Complement activation during sepsis in humans.
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Adult↗
Biomedical subjects
Manfred Weiss
Publications and source records attributed to Manfred Weiss.
Soluble CD163: An age-dependent, anti-inflammatory biomarker predicting outcome in sepsis.
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Age Factors↗
Active cytomegalovirus infection in patients with septic shock.
Cytomegalovirus (CMV) is a pathogen of emerging importance for patients with septic shock. In this prospective study, 25 immunocompetent CMV-seropositive patients with septic shock and an intensive care unit stay of > or =7 days were monitored by using quantitative pp65-antigenemia assay, shell vial culture, and virus isolation. Within 2 weeks, active CMV infection with low-level pp65-antigenemia (median 3 positive/5x10(5) leukocytes) developed in 8 (32%) patients. Infection was controlled within a few weeks (median 26 days) without use of antiviral therapy. Duration of intensive care and mechanical ventilation were significantly prolonged in patients with active CMV infection. CMV reactivation was associated with concomitant herpes simplex virus reactivation (p = 0.004). The association between active CMV infection and increased illness could open new therapeutic options for patients with septic shock. Future interventional studies are required.
Adult↗
Changes in the novel orphan, C5a receptor (C5L2), during experimental sepsis and sepsis in humans.
Sepsis is associated with extensive complement activation, compromising innate immune defenses, especially in neutrophils (PMN). Recently, a second C5a receptor (C5L2) was detected on PMN without evidence of intracellular signaling. The current study was designed to determine changes in C5L2 in blood PMN during sepsis. In vitro exposure of PMN to C5a, but not to fMLP, led to reduced content of C5L2. Following cecal ligation and puncture-induced sepsis in rats, PMN demonstrated a time-dependent decrease in C5L2. In vivo blockade of C5a during experimental sepsis resulted in preservation of C5L2. Similarly, PMN from patients with progressive sepsis showed significantly reduced C5L2 expression (n = 26), which was virtually abolished in patients who developed multiorgan failure (n = 10). In contrast, sepsis survivors exhibited retention of C5L2 (n = 12/13). The data suggest that C5L2 on PMN diminishes during sepsis due to systemic generation of C5a, which is associated with a poor prognosis.
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Effects of exogenous recombinant human granulocyte colony-stimulating factor (filgrastim, rhG-CSF) on neutrophils of critically ill patients with systemic inflammatory response syndrome depend on endogenous G-CSF plasma concentrations on admission.
OBJECTIVE: To investigate the effects of exogenous recombinant human granulocyte colony-stimulating factor (rhG-CSF; filgrastim) application on the neutrophils of patients at risk of sepsis following major trauma or operation. DESIGN: Randomized controlled trial. SETTING: Surgical intensive care unit and research laboratory of a university hospital. PATIENTS: Twenty-seven patients with systemic inflammatory response syndrome (SIRS). INTERVENTIONS: Thirteen patients were treated with filgrastim (1 micro g.kg.24 h) for 10 days as a continuous infusion. Fourteen patients served as controls. MEASUREMENTS AND RESULTS: Surface expression of FcgammaR type I (CD64), phagocytosis of E. coli, and the E. coli-induced oxidative burst of neutrophils were tested by flow cytometry. On the first postoperative/posttraumatic day, endogenous G-CSF plasma concentrations were <300 pg/ml in seven controls (subgroup 1) and nine filgrastim patients (subgroup 3), and were already elevated with >500 pg/ml in seven controls (subgroup 2) and four filgrastim patients (subgroup 4). G-CSF values ( P=0.0026, subgroup 1/3; P=0.0167, 2/4), neutrophil counts ( P=0.0026, 1/3; P=0.0167, 2/4), and CD64 expression ( P=0.0013, 1/3) were higher in filgrastim-treated than non-treated subgroups, but not phagocytic and burst activities. From day zero to day 1, phagocytosis decreased in subgroups 1 (5/7 patients) and 3 (5/9), but increased in subgroups 2 (5/7) and 4 (3/4), and respiratory burst activity decreased in subgroup 3 (8/9). CONCLUSIONS: Besides activation of neutrophil maturation, low-dose rhG-CSF application in postoperative patients with SIRS has different effects on neutrophil functions, in part depending on already endogenously produced G-CSF.
Adult↗
[What's new in ophthalmic anaesthesia?].
In the past few years, there have been many changes in ophthalmic anaesthesia. Application of drugs in general anaesthesia with excellent controllability enhances patient safety and allows a more efficient OR-management. Regional anaesthesia is gaining widespread use for ophthalmic surgery, especially topical anaesthesia for cataract surgery. Patients for ophthalmic surgery concomitantly often display high age and a high level of co-morbidity and, therefore, belong to the anaesthesiological risk groups ASA III-IV. Life-threatening adverse events including cardiovascular depression are associated with general and regional anaesthesia. Intervention by anaesthesiologists is frequently required for treatment of hypertension or dysrhythmias, and sedation. Thus, monitored anaesthesia care ("standby") is justified. Drugs applied for regional and general anaesthesia may change intraocular pressure. There are a lot of publications about the impact of anaesthesia on intraocular pressure (IOD), however, few on the effects of anaesthesia on pulsatile ocular blood flow. it has to be kept in mind that the effects of anaesthesia on intra-ocular pressure and pulsatile ocular blood flow may diverge. To avoid an increase of the IOD, especially during anaesthesia induction, drugs, such as succinylcholin, rocuronium and opiates, in particular remifentanil, can be applied. In addition, the use of the laryngeal mask may be advantageous compared to general anaesthesia associated with laryngoscopic tracheal intubation. The management of patients treated with anticoagulants and antiplatelet agents, has to be taken on the balance of risks. There are risks not only in continuing therapy, but also in discontinuing it perioperatively. Postoperative nausea and vomiting (PONV) remains a distressing and common problem after strabismus repair in particular in children. The incidence of PONV depends on the type of ophthalmic surgery and drugs applied. To reduce PONV in ophthalmic surgery, application of long-lasting opiates should be avoided, and non-opiate analgesics and, depending on the kind of operation, antiemetic prophylactics are recommended.
Adult↗
Transient leukocytosis, granulocyte colony-stimulating factor plasma concentrations, and apoptosis determined by binding of annexin V by peripheral leukocytes in patients with severe sepsis.
This study was undertaken to clarify the relation between transient increases in the numbers of leukocytes and granulocyte colony-stimulating factor (G-CSF) plasma concentrations as well as the degree of apoptosis, as determined by binding of annexin V by these cells in patients with severe sepsis and septic shock. Over a 6-month period, annexin V binding by leukocytes was determined daily using flow cytometry and FITC-labeled annexin V in 33 postoperative patients with severe sepsis or septic shock during their intensive care unit stay. The percentage of annexin V binding neutrophils, monocytes, and lymphocytes was significantly lower, and G-CSF plasma concentrations were higher in patients than in controls on most days. Nine, 19, and 18 peaks in neutrophil, monocyte, and lymphocyte counts (increase of >/=30% within 2 days, followed by a decrease of >/=30% within 2 days) occurred in 6, 11, and 16 patients. During leukocyte peaks, the absolute numbers of annexin V binding neutrophils, monocytes, and lymphocytes paralleled those of neutrophil, monocyte, and lymphocyte numbers. However, the percentage of annexin V binding neutrophils, monocytes, and lymphocytes did not differ significantly from one day to another. Increased G-CSF serum concentrations preceded neutrophil and monocyte peaks. In conclusion, apoptosis of leukocytes is lowered during severe sepsis and septic shock in critically ill patients. Moreover, the degree of apoptosis does not increase during transient leukocytosis. G-CSF might contribute to the low degree of apoptosis of neutrophils and monocytes in those patients.
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Peaks of endogenous G-CSF serum concentrations are followed by an increase in respiratory burst activity of granulocytes in patients with septic shock.
The relationship between peaks of G-CSF serum concentrations and respiratory burst activity of polymorphonuclear cells (PMN) was investigated in patients with postoperative or post-traumatic severe sepsis and septic shock. Over a 12 month period, a longitudinal analysis of G-CSF, TNF-alpha and IFN-gamma serum concentrations, burst activity of PMN, and expression of CD64 on the surface of PMN, were performed by ELISA technique and flow cytometric analysis, respectively, in 58 patients admitted to the intensive care unit (ICU) on a daily basis until discharge from the ICU or death. Out of these 58 patients, 27 with proven infections were in septic shock for at least 4 days' duration. Seventeen of these patients survived, whereas ten died. In 15 out of these 27 patients, 26 episodes of G-CSF peaks were observed, which were followed in most patients (13/15) by an increase in PMN burst activity, from 28% up to 540% (median 188%). Following the G-CSF peaks, CD64 expression on PMN remained at an increased level, followed by a marked decline 3 days later. TNF-alpha serum concentrations were elevated in most episodes (22/26), whereas IFN-gamma serum concentrations were below the detection level in 23/26 episodes. Taken together, peaks in G-CSF serum concentrations are followed by enhanced CD64 expression and increased burst activity of PMN in most patients with severe sepsis and septic shock. Thus, endogenous G-CSF increases neutrophil function in patients with severe sepsis and septic shock, necessary for resolution of bacterial infections in these patients.
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