Purpose: Treatment-resistant cluster headache can be successfully alleviated with deep brain stimulation (DBS) of the posterior hypothalamus [1]. Magnetoencephalography (MEG) is a non-invasive functional imaging technique with both high temporal and high spatial resolution. However, it is not known whether the inherent electromagnetic (EM) noise produced by high frequency DBS is compatible with MEG. Materials and methods: We used MEG to record brain activity in an asymptomatic cluster headache patient with a DBS implanted in the right posterior hypothalamus while he made small movements during periods of no stimulation, 7 Hz stimulation and 180 Hz stimulation. Results: We were able to measure brain activity successfully both during low and high frequency stimulation. Analysis of the MEG recordings showed similar activation in motor areas in during the patient’s movements as expected. We also observed similar activations in cortical and subcortical areas that have previously been reported to be associated with pain when the patient’s stimulator was turned on or off [2,3]. Conclusion: These results show that MEG can be used to measure brain activity regardless of the presence of high frequency deep brain stimulation.

Background: Injection therapy around the distal biceps tendon insertion is challenging. This therapy may be indicated in patients with a partial distal biceps tendon tear, bicipitoradial bursitis and tendinopathy. The primary goal of this study was to determine the accuracy of manually performed injections without ultrasound guidance around the biceps tendon. Methods: Seven upper limb specialists, two general orthopedic specialists and three orthopedic surgical residents manually injected a cadaver elbow with acrylic dye using an anterior and a lateral infiltration approach. After infiltration the cadaveric elbows were dissected to determine the location of the acrylic dye. Results: In total, 79% of the injections were localized near the biceps tendon. Of these injections, 20% were localized on the radius near the bicipitoradial bursa. In total, 53% of the performed infiltrations were injected by anterior and 47% by lateral approaches. Of the injections near the distal biceps (79%), 47% were injected by an anterior and 53% by a lateral approach. Of the injections on the radius (20%), 33% were injected by anterior and 67% by lateral approach. Of the inaccurate injections (21%), 75% were injected anterior and 25% lateral. Conclusion Manual infiltration without ultrasound guidance for distal biceps pathology lacks accuracy. We therefore recommend ultrasound guidance for more accurate infiltration.

Background: Injection therapy around the distal biceps tendon insertion is challenging. This therapy may be indicated in patients with a partial distal biceps tendon tear, bicipitoradial bursitis and tendinopathy. The primary goal of this study was to determine the accuracy of manually performed injections without ultrasound guidance around the biceps tendon. Methods: Seven upper limb specialists, two general orthopedic specialists and three orthopedic surgical residents manually injected a cadaver elbow with acrylic dye using an anterior and a lateral infiltration approach. After infiltration the cadaveric elbows were dissected to determine the location of the acrylic dye. Results: In total, 79% of the injections were localized near the biceps tendon. Of these injections, 20% were localized on the radius near the bicipitoradial bursa. In total, 53% of the performed infiltrations were injected by anterior and 47% by lateral approaches. Of the injections near the distal biceps (79%), 47% were injected by an anterior and 53% by a lateral approach. Of the injections on the radius (20%), 33% were injected by anterior and 67% by lateral approach. Of the inaccurate injections (21%), 75% were injected anterior and 25% lateral. Conclusion Manual infiltration without ultrasound guidance for distal biceps pathology lacks accuracy. We therefore recommend ultrasound guidance for more accurate infiltration.

PURPOSE: When integrating molecularly targeted compounds in radiotherapy, synergistic effects of the systemic agent and radiation may extend the limits of patient tolerance, increasing the demand for understanding the pathophysiological mechanisms of treatment toxicity. In this Pelvic Radiation and Vorinostat (PRAVO) study, we investigated mechanisms of adverse effects in response to the histone deacetylase (HDAC) inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) when administered as a potential radiosensitiser. MATERIALS AND METHODS: This phase I study for advanced gastrointestinal carcinoma was conducted in sequential patient cohorts exposed to escalating doses of vorinostat combined with standard-fractionated palliative radiotherapy to pelvic target volumes. Gene expression microarray analysis of the study patient peripheral blood mononuclear cells (PBMC) was followed by functional validation in cultured cell lines and mice treated with SAHA. RESULTS: PBMC transcriptional responses to vorinostat, including induction of apoptosis, were confined to the patient cohort reporting dose-limiting intestinal toxicities. At relevant SAHA concentrations, apoptotic features (annexin V staining and caspase 3/7 activation, but not poly-(ADP-ribose)-polymerase cleavage) were observed in cultured intestinal epithelial cells. Moreover, SAHA-treated mice displayed significant weight loss. CONCLUSION: The PRAVO study design implemented a strategy to explore treatment toxicity caused by an HDAC inhibitor when combined with radiotherapy and enabled the identification of apoptosis as a potential mechanism responsible for the dose-limiting effects of vorinostat. To the best of our knowledge, this is the first report deciphering mechanisms of normal tissue adverse effects in response to an HDAC inhibitor within a combined-modality treatment regimen.
Animals ; Apoptosis* ; Cells, Cultured ; Clinical Trials, Phase I as Topic ; Cohort Studies ; Drug-Related Side Effects and Adverse Reactions ; Epithelial Cells ; Gene Expression ; Histone Deacetylase Inhibitors* ; Histone Deacetylases* ; Histones* ; Humans ; Hydroxamic Acids ; Mice ; Microarray Analysis ; Radiotherapy* ; Weight Loss