LEAD COMPOSITE VS. NONLEAD PROTECTIVE GARMENTS: WHICH ARE BETTER? A MULTIVENDOR COMPARISON.

This study aims to provide more insight in attenuation characteristics and corresponding lead (Pb) equivalences of a broad range of commercially available lead composite and nonlead protective garments. Thirty garments of five manufacturers (listed as 0.25-0.35-0.50 mm Pb equivalent) were tested. Transmission values were determined at 70, 90 and 110 kVp using an inverse broad beam geometry. Pb equivalence was determined using lead sheets as reference material. A substantial variability in photon transmission across garments was found. Differences between lead composite and nonlead garments were not statistically significant. Depending on tube voltage, between 9 and 12 out of 30 garments had a lower Pb equivalence than the indicated value. This work shows that lead equivalence as indicated on a garment's label may overestimate its protective performance. Depending on the application a more thorough verification of the effectiveness of protective garments at the desired kVp is warranted.

MULTICENTRE COMPARISON OF PATIENT AND DETECTOR DOSE FOR X-RAY-GUIDED EMBOLISATIONS OF ARTERIOVENOUS MALFORMATIONS IN THE BRAIN.

Dosimetric benchmarking at four hospitals was performed to investigate incident entrance dose and dose rate on a phantom, and entrance detector dose and dose rate for protocols that are used in routine clinical practice for complex neuroradiological treatment of arteriovenous malformations (AVMs). Measurements were performed with a head phantom that simulates the attenuation and scattering of the human head for the lateral and posteroanterior (PA) views. For fluoroscopy, the measured incident entrance dose rate and entrance detector dose rate were in the range of 44-172 and 0.3-1.3 µGy s(-1), respectively. The pulse rate in fluoroscopy varied between 6.3 and 15 frames per second (fps). For digital subtraction angiography (DSA), incident entrance dose per frame and entrance detector dose per frame were in the range of 744-2800 and 2.6-8.1 µGy/frame, respectively. Optimisation of acquisition parameters such as pulse rate in fluoroscopy, dose per frame in DSA, beam filtration and tube voltage may further improve imaging protocols and lower the patient dose in very complex X-ray-guided embolisations of AVMs in the brain. However, differences in these acquisition parameters observed in this study were relatively small, suggesting that a relatively high degree of optimisation has already been achieved.

MULTICENTRE COMPARISON OF IMAGE QUALITY FOR LOW-CONTRAST OBJECTS AND MICROCATHETER TIPS IN X-RAY-GUIDED TREATMENT OF ARTERIOVENOUS MALFORMATION IN THE BRAIN.

The treatment of brain arteriovenous malformations (AVMs) can be performed as a minimally invasive X-ray-guided procedure using a microcatheter for navigation to reach the target site. The performance of the interventional vascular surgery devices used for AVM was compared in four hospitals. The relation between image quality and the entrance surface air kerma (ESAK) was assessed for the default protocols for digital subtraction angiography (DSA) and fluoroscopy. A custom phantom, built with PMMA and aluminium plates was used to mimic the attenuation properties of the patient head. Image quality was assessed using low-contrast objects and catheters embedded in two phantoms. Differences were found in the ESAK values, especially for the fluoroscopy, whereas for DSA, the ESAK values were similar. The differences in image quality can be related to acquisition parameters, such as kV and filtration, and post-processing. The proposed method can be used to optimise the existing AVM protocols.

COMPARISON OF WIRELESS DETECTORS FOR DIGITAL RADIOGRAPHY SYSTEMS: IMAGE QUALITY AND DOSE.

The purpose of this study was to compare dose and image quality of wireless detectors for digital chest radiography. Entrance dose at both the detector (EDD) and phantom (EPD) and image quality were measured for wireless detectors of seven different vendors. Both the local clinical protocols and a reference protocol were evaluated. In addition, effective dose was calculated. Main differences in clinical protocols involved tube voltage, tube current, the use of a small or large focus and the use of additional filtration. For the clinical protocols, large differences in EDD (1.4-11.8 µGy), EPD (13.9-80.2 µGy) and image quality (IQFinv: 1.4-4.1) were observed. Effective dose was <0.04 mSv for all protocols. Large differences in performance were observed between the seven different systems. Although effective dose is low, further improvement of imaging technology and acquisition protocols is warranted for optimisation of digital chest radiography.

Designing a strategy to implement cost-effective blood transfusion management in elective hip and knee arthroplasties: a study protocol.

BACKGROUND: Total hip and knee arthroplasties are two of the most commonly performed procedures in orthopedic surgery. Different blood-saving measures (BSMs) are used to reduce the often-needed allogenic blood transfusions in these procedures. A recent large randomized controlled trial showed it is not cost effective to use the BSMs of erythropoietin and perioperative autologous blood salvage in elective primary hip and knee arthroplasties. Despite dissemination of these study results, medical professionals keep using these BSMs. To actually change practice, an implementation strategy is needed that is based on a good understanding of target groups and settings and the psychological constructs that predict behavior of medical professionals. However, detailed insight into these issuses is lacking. Therefore, this study aims to explore which groups of professionals should be targeted at which settings, as well as relevant barriers and facilitators that should be taken into account in the strategy to implement evidence-based, cost-effective blood transfusion management and to de-implement BSMs. METHODS: The study consists of three phases. First, a questionnaire survey among all Dutch orthopedic hospital departments and independent treatment centers (n = 99) will be conducted to analyze current blood management practice. Second, semistructured interviews will be held among 10 orthopedic surgeons and 10 anesthesiologists to identify barriers and facilitators that are relevant for the uptake of cost-effective blood transfusion management. Interview questions will be based on the Theoretical Domains Interview framework. The interviews will be followed by a questionnaire survey among 800 medical professionals in orthopedics and anesthesiology (400 professionals per discipline) in which the identified barriers and facilitators will be ranked by frequency and importance. Finally, an implementation strategy will be developed based on the results from the previous phases, using principles of intervention mapping and an expert panel. DISCUSSION: The developed strategy for cost-effective blood transfusion management by de-implementing BSMs is likely to reduce costs for elective hip and knee arthroplasties. In addition, this study will lead to generalized knowledge regarding relevant factors for the de-implementation of non-cost-effective interventions and insight in the differences between implementation and de-implementation strategies.

Chronic deep posterior compartment syndrome of the leg in athletes: postoperative results of fasciotomy.

The present study evaluates the efficacy of two treatment regimens in individuals possibly suffering from chronic exercise induced compartment syndrome (CECS) of the deep posterior compartment of the leg. We hypothesised that the current method of fasciotomy of the deep posterior compartment of the leg is a procedure with a limited success rate. Dynamic intra-compartmental pressure measurements were applied to 46 patients that had symptomatology of a posterior CECS. Only those patients that met predefined pressure criteria, the "high-pressure group" (27 patients), were offered surgical treatment in the form of fasciotomy. The other 19 patients, "low-pressure group", received conservative treatment, consisting of inlays and physiotherapy. In addition, these patients were examined more closely in order to exclude different pathology. Efficacy of both approaches was evaluated by a questionnaire after a mean three-year follow-up. Fifty-two percent of the high-pressure group judged their operation successful, whereas 48 % did not. The majority of the low-pressure group (84 %) was free of symptoms, after conservative treatment as well as following treatment of other pathology. The present study shows that the success rate of patients surgically treated for posterior CECS is relatively low (52 %). The established cut-off points for the compartment pressure to deselect patients for an operation are justified based on the long-term success rate of the low-pressure group.

Solvable model for distribution networks on random graphs.

We propose a simple model that captures the salient properties of distribution networks, and study the possible occurrence of blackouts, i.e., sudden failings of large portions of such networks. The model is defined on a random graph of finite connectivity. The nodes of the graph represent hubs of the network, while the edges of the graph represent the links of the distribution network. Both, the nodes and the edges carry dynamical two state variables representing the functioning or dysfunctional state of the node or link in question. We describe a dynamical process in which the breakdown of a link or node is triggered when the level of maintenance it receives falls below a given threshold. This form of dynamics can lead to situations of catastrophic breakdown, if levels of maintenance are themselves dependent on the functioning of the net, once maintenance levels locally fall below a critical threshold due to fluctuations. We formulate conditions under which such systems can be analyzed in terms of thermodynamic equilibrium techniques, and under these conditions derive a phase diagram characterizing the collective behavior of the system, given its model parameters. The phase diagram is confirmed qualitatively and quantitatively by simulations on explicit realizations of the graph, thus confirming the validity of our approach.

Efficiency of von Willebrand factor-mediated targeting of interleukin-8 into Weibel-Palade bodies.

BACKGROUND: After de novo synthesis in endothelial cells, the chemokine interleukin-8 (IL-8) is targeted to endothelial cell-specific storage vesicles, the Weibel-Palade bodies (WPBs), where it colocalizes with von Willebrand factor (VWF). OBJECTIVE: In this study we investigated a putative regulator function for VWF in the recruitment of IL-8 to WPBs. METHODS: We performed a quantitative analysis of the entry of IL-8 into the storage system of the endothelium using pulse-chase analysis and subcellular fractionation studies. RESULTS: Using pulse-chase analysis of IL-1beta-stimulated human umbilical vein endothelial cells, we found that a small part of de novo synthesized IL-8 was retained in endothelial cells after 4 h. In density gradients of endothelial cell homogenates nearly equimolar amounts of VWF and IL-8 were present in subcellular fractions that contained WPBs. Furthermore, we found that IL-8 binds to immobilized VWF under the slightly acidic conditions thought to prevail in the lumen of the late secretory pathway. CONCLUSIONS: These observations indicate that the sorting efficiency of IL-8 into the regulated secretory pathway of the endothelium is tightly controlled by the entry of VWF into WPBs.

ADAMTS-13, von Willebrand factor and related parameters in severe sepsis and septic shock.

BACKGROUND: Insufficient control of von Willebrand factor (VWF) multimer size as a result of severely deficient ADAMTS-13 activity results in thrombotic thrombocytopenic purpura associated with microvascluar thrombosis and platelet consumption, features not seldom seen in severe sepsis and septic shock. METHODS: ADAMTS-13 activity and VWF parameters of 40 patients with severe sepsis or septic shock were compared with those of 40 healthy controls of the same age and gender and correlated with clinical findings and sepsis outcome. RESULTS: ADAMTS-13 activity was significantly lower in patients than in healthy controls [median 60% (range 27-160%) vs. 110% (range 63-200%); P < 0.001]. VWF parameters behaved reciprocally and both VWF ristocetin cofactor activity (RCo) and VWF antigen (VWF:Ag) were significantly (P < 0.001) higher in patients compared with controls. Neither ADAMTS-13 activity nor VWF parameters correlated with disease severity, organ dysfunction or outcome. However, a contribution of acute endothelial dysfunction to renal impairment in sepsis is suggested by the significantly higher VWF propeptide and soluble thrombomodulin levels in patients with increased creatinine values as well as by their strong positive correlations (creatinine and VWF propeptide r(s) = 0.484, P < 0.001; creatinine and soluble thrombomodulin r(s) = 0.596, P < 0.001). CONCLUSIONS: VWF parameters are reciprocally correlated with ADAMTS-13 activity in severe sepsis and septic shock but have no prognostic value regarding outcome.

[Double-sided juvenile osteochondritis dissecans of the lateral femoral condyle in a 15-year-old boy]. / Dubbelzijdige juveniele osteochondritis dissecans van de laterale femurcondyl bij een 15-jarige jongen.

A 15-year-old boy of Turkish origin presented with a painful swollen left knee. An X-ray revealed osteochondritis dissecans of the lateral femoral condyle. Arthrotomy was performed and the fragment was fixated with tissue glue and 2 absorbable pins. Eight months later, a large recurrent osteochondral fragment of the lateral femoral condyle was seen on X-ray. The patient was re-operated, during which operation the fragment was found and fixated with three compression screws. One year after the first operation the patient developed similar complaints in the contralateral knee; this knee also contained osteochondral fragments necessitating surgery. Osteochondritis dissecans of the knee is a multifactorial disease in which part of the cartilage of the femoral condyle becomes unattached from the subchondral stratum, usually on the lateral side of the medial femoral condyle. Initially, an inflammatory reaction was thought to be the cause of osteochondritis dissecans. Because of the lack of white blood cells, a previous trauma is a better explanation for the ultimate loosening of the cartilage. The treatments that are described for osteochondritis dissecans are conservative treatment, operative fixation, with or without subsequent chondrocyte transplantation or osteochondral autograft transplantation, and finally microfracturing.

Soil organic matter from pioneer species and its implications to phytostabilization of mined sites in the Sierra de Cartagena (Spain).

Pioneer plant species were observed growing on mined areas despite unfavourable conditions such as extreme pH, high salinity and phytotoxic levels of several elements. This study evaluated the contribution of pioneer species to the accumulation of soil organic matter (SOM). We collected 51 samples from 17 non-vegetated, natural and pioneer-vegetated sites in five highly saline mined areas in the Sierra de Cartagena (Spain). The composition of SOM was determined using total C, N and S elemental anlayzer, pyrolysis and solid state (13)C NMR spectroscopy. Results showed that pioneer species like Lygeum spartum had contributed approximately 11 kg SOM kg(-1) soil into the Balsa Rosa sites since 1991; it will take approximately 120 years of continuous growth for this plant to increase the SOM level comparable to natural site. In the Portman Bay area, Sarconia ramosissima and Phragmites australis can contribute SOM equivalent to present day SOM in natural sites in the next 30 years. Low quality SOM (C/N>20) deposited by pioneer plants was dominated by lignin-derived organic compounds such as phenols, guaiacols, syringols and aromatics while polyssacharides and alkyls were the major components in high quality SOM (C/N<20). The addition of SOM to mine wastes is similar to early stages of soil formation and with time, we expect the formation of well-developed Ah horizon on the surface of mine wastes. The presence of P. australis on several sites makes it a very good candidate for successful revegetation of hostile conditions found in many mined sites.

von Willebrand factor and its propeptide: the influence of secretion and clearance on protein levels and the risk of venous thrombosis.

BACKGROUND AND OBJECTIVES: Elevated levels of factor (F)VIII are associated with an increased risk of thrombosis. FVIII levels are determined mainly by von Willebrand factor (VWF). We have investigated the contribution of secretion and clearance rates to the elevated VWF antigen (VWF:Ag) and to the risk of thrombosis. VWF is secreted in equimolar amounts with its propeptide, which has a shorter half-life. VWF propeptide can be used as a measure of VWF secretion and allows estimation of the VWF half-life. METHODS AND RESULTS: We have measured VWF propeptide, VWF:Ag, FVIII:Ag and FVIII activity (FVIII:C) in the Leiden Thrombophilia Study. In controls, high VWF propeptide was associated with high VWF:Ag, FVIII:Ag and FVIII:C. In contrast to mature VWF:Ag, VWF propeptide was not influenced by blood groups. Using an ELISA-based assay we have shown that VWF propeptide lacks ABO antigens. Levels were higher in men and increased with age. A long VWF half-life was also associated with high VWF:Ag, FVIII:Ag and FVIII:C. The VWF half-life was influenced by blood group (10 h in O vs. 12 h in non-O individuals), but not by sex, and only slightly by age. VWF propeptide was higher in thrombosis patients than in controls. The VWF half-life was similar in patients and controls (11.4 and 11.1 h, respectively). CONCLUSIONS: Both secretion and clearance rates are important determinants of VWF and FVIII levels. However, mainly high VWF and FVIII levels caused by increased secretion seem to be associated with thrombosis. ABO blood group influences the clearance rates of VWF rather than VWF secretion rates.

Multiple B-cell clones producing antibodies directed to the spacer and disintegrin/thrombospondin type-1 repeat 1 (TSP1) of ADAMTS13 in a patient with acquired thrombotic thrombocytopenic purpura.

BACKGROUND: The cysteine-rich/spacer domains of ADAMTS13 contain a major binding site for antibodies in patients with acquired thrombotic thrombocytopenic purpura (TTP). OBJECTIVE: To study the heterogeneity of the antibody response towards these domains an immunoglobulin V-gene phage-display library was constructed to isolate monoclonal anti-ADAMTS13 antibodies from the immunoglobulin repertoire of a patient with acquired TTP. METHODS: Combined variable heavy chain (VH) and variable light chain (VL) segments, expressed as single-chain Fv fragments (scFv), were selected for binding to an ADAMTS13 fragment consisting of the disintegrin/thrombospondin type-1 repeat 1 (TSP1)/cysteine-rich/spacer domains. RESULTS: Seven different scFv antibody clones were identified that were assigned to four groups based on their homology to VH germline gene segments. Epitope-mapping revealed that scFv I-9 (VH1-69), I-26 (VH1-02), and I-41 (VH3-09) bind to an overlapping binding site in the ADAMTS13 spacer domain, whereas scFv I-16 (VH3-07) binds to the disintegrin/TSP1 domains. The affinity of scFv for the disintegrin/TSP1/cysteine-rich/spacer domain was determined by surface plasmon resonance analysis and the dissociation constants ranged from 3 to 254 nM. The scFv partially inhibited ADAMTS13 activity. However, full-length IgG prepared from the variable domains of scFv I-9 inhibited ADAMTS13 activity more profoundly. Plasma of six patients with acquired TTP competed for binding of scFv I-9 to ADAMTS13. CONCLUSION: Our data indicate that multiple B-cell clones producing antibodies directed against the spacer domain are present in the patient analyzed in this study. Our findings also suggest that antibodies with a similar epitope specificity as scFv I-9 are present in plasma of other patients with acquired TTP.

Early circulating levels of endothelial cell activation markers in aneurysmal subarachnoid haemorrhage: associations with cerebral ischaemic events and outcome.

OBJECTIVE: To investigate the relation of endothelial cell activation with delayed cerebral ischaemia (DCI) and outcome after subarachnoid haemorrhage (SAH). METHODS: Concentrations of soluble (s) intercellular adhesion molecule-1, sE-selectin, sP-selectin, ED1-fibronectin, von Willebrand Factor (vWf), and vWf propeptide were measured within three days of SAH onset. The associations with poor outcome were investigated at three months in 106 patients. In 90 patients in whom the occurrence of cerebral ischaemia could be dated accurately, two analyses were undertaken: one for all ischaemic events (n = 32), including those related to treatment, and another for spontaneous DCI (n = 11). Concentrations of markers were dichotomised at their medians. The associations of endothelial cell activation markers with outcome were expressed as odds ratios (OR) from logistic regression and those with ischaemic events as hazard ratios (HR) derived from Cox regression. RESULTS: Early vWf concentrations were associated with poor outcome (crude OR = 4.6 (95% CI, 2.0 to 10.9; adjusted OR = 3.3 (1.1 to 9.8). Early levels of vWf were also positively related to occurrence of all ischaemic events (crude HR = 2.3 (1.1 to 4.9); adjusted HR = 1.8 (0.8 to 3.9) and with occurrence of spontaneous DCI (crude HR = 3.5 (0.9 to 13.1); adjusted HR = 2.2 (0.5 to 9.8). None of the other markers showed any associations. CONCLUSIONS: Concentrations of sICAM-1, sP-selectin, sE-selectin, and ED1-fibronectin do not predict the occurrence of DCI or outcome. The positive associations of raised early vWf concentrations with ischaemic events and poor outcome after SAH may reflect a predisposition to further ischaemic injury through formation of microthrombi in the cerebral circulation.

Coloring random graphs and maximizing local diversity.

We study a variation of the graph coloring problem on random graphs of finite average connectivity. Given the number of colors, we aim to maximize the number of different colors at neighboring vertices (i.e., one edge distance) of any vertex. Two efficient algorithms, belief propagation and Walksat, are adapted to carry out this task. We present experimental results based on two types of random graphs for different system sizes and identify the critical value of the connectivity for the algorithms to find a perfect solution. The problem and the suggested algorithms have practical relevance since various applications, such as distributed storage, can be mapped onto this problem.

Proteolytic cleavage of protein S during the hemostatic response.

BACKGROUND: Protein S is a vitamin K-dependent protein with anticoagulant properties. It contains a so-called thrombin-sensitive region (TSR), which is susceptible to cleavage by coagulation factor Xa (FXa) and thrombin. Upon cleavage, the anticoagulant activity of protein S is abolished. OBJECTIVE: The aim of the present study was to determine whether protein S is cleaved within the TSR during activation of the coagulation system under near physiological conditions. RESULTS: In a reconstituted coagulation system containing apart from protein S only procoagulant constituents and synthetic phospholipid vesicles, protein S was cleaved at Arg60 by the FXa generated (3 mol min(-1) mol(-1) enzyme). FXa-catalyzed cleavage of protein S, however, was inhibited by factor Va and prothrombin by more than 70%. During clotting of recalcified citrated plasma in the presence of a synthetic lipid membrane, no FXa-catalyzed proteolysis of protein S was observed. Substituting platelets for phospholipid vesicles resulted both in the reconstituted system and in plasma in cleavage of the TSR. Cleavage was at Arg60 and was observed upon platelet activation, irrespective of the presence of FXa (13 pmol min(-1) 10(-8) platelets). No cleavage by thrombin was observed in either the reconstituted coagulation system or clotting plasma. CONCLUSION: These findings suggest that in vivo the anticoagulant activity of protein S is not down-regulated by FXa or thrombin during activation of coagulation. Our results rather suggest a role for a platelet protease in down-regulating the anticoagulant activity of protein S during the hemostatic response.

Cysteine-mutations in von Willebrand factor associated with increased clearance.

BACKGROUND: von Willebrand disease (VWD) is a bleeding disorder caused by the decrease of functional von Willebrand factor (VWF). Low levels of VWF can result from decreased synthesis, impaired secretion, increased clearance or combinations thereof. Several mutations lead to impaired synthesis or secretion of VWF, however, little is known about the survival of VWF in the circulation. OBJECTIVES: To evaluate the effect of several VWF mutations on VWF clearance. PATIENTS/METHODS: The effect of three cysteine-mutations (C1130F, C1149R or C2671Y) on the in vivo survival of VWF was studied in patients carrying these mutations and in a VWF-deficient mice model. RESULTS: In patients carrying these mutations, we observed increased propeptide/mature VWF ratios and rapid disappearance of VWF from the circulation after desmopressin treatment. Detailed analysis of in vivo clearance of recombinant VWF in a VWF-deficient mice model revealed a fourfold increased clearance rate of the mutants. The mutations C1130F, C1149R and C2671Y are each associated with reduced survival of VWF in the circulation. Detailed analysis of the recombinant mutant VWF demonstrated that increased clearance was not due to increased proteolysis by ADAMTS-13. We did not identify functional or structural characteristics that the mutant proteins have in common and could be associated with the phenomenon of increased clearance. CONCLUSIONS: Cysteine-mutations in VWF may result in reduced in vivo survival. The observation that various mutations are associated with increased in vivo clearance may have major implications for the therapeutic strategies that rely on the rise of endogenous VWF after desmopressin administration.