Lipopolysaccharide (LPS) has been shown to induce proliferation of human T‐lymphocytes only in the presence of monocytes and CD34+ hematopoietic cells (HCs) from peripheral blood. This finding ...provided evidence of an active role of CD34+ HCs during inflammation and immunological events. To investigate mechanisms by which CD34+ HCs become activated and exert their immune‐modulatory function, we used the human CD34+ acute myeloid leukemia cell line KG‐1a and CD34+ bone marrow cells (BMCs). We showed that culture supernatants of LPS‐stimulated mononuclear cells (SUPLPS) as well as tumor necrosis factor α (ΤNF‐α), but not LPS alone, can activate nuclear factor‐κB in KG‐1a cells. By cDNA subtraction and multiplex polymerase chain reaction, we revealed differential expression of cellular inhibitor of apoptosis protein‐1, inhibitor of κB (IκB)/IκBα (MAD‐3), and intercellular adhesion molecule‐1 (ICAM‐1) in SUPLPS‐stimulated KG‐1a cells and up‐regulation of interferon (IFN)‐inducible T cell‐chemoattractant, interleukin (IL)‐8, macrophage‐inflammatory protein‐1α (MIP‐1α), MIP‐1β, RANTES, CD70, granulocyte macrophage‐colony stimulating factor, and IL‐1β in stimulated KG‐1a cells and CD34+ BMCs. Although monokine induced by IFN‐γ, IFN‐inducible protein 10, and IFN‐γ were exclusively up‐regulated in KG‐1a cells, differential expression of monocyte chemoattractant protein‐1 (MCP‐1), macrophage‐derived chemokine, myeloid progenitor inhibitory factor‐2, and IL‐18 receptor was only detectable in CD34+ BMCs. More importantly, CD34+ BMCs stimulated by TNF‐α also showed enhanced secretion of MCP‐1, MIP‐1α, MIP‐1β, and IL‐8, and increased ICAM‐1 protein expression could be detected in stimulated KG‐1a cells and CD34+ BMCs. Furthermore, we revealed that T cell proliferation can be induced by TNF‐α‐stimulated KG‐1a cells, which is preventable by blocking anti‐ICAM‐1 monoclonal antibodies. Our results demonstrate that CD34+ HCs have the potential to express a variety of immune‐regulatory mediators upon stimulation by inflammatory cytokines including TNF‐α, which may contribute to innate‐ and adaptive‐immune processes.
The incidence of fungal infection as well as fungal sepsis has increased dramatically during the last decade. Changes of local microbial flora after broad-spectrum antibiotic therapy allow overgrowth ...of Candida species. Prophylactic strategies to lower fungal infection and sepsis include adequate and restrictive antibiotic therapy. Concerning the treatment of the septic syndrome, supportive as well as adjunctive strategies like early-goal-directed cardiovascular therapy, hydrocortisone replacement therapy, intense insulin application to achieve normoglycemia as well as the application of activated Protein C besides a consequent source control regimen and standard intensive care therapy, are able to improve significantly the outcome of septic patients.
A prospective, randomized, double-blind, placebo controlled multicenter trial was undertaken in 205 patients treated with total gastrectomy for gastric malignancies to evaluate whether local ...antimicrobial measures reduce the incidence of esophagojejunal anastomotic leakage.
Anastomotic leakage of the esophagojejunostomy is always a septic complication of total gastrectomy for gastric malignancies, but it never has been attempted to prevent this complication with the administration of topical antimicrobial agents during the critical phase of anastomotic wound healing.
To evaluate the efficacy and safety of topical decontamination, the study was carried out as a prospective, randomized, double-blind and placebo-controlled clinical multicenter trial in patients with total gastrectomy for gastric cancer. Patients received either placebo or decontamination with polymyxin B (100 mg), tobramycin (80 mg), vancomycin (125 mg), and amphotericin B (500 mg) four times per day orally from the day before the operation until the seventh postoperative day. All patients received a perioperative intravenous prophylaxis with cefotaxime 2 x 2 g. Other interventions including the administration of antibiotics and fluids, were not affected by the study protocol.
Of 260 patients who were randomized, total gastrectomy was not carried out in 55 patients. They dropped out of the study. Patients receiving an esophagojejunostomy were observed until day 42, when they were discharged from the clinic or died. An intention-to-treat analysis of the data was carried out. Among the 103 recipients of placebo, there were 11 (10.6%) with an anastomotic leakage of the esophagojejunostomy, and among the 102 recipients of decontamination, there were 3 (2.9%) with an anastomotic leakage of the esophagojejunostomy (p = 0.0492). Pulmonary infections were observed in 23 patients (22.3%) receiving placebo and in 9 patients (8.8%) who were decontaminated (p = 0.02). There were 11 deaths (10.6%) among the recipients of placebo and 5 deaths (4.9%) among the recipients of decontamination (p = 0.1).
Decontamination with polymyxin, tobramycin, vancomycin, and amphotericin B during anastomotic wound healing is safe and effective in the prevention of esophagojejunal anastomotic leakage after total gastrectomy.
Procalcitonin (PCT) was shown to be related to the severity of bacterial infection and is recommended as a new parameter of inflammation and infection. To evaluate the prognostic value in septic ...shock, PCT levels were repeatedly determined and compared with tumour necrosis factor-alpha (TNF-alpha)- and interleukin (IL)-6 bioactivity as well as with C-reactive protein (CRP) serum levels.
Twenty-four surgical patients with septic shock were included. Eight patients died within the study period of 14 days.
Serum levels of TNF-(WEHI 164) and IL-6 (B13-29 subclone 9) bioactivity, CRP and PCT were determined on days 1, 3, 5, 7, 10 and 14 following diagnosis of septic shock.
Survivors and non-survivors were comparable in terms of age and severity of sepsis characterized by the APACHE II score and multiple-organ-failure score. Predominant causes of sepsis were peritonitis and necrotiszing pancreatitis. TNF levels increased in non-survivors with no significant difference to survivors. IL-6 bioactivity was increased on day 1 (P = 0.06) and remained elevated in non-survivors, in whom it was significant on day 7 (P<0.05). CRP was constantly elevated with no difference between the groups. In nonsurvivors PCT remained increased, while the course of survivors was characterized by decreased values which were significantly lower (P<0.05) at every time point compared with those patients who died. A significant correlation could be found on day 1 (P<0.05) and at the end of the observation period (P<0.01) when comparing PCT levels with the multiple-organ-failure score.
PCT seems to be a more reliable prognostic parameter in septic shock than IL-6, while TNF and CRP did not show any difference between survivors and non-survivors. These data indicate that PCT may represent a valuable parameter not only in the diagnosis of sepsis but also in the clinical course of the disease.
Gender Differences in Human Sepsis Schröder, Jörg; Kahlke, Volker; Staubach, Karl-Hermann ...
Archives of surgery (Chicago. 1960),
11/1998, Letnik:
133, Številka:
11
Journal Article
Odprti dostop
BACKGROUND In animal studies, gender differences were related to hormonal and immunologic changes that were associated with an increased susceptibility to sepsis in males. OBJECTIVE In a prospective ...study, gender differences in patients with surgical sepsis were evaluated in terms of survival, sex hormones, and proinflammatory as well as anti-inflammatory mediators. SETTING Surgical intensive care unit of a university hospital. PATIENTS Fifty-two patients (19 women and 33 men) with surgical sepsis. MEASUREMENTS AND MAIN RESULTS In a prospective study, tumor necrosis factor α and interleukin 6 bioactivity and plasma levels of interleukin 10 (using enzyme-linked immunosorbent assay), total testosterone, and 17-β estradiol (using radioimmunoassay) were determined on days 1, 3, 5, 7, 10, and 14 after diagnosis of sepsis. There were no differences in characteristics of patients in age (mean age, 55.4 years for women and 53.1 years for men) or cause and severity of sepsis (Acute Physiology and Chronic Health Evaluation II score, 17.3 for women and 18.5 for men; multiple organ dysfunction score, 9.9 vs 10.8, respectively). Although no difference could be found in the multiple organ dysfunction score from day 1 to day 28, the prognosis of sepsis was significantly different in women compared with men. Hospital mortality rate was 70% (23 of 33 patients) in male and 26% (5 of 19) in female patients (P<.008, log-rank test). Bioactivity of tumor necrosis factor continuously increased in men after diagnosis of sepsis, with significantly elevated levels on day 10 (P<.05, Mann-Whitney U test with Bonferroni correction), whereas no difference was found for interleukin 6 bioactivity. Women displayed enhanced interleukin 10 levels compared with men from day 1 to day 10 that reached a significant difference on days 3 and 5 (P<.05). Total testosterone levels were below the normal range for men, and estradiol levels were initially increased in both men and postmenopausal women, with higher levels for women. CONCLUSIONS In this prospective study, gender differences were confirmed in human sepsis, with a significantly better prognosis for women, which may be related to increased levels of anti-inflammatory mediators. The hypothetical different ratio of proinflammatory and anti-inflammatory mediators may be important for further therapeutic interventions in sepsis.-->
MATISSE
® is a new endotoxin (ET) adsorption system. It comprises the FRESENIUS hemoadsorption machine 4008 ADS to maintain the extracorporeal circuits and disposables including the MATISSE
...®-adsorber based on macroporous beads immobilized with human serum albumin. In vivo and in vitro experiments with this new compound had shown favourable ET elimination properties. In a first study 19 healthy volunteers were included for the safety and tolerability of the endotoxin adsorber system. One single veno-venous hemoperfusion with this system was performed. Apheresis treatment with the human albumin immobilized adsorber seems to be safe and well tolerable in healthy volunteers. A slight decrease in platelet count as well as insulin level was observed. No serious adverse events were mentioned. Similar findings were made in an open uncontrolled trial in six patients with suspected Gram-negative sepsis. Here endotoxin adsorption seems to be safe and well tolerated without adsorber related major adverse events. In the last clinical trial including 145 patients mainly peritonitis patients (104), again no safety concerns were found during the apheresis. Trends in improvement of morbidity and organ dysfunction were found as well as efficient LPS removal in peritonitis patients. LPS whole blood immunoadsorption is a promising new method. No relevant side effects were observed so far. A large controlled study to prove clinical efficacy in patients with severe sepsis and confirmed endotoxemia (e.g. peritonitis) should be necessary.
A percutaneous osseointegrated anchoring device for above-knee implantation designed to enable permanent attachment of an artificial limb is described. In addition to a technical description, the ...two-stage operative procedure, together with the rehabilitation process in an 18-year-old man, is also detailed. Following amputation and complete healing of the soft tissues, a surface-structured metal pin capable of supporting large loads, is driven into the medullary canal of the thigh bone. A metal sleeve having an identical surface structure serves to close off the medullary canal and provide an interface with the soft tissues. Screwed to the end of the pin is a conical metal adapter to which is attached a silicone cylinder whose right-angled distal end is located subcutaneously and ends in a titanium mesh. The first part of the implantation procedure is concluded by closing the silicone cylinder with a plastic plug for 6 weeks to permit osseous integration and the ingrowth of tissue into the mesh. In a second step, the plastic plug is removed via a skin incision, and the permanent load-bearing metal adapter fitted. In the above-mentioned patient wound healing at the metal/tissue interface was complication-free, since the implanted silicone cylinder prevented the "wedge effect" caused by the build-up of "luxuriant" tissue. After a further healing phase of 6 weeks, rehabilitation with an exoprosthesis took only 2 weeks, after which time, the patient was able to walk without a walking aid, and returned to work.
Preconditioning pigs with low doses of monophosphoryl lipid A (MPL), a non toxic derivate of lipid A, has been shown to induce endotoxin hyporesponsiveness and to reduce the metabolic and hemodynamic ...consequences of endotoxin shock. However, the mechanism is presently unclear. This study was designed to elucidate the effects of pretreatment with MPL on tissue metabolism in different organs by in vivo microdialysis of interstitial fluid.
In a controlled animal study at the university research laboratory, seven female mixed-breed pigs were exposed to an endotoxin infusion (1 microg/kg b.w. per h) after pretreatment with MPL in incremental doses of endotoxin during days 5-2 before the experiments. Seven animals receiving a saline pretreatment served as a control group. Hemodynamic variables and blood gas analyses including blood lactate were determined every 30 min until the animals died. Interstitial lactate and glycerol levels were measured in muscle, subcutaneous tissue and liver using in vivo microdialysis.
Survival time was significantly prolonged after MPL preconditioning (8.95 (7.5-9.1) h vs. 5.35 (5.0-5.6) h, P<0.05). Hemodynamic parameters were not significantly different between the treatment and control groups, while mixed venous saturation (81% (70-93%) vs. 30% (22-48%)) and arterial blood pH (7.39 (7.33-7.44) vs. 7.21 (7.1-7.25)) and pO(2) were significantly higher in the preconditioned group (P<0.05). The interstitial concentrations of lactate and glycerol in all investigated tissues were significantly higher in control animals than the those who had been pretreated with MPL (P<0.05).
Preconditioning with low doses of monosphosphoryl lipid A attenuates the negative effects of endotoxemia on tissue metabolism, probably by reducing O(2)-consumption. These changes may be subtle and, hence, only fully detectable by monitoring tissue metabolism.
Background: Major vascular surgery with aortic cross-clamping is
associated with temporary ischaemia of the lower limb due to lack of tissue blood
flow. The present study was designed to determine if ...the short-term changes in
cellular metabolism occurring during this situation can be detected by subcutaneous
microdialysis. It was also hoped to ascertain if this new technique is useful in the
continuous bedside monitoring of metabolism during aortic surgery.
Methods: In a controlled clinical study 20 patients undergoing elective
aortic surgery were monitored using microdialysis probes that were inserted in the
subcutaneous tissue of the left lower limb and a non-ischaemic region (shoulder).
Interstitial fluid was obtained and the concentrations of glucose and lactate during
lower limb ischaemia and during reperfusion were measured and compared with
concentrations observed in fluid obtained from the non-ischaemic control tissue.
Results: Circulatory occlusion caused an immediate and significant
decrease in the glucose/lactate ratio from 3·1±1·3 to 0·48±0·5 (P<0·05) that
returned to preocclusion values within 2 h of commencing reperfusion.
Conclusion: We suggest that microdialysis may be used both to assess
acute changes in tissue metabolism during ischaemic periods and also to act as an
additional tool for the detection of peri-operative acute variations in limb blood
flow.
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