Prenatal diagnosis and treatment planning of congenital heart defects-possibilities and limits

BACKGROUND: Newborns with hypoplastic left heart syndrome (HLHS) or right heart syndrome or other malformations with a single ventricle physiology and associated hypoplasia of the great arteries continue to be a challenge in terms of survival. The vast majority of these forms of congenital heart defects relate to abnormal morphogenesis during early intrauterine development and can be diagnosed accurately by fetal echocardiography. Early knowledge of these conditions not only permits a better understanding of the progression of these malformations but encourages some researchers to explore new minimally invasive therapeutic options with a view to early pre- and postnatal cardiac palliation. DATA SOURCES: PubMed database was searched with terms of "congenital heart defects", "fetal echocardiography" and "neonatal cardiac surgery". RESULTS: At present, early prenatal detection has been applied for monitoring pregnancy to avoid intrauterine cardiac decompensation. In principle, the majority of congenital heart defects can be diagnosed by prenatal echocardiography and the detection rate is 85%-95% at tertiary perinatal centers. The majority, particularly of complex congenital lesions, show a steadily progressive course including subsequent secondary phenomena such as arrhythmias or myocardial insufficiency. So prenatal treatment of an abnormal fetus is an area of perinatal medicine that is undergoing a very dynamic development. Early postnatal treatment is established for some time, and prenatal intervention or palliation is at its best experimental stage in individual cases. CONCLUSION: The upcoming expansion of fetal cardiac intervention to ameliorate critically progressive fetal lesions intensifies the need to address issues about the adequacy of technological assessment and patient selection as well as the morbidity of those who undergo these procedures.

Rapid screening for carriage of methicillin-resistant Staphylococcus aureus by PCR and associated costs

PCR tests for the rapid and valid detection of methicillin-resistant Staphylococcus aureus (MRSA) are now available. We evaluated the costs associated with contact screening for MRSA carriage in a tertiary-care hospital with low MRSA endemicity. Between 1 October 2005 and 28 February 2006, 232 patients were screened during 258 screening episodes (644 samples) for MRSA carriage by GenoType MRSA Direct (Hain Lifescience GmbH, Nehren, Germany). Conventional culture confirmed all PCR results. According to in-house algorithms, 34 of 258 screening episodes (14.7%) would have qualified for preemptive contact isolation, but such isolation was not done upon negative PCR results. MRSA carriage was detected in 4 (1.5%) of 258 screening episodes (i.e., in four patients), of which none qualified for preemptive contact isolation. The use of PCR for all 258 screening episodes added costs (in Swiss francs [CHF]) of CHF 104,328.00 and saved CHF 38,528.00 (for preemptive isolation). The restriction of PCR screening to the 34 episodes that qualified for preemptive contact isolation and screening all others by culture would have lowered costs for PCR to only CHF 11,988.00, a savings of CHF 38,528.00. Therefore, PCR tests are valuable for the rapid detection of MRSA carriers, but high costs require the careful evaluation of their use. In patient populations with low MRSA endemicity, the broad use of PCR probably is not cost-effective.

Zebrafish (Danio rerio) neuromast: promising biological endpoint linking developmental and toxicological studies

Aquatic toxicology is facing the challenge to assess the impact of complex mixtures of compounds on diverse biological endpoints. So far, ecotoxicology focuses mainly on apical endpoints such as growth, lethality and reproduction, but does not consider sublethal toxic effects that may indirectly cause ecological effects. One such sublethal effect is toxicant-induced impairment of neurosensory functions which will affect important behavioural traits of exposed organisms. Here, we critically review the mechanosensory lateral line (LL) system of zebrafish as a model to screen for chemical effects on neurosensory function of fish in particular and vertebrates in general. The LL system consists of so-called neuromasts, composed of centrally located sensory hair cells, and surrounding supporting cells. The function of neuromasts is the detection of water movements that is essential for the fish's ability to detect prey, to escape predator, to socially interact or to show rheotactic behaviour. Recent advances in the study of these organs provided researchers with a broad area of molecular tools for easy and rapid detection of neuromasts dysfunction and/or disturbed development. Further, genes involved in neuromasts differentiation have been identified using auditory/mechanosensory mutants and morphants. A number of environmental toxicants including metals and pharmaceuticals have been shown to affect neuromasts development and/or function. The use of the LL organ for toxicological studies offers the advantage to integrate the available profound knowledge on developmental biology of the neuromasts with the study of chemical toxicity. This combination may provide a powerful tool in environmental risk assessment.

Monitoring of antiretroviral therapy and mortality in HIV programmes in Malawi, South Africa and Zambia: mathematical modelling study

OBJECTIVES Mortality in patients starting antiretroviral therapy (ART) is higher in Malawi and Zambia than in South Africa. We examined whether different monitoring of ART (viral load [VL] in South Africa and CD4 count in Malawi and Zambia) could explain this mortality difference. DESIGN Mathematical modelling study based on data from ART programmes. METHODS We used a stochastic simulation model to study the effect of VL monitoring on mortality over 5 years. In baseline scenario A all parameters were identical between strategies except for more timely and complete detection of treatment failure with VL monitoring. Additional scenarios introduced delays in switching to second-line ART (scenario B) or higher virologic failure rates (due to worse adherence) when monitoring was based on CD4 counts only (scenario C). Results are presented as relative risks (RR) with 95% prediction intervals and percent of observed mortality difference explained. RESULTS RRs comparing VL with CD4 cell count monitoring were 0.94 (0.74-1.03) in scenario A, 0.94 (0.77-1.02) with delayed switching (scenario B) and 0.80 (0.44-1.07) when assuming a 3-times higher rate of failure (scenario C). The observed mortality at 3 years was 10.9% in Malawi and Zambia and 8.6% in South Africa (absolute difference 2.3%). The percentage of the mortality difference explained by VL monitoring ranged from 4% (scenario A) to 32% (scenarios B and C combined, assuming a 3-times higher failure rate). Eleven percent was explained by non-HIV related mortality. CONCLUSIONS VL monitoring reduces mortality moderately when assuming improved adherence and decreased failure rates.

Recent skin self-examination and doctor visits in relation to melanoma risk and tumour depth

BACKGROUND Little is known about the potential benefit of skin self-examination for melanoma prevention and early detection. Objectives: To determine whether skin self-examination is associated with reduced melanoma risk, self-detection of tumours, and reduced risk of deeper melanomas. METHODS We used data from a population-based case-control study (423 cases, 678 controls) to assess recent skin self-examination in relation to self-detection, melanoma risk and tumour depth ( ≤1 mm; > 1 mm). Logistic regression was used to estimate odds ratios (ORs) and confidence intervals (CIs) for associations of interest. RESULTS Skin self-examination conducted 1-11 times during a recent year was associated with a possible decrease in melanoma risk (OR 0·74; 95% CI 0·54-1·02). Melanoma risk was decreased for those who conducted skin self-examination and saw a doctor (OR 0·52; 95% CI 0·30-0·90). Among cases, those who examined their skin were twice as likely to self-detect the melanoma (OR 2·23; 95% CI 1·47-3·38), but self-detection was not associated with shallower tumours. Tumour depth was reduced for those who conducted skin self-examination 1-11 times during a recent year (OR 0·39; 95% CI 0·18-0·81), but was not influenced by seeing a doctor, or by conducting skin self-examination and seeing a doctor. CONCLUSIONS Risk of a deeper tumour and possibly risk of melanoma were reduced by skin self-examination 1-11 times annually. Melanoma risk was markedly reduced by skin self-examination coupled with a doctor visit. We cannot, however, exclude the possibility that our findings reflect bias or confounding. Additional studies are needed to elucidate the potential benefits of skin self-examination for melanoma prevention and early detection.

Detection of pulmonary amylase activity in exhaled breath condensate

Amylase activity in exhaled breath condensate (EBC) is usually interpreted as an indication of oropharyngeal contamination despite the fact that amylase can be found in pulmonary excretions. The aim of this study was to recruit and refine an amylase assay in order to detect amylase activity in any EBC sample and to develop a method to identify EBC samples containing amylase of pulmonary origin. EBC was collected from 40 volunteers with an EcoScreen condenser. Amylase assays and methods to discriminate between oropharyngeal and pulmonary proteins were tested and developed using matched EBC and saliva samples. Our refined 2-chloro-4-nitrophenyl-α-D-maltotriosid (CNP-G3) assay was 40-fold more sensitive than the most sensitive commercial assay and allowed detection of amylase activity in 30 µl of EBC. We developed a dot-blot assay which allowed detection of salivary protein in saliva diluted up to 150 000-fold. By plotting amylase activity against staining intensity we identified a few EBC samples with high amylase activity which were aligned with diluted saliva. We believe that EBC samples aligned with diluted saliva contain amylase activity introduced during EBC collection and that all other EBC samples contain amylase activity of pulmonary origin and are basically free of oropharyngeal protein contamination.

The cyclotron laboratory and the RFQ accelerator in Bern

Two proton accelerators have been recently put in operation in Bern: an 18 MeV cyclotron and a 2 MeV RFQ linac. The commercial IBA 18/18 cyclotron, equipped with a specifically conceived 6 m long external beam line ending in a separate bunker, will provide beams for routine 18-F and other PET radioisotope production as well as for novel detector, radiation biophysics, radioprotection, radiochemistry and radiopharmacy developments. The accelerator is embedded into a complex building hosting two physics laboratories and four Good Manufacturing Practice (GMP) laboratories. This project is the result of a successful collaboration between the Inselspital, the University of Bern and private investors, aiming at the constitution of a combined medical and research centre able to provide the most cutting-edge technologies in medical imaging and cancer radiation therapy. The cyclotron is complemented by the RFQ with the primary goals of elemental analysis via Particle Induced Gamma Emission (PIGE), and the detection of potentially dangerous materials with high nitrogen content using the Gamma-Resonant Nuclear Absorption (GRNA) technique. In this context, beam instrumentation devices have been developed, in particular an innovative beam profile monitor based on doped silica fibres and a setup for emittance measurements using the pepper-pot technique. On this basis, the establishment of a proton therapy centre on the campus of the Inselspital is in the phase of advanced study.

Sensitive Questions in Online Surveys: An Experimental Evaluation of the Randomized Response Technique and the Crosswise Model

Self-administered online surveys provide a higher level of privacy protection to respondents than surveys administered by an interviewer. Yet, studies indicate that asking sensitive questions is problematic also in self-administered surveys. Because respondents might not be willing to reveal the truth and provide answers that are subject to social desirability bias, the validity of prevalence estimates of sensitive behaviors from online surveys can be challenged. A well-known method to overcome these problems is the Randomized Response Technique (RRT). However, convincing evidence that the RRT provides more valid estimates than direct questioning in online surveys is still lacking. A new variant of the RRT called the Crosswise Model has recently been proposed to overcome some of the deficiencies of existing RRT designs. We therefore conducted an experimental study in which different implementations of the RRT, including two implementations of the crosswise model, were tested and compared to direct questioning. Our study is a large-scale online survey (N = 6,037) on sensitive behaviors by students such as cheating in exams and plagiarism. Results indicate that the crosswise-model RRT---unlike the other variants of RRT we evaluated---yields higher prevalence estimates of sensitive behaviors than direct questioning. Whether higher estimates are a sufficient condition for more valid results, however, remains questionable.

A Comparison of Radiocolloid and Indocyanine Green Fluorescence Imaging, Sentinel Lymph Node Mapping in Patients with Cervical Cancer Undergoing Laparoscopic Surgery.

BACKGROUND AND PURPOSE (99)TC combined with blue-dye mapping is considered the best sentinel lymph node (SLN) mapping technique in cervical cancer. Indocyanine green (ICG) with near infrared fluorescence imaging has been introduced as a new methodology for SLN mapping. The aim of this study was to compare these two techniques in the laparoscopic treatment of cervical cancer. METHODS Medical records of patients undergoing laparoscopic SLN mapping for cervical cancer with either (99)Tc and patent blue dye (Group 1) or ICG (Group 2) from April 2008 until August 2012 were reviewed. Sensitivity, specificity, and overall and bilateral detection rates were calculated and compared. RESULTS Fifty-eight patients were included in the study-36 patients in Group 1 and 22 patients in Group 2. Median tumor diameter was 25 and 29 mm, and mean SLN count was 2.1 and 3.7, for Groups 1 and 2, respectively. Mean non-SLN (NSLN) count was 39 for both groups. SLNs were ninefold more likely to be affected by metastatic disease compared with NSLNs (p < 0.005). Sensitivity and specificity were both 100 %. Overall detection rates were 83 and 95.5 % (p = nonsignificant), and bilateral detection rates were 61 and 95.5 % (p < 0.005), for Groups 1 and 2, respectively. In 75 % of cases, SLNs were located along the external or internal iliac nodal basins. CONCLUSIONS ICG SLN mapping in cervical cancer provides high overall and bilateral detection rates that compare favorably with the current standard of care.

Impairments of peripheral motion change detection during smooth pursuit eye movements

Introduction: In team sports the ability to use peripheral vision is essential to track a number of players and the ball. By using eye-tracking devices it was found that players either use fixations and saccades to process information on the pitch or use smooth pursuit eye movements (SPEM) to keep track of single objects (Schütz, Braun, & Gegenfurtner, 2011). However, it is assumed that peripheral vision can be used best when the gaze is stable while it is unknown whether motion changes can be equally well detected when SPEM are used especially because contrast sensitivity is reduced during SPEM (Schütz, Delipetkose, Braun, Kerzel, & Gegenfurtner, 2007). Therefore, peripheral motion change detection will be examined by contrasting a fixation condition with a SPEM condition. Methods: 13 participants (7 male, 6 female) were presented with a visual display consisting of 15 white and 1 red square. Participants were instructed to follow the red square with their eyes and press a button as soon as a white square begins to move. White square movements occurred either when the red square was still (fixation condition) or moving in a circular manner with 6 °/s (pursuit condition). The to-be-detected white square movements varied in eccentricity (4 °, 8 °, 16 °) and speed (1 °/s, 2 °/s, 4 °/s) while movement time of white squares was constant at 500 ms. 180 events should be detected in total. A Vicon-integrated eye-tracking system and a button press (1000 Hz) was used to control for eye-movements and measure detection rates and response times. Response times (ms) and missed detections (%) were measured as dependent variables and analysed with a 2 (manipulation) x 3 (eccentricity) x 3 (speed) ANOVA with repeated measures on all factors. Results: Significant response time effects were found for manipulation, F(1,12) = 224.31, p < .01, ηp2 = .95, eccentricity, F(2,24) = 56.43; p < .01, ηp2 = .83, and the interaction between the two factors, F(2,24) = 64.43; p < .01, ηp2 = .84. Response times increased as a function of eccentricity for SPEM only and were overall higher than in the fixation condition. Results further showed missed events effects for manipulation, F(1,12) = 37.14; p < .01, ηp2 = .76, eccentricity, F(2,24) = 44.90; p < .01, ηp2 = .79, the interaction between the two factors, F(2,24) = 39.52; p < .01, ηp2 = .77 and the three-way interaction manipulation x eccentricity x speed, F(2,24) = 3.01; p = .03, ηp2 = .20. While less than 2% of events were missed on average in the fixation condition as well as at 4° and 8° eccentricity in the SPEM condition, missed events increased for SPEM at 16 ° eccentricity with significantly more missed events in the 4 °/s speed condition (1 °/s: M = 34.69, SD = 20.52; 2 °/s: M = 33.34, SD = 19.40; 4 °/s: M = 39.67, SD = 19.40). Discussion: It could be shown that using SPEM impairs the ability to detect peripheral motion changes at the far periphery and that fixations not only help to detect these motion changes but also to respond faster. Due to high temporal constraints especially in team sports like soccer or basketball, fast reaction are necessary for successful anticipation and decision making. Thus, it is advised to anchor gaze at a specific location if peripheral changes (e.g. movements of other players) that require a motor response have to be detected. In contrast, SPEM should only be used if a single object, like the ball in cricket or baseball, is necessary for a successful motor response. References: Schütz, A. C., Braun, D. I., & Gegenfurtner, K. R. (2011). Eye movements and perception: A selective review. Journal of Vision, 11, 1-30. Schütz, A. C., Delipetkose, E., Braun, D. I., Kerzel, D., & Gegenfurtner, K. R. (2007). Temporal contrast sensitivity during smooth pursuit eye movements. Journal of Vision, 7, 1-15.

Therapeutic drug monitoring of cefepime with micellar electrokinetic capillary chromatography: Assay improvement, quality assurance, and impact on patient drug levels

The improvement and performance of a micellar electrokinetic capillary chromatography assay for cefepime in human serum and plasma with a 50 μm id fused-silica capillary elongated from 40 to 60 cm is reported. Sample preparation with dodecylsulfate protein precipitation at pH 4.5, the pH 9.1 separation medium and the applied voltage were as reported previously[16]. The change resulted in a significant lower current, higher resolution and increased detection time intervals. The performance of the assay with multi-level internal calibration was assessed with calibration and control samples. Quality assurance data of a two year period assessed under the new conditions demonstrated the robustness of the assay. In serum samples of patients who received both cefepime and sulfamethoxazole, cefepime could not be detected due to the inseparability of the two compounds. The presence of an interference can be recognized by an increased peak width (width > 0.2 min), the appearance of a shoulder or an unresolved double peak. The patient data gathered during a three year period reveal that introduction of therapeutic drug monitoring led to a 50% reduction of the median drug level. The data suggest that therapeutic drug monitoring can help to minimize the risk of major adverse reactions and to increase drug safety on an individual basis. This article is protected by copyright. All rights reserved.

Multiplex suspension array for human anti-carbohydrate antibody profiling

Glycan-binding antibodies form a significant subpopulation of both natural and acquired antibodies and play an important role in various immune processes. They are for example involved in innate immune responses, cancer, autoimmune diseases, and neurological disorders. In the present study, a microsphere-based flow-cytometric immunoassay (suspension array) was applied for multiplexed detection of glycan-binding antibodies in human serum. Several approaches for immobilization of glycoconjugates onto commercially available fluorescent microspheres were compared, and as the result, the design based on coupling of end-biotinylated glycopolymers has been selected. This method requires only minute amounts of glycans, similar to a printed glycan microarray. The resulting glyco-microspheres were used for detection of IgM and IgG antibodies directed against ABO blood group antigens. The possibility of multiplexing this assay was demonstrated with mixtures of microspheres modified with six different ABO related glycans. Multiplexed detection of anti-glycan IgM and IgG correlated well with singleplex assays (Pearson's correlation coefficient r = 0.95-0.99 for sera of different blood groups). The suspension array in singleplex format for A/B trisaccharide, H(di) and Le(x) microspheres corresponded well to the standard ELISA (r > 0.94). Therefore, the described method is promising for rapid, sensitive, and reproducible detection of anti-glycan antibodies in a multiplexed format.

A review of full-body radiography in nontraumatic emergency medicine

This paper reports on the application of full-body radiography to nontraumatic emergency situations. The Lodox Statscan is an X-ray machine capable of imaging the entire body in 13 seconds using linear slit scanning radiography (LSSR). Nontraumatic emergency applications in ventriculoperitoneal (VP) shunt visualisation, emergency room arteriography (ERA), detection of foreign bodies, and paediatric emergency imaging are presented. Reports show that the fast, full-body, and low-dose scanning capabilities of the Lodox system make it well suited to these applications, with the same or better image quality, faster processing times, and lower dose to patients. In particular, the large format scans allowing visualisation of a greater area of anatomy make it well suited to VP shunt monitoring, ERA, and the detection of foreign bodies. Whilst more studies are required, it can be concluded that the Lodox Statscan has the potential for widespread use in these and other nontraumatic emergency radiology applications.

Can handheld micropower impulse radar technology be used to detect pneumothorax? Initial experience in a European trauma centre

BACKGROUND: Pneumothoraces are a common injury pattern in emergency medicine. Rapid and safe identification can reduce morbidity and mortality. A new handheld, battery powered device, the Pneumoscan (CE 561036, PneumoSonics Inc., Cleveland, OH, USA), using micropower impulse radar (MIR) technology, has recently been introduced in Europe for the rapid and reliable detection of PTX. However, this technology has not yet been tested in trauma patients. This is the first quality control evaluation to report on emergency room performance of a new device used in the trauma setting. MATERIAL AND METHODS: This study was performed at a Level I trauma centre in Switzerland. All patients with thoracic trauma and undergoing chest X-ray and CT-scan were eligible for the study. Readings were performed before the chest X-ray and CT scan. The patients had eight lung fields tested (four on each side). All readings with the Pneumoscan were performed by two junior residents in our department who had previously received an instructional tutorial of 15min. The qualitative MIR results were blinded, and stored on the device. We then compared the results of the MIR to those of the clinical examination, chest X-ray and CT-scan. RESULTS: 50 patients were included, with a mean age of 46 (SD 17) years. Seven patients presented with PTX diagnosed by CT; six of these were detected by Pneumoscan, leading to an overall sensitivity of 85.7 (95% confidence interval 42.1-99.6)%. Only two of seven PTX were found during clinical examination and on chest X-ray (sensitivity 28.6 (95% CI 3.7-71.0)%). Of the remaining 43 of 50 patients without PTX, one false-positive PTX was found by the Pneumoscan, resulting in a specificity of 97.7 (95% CI 87.7-99.9)%. DISCUSSION: The Pneumoscan is an easy to use handheld technology with reliable results. In this series, the sensitivity to detect a PTX by the Pneumoscan was higher than by clinical examination and chest X-ray. Further studies with higher case numbers and a prospective study design are needed to confirm our findings.

Human group II 14 kDa phospholipase A2 activates human platelets

Recombinant human group II phospholipase A2 (sPLA2) added to human platelets in the low microg/ml range induced platelet activation, as demonstrated by measurement of platelet aggregation, thromboxane A2 generation and influx of intracellular free Ca2+ concentration and by detection of time-dependent tyrosine phosphorylation of platelet proteins. The presence of Ca2+ at low millimolar concentrations is a prerequisite for the activation of platelets by sPLA2. Mg2+ cannot replace Ca2+. Mg2+, given in addition to the necessary Ca2+, inhibits sPLA2-induced platelet activation. Pre-exposure to sPLA2 completely blocked the aggregating effect of a second dose of sPLA2. Albumin or indomethacin inhibited sPLA2-induced aggregation, similarly to the inhibition of arachidonic acid-induced aggregation. Platelets pre-treated with heparitinase or phosphatidylinositol-specific phospholipase C lost their ability to aggregate in response to sPLA2, although they still responded to other agonists. This suggests that a glycophosphatidylinositol-anchored platelet-membrane heparan sulphate proteoglycan is the binding site for sPLA2 on platelets. Previous reports have stated that sPLA2 is unable to activate platelets. The inhibitory effect of albumin and Mg2+, frequently used in aggregation studies, and the fact that isolated platelets lose their responsiveness to sPLA2 relatively quickly, may explain why the platelet-activating effects of sPLA2 have not been reported earlier.