Assessment of isocenter alignment during CT colonography: Implications for clinical practice.

INTRODUCTION: Optimization of image quality and patient radiation dose is achieved in part by positioning the patient at the isocenter of the CT gantry. The aim of this study was to establish whether there was increased isocenter misalignment (IM) in CT colonography (CTC) scans by comparing patient position during the prone part of a CTC to patient position during renal stone protocol CT (CT-KUB) and patient position during the supine part of a CTC to patient position during abdominopelvic CT (CT-AP). METHODS: Two hundred and twenty two consecutive outpatient adult CTC studies performed between January and December 2016 were retrospectively analyzed. Automated dose-tracking software was used to quantify IM in the x and y planes. Renal stone CT-KUB (n = 100) and standard CT-AP (n = 100) were used as comparison studies. RESULTS: IM during CTC was significantly greater in the y-axis compared with the x-axis for both prone (p = 0.002) and supine (p < 0.001) scanning. IM was significantly greater during prone CTC compared with CT-KUB (p = 0.008) and during supine CTC compared with CT-AP (p = 0.0001). IM was shown to be slightly greater in studies performed by more experienced radiographers (p = 0.04). IM was not associated with patient age, gender or size (p > 0.05 for all). CONCLUSION: Isocenter misalignment is greater during CT colonography compared with CT-KUB or CT-AP. Strategies for improving patient positioning could include radiographer education and automated patient centering solutions.

Radiation exposure from diagnostic imaging in young patients with testicular cancer.

OBJECTIVES: Risks associated with high cumulative effective dose (CED) from radiation are greater when imaging is performed on younger patients. Testicular cancer affects young patients and has a good prognosis. Regular imaging is standard for follow-up. This study quantifies CED from diagnostic imaging in these patients. METHODS: Radiological imaging of patients aged 18-39 years, diagnosed with testicular cancer between 2001 and 2011 in two tertiary care centres was examined. Age at diagnosis, cancer type, dose-length product (DLP), imaging type, and frequency were recorded. CED was calculated from DLP using conversion factors. Statistical analysis was performed with SPSS. RESULTS: In total, 120 patients with a mean age of 30.7 ± 5.2 years at diagnosis had 1,410 radiological investigations. Median (IQR) surveillance was 4.37 years (2.0-5.5). Median (IQR) CED was 125.1 mSv (81.3-177.5). Computed tomography accounted for 65.3 % of imaging studies and 98.3 % of CED. We found that 77.5 % (93/120) of patients received high CED (>75 mSv). Surveillance time was associated with high CED (OR 2.1, CI 1.5-2.8). CONCLUSIONS: Survivors of testicular cancer frequently receive high CED from diagnostic imaging, mainly CT. Dose management software for accurate real-time monitoring of CED and low-dose CT protocols with maintained image quality should be used by specialist centres for surveillance imaging. KEY POINTS: • CT accounted for 98.3 % of CED in patients with testicular cancer. • Median CED in patients with testicular cancer was 125.1 mSv • High CED (>75 mSv) was observed in 77.5 % (93/120) of patients. • Dose tracking and development of low-dose CT protocols are recommended.

Non-contrast CT at comparable dose to an abdominal radiograph in patients with acute renal colic; impact of iterative reconstruction on image quality and diagnostic performance.

OBJECTIVES: The aim was to assess the performance of low-dose non-contrast CT of the urinary tract (LD-CT) acquired at radiation exposures close to that of abdominal radiography using adaptive statistical iterative reconstruction (ASiR). METHODS: Thirty-three patients with clinically suspected renal colic were prospectively included. Conventional dose (CD-CT) and LD-CT data sets were contemporaneously acquired. LD-CT images were reconstructed with 40 %, 70 % and 90 % ASiR. Image quality was subjectively and objectively measured. Images were also clinically interpreted. RESULTS: Mean ED was 0.48 ± 0.07 mSv for LD-CT compared with 4.43 ± 3.14 mSv for CD-CT. Increasing the percentage ASiR resulted in a step-wise reduction in mean objective noise (p < 0.001 for all comparisons). Seventy % ASiR LD-CT images had higher diagnostic acceptability and spatial resolution than 90 % ASiR LD-CT images (p < 0.001). Twenty-seven calculi (diameter = 5.5 ± 1.7 mm), including all ureteric stones, were correctly identified using 70 % ASiR LD-CT with two false positives and 16 false negatives (diameter = 2.3 ± 0.7 mm) equating to a sensitivity and specificity of 72 % and 94 %. Seventy % ASiR LD-CT had a sensitivity and specificity of 87 % and 100 % for detection of calculi >3 mm. CONCLUSION: Reconstruction of LD-CT images with 70 % ASiR resulted in superior image quality than FBP, 40 % ASIR and 90 % ASIR. LD-CT with ASIR demonstrates high sensitivity and specificity for detection of calculi >3 mm. TEACHING POINTS: • Low-dose CT studies for urinary calculus detection were performed with a mean dose of 0.48 ± 0.07 mSv • Low-dose CT with 70 % ASiR detected calculi >3 mm with a sensitivity and specificity of 87 % and 100 % • Reconstruction with 70 % ASiR was superior to filtered back projection, 40 % ASiR and 90 % ASiR images.

Impaired long-term potentiation in the prefrontal cortex of Huntington's disease mouse models: rescue by D1 dopamine receptor activation.

BACKGROUND: The introduction of gene testing for Huntington's disease (HD) has enabled the neuropsychiatric and cognitive profiling of human gene carriers prior to the onset of overt motor and cognitive symptoms. Such studies reveal an early decline in working memory and executive function, altered EEG and a loss of striatal dopamine receptors. Working memory is processed in the prefrontal cortex and modulated by extrinsic dopaminergic inputs. OBJECTIVE: We sought to study excitatory synaptic function and plasticity in the medial prefrontal cortex of mouse models of HD. METHODS: We have used 2 mouse models of HD, carrying 89 and 116 CAG repeats (corresponding to a preclinical and symptomatic state, respectively) and performed electrophysiological field recording in coronal slices of the medial prefrontal cortex. RESULTS: We report that short-term synaptic plasticity and long-term potentiation (LTP) are impaired and that the severity of impairment is correlated with the size of the CAG repeat. Remarkably, the deficits in LTP and short-term plasticity are reversed in the presence of a D(1) dopamine receptor agonist (SKF38393). CONCLUSION: In a previous study, we demonstrated that a deficit in long-term depression (LTD) in the perirhinal cortex could also be reversed by a dopamine agonist. These and our current data indicate that inadequate dopaminergic modulation of cortical synaptic function is an early event in HD and may provide a route for the alleviation of cognitive dysfunction.

CT fluoroscopically guided percutaneous placement of transiliosacral rod for sacral insufficiency fracture: case report and technique.

Treatment of sacral insufficiency fractures (SIFs) has traditionally been conservative, but several patients have been treated with percutaneous sacroplasty. Unfortunately, in the setting of severe, bilateral SIFs, cement may not withstand shear forces present at the lumbosacral junction, and surgical hardware may not provide adequate fixation in osteoporotic, cancellous bone of the sacrum, leading to eventual pseudarthrosis. Thus, we propose a novel technique in which guidance with CT fluoroscopy allows placement of a transiliosacral bar in conjunction with sacroplasty.

Autonomous activity of CaMKII is only transiently increased following the induction of long-term potentiation in the rat hippocampus.

A major role has been postulated for a maintained increase in the autonomous activity of CaMKII in the expression of long-term potentiation (LTP). However, attempts to inhibit the expression of LTP with CaMKII inhibitors have yielded inconsistent results. Here we compare the changes in CaMKII autonomous activity and phosphorylation at Thr286 of alphaCaMKII in rat hippocampal slices using chemical or tetanic stimulation to produce either LTP or short-term potentiation (STP). Tetanus-induced LTP in area CA1 requires CaMKII activation and Thr286 phosphorylation of alphaCaMKII, but we did not observe an increase in autonomous activity. Next we induced LTP by 10 min exposure to 25 mM tetraethyl-ammonium (TEA) or 5 min exposure to 41 mM potassium (K) after pretreatment with calyculin A. Exposure to K alone produced STP. These protocols allowed us to monitor temporal changes in autonomous activity during and after exposure to the potentiating chemical stimulus. In chemically induced LTP, autonomous activity was maximally increased within 30 s whereas this increase was significantly delayed in STP. However, in both LTP and STP the two-fold increase in autonomous activity measured immediately after stimulation was short-lived, returning to baseline within 2-5 min after re-exposure to normal ACSF. In LTP, but not in STP, the phosphorylation of alphaCaMKII at Thr286 persisted for at least 60 min after stimulation. These results confirm that LTP is associated with a maintained increase in autophosphorylation at Thr286 but indicate that a persistent increase in the autonomous activity of CaMKII is not required for the expression of LTP.

Long term visual and neurological prognosis in patients with treated and untreated cavernous sinus aneurysms.

OBJECTIVE: To determine the long term visual and neurological outcome of patients diagnosed with cavernous sinus aneurysms (CCAs). METHODS: Prospective follow up for at least five years or until death of 31 retrospectively recruited patients (27 women, 4 men) with treated and untreated CCAs. RESULTS: There were 40 aneurysms in all. Mean age at diagnosis was 60.4 years (range 25 to 86; median 64). The most common symptoms were diplopia (61%), headache (53%), and facial or orbital pain (32%). Fifteen patients (48%) were diagnosed after they developed cranial nerve pareses, four (13%) after they developed carotid-cavernous sinus fistulas (CCFs), and 12 (39%) by neuroimaging studies done for unrelated symptoms. Twenty one patients (68%) had treatment to exclude the aneurysm from circulation, 10 shortly after diagnosis and 11 after worsening symptoms. Immediate complications of treatment occurred in six patients and included neurological impairment, acute ophthalmoparesis, and visual loss. Ten patients (32%) were observed without intervention. Over a mean (SD) follow up period of 11.8 (7.7) years, eight had improvement in symptoms, five remained stable, and eight deteriorated. Among the 10 patients followed without intervention, none improved spontaneously, three remained stable, and seven worsened. CONCLUSIONS: Most treated patients in this series improved or remained stable after treatment, but none improved without treatment. The long term prognosis for treated cases is relatively good, with most complications occurring immediately after the procedure. Endovascular surgery has decreased the morbidity and mortality of treatment so should be considered for any patient with a CCA.

Tibioperoneal angioplasty and bypass.

Revascularisation by angioplasty or bypass of narrowing and occlusion of the tibio-peroneal segment is done infrequently compared with the more proximal arteries, particularly the superficial femoral artery. The indication for intervention is critical limb ischaemia and the pattern of disease when it predominantly affects the calf arteries is most commonly seen in diabetics. Surgical bypass is the orthodox technique, with well-documented long-term results. Balloon dilation has recently been tried, particularly using the sub-intimal technique. The advantage of minimal invasiveness has to be set against the inapplicability of the method if severe calcification is present, as is often the case in diabetics, the high restenosis rate, and the absence of controlled trials showing good evidence of long-term patency.

Array-based ELISAs for high-throughput analysis of human cytokines.

In this report, we describe the development of a mini-array system suitable for high-throughput quantification of proteins. This mini-array is a multiplexed, sandwich-type ELISA that measures the concentration of seven different human cytokines--TNF-alpha, IFN alpha, IFN gamma, IL-1 alpha, IL-1 beta, IL-6, and IL-10--from a single sample in each well of a 96-well plate. The mini-array is produced by spotting monoclonal antibodies (mAbs) in a 3 x 3 pattern in the bottom of the wells of 96-well polystyrene plates. Cytokines that are captured by the arrayed mAbs are detected by using biotinylated mAbs, followed by the addition of a streptavidin-horseradish peroxidase (HRP) conjugate and a chemiluminescent substrate. The light produced from the HRP-catalyzed oxidation of the substrate is measured at each spot in the array by imaging the entire plate with a commercially available CCD camera. Here, we demonstrate that these 96-well-plate format mini-arrays have performance characteristics that make them suitable for the high-throughput screening of anti-inflammatory compounds.

Arthroscopic release for lateral epicondylitis.

PURPOSE: This study was performed to review the results of our early experience with recalcitrant lateral epicondylitis treated arthroscopically. TYPE OF STUDY: This study is a case series consisting of consecutive patients with lateral epicondylitis treated arthroscopically by 1 surgeon. METHODS: Patients failing a minimum of 6 months of conservative treatment underwent arthroscopic release of the extensor carpi radialis brevis (ECRB) origin using the proximal medial and proximal lateral portals. Associated intra-articular pathology was noted and addressed. The ECRB lesions were classified according to their gross morphology and resected with a shaver. The lateral epicondyle was then decorticated with a burr. RESULTS: Sixteen patients with recalcitrant lateral epicondylitis were treated with arthroscopic release of the ECRB origin on the lateral epicondyle. Of the 16 elbows undergoing surgery, 5 (31.3%) were noted to have a type I lesion, characterized as fraying of the undersurface of the ECRB. Five (31.3%) had a type II lesion noted by linear tears within the ECRB, and 6 (37.5%) had a type III lesion, consisting of a partial or complete avulsion of the ECRB origin. Concurrent intra-articular pathology (synovitis, osteophytes) was noted in 3 of 16 elbows (18.8%) and was addressed arthroscopically. All patients were followed-up for a minimum of 1 year; however, 4 patients were lost to follow-up for this retrospective review due to military reassignment. Follow-up was obtained on 12 of 16 (75%) of patients at an average length of 24.1 months (range, 15 to 33 months). All patients reported improvement with the procedure. The average return to unrestricted work was 6.0 days (range, 0 to 28 days). CONCLUSIONS: Arthroscopic release effectively treats lateral epicondylitis while also affording visualization of the joint space to address associated intra-articular pathology. Additionally, arthroscopic release is minimally invasive and allows early rehabilitation and return to normal activities.

Van't Hoff and calorimetric enthalpies from isothermal titration calorimetry: are there significant discrepancies?

The enthalpy of a reaction is most often determined through one of two means; it can be determined directly using calorimetry or indirectly by measuring the temperature dependence of the equilibrium constant (i.e., the van't Hoff method). Recently, discrepancies have been noted between the enthalpy measured by calorimetry, and the enthalpy determined by the van't Hoff method,. This has been suggested to indicate that the binding reaction is more complex than the simple one-to-one binding model used to describe the data. To better understand possible discrepancies between and, we have undertaken both experimental studies using isothermal titration calorimetry to measure the binding energetics of Ba(2+) binding 18-crown-6 ether and 2'-CMP binding RNase A, along with a simulation of a system involving a molecule in conformational equilibrium coupled with binding. We find that when experimental setup and analysis are correctly performed, no statistically significant discrepancies between and exist even for the linked system.

Identification of a dominant negative homeodomain mutation in Rieger syndrome.

Mutations in the PITX2 bicoid-like homeobox gene cause Rieger syndrome. Rieger syndrome is an autosomal-dominant human disorder characterized by glaucoma as well as dental hypoplasia, mild craniofacial dysmorphism, and umbilical stump abnormalities. PITX2 has also been implicated in the development of multiple organs and left-right asymmetry in the body plan. The PITX2 homeodomain has a lysine at position 50, which has been shown to impart the bicoid-type (TAATCC) DNA binding specificity to other homeodomain proteins. A mutation (K88E), found in a Rieger syndrome patient, changes this lysine to glutamic acid. We were intrigued by the relatively pronounced phenotypic consequences of this K88E mutation. In the initial analyses, the mutant protein appeared to simply be inactive, with essentially no DNA binding and transactivation activities and, unlike the wild type protein, with an inability to synergize with another transcription factor, Pit-1. However, when the K88E DNA was cotransfected with wild type PITX2, analogous to the patient genotype, the K88E mutant suppressed the synergism of wild type PITX2 with Pit-1. In contrast, a different PITX2 homeodomain mutant, T68P, which is also defective in DNA binding, transactivation, and Pit-1 synergism activities, did not suppress the wild type synergism with Pit-1. These results describe the first dominant negative missense mutation in a homeodomain and support a model that may partially explain the phenotypic variation within Rieger syndrome.

Thermodynamics of the helix-coil transition: Binding of S15 and a hybrid sequence, disulfide stabilized peptide to the S-protein.

Pancreatic ribonuclease A may be cleaved to produce two fragments: the S-peptide (residues 1-20) and the S-protein (residues 21-124). The S-peptide, or a truncated version designated as the S15 peptide (residues 1-15), combines with the S-protein to produce catalytically active complexes. The conformation of these peptides and many of their analogues is predominantly random coil at room temperature; however, they populate a significant fraction of helical form at low temperature under certain solution conditions. Moreover, they adopt a helical conformation when bound to the S-protein. A hybrid sequence, disulfide-stabilized peptide (ApaS-25), designed to stabilize the helical structure of the S-peptide in solution, also combines with the S-protein to yield a catalytically active complex. We have performed high-precision titration microcalorimetric measurements to determine the free energy, enthalpy, entropy, and heat capacity changes for the binding of ApaS-25 to S-protein within the temperature range 5-25 degrees C. The thermodynamic parameters for both the complex formation reactions and the helix-to-coil transition also were calculated, using a structure-based approach, by calculating changes in accessible surface area and using published empirical parameters. A simple thermodynamic model is presented in an attempt to account for the differences between the binding of ApaS-25 and the S-peptide. From this model, the thermodynamic parameters of the helix-to-coil transition of S15 can be calculated.

Contrast-enhanced MR angiography: the effects of k-space truncation on luminal representation in a carotid artery phantom model.

Using carotid bifurcation phantom models with different degrees of stenoses, we evaluated the accuracy of vessel lumen representation on MR images obtained from the inverse Fourier transform of different k-space percentages. Our results show that the lower thresholds of truncated k-space sampling are dictated by the severity of luminal narrowing. The defined thresholds may help improve efficiency of 3D MR imaging of the carotid arteries while maintaining adequate luminal representation.

Abnormal synaptic plasticity and impaired spatial cognition in mice transgenic for exon 1 of the human Huntington's disease mutation.

Huntington's disease (HD) is an autosomal dominant progressive and fatal neurodegenerative brain disorder caused by an expanded CAG/polyglutamine repeat in the coding region of the gene. Presymptomatic Huntington's disease patients often exhibit cognitive deficits before the onset of classical symptoms. To investigate the possibility that changes in synaptic plasticity might underlie cognitive impairment in HD, we examined hippocampal synaptic plasticity and spatial cognition in a transgenic mouse (R6/2 line) expressing exon 1 of the human Huntington's disease gene containing an expanded CAG repeat. This mouse exhibits a progressive and fatal neurological phenotype that resembles Huntington's disease. We report that R6/2 mice show marked alterations in synaptic plasticity at both CA1 and dentate granule cell synapses, and impaired spatial cognitive performance in the Morris water maze. The changes in hippocampal plasticity were age dependent, appearing at CA1 synapses several weeks before they were observed in the dentate gyrus. Deficits in synaptic plasticity at CA1 synapses occurred before an overt phenotype. This suggests that altered synaptic plasticity contributes to the pre-symptomatic changes in cognition reported in human carriers of the Huntington' disease gene. The temporal and regional changes in synaptic plasticity within the hippocampus mirror the appearance of neuronal intranuclear inclusions, suggesting a relationship between polyglutamine aggregation and dysfunction.

Xplore mRNA assays for the quantification of IL-1 beta and TNF-alpha mRNA in lipopolysaccharide-induced mouse macrophages.

Because the accurate measurement of a number of cytokine mRNA transcripts provides valuable knowledge about cytokine gene regulation, we have developed the Xplore assay for the quantification of cytokine mRNA. This microplate-based assay is rapid (under four hours), quantitative over three orders of magnitude and carries no risk of false-positive values from contamination with amplified target. Here, we describe the use of Xplore assays to measure the steady-state mRNA levels of TNF-alpha and IL-1 beta produced by mouse WEHI and J774 macrophage-like cell lines.

Employment and social issues in adults with cerebral palsy.

OBJECTIVE: To assess the social and employment status of adults with cerebral palsy. DESIGN: Detailed medical history, physical examination, and functional rating in the PULTIBEC system were performed on all study participants; they also responded to a standardized social adaptation questionnaire. SETTING: Outpatient clinic. SUBJECTS: Volunteer participants (n = 101), all with cerebral palsy, between the ages of 27 and 74 years, living independently in the community. RESULTS: More than 80% wished that their physician knew more about cerebral palsy. The majority (84%) felt their parents overprotected them in childhood. More than 90% desired more sexual education. More than half (67%) lived independently, 34% with and 33% without attendant. Of the 53% who were competitively employed, 22% earned an income high enough that advancement would cause financial loss through termination of disability benefits. Speech deficits severely compromised functional verbal communication in 50%. Type of employment correlated more with adequate cognition than with physical or communicative impairments. CONCLUSIONS: Compared with earlier studies, the present study showed more adults with cerebral palsy achieving competitive employment and independent living, despite moderate to severe physical disability. Advances in rehabilitation technology, better home support services, and legal mandates in education and environmental access may have facilitated positive change for persons with cerebral palsy. Further studies are encouraged with emphasis on longitudinal designs.

The energetics of phosphate binding to a protein complex.

The heat of binding the serine protease, porcine pancreatic elastase, by the inhibitor, turkey ovomucoid third domain, is dependent on the presence of inorganic phosphate. This dependence is saturable and can be accurately modeled as the phosphate binding to a single site on the protease-inhibitor complex; thus, the elastase-ovomucoid system provides a unique opportunity to study phosphate-protein interactions. We have used isothermal titration calorimetry to investigate this binding, thereby providing one of the few complete thermodynamic characterizations of phosphate interacting with proteins. The binding is characterized by a small favorable deltaG degrees, a large unfavorable deltaH degrees, and a positive deltaCp, thermodynamics consistent with the release of water being linked to phosphate binding. These measurements provide insight into the binding of phosphotyrosine containing peptides to SH2 domains by suggesting the energetic consequences of binding phosphate free from other interactions.

Tattooed Army soldiers: examining the incidence, behavior, and risk.

Primary prevention is a priority for medical personnel. Despite societal popularity and a long association of the military with tattooing, little is known about the tattooed Army soldier, which hampers primary health planning. Basic recruits and advanced individual training students (N = 1,835) at one mid-western military installation completed a questionnaire about any tattooing experiences. Almost half (48%) of the soldiers were serious/very serious about getting a tattoo, with 31% stating that there were "no reasons" to keep them from getting a tattoo. More than one-third (36%) were tattooed, with 22% possessing three or more tattoos. Many soldiers (64%) entered the military with the tattoos. Limited use (15%) of alcohol and/or drugs before tattooing was reported. Findings included a high incidence of tattooing, a strong determination to obtain tattoos, the possession of tattoos for self-identity reasons, and the supportive role of friends. Reported procedural bleeding (76%) documents the potential for blood-borne disease transmission. These results confirm the need for targeted health education regarding the safety and potential risks of tattooing.