Factors influencing preoperative stress response in coronary artery bypass graft patients

BACKGROUND: In many studies investigating measures to attenuate the hemodynamic and humoral stress response during induction of anaesthesia, primary attention was paid to the period of endotracheal intubation since it has been shown that even short-lasting sympathetic cardiovascular stimulation may have detrimental effects on patients with coronary artery disease. The aim of this analysis was, however, to identify the influencing factors on high catecholamine levels before induction of anaesthesia. METHODS: Various potential risk factors that could impact the humoral stress response before induction of anaesthesia were recorded in 84 males undergoing coronary aortic bypass surgery, and were entered into a stepwise linear regression analysis. The plasma level of norepinephrine measured immediately after radial artery canulation was chosen as a surrogate marker for the humoral stress response, and it was used as the dependent variable in the regression model. Accordingly, the mean arterial blood pressure, heart rate and the calculated pressure-rate product were taken as parameters of the hemodynamic situation. RESULTS: Stepwise regression analysis revealed that the oral administration of low-dose clonidine (mean dose 1.75 μg·kg(-1)) on the morning of surgery was the only significant predictor (p = 0.004) of the high variation in preoperative norepinephrine plasma levels. This intervention decreased norepinephrine levels by more than 40% compared to no clonidine administration, from 1.26 to 0.75 nmol·l(-1). There was no evidence for dose-responsiveness of clonidine. All other potential predictors were removed from the model as insignificant (p > 0.05). The use of beta-blocker, ace-inhibitors, ejection fraction, and body mass index were significant determinants for the hemodynamic situation (heart rate, mean arterial pressure, pressure rate product) of the patient during the pre-induction period. CONCLUSION: The oral administration of clonidine is the only significant predictor for the observed variation of norepinephrine levels during the preoperative period. Lack of significant dose responsiveness suggests that even a low dose of the drug can attenuate the preoperative stress response and thus is recommended in cardiovascular high risk patients

Targeting the Neurokinin Receptor 1 with Aprepitant: A Novel Antipruritic Strategy

Chronic pruritus is a global clinical problem with a high impact on the quality of life and lack of specific therapies. It is an excruciating and frequent symptom of e.g. uncurable renal, liver and skin diseases which often does not respond to conventional treatment with e.g. antihistamines. Therefore antipruritic therapies which target physiological mechanisms of pruritus need to be developed. Substance P (SP) is a major mediator of pruritus. As it binds to the neurokinin receptor 1 (NKR1), we evaluated if the application of a NKR1 antagonist would significantly decrease chronic pruritus.Twenty hitherto untreatable patients with chronic pruritus (12 female, 8 male; mean age, 66.7 years) were treated with the NKR1 antagonist aprepitant 80 mg for one week. 16 of 20 patients (80%) experienced a considerable reduction of itch intensity, as assessed by the visual analog scale (VAS, range 0 to 10). Considering all patients, the mean value of pruritus intensity was significantly reduced from 8.4 VAS points (SD +/-1.7) before treatment to 4.9 VAS points (SD +/-3.2) (p<0.001, CI 1.913-5.187). Patients with dermatological diseases (e.g. atopic diathesis, prurigo nodularis) had the best profit from the treatment. Side-effects were mild (nausea, vertigo, and drowsiness) and only occurred in three patients.The high response rate in patients with therapy refractory pruritus suggests that the NKR1 antagonist aprepitant may indeed exhibit antipruritic effects and may present a novel, effective treatment strategy based on pathophysiology of chronic pruritus. The results are promising enough to warrant confirming the efficacy of NKR1 antagonists in a randomized, controlled clinical trial

Sciatic lateral popliteal block with clonidine alone or clonidine plus 0.2% ropivacaine: effect on the intra-and postoperative analgesia for lower extremity surgery in children: a randomized prospective controlled study

<p>Abstract</p> <p>Background</p> <p>The effect of adding clonidine to local anesthetics for nerve or plexus blocks remains unclear. Most of the studies in adults have demonstrated the positive effects of clonidine on intra- and postoperative analgesia when used as an adjunctive agent or in some cases as a single to regional techniques. In the pediatric population, there are only few trials involving clonidine as an adjunct to regional anesthesia, and the analgesic benefits are not definite in this group of patients. The evidence concerning perineural administration of clonidine is so far inconclusive in children, as different types and volume of local anesthetic agents have been used in these studies. Moreover, the efficacy of regional anesthesia is largely affected by the operator's technique, accuracy and severity of operation.</p> <p>Methods</p> <p>The use of clonidine alone or combined with 0.2% ropivacaine for effective analgesia after mild to moderate painful foot surgery was assessed in 66 children, after combined sciatic lateral popliteal block (SLPB) plus femoral block. The patients were randomly assigned into three groups to receive placebo, clonidine, and clonidine plus ropivacaine. Time to first analgesic request in the groups was analyzed by using Kaplan-Meier and the log-rank test (mean time, median time, 95% CI).</p> <p>Results</p> <p>In our study, clonidine administered alone in the SLPB seems promising, maintaining intraoperatively the hemodynamic parameters SAP, DAP, HR to the lower normal values so that no patient needed nalbuphine under 0.6 MAC sevoflurane anesthesia, and postoperatively without analgesic request for a median time of 6 hours. In addition, clonidine administered as adjuvant enhances ropivacaine's analgesic effect for the first postoperative day in the majority of children (p = 0.001). Clonidine and clonidine plus ropivacaine groups also didn’t demonstrate PONV, motor blockade, and moreover, the parents of children expressed their satisfaction with the excellent perioperative management of their children, with satisfaction score 9.74 ± 0.45 and 9.73 ± 0.70 respectively. On the contrary all the patients in the control group required rescue nalbuphine in the recovery room, and postoperatively, along with high incidence of PONV, and the parents of children reported a low satisfaction score (7.50 ± 0.70).</p> <p>Conclusions</p> <p>Clonidine appears promising more as an adjuvant in 0.2% ropivacaine and less than alone in the SLPB plus femoral block in children undergoing mild to moderate painful foot surgery, with no side effects.</p> <p>Trial registration</p> <p>ClinicalTrials.gov, <a href="http://www.controlled-trials.com/ISRCTN90832436">ISRCTN90832436</a>, (ref: CCT-NAPN-20886).</p

Evidence of Transfer by Conjugation of Type IV Secretion System Genes between Bartonella Species and Rhizobium radiobacter in Amoeba

Background: Bartonella species cospeciate with mammals and live within erythrocytes. Even in these specific niches, it has been recently suggested by bioinformatic analysis of full genome sequences that Lateral Gene Transfer (LGT) may occur but this has never been demonstrated biologically. Here we describe the sequence of the B. rattaustraliani (AUST/NH4 T) circular plasmid (pNH4) that encodes the tra cluster of the Type IV secretion system (T4SS) and we eventually provide evidence that Bartonella species may conjugate and exchange this plasmid inside amoeba. Principal Findings: The T4SS of pNH4 is critical for intracellular viability of bacterial pathogens, exhibits bioinformatic evidence of LGT among bacteria living in phagocytic protists. For instance, 3 out of 4 T4SS encoding genes from pNH4 appear to be closely related to Rhizobiales, suggesting that gene exchange occurs between intracellular bacteria from mammals (bartonellae) and plants (Rhizobiales). We show that B. rattaustraliani and Rhizobium radiobacter both survived within the amoeba Acanthamoeba polyphaga and can conjugate together. Our findings further support the hypothesis that tra genes might also move into and out of bacterial communities by conjugation, which might be the primary means of genomic evolution for intracellular adaptation by cross-talk of interchangeable genes between Bartonella species and plant pathogens. Conclusions: Based on this, we speculate that amoeba favor the transfer of genes as phagocytic protists, which allows fo

Posttraumatic stress disorder among female street-based sex workers in the greater Sydney area, Australia

BACKGROUND: This paper examines rates of exposure to work-related violence and other trauma, and the prevalence of lifetime and current posttraumatic stress disorder (PTSD) among female street-based sex workers. It also investigates associations between current PTSD symptoms and: demographic characteristics, psychiatric comorbidity, injecting and sex risk behaviours, and trauma history. METHODS: Cross sectional data collected from 72 women via face to face structured interviews. The interview included structured diagnostic assessment of DSM-IV PTSD; drug dependence; depression; experience of childhood trauma; and an assessment of sex working history. RESULTS: All but one of the women interviewed reported experiencing trauma, with the majority reporting multiple traumas that typically began in early childhood. Child sexual abuse, adult sexual assault and work related violence were commonly reported. Just under half of the women met DSM-IV criteria for PTSD and approximately one-third reported current PTSD symptoms. Adult sexual assault was associated with current PTSD symptoms. Depression and drug dependence were also highly prevalent; cocaine dependence in particular was associated with elevated rates of injecting risk and sexual risk behaviours. CONCLUSION: These women reported complex trauma histories and despite ongoing opportunities for clinical intervention, they continued to experience problems, suggesting that current models of treatment may not be appropriate. More targeted interventions, and integrated mental health and drug treatment services are needed to address the problems these women are experiencing. Outreach services to these women remain a priority. Education strategies to reduce risky injecting and sexual behaviours among sex workers should also remain a priority

Epstein-Barr virus as a marker of biological aggressiveness in breast cancer

International audienceAlthough a potential role of the Epstein-Barr virus (EBV) in the pathogenesis of breast cancer (BC) has been underlined, results remain conflicting. Particularly, the impact of EBV infection on biological markers of BC has received little investigation

Prostaglandin D2-supplemented “functional eicosanoid testing and typing” assay with peripheral blood leukocytes as a new tool in the diagnosis of systemic mast cell activation disease: an explorative diagnostic study

Background: Systemic mast cell activation disease (MCAD) is characterized by an enhanced release of mast cell-derived mediators, including eicosanoids, which induce a broad spectrum of clinical symptoms. Accordingly, the diagnostic algorithm of MCAD presupposes the proof of increased mast cell mediator release, but only a few mediators are currently established as routine laboratory parameters. We thus initiated an explorative study to evaluate in vitro typing of individual eicosanoid pattern of peripheral blood leukocytes (PBLs) as a new diagnostic tool in MCAD. Methods: Using the “functional eicosanoid testing and typing” (FET) assay, we investigated the balance (i.e. the complex pattern of formation, release and mutual interaction) of prostaglandin E2 (PGE2) and peptido-leukotrienes (pLT) release from PBLs of 22 MCAD patients and 20 healthy individuals. FET algorithms thereby consider both basal and arachidonic acid (AA)-, acetylsalicylic acid (ASA)-, and substance P (SP)-triggered release of PGE2 and pLT. The FET assay was further supplemented by analyzing prostaglandin D2 (PGD2), as mast cell-specific eicosanoid. Results: We observed marked PGE2-pLT imbalances for PBLs of MCAD patients, as indicated by a markedly enhanced mean FET value of 1.75 ± 0.356 (range: 1.14–2.36), compared to 0.53 ± 0.119 (range: 0.36-0.75) for healthy individuals. In addition, mean PGD2 release from PBLs of MCAD patients was significantly, 6.6-fold higher than from PBLs of healthy individuals (946 ± 302.2 pg/ml versus 142 ± 47.8 pg/ml; P < 0.001). In contrast to healthy individuals, PGD2 release from PBLs of MCAD patients was markedly triggered by SP (mean: 1896 ± 389.7 pg/ml; P < 0.001), whereas AA and ASA caused individually varying effects on both PGD2 and pLT release. Conclusions: The new in-vitro FET assay, supplemented with analysis of PGD2, demonstrated that the individual patterns of eicosanoid release from PBLs can unambiguously distinguish MCAD patients from healthy individuals. Notably, in our analyses, the FET value and both basal and triggered PGD2 levels were not significantly affected by MCAD-specific medication. Thus, this approach may serve as an in-vitro diagnostic tool to estimate mast cell activity and to support individualized therapeutic decision processes for patients suffering from MCAD

Plasmids and Rickettsial Evolution: Insight from Rickettsia felis

BACKGROUND: The genome sequence of Rickettsia felis revealed a number of rickettsial genetic anomalies that likely contribute not only to a large genome size relative to other rickettsiae, but also to phenotypic oddities that have confounded the categorization of R. felis as either typhus group (TG) or spotted fever group (SFG) rickettsiae. Most intriguing was the first report from rickettsiae of a conjugative plasmid (pRF) that contains 68 putative open reading frames, several of which are predicted to encode proteins with high similarity to conjugative machinery in other plasmid-containing bacteria. METHODOLOGY/PRINCIPAL FINDINGS: Using phylogeny estimation, we determined the mode of inheritance of pRF genes relative to conserved rickettsial chromosomal genes. Phylogenies of chromosomal genes were in agreement with other published rickettsial trees. However, phylogenies including pRF genes yielded different topologies and suggest a close relationship between pRF and ancestral group (AG) rickettsiae, including the recently completed genome of R. bellii str. RML369-C. This relatedness is further supported by the distribution of pRF genes across other rickettsiae, as 10 pRF genes (or inactive derivatives) also occur in AG (but not SFG) rickettsiae, with five of these genes characteristic of typical plasmids. Detailed characterization of pRF genes resulted in two novel findings: the identification of oriV and replication termination regions, and the likelihood that a second proposed plasmid, pRFδ, is an artifact of the original genome assembly. CONCLUSION/SIGNIFICANCE: Altogether, we propose a new rickettsial classification scheme with the addition of a fourth lineage, transitional group (TRG) rickettsiae, that is unique from TG and SFG rickettsiae and harbors genes from possible exchanges with AG rickettsiae via conjugation. We offer insight into the evolution of a plastic plasmid system in rickettsiae, including the role plasmids may have played in the acquirement of virulence traits in pathogenic strains, and the likely origin of plasmids within the rickettsial tree

Soy isoflavones and their relationship with microflora: beneficial effects on human health in equol producers

The bioavailability of soy isoflavones depends on the composition of the microflora for each subject. Bacteria act on different isoflavones with increased or reduced absorption and cause biotransformation of these compounds into metabolites with higher biological activity. S-equol is the most important metabolite and only 25–65 % of the population have the microflora that produces this compound. The presence of equol-producing bacteria in soy product consumers means that the consumption of such products for prolonged periods leads to lower cardiovascular risk, reduced incidence of prostate and breast cancer, and greater relief from symptoms related to the menopause such as hot flushes and osteoporosis

Prevention of acute kidney injury and protection of renal function in the intensive care unit

Acute renal failure on the intensive care unit is associated with significant mortality and morbidity. To determine recommendations for the prevention of acute kidney injury (AKI), focusing on the role of potential preventative maneuvers including volume expansion, diuretics, use of inotropes, vasopressors/vasodilators, hormonal interventions, nutrition, and extracorporeal techniques. A systematic search of the literature was performed for studies using these potential protective agents in adult patients at risk for acute renal failure/kidney injury between 1966 and 2009. The following clinical conditions were considered: major surgery, critical illness, sepsis, shock, and use of potentially nephrotoxic drugs and radiocontrast media. Where possible the following endpoints were extracted: creatinine clearance, glomerular filtration rate, increase in serum creatinine, urine output, and markers of tubular injury. Clinical endpoints included the need for renal replacement therapy, length of stay, and mortality. Studies are graded according to the international Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) group system Several measures are recommended, though none carries grade 1A. We recommend prompt resuscitation of the circulation with special attention to providing adequate hydration whilst avoiding high-molecular-weight hydroxy-ethyl starch (HES) preparations, maintaining adequate blood pressure using vasopressors in vasodilatory shock. We suggest using vasopressors in vasodilatory hypotension, specific vasodilators under strict hemodynamic control, sodium bicarbonate for emergency procedures administering contrast media, and periprocedural hemofiltration in severe chronic renal insufficiency undergoing coronary intervention