Cardiac tamponade following post-pericardiotomy syndrome.

SUMMARY: Subxyphoid pericardial window (SPW) is performed as both a diagnostic and therapeutic intervention in patients presenting with a penetrating cardiac injury (PCI). Post-pericardiotomy syndrome (PPS) with cardiac tamponade has been reported after penetrating cardiac trauma and after transdiaphragmatic pericardial window. We describe the first PPS with acute tamponade, weeks after diagnostic SPW for a PCI.

Molecular signatures that can be transferred across different omics platforms.

MOTIVATION: Molecular signatures for treatment recommendations are well researched. Still it is challenging to apply them to data generated by different protocols or technical platforms. RESULTS: We analyzed paired data for the same tumors (Burkitt lymphoma, diffuse large B-cell lymphoma) and features that had been generated by different experimental protocols and analytical platforms including the nanoString nCounter and Affymetrix Gene Chip transcriptomics as well as the SWATH and SRM proteomics platforms. A statistical model that assumes independent sample and feature effects accounted for 69-94% of technical variability. We analyzed how variability is propagated through linear signatures possibly affecting predictions and treatment recommendations. Linear signatures with feature weights adding to zero were substantially more robust than unbalanced signatures. They yielded consistent predictions across data from different platforms, both for transcriptomics and proteomics data. Similarly stable were their predictions across data from fresh frozen and matching formalin-fixed paraffin-embedded human tumor tissue. AVAILABILITY AND IMPLEMENTATION: The R-package 'zeroSum' can be downloaded at https://github.com/rehbergT/zeroSum . Complete data and R codes necessary to reproduce all our results can be received from the authors upon request. CONTACT: rainer.spang@ur.de.

[Bearing selection in total hip arthroplasty]. / Wahl der richtigen Gleitpaarung in der Hüftendoprothetik.

Different bearing materials are available in total hip arthroplasty and it's the surgeon who has the choice between hard-on-soft, hard-on-hard and alternative materials. Ideally, the material selection should rely on evidence-based data regarding the wear performance, the incidence of revision surgery and other potential bearing-associated risk factors for the corresponding combinations of materials in the individual patient. While there are high-quality studies available for some materials, adequate data is lacking for other materials. Therefore, the current article aims to provide bearing selection criteria for the surgeon and to review the current literature regarding different combinations of bearing materials in total hip arthroplasty.

Review of anal cancer patients at the Ottawa hospital.

BACKGROUND: Anal cancer is uncommon. We reviewed the treatment and outcomes of anal cancer patients in a population referred to the Ottawa Hospital Cancer Centre (TOHCC) over a 12-year period. METHODS: A chart review was conducted with patient data collected from hospital records, including: demographic, treatment and outcome information. Outcomes of interest included: overall survival (OS), disease free survival (DFS), and colostomy free survival (CFS). RESULTS: 180 patients were included in the study population. 72% (n = 130) female and 28% (n = 50) male. 6.7% (n = 12 males) of patients were HIV positive - all were on anti-retroviral therapy. 60% (n = 108) of patients were ever-smokers, mean patient age was 62 [range 35-90] years. The most frequent presenting symptoms were blood per rectum and anal pain. Treatment intent was curative in 87%. Treatment included radiotherapy (94%), brachytherapy (26%), chemotherapy (73%). Among patients treated with curative-intent, 72% had a complete response, 31% had local/regional recurrence, 16% required salvage surgery and 21% had distant recurrence. The colostomy rate was 23%. 5 year overall survival (OS) was not significantly different for patients by HIV status. Survival was superior if MMC-FU was used first vs. CIS-FU; OS HR 0.47 (0.24-0.94), p < 0.033. CONCLUSIONS: The outcomes of patients in this large retrospective cohort study are similar to the outcomes of patients in highly selective clinical trials. Five year overall survival and colostomy free survival are encouraging. MMC-FU was found to be superior to CIS-FU.

Direct access: lessons learnt from the Netherlands.

OBJECTIVE: To use a qualitative approach to examine the perceptions of policy makers, general dental practitioners, dental hygienists, dental students and dental hygiene students in the Netherlands following the introduction of a direct access policy in 2006. METHODS: Semi-structured interviews and focus groups were undertaken with a variety of policy makers and clinicians in the Netherlands. These were recorded and transcribed verbatim into MS Word documents. The transcripts were line numbered and subjected to thematic analysis to develop a coding frame using NVivo. RESULTS: Four main themes are reported, which represent a subset of a policy analysis of direct access in the Netherlands. These were entitled: 'The narrative of implementation', 'Working models of direct access', 'Relationship between old- and new-style hygienists' and 'Public attitudes'. CONCLUSIONS: Working relationships within integrated practices in the Netherlands are positive, but attitudes towards independent practice are mixed. Good examples of collaborative working across practices were observed, but relationships between the professional bodies remain difficult seven years on since the introduction of the policy.

Strong reduction of AGO2 expression in melanoma and cellular consequences.

BACKGROUND: Processing of microRNAs (miRNAs) is a highly controlled process. Deregulation of miRNA expression was observed in several types of cancer but changes in the miRNA-processing enzymes have not been analysed until today. In this study, we analysed Argonaute2 (AGO2, EIF2C2), as one main factor of the miRNA processing ensemble, in the context of cancer development, especially in melanoma. METHODS: We determined the AGO2 expression level in melanoma, as well as in other cancers, with biochemical approaches (qRT-PCR, western blot and immunofluorescence studies) and analysed the cell behaviour in migration assays. RESULTS: Specifically in melanoma, we revealed a strong reduction of AGO2 expression compared with primary melanocytes. The reduction of AGO2 expression was only found on protein level, whereas the mRNA level stayed unchanged hinting to post-transcriptional regulation. We could show that re-expression of AGO2 in melanoma leads to a strong improvement of regulatory effects due to increased functionality of small-interfering RNAs and short hairpin RNAs. CONCLUSION: We identified melanoma-specific downregulation of AGO2 and corresponding reduced RNAi efficiency. These findings will help to understand the molecular basis of malignant melanoma and can potentially lead to an improvement of therapeutic strategies.

[Metal ion concentrations in patients with metal-metal bearings in prostheses]. / Metallkonzentrationen bei Patienten mit Metall-Metall-Gleitpaarungs-Prothese.

Increased wear leads to elevated systemic and local metal ion concentrations for patients treated with metal-on-metal bearings. The local metal ion content in the close environment of the joint replacement (e.g. joint aspirate or tissue) is several times higher compared to the systemic metal content (e.g. in blood or serum). As a result of increased metal ion levels, local and systemic effects, such as osteolysis, pseudotumors, sensitization or in rare cases toxicity may occur. Although the definition of a specific threshold to define clinical problems is difficult due to a lack of sensitivity, the systemic metal concentration is frequently measured clinically. Currently a threshold for cobalt and chromium between 4 µg/l and 7 µg/l is under debate. Very high levels (≥ 20 µg/l) or a steady increase over time should be a warning sign; however, metal ion levels should not be interpreted as a single diagnostic tool but rather in the entire context of the clinical, radiological and cross-sectional imaging, metal artefact reduction sequence (MARS) magnetic resonance imaging (MRI), ultrasound and computed tomography (CT) findings.

In vivo serum titanium ion levels following modular neck total hip arthroplasty--10 year results in 67 patients.

The objective of the present cross-sectional study was to determine in vivo titanium ion levels following cementless total hip arthroplasty (THA) using a modular stem system with different shapes for femoral canal fit and multiple neck options. A consecutive series of 173 patients (190 hips) who underwent cementless modular neck THA and a ceramic on polyethylene bearing with a median follow-up of 9 (7-13) years was evaluated retrospectively. According to a standardized protocol, titanium ion measurements were performed on 67 patients using high-resolution inductively coupled plasma-mass spectrometry. Ion levels were compared to a control group comprising patients with non-modular titanium implants (n=11) and to individuals without implants (n=23). Modular neck THA did not result in elevated titanium ion levels compared to non-modular THA. Compared to individuals without implants, both modular THA and non-modular THA showed elevated titanium ion levels. Absolute titanium ion levels, however, were comparatively low for both implants. The data suggest that the present modular stem system does not result in elevated systemic titanium ion levels in the medium term when compared to non-modular stems. Further longitudinal studies are needed to evaluate the use of systemic titanium ion levels as an objective diagnostic tool to identify THA failure and to monitor patients following revision surgery.

[Principles of tribological analysis of endoprostheses]. / Grundlagen zur tribologischen Analyse von Endoprothesen.

For the tribological characterization of artificial joints, various experimental methods are currently available. However, the in vitro test conditions applied are only comparable in a limited way and transferability to the in vivo situation is also restricted. This is due to the different wear simulation concepts used and partly insufficient simulation of clinical worst case situations. In the present paper current scientific methods and procedures for tribological testing of artificial joints are presented. In addition, the biological effects of wear products are described enabling clinicians to challenge tribological studies and to facilitate specific interpretation of scientific results taking the clinical situation into account.

[The collaboration between dentists and dental hygienists: from paradox to resolution]. / De samenwerking tussen tandartsen en mondhygiënisten: van paradox naar oplossing.

The occupation of dental hygienist has changed since the introduction of vertical task redistribution. However, this change has not yet resulted in an optimal collaboration between dentists and dental hygienists. Four typical characteristics of vertical task redistribution are considered to be influentialfactors with respect to collaboration and the acceptance of vertical task redistribution: the transition from a hierarchical work relation to a more functional work relation, educational level as related to competence and social status, the relation between vertical task redistribution and professional identity and the perceived usefulness of interprofessional collaboration and task redistribution. Implications for educational development are based on scientific literature and are illustrated by an example from the dental curriculum in the Dutch city of Groningen. Even though interprofessional collaboration does not seem to be optimal at the present time, there are insights that suggest ways of improving interprofessional collaboration between dentists and dental hygienists. However, more clues are needed. In particular, the paradox between professional identity and interprofessional collaboration has not yet received much scientific attention.

Preoperative chemoradiotherapy for esophageal or junctional cancer.

BACKGROUND: The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established. We compared chemoradiotherapy followed by surgery with surgery alone in this patient population. METHODS: We randomly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin (doses titrated to achieve an area under the curve of 2 mg per milliliter per minute) and paclitaxel (50 mg per square meter of body-surface area) for 5 weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. RESULTS: From March 2004 through December 2008, we enrolled 368 patients, 366 of whom were included in the analysis: 275 (75%) had adenocarcinoma, 84 (23%) had squamous-cell carcinoma, and 7 (2%) had large-cell undifferentiated carcinoma. Of the 366 patients, 178 were randomly assigned to chemoradiotherapy followed by surgery, and 188 to surgery alone. The most common major hematologic toxic effects in the chemoradiotherapy-surgery group were leukopenia (6%) and neutropenia (2%); the most common major nonhematologic toxic effects were anorexia (5%) and fatigue (3%). Complete resection with no tumor within 1 mm of the resection margins (R0) was achieved in 92% of patients in the chemoradiotherapy-surgery group versus 69% in the surgery group (P<0.001). A pathological complete response was achieved in 47 of 161 patients (29%) who underwent resection after chemoradiotherapy. Postoperative complications were similar in the two treatment groups, and in-hospital mortality was 4% in both. Median overall survival was 49.4 months in the chemoradiotherapy-surgery group versus 24.0 months in the surgery group. Overall survival was significantly better in the chemoradiotherapy-surgery group (hazard ratio, 0.657; 95% confidence interval, 0.495 to 0.871; P=0.003). CONCLUSIONS: Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer. The regimen was associated with acceptable adverse-event rates. (Funded by the Dutch Cancer Foundation [KWF Kankerbestrijding]; Netherlands Trial Register number, NTR487.).

What's next? Alternative materials for articulation in total joint replacement.

The use of an artificial joint is always related to a certain amount of wear. Its biological effects, e.g., the osteolysis potential, are a function of the bulk material as well as its debris. Following comprehensive experiences with polyethylene (PE) wear, material science is tracking two ways to minimize the risk of a particle-induced aseptic implant loosening: (i) reduction of the PE debris by a low-wearing articulation partner; and (ii) replacement of the PE by other materials. Therefore, new ceramics (e.g., ZTA, Si(3)N(4)), as well as coatings (e.g., TiN, "diamond-like" carbon) and modifications of a bulk metal (e.g., oxidizes zirconium) or cushion bearings (polyurethane, hydrogels), are currently available for total joint replacements or have been used for pre-clinical testing. This review gives a brief overview and evaluates the potential of those that have recently been published in literature.

Raf kinases mediate the phosphorylation of eukaryotic translation elongation factor 1A and regulate its stability in eukaryotic cells.

We identified eukaryotic translation elongation factor 1A (eEF1A) Raf-mediated phosphorylation sites and defined their role in the regulation of eEF1A half-life and of apoptosis of human cancer cells. Mass spectrometry identified in vitro S21 and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1 whereas S21 was phosphorylated on eEF1A2 by both B- and C-Raf. Interestingly, S21 belongs to the first eEF1A GTP/GDP-binding consensus sequence. Phosphorylation of S21 was strongly enhanced when both eEF1A isoforms were preincubated prior the assay with C-Raf, suggesting that the eEF1A isoforms can heterodimerize thus increasing the accessibility of S21 to the phosphate. Overexpression of eEF1A1 in COS 7 cells confirmed the phosphorylation of T88 also in vivo. Compared with wt, in COS 7 cells overexpressed phosphodeficient (A) and phospho-mimicking (D) mutants of eEF1A1 (S21A/D and T88A/D) and of eEF1A2 (S21A/D), resulted less stable and more rapidly proteasome degraded. Transfection of S21 A/D eEF1A mutants in H1355 cells increased apoptosis in comparison with the wt isoforms. It indicates that the blockage of S21 interferes with or even supports C-Raf induced apoptosis rather than cell survival. Raf-mediated regulation of this site could be a crucial mechanism involved in the functional switching of eEF1A between its role in protein biosynthesis and its participation in other cellular processes.

Incidence of bactobilia increases over time after endoscopic sphincterotomy.

Patients with choledochocystolithiasis are usually treated by endoscopic retrograde cholangiography with endoscopic sphincterotomy (ES) followed by laparoscopic cholecystectomy (LC). LC after ES is more difficult than in uncomplicated gallstone disease, possibly due to bacterial colonization of the common bile duct. The goal of this study was to evaluate if bactobilia influences the peri- and postoperative outcomes. Data were obtained from a randomized trial on the timing of LC after ES. Ninety-six patients were randomized after ES to LC either within 72 h (early LC [ELC]) or in 6-8 weeks (delayed LC [DLC]). In 64 of 96 patients bile samples were obtained peroperatively. The overall prevalence of bactobilia was 62.5% [40/64; 50% of ELC patients (n = 13) vs. 71.1% in the DLC group (n = 27); p = 0.088]. Age and group (i.e. ELC/DLC) were independent and significant predictors for the presence of bactobilia. The presence of bactobilia did not influence operating time and difficulty or conversion rate. Patients with bactobilia developed more biliary events in the period between ES and LC (44 vs. 28%). After ES for choledochocystolithiasis, 62.5% of patients have bactobilia at the time of surgery. The prevalence of bactobilia increases with age and time. Patients with bactobilia tend to develop more biliary-related complications awaiting surgery.

Development and application of an LC-MS/MS method for measuring the effect of (partial) agonists on cAMP accumulation in vitro.

Cyclic-adenosine monophosphate (cAMP) plays an important role in cell signalling and is widely used as a marker for receptor activation and as a target for treating various diseases. In this paper we present the development and validation of a new method for the determination of cAMP and ATP (adenosine triphosphate) and other nucleotides in a biological system by combining zwitterionic hydrophilic interaction liquid chromatography (HILIC) and tandem mass spectrometry (MS/MS). The HILIC-MS/MS method was developed for the simultaneous quantitative analysis of cAMP and ATP, and was validated by assessment of linearity (over a range from 0.5 to 100nM for cAMP and 50 nM to 50 microM for ATP (r(2)>0.999)), resolution, limit of detection (0.5 and 50 nM for cAMP and ATP, respectively) and reproducibility. Furthermore, the method was validated and applied in vitro to determine cAMP accumulation in biological samples. The effect of several dopamine D(2) (partial) agonists and antagonists on cAMP accumulation was assessed by determination of the cAMP/ATP ratio in cells transfected with the human dopamine D(2L) receptor. Quinpirole, dopamine and ropinirole produced agonist effects on cAMP accumulation, with a potency of quinpirole>ropinirole>dopamine. Lisuride, terguride and bifeprunox were found to be partial agonists with efficacies of lisuride>terguride>bifeprunox. As expected, haloperidol, (-)-sulpiride and LY-741626 were antagonists. These results demonstrate that the present analytical method was robust, fast, sensitive, and selective. Moreover, it showed utility in determining cAMP/ATP in biological systems and the ability to study the effect of (partial) agonists and antagonists which makes it a useful tool for drug discovery.

[Seven means of measuring fear of treatment: reliability and convergent validity]. / Zeven instrumenten voor het meten van behandelangst. Betrouwbaarheid en convergente validiteit.

Fear of dental treatment sometimes already begins during childhood. Different kinds of diagnostic instruments can measure children's dental anxiety. In this study the reliability and convergent validity of 7 instruments are compared. Results show that there is no 'gold standard' with which convergent validity can be established unambiguously. Furthermore, self report measures are investigated more often than observational measures even though the latter are more commonly used. Generally, the compared measures are satisfactory in respect to their reliability. Nevertheless, sufficient interest coherence is sometimes lacking. This could be explained by the multidimensional character of the construct 'fear' and, in some cases, the type of measuring-method. In almost none of the compared studies were norms defined prior to the study by means of which statistical indicators could be unambiguously interpreted. In the present study, such norms were established.

Progress on the development of human in vitro dendritic cell based assays for assessment of the sensitizing potential of a compound.

Allergic contact dermatitis is the result of an adaptive immune response of the skin to direct exposure to an allergen. Since many chemicals are also allergens, European regulations require strict screening of all ingredients in consumer products. Until recently, identifying a potential allergen has completely relied on animal testing (e.g.: Local Lymph Node Assay). In addition to the ethical problems, both the 7th Amendment to the Cosmetics Directive and REACH have stimulated the development of alternative tests for the assessment of potential sensitizers. This review is aimed at summarising the progress on cell based assays, in particular dendritic cell based assays, being developed as animal alternatives. Primary cells (CD34(+) derived dendritic cells, monocyte derived dendritic cells) as well as dendritic cell-like cell lines (THP-1, U-937, MUTZ-3, KG-1, HL-60, and K562) are extensively described along with biomarkers such as cell surface markers, cytokines, chemokines and kinases. From this review, it can be concluded that no single cell based assay nor single marker is yet able to distinguish all sensitizers from non-sensitizers in a test panel of chemicals, nor is it possible to rank the sensitizing potential of the test chemicals. This suggests that sensitivity and specificity may be increased by a tiered assay approach. Only a limited number of genomic and proteomic studies have been completed until now. Such studies have the potential to identify novel biomarkers for inclusion in future assay development. Although progress is promising, this review suggests that it may be difficult to meet the up and coming European regulatory deadlines.

[Familial schwannomatosis, a new entity distinct from neurofibromatosis type 1 and 2]. / Familiaire schwannomatose, een nieuwe entiteit te onderscheiden van neurofibromatose 1 en 2.

A Dutch family was diagnosed with familial schwannomatosis, a disorder that is distinct from neurofibromatosis (NF) type 1 and 2. The proband and 4 relatives had schwannomas on spinal roots, cranial nerves, plexuses, and peripheral nerves; no vestibular schwannomas were found. One of the affected relatives was later diagnosed with intracerebral glioma; schwannomas were not found. None of the living affected relatives had genomic defects affecting the NF2 gene. Large deletions in the proximal region of chromosome 22 were found in all resected schwannomas. Schwannomatosis can occur sporadically or be inherited. Pain is often the clinical manifestation of schwannomas. Resection should be reserved for tumours that are symptomatic or threaten to cause spinal cord compression.

Parenting by persons with intellectual disability: an explorative study in the Netherlands.

BACKGROUND: As a sequel to a report by the Health Council of the Netherlands on contraception in persons with intellectual disabilities (IDs), a fierce debate about parenthood by such persons occurred, in which a lack of knowledge about parenting competences became clear. Therefore, the Ministry of Health commissioned a study investigating examples of 'successful parenthood' by persons with IDs. METHODS: In conformity with the literature and with legal categories, we defined 'successful parenthood' as 'good enough parenthood', meaning no indications for child abuse and/or neglect, no dealings with child protection agencies and no legal custody. We combined a nationwide quantitative questionnaire study with a qualitative interview study. Questionnaires were sent to all institutions involved in caring for persons with ID, interviews were held with 'good enough' parents and their professional caregivers, selected on the basis of returned questionnaires. RESULTS: Parenthood occurs in around 1.5% of persons with ID in the Netherlands and is mostly restricted to those with mild handicaps. In total, 51% of the cases were regarded, by caregivers, as not-good-enough parenthood, 33% were clearly good enough and 16% were doubtful. Predicting factors included the ability and the willingness to follow advice, the quality of the social network and the acceptance of parenting in the community. However, there is not one decisive predicting factor; particularly, the predictive value of the IQ alone is small. CONCLUSIONS: A general policy of discouragement of parenthood, as advocated by the Dutch Ministry, is not supported by our results; moreover, it would probably be impossible and have negative effects on social acceptance of parents with ID. The overall conclusion from the study therefore is that some kind of balancing model, in which positive and negative factors are weighed, may be useful to predict success and need for support.