The effects of low intensity focused ultrasound on neuronal activity in pain processing regions in a rodent model of common peroneal nerve injury.

BACKGROUND: Non-invasive, external low intensity focused ultrasound (liFUS) offers promise for treating neuropathic pain when applied to the dorsal root ganglion (DRG). OBJECTIVE: We examine how external liFUS treatment applied to the L5 DRG affects neuronal changes in single-unit activity from the primary somatosensory cortex (SI) and anterior cingulate cortex (ACC) in a common peroneal nerve injury (CPNI) rodent model. METHODS: Male Sprague Dawley rats were divided into two cohorts: CPNI liFUS and CPNI sham liFUS. Baseline single-unit activity (SUA) recordings were taken 20 min prior to treatment and for 4 h post treatment in 20 min intervals, then analyzed for frequency and compared to baseline. Recordings from the SI and ACC were separated into pyramidal and interneurons based on waveform and principal component analysis. RESULTS: Following CPNI surgery, all rats (n = 30) displayed a significant increase in mechanical sensitivity. In CPNI liFUS rats, there was a significant increase in pyramidal neuron spike frequency in the SI region compared to the CPNI sham liFUS animals beginning at 120 min following liFUS treatment (p < 0.05). In the ACC, liFUS significantly attenuated interneuron firing beginning at 80 min after liFUS treatment (p < 0.05). CONCLUSION: We demonstrate that liFUS changed neuronal spiking in the SI and ACC regions 80 and 120 min after treatment, respectively, which may in part correlate with improved sensory thresholds. This may represent a mechanism of action how liFUS attenuates neuropathic pain. Understanding the impact of liFUS on pain circuits will help advance the use of liFUS as a non-invasive neuromodulation option.

Low Intensity Focused Ultrasound Increases Duration of Anti-Nociceptive Responses in Female Common Peroneal Nerve Injury Rats.

OBJECTIVE: Chronic pain affects 7%-10% of Americans, occurs more frequently and severely in females, and available treatments have been shown to have less efficacy in female patients. Preclinical models addressing sex-specific treatment differences in the treatment of chronic pain have been limited. Here we examine the sex-specific effects of low intensity focused ultrasound (liFUS) in a modified sciatic nerve injury (SNI) model. MATERIALS AND METHODS: A modified SNI performed by ligating the common peroneal nerve (CPN) was used to measure sensory, behavioral pain responses, and nerve conduction studies in female and male rats, following liFUS of the L5 dorsal root ganglion. RESULTS: Using the same dose of liFUS in females and males of the same weight, CPN latency immediately after treatment was increased for 50 min in females compared to 25 min in males (p < 0.001). Improvements in mechanical pain thresholds after liFUS lasted significantly longer in females (seven days; p < 0.05) compared to males (three days; p < 0.05). In females, there was a significant improvement in depression-like behavior as a result of liFUS (N = 5; p < 0.01); however, because males never developed depression-like behavior there was no change after liFUS treatment. CONCLUSIONS: Neuromodulation with liFUS has a greater effect in female rats on CPN latency, mechanical allodynia duration, and depression-like behavior. In order to customize neuromodulatory techniques for different patient phenotypes, it is essential to understand how they may alter sex-specific pathophysiologies.

Effects of external low intensity focused ultrasound on inflammatory markers in neuropathic pain.

BACKGROUND: Changes in inflammatory cytokine levels contribute to the induction and maintenance of neuropathic pain. We have shown that external low intensity focused ultrasound (liFUS) reduces allodynia in a common peroneal nerve injury (CPNI). Here, we investigate an underlying mechanism of action for this treatment and measure the effect of liFUS on inflammatory markers. METHODS: Male rats were divided into four groups: CPNI/liFUS, CPNI/shamliFUS, shamCPNI/liFUS, and shamCPNI/shamliFUS. Mechanical nociceptive thresholds were measured using Von Frey filaments (VFF) to confirm the absence/presence of allodynia at baseline, after CPNI, and after liFUS. Commercial microarray and ELISA assays were used to assess cytokine expression in the treated L5 dorsal root ganglion (DRG) and dorsal horn (DH) tissue 24 and 72 h after liFUS. RESULTS: VFF thresholds were significantly reduced following CPNI in both groups that received the injury (p < 0.001). After liFUS, only the CPNI/liFUS cohort showed a significant increase in mechanical thresholds (p < 0.001). CPNI significantly increased TNFa, IL6, CNTF, IL1b (p < 0.05 for all) levels in the DRG and DH, compared to baseline, consistent with previous work in sciatic nerve injury. LiFUS in CPNI rats resulted in a decrease in these cytokines in DRG 72 h post-therapy (TNFa, IL6, CNTF and IL1b, p < 0.001). In the DH, IL1b, CNTF, and TNFa (p < 0.05 for all) decreased 72 h after liFUS. CONCLUSION: We have demonstrated that liFUS modifies inflammatory cytokines in both DRG and DH in CPNI rats. These data provide evidence that liFUS, reverses the allodynic phenotype, in part, by altering inflammatory cytokine pathways.

Pilot study on the effects of low intensity focused ultrasound in a swine model of neuropathic pain.

OBJECTIVE: The authors' laboratory has previously demonstrated beneficial effects of noninvasive low intensity focused ultrasound (liFUS), targeted at the dorsal root ganglion (DRG), for reducing allodynia in rodent neuropathic pain models. However, in rats the DRG is 5 mm below the skin when approached laterally, while in humans the DRG is typically 5-8 cm deep. Here, using a modified liFUS probe, the authors demonstrated the feasibility of using external liFUS for modulation of antinociceptive responses in neuropathic swine. METHODS: Two cohorts of swine underwent a common peroneal nerve injury (CPNI) to induce neuropathic pain. In the first cohort, pigs (14 kg) were iteratively tested to determine treatment parameters. liFUS penetration to the L5 DRG was verified by using a thermocouple to monitor tissue temperature changes and by measuring nerve conduction velocity (NCV) at the corresponding common peroneal nerve (CPN). Pain behaviors were monitored before and after treatment. DRG was evaluated for tissue damage postmortem. Based on data from the first cohort, a treatment algorithm was developed, parameter predictions were verified, and neuropathic pain was significantly modified in a second cohort of larger swine (20 kg). RESULTS: The authors performed a dose-response curve analysis in 14-kg CPNI swine. Specifically, after confirming that the liFUS probe could reach 5 cm in ex vivo tissue experiments, the authors tested liFUS in 14-kg CPNI swine. The mean ± SEM DRG depth was 3.79 ± 0.09 cm in this initial cohort. The parameters were determined and then extrapolated to larger animals (20 kg), and predictions were verified. Tissue temperature elevations at the treatment site did not exceed 2°C, and the expected increases in the CPN NCV were observed. liFUS treatment eliminated pain guarding in all animals for the duration of follow-up (up to 1 month) and improved allodynia for 5 days postprocedure. No evidence of histological damage was seen using Fluoro-Jade and H&E staining. CONCLUSIONS: The results demonstrate that a 5-cm depth can be reached with external liFUS and alters pain behavior and allodynia in a large-animal model of neuropathic pain.

Modeling of Interstitial Ultrasound Ablation for Continuous Applicator Rotation With MR Validation.

The primary objective of cancer intervention is the selective removal of malignant cells while conserving surrounding healthy tissues. However, the accessibility, size and shape of the cancer can make achieving appropriate margins a challenge. One minimally invasive treatment option for these clinical cases is interstitial needle based therapeutic ultrasound (NBTU). In this work, we develop a finite element model (FEM) capable of simulating continuous rotation of a directional NBTU applicator. The developed model was used to simulate the thermal deposition for different rotation trajectories. The actual thermal deposition patterns for the simulated trajectories were then evaluated using magnetic resonance thermal imaging (MRTI) in a porcine skin gelatin phantom. An MRI-compatible robot was used to control the rotation motion profile of the physical NBTU applicator to match the simulated trajectory. The model showed agreement when compared to experimental measurements with Pearson correlation coefficients greater than 0.839 when comparing temperature fields within an area of 12.6 mm radius from the ultrasound applicator. The average temperature error along a 6.3 mm radius profile from the applicator was 1.27 °C. The model was able to compute 1 s of thermal deposition by the applicator in 0.2 s on average with a 0.1 mm spatial resolution and 0.5 s time steps. The developed simulation demonstrates performance suitable for real-time control which may enable robotically-actuated closed-loop conformal tumor ablation.

Effects of external low intensity focused ultrasound on electrophysiological changes in vivo in a rodent model of common peroneal nerve injury.

Non-invasive treatment methods for neuropathic pain are lacking. We assess how modulatory low intensity focused ultrasound (liFUS) at the L5 dorsal root ganglion (DRG) affects behavioral responses and sensory nerve action potentials (SNAPs) in a common peroneal nerve injury (CPNI) model. Rats were assessed for mechanical and thermal responses using Von Frey filaments (VFF) and the hot plate test (HPT) following CPNI surgery. Testing was repeated 24 h after liFUS treatment. Significant increases in mechanical and thermal sensory thresholds were seen post-liFUS treatment, indicating a reduction in sensitivity to pain (p < 0.0001, p = 0.02, respectively). Animals who received CPNI surgery had significant increases in SNAP latencies compared to sham CPNI surgery animals (p = 0.0003) before liFUS treatment. LiFUS induced significant reductions in SNAP latency in both CPNI liFUS and sham CPNI liFUS cohorts, for up to 35 min post treatment. No changes were seen in SNAP amplitude and there was no evidence of neuronal degeneration 24 h after liFUS treatment, showing that liFUS did not damage the tissue being modulated. This is the first in vivo study of the impact of liFUS on peripheral nerve electrophysiology in a model of chronic pain. This study demonstrates the effects of liFUS on peripheral nerve electrophysiology in vivo. We found that external liFUS treatment results in transient decreased latency in common peroneal nerve (CPN) sensory nerve action potentials (SNAPs) with no change in signal amplitude.

Low Intensity Focused Ultrasound Modulation of Vincristine Induced Neuropathy.

Previously, we showed internal low intensity focused ultrasound (liFUS) improves nociceptive thresholds in rats with vincristine-induced neuropathy (VIN) for 48-h post-treatment. Here, we perform more rigorous behavioral testing with the internal device and introduce external liFUS treatment. Behavioral testing confirmed VIN (Von Frey fibers, VFF; hot plate, HPT; locomotion, OFT). This was followed by internal or external liFUS treatment (2.5 W or 8 W, for 3 min, respectively) to the left L5 dorsal root ganglia (DRG). A thermocouple placed at the DRG documented temperature changes during treatment, to confirm the modulatory nature of our treatment. Behavioral testing was performed pre-liFUS, and for five consecutive days post-liFUS. Groups included: (1) VIN/liFUS, (2) saline/liFUS, (3) VIN/sham liFUS, and (4) saline/sham liFUS. Significant improvements in mechanical (VFF) and thermal (HPT) nociceptive thresholds were seen in the VIN/liFUS group following both internal and external treatment. Hematoxylin and Eosin, and Fluorojade staining showed no histological damage to the DRG. Internal liFUS treatment produced a mean temperature rise of 3.21 ±â€¯0.30 °C, whereas external liFUS resulted in a mean temperature rise of 1.78 °C ±â€¯0.21 °C. We demonstrate that, in a VIN rat model, external liFUS treatment of the L5 DRG significantly reduces nociceptive sensitivity thresholds without causing tissue damage.

The use of focused ultrasound for the treatment of cutaneous allodynia associated with chronic migraine.

Chronic migraines (CM) are the third most common disease and are refractory to medical treatment in 15% of patients. Currently, temporary relief is achieved with steroid blocks or pulsed radiofrequency ablation, which have short-term benefits. Our project aims to develop a non-invasive treatment for medically refractory chronic migraine, which does not require a permanent implant. This project investigates the safety and effectiveness of pulsed focused ultrasound (FUS) in a validated rodent headache model of cutaneous allodynia associated with chronic migraine (CM) as compared to sumatriptan and ablative lesioning. We demonstrate a significant reduction in mechanical thresholds as measured through Von Frey filaments in CM in the forepaw and periorbital region (p < 0.001). Sumatriptan and pulsed FUS both significantly improve thresholds at day 3 after treatment in the periorbital region. Ablative lesioning has no effect. This study provides initial evidence that FUS may provide an important therapeutic option for patients suffering from CM.

External focused ultrasound treatment for neuropathic pain induced by common peroneal nerve injury.

Neuropathic pain caused by nerve injury or compressive lesions is a debilitating condition lacking effective, long-term treatments. Our objective was to assess the effects of external focused ultrasound on sensory thresholds utilizing a common peroneal injury rat model. CPNI was induced by ligating the CPN of the left hind paw. Neuropathic phenotype was confirmed using the Von Frey Fibers (VFF) with a 50% mechanical detection threshold below 4.0. The Place Escape Avoidance Paradigm (PEAP) was employed as a behavioral correlate. External FUS treatment was applied to the left L4,5 DRG at 8 W for 3-min. There were two treatment groups; one received a single FUS treatment, while the other received two. Control groups consisted of one sham CPNI group that received FUS treatment and a CPNI group that received sham FUS treatment. Behavioral tests were conducted pre-CPNI surgery, 1-week post-surgery, and for 1-week post-FUS treatment(s). CPNI surgery resulted in lower VFF mechanical thresholds in the left hind paw compared to baseline (p < 0.0001) and increased proportion of time spent on bright side compared to baseline values on PEAP (p = 0.0473), indicating neuropathic state. FUS treatment increased VFF thresholds after 24-hours (p < 0.0001), 48-h (p = 0.0079), and 72-h (p = 0.0164). VFF returned to baseline values from day 4-7. Following a second FUS treatment on day 8, increased mechanical thresholds were similarly observed after 24-h (p = 0.0021), 48-h (p < 0.0001), and 72-h (p = 0.0256). Control group analysis showed (1) CPNI rats experienced no change in mechanical thresholds following sham FUS treatment and (2) Sham CPNI rats receiving FUS did not experience significantly different mechanical thresholds compared to baseline and post-CPNI values. Post-FUS histological analysis demonstrated healthy ganglion cells without chromatolysis. Our results demonstrate changes in VFF and PEAP in rats who underwent CPNI. Single and multiple doses of external FUS increase mechanical thresholds without inducing histological damage. Based on our results, we have demonstrated the potential of FUS to serve as a non-pharmacological and non-ablative neuromodulatory approach for the treatment of allodynia and neuropathic pain.

Patient knowledge and expectations in endoscopic sinus surgery.

BACKGROUND: The potential for patient misconceptions about endoscopic sinus surgery (ESS) has implications for the informed consent process. An understanding of patients' baseline knowledge and sources of information regarding ESS would improve surgeons' ability to counsel patients preoperatively and provide effective educational materials. METHODS: A prospective patient survey was performed at 2 independent tertiary care medical centers. Patients who were offered ESS as part of routine rhinology care were queried about expectations, knowledge, and sources of information regarding ESS before preoperative counseling. RESULTS: Of the 30 patients who completed the survey, 70% of patients reported doing research on ESS before the visit. The most common sources of information were friends and family (40%), YouTube (30.0%), and WebMD (26.7%). The most important factors researched included risks (95%), benefits (85%), and recovery related issues (70%). Patients in the younger group used healthcare and physician rating websites whereas none of the patients older than the median age of 44 years reported using them (33.3% vs 0%, p = 0.028). The older group more often relied upon healthcare providers than the younger group (71.5% vs 18.8%, p = 0.011). A range of responses were noted regarding early postoperative symptoms and recovery time. CONCLUSION: This study identified a varied understanding of ESS including significant misconceptions about risks, anesthesia, and need for ongoing therapy, among others. Patients obtain their information from a variety of sources including peers, other doctors, and the Internet. Awareness of the gaps in patient knowledge and the sources of information will improve preoperative counseling.

Pharyngeal Residue Severity Rating Scales Based on Fiberoptic Endoscopic Evaluation of Swallowing: A Systematic Review.

Identification of pharyngeal residue severity located in the valleculae and pyriform sinuses has always been a primary goal during fiberoptic endoscopic evaluation of swallowing (FEES). Pharyngeal residue is a clinical sign of potential prandial aspiration making an accurate description of its severity an important but difficult challenge. A reliable, validated, and generalizable pharyngeal residue severity rating scale for FEES would be beneficial. A systematic review of the published English language literature since 1995 was conducted to determine the quality of existing pharyngeal residue severity rating scales based on FEES. Databases were searched using controlled vocabulary words and synonymous free text words for topics of interest (deglutition disorders, pharyngeal residue, endoscopy, videofluoroscopy, fiberoptic technology, aspiration, etc.) and outcomes of interest (scores, scales, grades, tests, FEES, etc.). Search strategies were adjusted for syntax appropriate for each database/platform. Data sources included MEDLINE (OvidSP 1946-April Week 3 2015), Embase (OvidSP 1974-2015 April 20), Scopus (Elsevier), and the unindexed material in PubMed (NLM/NIH) were searched for relevant articles. Supplementary efforts to identify studies included checking reference lists of articles retrieved. Scales were compared using qualitative properties (sample size, severity definitions, number of raters, and raters' experience and training) and psychometric analyses (randomization, intra- and inter-rater reliability, and construct validity). Seven articles describing pharyngeal residue severity rating scales met inclusion criteria. Six of seven scales had insufficient data to support their use as evidenced by methodological weaknesses with both qualitative properties and psychometric analyses. There is a need for qualitative and psychometrically reliable, validated, and generalizable pharyngeal residue severity rating scales that are anatomically specific, image-based, and easily learned by both novice and experienced clinicians. Only the Yale Pharyngeal Residue Severity Rating Scale, an anatomically defined and image-based tool, met all qualitative and psychometric criteria necessary for a valid, reliable, and generalizable vallecula and pyriform sinus severity rating scale based on FEES.

Comparison of intranasal fluticasone spray, budesonide atomizer, and budesonide respules in patients with chronic rhinosinusitis with polyposis after endoscopic sinus surgery.

BACKGROUND: Nasal steroids are a critical part of the management of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) after endoscopic sinus surgery (ESS). Increasingly, practitioners are using budesonide respules delivered to the sinonasal cavities, which is an off-label use, in lieu of traditional nasal steroids. There has been little research comparing budesonide with traditional nasal steroids and the most effective delivery method of budesonide. METHODS: A randomized controlled trial was performed on patients after ESS for CRSwNP in a tertiary care center. Patients were randomized into 1 of 3 groups: group A received fluticasone nasal spray twice daily; group B received budesonide respules via a mucosal atomization device (MAD) twice daily; and group C received budesonide respules instilled via the vertex-to-floor (VF) position twice daily. Primary endpoints were 22-item Sino-Nasal Outcome Test (SNOT-22) and Lund-Kennedy scores at 6 months. RESULTS: Thirty-two patients were enrolled in the study, 23 of whom completed the 6-month trial. There were no significant differences among groups A, B, and C with respect to age, gender, asthma, aspirin sensitivity, or previous ESS. Group B had a statistically significant greater reduction in SNOT-22 and Lund-Kennedy scores at the primary endpoint of 6 months compared to groups A and C. Group C had the next greatest reduction, which was statistically significant, followed by group A. CONCLUSION: Patients treated with budesonide after ESS for CRSwNP had greater improvement in SNOT-22 and Lund-Kennedy scores compared to fluticasone at 6 months. The data supports the use of budesonide respules, particularly with a MAD, over fluticasone for CRSwNP patients after ESS.

The Yale Pharyngeal Residue Severity Rating Scale: An Anatomically Defined and Image-Based Tool.

The Yale Pharyngeal Residue Severity Rating Scale was developed, standardized, and validated to provide reliable, anatomically defined, and image-based assessment of post-swallow pharyngeal residue severity as observed during fiberoptic endoscopic evaluation of swallowing (FEES). It is a five-point ordinal rating scale based on residue location (vallecula and pyriform sinus) and amount (none, trace, mild, moderate, and severe). Two expert judges reviewed a total of 261 FEES evaluations and selected a no residue exemplar and three exemplars each of trace, mild, moderate, and severe vallecula and pyriform sinus residue. Hard-copy color images of the no residue, 12 vallecula, and 12 pyriform sinus exemplars were randomized by residue location for hierarchical categorization by 20 raters with a mean of 8.3 years of experience (range 2-27 years) performing and interpreting FEES. Severity ratings for all images were performed by the same 20 raters, 2 weeks apart, and with the order of image presentations randomized. Intra-rater test-retest reliability, inter-rater reliability, and construct validity were determined by pooled multi-category multi-rater kappa statistics. Residue ratings were excellent for intra-rater reliability for vallecula (kappa = 0.957 ± 0.014) and pyriform sinus (kappa = 0.854 ± 0.021); very good to excellent for inter-rater reliability for vallecula (kappa = 0.868 ± 0.011) and pyriform sinus (kappa = 0.751 ± 0.011); and excellent for validity for vallecula (kappa = 0.951 ± 0.014) and pyriform sinus (kappa = 0.908 ± 0.017). Clinical uses include accurate classification of vallecula and pyriform sinus residue severity patterns as none, trace, mild, moderate, or severe for diagnostic purposes, determination of functional therapeutic change, and precise dissemination of shared information. Scientific uses include tracking outcome measures, demonstrating efficacy of interventions to reduce pharyngeal residue, investigating morbidity and mortality in relation to pharyngeal residue severity, and improving training and accuracy of FEES interpretation by students and clinicians. The Yale Pharyngeal Residue Severity Rating Scale is a reliable, validated, anatomically defined, and image-based tool to determine residue location and severity based on FEES.

The correlation between obesity, obstructive sleep apnea, and superior semicircular canal dehiscence: a new explanation for an increasingly common problem.

OBJECTIVE: To investigate rates of obesity and obstructive sleep apnea (OSA) in patients with a diagnosis of superior semicircular canal dehiscence (SSCD). STUDY DESIGN: Retrospective cohort study. SETTING: Two tertiary referral centers. PATIENTS: Thirty-one patients with SSCD were identified from patient records at Yale between January 1, 2003 and August 1, 2013 and from the University of Cincinnati between November 1, 2008 and November 1, 2013. The control cohort consisted of 100 consecutive adult patients who obtained high-resolution CT imaging of their temporal bones at Yale University for any reason. INTERVENTIONS: CT images were reviewed by two authors in double blind fashion and patient data was analyzed statistically. MAIN OUTCOME MEASURES: Rates of OSA, body mass index (BMI), and presence of tegmental defects in patients with SSCD were compared to the control cohort. RESULTS: The 31 patients with SSCD demonstrated higher BMIs [SSCD avg. 31.62, standard deviation (SD) 8.6 vs. no SSCD 28.01, SD 6.3, P = 0.036], rates of OSA (SSCD 29.03% vs. no SSCD 7.00, P = 0.001), and rates of tegmental defects (SSCD avg. 64.5% vs. no SSCD 16%, P = 1.24 × 10(-7)), in comparison to the control cohort. SSCD was found in 6 of 100 consecutively reviewed adult CT scans and in 0 of 41 scans obtained in those under 17 years of age. CONCLUSIONS: Patients with SSCD demonstrated higher BMIs, higher rates of OSA, and were more likely to have accompanying tegmental defects. These results may support a possible causality between increased intracranial pressure and the formation of superior semicircular canal dehiscence.

Delayed platysma myocutaneous turnover flap for repair of pharyngocutaneous fistula.

INTRODUCTION: Pharyngocutaneous fistula (PCF) is a common and serious complication after total laryngectomy. Numerous surgical and non-surgical treatment approaches have been described. Here we describe a platysma myocutaneous turnover flap for repair of PCF. MATERIALS AND METHODS: Platysma myocutaneous turnover flap is described and two patients are used as examples. RESULTS: Repair was initially successful in both patients; however, one patient had recurrence of fistula after her cancer recurred at the stoma. DISCUSSION: Numerous surgical techniques have been described for repair of PCF. Here a turnover flap was used, a technique not previously described for this problem. The delay technique enhances the viability of the flap thought to be through numerous mechanisms. CONCLUSION: The platysma myocutaneous turnover flap is useful for closure of pharyngocutaneous fistula when non-operative measures have failed.

The impact of dairy consumption on salivary inoculum.

Quantitative levels of harmful oral microbes present following complex surgical excisions of head and neck cancer are important since wounds are often contaminated through direct connection to the oral cavity and its flora. This possibility is especially important in irradiated patients who have decreased protective salivary function. In addition, high oral microbial levels increase and intensify oral mucositis leading to significant morbidity in patients treated with radiation therapy. One previously untested surgical teaching to decrease the bacterial inoculum present in the oral cavity is to counsel patients against consuming otherwise nutritious dairy products, as they are thought to coat the oral cavity with rate-limiting nutrients vital for bacterial growth. This risk may extend to individuals with chronic laryngeal penetration or aspiration, since salivary bacterial load might represent a lethal threat in the presence of marginal pulmonary reserve. A crossover study using six healthy adult volunteers and six patients who had previously undergone radiation therapy to an oropharyngeal primary site was performed. Saliva samples were quantitatively cultured in both groups with and without the consumption of dairy products at 1-h and 5-h intervals. Analysis of quantitative cultures demonstrated that the consumption of dairy products had no influence on bacterial levels present in previously radiated subjects and nonirradiated controls. Additionally, the consumption of dairy did not affect the composition of microbes present. Due to the lack of changes in both quantity and composition of oral bacteria seen in this study, patients would not benefit from the avoidance of dairy products.

Ultrasound-guided characterization of interstitial ablated tissue using RF time series: feasibility study.

This paper presents the results of a feasibility study to demonstrate the application of ultrasound RF time series imaging to accurately differentiate ablated and nonablated tissue. For 12 ex vivo and two in situ tissue samples, RF ultrasound signals are acquired prior to, and following, high-intensity ultrasound ablation. Spatial and temporal features of these signals are used to characterize ablated and nonablated tissue in a supervised-learning framework. In cross-validation evaluation, a subset of four features extracted from RF time series produce a classification accuracy of 84.5%, an area under ROC curve of 0.91 for ex vivo data, and an accuracy of 85% for in situ data. Ultrasound RF time series is a promising approach for characterizing ablated tissue.

IL-17 producing gammadelta T cells are required for a controlled inflammatory response after bleomycin-induced lung injury.

BACKGROUND: gammadelta T cells play a key role in the regulation of inflammatory responses in epithelial tissue, and in adaptive immunity, as gammadelta T cell deficient mice have a severely impaired capacity to clear lung pathogens. gammadelta T cells regulate the initial inflammatory response to microbial invasion and thereby protect against tissue injury. Here we examined the response of gammadelta T cells to lung injury induced by bleomycin, in an effort to study the inflammatory response in the absence of any adaptive immune response to a pathogen. RESULTS: After lung injury by bleomycin, we localized the gammadelta T cells to the lung lesions. gammadelta T cells were the predominant source of IL-17 (as detected by flow cytometry and real-time PCR). Moreover, gammadelta T cell knockout mice showed a significant reduction in cellular infiltration into the airways, reduced expression of IL-6 in the lung, and a significant delay in epithelial repair. CONCLUSION: Mouse gammadelta T cells produce IL-17 in response to lung injury and are required for an organized inflammatory response and epithelial repair. The lack of gammadelta T cells correlates with increased inflammation and fibrosis.