Artificial device for extracorporeal blood oxygenation in rats

Abstract:  Blood oxygenation devices are an essential component of any cardiopulomonary bypass circuit in various species of laboratory animals. When using larger animals like dogs or pigs, the human and pediatric blood oxygenators could be easily used, but the disadvantage of these species is the scarcity of biochemical and genetic assays for experimental follow-up. However, small rodents like rats have plenty of biochemical assays, but their size requires special oxygenators adapted for their small blood volume and often primed with blood of another animal or other physiological solution. We showed the new design of a blood oxygenator with direct blood–gas contact in an open circuit, specially designed for rats in which the blood oxygenation takes place in a slowly rotating plastic tube with blood spread onto its inner walls in a thin layer. The oxygenator is simple and efficient, does not require priming with the blood of another rat, has a small dead volume, is reusable, and easy to clean and sterilize.     

Cross-sectional study on bone density-related sonographic parameters in children with asthma: correlation to therapy with inhaled corticosteroids and disease severity

The aim of this study was to screen asthmatic children for bone density-related sonographic parameters on the calcaneal bone. Findings were correlated to therapy with inhaled corticosteroids (ICS) as well as with asthma severity (AS), concomitance and severity of atopic dermatitis (AD), and rhinitis (AR). We enrolled 173 children with AS1-3 consecutively; 44% (AS1) had not received any ICS medication; 56% (AS2 and -3) received ICS therapy for > or =6 months (medium daily dose, 286 microg fluticasone-proprionate-equivalent/maximum 500 microg); and in addition 38% (n = 65) presented with AD and 66% (n = 115) with AR. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) results were compared to regional normative values of 3299 children obtained with the identical system. ICS-treated children showed a tendency toward reduced age-, weight-, and height-adjusted standard deviation scores (SDS) for SOS compared to children without ICS treatment, which tendency did not reach statistical significance and was not as consistent for BUA (mean of ICS-treated children compared to our controls: SOS-SDS, -0.29/-0.31/-0.30; BUA-SDS, -0.23/-0.17/-0.05). For ICS-treated children, the proportion of patients with BUA and SOS values below -1 SDS was statistically significant higher for age-adjusted BUA and SOS than for children without ICS medication (BUA 15.00% vs. 5.41%; SOS 32.98% vs. 17.56%). However, we cannot differentiate possible negative effects of ICS from influences of the underlying inflammatory disease because higher asthma severity was associated with greater use of ICS medication. Additionally, the higher physical activity of children with less severe asthma can have influenced quantitative ultrasound (QUS) parameters positively, compared to patients with a higher degree of exercise-induced symptoms. For differentiation of possible negative effect of ICS on ultrasonic bone quality and for evaluation of the potentials of the method, further longitudinal QUS assessment of asthmatics receiving a new ICS treatment is needed.     

Unique site- and time-specific patterns of recurrence following resection of colorectal carcinoma hepatic metastases in patients staged by FDG-PET

BACKGROUND/PURPOSE: We recently reported that patients staged by positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) prior to liver resection for metastatic colorectal cancer had an excellent 5-year survival. In this study, the site- and time-specific patterns of recurrence were examined in patients staged by FDG-PET and the results compared to historical literature control data. METHODS: From March 1995 to June 2002, all patients having hepatic resection for colorectal cancer metastases had preoperative FDG-PET. A prospective database was maintained. RESULTS: One hundred patients were studied; 48 patients had no evidence of recurrence, 30 patients had recurrence within 12 months of resection, and 22 patients had recurrence after 12 months. Seventy percent of patients with recurrence within 1 year of resection had intrahepatic recurrence. Furthermore, 86% of patients with recurrence more than 1 year after resection had extrahepatic recurrence. We reviewed all published case series of conventionally staged patients. This pattern of early recurrence in the liver and later recurrence in extrahepatic sites has not been reported in any of the conventionally staged series. CONCLUSIONS: There is an interesting difference in the pattern of recurrence of FDG-PET-staged patients and conventionally staged patients who undergo liver resection. Several explanations seem possible. One potential explanation requiring further study is that the pattern of recurrence is due to the convergence of two factors-that FDG-PET more effectively detects extrahepatic disease than conventional staging and that liver resection gives a growth spurt to hepatic metastases.     

Transfusion-transmissible infections and transfusion-related immunomodulation

In recent decades the risk of acquiring a transfusion-transmitted infection has declined substantially. After transmission of HIV and hepatitis B and C virus was successfully reduced, due to a rising number of immunocompromised transfusion recipients cytomegalovirus has become an important issue in transfusion medicine. Besides that, new pathogens are threatening the safety of blood supply (West Nile virus, TT virus, SEN virus). Although relatively rare in Western countries, on a global scale malaria is one of the most common transfusion-transmitted infections. Despite new standards in the manufacture and storage of blood product, bacterial contamination still remains a considerable cause of transfusion-related morbidity and mortality.Transfusion-related immunomodulation is known to occur unequivocally, but its clinical significance remains controversial and its pathomechanism is not yet precisely understood. There is evidence that allogeneic blood transfusions may either cause alloimmunization, tolerance, or immunosuppression. However, research on transfusion-related acute lung injury indicates that allogeneic blood transfusions may induce a pro-inflammatory state. The specific immunomodulatory constituents are still unknown, though allogeneic mononuclear cells, HLA peptides, and soluble biological response modifiers are highly suspected. The contribution of white blood cells as causal agents of transfusion-related immunomodulation remains uncertain, and no clear statement on a possible benefit of leukoreduction on overall mortality, infectious complications, or cancer recurrence rate is possible today. However, nosocomial infections are more frequent in transfused than in non-transfused patients.Transfusing blood products remains potentially harmful and thus should be reduced to an absolute minimum.

Conflict of interest statement

Felix Buddeberg and Beatrice Beck Schimmer have no conflicts of interest. Donat R. Spahn's academic department is currently receiving grant support from the University of Zurich, the Research Award Center for Zurich Integrative Human Physiology, the Swiss National Science Foundation, the International Anesthesia Research Foundation (IARS), the European Society of Anaesthesiology (ESA), the Swiss Society of Anesthesiology and Reanimation (SGAR), the Gebert Ruef Foundation, the Swiss Life Foundation, the Olga Mayenfisch Foundation, EMDO-Foundation, the Herzstiftung Olten, Abbott AG, Switzerland and B. Braun, Switzerland. Dr. Spahn is the chairman of the ABC Faculty and a member of the ABC Trauma Faculty which both are managed by Thomson Physicians World GmbH and sponsored by an unrestricted grant from Novo Nordisk. In addition, in the past 5 years, Dr Spahn has received honoraria for consulting or lecturing from the following companies: Abbott, Astra-Zeneca, B. Braun, CSL Behring, Fresenius, Galenica (including Vifor), GlaxoSmithKline, Janssen-Cilag, Kabi, Novo Nordisk, Organon and Roche.     

Three-dimensional constructive interference in steady-state magnetic resonance imaging in syringomyelia: advantages over conventional imaging

OBJECT: Neuroradiology has become indispensable in detecting the pathophysiology in syringomyelia. Constructive interference in steady-state (CISS) magnetic resonance (MR) imaging can provide superior contrast at the sub-arachnoid tissue borders. As this region is critical in preoperative evaluation, the authors hypothesized that CISS imaging would provide superior assessment of syrinx pathology and surgical planning. METHODS: Based on records collected from a database of 130 patients with syringomyelia treated at the authors' institution, 59 patients were prospectively evaluated with complete neuroradiological examinations. In addition to routine acquisitions with FLAIR, T1- and T2-weighted, and contrast-enhanced MR imaging series, the authors obtained sagittal cardiac-gated sequences to visualize cerebrospinal fluid (CSF) pulsations and axial 3D CISS MR sequences to detect focal arachnoid webs. Statistical qualitative and quantitative evaluations of spinal cord/CSF contrast, spinal cord/CSF delineation, motion artifacts, and artifacts induced by pulsatile CSF flow were performed. RESULTS: The 3D CISS MR sequences demonstrated a contrast-to-noise ratio significantly better than any other routine imaging sequence (p < 0.001). Moreover, 3D CISS imaging can detect more subarachnoid webs and cavitations in the syrinx than T2-weighted MR imaging with less flow-void artifact. The limitation of 3D CISS imaging is a susceptibility to motion artifacts that can cause reduced spatial resolution. Lengthy acquisition times for axial segments can be reduced with multiplanar reconstruction of 3D CISS-generated sagittal images. CONCLUSIONS: Constructive interference in steady-state imaging is the MR sequence of choice in the preoperative evaluation of syringomyelia, allowing significantly higher detection rates of focal subarachnoid webs, whereas standard T2-weighted MR imaging shows turbulent CSF flow voids. Constructive interference in steady-state MR imaging enables the neurosurgeon to accurately identify cases requiring decompression for obstructed CSF. Motion artifacts can be eliminated with technical variations.     

Intravenous clonidine infusion in infants after cardiovascular surgery

BACKGROUND: The aim of this study was to investigate the hemodynamic profile and heart rhythm in infants who were given intravenous clonidine infusion after prolonged analgesia/sedation following cardiac surgery. METHODS: This is a single center retrospective review. A total of 542 cardiovascular surgical procedures in infants aged 0-24 months with congenital heart disease were performed between 01/2003 and 12/2005 at the Deutsches Herzzentrum in Berlin. The majority received no long-term analgesia/sedation, but 50 (9%) of these infants received clonidine (dosed at 0.18-3.6 microg.kg(-1).h(-1)) for sedation and to reduce withdrawal symptoms such as CNS hyperactivation, hypertension, tachycardia, and fever. The hospital records of these infants were studied. RESULTS: Fifty infants (median age 5.0 months, median body weight 5.3 kg, 32 males/18 females) received prolonged analgesia/sedation to ensure hemodynamic stability. Clonidine infusion started on day 5 (median) after surgery. During clonidine treatment we found an age-related normalized profile of hemodynamic parameters with a reduction of heart rate and mean arterial pressure from the upper norm to the mean within 24 h (P < 0.001). In no case did clonidine cause low blood pressure resulting in additional therapy to reach the target blood pressure. There were no adverse effects on cardiac rhythm, especially no onset of atrioventricular block. Midazolam, fentanyl, and other opioids could be ended on day 4 of clonidine treatment. CONCLUSIONS: Although off-label, it is feasible to use clonidine infusions in infants in the PICU setting after cardiac surgery without hemodynamic problems arising.     

Low-dose arsenic trioxide sensitizes glucocorticoid-resistant acute lymphoblastic leukemia cells to dexamethasone via an Akt-dependent pathway

Incorporation of apoptosis-inducing agents into current therapeutic regimens is an attractive strategy to improve treatment for drug-resistant leukemia. We tested the potential of arsenic trioxide (ATO) to restore the response to dexamethasone in glucocorticoid (GC)-resistant acute lymphoblastic leukemia (ALL). Low-dose ATO markedly increased in vitro GC sensitivity of ALL cells from T-cell and precursor B-cell ALL patients with poor in vivo response to prednisone. In GC-resistant cell lines, this effect was mediated, at least in part, by inhibition of Akt and affecting downstream Akt targets such as Bad, a proapoptotic Bcl-2 family member, and the X-linked inhibitor of apoptosis protein (XIAP). Combination of ATO and dexamethasone resulted in increased Bad and rapid down-regulation of XIAP, while levels of the antiapoptotic regulator Mcl-1 remained unchanged. Expression of dominant-active Akt, reduction of Bad expression by RNA interference, or overexpression of XIAP abrogated the sensitizing effect of ATO. The inhibitory effect of XIAP overexpression was reduced when the Akt phosphorylation site was mutated (XIAP-S87A). These data suggest that the combination of ATO and glucocorticoids could be advantageous in GC-resistant ALL and reveal additional targets for the evaluation of new antileukemic agents.     

Expression of the granzyme B inhibitor PI9 predicts outcome in nasal NK/T-cell lymphoma: results of a Western series of 48 patients treated with first-line polychemotherapy within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials

Nasal NK/T-cell lymphoma is a rare disease entity with a poor outcome. Expression of antiapoptotic proteins has not been extensively investigated in this entity. Forty-eight patients with nasal T/NK-cell lymphoma who received first-line polychemotherapy (n = 44) or chemoradiotherapy (n = 4) were analyzed for expression of active caspase-3 (aC3), granzyme B protease inhibitor 9 (PI9), and Bcl-2 proteins. Lymphomas were CD3+/CD5-/granzyme B+ and EBV-associated. Median age was 46 years. Stage I/II disease was present in 75% of the cases and an International Prognostic Index (IPI) score less than 1 in 65%. With a median follow-up of 6.3 years, 5-year event-free survival (EFS) and overall survival (OS) rates were 39% and 49%, respectively. Apoptotic index was scored as high in 32% of cases and PI9 expression as positive in 68%, whereas 35% disclosed a high number of aC3+ tumor cells. Univariate analysis showed that absence of PI9 and low apoptotic index were associated with poor outcome, but not aC3 expression nor IPI score. By multivariate analysis, both parameters affected independently EFS (P = .02 and .08, respectively) and OS (P = .009 and .04). In view of its constitutive expression by normal NK cells, it is suggested that loss of PI9 expression in tumor cells may reflect some mechanism associated with progression.     

Lumpectomy plus tamoxifen or anastrozole with or without whole breast irradiation in women with favorable early breast cancer

PURPOSE: In women with favorable early breast cancer treated by lumpectomy plus tamoxifen or anastrazole, it remains unclear whether whole breast radiotherapy is beneficial. METHODS AND MATERIAL: Between January 1996 and June 2004, the Austrian Breast and Colorectal Cancer Study Group (ABCSG) randomly assigned 869 women to receive breast radiotherapy +/- boost (n = 414) or not (n = 417) after breast-conserving surgery (ABCSG Study 8A). Favorable early breast cancer was specified as tumor size <3 cm, Grading 1 or 2, negative lymph nodes, positive estrogen and/or progesterone receptor status, and manageable by breast-conserving surgery. Breast radiotherapy was performed after lumpectomy with 2 tangential opposed breast fields with mean 50 Gy, plus boost in 71% of patients with mean 10 Gy, in a median of 6 weeks. The primary endpoint was local relapse-free survival; further endpoints were contralateral breast cancer, distant metastases, and disease-free and overall survival. The median follow-up was 53.8 months. RESULTS: The mean age was 66 years. Overall, there were 21 local relapses, with 2 relapses in the radiotherapy group (5-y rate 0.4%) vs. 19 in the no-radiotherapy group (5.1%), respectively (p = 0.0001, hazard ratio 10.2). Overall relapses occurred in 30 patients, with 7 events in the radiotherapy group (5-y rate 2.1%) vs. 23 events in the no-radiotherapy group (6.1%) (p = 0.002, hazard ratio 3.5). No significant differences were found for distant metastases and overall survival. CONCLUSION: Breast radiotherapy +/- boost in women with favorable early breast cancer after lumpectomy combined with tamoxifen/anastrazole leads to a significant reduction in local and overall relapse.