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  • 1
    ISSN: 1432-1076
    Keywords: Neisseria meningitidis ; Complement system ; Properdin deficiency ; Protein C deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the complement system in 29 children (mean age: 4.5 years) who survived fulminant meningococcal septic shock. No terminal complement deficiencies were found. One patient, who experienced the most dramatic disease course, had a decreased haemolytic activity in the haemolytis-in-gel test for the alternative pathway. The properdin concentration in serum of this patient was 〈 0.1 μg/ml (n = 17.1−27.7 μg/ml). Coagulation studies revealed a heterozygeous type I protein C deficiency as well. He was the only patient with aNeisseria meningitidis group Y infection.
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  • 2
    ISSN: 1432-1076
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 3
    ISSN: 1432-1238
    Keywords: Key words Meningococcal disease ; Meningococcal meningitis ; Meningococcal septic shock ; Sepsis ; Severity of illness index ; Mortality rate ; Prognostication
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To investigate the accuracy of eight different prognostic scores (Stiehm, Niklasson, Leclerc, Garlund, the MOC score, Tesero, the Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS) and Tüyzüs) in the prediction of fatal outcome in meningococcal disease. Design: Combined prospective and retrospective study. Setting: A 175-bed pediatric department of a university hospital providing secondary care to ±180,000 inhabitants and serving as a referral center. The Pediatric Intensive Care (14 beds) is one of the six PICUs in the Netherlands and provides tertiary care for children under 18 years. Patients: During an 8-year period (1986–1994) 125 children (mean age 4 years, 10 months) with culture- proven meningococcal disease were studied: 34 patients presenting with meningitis, 33 patients with septic shock and 58 patients with meningitis and septic shock. Main results: All eight scores discriminated above average between survivors and non-survivors, as expressed by the corresponding Receiver Operator Characteristic (ROC) curves. The area under the ROC curve (AUC) ranged from 0.74 for the Garlund score to 0.93 for the GMSPS. The GMSPS performed significantly better than its competitors, even after exclusion of the base deficit as one of the score components (AUC=0.92). It showed above average calibration when logistically transformed into a probability of mortality, and accurately identified a subgroup of patients with no mortality. None of the scores correctly identified non-survivors. Conclusion: The GMSPS is a simple score that can be reliably used for risk classification and the identification of low-risk patients.
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  • 4
    ISSN: 1432-1238
    Keywords: Key words Oxygen consumption ; Endotoxemia ; Tumor necrosis factor ; Interleukin-6 ; Hypermetabolism ; Post-perfusion syndrome ; Cardiac surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: The aim of this study was to determine whether the increase in post-operative oxygen consumption (ΔVO2) in cardiac surgery patients is related to endotoxemia and subsequent cytokine release and whether ΔVO2 can be used as a parameter of post-perfusion syndrome. Design: Prospective study. Setting: Operating room and intensive care unit of a university hospital. Patients: Twenty-one consecutive male patients undergoing elective coronary artery bypass surgery without major organ dysfunction and not receiving corticosteroids. Measurements and results: Plasma levels of endotoxin, tumor necrosis factor (TNF) and interleukin-6 (IL-6) were measured before, during and for 18 h after cardiac surgery. Oxygen consumption, haemodynamics, the use of IV fluids and dopamine, body temperature and the time of extubation were also measured. Measurements from patients with high ΔVO2 (≥median value of the entire group) were compared with measurements from patients with low ΔVO2 (〈median). Patients with high ΔVO2 had higher levels of circulating endotoxin (P=0.004), TNF (P=0.04) and IL-6 (P=0.009) received more IV fluids and dopamine while in the ICU, and were extubated later than patients with low ΔVO2. Several hours after ΔVO2 the patient‘s body temperature rose. Forward stepwise regression analysis showed that circulating endotoxin and TNF explained 50% of the variability of ΔVO2. Conclusions: This study demonstrates that patients with high post operative oxygen consumption after elective cardiac surgery have higher circulating levels of endotoxin, TNF and IL-6 and also have more symptoms of post-perfusion syndrome. Early detection of high VO2 might be used as a clinical signal to improve circulation in order to meet the high oxygen demand of inflammation. In addition, continuous measurement of VO2 provides us with a clinical parameter of inflammation in interventional studies aiming at a reduction of endotoxemia or circulating cytokines.
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  • 5
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Inflammatory bowel disease presents in various forms. Its increasing incidence indicates that modern lifestyle triggers disease in genetically susceptible individuals. We present a model for inflammatory bowel disease pathophysiology and review the new biological therapies available. These biological agents have been developed to antagonise the processes of pathogenic inflammation, such as the reduction in T-lymphocyte apoptosis, increase in T-lymphocyte proliferation and increase in T-lymphocyte trafficking into the intestinal mucosa. Inhibitors of various inflammatory cytokines, including some antagonists to tumour necrosis factor, are effective therapies for inflammatory bowel disease. However, this class is associated with the risk of rare, but serious, side-effects, such as opportunistic infections and demyelinating diseases. The administration of anti-inflammatory cytokines, including interleukin-10 and interleukin-11, may theoretically be effective in reducing inflammation, although the clinical development of some of these therapies has been terminated. The selective inhibition of the adhesion molecules involved in T-lymphocyte trafficking can be effective in reducing gut inflammation. Of the selective adhesion molecule inhibitors under investigation, natalizumab has demonstrated efficacy in inflammatory bowel disease. The future of biological therapy for inflammatory bowel disease shows promise.
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  • 6
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Interleukin (IL-)10 has been demonstrated to inhibit endotoxin-induced production of a number of pro-inflammatory cytokines. The present study sought to compare the appearances in the circulation of IL-10, IL-6 and IL-8, and to assess the roles ofendogenously produced platelet-activating factor (PAF) and IL-6 in IL-10 release during endotoxaemia in chimpanzees. Intravenous injection of endotoxin (lot EC-5, 4 ng/kg, n = 8) induced a transient rise in serum IL-10concentrations, peaking after 2 h (213 ± 70 pg/ml; P 〈 0.05). No correlations existed between peak IL-10 levels, and peak IL-6 and IL-8 levels. Neither infusion of the specific PAF antagonist TCV-309(n = 4), nor infusion of a neutralizing anti-IL-6 monoclonal antibody (n = 4) influenced endotoxin-induced IL-10 release. IL-10 release elicited by injection of endotoxin is not mediated by PAF or IL6. Tom van der Poll MD, Academic Medical Center, Department of Internal Medicine, F4222, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
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  • 7
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Infusion of anti-tumour necrosis factor-α appears to be highly effective in patients with Crohn's disease.Aim : To assess the effect of infliximab on the quality of life in patients with active or fistulizing disease, as measured by the inflammatory bowel disease questionnaire, and to examine the impact on its four dimensions.Methods : An observational study was conducted in 65 patients. An infusion of 5 mg/kg infliximab was given at week 0 in patients with active disease and at week 0, 2 and 6 in fistulizing disease. Changes from baseline in the total and dimensional inflammatory bowel disease questionnaire scores were calculated and compared between the patient groups. Potential predictors of change in the quality of life were identified.Results : In the active disease group, at week 4, the mean total and dimensional inflammatory bowel disease questionnaire scores improved compared to baseline (P 〈 0.001). In the fistulizing group, at week 6, all scores changed from baseline (P 〈 0.05). Improvement in the total inflammatory bowel disease questionnaire score correlated well with the improvement of the Crohn's disease activity index. Systemic and social scores improved more than bowel and emotional scores. Inflammatory Crohn's disease and a young age at diagnosis were predictors for a better response to infliximab therapy.Conclusions : Infliximab therapy improves all dimensions of the quality of life in patients with Crohn's disease.
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  • 8
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The high mortality rate in patients with upper gastrointestinal bleeding appears to be particularly related to re-bleeding. The haemostatic mechanisms that may influence the re-bleeding of ulcers are largely unknown.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:We studied and analysed fibrinolytic activity in bleeding ulcer patients and the effect of acid suppression on this activity.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Fibrinolytic activity was analysed in mucosal biopsies from 29 bleeding gastroduodenal ulcer patients and six controls. We analysed levels of D-Dimer, fibrin plate lysis area, plasminogen activator activity, plasminogen activator inhibitor activity, and plasmin antiplasmin complexes.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Significantly more fibrinolytic activity was detected in biopsies from patients with bleeding ulcers compared to controls. Moreover, in patients with endoscopic stigmata of recent haemorrhage, mucosal fibrinolytic activity was higher compared to patients without stigmata of recent haemorrhage. In mucosal biopsies of patients that had used acid suppression before admission, a decreased fibrinolytic activity was found compared to patients without such therapy. This effect of acid suppression on fibrinolytic activity was confirmed in nine patients before and after a 24-h ranitidine infusion.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:Fibrinolytic activity is enhanced in patients with bleeding gastroduodenal ulcers. Acid suppressive therapy decreases this increased activity, which may be one of the mechanisms explaining the potential beneficial effect of this therapy.
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  • 9
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The intestinal epithelium plays an important role in the recognition of pathogenic organisms and in the recruitment of inflammatory cells to the mucosa. Epithelial chemokine production may constitute a key target in future therapies for inflammatory bowel disease (IBD).Chemokines are divided into two subfamilies, the C-C family and C-X-C family. Most C-C chemokines target mononuclear cells and many C-X-C chemokines attract neutrophils. Interleukin-8 (IL-8), a C-X-C chemokine, acts as a motor for the recruitment of neutrophils into the non-inflamed mucosa and is present in both enterocytes and mucosal inflammatory cells. Epithelial cells may be the first to signal the presence of pathogens, as well as contributing to IL-8 production in IBD. Data have also shown that intestinal epithelial cells are able to respond to IL-1β and tumour necrosis factor-alpha (TNF-α) at concentrations known to occur in the inflamed mucosa. Monocyte chemotactic protein-1 (MCP-1), a member of the C-C chemokine family, is noticeably increased in IBD. These data show that C-X-C and C-C chemokines are equally important properties of mucosal epithelial cells.The effects of two anti-inflammatory drugs (dexamethasone and cyclosporin) on chemokine production are significantly different and this provides a rationale for combination therapy.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Intensive care medicine 23 (1997), S. 487-488 
    ISSN: 1432-1238
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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