The influence of arm positions on abdominal image quality of whole-body computed tomography in trauma: systematic review.

PURPOSE: Whole-body computed tomography (WBCT) is the standard diagnostic method for evaluating polytrauma patients. When patients are unable to elevate their arms, the arms are placed along the body, which affects the image quality negatively. Aim of this systematic review is to evaluate the influence of below the shoulder arm positions on image quality of WBCT. METHODS: Literature in PubMed and Scopus databases was systematically searched. Results of the papers were stratified into 4 categories: arms elevated, 1 arm up 1 arm down, arms ventrally supported, arms along the body. A qualitative analysis was performed on subjective image quality and a quantitative analysis on objective quality (image noise). RESULTS: Eight studies were included with 1421 participants. Various studies reported significantly higher quality scores with arms elevated, compared to arms along the body. Significant differences in objective image quality were found between the arms elevated and the arms ventrally on support group. The arms ventrally supported group had a significantly higher image quality than the arms along the body group. A statistically significant difference was found in objective image quality between the 1 arm up 1 arm down and arms along the body group. No preferential below the shoulders position could be identified. CONCLUSION: Positioning the arms alongside the body results in a poor image quality. Placing the arms on a pillow ventrally to the chest improves image quality. Interestingly, asymmetrical arm positioning has potential to improve the image quality for patients that are unable to elevate the arms.

Abdominal aortic calcification on a plain X-ray and the relation with significant coronary artery disease in asymptomatic chronic dialysis patients.

BACKGROUND: Coronary artery disease (CAD) is common in asymptomatic chronic dialysis patients and plays an important role in their poor survival. Early identification of these high-risk patients could improve treatment and reduce mortality. Abdominal aortic calcification (AAC) has previously been associated with CAD in autopsy studies. Since the AAC can be quantified easily using a lateral lumbar X-ray we hypothesized that the extent of AAC as assessed on a lateral lumbar X-ray might be predictive of the presence of significant CAD in dialysis patients. METHODS: All patients currently enrolled in the ICD2 trial without a history of CABG or a PCI with stent implantation were included in this study. All patients underwent CT-angiography (CTA) and a lateral X-ray of the abdomen. AAC on X-ray was quantified using a previously validated scoring system whereupon the association between AAC and the presence of significant CAD was assessed. RESULTS: A total of 90 patients were included in this study (71% male, 67 ± 7 years old). Forty-six patients were found to have significant CAD. AAC-score was significantly higher in patients with CAD (10.1 ± 4.9 vs 6.3 ± 4.6 (p < 0.05). Multivariate regression analysis revealed that AAC score is an independent predictor for the presence of CAD with a 1,2 fold higher risk per point increase (p < 0.01). The AAC score has a sensitivity of 85% and a specificity of 57% for the presence of significant CAD. CONCLUSION: This study shows that abdominal aortic calcification as assessed on a lateral lumbar X-ray is predictive for the presence of significant coronary artery disease in asymptomatic dialysis patients. This simple, non-invasive and cheap screening method could contribute to early identification of patients eligible for further screening of CAD. TRIAL REGISTRATION: NTR948 , registered 10-4-2007 ; ISRCTN20479861 , registered 2-5-2007.

The dialysis procedure as a trigger for atrial fibrillation: new insights in the development of atrial fibrillation in dialysis patients.

AIMS: Atrial fibrillation (AF) is common in dialysis patients and is associated with increased morbidity and mortality. The pathophysiology may be related to common risk factors for both AF and renal disease or to dialysis-specific factors. The purpose of this study was to determine whether and how AF onset relates to the dialysis procedure itself. METHODS: All dialysis patients enrolled in the implantable cardioverter defibrillator-2 (ICD-2) trial until January 2012, who were implanted with an ICD, were included in this study. Using the ICD remote monitoring function, the exact time of onset of all AF episodes was registered. Subsequently, this was linked to the timing of dialysis procedures. RESULTS: For the current study, a total of 40 patients were included, follow-up was 28 ± 16 months, 80% male, 70 ± 8 years old. A total of 428 episodes of AF were monitored in 14 patients. AF onset was more frequent on the days of haemodialysis (HD) (p<0.001) and specifically increased during the dialysis procedure itself (p=0.04). Patients with AF had a larger left atrium (p<0.001) and a higher systolic blood pressure before and after HD (p<0.001). CONCLUSION: This study provides insight in the exact timing of AF onset in relation to the dialysis procedure itself. In HD patients, AF occurred significantly more often on a dialysis day and especially during HD. These findings might help to elucidate some aspects of the pathophysiology of AF in dialysis patients and could facilitate early detection of AF in these high-risk patients.

Different value of coronary calcium score to predict obstructive coronary artery disease in patients with and without moderate chronic kidney disease.

PURPOSE: The coronary calcium score (CCS) predicts significant coronary artery disease (CAD) in the general population. While moderate chronic kidney disease (CKD) is associated with high CCS, the use of CCS to predict significant CAD in these patients is unknown. METHODS: A total of 704 patients underwent computed tomography coronary angiography for the assessment of CCS and CAD. Sixty-nine (10 %) patients had moderate CKD, defined by an estimated glomerular filtration rate (eGFR) between 30 and 59 mL/min/1.73m(2), and the remaining patients were considered to be without significant CKD (eGFR ≥ 60 mL/min/1.73m(2)). RESULTS: Patients with moderate CKD were older, had a higher CCS, and a higher prevalence of obstructive CAD than patients without significant CKD. Receiver-operator curve analysis showed that CCS predicted the presence of obstructive CAD in both patients with moderate CKD and those without significant CKD. In patients with moderate CKD, the optimal cut-off value of CCS to diagnose obstructive CAD was 140 (sensitivity 73 % and specificity of 70 %), and is 2.8 fold higher than in patients without significant CKD (cut-off value = 50; sensitivity 75 % and specificity 75 %). CONCLUSION: The present results demonstrate that CCS can predict obstructive CAD in patients with moderate CKD, although the optimal cut-off value is higher than in patients without significant CKD.

The use of digital games and simulators in veterinary education: an overview with examples.

In view of current technological possibilities and the popularity of games, the interest in games for educational purposes is remarkably on the rise. This article outlines the (future) use of (digital) games and simulators in several disciplines, especially in the veterinary curriculum. The different types of game-based learning (GBL)-varying from simple interactive computer board games to more complex virtual simulation strategies-will be discussed as well as the benefits, possibilities, and limitations of the educational use of games. The real breakthrough seems to be a few years away. Technological developments in the future might diminish the limitations and stumbling blocks that currently exist. Consequently, educational games will play a new and increasingly important role in the future veterinary curriculum, providing an attractive and useful way of learning.

The novel calicheamicin-conjugated CD22 antibody inotuzumab ozogamicin (CMC-544) effectively kills primary pediatric acute lymphoblastic leukemia cells.

We investigated whether the newly developed antibody (Ab) -targeted therapy inotuzumab ozogamicin (CMC-544), consisting of a humanized CD22 Ab linked to calicheamicin, is effective in pediatric primary B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells in vitro, and analyzed which parameters determine its efficacy. CMC-544 induced dose-dependent cell kill in the majority of BCP-ALL cells, although IC(50) values varied substantially (median 4.8 ng/ml, range 0.1-1000 ng/ml at 48 h). The efficacy of CMC-544 was highly dependent on calicheamicin sensitivity and CD22/CMC-544 internalization capacity of BCP-ALL cells, but hardly on basal and renewed CD22 expression. Although CD22 expression was essential for uptake of CMC-544, a repetitive loop of CD22 saturation, CD22/CMC-544 internalization and renewed CD22 expression was not required to achieve intracellular threshold levels of calicheamicin sufficient for efficient CMC-544-induced apoptosis in BCP-ALL cells. This is in contrast to studies with the comparable CD33 immunotoxin gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia (AML) patients, in which complete and prolonged CD33 saturation was required for apoptosis induction. These data suggest that CMC-544 treatment may result in higher response rates in ALL compared with response rates obtained in AML with Mylotarg, and that therefore clinical studies in ALL, preferably with multiple low CMC-544 dosages, are warranted.

TCRB gene rearrangements in childhood and adult precursor-B-ALL: frequency, applicability as MRD-PCR target, and stability between diagnosis and relapse.

Using the multiplex PCR tubes of the BIOMED-2 Concerted Action, TCRB gene rearrangements were detected in 35% of childhood (n=161) and adult (n=172) precursor-B-ALL patients (Vbeta-(Dbeta)-Jbeta in 25%; Dbeta-Jbeta in 15%). The presence of TCRB rearrangements showed a significant relation with age (highest frequency of 46% between 5 and 10 years of age) and the presence of TEL-AML1 transcripts, and was associated with relatively high frequencies of IGK-Kde, TCRG, and Vdelta2-Jalpha rearrangements. In 62 out of 65 patients with Southern blot-detected Vbeta-(Dbeta)-Jbeta and/or Dbeta-Jbeta rearrangements, at least one TCRB gene rearrangement was detected by PCR. Based on combined Southern blot and PCR analysis, oligoclonal TCRB gene rearrangements were observed in only 12% of patients. Analysis of paired diagnosis and relapse samples (n=26) showed that 20 out of 24 (83%) Vbeta-(Dbeta)-Jbeta rearrangements and eight out of 14 (57%) Dbeta-Jbeta rearrangements remained stable. Using real-time quantitative PCR, a quantitative range < or =10(-4) was obtained in 64% of TCRB gene rearrangements and in 86% of cases a sensitivity < or =10(-4) was obtained. In conclusion, TCRB gene rearrangements occur in 35% of precursor-B-ALL patients and are relatively stable and sensitive PCR targets for detection of minimal residual disease, particularly if this concerns complete Vbeta-(Dbeta)-Jbeta rearrangements.

Apoptotic versus autophagic cell death in heart failure.

OBJECTIVE: Progressive loss of cardiomyocytes is one of the most important pathogenic characteristics of heart failure. Apoptosis may be an important mode of cell death in heart failure but it must be demonstrated by multiple criteria and not just TUNEL staining alone. Previously, we and others have demonstrated that besides apoptosis other phenomena like active gene transcription can result in TUNEL positivity. Moreover, other types of cell death that are caspase-independent could be important in heart failure. This study examined the hypothesis whether TUNEL labeling parallels caspase activation. METHODS: Cardiac tissue of patients in the terminal stage of heart failure as a consequence of ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) were studied. Embryonic mice hearts were used for positive control for detection of the classical apoptosis. RESULTS: In mice embryonic hearts we could clearly find apoptotic cell death detected by TUNEL labeling and immunohistochemistry for activated caspase-3. In heart failure, TUNEL-positive cardiomyocytes were negative for active caspase-3 but showed signs of active gene transcription (SC-35). However, autophagic cell death could be found in 0.3% of the cardiomyocytes. Autophagic cell death was demonstrated by granular cytoplasmic ubiquitin inclusions, an established marker of autophagocytosis in neurons. Interestingly, these autophagic cardiomyocytes were TUNEL and activated caspase-3 negative but were also negative for C9, a marker for necrosis. Western blot analysis confirmed that in cardiomyopathies no cleavage of caspase-3 and caspase-7 occurred. CONCLUSION: The present study demonstrates two fundamentally different situations of cell death in cardiac tissue. In embryonic mice, cardiomyocytes undergo caspase-dependent cell death. However, cardiomyocytes in heart failure show caspase-independent autophagic cell death rather than apoptotic cell death.

Cytoarchitectural and metabolic adaptations in muscles with mitochondrial and cytosolic creatine kinase deficiencies.

We have blocked creatine kinase (CK) mediated phosphocreatine (PCr) <==> ATP transphosphorylation in mitochondria and cytosol of skeletal muscle by knocking out the genes for the mitochondrial (ScCKmit) and the cytosolic (M-CK) CK isoforms in mice. Animals which carry single or double mutations, if kept and tested under standard laboratory conditions, have surprisingly mild changes in muscle physiology. Strenuous ex vivo conditions were necessary to reveal that MM-CK absence in single and double mutants leads to a partial loss of tetanic force output. Single ScCKmit deficiency has no noticeable effects but in combination the mutations cause slowing of the relaxation rate. Importantly, our studies revealed that there is metabolic and cytoarchitectural adaptation to CK defects in energy metabolism. The effects involve mutation type-dependent alterations in the levels of AMP, IMP, glycogen and phosphomonoesters, changes in activity of metabolic enzymes like AMP-deaminase, alterations in mitochondrial volume and contractile protein (MHC isoform) profiles, and a hyperproliferation of the terminal cysternae of the SR (in tubular aggregates). This suggests that there is a compensatory resiliency of loss-of-function and redirection of flux distributions in the metabolic network for cellular energy in our mutants.

The effect of ischemia and reperfusion on mitochondrial contact sites in isolated rat hearts.

Contact sites may be described as energy channels between the mitochondria and the cytosol, created by fusion of the inner and the outer mitochondrial membranes, and their number depends highly on the energy state of the cell. The aim of the present study was to examine the early changes of ischemia and reperfusion on the number of mitochondrial contact sites. Therefore isolated rat hearts were subjected to short periods of ischemia followed by reperfusion. The left ventricular pressure (LVP), the contractility (dP/dtmax) and the heart rate were measured. The number of contact sites was morphometrically evaluated. As the flow was stopped, LVP, dP/dtmax and HR declined rapidly and became undetectable after 2 min of ischemia. The number of contact sites fell to a minimum after 10 min of ischemia after an initial increase (1 min of ischemia). A 15 min ischemic period resulted in a high number of contact sites which decreased again after 20 min of ischemia. Reperfusion after 2 min of ischemia caused an immediate functional recovery and a high presence of contact sites. After 15 min of reperfusion, all values returned to control values. Reperfusion after 10 min of ischemia resulted in a slow recovery of the number of contact sites and after 15 min of ischemia the number of contact sites remained low upon reperfusion. We may conclude that mitochondria lose the ability to form contact sites after more than 15 min of ischemia and this might be a first indication of irreversible injury.

The effect of calcium on mitochondrial contact sites: a study on isolated rat hearts.

Mitochondrial contact sites are dynamic structures created by fusion of the inner and outer mitochondrial membranes. Stimulation of the metabolism results in an increase of the number of contact sites. Functionally, it is shown that mitochondrial creatine kinase (Mi-CK) is active in contact sites and therefore, Mi-CK cytochemistry was performed (using a tetrazolium salt) to improve the visibility of the contact sites. As calcium is involved as an intracellular messenger of hormonal stimulation, the effect of increasing extracellular calcium concentrations on the number of contact sites was investigated. Therefore, isolated rat hearts were perfused with Krebs-Henseleit buffers differing in their calcium content. During the perfusions the heart function was evaluated and at the end of each experiment, the hearts were processed for Mi CK cytochemistry and the number of contact sites was expressed as the ratio of surface densities contact sites to mitochondrial membranes (Ss). At 2.2 mM calcium perfusion, the physiological parameters and the Ss reached a maximum. This was in contrast to the 0.6 and the 3.6 mM of calcium perfusions whereby both the physiological values and the Ss were decreased. Treatment with noradrenaline in vivo, as was done in previous studies or perfusion with 2.2 mM of calcium ends up with similar values for Ss. From these results, it could be suggested that there might be a link between calcium, heart function and the formation of Mi CK active contact sites.

Ultrastructural localisation of carnitine acetyltransferase activity in mitochondria of rat myocardium.

The acetyl CoA/CoA ratio is an important regulating factor of beta-oxidation in mitochondria and hence of energy production in the myocardium. Carnitine acetyltransferase provides one of the control mechanisms for this ratio during changing energy demand in the heart muscle, possibly by buffering the CoA and carnitine concentration for sustained beta-oxidation. In search for a possible correlation between the activity of this enzyme and ultrastructural changes in heart mitochondria, carnitine acetyltransferase was cytochemically localised in rat myocardium, brought into different metabolic states. In this work we confirm previous observations, namely the formation of contact sites between inner and outer mitochondrial membranes upon catecholaminergic stimulation of the myocardium. It is further shown that this contact site formation might be a prerequisite for carnitine acetyltransferase to demonstrate enzymatic activity and hence control of beta-oxidation in myocardial mitochondria.

Increased extracellular calcium concentrations in the isolated rat heart: effects on mitochondrial contact site formation.

In our previous study, mitochondrial creatine kinase (Mi-CK) activity is localised cytochemically in heart tissue. The activity was found to be exclusively localised in mitochondrial contact sites and the surface density of Mi-CK was increased upon myocardial stimulation (Biermans et al., 1989). As calcium is involved as an intracellular messenger of stimulation, we compared hearts noradrenaline-stimulated in vivo with isolated hearts perfused with buffers containing different calcium concentrations on the surface density Mi-CK.

Ultrastructural localisation of creatine kinase activity in the contact sites between inner and outer mitochondrial membranes of rat myocardium.

The mitochondrial isoenzyme of creatine kinase, together with the ADP/ATP translocase, most probably belongs to a functional multi-enzyme complex located on the inner mitochondrial membrane. The outer membrane is a necessary constituent of this microcompartment. On the other hand, electron microscopic visualisation demonstrated the formation of contact sites between inner and outer mitochondrial membranes as a reaction to variations of the energy metabolism. In search for a possible correlation between these biochemical and morphological phenomena, rat myocardia were brought into the required energy state by stimulation through catecholaminergic mechanisms or adjusted perfusion with amytal. Subsequently, creatine kinase was cytochemically localised. Creatine kinase activity is demonstrated in membrane contacts between inner and outer mitochondrial membranes. The extent of contact sites and creatine kinase activity depends on the metabolic state as shown by morphometric analysis of the surface density of cytochemical reaction product. This surface density diminishes drastically after inhibiting the metabolic activity with amytal. It is concluded that these contact sites are dynamic micro-environments in which the active site of creatine kinase, oxidative phosphorylation and ADP/ATP transport interact during basal and stimulated metabolism.

Character neuroses and behavioural disorders in children: their treatment with pipamperone (Dipiperon). A clinical study.

Dipiperon drops 30-180 mg/day were given for eight weeks to 29 children with character neuroses and behavioural disorders. A 16-item rating-scale covering several features of behaviour disorder was completed by a psychologist and a teacher independent from each other. The individual number of pathological scores showed a decrease already within the first treatment week and a further decrease by the end of the trial, especially for the items of capriciousness, obstinacy, irritability and restlessness. The therapeutic benefit was not accompanied by an adverse effect on the school performance of the children. No side-effects were reported or observed.