Extracorporeal photopheresis for the treatment of severe,refractory steroid dependent pediatric Crohn's Disease

Crohn's disease is a chronic, inflammatory disease of the gastrointestinal tract, affecting both children and adults. Extracorporeal photopheresis (ECP) has been used in steroid dependent adults with moderate to severely active Crohn's disease, with response rates up to 50%, with up to 25% complete responses. A 12‐year‐old male patient had severe unremitting Crohn's disease for one year, despite treatment with anti‐inflammatory, immunosuppressive, and biologic agents. He failed elemental enteral nutrition and required total parenteral nutrition (TPN). A diverting colostomy for perforation was required. He required frequent hospitalizations and required homebound schooling. Endoscopy revealed severe inflammation and ulcerations of the entire colon. ECP was begun twice weekly for 4 weeks, then twice per week every 14 days for a total of 28 weeks. ECP was well tolerated and prednisone was gradually discontinued. He continued daily azathioprine and infliximab at 6 week intervals. TPN was weaned as enteral intake improved. Disease abatement allowed a return to school and normal activities. Endoscopy at completion of ECP course revealed normal upper tract, normal ano‐rectum, and decreased, although significant, colonic disease. This response has continued for at least 16 months since completion of ECP. We conclude that ECP is useful for pediatric patients with steroid dependent Crohn's disease and prospective evaluation is warranted. J. Clin. Apheresis 28:381–386, 2013. © 2013 Wiley Periodicals, Inc.     

Design and characterization of a dynamic vibrational culture system

To engineer a functional vocal fold tissue, the mechanical environment of the native tissue needs to be emulated in vitro. We have created a dynamic culture system capable of generating vibratory stimulations at human phonation frequencies. The novel device is composed of a function generator, a power amplifier, an enclosed loudspeaker and a circumferentially‐anchored silicone membrane. The vibration signals are translated to the membrane aerodynamically by the oscillating air pressure underneath. The vibration profiles detected on the membrane were symmetrical relative to the centre of the membrane as well as the resting position over the range of frequencies (60–300 Hz) and amplitudes tested (1–30 µm). The oscillatory motion of the membrane gave rise to two orthogonal, in‐plane strain components that are similar in magnitude (0.47%) and are strong functions of membrane thickness. Neonatal foreskin fibroblasts (NFFs) attached to the membrane were subjected to a 1 h vibration at 60, 110 and 300 Hz, with the displacement at the centre of the membrane varying in the range 1–30 µm, followed by a 6 h rest. These regimens did not cause morphological changes to the cells. An increase in cell proliferation was detected when NFFs were driven into oscillation at 110 Hz with a normal displacement of 30 µm. qPCR results showed that the expression of genes encoding some extracellular matrix proteins was altered in response to changes in vibratory frequency and amplitude. The dynamic culture device provides a potentially useful in vitro platform for evaluating cellular responses to vibration. Copyright © 2011 John Wiley & Sons, Ltd.     

Three-Fraction Stereotactic Radiosurgery for Treatment of Vestibular Schwannoma (Acoustic Neuroma) in Patients with Neurofibromatosis Type 2

Neurofibromatosis type 2 (NF2) patients risk complete deafness from either bilateral vestibular schwannoma (VS) or its treatment. Both microsurgical resection and Stereotactic radiosurgery (SRS) have been associated with poorer rates of hearing preservation in patients with NF2 than in sporadic VS. In an attempt to maximize hearing preservation while maintaining good tumor control, we have conducted a prospective trial of three fraction SRS for the treatment of VS in patients with NF2. Eleven VS in 10 patients with NF2 were treated. Conventional frame-based Stereotactic localization was used. Mean maximal tumor diameter was 19.5 mm (range 11–28). A total dose of 21 Gy was administered in 7 Gy fractions with a mean interfraction interval of 12 hours. Patients were evaluated with neurologic examination, MRI, and audiometry. No patients were lost to follow-up. One patient died due to complications following surgical resection of a contralateral VS. Tumor (10–46 months posttreatment, mean 26 months) was stable or decreased in 9 of 10 tumors (90%). One patient experienced slight tumor enlargement at 27 months, which subsequently regressed. Actuarial rate of hearing preservation at 2 years was 67%. All patients (n = 5) with good pretreatment hearing (Gardner–Robertson grade 1 or 2) had preserved useful hearing (grade 1–3) at 1 year. Two patients (grade 3 and 4 hearing) lost all hearing within 24 hours of treatment; another patient with grade 3 hearing lost residual hearing over 6 months. One patient developed facial spasms. Three-fraction SRS for acoustic neuroma is well tolerated in patients with NF2 and is associated with a lower risk of hearing loss and other cranial neuropathy than single-fraction treatment. Continued follow-up will be necessary to evaluate long-term tumor control and hearing preservation.     

A preliminary study of the effects of working memory training on brain function

Working memory (WM) training improves WM ability in Attention-Deficit/Hyperactivity Disorder (ADHD), but its efficacy for non-cognitive ADHD impairments ADHD has been sharply debated. The purpose of this preliminary study was to characterize WM training-related changes in ADHD brain function and see if they were linked to clinical improvement. We examined 18 adolescents diagnosed with DSM-IV Combined-subtype ADHD before and after 25 sessions of WM training using a frequently employed approach (Cogmed?) using a nonverbal Sternberg WM fMRI task, neuropsychological tests, and participant- and parent-reports of ADHD symptom severity and associated functional impairment. Whole brain SPM8 analyses identified ADHD activation deficits compared to 18 non-ADHD control participants, then tested whether impaired ADHD frontoparietal brain activation would increase following WM training. Post hoc tests examined the relationships between neural changes and neurocognitive or clinical improvements. As predicted, WM training increased WM performance, ADHD clinical functioning, and WM-related ADHD brain activity in several frontal, parietal and temporal lobe regions. Increased left inferior frontal sulcus region activity was seen in all Encoding, Maintenance, and Retrieval Sternberg task phases. ADHD symptom severity improvements were most often positively correlated with activation gains in brain regions known to be engaged for WM-related executive processing; improvement of different symptom types had different neural correlates. The responsiveness of both amodal WM frontoparietal circuits and executive process-specific WM brain regions was altered by WM training. The latter might represent a promising, relatively unexplored treatment target for researchers seeking to optimize clinical response in ongoing ADHD WM training development efforts.     

Problem alcohol use in veterans with mild traumatic brain injury: Associations with cognitive performance and psychiatric symptoms

Introduction: Given that little is known about the associations between alcohol use, cognition, and psychiatric symptoms among veterans with a history of mild traumatic brain injury (mTBI), we aimed to (a) characterize how they differ from veteran controls on a measure of problem drinking; (b) investigate whether problem drinking is associated with demographic or mTBI characteristics; and (c) examine the associations between alcohol use, mTBI history, psychiatric functioning, and cognition. Method: We assessed 59 veterans (n = 32 with mTBI history; n = 27 military controls) for problem alcohol use (Alcohol Use Disorders Identification Test: AUDIT), psychiatric symptoms, and neuropsychological functioning. Results: Compared to controls, veterans with mTBI history were more likely to score above the AUDIT cutoff score of 8 (p = .016), suggesting a higher rate of problem drinking. Participants with mTBI history also showed elevated psychiatric symptoms (ps < .001) and lower cognitive scores (ps < .05 to < .001). Veterans with higher AUDIT scores were younger (p = .05) and had less education (p < .01) and more psychiatric symptoms (ps < .01), but mTBI characteristics did not differ. After controlling for combat and mTBI history (R² = .04, ns) and posttraumatic stress disorder (PTSD) symptoms (ΔR² = .08, p = .05), we found that higher AUDIT scores were associated with poorer attention/processing speed, F(9, 37) = 2.55, p = .022; ΔR² = .26, p = .03. Conclusions: This preliminary study suggested that veterans with mTBI history may be at increased risk for problem drinking. Problem alcohol use was primarily associated with more severe PTSD symptoms and poorer attention/processing speed, though not with combat or mTBI characteristics per se. Importantly, findings emphasize the importance of assessing for and treating problematic alcohol use and comorbid psychiatric symptoms among veterans, including those with a history of neurotrauma.     

High-resolution MRI and micro-CT in an ex vivo rabbit anterior cruciate ligament transection model of osteoarthritis

OBJECTIVE: The aim of this study was to investigate the potential of using non-invasive, multi-modality imaging techniques to quantify disease progression in a rabbit model of experimentally induced osteoarthritis (OA). METHODS: High-resolution 4-T magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) techniques were implemented and validated in an ex vivo rabbit anterior cruciate ligament transection (ACLT) model of OA. A three-dimensional (3-D) rigid body registration technique was executed and evaluated to allow combined MR-CT analysis in co-registered image volumes of the knee. RESULTS: The 3-D MRI and micro-CT data formats made it possible to quantify cartilage damage, joint-space, and osseous changes in the rabbit ACLT model of OA. Spoiled gradient-recalled echo and fast-spin echo (FSE) sequences were jointly used to evaluate femorotibial cartilage and determine the sensitivity (78.3%) and specificity (95.3%) of 4-T MRI to detect clinically significant cartilage lesions. Overall precision error of the micro-CT technique for analysis of joint-space, volumetric bone mineral density (vBMD), and bone volume fraction (BV/TV) was 1.8%, 1.2%, and 2.0%, respectively. Co-registration of the 3-D data sets was achieved to within 0.36 mm for completed intermodality registrations, 0.22 mm for extrapolated intramodality registrations, and 0.50mm for extrapolated intermodality registrations. CONCLUSIONS: These results indicate that high-resolution 4-T MRI and micro-CT can be used to accurately quantify cartilage damage and calcified tissue changes in the rabbit ACLT model of OA. In addition, image volumes can be successfully co-registered to facilitate a comprehensive multi-modality examination of localized changes in both soft tissue and bone within the rabbit femorotibial joint.