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BACKGROUND Neuroprotective agents have the potential to improve the outcomes of revascularisation therapies in acute ischemic stroke patients (AIS) and in those unable to receive revascularisation. Afamelanotide, a synthetic α-melanocyte stimulating hormone analogue, is a potential novel neuroprotective agent. We set out to assess the feasibility and safety of afamelanotide for the first time in AIS patients. METHODS AIS patients within 24 hours of onset, with perfusion abnormality on imaging (Tmax) and otherwise ineligible for revascularisation therapies were enrolled. Afamelanotide 16 mg implants were administered subcutaneously on Day 0 (D0, day of recruitment), D1 and repeated on D7 and D8, if not well recovered. Treatment emergent adverse events (TEAEs) and neurological assessments were recorded regularly up to D42. Magnetic resonance imaging (MRI) with FLAIR sequences were also performed on D3 and D9. RESULTS Six patients (5 women, median age 81, median NIHSS 6) were recruited. Two patients received 4 doses and four patients received 2. One patient (who received 2 doses), suffered a fatal recurrent stroke on D9 due to a known complete acute internal carotid artery occlusion, assessed as unrelated to the study drug. There were no other local or major systemic TEAEs recorded. In all surviving patients, the median NIHSS improved from 6 to 2 on D7. The median Tmax volume on D0 was 23 mL which was reduced to a FLAIR volume of 10 mL on D3 and 4 mL on D9. CONCLUSIONS Afamelanotide was well tolerated and safe in our small sample of AIS patients. It also appears to be associated with good recovery and radiological improvement of salvageable tissue which needs to be tested in randomized studies. ClinicalTrials.gov Identifier: NCT04962503

BACKGROUND AND PURPOSE Pain information from the face enters the pons via the trigeminal nerve before creating an anatomical “elbow” that turns caudally into the spinal trigeminal tract (SpTV). Visualization of the descending tract of the trigeminal nerve as it begins its descent from the nerve root entry zone (NREZ) in the pons would improve the accuracy of current procedures aimed at altering or lesioning the trigeminal nerve within the brainstem. The focus of this study was to develop a standardized protocol using diffusion tensor imaging (DTI) and deterministic tractography methods to image the SpTV. There are currently no standard techniques used to visualize the trigeminal nerve using DTI. METHODS DTI and tractography were performed on 20 patients: 17 with trigeminal neuralgia (TN), 1 with hemifacial spasm, 1 with a facial nerve tumor, and 1 with an arteriovenous malformation. A standardized protocol was developed using regions of interest (ROIs) located at the SpTV, as determined by a brainstem atlas, and the NREZ. RESULTS Using our standardized protocol, the descending tract of the trigeminal nerve was successfully visualized in all 20 patients. Trigeminal fibers entered the pons at the NREZ and descended through the SpTV. The accuracy of the visualized tract was confirmed through coregistration with a stereotactic atlas and anatomical scan. CONCLUSION A successful, robust DTI imaging and postprocessing protocol of the SpTV contributes to our understanding of its anatomical distribution within the brainstem and is a potentially new neurosurgical planning tool.

This article discusses three patients with likely Hirayama disease. They have no other significant past medical history and no personal or family history of other neurological disorders. Hirayama disease is a form of cervical myelopathy attributed to forward displacement of the posterior cervical dural sac on neck flexion with resultant cord compression and/or venous congestion. It is characterized by a pure motor focal amyotrophy in the distribution of C7, C8 and T1 spinal segmental-innervated muscles and differs from other motor neuron diseases by virtue of its ultimately non-progressive course.

We report the case of a 68-year-old male with right eye vision loss secondary to a compressive optic neuropathy from Waldenstrom macroglobulinaemia relapse in both cavernous sinuses. Central nervous system involvement is extremely uncommon in lymphoplasmacytic lymphoma. Known as Bing-Neel syndrome, this has not been previously reported to present simultaneously in bilateral cavernous sinuses. We discuss the pathophysiology, diagnostic and neuroradiological features of Bing-Neel syndrome. In this case, there was marked clinical and radiological response to chemotherapy. As outcomes following treatment for Waldenstrom macroglobulinaemia improve, greater awareness of its less common manifestations becomes important. Neurosurgical intervention may be indicated to obtain histological diagnosis or decompress critical structures.

Pain information from the face enters the pons via the trigeminal nerve before creating an anatomical "elbow" that turns caudally into the spinal trigeminal tract (SpTV). Visualization of the descending tract of the trigeminal nerve as it begins its descent from the nerve root entry zone (NREZ) in the pons would improve the accuracy of current procedures aimed at altering or lesioning the trigeminal nerve within the brainstem. The focus of this study was to develop a standardized protocol using diffusion tensor imaging (DTI) and deterministic tractography methods to image the SpTV. There are currently no standard techniques used to visualize the trigeminal nerve using DTI.DTI and tractography were performed on 20 patients: 17 with trigeminal neuralgia (TN), 1 with hemifacial spasm, 1 with a facial nerve tumor, and 1 with an arteriovenous malformation. A standardized protocol was developed using regions of interest (ROIs) located at the SpTV, as determined by a brainstem atlas, and the NREZ.Using our standardized protocol, the descending tract of the trigeminal nerve was successfully visualized in all 20 patients. Trigeminal fibers entered the pons at the NREZ and descended through the SpTV. The accuracy of the visualized tract was confirmed through coregistration with a stereotactic atlas and anatomical scan.A successful, robust DTI imaging and postprocessing protocol of the SpTV contributes to our understanding of its anatomical distribution within the brainstem and is a potentially new neurosurgical planning tool.

To evaluate the safety and efficacy of once-daily intraclot injections of low doses (≤ 10 mg) of tissue plasminogen activator (tPA) for thrombolysis of venous thrombosis.In prospective studies, 33 patients with subclavian, jugular, and central venous thrombosis (SJ-CVT) (all but two cases associated with central catheters) were treated once a day with ≤ 4 mg/day of tPA, and 30 patients with acute deep vein thrombosis of the lower extremity (DVT-LE)14 days old were treated once a day with ≤ 10 mg/leg/day of tPA by intraclot "lacing" of thrombus without continuous infusions of tPA.Patency was restored in 26 (79%) of 33 patients with SJ-CVT using an average total dose of 7.1 mg of tPA/per patient and average of 2.1 treatments or days of therapy. Five patients received thrombolytic therapy for SJ-CVT as outpatients. Initial patency was restored in 29 (97%) of 30 patients with acute DVT-LE using an average total dose of 20 mg of tPA per patient over an average of 2.7 treatments/or days per patient. Follow-up imaging examinations at 6 months showed continued patency in 27 (96%)/of 28 patients. There were no major bleeding complications, and no patient required a blood transfusion.Intraclot injection of low doses of alteplase is effective for acute venous thrombosis, and pharmacokinetic data suggest potentially greater safety.

An 82-year old male, with no significant past medical history, presented with a subacute right foot drop in the setting of a 14-month history of generalised weakness, highly-responsive to steroids. Temporal artery and vastus lateralis biopsies were normal. Vasculitic screen and inflammatory markers were normal. Lumbar puncture revealed elevated cerebrospinal fluid (CSF) protein without oligoclonal bands. Visual evoked response (VER) was normal. Magnetic resonance imaging (MRI) of his lumbar spine showed compression of exiting L5 nerve root. He had three cerebral MRI scans spaced over the 12 month period, which showed a progressive increase of T2 and fluid attenuated inversion recovery (FLAIR) hyperintense lesions consistent with active demyelinating plaques. He was treated with intravenous methylprednisolone 1 g daily for three days with a weaning regimen of oral prednisolone, resulting in a full return of power and a resolution of his right foot drop. He was diagnosed with late-onset multiple sclerosis (LOMS), and was treated with monthly natalizumab. A literature review of LOMS is discussed.

SummaryThrombomodulin (TM), which variably contains a chondroitin sulfate (±CS), forms an anticoagulant complex with thrombin (IIa). IIaTM(±CS) converts protein C (PC) into activated PC (APC), which then inactivates activated factors V (FVa) and VIII (FVIIIa). This reduces prothrombinase and tenase complexes that generate IIa. Heparin (H) increases the rate of IIa-TM inhibition by antithrombin (AT) and enhances FV cleavage by APC. Our novel covalent AT-H (ATH) product, has superior anticoagulant activity compared to AT + unfractionated H (UFH). We studied mechanisms by which ATH versus AT + UFH inhibits IIaTM(±CS), and ATH influences on APC cleavage of FV/FVa compared to UFH. Findings would determine how these reactions moderate ATH’s overall effects as an anticoagulant. Discontinuous second order rate inhibition assays of IIa-TM(±CS) inhibition by AT + UFH or ATH were performed in presence or absence of human umbilical vein endothelial cells (HUVECs). FV/FVa cleavage by APC in the presence of UFH or ATH was analysed by Western blots. ATH increased IIa-TM(±CS) inhibition to a greater degree than AT + UFH, both on plastic and HUVEC surfaces. Unlike UFH, ATH did not accelerate FV cleavage by APC, but ATH did enhance FVa cleavage relative to UFH. Increased IIa-TM inhibition by ATH downregulates PC activation. However, ATH does accelerate downstream inactivation of FVa, which increases its potency for IIa generation inhibition compared to UFH. This trend holds true in the presence of APC’s cofactor, protein S. Overall, ATH may have a balanced function towards inhibiting or accelerating PC pathway activities.

The objective of this study was to develop anatomically correct whole body human models of an adult male (34 years old), an adult female (26 years old) and two children (an 11-year-old girl and a six-year-old boy) for the optimized evaluation of electromagnetic exposure. These four models are referred to as the Virtual Family. They are based on high resolution magnetic resonance (MR) images of healthy volunteers. More than 80 different tissue types were distinguished during the segmentation. To improve the accuracy and the effectiveness of the segmentation, a novel semi-automated tool was used to analyze and segment the data. All tissues and organs were reconstructed as three-dimensional (3D) unstructured triangulated surface objects, yielding high precision images of individual features of the body. This greatly enhances the meshing flexibility and the accuracy with respect to thin tissue layers and small organs in comparison with the traditional voxel-based representation of anatomical models. Conformal computational techniques were also applied. The techniques and tools developed in this study can be used to more effectively develop future models and further improve the accuracy of the models for various applications. For research purposes, the four models are provided for free to the scientific community.

We measured serum C-peptide (at least 0.167 nmol/l) in 54 of 141 (38%) patients with chronic type 1 diabetes and sought factors that might differentiate those with detectable C-peptide from those without it. Finding no differences, and in view of the persistent anti-beta cell autoimmunity in such patients, we speculated that the immunosuppression (to weaken autoimmune attack) and euglycaemia accompanying transplant-based treatments of type 1 diabetes might promote recovery of native pancreatic beta cell function. We performed arginine stimulation tests in three islet transplant and four whole-pancreas transplant recipients, and measured stimulated C-peptide in select venous sampling sites. On the basis of each sampling site’s C-peptide concentration and kinetics, we differentiated insulin secreted from the individual’s native pancreatic beta cells and that secreted from allografted beta cells. Selective venous sampling demonstrated that despite long-standing type 1 diabetes, all seven beta cell allograft recipients displayed evidence that their native pancreas secreted C-peptide. Yet even if chronic immunosuppression coupled with near normal glycaemia did improve native pancreatic C-peptide production, the magnitude of the effect was quite small. Some native pancreatic beta cell function persists even years after disease onset in most type 1 diabetic patients. However, if prolonged euglycaemia plus anti-rejection immunosuppressive therapy improves native pancreatic insulin production, the effect in our participants was small. We may have underestimated pancreatic regenerative capacity by studying only a limited number of participants or by creating conditions (e.g. high circulating insulin concentrations or immunosuppressive agents toxic to beta cells) that impair beta cell function. ClinicalTrials.gov NCT00246844 and NCT00006505.

Context: Selective intraarterial calcium injection of the major pancreatic arteries with hepatic venous sampling [calcium arterial stimulation (CaStim)] has been used as a localizing tool for insulinomas at the National Institutes of Health (NIH) since 1989. The accuracy of this technique for localizing insulinomas was reported for all cases until 1996. Objectives: The aim of the study was to assess the accuracy and track record of the CaStim over time and in the context of evolving technology and to review issues related to result interpretation and procedure complications. CaStim was the only invasive preoperative localization modality used at our center. Endoscopic ultrasound (US) was not studied. Design and Setting: We conducted a retrospective case review at a referral center. Patients: Twenty-nine women and 16 men (mean age, 47 yr; range, 13–78) were diagnosed with an insulinoma from 1996–2008. Intervention: A supervised fast was conducted to confirm the diagnosis of insulinoma. US, computed tomography (CT), magnetic resonance imaging (MRI), and CaStim were used as preoperative localization studies. Localization predicted by each preoperative test was compared to surgical localization for accuracy. Main Outcome: We measured the accuracy of US, CT, MRI, and CaStim for localization of insulinomas preoperatively. Results: All 45 patients had surgically proven insulinomas. Thirty-eight of 45 (84%) localized to the correct anatomical region by CaStim. In five of 45 (11%) patients, the CaStim was falsely negative. Two of 45 (4%) had false-positive localizations. Conclusion: The CaStim has remained vastly superior to abdominal US, CT, or MRI over time as a preoperative localizing tool for insulinomas. The utility of the CaStim for this purpose and in this setting is thus validated.

The purpose of the study was to assess the feasibility of intermittent hepatic vein balloon occlusion during percutaneous radiofrequency (RF) ablation. Eight non-anticoagulated patients who had primary (n = 2) and metastatic (n = 6) liver tumors with a mean diameter of 4.2 cm (range 2.4–6.5 cm) were treated, resulting in a mean ablation diameter of 6.3 cm (range 4.3–9.3 cm). Six of 9 (67%) of the balloon-occluded hepatic veins were patent. No clinical sequelae of thrombosis were noted. Mean length of follow-up with CT and/or MRI was 12 months. Local tumor control was achieved in 5 of 8 patients. Intermittent hepatic vein balloon occlusion could potentially be a low-risk adjunctive maneuver for thermal ablation therapy in the treatment of large tumors and tumors adjacent to large vessels.

A serious complication for any thermal radiofrequency ablation is thermal injury to adjacent structures, particularly the bowel, which can result in additional major surgery or death. Several methods using air, gas, fluid, or thermometry to protect adjacent structures from thermal injury have been reported. In the cases presented in this report, 5% dextrose water (D5W) was instilled to prevent injury to the bowel and diaphragm during radiofrequency ablation. Creating an Insulating envelope or moving organs with D5W might reduce risk for complications such as bowel perforation.

Purpose We conducted a phase I study of a 30-minute hepatic artery infusion of melphalan via a percutaneously placed catheter and hepatic venous hemofiltration using a double balloon catheter positioned in the retrohepatic inferior vena cava to shunt hepatic venous effluent through an activated charcoal filter and then to the systemic circulation. The purpose of the study was to demonstrate feasibility in an initial cohort and subsequently determine the maximum tolerated dose and dose-limiting toxicity of melphalan. Patients and Methods The initial cohort (n = 12) was treated with 2.0 mg/kg of melphalan before dose escalation to 3.5 mg/kg (n = 16). Total hepatic drug delivery, systemic levels, and percent filter efficiency were determined. Patients were assessed for hepatic and systemic toxicity and response. Results A total of 74 treatments were administered to 28 patients. Twelve patients with primary and metastatic hepatic tumors received 30 treatments (mean, 2.5 per patient) at an initial melphalan dose of 2.0 mg/kg. At 3.5 mg/kg, a dose-limiting toxicity (neutropenia and/or thrombocytopenia) was observed in two of six patients. Transient grade 3/4 hepatic and systemic toxicity was seen after 19% and 66% of treatments, respectively. An overall radiographic response rate of 30% was observed in treated patients. In the 10 patients with ocular melanoma, a 50% overall response rate was observed, including two complete responses. Conclusion Delivery of melphalan via this system is feasible, with limited, manageable toxicity and evidence of substantial antitumor activity; 3 mg/kg is the maximum safe tolerated dose of melphalan administered via this technique.

A 73-year-old man, with a history of hypertension and left supraclavicular fossa arteriovenous malformation with multiple previous uncomplicated vessel embolisation procedures, presented with acute spastic quadriparesis and urinary retention following upper limb angiography and embolisation. There was no evidence of preceding infection or neurological disease prior to the event. Cerebrospinal fluid analysis was unremarkable. MRI of the cervical spine with a 1.5 Tesla magnet performed 13 hours from symptom onset revealed bilateral paramedian intramedullary T2-weighted signal change without gadolinium enhancement limited to the grey matter with corresponding diffusion restriction extending from C5-6 down to the mid-T1. The diagnosis of cervical spinal cord infarction (SCI) was made and the patient was given regular aspirin and atorvastatin. On follow-up at 3 months, there was modest improvement with respect to his quadriparesis and was walking unaided. An extensive literature review on the role of MRI in SCI is discussed.

Patients with symptomatic septal perforations require treatment, with many surgeons advocating primary treatment with an obturator if conservative measures fail. Twenty nasal Button Outcome Questionnaires were sent to patients who had undergone insertion of a septal button between 1990 and 2000 in our unit. Fourteen questionnaires were returned. This study reveals that despite a reduction in symptom score in nine patients, septal buttons are poorly tolerated by patients with only 45 per cent of obturators ultimately being in situ. In view of these findings, patients are now offered a choice between primary surgical and mechanical closure in our unit.

Due to the proliferation of smart inverters, there have been recent proposals to perform automatic, fast, closed-loop voltage control via VAR injection/absorption. The stability of such feedback loops has only been briefly investigated, either experimentally, or theoretically but under the assumption that all smart inverters act synchronously. This paper attempts to fill a theoretical gap with a rigorous mathematical analysis of the stability criterion of distributed and asynchronous VAR injection over an arbitrary radial feeder, where each unit (out of potentially 100s) faces different impedances and independently runs closed-loop control based on its local voltage, with no global knowledge. We employ Lyapunov analysis, modified to allow non-deterministic system evolution. Our main theorem is a simple and intuitive stability criterion that allows arbitrary sequence of actions (periodic or aperiodic) by the distributed smart inverters. We also show that while both synchronous and asynchronous cases exhibit a tradeoff between voltage correction and stability, the asynchronous case has a much larger stability region and therefore allows much better voltage correction.

We describe three cases of severe necrotizing pancreatitis, with Apache II scores of 11, 17 and 22, respectively. There was no significant pancreatic parenchymal perfusion in any of the three patients on contrast-enhanced computed tomography. All three patients were primarily treated with percutaneous drains and all three subsequently required open laparotomies. We do not recommend percutaneous drainage as a definitive therapy for severe necrotizing pancreatitis.

Upper limb amyotrophy may occur as an indirect consequence of various spinal disorders, including ventral longitudinal intraspinal fluid collection, Hirayama disease and high cervical cord compression. We present patients who suffer from each of these and review the literature on the three conditions with emphasis on the pathogenesis of amyotrophy. We propose that pathology some distance from the lower cervical spinal cord may affect normal venous drainage, resulting in venous congestion and reduced perfusion pressure which, in turn, could result in anterior horn cell dysfunction in all three disorders.

Background This paper describes the rationale and design of the ENVIS-ion Study, which aims to determine whether low-dose aspirin reduces the development of white matter hyper-intense (WMH) lesions and silent brain infarction (SBI). Additional aims include determining whether a) changes in retinal vascular imaging (RVI) parameters parallel changes in brain magnetic resonance imaging (MRI); b) changes in RVI parameters are observed with aspirin therapy; c) baseline cognitive function correlates with MRI and RVI parameters; d) changes in cognitive function correlate with changes in brain MRI and RVI and e) whether factors such as age, gender or blood pressure influence the above associations. Methods/Design Double-blind, placebo-controlled trial of three years duration set in two Australian academic medical centre outpatient clinics. This study will enrol 600 adults aged 70 years and over with normal cognitive function and without overt cardiovascular disease. Subjects will undergo cognitive testing, brain MRI and RVI at baseline and after 3 years of study treatment. All subjects will be recruited from a 19,000-patient clinical outcome trial conducted in Australia and the United States that will evaluate the effects of aspirin in maintaining disability-free longevity over 5 years. The intervention will be aspirin 100 mg daily versus matching placebo, randomized on a 1:1 basis. Discussion This study will improve understanding of the mechanisms at the level of brain and vascular structure that underlie the effects of aspirin on cognitive function. Given the limited access and high cost of MRI, RVI may prove useful as a tool for the identification of individuals at high risk for the development of cerebrovascular disease and cognitive decline. Trial Registration clinicaltrials.gov Identifier: NCT01038583

Hemichorea-hemiballismus is a rare complication of nonketotic hyperglycaemia in type 2 diabetes. It is associated with contralateral striatal radiological abnormality, most typically T1 hyperintensity on MRI. We report a case of a 91 year old woman who presented in a nonketotic hyperglycaemic state with right sided hemichorea. Brain CT revealed hyperdensity of the left lentiform nucleus and MRI 15 days post presentation showed left lentiform T1 hyperintensity and enlargement. The chorea improved after control of blood glucose levels. The pathophysiology of this syndrome remains controversial. It is likely that a combination of hyerglycaemia induced basal ganglia metabolic derangement and failure of cerebral blood flow autoregulation contribute to the syndrome.

The review by Ramli et al. in a recent issue of the Journal of Clinical Neuroscience provides a short general overview of the past, present and future of imaging in multiple sclerosis (MS). The nature of such a review is by no means exhaustive, but rather helps give an insight into ongoing developments in MS imaging. The article will be of interest to individuals involved in the clinical management MS patients, as well as individuals interested in pursuing MS-related research. The introduction of MRI to the assessment of patients with multiple sclerosis (MS) has dramatically altered our understanding of this most complex disease. Due to its superior sensitivity, MRI has become an established clinical tool not only in the diagnosis of MS, but also to monitor its natural course and response to immunomodulatory treatment. Conventional MRI techniques such as T2 lesion load, gadolinium enhancement, T1 hypointensity, and spatial and temporal disease dissemination assessment have long become established in everyday clinical MS imaging. Due to the many MS mimickers seen on clinical imaging, however, researchers are constantly striving to ensure that any proposed diagnostic criteria have a high specificity without sacrificing sensitivity. Since the commonly used 2001 McDonald criteria, changes have been towards simplifying the diagnostic criteria so that they become easier to use. Further simplification in terms of dissemination in time and space has been proposed, while being more sensitive than the 2001 and 2005 McDonald criteria without sacrificing specificity. It is well known that lesions detectable on conventional MRI techniques may only weakly correlate with the patient’s clinical status. One explanation for such clinical–radiologic discrepancy is the lack of specificity of T2-weighted MRI, which discriminates between focal MS lesions and normal-appearing white matter but not between the underlying pathologic entities (oedema, demyelination, remyelination, gliosis and axonal loss) that contribute differently to clinical symptoms. As such, tremendous efforts are being devoted to new uses of conventional imaging as well as non-conventional advanced imaging techniques in an attempt to overcome such limitation. Novel post-processing techniques employed in clinical trials have incorporated cerebral volume measurements using conven

To prospectively evaluate the outcome of patients with acute deep vein thrombosis (DVT) of the lower extremity treated with "lacing" of the thrombus with alteplase (recombinant tissue plasminogen activator, or rTPA).This HIPAA-compliant study was approved by the Institutional Review Board of the National Heart, Lung, and Blood Institute and was funded by the National Institutes of Health. After giving written consent, 20 patients with first-onset acute DVT were treated with direct intraclot lacing of the thrombus with alteplase (maximum daily dose, 50 mg per leg per day; maximum of four treatments) and full systemic anticoagulation. Alteplase was chosen because its high fibrin affinity obviates continuous infusion of this thrombolytic agent. Ventilation-perfusion (V/Q) scans were performed for evaluation of embolic risks, and clinical and imaging examinations were supplemented with pharmacokinetic studies to enable further assessment of treatment outcomes.The 20 patients included 13 men and seven women aged 18-79 years. Antegrade blood flow was restored throughout the deep venous system in 16 patients (80%) during thrombolytic therapy, with complete resolution of symptoms in 18 patients (90%) after 6 months of anticoagulation. Pharmacokinetic studies showed rapid clearance of circulating alteplase and recovery of plasminogen activator inhibitor-1 levels within 2 hours after termination of alteplase treatment. V/Q scans revealed a 40% incidence of pulmonary embolism before treatment and a 15% incidence of asymptomatic pulmonary embolism during thrombolytic therapy. There were no cases of clinically important pulmonary embolism or serious bleeding during thrombolytic therapy. During a mean follow-up period of 3.4 years, no patient developed a postthrombotic syndrome or recurrent thromboembolism.Intraclot injection or lacing of the thrombus with a fibrin-binding thrombolytic agent such as alteplase is an alternative to continuous-infusion thrombolytic regimens and minimizes the duration of systemic exposure to thrombolytic agents.

ims: Impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes arise due to insufficient insulin secretion and are risk factors for cardiovascular (CV) events. Thus, targeting normal fasting glucose levels with insulin may reduce CV events. Previous studies suggest that omega-3 fatty acid supplements may reduce CV death ; however, their effect in high- risk dysglycemic individuals is not known. Methods: People aged > or = 50 years with evidence of CV disease and with IFG, IGT, newly detected or established diabetes (on 0 or 1 oral agent), and a local glycated hemoglobin < 150% of the upper limit of normal for that assay were recruited and allocated to (a) either 1 daily injection of insulin glargine with the dose titrated to achieve a fasting plasma glucose < or = 5.3 mmol/L (95 mg/dL), or standard glycemic care ; and (b) either omega-3-acid ethyl esters 90 (1 g consisting of EPA 465 mg and DHA 375 mg) or identical placebo, according to a 2 x 2 factorial design. The 2 different primary outcomes for the insulin and omega-3 fatty acid arms are CV events and CV death, respectively. Results: A total of 12, 612 (mean age 64, 35% women) people in 40 countries were randomized during a 2-year period ending December 2005. Eighty-two percent had established diabetes, 6% had new diabetes, and 12% had IGT or IFG ; the mean fasting plasma glucose was 7.3 mmol/L (131 mg/dL). Conclusions: The ORIGIN trial will determine whether or not either or both of these interventions can reduce CV events.

For a limited range of exposure parameters, pulsed high intensity focused ultrasound (HIFU) has been shown to increase the delivery of certain systemically administered macromolecular diagnostic and therapeutic agents in mice. The mechanism for the enhanced delivery has not been demonstrated definitively and, in principle, can include thermal, cavitational, and non‐cavitation mechanical effects. The sonicated tissue has no damage on histology. As a step towards clinical translation, the safety of this technique needs to be assessed in a clinically relevant manner. In this study, the safety of pulsed HIFU is evaluated with near real‐time phase shift magnetic resonance (MR) thermometry and anatomic MR imaging using rabbits as subjects. MR guidance enables pulsed HIFU enhanced delivery to be implemented safely from a thermal standpoint. Although the effects of pulsed HIFU are not seen on anatomic MR images, they may be detected on MR sequences sensitive to permeability, diffusion, and elasticity. Such work t...

This report describes two cases of post-traumatic, high flow carotid–cavernous fistulas that demonstrated residual shunting after initial embolization with coils and Onyx, and that were successfully closed with pipeline embolization devices. Following their combined endovascular treatments, the patients experienced clinical improvement of symptoms with durable obliteration of the fistulous communications.

The aim of this presentation is to raise awareness of this relatively benign condition when evaluating those patients presenting with lower quadrant pain, in particular, left lower quadrant pain. The image in fig 1 depicts the typical ultrasound appearance of epiploic appendagitis. Historically a rare surgical diagnosis, it is increasingly being recognised on ultrasound and computed tomography (CT) examinations. Epiploic appendagitis …

Within a certain range of parameters, pulsed high intensity focused ultrasound (HIFU) has been shown to increase the delivery of systemically administered drugs and plasmid DNA in tumors in mice. The sonicated tissue is not damaged by light microscopy. The mechanism for the enhanced delivery has not been shown conclusively and can include thermal, cavitational, and non‐cavitation mechanical effects. In order to assess the effects of pulsed HIFU in a manner that allows for clinical translation, pulsed HIFU is performed within a magnetic resonance (MR) scanner. In this work, the thermal effect is evaluated with phase‐shift MR thermometry in ex vivo chicken muscle. The thermal effect is small at the most common exposure parameters. In the future, non‐thermal effects like permeability, diffusion, and elasticity changes will be evaluated with dynamic contrast enhanced MRI, diffusion‐weighted MRI, and MR elastography. If changes in permeability, diffusion, and shear modulus are associated with pulsed HIFU enhan...

To demonstrate the feasibility of CT and B‐mode Ultrasound (US) targeted HIFU, a prototype coaxial focused ultrasound transducer was registered and integrated to a CT scanner. CT and diagnostic ultrasound were used for HIFU targeting and monitoring, with the goals of both thermal ablation and non‐thermal enhanced drug delivery. A 1 megahertz coaxial ultrasound transducer was custom fabricated and attached to a passive position‐sensing arm and an active six degree‐of‐freedom robotic arm via a CT stereotactic frame. The outer therapeutic transducer with a 10 cm fixed focal zone was coaxially mounted to an inner diagnostic US transducer (2–4 megahertz, Philips Medical Systems). This coaxial US transducer was connected to a modified commercial focused ultrasound generator (Focus Surgery, Indianapolis, IN) with a maximum total acoustic power of 100 watts. This pre‐clinical paradigm was tested for ability to heat tissue in phantoms with monitoring and navigation from CT and live US. The feasibility of navigation via image fusion of CT with other modalities such as PET and MRI was demonstrated. Heated water phantoms were tested for correlation between CT numbers and temperature (for ablation monitoring). The prototype transducer and integrated CT/US imaging system enabled simultaneous multimodality imaging and therapy. Pre‐clinical phantom models validated the treatment paradigm and demonstrated integrated multimodality guidance and treatment monitoring. Temperature changes during phantom cooling corresponded to CT number changes. Contrast enhanced or non‐enhanced CT numbers may potentially be used to monitor thermal ablation with HIFU. Integrated CT, diagnostic US, and therapeutic focused ultrasound bridges a gap between diagnosis and therapy. Preliminary results show that the multimodality system may represent a relatively inexpensive, accessible, and simple method of both targeting and monitoring HIFU effects. Small animal pre‐clinical models may be translated to large animals and humans for HIFU‐induced ablation and drug delivery. Integrated CT‐guided focused ultrasound holds promise for tissue ablation, enhancing local drug delivery, and CT thermometry for monitoring ablation in near real‐time.

We report the rare entity of an inverted papilloma arising from the sphenoid sinus that we expected to be a pituitary tumour on the basis of history, examination and pre-operative investigations, especially MRI appearance. Inverted sinonasal papilloma should be considered in the differential diagnosis of pituitary macroadenoma invading the sphenoid sinus.

The technology and engineering of tumor ablation are evolving more rapidly than the clinical validation. Technical descriptions risk being obsolete by publication time. General principles and developing technical paradigms provide a simplified framework to practice and study radiofrequency ablation (RFA).This chapter reviews the general limitations of tissue ablation methods, the optimization of ablation in the radiofrequency range, and several emerging technologies and paradigms feasible in the laboratory and possibly translatable to clinical practice.

Radiofrequency ablation (RFA) has been used for over 18 years for treatment of nerve-related chronic pain and cardiac arrhythmias. In the last 10 years, technical developments have increased ablation volumes in a controllable, versatile, and relatively inexpensive manner. The host of clinical applications for RFA have similarly expanded. Current RFA equipment, techniques, applications, results, complications, and research avenues for local tumor ablation are summarized.

Thermal injury to collateral structures is a known complication of thermal ablation of tumors. The authors present the use of CO(2) dissection and inserted balloons to protect the bowel during percutaneous radiofrequency (RF) ablation and cryotherapy of primary and locally recurrent renal cell carcinoma. These techniques offer the potential to increase the number of tumors that can be treated with RF ablation or cryotherapy from a percutaneous approach.

A fundamental dogma has developed over the past 20 years that non-enzymatic glycation involving saccharide chains of greater than 3 to 4 residues is an extremely unlikely reaction. Our investigations using glycosaminoglycans have shown that, given sufficient time, polypeptide-polysaccharide conjugates form via the Schiff base-Amadori rearrangement mechanism. Further, even though these straight chain polysaccharides are relatively charged and sterically hindered, spontaneous glycation can also occur in vivo. A complete reinvestigation of all aldose terminating polysaccharides is required to elucidate this new class of macromolecules, which is likely to contain unusual polypeptide-polysaccharide combinations and functions.