Prevalence of flat lesions in a large screening population and their role in colonoscopy quality improvement.

BACKGROUND AND STUDY AIMS: Flat lesions pose new challenges for endoscopists, but the importance of detecting them is still controversial. Most screening studies do not survey macroscopic polyp morphology. The aims were to evaluate the percentage of flat polyp findings in a large asymptomatic adult screening population (n = 52 521), to assess the impact of shape and size on malignant transformation, and to assess the role of flat lesions regarding quality assurance in colorectal cancer prevention. MATERIAL AND METHODS: Retrospective analysis of screening colonoscopies performed between 2007 and 2011 according to the Austrian "Quality management for colon cancer prevention" program. RESULTS: 17 771 patients with polyps were included in the study. Patients with flat polyps represented 24.2 % (n = 4293), 62.4 % (n = 11 097) were classified as having sessile and 13.4 % (n = 2381) as pedunculated polyps. Among those with flat polyps 51.4 % had adenomas (n = 2207). High grade dysplasia (HGD) was found in 2.1 % (n = 47) of flat adenomas, in 1.5 % (n = 89) of sessile adenomas and 4.7 % (n = 92) of pedunculated adenomas (P < 0.0001. The risk for containing HGD was 1.0 % for flat lesions ≤ 10 mm in size compared with 10.3 % for lesions > 10 mm, and 1.0 % for polypoid lesions ≤ 10 mm compared with 9.3 % for lesions > 10 mm (P < 0.0001). Multivariable logistic regression showed that polyp size (P < 0.0001) but not polyp shape (P = 0.438) is an independent predictor for HGD. Adenoma detection rate (ADR) correlated weakly with the flat polyp detection rate (Pearson r = 0.24). CONCLUSION: Malignant potential of polyps is mostly affected by size but not by shape. Since flat polyp detection rate only correlates poorly with ADR we do not recommend its incorporation in quality assured screening colonoscopy.

Safety of gelatin for volume resuscitation--a systematic review and meta-analysis.

PURPOSE: Gelatin is frequently used as a volume expander in critical care. Our goal was to investigate its safety. METHODS: Systematic review of randomized controlled trials (RCT) in patients receiving gelatin for resuscitation in comparison to albumin or crystalloids. RESULTS: We identified 40 RCTs published between 1976 and 2010 with 3,275 patients. Median sample size in the gelatin groups was 15 patients (range 10-249). Median gelatin dose was 17 ml/kg (range 6-57 ml/kg). In 32 RCTs (n = 1,946/3,275, 59 % of all patients), the study period was ≤24.0 h. Twenty-nine RCTs (n = 2,001) investigated elective surgical patients, mostly undergoing cardiac surgery (18 RCTs, n = 819). Three RCTs (n = 723) investigated critically ill adults. Two RCTs (n = 59) were performed in emergency room patients, and six RCTs (n = 492) were performed in neonates or children. No study was adequately powered to investigate the frequency of patient-important outcomes. Risks were not statistically significantly different for mortality (RR 1.12, 95 % confidence interval, 0.87-1.44) and exposure to allogeneic transfusion (RR 1.28, 0.89-1.83). On account of only few included studies and the small number of patients, subgroup analyses (high vs. low dose, >24 h vs. shorter periods, and critically ill patients vs. others) were uninformative. Only three RCTs reported the occurrence of acute renal failure. CONCLUSION: Despite over 60 years of clinical practice, the safety and efficacy of gelatin cannot be reliably assessed in at least some settings in which it is currently used. We suggest the need to investigate and establish such safety.

[Supportive and adjunctive sepsis therapy]. / Supportive und adjunktive Therapie der Sepsis.

Severe sepsis and septic shock have an increasing incidence but an unchanged mortality. It has been demonstrated that the time until the start of supportive therapy affects the progress of multiorgan failure and patient outcome. Early goal-directed therapy guided by central venous oxygen saturation is associated with a significant reduction in mortality, as is the use of lung-protective mechanical ventilation and recombinant activated protein C (rhAPC) in eligible patients. The use of starches for volume resuscitation, low-dose dopamine and hydrocortison as well as an intensive insulin protocol for restoration of euglycemia is not recommended. The German Competence Network Sepsis (SepNet) is currently studying further relevant questions.

The role of procalcitonin in febrile neutropenic patients: review of the literature.

BACKGROUND: Procalcitonin (PCT) has been increasingly used as an inflammatory marker to identify patients with systemic infection. Moreover, PCT guidance allowed significant reduction of antibiotic therapy in patients with respiratory disease. The aim of this qualitative review was, therefore, to evaluate the role of PCT measurements in febrile neutropenic patients in differentiating between various causes of fever and to investigate the value of PCT levels in terms of diagnosing infection or predicting outcome in these patients. PATIENTS AND METHODS: A MEDLINE search was performed using the keyword 'procalcitonin' crossed with 'febrile neutropenia', 'neutropenia', 'fever', 'bone marrow transplantation', and 'stem cell transplantation', and limited to human studies published between January 1990 and October 2006. Bibliographies of identified articles were also searched. Predefined variables were collected from the articles, including year of publication, study design, number of patients included, age group, disease group, markers other than PCT, and study results. RESULTS: From the 30 articles included, PCT seems to be able to discriminate fever due to systemic forms of infection from non-infectious etiologies. Patients with fungal infection may have a delayed increase in PCT levels. PCT has a minimal role, if any, in discriminating Gram-negative from Gram-positive infections. PCT may be useful in outcome prediction in patients with febrile neutropenia but is not superior to interleukin-6 or C-reactive protein concentrations for this purpose. CONCLUSIONS: Despite lack of standard definitions, heterogeneity of study populations, and small numbers of patients included in some studies, our review provides important insight into the value of PCT as a diagnostic and prognostic tool in patients with febrile neutropenia.

Effects of hydroxyethyl starch administration on renal function in critically ill patients.

BACKGROUND: The influence of hydroxyethyl starch (HES) solutions on renal function is controversial. We investigated the effect of HES administration on renal function in critically ill patients enrolled in a large multicentre observational European study. METHODS: All adult patients admitted to the 198 participating intensive care units (ICUs) during a 15-day period were enrolled. Prospectively collected data included daily fluid administration, urine output, sequential organ failure assessment (SOFA) score, serum creatinine levels, and the need for renal replacement therapy (RRT) during the ICU stay. RESULTS: Of 3147 patients, 1075 (34%) received HES. Patients who received HES were older [mean (SD): 62 (SD 17) vs 60 (18) years, P = 0.022], more likely to be surgical admissions, had a higher incidence of haematological malignancy and heart failure, higher SAPS II [40.0 (17.0) vs 34.7 (16.9), P < 0.001] and SOFA [6.2 (3.7) vs 5.0 (3.9), P < 0.001] scores, and less likely to be receiving RRT (2 vs 4%, P < 0.001) than those who did not receive HES. The renal SOFA score increased significantly over the ICU stay independent of the type of fluid administered. Although more patients who received HES needed RRT than non-HES patients (11 vs 9%, P = 0.006), HES administration was not associated with an increased risk for subsequent RRT in a multivariable analysis [odds ratio (OR): 0.417, 95% confidence interval (CI): 0.05-3.27, P = 0.406]. Sepsis (OR: 2.03, 95% CI: 1.37-3.02, P < 0.001), cardiovascular failure (OR: 6.88, 95% CI: 4.49-10.56, P < 0.001), haematological cancer (OR: 2.83, 95% CI: 1.28-6.25, P = 0.01), and baseline renal SOFA scores > 1 (P < 0.01 for renal SOFA 2, 3, and 4 with renal SOFA = 0 as a reference) were all associated with a higher need for RRT. CONCLUSIONS: In this observational study, haematological cancer, the presence of sepsis, cardiovascular failure, and baseline renal function as assessed by the SOFA score were independent risk factors for the subsequent need for RRT in the ICU. The administration of HES had no influence on renal function or the need for RRT in the ICU.

Transcriptomic and proteomic patterns of systemic inflammation in on-pump and off-pump coronary artery bypass grafting.

BACKGROUND: Coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) provides controlled operative conditions but induces a whole-body inflammatory response capable of initiating devastating morbidity and mortality. Although technically more demanding, deliberate avoidance of CPB in off-pump surgery attenuates the physiological insult associated with CABG. METHODS AND RESULTS: To systematically assess the molecular mechanisms underlying the better-preserved remote organ function, we studied gene expression patterns in leukocytes and plasma proteomic response to on-pump and off-pump CABG. Proteomic analysis confirmed (tumor necrosis factor-alpha, interleukin [IL]-6, IL-10) and expanded (eg, interferon [IFN]-gamma, granulocyte colony-stimulating factor [G-CSF], monocyte chemotactic protein-1, macrophage inflammatory protein-1beta) the mediators released on CPB, whereas blood leukocyte transcriptomics suggested that circulating leukocytes are not primarily responsible for this response. Interestingly, release of some cytokines (eg, IL-6, IFN-gamma, G-CSF) was observed on off-pump surgery to a similar extent but with delayed kinetics. A total of 45 of 4868 transcripts were identified to be significantly altered as a result of initiation of CPB. Systematic analysis of transcriptional activation by CPB revealed primarily genes involved in inflammation-related cell-cell communication (such as L-selectin or intercellular adhesion molecule-2) and signaling (such as IL-1, IL-8, or IL-18 receptors and toll-like receptors 4, 5, and 6), thus confirming a "primed" phenotype of circulating peripheral blood mononuclear cells. CONCLUSIONS: Gene array and multiplex protein analysis, only in concert, can illuminate the molecular mechanisms responsible for systemic sequelae of CPB and indicate that circulating leukocytes overexpress adhesion and signaling factors after contact with CPB, which potentially facilitates their trapping, eg, in the lungs and may promote a subsequent tissue-associated inflammatory response.

[On the use of ultrasound to assist central vein cannulation in Germany: a surgery of 817 departments of anesthesia]. / Zur Anwendung von Ultraschall bei der Anlage zentraler Venenkatheter in Deutschland: Eine Umfrage unter 817 Anästhesieabteilungen.

OBJECTIVE AND METHODS: A survey on the current practice in using portable ultrasound machines to assist central vein cannulation was performed by sending a questionnaire to 817 departments of anaesthesiology and intensive care medicine in Germany. Also, incomplete questionnaires were included in the analysis. RESULTS: There was a 54 % response rate. Ultrasound guidance is used by 83 (18.7 %) departments for central vein cannulation. Of these, only 7 (8.4 %) use it routinely and 43 (51.8 %) use it when faced with a difficult vein cannulation. Only one third of the departments with ultrasound facilities are using it optimally, e. g. cannulation under ultrasound guidance. Of those units not using ultrasound for central vein cannulation, 136 (37.7 %) said it was because of lack of equipment and 199 (55.1 %) did not think that it was necessary. CONCLUSION: In Germany, placement of central venous catheters is usually based on anatomical landmarks. Every anaesthetist and intensive care physician should be able to place central venous catheters without an ultrasound device. Still there is not a doubt that ultrasound assistance is useful for beginners, in children, and when blind cannulation fails. Also in patients in whom catheterisation is likely to be difficult (e. g. patients, with previous central venous catheters, with abnormal anatomy etc.) Due to our data a promotion of ultrasound assistance seems urgently required.

Equivalence of hydroxyethyl starch HES 130/0. 4 and HES 200/0. 5 for perioperative volume replacement in major gynaecological surgery.

BACKGROUND: Hydroxyethyl starch solutions (HES) are increasingly used for the compensation of surgical blood loss. The objective of this clinical trial was to compare a novel 6% HES 130/0.4 solution with a favourable pharmacological profile and a standard 6% HES 200/0.5 solution for maintenance of haemodynamic stability in major gynaecological surgery. METHODS: Sixty female patients aged 18-80 years undergoing major gynaecological surgery with indication for perioperative colloidal volume replacement were enrolled in this prospective, randomized double-blinded clinical study. The administration of study medication was dependent on individual requirements to maintain haemodynamic stability. The amount of study medication required from induction of anaesthesia until 6 h postoperatively served as the primary investigative parameter. RESULTS: The two one-sided test procedure by Westlake demonstrated equivalence of mean infused volumes between HES 130/0.4 and HES 200/0.5 during the study period (1224 +/- 544 ml and 1389 +/- 610 ml, respectively, P < 0.05). Perioperatively, haemodynamics did not differ significantly between treatment groups. While none of the mean values of coagulation parameters shifted outside the normal range, the degree of haemodilution revealed reduced haematocrit values in HES 200/0.5 treated patients at 6 h postoperatively (P < 0.05). Moreover, prothrombin time (PT) was higher and consequently international normalized ratio (INR) was lower at the same time point for patients who received HES 130/0.4 (P < 0.05). CONCLUSION: This clinical trial demonstrated therapeutic equivalence of this novel low-substituted HES 130/0.4 solution and a standard HES 200/0.5 solution for perioperative volume replacement. Moreover, both HES preparations were equally well-tolerated and safe.

Left ventricular regional wall motion abnormalities during pneumoperitoneum in children.

BACKGROUND: In adult patients, certain levels of PEEP (16 and 20 cm H(2)O) have been associated with left ventricular (LV) regional wall motion abnormalities. Since any increase in intra-abdominal pressure (IAP) exerted by a pneumoperitoneum is transmitted to the intrathoracic cavity, similar effects on LV regional wall motion cannot be ruled out. METHODS: To investigate the effects of pneumoperitoneum on LV regional wall motion, we performed a post hoc analysis of a transoesophageal echocardiography study in eight small children (mean age 3 yr, range 15-63 months) undergoing laparoscopic herniorrhaphy under anaesthesia with sevoflurane in nitrous oxide/oxygen and a PEEP of 5 cm H(2)O. During carbon dioxide insufflation, end-tidal carbon dioxide concentration ()was kept constant by increasing minute volume. RESULTS: An IAP of 12 mm Hg caused significant septal hypokinesia compared with baseline, while anterior and posterior wall motion was not affected. In addition, a lateral hyperkinesia occurred, though this change was not statistically significant. CONCLUSIONS: Pneumoperitoneum may affect LV regional wall motion in paediatric patients undergoing laparoscopic surgery.

[Transesophageal echocardiography and intraoperative management of patients with renal cell carcinoma and rena cava extension]. / TEE bei intracavaler Ausdehnung von Nierenzellkarzinomen. Intraoperatives Management mit transösophagealer Echokardiographie.

OBJECTIVE: To evaluate the role of intraoperative real-time transesophageal echocardiography (TEE) for the anesthetic and surgical management of patients with renal cell carcinoma and vena cava extension. METHODS: Retrospective analysis of the intraoperative application of TEE in a series of 4 patients. RESULTS: Real-time TEE with a multiplane probe allowed visualization of inferior vena cava tumor extensions, accurate assessment of the distal extent of vena cava invasion into hepatic veins and right atrium, monitoring of embolism and evaluation of cardiac preload and function in all patients. CONCLUSION: Intraoperative TEE is a useful adjunct to the anesthetic and surgical management of patients with renal cell carcinoma and vena cava extension.

[New treatment approaches in sepsis]. / Neue Therapieansätze bei Sepsis.

The treatment of sepsis consists of focus control as well as supportive and adjuvant therapy. Especially the last option has been investigated during the last years. Different approaches showed promising results in animal experiments and phase-I trials but did not prove to be successful in large multicenter studies. The application of TNF-receptors or interleukin-1 receptor antagonists did not lead to an improvement of outcome in patients with sepsis. Most studies with TNF-antibodies also presented negative results. However, a recent large study with a monoclonal antibody against TNFalpha demonstrated a significant survival benefit. The recently published PROWESS study is the first investigation demonstrating the decrease of mortality in patients with sepsis after administration of protein C. Additionally, current data support the low-dose hydrocortisone therapy in patients with vasopressor dependent septic shock.

Procalcitonin and CGRP-1 mrna expression in various human tissues.

Procalcitonin (PCT) is a highly sensitive and specific marker of systemic bacterial infection and sepsis. In contrast to its diagnostic significance, the cellular sources of plasma procalcitonin remain to be clarified. Two forms of PCT mRNAs originate from calcitonin/calcitonin gene-related peptide gene (CALC-I gene) along with mRNA for calcitonin gene-related peptide-I (CGRP-I). Reverse transcription polymerase chain reaction with newly designed primers detecting different PCT mRNAs and CGRP-I mRNA was used to identify tissues that might contribute to PCT production. Our study indicates that a variety of human tissues (13 of the 16 analyzed overall) express PCT-I, PCT-II, and/or CGRP-I mRNAs, with the highest levels detected for liver, testis, lung, prostate, kidney, and small intestine. Various tissues differ in the proportions of PCT-I, PCT-II, and CGRP-I mRNA expression levels. Thus we demonstrate the complexity of tissue-specific regulation of CALC-I gene expression and suppose a variety of tissues as a potential source of CALC-I-encoded peptides.

Anti-tumor necrosis factor therapy in sepsis: update on clinical trials and lessons learned.

OBJECTIVE: Tumor necrosis factor (TNF) is an important mediator involved in the pathogenesis of sepsis. We review clinical studies investigating the efficacy of anti-TNF therapy in decreasing mortality rates in septic patients. DATA SOURCES: We conducted a computerized bibliographic search of randomized, clinical, multicenter trials studying the effects of anti-TNF therapy in the treatment of sepsis. We included all primary studies, reviewed all published meta-analyses, and contacted primary investigators of multicenter trials where necessary. DATA SYNTHESIS: Almost all randomized studies targeting TNF during sepsis show a small, albeit nonsignificant, benefit in decreasing mortality. Strategies using monoclonal antibodies are more effective than are strategies using TNF receptor proteins. Analysis of randomized multicenter trials shows a small but significant benefit with anti-TNF therapeutic strategies. Furthermore, a recent study in 2634 septic patients using a murine anti-TNF antibody shows a 3.6% significant benefit in reducing mortality. CONCLUSIONS: Anti-TNF strategies are only partially effective in patients with sepsis. Although individual studies show small, nonsignificant benefits, analysis of all trial data as well as data from a recent trial in a large population of septic patients show that anti-TNF strategies may confer a small survival benefit. Better characterization of patients and a more multimodal approach by concomitantly targeting other mediators involved in sepsis may be helpful in enlarging the clinical benefit of anti-TNF therapy.

Randomized, placebo-controlled trial of the anti-tumor necrosis factor antibody fragment afelimomab in hyperinflammatory response during severe sepsis: The RAMSES Study.

OBJECTIVE: This study investigated whether treatment with the anti-tumor necrosis factor-alpha monoclonal antibody afelimomab would improve survival in septic patients with serum interleukin (IL)-6 concentrations of >1000 pg/mL. DESIGN: Multicenter, double-blind, randomized, placebo-controlled study. SETTING: Eighty-four intensive care units in academic medical centers in Europe and Israel. PATIENTS: A total of 944 septic patients were screened and stratified by the results of a rapid qualitative immunostrip test for serum IL-6 concentrations. Patients with a positive test kit result indicating IL-6 concentrations of >1000 pg/mL were randomized to receive either afelimomab (n = 224) or placebo (n = 222). Patients with a negative IL-6 test (n = 498) were not randomized and were followed up for 28 days. INTERVENTIONS: Treatment consisted of 15-min infusions of 1 mg/kg afelimomab or matching placebo every 8 hrs for 3 days. Standard surgical and intensive care therapy was otherwise delivered. MEASUREMENTS AND MAIN RESULTS: The study was terminated prematurely after an interim analysis estimated that the primary efficacy end points would not be met. The 28-day mortality rate in the nonrandomized patients (39.6%, 197 of 498) was significantly lower (p <.001) than that found in the randomized patients (55.8%, 249 of 446). The mortality rates in the IL-6 test kit positive patients randomized to afelimomab and placebo were similar, 54.0% (121 of 224) vs. 57.7% (128 of 222), respectively. Treatment with afelimomab was not associated with any particular adverse events. CONCLUSIONS: The IL-6 immunostrip test identified two distinct sepsis populations with significantly different mortality rates. A small (3.7%) absolute reduction in mortality rate was found in the afelimomab-treated patients. The treatment difference did not reach statistical significance.

Cellular and biochemical mechanisms by which environmental oestrogens influence reproductive function.

The biology and physiology of the male as well as female reproductive system is hormonally regulated. Abnormalities in the dynamics of hormone production, metabolism and elimination, as well as their binding to certain target tissues, has been associated with pathophysiological conditions of the reproductive system. Although oestrogens are known to be one of the major hormone groups in regulating the reproductive function and the fertilization process, the cellular and biochemical mechanism or mechanism(s) via which oestrogens induce their effects are still not fully defined. Moreover, in a modern environment we are also exposed to a wide battery of environmental agents which are structurally similar to oestrogens, and termed 'environmental oestrogens'. Because environmental oestrogens have been shown to mimic some of the effects of oestradiol, it has been postulated that these exogenous chemicals may influence or interfere with the oestrogen-dependent reproductive processes, and may be associated with beneficial as well as deleterious effects on the reproductive system. In this regard, two classes of environmental oestrogens have been widely studied, i.e. phyto-oestrogens (plant-derived dietary oestrogens) and xeno-oestrogens (industrial chemicals, including polychlorinated biphenyls, DDT, TCDD, dioxins, etc.). The main focus of this review is to provide an overview on the cellular and biochemical mechanism(s) by which xeno-oestrogens and phyto-oestrogens influence the oestrogen-dependent reproductive functions and induce their deleterious or protective effects on the reproductive system.

Transoesophageal echocardiographic assessment of haemodynamic changes during laparoscopic herniorrhaphy in small children.

Laparoscopic techniques for surgery are gradually becoming established in paediatric surgery. Technical aspects, such as the maximum safe gas insufflation pressure, are still open to discussion. We used transoesophageal echocardiography to study the haemodynamic changes in eight small children undergoing laparoscopic herniorrhaphy, with two different levels of intra-abdominal pressure (IAP), 6 and 12 mm Hg. End-tidal carbon dioxide tension was maintained constant at 4.3-4.7 kPa. After baseline measurements, an IAP of 12 mm Hg was applied for 10 min. Next, IAP was decreased to 6 mm Hg, followed by a second period of 12 mm Hg. Haemodynamic measurements were obtained at each stage. A further measurement was obtained 10 min after abdominal deflation at the end of surgery while anaesthesia was unchanged. Cardiac index (CI) decreased significantly only after the first 12 mm Hg level of IAP. The subsequent decrease in IAP to 6 mm Hg caused return of CI to baseline levels. The second increase in IAP did not cause any reduction in CI. The initial reduction in CI, although statistically significant, did not appear to be clinically important. We conclude that an IAP of up to 12 mm Hg appeared to be safe in healthy small children undergoing laparoscopic herniorrhaphy.

Discriminative power of inflammatory markers for prediction of tumor necrosis factor-alpha and interleukin-6 in ICU patients with systemic inflammatory response syndrome (SIRS) or sepsis at arbitrary time points.

OBJECTIVES: To determine the correlations and predictive strength of surrogate markers (body temperature, leukocyte count, C-reactive protein (CRP) and procalcitonin (PCT)) with elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in septic patients on randomly chosen days. DESIGN: Prospective consecutive case series. SETTING: Surgical intensive care unit (ICU) of a university hospital. PATIENTS: Two hundred forty-three patients experiencing ICU stays of longer than 48 h categorized for sepsis according to ACCP/SCCM Consensus Conference criteria. MEASUREMENTS AND MAIN RESULTS: CRP and PCT were both significantly correlated with TNF-alpha and IL-6. Based on the area under the curve (AUC) of the receiver operating characteristic (ROC) curves, predictive capability was highest for PCT (0.846 for TNF-alpha>40 pg/ml and 0.837 for IL-6>500 pg/ml), moderate with CRP (0.744 and 0.748, respectively), and lowest for leukocyte count (0.562 and 0.534, respectively) and body temperature (0.570 and 0.623, respectively). Sensitivity, specificity, positive and negative predictive values and test effectiveness all followed this same pattern of being highest for PCT followed by CRP, with leukocyte count and body temperature being lowest. CONCLUSION: PCT may be an early and better marker of elevated cytokines than the more classic criteria of inflammation.

Sensitivity and specificity of various markers of inflammation for the prediction of tumor necrosis factor-alpha and interleukin-6 in patients with sepsis.

OBJECTIVES: To determine correlations and predictive strength of surrogate markers (body temperature, leukocyte count, C-reactive protein [CRP], and procalcitonin [PCT]) with elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in septic patients. DESIGN: Prospective consecutive case series. SETTING: Surgical intensive care unit (ICU) of a university hospital. PATIENTS: A total of 175 patients experiencing intensive care unit stays >48 hrs categorized for sepsis according to ACCP/ SCCM Consensus Conference criteria. MEASUREMENTS AND MAIN RESULTS: CRP and PCT were both significantly correlated with TNF-alpha and IL-6. Based on the area-under-the-curve of the receiver operating characteristics curves, predicting capability was highest for PCT (0.814 for TNF-alpha >40 pg/mL and 0.794 for IL-6 >500 pg/mL), moderate with CRP (0.732 and 0.716, respectively), and lowest for leukocyte count (0.493 and 0.483, respectively) and body temperature (0.587 and 0.589, respectively). Sensitivity, specificity, positive, and negative predictive values and test effectiveness all followed this same pattern of being highest for PCT followed by CRP, with leukocyte count and body temperature being lowest. CONCLUSION: PCT may be an early and better marker of elevated cytokines than the more classic criteria of inflammation.

Xeno-oestrogens and phyto-oestrogens induce the synthesis of leukaemia inhibitory factor by human and bovine oviduct cells.

In bovine oviduct cells 17beta-oestradiol can induce the synthesis of leukaemia inhibitory factor (LIF), a glycoprotein essential for embryo implantation. Therefore substances which are structurally similar to 17beta-oestradiol and possess oestrogenic activity may also modulate LIF synthesis and influence the reproductive process. We used primary cultures of bovine and human oviduct cells (epithelial cells:fibroblasts 1:1) to compare the effects of 17beta-oestradiol, phyto-oestrogens (genistein, biochanin A, daidzein, formononetin, and equol) and xeno-oestrogens [polychlorinated biphenyls (PCB): trichlorobiphenyl, 4-hydroxy-trichlorobiphenyl and 4-hydroxy-dichlorobiphenyl] on LIF synthesis. Immunoreactive LIF-enzyme-linked immunosorbent assay was used to determine the concentration of LIF in the culture medium. Similar to 17beta-oestradiol, genistein (0.02-2 micromol/l) induced LIF synthesis in bovine oviduct cells in a concentration-dependent manner. Equol, biochanin A and daidzein (2 micromol/l), 4-hydroxy-trichlorobiphenyl and 4-hydroxy-dichlorobiphenyl (0.01-10 micromol/l) but not formononetin (2 micromol/l) also induced LIF synthesis in bovine cells. Phyto-oestrogens and xeno-oestrogens also induced LIF synthesis in human oviduct cells (P < 0.05). The stimulatory effects of PCB, phyto-oestrogens and 17beta-oestradiol were blocked by ICI 182,780 (1 micromol/l). Moreover, 17beta-oestradiol, 4-hydroxy-trichlorobiphenyl, 4-hydroxy-dichlorobiphenyl, genistein, tamoxifen and ICI 182,780 displaced [(3)H]17beta-oestradiol from cytosolic oestrogen receptors in bovine oviduct cells. These results suggest that phyto-oestrogens and PCB mimic the effects of oestradiol in inducing LIF synthesis by bovine and human oviduct cells and that these stimulatory effects are oestrogen receptor-mediated. Environmental oestrogens act as endocrine modulators/disrupters and may induce deleterious effects on the reproductive process by influencing LIF synthesis in a non-cyclic fashion leading to tubal infertility.

Molecular aspects and natural source of procalcitonin.

The search for sensitive and specific markers of systemic infection has shown that procalcitonin levels are increased in sepsis, and, consequently, this plasma protein has come into the focus of clinical research. Human procalcitonin is encoded by the Calc-l gene, which gives rise to two alternatively spliced transcripts. Despite systemic investigation of the Calc-l gene and mechanisms of the tissue-specific regulation and alternative splicing, little is known about the biology of procalcitonin and the cells which express this protein during inflammation. Here we focus on the molecular and biochemical properties of the molecule and summarize the known biological functions of procalcitonin. We report on the structure of the Calc-l gene, the amino acid conservation of procalcitonin in different species, and the consensus sequences of the protein with regard to sites relevant for posttranslational modification, spatial distribution, and homologies to other cytokines. We discuss aspects of intracellular location of procalcitonin and demonstrate that it has the characteristics of a secreted protein.