischen Intensivpatienten (ICU) mit systemischer Entzundungsreaktion (SIRS) wird das Risiko fur die Entwicklung einer Sepsis mit 20–40% angegeben [1,2]. Der Granulozyten Kolonien-stimulierender Faktor (G-CSF) reguliert die Reifung and verbessert die Funktion neutrophiler Granulozyten [3–5]. In tierexperimentellen Sepsis-Studien konnte rhG-CSF die Mortalitat senken [6]. In einer ersten Pilot-Studie mit rhG-CSF bei ICU-Patienten fanden sich Ansatze fur die Wirksamkeit bei fehlen-den negativen Effekten [7].

Low dose granulocyte colony-stimulating factor boosts neutrophil function and concomitantly improves an antiinflammatory cytokine response in postoperative/posttraumatic patients at risk of or with sepsis

ConclusionsLow dose filgrastim in postoperative/posttraumatic patients at risk of and with sepsis may boost host defense by stimulating neutrophil function and simultaneously counteract progression of sepsis by improving an antiinflammatory cytokine response with protective effects on the endothelium.