Electroencephalographic changes during experimental hangover.

The EEG was recorded in 27 subjects during hangover. Male healthy volunteers drank 1.75 g/kg body weight of ethanol in 3 h and the EEG was recorded 14-16 h later when the degree of hangover was highest. For control purposes a second EEG was recorded after a similar session when subjects drank water instead of ethanol. A third record was taken in normal laboratory conditions. T5-A1 and O1-A1 derivations were subjected to computer analysis from which spectral and frequency parameters were calculated. Visual analysis of the EEG during hangover showed a decrease and slowing of alpha activity and an increase in theta activity. Spectral analysis of the EEG gave a statistically significant increase in 7-8 c/sec activity during hangover. The EEG change could not be explained in terms of blood alcohol level, hypoglycaemia or acidosis. Also fatigue could be excluded as a cause of EEG change by means of "water controls". The conclusion is that the slowing of the EEG during hangover is caused by the depressant action of ethanol, or its metabolites, on cortical function.     

Low cdc27 and high securin expression predict short survival for breast cancer patients

Cell cycle regulators cdc27 and securin participate in control of the mitotic checkpoint and survey the mitotic spindle to maintain chromosomal integrity. This is achieved by their functions in metaphase–anaphase transition, DNA damage repair, enhancement of mitotic arrest and apoptosis. We report on the roles of cdc27 and securin in aneuploidy and prognosis of breast cancer. The study comprises 429 breast cancer patients with up to 22 years of follow‐up. DNA content was determined by image cytometry, and immunopositivity for cdc27 and securin was based on tissue microarrays. An inverse association between cdc27 and securin expression was observed in both image cytometric and immunohistochemical analyses. Low cdc27 and high securin expression identified patients with significant difference in disease outcome. Cdc27 and securin immunoexpression identified patients at risk of early cancer death within five years from diagnosis. In multivariate analysis, the combination of cdc27 and securin immunohistochemistry was the strongest predictor of cancer death after lymph node status. We demonstrate, for the first time in human breast cancer, the prognostic value of cdc27 and securin immunohistochemistry. Cdc27 and securin appear promising biomarkers for applications in predicting disease progression, prognostication of individual patients and potential in anti‐mitotic drug development.     

Nitric oxide boosts TLR‐4 mediated lipocalin 2 expression in chondrocytes

Lipocalin 2 (LCN2) has recently emerged as a novel adipokine involved in different processes including arthritis and chondrocyte inflammatory response. However, little is known about its activity on chondrocyte homeostasis and its regulation by nitric oxide (NO) Hence, we performed a set of experiments aimed to achieve a better understanding of this relationship. Cell vitality was tested in the ATDC5 cell line by the MTT colorimetric assay. Protein expression and gene expression was evaluated by Western blot and real time RT‐PCR, respectively. NO production (determined as nitrite accumulation) was assayed by the Griess reaction. First, we demonstrated that LCN2 decreased murine chondrocytes vitality. Next, LCN2 co‐stimulation with LPS enhanced NOS2 protein expression by murine chondrocytes. In addition, inhibition of LPS‐induced nitric oxide production by aminoguanidine, a selective NOS2 inhibitor, significantly reduced LPS‐mediated LCN2 expression. In contrast, treatment of murine chondrocytes with sodium nitroprussiate (SNP), a classic NO donor, scarcely induced LCN2 expression. Intriguingly, SNP addition to LPS‐challenged chondrocytes, treated with aminoguanidine, provoked a strong induction of LCN2 expression. Finally, murine ATDC5 cells, co‐cultured with LPS pre‐challenged macrophages, had higher LCN2 expression in comparison with murine chondrocytes co‐cultured with non pre‐challenged macrophages. In this work we have described for the first time that NO is able to exert a control on LCN2 expression, suggesting the existence of a feedback loop regulating its expression. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1046–1052, 2013     

Dexmedetomidine impairs success of patient-controlled sedation in alcoholics during ERCP: a randomized, double-blind, placebo-controlled study

Background

There is a lack of studies about procedural sedation of alcoholics. Dexmedetomidine is recommended for procedural sedation and reported effective for alcohol withdrawal. We evaluated the suitability of dexmedetomidine for sedation of alcoholics during endoscopic retrograde cholangiopancreatography (ERCP).

Methods

Fifty patients with chronic alcoholism scheduled for elective ERCP were randomized 1:1 to receive dexmedetomidine (Dex group) (loading dose 1 μg kg^?1 over 10 min, followed by constant intravenous infusion 0.7 μg kg^?1 h^?1) or saline placebo (P group). Patient-controlled sedation with propofol–alfentanil was used by patients as a rescue method. Sedation was considered as successful if no intervention of an anesthesiologist was needed. Consumption of sedatives was registered, and sedation levels and vital signs were monitored.

Results

Dexmedetomidine alone was insufficient in all patients. The mean ± SD consumption of propofol was 159 ± 72 mg in the P group, and 116 ± 61 mg in the Dex group (p = 0.028). Sedation was successful in 19 of 25 (76 %) patients in the Dex group and in all patients in the P group (p = 0.022). The incidence of sedation adverse events did not differ between the groups. Dexmedetomidine was associated with delayed recovery.

Conclusions

Patient-controlled sedation with propofol and alfentanil but not dexmedetomidine can be recommended for sedation of alcoholics during ERCP.     

High survival in adult patients with acute respiratory distress syndrome treated by extracorporeal membrane oxygenation, minimal sedation, and pressure supported ventilation

OBJECTIVES: To evaluate the results of treatment of severe acute respiratory distress syndrome (ARDS) with extracorporeal membrane oxygenation (ECMO), minimal sedation, and pressure supported ventilation. DESIGN AND SETTING: Observational study in a tertiary referral center, Intensive Care Unit, Astrid Lindgren Children's Hospital at Karolinska Hospital, Stockholm, Sweden. SUBJECTS AND METHODS: Seventeen adult patients with ARDS were treated with venovenous or venoarterial ECMO after failure of conventional therapy. The Murray score of pulmonary injury averaged 3.5 (3.0-4.0) and the mean PaO2/FIO2 ratio was 46 (31-65). A standard ECMO circuit with nonheparinized surfaces was used. The patients were minimally sedated and received pressure-supported ventilation. High inspiratory pressures were avoided and arterial saturation as low as 70% was accepted on venovenous bypass. RESULTS: In one patient a stable bypass could not be established. Among the remaining 16 patients 13 survived (total survival rate 76%) after 3-52 days (mean 15) on bypass. Major surgical procedures were performed in several patients. The cause of death in the three nonsurvivors was intracranial complications leading to total cerebral infarction. CONCLUSION: A high survival rate can be obtained in adult patients with severe ARDS using ECMO and pressure-supported ventilation with minimal sedation. Surgical complications are amenable to surgical treatment during ECMO. Bleeding problems can generally be controlled but require immediate and aggressive approach. It is difficult or impossible to decide when a lung disease is irreversible, and prolonged ECMO treatment may be successful even in the absence of any detectable lung function.     

Carotid and femoral artery stiffness in Takayasu's arteritis. An ultrasound study

PURPOSE: To determine the stiffness of large arteries in patients with Takayasu's arteritis (TA). MATERIALS AND METHODS: A noninvasive ultrasonic method was used to measure Peterson's elastic modulus (Ep), Young's elastic modulus (YM). and the stiffness constant beta of the common carotid arteries in 13 and of the common femoral arteries in 16 patients with TA and in healthy control subjects. RESULTS: The median carotid artery Ep, YM, and stiffness index beta were statistically significantly higher in patients with TA than in controls (p=0.019, 0.013, and 0.004, respectively). The median femoral artery Ep and YM were also higher in patients with TA than in controls (p=0.005 and 0.039, respectively), and the stiffness constant beta (p=0.127) also tended to be higher in patients with TA relative to healthy persons. CONCLUSIONS: Carotid artery compliance is strongly diminished in patients with TA. A comparable but somewhat less conspicuous change is seen in the femoral arteries.     

Endostatin reduces vascularization,blood flow,and growth in a rat gliosarcoma.

Endostatin, the 20-kDa C-terminal fragment of collagen XVIII, has previously been shown to inhibit growth and induce regression of different experimental tumors in rodents. In this study, we show that recombinant murine and human endostatin, produced in 293 EBNA cells and yeast, respectively, inhibit ectotopic as well as orthotopic growing BT4Cn gliosarcomas in BD-IX rats. In rats in which s.c. gliomas were grown for a total of 29 days, systemic treatment with recombinant murine endostatin induced about 50% reduction of intratumoral blood flow and tumor size after only 10 days of therapy. In contrast, the blood flow to irrelevant organs was unaffected by endostatin, indicating its specificity of action. Tumors were not observed to increase in size or regrow after cessation of therapy. Furthermore, endostatin-treated rats with i.c. tumors had significantly longer survival time than did untreated controls. In the treated rats, endostatin therapy resulted in a reduced tumor blood vessel volume and an increased tumor cell density with an increased apoptotic index within a given tumor volume, as verified by flow cytometry and by staining with deoxynucleotidyltransferase-mediated dUTP nick-end labeling. This work verifies the general anti-angiogenic and antitumor effects of endostatin and indicates that the protein may also be considered as a treatment strategy for malignant brain tumors.     

Pharmacodynamics and pharmacokinetics of high-dose oxycodone infusion during and after coronary artery bypass grafting

OBJECTIVE: In small to moderate doses, oxycodone has similar analgesic efficacy to morphine with fewer side effects. The present study evaluated the pharmacokinetics and dynamics of high doses of oxycodone during anesthesia for primary coronary artery bypass grafting. DESIGN: A randomized, prospective clinical evaluation. SETTING: A major Scandinavian university clinic. PARTICIPANTS: Two groups with 10 patients each were studied. INTERVENTIONS: Invasive hemodynamics, echocardiograms, and electrocardiograms were monitored. Oxycodone kinetics, histamine liberation, and plasma cortisol levels were measured. Anesthesia was induced with 1.0 mg/kg of oxycodone and, thereafter, in a random order, maintained with a continuous infusion of oxycodone at a rate of either 0.5 mg/kg/h (group OX 0.5, 10 patients) or 1.0 mg/kg/h (group OX 1.0, 10 patients). An additional bolus dose of 0.5 mg/kg (OX 0.5) or 1.0 mg/kg (OX 1.0) of oxycodone was given before the incision. Enflurane was administered according to hemodynamic criteria. MEASUREMENTS AND MAIN RESULTS: The induction of and the course of anesthesia were hemodynamically stable in all patients. Enflurane was given to every patient. The mean total doses of oxycodone were 3.5 mg/kg (OX 0.5) and 6.2 mg/kg (OX 1.0). The median t(1/2) of oxycodone varied from 5.1 to 5.9 hours. No hemodynamic differences were found between the groups. No histamine liberation was detected. During anesthesia, the predominant waves in the EEG were theta;- and delta-waves. The mean times to awakening were 3.8 hours and 7.0 hours in the groups OX 0.5 and 1.0, respectively. All patients were intubated until the first postoperative morning. No recall of awareness was reported. CONCLUSION: A combination of oxycodone and enflurane provides hemodynamically stable anesthesia. No advantages were gained with the higher dose. Elimination of oxycodone was slower than reported previously.