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The appropriate expression of the roughly 30,000 human genes requires multiple layers of control. The oncoprotein MYC, a transcriptional regulator, contributes to many of the identified control mechanisms, including the regulation of chromatin, RNA polymerases, and RNA processing. Moreover, MYC recruits core histone-modifying enzymes to DNA. We identified an additional transcriptional cofactor complex that interacts with MYC and that is important for gene transcription. We found that the trithorax protein ASH2L and MYC interact directly in vitro and co-localize in cells and on chromatin. ASH2L is a core subunit of KMT2 methyltransferase complexes that target histone H3 lysine 4 (H3K4), a mark associated with open chromatin. Indeed, MYC associates with H3K4 methyltransferase activity, dependent on the presence of ASH2L. MYC does not regulate this methyltransferase activity but stimulates demethylation and subsequently acetylation of H3K27. KMT2 complexes have been reported to associate with histone H3K27-specific demethylases, while CBP/p300, which interact with MYC, acetylate H3K27. Finally WDR5, another core subunit of KMT2 complexes, also binds directly to MYC and in genome-wide analyses MYC and WDR5 are associated with transcribed promoters. Thus, our findings suggest that MYC and ASH2L-KMT2 complexes cooperate in gene transcription by controlling H3K27 modifications and thereby regulate bivalent chromatin.

The function and regulation of poly(ADP-ribosyl)ation is partially understood. By contrast, little is known about intracellular mono(ADP-ribosyl)ation (MARylation) by ADP-ribosyl transferases. Recent findings indicate that MARylation regulates signalling and transcription by modifying key components in these processes, and that specific macrodomain-containing proteins 'read' and 'erase' this modification. Supplementary information The online version of this article (doi:10.1038/nrm3601) contains supplementary material, which is available to authorized users., ADP-ribosylation of proteins was first described in the early 1960's, and today the function and regulation of poly(ADP-ribosyl)ation (PARylation) is partially understood. By contrast, little is known about intracellular mono(ADP-ribosyl)ation (MARylation) by ADP-ribosyl transferase (ART) enzymes, such as ARTD10. Recent findings indicate that MARylation regulates signalling and transcription by modifying key components in these processes. Emerging evidence also suggests that specific macrodomain-containing proteins, including ARTD8, macroD1, macroD2 and C6orf130, which are distinct from those affecting PARylation, interact with MARylation on target proteins to 'read' and 'erase' this modification. Thus, studying macrodomain-containing proteins is key to understanding the function and regulation of MARylation. Supplementary information The online version of this article (doi:10.1038/nrm3601) contains supplementary material, which is available to authorized users.

ADP-ribosylation is an important post-translational protein modification (PTM) that regulates diverse biological processes. ADP-ribosyltransferase diphtheria toxin-like 10 (ARTD10, also known as PARP10) mono-ADP-ribosylates acidic side chains and is one of eighteen ADP-ribosyltransferases that catalyze mono- or poly-ADP-ribosylation of target proteins. Currently, no enzyme is known that reverses ARTD10-catalyzed mono-ADP-ribosylation. Here we report that ARTD10-modified targets are substrates for the macrodomain proteins MacroD1, MacroD2 and C6orf130 from Homo sapiens as well as for the macrodomain protein Af1521 from archaebacteria. Structural modeling and mutagenesis of MacroD1 and MacroD2 revealed a common core structure with Asp102 and His106 of MacroD2 implicated in the hydrolytic reaction. Notably, MacroD2 reversed the ARTD10-catalyzed, mono-ADP-ribose-mediated inhibition of glycogen synthase kinase 3β (GSK3β) in vitro and in cells, thus underlining the physiological and regulatory importance of mono-ADP-ribosylhydrolase activity. Our results establish macrodomain-containing proteins as mono-ADP-ribosylhydrolases and define a class of enzymes that renders mono-ADP-ribosylation a reversible modification.

We report an unusual complication following placement of a thoracic epidural catheter in a patient that had undergone surgery for pulmonary metastases of a malignant melanoma. The intra- and postoperative course was initially without complications. At 2 days, there was a small, conspicuous swelling above the site of epidural puncture, which was neither reddened nor painful. No neurological deficits were observed, and the patient explained that he had been aware of the swelling for more than 6 months; thus, the epidural catheter was not deemed to be responsible. After catheter removal on day 4, an apparently purulent fluid drained from the puncture site. Although the patient had not reported this in the initial medical examination, he now explained that this cutaneous process had been squeezed out by his wife several times before. We initially obtained an exudate by means of ultrasound-guided puncture, and two epidermal cysts were detected on subsequent magnetic resonance imaging (MRI). The epidural catheter had been placed through one of these epidermal cysts. After reassessing the medical files, we found the earlier reports of two positron emission tomographies in which two epidermoid cysts were described at the level of thoracic vertebra 5/6 and 6/7. Facklamia hominis was detected in the pure culture. To avoid bacterial infection, we treated the patient for 7 days with antibiotics. The clinical course was without further pathological findings.

The direct oral anticoagulants (DOACs) present a valid therapeutic alternative to vitamin K antagonists in patients with non-valvular atrial fibrillation, for the prevention of venous thromboembolism, and for the treatment and prevention of the recurrence of pulmonary embolisms and deep vein thrombosis. Despite Idarucizumab as an antagonist of Dabigatran there are no other specific antidotes available yet. Therefore, perioperative coagulation management by DOACs is challenging in patients undergoing emergency surgical procedures with a high risk of bleeding complications. This case study describes the perioperative procedure during ascending aorta replacement after aortic dissection with apixaban administration.

16 patients (nine men, seven women; mean age 45 [23-62] years) with end-stage pulmonary disease underwent lung transplantation, 14 unilateral, three bilateral (one bilateral retransplantation). The diagnoses were: emphysema (n = 5), idiopathic pulmonary fibrosis (n = 5), emphysema in alpha 1-antitrypsin deficiency (n = 1), mucoviscidosis (n = 1), drug-induced fibrosis (n = 1), chronic lung rejection after heart-lung transplantation (n = 1), secondary pulmonary hypertension with persistent ductus arteriosus (n = 1), sarcoidosis (n = 1) and chronic transplant failure after unilateral transplantation (n = 1). Eleven patients survived long-term (mean follow-up period 247 [8-585] days). Ten of these patients have been independent of additional oxygen after an average of 8 months postoperatively, eight are physically active according to their age. Three patients died of reperfusion damage intraoperatively or in the early postoperative period. The two other patients died from septicaemia 5 1/2 and 7 months postoperatively. It is concluded that lung transplantation in end-stage pulmonary disease provides the only therapeutic means with any expectation of physical rehabilitation.

Objective: Endoscopic ultrasound (EUS) is a highly reliable procedure to localize insulinomas preoperatively. It has been considered to be important in planning surgical strategy, especially considering a minimal invasive approach. However, even under ideal conditions experienced examiners miss about 10–20% of insulinomas by EUS imaging. Design and methods: This retrospective study aimed to identify factors associated with negative EUS imaging. Twenty-nine consecutive patients (24 benign and 5 malignant) with sporadic pancreatic insulinomas confirmed by successful surgery and positive histopathology were included. All EUS examinations were performed by one single experienced examiner over a period of one decade. Results: Three of the tumors were not detected by preoperative EUS as they were isoechoic to the surrounding healthy pancreatic tissue; 25 could be detected as hypoechoic lesions, (including all malignant tumors), and one lesion was hyperechoic. Low body mass index (P=0.053) and young age (P=0.037) were associated with negative EUS imaging. All patients with negative imaging were females. The position on the examiner’s learning curve, the diameter and location of insulinoma, and endocrine parameters (insulin concentrations and insulin–glucose ratios in the prolonged fasting test) had no influence on the success of EUS imaging. Conclusions: Some insulinomas are missed by preoperative EUS imaging as they are completely isoechoic. A low body mass index, female gender, and young age might be risk factors for negative imaging.

The American Society of Echocardiography has published guidelines relating to standards for training (and certification), performance, nomenclature and measurement, and quality improvement related to echocardiography.1-15 However, the Society has not previously made recommendations about what constitutes the core variables, ie, measurements and other elements, to be included in a transthoracic echocardiographic report. A document addressing this topic would be timely and could serve the following purposes: (1) Promote quality by defining the basic core of measurements and statements that constitute the report; (2) encourage the comparison of serial echocardiograms performed in patients at the same site or different sites; (3) improve communication by expediting development of structured report form software; and (4) facilitate multicenter research and analyses of cost-effectiveness. Because of these considerations, Dr Richard Kerber, President of the American Society of Echocardiography, appointed a task force in 1998 to develop recommendations for a standardized report for adult echocardiography.Various international societies have recently addressed this issue and recommended standards. The purpose of this report is not to define how to record a proper adult cardiac ultrasound examination or how to perform the measurements but, rather, to serve as a guideline to what measurements and descriptive items should be included. It is the hope of the Task Force that publication of this document will further our ongoing efforts to improve the overall quality of the practice of echocardiography.

We report on a case of a lumbar epidural abscess with staphylococcus aureus following a catheter epidural anaesthesia in a previously healthy and not immunosuppressed 34-year-old female. The indication for the epidural anaesthesia was mobilization of the right knee following arthrotomy due to chronic synovitis. On postoperative day 7 the patient experienced lumbar pain, headache and meningism. Magnetic resonance imaging revealed an epidural abscess at the height of the 3rd and 4th lumbar vertebrae. A right-sided intralaminar fenestration with debridement and drainage of the abscess was carried out immediately after confirmation of the diagnosis. The patient was discharged from hospital on postoperative day 21 without any neurological sequelae. This is another addition to the published cases of epidural abscess following a epidural technique. It underlines the need for a proper aseptic technique, to abandon frequent changes of bacterial filters, daily examination of the entry site of the catheter and strategies for close and continuous monitoring of patients following epidural anaesthesia.

Cell Communication and Signaling 11, 5 (2013). doi:10.1186/1478-811X-11-5, Published by Biomed Central, London

Summary ADP-ribosyltransferases (ARTs) catalyze the transfer of ADP-ribose from NAD + onto substrates. Some ARTs generate in an iterative process ADP-ribose polymers that serve as adaptors for distinct protein domains. Other ARTs, exemplified by ARTD10, function as mono-ADP-ribosyltransferases, but it has been unclear whether this modification occurs in cells and how it is read. We observed that ARTD10 colocalized with ARTD8 and defined its macrodomains 2 and 3 as readers of mono-ADP-ribosylation both in vitro and in cells. The crystal structures of these two ARTD8 macrodomains and isothermal titration calorimetry confirmed their interaction with ADP-ribose. These macrodomains recognized mono-ADP-ribosylated ARTD10, but not poly-ADP-ribosylated ARTD1. This distinguished them from the macrodomain of macroH2A1.1, which interacted with poly- but not mono-ADP-ribosylated substrates. Moreover, Ran, an ARTD10 substrate, was also read by ARTD8 macrodomains. This identifies readers of mono-ADP-ribosylated proteins, defines their structures, and demonstrates the presence of this modification in cells.

ADP-ribosylation is a post-translational modification that regulates various physiological processes, including DNA damage repair, gene transcription and signal transduction. Intracellular ADP-ribosyltransferases (ARTDs or PARPs) modify their substrates either by poly- or mono-ADP-ribosylation. Previously we identified ARTD10 (formerly PARP10) as a mono-ADP-ribosyltransferase, and observed that exogenous ARTD10 but not ARTD10-G888W, a catalytically inactive mutant, interferes with cell proliferation. To expand on this observation, we established cell lines with inducible ARTD10 or ARTD10-G888W. Consistent with our previous findings, induction of the wild-type protein but not the mutant inhibited cell proliferation, primarily by inducing apoptosis. During apoptosis, ARTD10 itself was targeted by caspases. We mapped the major cleavage site at EIAMD406↓S, a sequence that was preferentially recognized by caspase-6. Caspase-dependent cleavage inhibited the pro-apoptotic activity of ARTD10, as ARTD10(1-406) and ARTD10(407-1025), either alone or together, were unable to induce apoptosis, despite catalytic activity of the latter. Deletion of the N-terminal RNA recognition motif in ARTD10(257-1025) also resulted in loss of pro-apoptotic activity. Thus our findings indicate that the RNA recognition motif contributes to the pro-apoptotic effect, together with the catalytic domain. We suggest that these two domains must be physically linked to stimulate apoptosis, possibly targeting ARTD10 through the RNA recognition motif to specific substrates that control cell death. Moreover, we established that knockdown of ARTD10 reduced apoptosis in response to DNA-damaging agents. Together, these findings indicate that ARTD10 is involved in the regulation of apoptosis, and that, once apoptosis is activated, ARTD10 is cleaved as part of negative feedback regulation.

Mortality of severe acute respiratory distress syndrome (ARDS) in Germany is about 60%. Respiratory therapy can make the lung injury worse by high positive airway pressures, high tidal volumes and high inspiratory oxygen concentrations. Extracorporeal membrane oxygenation (ECMO) was employed to reduce aggressive mechanical ventilation, but it has not been proved to be superior to conventional ventilation. However, encouraged by recently developed improvements in the technique and concept of ECMO, we introduced this therapy into our program for the treatment of ARDS. PATIENTS AND METHODS. All patients with severe ARDS (lung injury score > 2.5) admitted to our multidisciplinary intensive care unit from March 1992 to March 1995 were evaluated prospectively. After admission, the patients first underwent a conventional therapeutic approach, including pressure-controlled inverse-ratio ventilation, permissive hypercapnia, changes in body position (in particular, the prone position), negative fluid balance, anti-biotics, and low-dose hydrocortisone infusion. ECMO via a covalently heparin-coated, venovenous bypass-system with a vortex pump and two membrane lungs was performed if ARDS did not improve after 24-96 h of conventional therapy and if two of three of the slow-entry criteria for ECMO were fulfilled: (1) PaO2/FiO2 5 mbar; (2) semistatic compliance 30%. Only in cases of life-threatening hypoxemia (PaO2 5 mbar for > 2 h (fast-entry criteria) was ECMO instituted immediately. RESULTS. Sixty patients fulfilled the entry criteria for our study. Thirty-nine patients were treated with a conventional protocol, 37 after improvement of ARDS and 2 who had not improved but in whom there were contraindications to the use of ECMO. ECMO was performed in 10 patients who had not improved, but who fulfilled the slow-entry criteria and in 11 primarily hypoxemic patients who fulfilled the fast-entry criteria. The survival rate was 30/39 (77%) for the conventional therapy group, 6/10 (60%) for the slow-entry group, and 11/11 (100%) for the fast-entry group. The onset of ECMO allowed a significant decrease in peak and mean airway pressures, tidal volume, ventilatory rate, minute volume and inspiratory oxygen concentration. Sufficient gas exchange was provided, and pulmonary artery pressures significantly decreased on bypass. The most frequent complications on bypass were pneumothorax (15/21 patients) and bleeding (7/21 patients). CONCLUSION. In comparison with the historical results at our own institution, the present study demonstrates an improvement in the survival rate from 56% to 78% since ECMO has become available. We conclude that venovenous ECMO with a heparin-bonded bypass circuit is an effective additional option for the treatment of patients with severe ARDS.

Activated recombinant factor VII (rFVIIa) has been approved for the treatment of bleeding diathesis. A growing number of case reports suggest that rFVIIa might have a distinct role in otherwise intractable surgical bleeding in patients without bleeding diathesis. We report here on a 22-year-old pregnant (week 26) patient who was involved in a car accident leading to premature placental separation. After emergency cesarean section during which 4 units of packed erythrocytes, 6 units of fresh frozen plasma and 32 pg of desmopressin were given, the patient was transferred to the ICU, where bleeding from wound drainages continued at a rate of > 300 mL/h. Despite a tendency towards normalization of the conventional laboratory coagulation parameters, and despite application of another 17 units of packed erythrocytes, 16 units of fresh frozen plasma, 2 units of thrombocytes and 2000 IU of antithrombin, bleeding could not be stopped. The decision was therefore taken to do a re-laparotomy to rule out any surgical source of bleeding that might have been overlooked. Because of hemodynamic instability and as an ultima ratio 360 kilounits (kIU) of rFVIIa were applied before transferring the patient to the operating theatre. Bleeding stopped immediately. No bleeding source could be identified upon surgical inspection. The post-operative course was uneventful and the patient could be discharged from the hospital on day 10. We assume that this otherwise untractable bleeding was stopped by the application of rFVIIa and feel that a broader indication for rFVIIa should be considered.

Die Pulskonturanalyse ist ein einfach anzuwendendes Verfahren zur kontinuierlichen Bestimmung des Herzzeitvolumens (PCCO) bei kritisch kranken Patienten. Die Berechnung des Schlagvolumens erfolgt uber die Analyse der arteriellen Pulsdruckkurve zusammen mit einem fur jeden Patienten mittels Referenzverfahren individuell zu bestimmenden Kalibrationsfaktor. PCCO wurde an 20 Intensivpatienten uber eine Gesamtzeit von 110 h gemessen und mit Thermodilutionswerten (TDCO) verglichen. Die relative Abweichung (±2 SD) von PCCO gegenuber TDCO wurde ermittelt: (1) unter hamodynamisch stabilen Bedingungen, und (2) unter Bedingungen von verandertem Vasotonus und Hamodynamik bei Dosisanderungen vasoaktiver Substanzen. Insgesamt wurden an 165 Meszeitpunkten TDCO-Messungen durchgefuhrt und die korrespondierenden PCCO-Werte registriert. Die relative Abweichung von PCCO gegenuber TDCO betrug ±23,9% (SD=0,85 l·min −1 ), wenn die PCCO-Methode einmalig bei jedem Patienten vor Beginn der Messerien kalibriert wurde. Die Differenz der Mittelwerte der Herzzeitvolumina (CO) beider Methoden (Bias) war dabei −0,09 l·min −1 . Durch zusatzliche Kalibrationen konnte die relative Abweichung (±2 SD) auf ±15,7% verbessert werden (SD= 0,56 l·min −1 ; Bias 0,003 l·min −1 ). Anderungen in der Dosierung vasoaktiver Substanzen in klinisch ublichen Grosenordnungen hatten keinen Einflus auf die Mesgenauigkeit von PCCO. Es konnte gezeigt werden, das die Pulskonturanalyse ein leicht anzuwendendes und klinisch ausreichend genaues Verfahren zur kontinuierlichen Messung des CO darstellt.

The risk factors for systemic fungal infections were analysed retrospectively in 186 orthotopic liver transplant procedures performed in 152 patients between June 1985 and January 1993. The total incidence of systemic fungal infections was 16.5% (25/152). The incidence of disseminated candidiasis, aspergillosis, and combined candidiasis and aspergillosis was 6.5% (n = 10), 7.2% (n = 11) and 2.6% (n = 4), respectively. Mortality associated with systemic fungal infections was 80% (20 of 25 patients). There were ten cases of disseminated candidiasis, with 4 patients surviving, and 11 cases of invasive aspergillosis, with 1 patient surviving. All patients with combined systemic fungal infection died. To identify perioperative risk factors, 39 variables were used to compare patients with systemic fungal infections versus those without fungal infections. Fourteen variables were significantly associated with systemic fungal infections by univariate analysis. A consecutive logistic regression analysis revealed that the amount of fresh frozen plasma transfused due to poor initial function of the allograft and acute renal failure requiring hemofiltration were independently significant risk factors for systemic fungal infections. There was no statistical correlation between systemic fungal infections and the underlying liver disease, previous long-term corticosteroids and the postoperative immunosuppressive therapy. Risk factors identified in this study should be considered in the postoperative care of the individual liver transplant recipient. In our study a poor initial function of the hepatic allograft substantially increased the risk of systemic fungal infection.

To compare 4 general severity classification scoring systems concerning prognosis of outcome in 123 liver transplant recipients. The compared scoring systems were: the mortality prediction model (admission model and 24 h model); the simplified acute physiology score; the acute physiology and chronic health evaluation (Apache II) and the acute organ systems failure score.Retrospective, consecutive sample.Adult intensive care unit in a university hospital.123 adult liver allograft recipients after admission to the intensive care unit.The scoring systems were calculated as described by the authors to classify the severity of illness after admission of the allograft recipients to the intensive care unit. The mean and median values of survivors and the group of patients, that died during hospital stay were compared. Receiver-operating characteristics were plotted for all scoring systems and the areas under the curves of receiver-operating characteristics were calculated. The predictive value of the 4 scoring systems was tested using a variety of sensitivity analyses. The mortality prediction model (24 h model) was found to have a high significance (p0.001) in predicting mortality and showed the greatest area under the curve (0.829). Simplified acute physiology score (p0.001) and acute physiology and chronic health evaluation (Apache II) (p0.01) had a high significance as well, but did not hit the level of prognosis of mortality prediction model, as shown in the area under the curves. Accordingly, sensitivity was highest in MPM-24 h (83%), followed by SAPS (72%) and Apache II (71%). MPM-24 h had a total misclassification rate of 22% (SAPS = 32%, Apache II = 33%). MPM-admission failed in predicting mortality (sensitivity = 52%). Organ systems failure score seemed not to be useful in liver transplant recipients.General disease classification systems, such as the mortality prediction model, simplified acute physiology score or acute physiology and chronic health evaluation are good mortality prediction models in patients after liver transplantation. We suggest that there is no need for improvement of a special scoring system.

Adenosine diphosphate-ribosylation is a post-translational modification mediated by intracellular and membrane-associated extracellular enzymes and many bacterial toxins. The intracellular enzymes modify their substrates either by poly-ADP-ribosylation, exemplified by ARTD1/PARP1, or by mono-ADP-ribosylation. The latter has been discovered only recently, and little is known about its physiological relevance. The founding member of mono-ADP-ribosyltransferases is ARTD10/PARP10. It possesses two ubiquitin-interaction motifs, a unique feature among ARTD/PARP enzymes. Here, we find that the ARTD10 ubiquitin-interaction motifs bind to K63-linked poly-ubiquitin, a modification that is essential for NF-κB signalling. We therefore studied the role of ARTD10 in this pathway. ARTD10 inhibits the activation of NF-κB and downstream target genes in response to interleukin-1β and tumour necrosis factor-α, dependent on catalytic activity and poly-ubiquitin binding of ARTD10. Mechanistically ARTD10 interferes with poly-ubiquitination of NEMO, which interacts with and is a substrate of ARTD10. Our findings identify a novel regulator of NF-κB signalling and provide evidence for cross-talk between K63-linked poly-ubiquitination and mono-ADP-ribosylation.

Cell Communication and Signaling 10(1), 28 (2012). doi:10.1186/1478-811X-10-28, Published by Biomed Central, London

Continuous monitoring of blood gases and pH could add substantially to patient safety. During the last decade, efforts have been made to develop continuous optochemical blood gas sensors. The initial evaluation of such fibreoptic-based systems showed major patient-interface problems [11]. We evaluated a new intra-arterial blood gas monitoring system (PB3300, Puritan-Bennett, Carlsbad CA) under routine clinical conditions. Methods. After institutional review board approval and with written informed consent, 38 sensors were tested in 25 patients with acute respiratory failure (e.g., the acute respiratory distress syndrome, complications after lung transplantation). Two conventional bench-top blood gas analysers (ABL 520 and ABL 300, Radiometer, Copenhagen) served as criterion standards. The mean differences (bias) and standard deviations (SD) of the differences (precision) were calculated according to the method of Bland and Altman [2]. In addition, linear regression analysis and correlation coefficients were calculated. The quality of blood pressure tracings was assessed using a grading system. Results. The median sensor lifetime was 81.3 h; 869 blood samples (median 14 per sensor) were analysed for the comparison of continuous and conventional blood gas analysis. The ranges for measured parameters were: pH: 6.92 to 7.55; PCO2: 20 to 83 torr; PO2: 31 to 518 torr. The mean differences (SD) were: pH: −0.03 (0.03) or −0.4 (0.4)%; PCO2: −2.6 (4.1) torr or −6.9 (10.9)%; PO2: −3.4 (10.5) torr or −2.9 (7.0)%. The results of linear regression analysis and the correlation coefficients are depicted in Table 2. The mean grade of blood pressure tracings was satisfactory for the clinical setting. Conclusions. The continuous blood gas monitor is sufficiently accurate and precise for clinical use. Bias and precision are better than those known from former studies evaluating fibreoptic blood gas monitors under experimental conditions [7]. Cost-effectiveness was not an issue of this study.

Based on the imaging studies obtained from 13 patients after lung transplantation, radiological findings have been correlated with the clinical charts. The intention was to describe the radiological manifestations of the particular transplant complications of these patients. 12 episodes of reimplantation response were seen in the early postoperative period as a perihilar accented perivasal consolidation with typically short-termed appearances. 16 episodes of acute rejection showed various manifestations on the radiographs. They were characterised by immediate response to a bolus therapy with corticosteroids. This decisive observation allows the exclusion of other causes contributing to a condition following thoracotomy with similar radiological manifestations. Stenoses of the pulmonary or the bronchial anastomoses occurred once each and were confirmed in the course of further examinations. Chest radiograph proved to be the appropriate tool for the diagnosis of technical complications following iatrogenic measures (pleural effusion, pneumothorax). Clinical symptoms and follow-up observations are necessary for the interpretation of the radiographs. Chest radiography represents an important help concerning problems in differential diagnosis and further therapeutic decisions.

We present an unusual case of suprahepatic caval anastomotic stenosis after adult liver transplantation in the early postoperative period. Color flow Doppler sonography and cavography were used to confirm the clinical diagnosis. Success-ful nonoperative treatment of the obstruction was achieved by balloon dilatation and subsequent implantation of a vascular stent.

Entsprechend dem Konzept der Abhängigkeit der O2-Aufnahme vom O2-Transρort kann bei kritisch Kranken durch eine Steigerung des systemischen Sauerstoffange-bots auch die Gewebeoxygenierung verbessert werden. Eine kritische Bewertung der klinischen Befunde zeigt jedoch, daß nicht in alien Fallen, in denen eine positive Korrelation zwischen O2-Transport und O2-Aufnahme beschrieben wurde, auch eine «pathologische» Abhängigkeit beider Größen vorgelegen haben muß. Fehlermöglichkeiten bei der Interpretation der erhobenen Daten, wie die mathematische Kopplung der Meßwerte, Änderungen des O2-Bedarfs infolge wechselnder Sedierung und der kalorigenen Effekte von Katecholaminen, werden diskutiert.

Background: While continuous positive airway pressure (CPAP) effectively treats obstructive sleep apnea (OSA), adherence to CPAP is suboptimal. The short-term efficacy of and adherence with a convenient expiratory positive airway pressure (EPAP) nasal device was evaluated in OSA patients non-adherent with CPAP. Methods: Participants were OSA patients who refused CPAP or used CPAP less than 3 h per night. After demonstrating tolerability to the EPAP device during approximately 1 week of home use, patients underwent a screening/baseline polysomnogram (PSG1) and a treatment PSG (PSG2). Patients meeting prespecified efficacy criteria underwent PSG3 after about 5 weeks of EPAP treatment. Results: Forty-seven of 59 eligible patients (80%) tolerated the device and underwent PSG1. Forty-three patients (27 m, 16 f; 53.7 ± 10.9 years) met AHI entry criteria and underwent PSG2. Mean AHI decreased from 43.3 ± 29.0 at baseline to 27.0 ± 26.7 (p < 0.001) at PSG2. Twenty-four patients (56%) met efficacy criteria; their mean AHI was 31.9 ± 19.8, 11.0 ± 7.9, 16.4 ± 12.2 at PSG1, PSG2, and PSG3, respectively (p < 0.001, PSG1 vs. both PSG2 and PSG3). Mean Epworth Sleepiness Scale (ESS) scores were 12.3 ± 4.8 at baseline, 11.1 ± 5.1 at PSG1, and 8.7 ± 4.4 at PSG3 (p = 0.001 compared to baseline). Device use was reported an average of 92% of all sleep hours. Conclusions: The improvements in AHI and ESS, combined with the high degree of treatment adherence observed, suggest that the convenient EPAP device tested may become a useful therapeutic option for OSA. 2010 Elsevier B.V. All rights reserved.

Nosocomial pneumonia continues to represent a significant cause of morbidity and mortality in hospitalized patients. Bacteria are responsible for greater than 90% of the pneumonias, the most common isolates being aerobic Gram-negative bacilli and S. aureus. Cornerstones of treatment are intravenous antibiotics and supportive care. In the individual case the true etiology is usually unknown; therefore empiric broad spectrum treatment is commonly used based on the prevalence of local pathogens, their antibiotic sensitivity pattern and on host factors. Combination antibiotic regimens, including beta-lactams and aminoglycosides, are considered as standard therapy and are associated with clinical success rates of greater than 80%. Monotherapy with broad spectrum antibiotics, such as third generation cephalosporins, imipenem and fluoroquinolones, can be considered as equally effective in non-neutropenic patients and in the absence of P. aeruginosa infection. More active and less toxic antibiotics are still needed for problematic pathogens such as methicillin-resistant S. aureus strains, multiresistant Enterobacteriaceae and Pseudomonas species. Because further improvement in morbidity and mortality may be limited with antibiotics alone, new emphasis should be placed on prevention of infection and the use of immunotherapy.

Since the first characterization of the adult respiratory distress syndrome (ARDS), knowledge of its aetiology and pathogenesis has grown considerably. In spite of this, mortality remains up to 50 to 90%, particularly if multiple organ failure is present. Because no causative clinical therapy is available up to now, significant attention is given to preventive measures like early operative stabilisation of long bone fractures, or prophylaxis of nosocomial infections. After clinical manifestation of ARDS, treatment focuses on functional disturbances of the cardiopulmonary system and on the underlying disease. The aim of this symptomatic therapy is to ensure oxygen supply according to the organisms demand. It is still unknown, however, whether the mortality of patients with ARDS can be reduced by optimising the oxygen supply. In general, oxygen supply can be enhanced by improving pulmonary gas exchange, cardiac output and blood oxygen transport capacity. For practical use the therapy often ends up with a therapeutical dilemma: On one hand, the improvement of the pulmonary gas exchange by application of PEEP can be associated with a critical decline in cardiac output, particularly if the afterload of the right ventricle is elevated. On the other hand, to increase cardiac output, both volume replacement and vasodilators can severely affect pulmonary gas exchange if the alveolo-capillary permeability is increased and pulmonary hypoxic vasoconstriction is disturbed. Thus, oxygen supply can be optimised only via invasive monitoring of the cardiorespiratory system. Although still experimental, the most promising approaches seem to be pharmacological interventions directed at suppressing the formation and effects of various humoral and cellular mediators. An improved understanding of the inflammatory processes might provide new insights in the pathophysiology of ARDS and the related therapeutic interventions.

We have investigated the effects of open chest and open pericardium on the distribution of myocardial blood flow assessed with the radioactive microsphere technique (15 microns). Five dogs with intact thorax served as controls (group I) and six dogs were studied after a right-sided thoracotomy and pericardiotomy (group II). Global myocardial blood flow (mean +/- S.D.) was 0.73 +/- 0.17 ml.min-1.g-1 in group I and 1.22 +/- 0.09 ml.min-1.g-1 in group II (p less than 0.05). Analysis of transmural blood flow distribution revealed that flow was 44% higher in the right and 60% higher in the left ventricular endocardial layers in the open-chest animals, whereas epicardial flow increased by 105% and 90%, respectively. As a result of the preferential blood flow to the epicardial layers of the right ventricle, the endo/epi ratio was reduced from 1.30 +/- 0.26 in group I to 0.86 +/- 0.11 in the open-chest group (p less than 0.05). Left ventricular endo/epi ratio was 1.27 +/- 0.16 and 1.06 +/- 0.11 (n.s.), respectively. External work and diastolic filling pressure of the right ventricle did not differ between the two groups and therefore cannot account for the redistribution of myocardial blood flow. It is concluded that the distribution of myocardial blood flow, particularly in the RV, is severely disturbed by thoracotomy and pericardiotomy. This is an important aspect for the planning and evaluation of studies under open-chest/open-pericardium conditions.

Untreated, one third of patients who undergo surgery will have postoperative nausea and vomiting. Although many trials have been conducted, the relative benefits of prophylactic antiemetic interventions given alone or in combination remain unknown.In a randomized, controlled trial of factorial design, 5,199 patients at high risk for postoperative nausea and vomiting were randomly assigned to 1 of 64 possible combinations of 6 prophylactic interventions: 1) 4 mg of ondansetron or no ondansetron; 2) 4 mg of dexamethasone or no dexamethasone; 3) 1.25 mg of droperidol or no droperidol; 4) propofol or a volatile anesthetic; 5) nitrogen or nitrous oxide; 6) remifentanil or fentanyl. The primary aim parameter was nausea and vomiting within 24 h after surgery, which was evaluated blindly.Ondansetron, dexamethasone, and droperidol each reduced the risk of postoperative nausea and vomiting by about 26%, propofol reduced the risk by 19%, and nitrogen by 12%. The risk reduction with both of these agents (i.e., total intravenous anesthesia) was thus similar to that observed with each of the antiemetics alone. All the interventions acted independently of each other and independently of the patients' baseline risk. Consequently, the relative risks associated with the combined interventions could be estimated by multiplying the relative risks associated with each intervention. However, absolute risk reduction was a critical function of patients' baseline risk.Because antiemetic interventions are similarly effective and act independently, the safest or least expensive should be used first. Prophylaxis is rarely warranted in low-risk patients, moderate-risk patients may benefit from a single intervention, and multiple interventions should be reserved for high-risk patients.

Despite the low incidence of the acute porphyrias, a profound knowledge of the disease is essential for anaesthesiologists, as a variety of perioperatively administered drugs are potential triggers of an acute attack. There is an ongoing discussion about the use of volatile anaesthetics in porphyrias, but halothane and isoflurane seem to be safe. There is no clinical data or case report about the use of desflurane in this specific patient group, but its fast and relatively unchanged elimination and the minimal induction of the cytochrome P 450 system seem to be favorable in this setting. We report the use of desflurane in a patient with acute intermittent porphyria, scheduled for hemihepatectomy. To minimize perioperative distress by pain or the need for postoperative mechanical ventilation, we chose a balanced anaesthesia technique with desflurane, sufentanil and atracurium in combination with a continuous epidural analgesia (bupivacain and fentanyl) for the postoperative period. Preoperatively the porphyrin precursors were analyzed in serum and urine and postoperatively the 24 h-urine was screened every 2 days until postoperative day 6 to monitor the porphyria activity. The preoperative data showed high concentrations of porphyrin precursor excretion, confirming the diagnosis of AIP. The postoperative data in the 24 h-urine were significantly lower than preoperative levels and reached normal levels at postoperative day 5. There were no clinical symptoms of a porphyric attack during the postoperative hospitalization. The patient was discharged on postoperative day 21 in excellent condition. We conclude that our perioperative management prevented an acute porphyric attack in this case. Desflurane might be a valuable alternative to other hypnotics in patients with AIP.

Glucocorticoids are frequently used in clinical anaesthesiology and intensive care because of their antiallergic, antiinflammatory and antioedematous properties and anaphylactic reactions are rare. We report on a 62-year-old asthmatic patient with evidence of aspirin sensitivity. We administered 100 mg of hydrocortisone-21-hemisuccinate (PharmaciaUpjohn, Erlangen, Germany) dissolved in 100 ml 0.9% sodium chloride solution for perioperative corticoid substitution. The patient immediately developed severe bronchospasm and anaphylactic shock requiring intubation and mechanical ventilation. He received adrenaline, isoflurane, ketamine and inhalational fenoterol. He then developed atrioventricular block type III for which we transcutaneously paced the patient. Subsequently he was tested via skin prick tests, intracutaneous tests and i.v.-challenges resulting in the patient having positive reactions to hydrocortisone-21-hemisuccinate. Thus when allergic-like reactions result from glucocorticoid therapy one should consider corticoid allergy as a differential diagnosis.

One of the factors that can alter the response to drugs is the concurrent administration of other drugs. There are several mechanisms by which drugs may interact, but most can be categorised as pharmacokinetic (absorption, distribution, metabolism, excretion), pharmacodynamic, or combined toxicity. Knowledge of the mechanism by which a given drug interaction occurs is often clinically useful and may help to avoid serious adverse events and perioperative morbidity. Although every tissue has some ability to metabolise drugs, the liver is the principal organ of drug metabolism and at the subcellular level the cytochrome P450 enzyme system is the main source of drug interaction. This article reviews the basic principles of drug metabolism and the role of cytochrome P450 in this scenario. Drugs frequently used in anaesthesia and critical care medicine such as benzodiazepines, opioid analgesics, antihypertensive and antiarrhythmic agents, antibiotics and antifungal drugs, antiemetics, histamine-receptor-antagonists, theopylline and paracetamol will be considered. The development of methods and tools which are practical and also economic, are of utmost importance since drug interaction is predictable if the metabolic pathway and the activity (genetic polymorphism) of the enzyme is known.

Laparoscopic surgery of the gallbladder has increasingly replaced open techniques due to postoperative benefits (less pulmonary complications, less postoperative pain, earlier mobilisation). Specific intraoperative effects of pneumoperitoneum have led to some uncertainty if cardiac and/or pulmonary high-risk cases should be done laparoscopically. We describe anaesthesiological management of a 72 year old patient with a unilateral leftsided honeycomb lung (two very large cysts) to undergo laparoscopic cholecystectomy. Vital capacity was reduced to 45%, forced expiratory 1 second volume to 41%, preoperative bloodgas analysis revealed a paO2 of 64 mmHg and a paCO2 of 40 mmHg. Under spontaneous breathing the patient was fiberoptically intubated with a left sided double lumen tube (Mallinckrodt, Athlone/Irland; 37 Ch) using balanced anaesthesia. The healthy right lung was hand ventilated with 100% oxygen to avoid excessive airway pressures (peak airway pressure 27 mbar, mean airway pressure 22-24 mbar). The diseased left lung was passively insufflated with oxygen. The intraabdominal pressure was limited to 10 mmHg. Muscle relaxation was achieved with atracurium under monitoring using a nerve stimulator. The paCO2 increased from 40 to 57 mmHg during the operation, but returned to normal immediately postoperatively. All other ventilatory and hemodynamic parameters were uneventful during the 35 minute procedure. The patient was extubated at the end of the procedure and monitored on the intensive care ward for one night. A postoperative chest X-ray revealed a mediastinal shift of 2 cm to the right, healthy side as well as an atelectasis on this side. The shift was most likely due to hypoventilation of the right lung, with the ensuing atelectasis drawing the mediastinum to the right. Under physiotherapy this shift had resolved by the next morning. The patient could be discharged from hospital on day seven and fully recovered. Especially the severely cardiopulmonary compromised patient benefits from a laparoscopic procedure, due to less postoperative reduction of pulmonary function. Careful and individually adapted monitoring and anaesthetic techniques are necessary to successfully counteract the special implications of pnemoperitoneum.