High-Resolution Gadolinium-Enhanced MR Cisternography Using Compressed-Sensing T1 SPACE Technique for Detection of Intracranial CSF Leaks.

In patients with CSF rhinorrhea, accurate identification of the CSF leakage site is crucial for surgical planning. We describe the application of a novel gadolinium-enhanced high-resolution 3D compressed-sensing T1 SPACE technique for MR cisternography and compare findings with CT cisternography and intraoperative results. In our pilot experience with 7 patients, precise detection of CSF leaks was feasible using compressed-sensing T1 SPACE, which appeared to be superior to CT cisternography.

Clinical Evaluation of Highly Accelerated Compressed Sensing Time-of-Flight MR Angiography for Intracranial Arterial Stenosis.

BACKGROUND AND PURPOSE: Time-of-flight MR angiography is the preferred imaging technique to assess intracranial arterial stenosis but is limited by a relatively long acquisition time. Compressed sensing provides an innovative approach in undersampling k-space to minimize the data-acquisition time. We aimed to evaluate the diagnostic accuracy of compressed sensing TOF for detecting intracranial arterial stenosis by comparison with conventional parallel imaging TOF-MRA. MATERIALS AND METHODS: Compressed sensing TOF and parallel imaging TOF were performed in 22 patients with intracranial arterial stenosis. The MRA scan times were 2 minutes and 31 seconds and 4 minutes and 48 seconds for compressed sensing TOF and parallel imaging TOF, respectively. The reconstructed resolutions were 0.4 × 0.4 × 0.4 and 0.4 × 0.4 × 0.6 mm3 for compressed sensing TOF and parallel imaging TOF, respectively. The diagnostic quality of the images and visibility of the stenoses were independently ranked by 2 neuroradiologists blinded to the type of method and were compared using the Wilcoxon signed rank test. Concordance was calculated with the Cohen κ. Edge sharpness of the arteries and the luminal stenosis ratio were analyzed and compared using a paired-sample t test. RESULTS: The interrater agreement was good to excellent. Compressed sensing TOF resulted in image quality comparable with that of parallel imaging TOF but boosted confidence in diagnosing arterial stenoses (P = .025). The edge sharpness of the intracranial arteries for compressed sensing TOF was significantly higher than that for parallel imaging TOF (P < .001). The luminal stenosis ratio on compressed sensing TOF showed no significant difference compared with that on parallel imaging TOF. CONCLUSIONS: Compressed sensing TOF both remarkably reduced the scan time and provided adequate image quality for the diagnosis of intracranial arterial stenosis.

Use of the embedded peritoneal dialysis catheter.

Introduction The use of embedded peritoneal dialysis (PD) catheters is purported to offer numerous benefits over standard placement. However, the optimum period of embedment and the effect of prolonged embedment on subsequent catheter function remain unclear. Methods This retrospective observational study looked at adult patients undergoing embedded PD catheter insertion in a large tertiary referral centre in the UK. Possible predictors for catheter non-function at externalisation were investigated. These included patient factors (age, sex, diabetic status, body mass index, ethnicity, smoking status, previous surgery, estimated glomerular filtration rate), procedural factors (modality of surgery, concurrent surgical procedure), duration of catheter embedment and catheter damage at externalisation. Outcomes examined were proportion of catheters functioning after externalisation, futile placement rate, surgical reintervention rate, infectious complication rate and proportion of externalised catheters lost owing to malfunction. Results Sixty-six catheters were embedded and two-thirds (n=47, 63.6%) were externalised after a median embedment period of 39.4 weeks. Of these, 25 (53.2%) functioned on externalisation. Fourteen (63.6%) of the 22 non-functioning catheters were salvaged. The overall utilisation of PD was 34/47 (72.3%) and the futile placement rate was 12.1%. Over half of the externalised catheters (n=27, 57.4%) were lost directly as a result of catheter related complications, with a median survival time of 39.4 weeks. In adjusted analysis, increasing embedment duration was significantly predictive of catheter non-function at externalisation (adjusted odds ratio: 0.957, 95% confidence interval [CI]: 0.929-0.985, p=0.003) while subsequent catheter loss was highly dependent on catheter function at externalisation (hazard ratio: 0.258, 95% CI: 0.112-0.594, p=0.001). Conclusions Prolonged embedment of PD catheters is associated with a significantly higher likelihood of catheter dysfunction following externalisation, which is in turn associated with subsequent catheter loss. We have discontinued the use of this technique in our unit.

Openspritzer: an open hardware pressure ejection system for reliably delivering picolitre volumes.

The ability to reliably and precisely deliver picolitre volumes is an important component of biological research. Here we describe a high-performance, low-cost, open hardware pressure ejection system (Openspritzer), which can be constructed from off the shelf components. The device is capable of delivering minute doses of reagents to a wide range of biological and chemical systems. In this work, we characterise the performance of the device and compare it to a popular commercial system using two-photon fluorescence microscopy. We found that Openspritzer provides the same level of control over delivered reagent dose as the commercial system. Next, we demonstrate the utility of Openspritzer in a series of standard neurobiological applications. First, we used Openspritzer to deliver precise amounts of reagents to hippocampal neurons to elicit time- and dose-precise responses on neuronal voltage. Second, we used Openspritzer to deliver infectious viral and bacterial agents to living tissue. This included viral transfection of hippocampal interneurons with channelrhodopsin for the optogenetic manipulation of hippocampal circuitry with light. We anticipate that due to its high performance and low cost Openspritzer will be of interest to a broad range of researchers working in the life and physical sciences.

CoroEval: a multi-platform, multi-modality tool for the evaluation of 3D coronary vessel reconstructions.

We present a software, called CoroEval, for the evaluation of 3D coronary vessel reconstructions from clinical data. It runs on multiple operating systems and is designed to be independent of the imaging modality used. At this point, its purpose is the comparison of reconstruction algorithms or acquisition protocols, not the clinical diagnosis. Implemented metrics are vessel sharpness and diameter. All measurements are taken from the raw intensity data to be independent of display windowing functions. The user can either import a vessel centreline segmentation from other software, or perform a manual segmentation in CoroEval. An automated segmentation correction algorithm is provided to improve non-perfect centrelines. With default settings, measurements are taken at 1 mm intervals along the vessel centreline and from 10 different angles at each measurement point. This allows for outlier detection and noise-robust measurements without the burden and subjectivity a manual measurement process would incur. Graphical measurement results can be directly exported to vector or bitmap graphics for integration into scientific publications. Centreline and lumen segmentations can be exported as point clouds and in various mesh formats. We evaluated the diameter measurement process using three phantom datasets. An average deviation of 0.03 ± 0.03 mm was found. The software is available in binary and source code form at http://www5.cs.fau.de/CoroEval/.

Probing the location of displayed cytochrome b562 on amyloid by scanning tunnelling microscopy.

Amyloid fibres displaying cytochrome b562 were probed using scanning tunnelling microscopy (STM) in vacuo. The cytochromes are electron transfer proteins containing a haem cofactor and could, in principle, mediate electron transfer between the tip and the gold substrate. If the core fibres were insulating and electron transfer within the 3D haem network was detected, then the electron transport properties of the fibre could be controlled by genetic engineering. Three kinds of STM images were obtained. At a low bias (<1.5 V) the fibres appeared as regions of low conductivity with no evidence of cytochrome mediated electron transfer. At a high bias, stable peaks in tunnelling current were observed for all three fibre species containing haem and one species of fibre that did not contain haem. In images of this kind, some of the current peaks were collinear and spaced around 10 nm apart over ranges longer than 100 nm, but background monomers complicate interpretation. Images of the third kind were rare (1 in 150 fibres); in these, fully conducting structures with the approximate dimensions of fibres were observed, suggesting the possibility of an intermittent conduction mechanism, for which a precedent exists in DNA. To test the conductivity, some fibres were immobilized with sputtered gold, and no evidence of conduction between the grains of gold was seen. In control experiments, a variation of monomeric cytochrome b562 was not detected by STM, which was attributed to low adhesion, whereas a monomeric multi-haem protein, GSU1996, was readily imaged. We conclude that the fibre superstructure may be intermittently conducting, that the cytochromes have been seen within the fibres and that they are too far apart for detectable current flow between sites to occur. We predict that GSU1996, being 10 nm long, is more likely to mediate successful electron transfer along the fibre as well as being more readily detectable when displayed from amyloid.

Pediatric paranasal sinus mucoceles: etiologic factors, management and outcome.

OBJECTIVES: To study the local and general etiological factors of paranasal sinus mucoceles in the pediatric population and to evaluate and discuss the clinical management and the results of endonasal marsupialization. DESIGN: Retrospective study. PATIENTS AND METHODS: A series of 10 cases of paranasal sinus mucocele in children were managed. For imaging, CT-scan and, sometimes MRI were performed. An ophthalmologic evaluation was performed preoperatively in all cases, and post-operatively in case of preoperative trouble. All patients were treated with endoscopic surgical procedure. Authors also looked for etiological factors. RESULTS: Cystic fibrosis was found in 6 cases out of 10. Others etiological factors were trauma and inflammatory process; one case was strictly idiopathic. Three patients out of 10 had ophthalmologic trouble related with the mucocele. With a mean follow-up of 17 months, neither recurrence nor complication were noted. All patients with ophthalmologic complain were free of trouble after surgery. CONCLUSION: Paranasal sinus mucoceles in children are still rare. In our experience, 9 out of 10 patients had predisposing factors, especially cystic fibrosis. Imaging with CT-scan and MRI allow the physician to rule out other tumors such as meningoceles or rhabdomyosarcoma. Endoscopic endonasal surgery is nowadays the gold standard for the treatment of paranasal sinus mucoceles.

[A case of nasal septum schwannoma: endoscopic resection]. / Le schwannome du septum nasal. A propos d'un cas.

OBJECTIVES: To define clinical and radiological characteristics of nasal septal schwannoma, and to propose endoscopic surgery. PATIENT AND METHODS: We report a case of an isolated schwannoma of the anterior part of the nasal septum, without involvement of any local structure. The only preoperative symptom was nasal obstruction. Imaging study included a CT scan and an MRI study. RESULTS: Schwannoma is a sheath tumor originating from Schwann cells of peripheral nerves. It rarely occurs in nasal and paranasal sinuses and its development on the nasal septum is extremely rare. Complete removal of the tumor was performed by endoscopic sinus surgery technique. Limits of the excision were free of tumor and the histological type was Antoni type A Schwannoma. After a year of follow up, the patient is free of recurrence. CONCLUSION: The Schwannoma of the nasal septum is a rare tumour whose clinical and radiological diagnosis by CT scan and IRM is relatively easy. Its treatment is surgical and the endoscopic surgery can be proposed in the forms slightly extensive.

Affecting the value chain through supplier kaizen.

In the aerospace industry, typically 60 percent of a product's cost and 70 percent of the lead time are due to purchased material. To affect price and customer responsiveness, improvement initiatives must be extended into the supply chain. Many companies have developed supply base management systems that include long-term agreements with suppliers, partnering with suppliers in risk taking and product design, information sharing, and quality and delivery rating systems. The premise is that suppliers are an extension of the factory. But to take full advantage of customer-supplier relationships, the suppliers must be "developed" in the same manner as a manufacturing unit. Supplier kaizen is a method of bringing suppliers to the same level of operations as the parent company, through training and improvement projects, to ensure superior performance and nurture the trust that is required for strong partnerships. This article describes Sikorsky Aircraft's use of kaizen to improve its supply base management.

Metabolism and testicular toxicity of 1,3-dinitrobenzene in rats of different ages.

Susceptibility to 1,3-dinitrobenzene (1,3-DNB)-induced testicular damage is known to increase with age. The present study investigated the possibility that age-dependent differences in metabolism and disposition could account for differences in toxicity. [14C]1,3-DNB (25 mg/kg, ip) was administered to Sprague-Dawley rats which were 31, 75, or 120 days of age. Levels of 1,3-DNB and 1,3-DNB metabolites were determined in blood and urine. As animal age increased, peak blood concentrations of 1,3-DNB were lower and declined more slowly indicating an age-dependent decrease in rate of metabolism and a possible increase in volume of distribution. In younger animals, faster elimination rates were associated with higher blood levels of metabolites. Urinary metabolites were generally similar for all age groups with the exception of the diacetamidobenzene metabolite which was significantly lower in the urine of 31 days old rats. There were clear differences in the toxicokinetic profile for 1,3-DNB between the 31 day old rats and the other two age groups. However, differences between the 75 and 120 day old animals were less marked. Testicular damage induced by 1,3-DNB (25 mg/kg, ip) was hardly detectable in the youngest animals, while the intermediate age group showed a moderate lesion particularly in later stages of spermatogenesis. For the oldest animals, testicular damage was more severe, particularly in the earlier stages of spermatogenesis. Overall, the rapid elimination rate could account for the lack of 1,3-DNB toxicity in very young animals. However, simple metabolic differences were less likely to adequately explain the increase in testicular damage found as animal age increased from 75 to 120 days.

Mouse antibody to phosphocholine can protect mice from infection with mouse-virulent human isolates of Streptococcus pneumoniae.

Previous studies have demonstrated that mouse antibodies to phosphocholine (PC) can protect mice against fatal infection caused by several, but not all, mouse-virulent laboratory strains of Streptococcus pneumoniae. Because the pneumococcal strains used in previous studies had been mouse passed and were propagated for many years outside of humans, it was not known whether antibody to PC would be able to protect mice against S. pneumoniae freshly isolated from humans. In the present study, we examined the ability of an immunoglobulin G (IgG) monoclonal antibody (MAb) to PC to protect against infections in mice caused by 14 pneumococcal strains of capsular types 3, 4, 6A, and 6B. Nine of these strains were selected as the most virulent strains for mice from a group of 69 fresh clinical isolates. Five were mouse-passed laboratory strains. Mouse IgG3 MAb to PC was able to exhibit protective effects (survival or increased time to death) against infection with virtually all of the strains injected intravenously and against infection with 70% of the strains injected intraperitoneally. The protective effects of antibody to PC appeared to be partially dependent on capsular type. MAb to PC was most effective against capsular type 3 strains and least effective against type 4 strains. With type 3 and type 4 strains, MAb to PC could frequently protect against larger numbers of CFU injected intravenously than intraperitoneally. For capsular type 6A and 6B strains the reverse was true.

Strong association between capsular type and virulence for mice among human isolates of Streptococcus pneumoniae.

The relationship between capsular type and virulence for mice was examined with 69 fresh human isolates of Streptococcus pneumoniae. These isolates represented eight capsular types or groups. Serologic and molecular weight differences in PspA (pneumococcal surface protein A) indicated that the strains were clonally distinct. Mice were infected intravenously with washed bacteria of all 69 isolates in sterile salt solutions. Twenty-eight of the isolates were also injected intraperitoneally to permit comparisons between the intravenous and intraperitoneal routes. With a few exceptions, there was concordance between the ability of strains to cause fatal infections by the two routes. About 30% of the 69 isolates were virulent for mice. The abilities of the isolates to kill mice and the length of time between inoculation and death were strongly associated with capsular type. All type 4 isolates, 40% of type 3 isolates, and 60% of group 6 isolates were virulent for mice; type 1 isolates were marginally virulent; and all type or group 14, 19, and 23 isolates were avirulent. Times to death were generally longer for mice infected with group 6 or type 1 than for those infected with type 3 or 4 pneumococci. There was no relationship between clinical diagnosis or tissue source of the isolates and virulence for mice.

Antipneumococcal effects of C-reactive protein and monoclonal antibodies to pneumococcal cell wall and capsular antigens.

Antibodies to pneumococcal capsular polysaccharides are well known for their ability to protect against pneumococcal infection. Recent studies indicate that antibodies to cell wall antigens, including pneumococcal surface protein A and the phosphocholine (PC) determinant of teichoic acids as well as human C-reactive protein (which also binds to PC), can protect mice against pneumococcal infection. In the present study we compared the protective effects of these agents as measured by mouse protection, the blood bactericidal assay, and clearance of pneumococci from the blood and peritoneal cavity. Our findings extend previous results indicating that human C-reactive protein and antibodies to noncapsular antigens are generally less protective than anticapsular antibodies. The new results obtained indicate the following: (i) mouse protection studies with intraperitoneal and intravenous infections provide very similar results; (ii) monoclonal immunoglobulin G2a (IgG2a) antibodies to PC, like IgG1, IgG2b, and IgG3 antibodies to PC, are highly protective against pneumococcal infection in mice; (iii) human antibody to PC is able to protect against pneumococcal infection in mice; (iv) antibodies to PspA are effective at mediating blood and peritoneal clearance of pneumococci; (v) complement is required for the in vivo protective effects of both IgG and IgM antibodies to PC; (vi) IgG1, IgG2b, and IgG3 anti-PC antibodies all mediate complement-dependent lysis of PC-conjugated erythrocytes; and (vii) antibodies and human C-reactive proteins that are reactive with capsular antigens but not cell wall antigens are able to mediate significant antibacterial activity in the blood bactericidal assay.

Blood clearance by anti-phosphocholine antibodies as a mechanism of protection in experimental pneumococcal bacteremia.

Previous studies have demonstrated that monoclonal IgG and IgM antibodies to phosphocholine (PC), a determinant in the cell wall of Streptococcus pneumoniae, can protect mice from fatal infection with S. pneumoniae. In this study we demonstrate that both passive and naturally occurring anti-PC antibodies promote the clearance of S. pneumoniae from the blood. The bulk of the cleared pneumococci are apparently killed, because they fail to accumulate in reticuloendothelial tissues. These findings suggest that their protective effect is probably dependent on their ability to promote phagocytosis. We have found that on a weight basis IgG antibody is more effective at promoting blood clearance than IgM antibody. This observation fits with our earlier findings that IgG anti-PC antibody is more protective against i.v. infection than IgM anti-PC antibody. We have also demonstrated that anti-PC antibodies are protective against S. pneumoniae infection when given as late as 24 hr postinfection. This finding makes it unlikely that the ability to protect against pneumococcal infection with anti-PC antibody is dependent on an artifact associated with either their in vitro growth or the harvesting procedure.

The effects of idiotype on the ability of IgG1 anti-phosphorylcholine antibodies to protect mice from fatal infection with Streptococcus pneumoniae.

Anti-phosphorylcholine (PC) antibodies of the mouse are found in three different idiotype families: T15, M603 and M511. These subgroups exhibit different specificities for PC analogs and utilize light chains of different VL subgroups. In this study we have found that IgG1 antibodies of the T15 idiotype are much more protective against pneumococcal infection than IgG1 antibodies of the M511 or M603 idiotypes. This finding provides additional evidence that the T15 VH and VL genes may have evolved to protect mice from infection with PC-bearing pathogens.

The effects of subclass on the ability of anti-phosphocholine antibodies to protect mice from fatal infection with Streptococcus pneumoniae.

We have compared the abilities of IgG1, IgG2b, and IgG3 antibodies to protect mice against infection with a bacterial pathogen for which antibody-mediated protection is thought to be a function of killing by phagocytes rather than complement-mediated lysis. For this study, we used anti-phosphocholine (PC) antibodies of the T15 idiotype, since they are known to have very similar binding sites and have the ability to protect mice from Streptococcus pneumoniae infection. Our results indicated that antibodies with the three different IgG constant regions gave similar degrees of protection. This finding was surprising, since earlier data showed a strong restriction of anti-carbohydrate and anti-PC antibodies to the IgG3 subclass. Our data raise the possibility that the restriction of most immune responses to particular IgG subclasses may be more to allow isotype-specific regulation than to utilize special effector functions of different IgG isotypes.

Anti-phosphorylcholine antibodies of the T15 idiotype are optimally protective against Streptococcus pneumoniae.

In the mouse, most anti-PC antibody is found in one of the three murine anti-PC idiotype families: T15, M603, or M511. The antibodies within each of these idiotypic families have characteristic fine specificities for phosphorylcholine (PC)-analogues. In this paper we compare the ability of hybridoma IgM anti-PC antibodies of the three idiotype families to protect mice from fatal infection with S. pneumoniae. Antibody bearing the T15 idiotype was approximately 8 times as effective as antibody with the M603 idiotype and approximately 30 times as protective as antibody with the M511 idiotype. Reports by others have shown that the heavy chains of virtually all mouse anti-PC antibodies are produced by translocation of a single variable region gene and that the direct translation of this gene (in the absence of somatic mutations) results in heavy chains characteristic of the T15 idiotype. Thus, our findings suggest that the T15 germ line heavy chain variable region gene may have been selected through evolution to code for antibody binding PC-containing pathogens such as S. pneumoniae. Our observations may also explain the existence of regulatory mechanisms that result in maintenance of T15 idiotype expression in murine anti-PC immune responses.

Protection of mice from infection with Streptococcus pneumoniae by anti-phosphocholine antibody.

Anti-phosphocholine (PC) antibody mediated protection against many strains of Streptococcus pneumoniae, and hybridoma anti-PC antibodies protected mice from fatal infections with types 1 and 3 S. pneumoniae. Live types 1, 3, 5, 6A, and 19F S. pneumoniae had similar amounts of surface PC accessible to antibody. Furthermore, mice expressing the X-linked immunodeficiency (xid) of the CBA/N strain were found to be more susceptible to infection with S. pneumoniae of types 3, 6A, and 19F than were immunologically normal mice. The only exception to these results was with the type 5 strain, which was highly virulent for both xid and normal mice. In addition, we were unable to protect mice against infection with the type 5 strain by using anti-PC antibody.