Using the Real-Ear-to-Coupler Difference within the American Academy of Audiology Pediatric Amplification Guideline: Protocols for Applying and Predicting Earmold RECDs.

BACKGROUND: Real-ear-to-coupler difference (RECD) measurements are used for the purposes of estimating degree and configuration of hearing loss (in dB SPL ear canal) and predicting hearing aid output from coupler-based measures. Accurate measurements of hearing threshold, derivation of hearing aid fitting targets, and predictions of hearing aid output in the ear canal assume consistent matching of RECD coupling procedure (i.e., foam tip or earmold) with that used during assessment and in verification of the hearing aid fitting. When there is a mismatch between these coupling procedures, errors are introduced. PURPOSE: The goal of this study was to quantify the systematic difference in measured RECD values obtained when using a foam tip versus an earmold with various tube lengths. Assuming that systematic errors exist, the second goal was to investigate the use of a foam tip to earmold correction for the purposes of improving fitting accuracy when mismatched RECD coupling conditions occur (e.g., foam tip at assessment, earmold at verification). STUDY SAMPLE: Eighteen adults and 17 children (age range: 3-127 mo) participated in this study. DATA COLLECTION AND ANALYSIS: Data were obtained using simulated ears of various volumes and earmold tubing lengths and from patients using their own earmolds. Derived RECD values based on simulated ear measurements were compared with RECD values obtained for adult and pediatric ears for foam tip and earmold coupling. RESULTS: Results indicate that differences between foam tip and earmold RECDs are consistent across test ears for adults and children which support the development of a correction between foam tip and earmold couplings for RECDs that can be applied across individuals. CONCLUSIONS: The foam tip to earmold correction values developed in this study can be used to provide improved estimations of earmold RECDs. This may support better accuracy in acoustic transforms related to transforming thresholds and/or hearing aid coupler responses to ear canal sound pressure level for the purposes of fitting behind-the-ear hearing aids.

Microbubbles are detected prior to larger bubbles following decompression.

Using dual-frequency ultrasound (DFU), microbubbles (<10 µm diameter) have been detected in tissue following decompression. It is not known if these microbubbles are the precursors for B-mode ultrasound-detectable venous gas emboli (bmdVGE). The purpose of this study was to determine if microbubbles could be detected intravascularly postdecompression and to investigate the temporal relationship between microbubbles and larger bmdVGE. Anesthetized swine (n = 15) were exposed to 4.0-4.5 ATA for 2 h, followed by decompression to 0.98 ATA. Microbubble presence and VGE grade were measured using DFU and B-mode ultrasound, respectively, before and for 1 h postdecompression, approximately every 4-5 min. Microbubbles appeared in the bloodstream postdecompression, both in the presence and absence of bmdVGE. In swine without bmdVGE, microbubbles remained elevated for the entire 60-min postdecompression period. In swine with bmdVGE, microbubble signals were detected initially but then returned to baseline. Microbubbles were not detected with the sham dive. Mean bmdVGE grade increased over the length of the postdecompression data collection period. Comparison of the two response curves revealed significant differences at 5 and 10 min postdecompression, indicating that microbubbles preceded bmdVGE. These findings indicate that decompression-induced microbubbles can 1) be detected intravascularly at multiple sites, 2) appear in the presence and absence of bmdVGE, and 3) occur before bmdVGE. This supports the hypothesis that microbubbles precede larger VGE bubbles. Microbubble presence may be an early marker of decompression stress. Since DFU is a low-power ultrasonic method, it may be useful for operational diving applications.

FDG-PET metabolic response predicts outcomes in anal cancer managed with chemoradiotherapy.

BACKGROUND: The aim was to investigate the correlation between (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) metabolic response to chemoradiotherapy and clinical outcomes in squamous cell carcinoma (SCC) of the anus. METHODS: A total of 48 patients with biopsy-proven anal SCC underwent FDG-PET scans at baseline and post chemoradiotherapy (54 Gy, concurrent 5-FU/mitomycin). Kaplan-Meier analysis was used to determine survival outcomes according to FDG-PET metabolic response. RESULTS: In all, 79% patients (n=38) had a complete metabolic response (CMR) at all sites of disease, 15% (n=7) had a CMR in regional nodes but only partial response in the primary tumour (overall partial metabolic response (PMR)) and 6% (n=3) had progressive distant disease despite CMR locoregionally (overall no response (NR)). The 2-year progression-free survival (PFS) was 95% for patients with a CMR, 71% for PMR and 0% for NR (P<0.0001). The 5-year overall survival (OS) was 88% in CMR, 69% in PMR and 0% in NR (P<0.0001). Cox proportional hazards regression analyses for PFS and OS found significant associations for incomplete (PMR+NR) vs complete FDG-PET response to treatment only, (HR 4.1 (95% CI: 1.5-11.5, P=0.013) and 6.7 (95% CI: 2.1-21.6, P=0.002), respectively). CONCLUSION: FDG-PET metabolic response to chemoradiotherapy in anal cancer is significantly associated with PFS and OS, and in this cohort incomplete FDG-PET response was a stronger predictor than T or N stage.

Clinical responses observed with imatinib or sorafenib in melanoma patients expressing mutations in KIT.

BACKGROUND: Mutations in KIT are more frequent in specific melanoma subtypes, and response to KIT inhibition is likely to depend on the identified mutation. METHODS: A total of 32 patients with metastatic acral or mucosal melanoma were screened for mutations in KIT exons 11, 13 and 17. RESULTS: KIT mutations were found in 38% of mucosal and in 6% of acral melanomas. Three patients were treated with imatinib and one with sorafenib. All four patients responded to treatment, but three have since progressed within the brain. CONCLUSION: The observed clinical responses support further investigation of KIT inhibitors in metastatic melanoma, selected according to KIT mutation status.

Evaluation of pulmonary nodules and lung cancer with one-inch crystal gamma coincidence positron emission tomography/CT versus dedicated positron emission tomography/CT.

Dedicated positron emission tomography (PET)/CT scanners using BGO and related detectors (d-PET) have become standard imaging instruments in many malignancies. Hybrid gamma camera systems using NaI detectors in coincidence mode (g-PET) have been compared to d-PET but reported usefulness has been variable when gamma cameras with half-inch to three-fourth-inch thick crystals have been used without CT. Our aim was to compare g-PET with a 1-in.-thick crystal and inbuilt CT for lesion localization and attenuation correction (g-PET/CT) and d-PET/CT in patients presenting with potential and confirmed lung malignancies. One hour after (18)F-fluorodeoxyglucose (FDG), patients underwent BGO d-PET/CT from jaw to proximal thigh. This was followed by one to two bed position g-PET/CT 194 +/- 27 min after FDG. Each study pair was independently analysed with concurrent CT. d-PET/CT was interpreted by a radiologist experienced in both PET and CT, and g-PET/CT by consensus reading of an experienced PET physician and an experienced CT radiologist. A TNM score was assigned and studies were then unblinded and compared. Fifty-seven patients underwent 58 scan pairs over 2 years. Eighty-nine per cent concordance was shown between g-PET/CT and d-PET/CT for the assessment of intrapulmonary lesions, with 100% concordance for intrapulmonary lesions >10 mm (36 of 36). Eighty-eight per cent (51 of 58) concordance was shown between g-PET/CT and d-PET/CT for TNM staging. Coincidence imaging using an optimized dual-head 1-in.-thick crystal gamma camera with inbuilt CT compares reasonably well with dedicated PET/CT for evaluation of indeterminate pulmonary lesions and staging of pulmonary malignancies and may be of some value when d-PET/CT is not readily available.

Comparison of transendocardial and retrograde coronary venous intramyocardial catheter delivery systems in healthy and infarcted pigs.

UNLABELLED: We compared two routes for myocardial delivery of therapeutics, transendocardial (TE) delivery with an intramyocardial injection catheter, and retrograde coronary venous (RCV) delivery with a balloon occlusion catheter in the interventricular vein. METHODS: TE and RCV injection of 15 microM, neutron-activatable microspheres was compared in healthy pigs (Group I, n = 3), pigs with a 1-week-old myocardial infarction (MI; group II, n = 5), and pigs with a 2-weeks-old MI (group III, n = 4). The MI was induced by a 1-hr balloon occlusion in the LAD. Both methods were compared in the same animal using different microspheres. The RCV catheter allowed for continuous measurement of distal pressure and 2.5 x 10(6) microspheres were injected in 10 ml at 300 mmHg above balloon occlusion pressure. The TE injections were targeted to the infarct zone and 2.5 x 10(6) microspheres were distributed over 10 injections of 200 microl. RESULTS: The retention of microspheres decreased with increase in MI age, but was comparable between devices within the groups. RCV delivery resulted in (14.3 +/- 0.9)% microsphere retention in Group I, (10.3 +/- 0.2)% in Group II, and (6.4 +/- 0.1)% in group III (P < 0.05 versus group I). Microsphere retention after TE was (15.1 +/- 0.7)% in group I, (18.9 +/- 0.6)% in group II, (4.1 +/- 0.1)% in Group III (P < 0.05 versus groups I and II). The RCV catheter delivered primarily to midventricular, antero-septal segments, whereas TE targeted apical areas predominantly. CONCLUSIONS: Delivery efficacy was comparable between devices in each group however RCV targeted midventricular areas whereas TE targeted apical areas.

Inhibition of in-stent restenosis by oral copper chelation in porcine coronary arteries.

Stress-induced release of IL-1alpha and fibroblast growth factor-1 is dependent on intracellular copper and is a major driver of neointimal hyperplasia. Therefore, we assessed the effect of tetrathiomolybdate (TTM), a clinically proven copper chelator, on in-stent restenosis. Nine pigs were treated with TTM (5 mg/kg po) twice daily for 2 wk before stent implantation and for 4 wk thereafter, and nine pigs served as controls. In-stent restenosis was assessed by quantitative coronary angiography (QCA), intravascular ultrasound (IVUS), and histomorphometry. Serum ceruloplasmin activity was used as a surrogate marker of copper bioavailability. In TTM-treated animals, ceruloplasmin dropped 70 +/- 10% below baseline levels. Baseline characteristics were comparable in TTM-treated and control animals. At 4-wk follow-up, all parameters relevant to in-stent restenosis were significantly reduced in TTM-treated animals: minimal lumen diameter by QCA was 2.03 +/- 0.57 and 1.47 +/- 0.45 mm in TTM-treated and control animals, respectively (P < 0.05), percent stenosis diameter was 39% less in TTM-treated animals (27.1 +/- 16.6% vs. 44.5 +/- 16.1%, P < 0.05), minimal lumen area by IVUS was 60% larger in TTM-treated animals (4.27 +/- 1.56 vs. 2.67 +/- 1.19 mm(2), P < 0.05), and neointimal volume by histomorphometry was 37% less in TTM-treated animals (34.9 +/- 11.5 vs. 55.2 +/- 19.6 mm(3), P < 0.05). We conclude that systemic copper chelation with a clinically approved chelator significantly inhibits in-stent restenosis.

Nonlinear dynamics of respiratory patterns during maturation.

OBJECTIVES: In this paper, we quantify the fractal scaling characteristics of phrenic neurograms during eupnea in piglets, the output of the respiratory neural network that accompany maturation We also attempt to investigate whether the fractal properties are altered with maturation. METHODS: The phrenic neurogram in piglets was recorded from the C5 phrenic nerve during eupnea at four postnatal ages; the 3-6 days, the 7-14 days, 15-21 days and the 26-31 days age groups and analyzed using the maximum likelihood estimator (MLE). RESULTS: Our results suggest that the mean fractal measures over a recording of five consecutive breaths during eupnea for each piglet in each group were higher during the first 6 days and slightly decreased for the 7-14 days and significantly decreased for the 15-21 days and significantly increased for subsequent maturation (the 26-31 days old group). CONCLUSIONS: We suggest that there is a significant alteration in the fractal organization in piglet respiratory patterns during maturation and a decrease in the fractal value is unique to the 15-21 days old group.

Microwave thermal imaging: initial in vivo experience with a single heating zone.

The deployment of hyperthermia as a routine adjuvant to radiation or chemotherapy is limited largely by the inability to devise treatment plans which can be monitored through temperature distribution feedback during therapy. A non-invasive microwave tomographic thermal imaging system is currently being developed which has previously exhibited excellent correlation between the recovered electrical conductivity of a heated zone and its actual temperature change during phantom studies. To extend the validation of this approach in vivo, the imaging system has been re-configured for small animal experiments to operate within the bore of a CT scanner for anatomical and thermometry registration. A series of 5-7 day old pigs have been imaged during hyperthermia with a monopole antenna array submerged in a saline tank where a small plastic tube surgically inserted the length of the abdomen has been used to create a zone of heated saline at pre-selected temperatures. Tomographic microwave data over the frequency range of 300-1000 MHz of the pig abdomen in the plane perpendicular to the torso is collected at regular intervals after the tube saline temperatures have settled to the desired settings. Images are reconstructed over a range of operating frequencies. The tube location is clearly visible and the recovered saline conductivity varies linearly with the controlled temperature values. Difference images utilizing the baseline state prior to heating reinforces the linear relationship between temperature and imaged saline conductivity. Demonstration of in vivo temperature recovery and correlation with an independent monitoring device is an important milestone prior to clinical integration of this non-invasive imaging system with a thermal therapy device.

Real-ear-to-coupler difference predictions as a function of age for two coupling procedures.

The predicted real-ear-to-coupler difference (RECD) values currently used in pediatric hearing instrument prescription methods are based on 12-month age range categories and were derived from measures using standard acoustic immittance probe tips. Consequently, the purpose of this study was to develop normative RECD predicted values for foam/acoustic immittance tips and custom earmolds across the age continuum. To this end, RECD data were collected on 392 infants and children (141 with acoustic immittance tips, 251 with earmolds) to develop normative regression equations for use in deriving continuous age predictions of RECDs for foam/acoustic immittance tips and earmolds. Owing to the substantial between-subject variability observed in the data, the predictive equations of RECDs by age (in months) resulted in only gross estimates of RECD values (i.e., within +/- 4.4 dB for 95% of acoustic immittance tip measures; within +/- 5.4 dB in 95% of measures with custom earmolds) across frequency. Thus, it is concluded that the estimates derived from this study should not be used to replace the more precise individual RECD measurements. Relative to previously available normative RECD values for infants and young children, however, the estimates derived through this study provide somewhat more accurate predicted values for use under those circumstances for which individual RECD measurements cannot be made.

Comparison of photosensitizer (AIPcS2) quantification techniques: in situ fluorescence microsampling versus tissue chemical extraction.

A noninvasive in situ fluorescence-based method for the quantification of the photosensitizer chloroaluminum disulfonated phthalocyanine was compared to the highly accurate but nonreal time ex vivo spectrofluorometry method. Our in vivo fluorescence technique is designed to allow real-time assessment of photosensitizer in tumor and normal tissues and therefore temporally optimal light delivery. Laser-induced fluorescence was used to measure photosensitizer concentration from multiple microscopic regions of tissue. Ex vivo chemical extraction was used to quantify photosensitizer concentration in the same volume of tissue. The amount of photosensitizer in the vascular and/or parenchymal compartments of skeletal muscle and liver was determined by quantifying fluorescent signal in vivo, ex vivo and after blood removal. Confocal microscopy was used to spatially document photosensitizer localization 30 min and 24 h after delivery. While a linear correlation can exist between the fluorescence intensity measured by our fiber-optic bundle system and actual tissue concentration, temporal changes to this calibration line exist as the photosensitizer changes its partitioning fraction between the blood (vasculature) and the tissue parenchyma. In situ photosensitizer fluorescence microsampling (dosimetry) systems can be performed in real time and linearly correlated to actual tissue concentration with minimal intertissue variance. Tissue-specific differences may require temporal alterations in the calibration.

Microwave thermal keratoplasty for myopia: keratoscopic evaluation in porcine eyes.

PURPOSE: Microwave thermal keratoplasty applies microwave energy to elevate the temperature of the paracentral stroma of the cornea to its thermal shrinkage temperature of about 60 degrees C. A suitable pattern of shrinkage in the paracentral cornea can flatten the central cornea. A surface cooling system preserves the epithelium during the procedure. METHODS: Fourteen enucleated porcine eyes were treated with a prototype microwave thermal keratoplasty applicator that heated in a ring pattern with inner diameter of 3.2 mm and width of 0.7 mm. The change in corneal power was quantified by a videokeratoscope. Slit-lamp microscope examinations and histological assessments were made. RESULTS: The 3-mm simulated keratometry reading showed an average of 6.60+/-6.00 D (standard deviation) of flattening. The region of opacity associated with shrinkage extended to 62% (+/-26%) of the corneal thickness. The epithelium was intact in all eyes. CONCLUSIONS: Microwave thermal keratoplasty applied in the paracentral cornea may flatten the central cornea.

Postnatal development of corneal curvature and thickness in the cat.

OBJECTIVE: To evaluate the postnatal development of central corneal curvature and thickness in the domestic cat. Animals studied Six Domestic Short-haired (DSH) kittens starting at 9 weeks of age and 6 adult cats. PROCEDURES: Kittens were evaluated biweekly to monthly for a 12-month period, starting at age 9 weeks. Corneal development was monitored by hand-held keratometry and ultrasound biomicroscopy. Standard regression analysis using a nonlinear least squares method was used to generate a formula that would predict corneal curvature as a function of age. RESULTS: Mean keratometry (K) values for the 9-week-old cats were 54.51 (+/-1.02) diopters (D) and these values steeply declined over the next 3 months to 44.95 (+/-0.90) D. Thereafter, K-values gradually decreased to reach a plateau by 12-15 months of age of 39.90 (+/-0.42) D. Because K-values still appeared to be slightly diminishing at this point, six other > 2-year-old cats were evaluated by keratometry and were found to have K-values of 38.99 (+/-0.81). Two to four diopters of astigmatism was common in young kittens whereas adult cats had a low mean degree of astigmatism (< 1 D). A formula that predicted keratometry values in diopters (K) as a function of age in weeks (w) was established as follows: K = 39.83 + 26.87 exp(-0.074 w). The central cornea increased in thickness primarily during the first 4 months of life with 9 week-old kittens having values of 0.379 (+/-0.012) mm; 16-week-old kittens, 0.548 (+/-0.021) mm and 67 week-old cats, 0.567 (+/-0.012) mm. CONCLUSIONS: The maturation process of the feline cornea proceeds over the first 1-2 years of life to attain an adult status that is characterized by a roughly spherical state of approximately 39 D corneal curvature, substantially flatter than the human cornea, and a central thickness similar to the human cornea. Research studies of the refractive or optical properties of the cornea in which cats are used as experimental animals should be conducted on animals greater than 18 months of age.

Preferred listening levels of children who use hearing aids: comparison to prescriptive targets.

The preferred listening levels (PLLs) of children with sensorineural hearing loss were elicited using conversation-level speech, heard through the children's own hearing aids. All hearing aids were fitted using the desired sensation level (DSL) method. Comparisons were made between the PLL and targets from the following prescriptive formulae: DSL version 4.1 and two versions of the National Acoustic Laboratories (NAL) procedure, including NAL revised for severe-profound losses (NAL)-RP and NAL nonlinear NAL/NL1. Results for this sample of children indicated that the PLL was similar to the DSL targets, and that, on average, NAL-RP/NL1 targets recommended less gain than that preferred by the majority of children in this study. The implications of factors such as acclimatization, test levels, and clinical procedures on these results are discussed.

Predictive validity of a procedure for pediatric hearing instrument fitting.

In 1994, Moodie, Seewald, & Sinclair described the development of a clinical procedure for predicting real-ear hearing instrument performance in young children. The purpose of the present study was to determine the validity of this procedure for predicting the real-ear aided gain (REAG) and real-ear saturation response (RESR) of hearing instruments worn by children. To this end, both the REAG and RESR were measured, through probe-microphone measures, and predicted, using the Moodie et al. procedure. The findings confirmed that the 2-cc coupler-based procedure, with individualized acoustic transforms, described by Moodie et al., resulted in highly accurate predictions of real-ear hearing instrument performance for both REAG and RESR at five test frequencies. The implications of these findings for the clinical fitting of hearing instruments in infants and young children are discussed.

The esophageal detector device can give false positives for tracheal intubation.

The esophageal detector device is a useful, inexpensive, portable device for the detection of inadvertent intubation of the esophagus. It has been extensively tested. It is very accurate with occasional false negatives for tracheal intubation but only two reported cases of false positives for tracheal intubation previously described. This article presents two further cases of false positives for tracheal intubation using the esophageal detector device and warns that although it is the more accurate of the cheap and portable devices available, it is not perfect.

Safety and immunogenicity of a new Haemophilus influenzae type b vaccine in infants under one year of age.

64 healthy infants 2-3 months old, were randomly assigned to one of three vaccination groups which received either diphtheria-pertussis-tetanus (DPT) vaccine, Haemophilus influenzae type b capsular polysaccharide polyribosyl-ribitol phosphate (PRP) vaccine, or PRP + P (with pertussis adjuvant) vaccine in three doses at intervals of 2 months. Local and systemic reactions occurred most frequently after DPT vaccination and least frequently for PRP alone. Data for 60 infants from whom complete sera sets were available indicated that 70% of the infants who received three doses of PRP + P showed 2-fold or greater increases in titres of antibody to PRP with final values above the level assumed to give protection against invasive H. influenzae type b disease (greater than or equal to 0.15 microgram/ml). In contrast, less than 10% of the infants who received PRP vaccine alone showed 2-fold or greater increases.