Clinical and diagnostic evaluation of intraocular expulsion of a corneal epithelial inclusion cyst in a dog.

CASE DESCRIPTION: An 8-year-old spayed female mixed-breed dog was presented for evaluation of an axial, raised, vascularized, lightly pigmented 3 mm diameter corneal lesion affecting the left eye (OS) that was present since adoption three years prior to presentation. The presumed cyst ruptured into the anterior chamber 5 months following initial presentation with progressive extrusion of intralesional contents into the anterior chamber. High-frequency ultrasound and in vivo confocal microscopy revealed minimal normal stroma posterior to the corneal lesion. Due to the lack of stroma, a deep anterior lamellar keratoplasty (DALK) was attempted using the viscodissection technique. While separating the stroma from Descemet's membrane, a tear in the membrane was observed, and the procedure was converted to a penetrating keratoplasty (PK). The mass was excised en bloc, and a frozen corneal allograft and conjunctival pedicle graft were utilized to restore corneal thickness. The extruded material was irrigated out of the anterior chamber and submitted for culture and cytology. There was no growth on aerobic, anaerobic, or fungal cultures, and cytology revealed mixed neutrophilic and macrophagic inflammation with keratinizing squamous epithelium. Histopathology identified the mass to be a corneal epithelial inclusion cyst lined with well-differentiated stratified squamous epithelium. The dog is doing well 10 months post-operatively with no signs of recurrence along with good comfort and vision.

Exploring the Neural Bases of Primary Muscle Tension Dysphonia: A Case Study Using Functional Magnetic Resonance Imaging.

Primary muscle tension dysphonia (pMTD) is a voice disorder that occurs in the absence of laryngeal pathology. Dysregulated activity of the paralaryngeal muscles is considered the proximal cause; however, the central origin of this aberrant laryngeal muscle activation is unclear. The Trait Theory (Roy and Bless, 2000a,b) proposed that specific personality traits can predispose one to laryngeal motor inhibition and pMTD, and this inhibition is mediated by a hyperactive "behavioral inhibition system (BIS)" composed of limbic system structures (and associated prefrontal connections). This case study used functional magnetic resonance imaging to detect brain activation changes associated with successful management of pMTD, thereby evaluating possible neural correlates of this poorly understood disorder. METHOD: A 61-year-old woman with moderate-to-severe pMTD underwent functional magnetic resonance imaging scans before and immediately after successful treatment using manual circumlaryngeal techniques. Experimental stimuli were blocks of repeated vowel production and overt sentence reading. RESULTS: Significantly greater activation was observed pre- versus posttreatment in all regions of interest during sentence production, that is, periaqueductal gray, amygdala, hypothalamus, anterior cingulate cortex, hippocampus, dorsolateral prefrontal cortex, Brodmann area 10, and premotor and inferior sensorimotor cortex. CONCLUSIONS: Our findings are compatible with overactivation of neural regions associated with the BIS (cingulate cortex, amygdala, hypothalamus, periaqueductal gray) and motor inhibition networks (eg, [pre-]supplementary motor area) along with the dorsolateral prefrontal cortex and medial prefrontal cortex. Heightened input from limbic regions combined with dysfunctional prefrontal regulation may interfere with laryngeal motor preparation, initiation, and execution thereby contributing to disordered voice in pMTD.

Ophthalmic examination findings and intraocular pressures in wild-caught African giant pouched rats (Cricetomys spp.).

PURPOSE: To report ophthalmic examination findings and intraocular pressures (IOPs) in wild-caught African giant pouched rats (Cricetomys ansorgei and gambianus) from Tanzania and Ghana. PROCEDURES: After being placed under general anesthesia for examination, slit-lamp biomicroscopy before and after pharmacologic mydriasis and indirect ophthalmoscopy was performed. Eyes were fluorescein stained and IOPs measured by rebound tonometry using the TonoVet® . RESULTS: Thirty-two sexually mature pouched rats (64 eyes) were examined, including 16 males and 16 females. The mean IOP (± standard deviation) was 7.7 (±2.9) mmHg. Fluorescein staining was negative in all eyes. One or more ocular abnormalities were detected in 21 pouched rats (35 eyes). These ocular lesions included the following: lens opacities (n = 23 eyes), persistent pupillary membranes (n = 5), chorioretinal scarring (n = 3), corneal vascularization (n = 2), palpebral margin defect with focal trichiasis (n = 2), phthisis bulbi (n = 1), and posterior synechiae (n = 1). Lens opacities included incipient anterior cortical opacities (n = 7), immature cataract (n = 6), incipient nuclear opacities (n = 5), punctate pigment on anterior lens capsule (n = 2 eyes), incipient suture tip opacities (n = 2), and hypermature cataract (n = 1). CONCLUSIONS: Ocular abnormalities were common in the evaluated population of giant pouched rats; however, most of the detected lesions were mild and believed to have minimal impact on vision. Rebound tonometry with the TonoVet® was a reliable and simple technique to measure IOPs in the anesthetized pouched rats.

Design, synthesis and SAR of substituted indoles as selective TrkA inhibitors.

A series of substituted indoles were examined as selective inhibitors of tropomyosin-related kinase receptor A (TrkA), a therapeutic target for the treatment of pain. An SAR optimization campaign based on ALIS screening lead compound 1 is reported.

Structural characterization of nonactive site, TrkA-selective kinase inhibitors.

Current therapies for chronic pain can have insufficient efficacy and lead to side effects, necessitating research of novel targets against pain. Although originally identified as an oncogene, Tropomyosin-related kinase A (TrkA) is linked to pain and elevated levels of NGF (the ligand for TrkA) are associated with chronic pain. Antibodies that block TrkA interaction with its ligand, NGF, are in clinical trials for pain relief. Here, we describe the identification of TrkA-specific inhibitors and the structural basis for their selectivity over other Trk family kinases. The X-ray structures reveal a binding site outside the kinase active site that uses residues from the kinase domain and the juxtamembrane region. Three modes of binding with the juxtamembrane region are characterized through a series of ligand-bound complexes. The structures indicate a critical pharmacophore on the compounds that leads to the distinct binding modes. The mode of interaction can allow TrkA selectivity over TrkB and TrkC or promiscuous, pan-Trk inhibition. This finding highlights the difficulty in characterizing the structure-activity relationship of a chemical series in the absence of structural information because of substantial differences in the interacting residues. These structures illustrate the flexibility of binding to sequences outside of-but adjacent to-the kinase domain of TrkA. This knowledge allows development of compounds with specificity for TrkA or the family of Trk proteins.

Sudden acquired retinal degeneration in dogs: breed distribution of 495 canines.

PURPOSE: The purpose of this study was to describe breed, age, gender, and weight distribution of dogs affected with sudden acquired retinal degeneration (SARD) and to investigate whether SARD is more common in small breed dogs. METHODS: Medical records of dogs diagnosed with SARD confirmed by an electroretinogram were reviewed. Breed, age, gender, and weight were recorded when available. The same data were obtained for dogs with SARD described in the veterinary literature. RESULTS: Three hundred and two dogs were included from the ophthalmology practices and 193 dogs from the veterinary literature. Sixty breeds were present in the study. Mixed-breed dogs were the most common at 108 dogs (21.8%), followed by the Dachshund (68, 13.7%), Chinese Pug (44, 8.9%), Miniature Schnauzer (39, 7.9%), Maltese (23, 4.6%), Cocker Spaniel (22, 4.4%), Bichon Frise (18, 3.6%), Beagle (16, 3.2%), Brittany (15, 3.0%), and Pomeranian (10, 2.0%). Fifty other breeds were represented by 1-9 dogs each. The median age was 9 years (range = 10 months-16 years). The weight was known for 197 dogs. About 60.9% of dogs were less than 25 pounds, 31.5% were between 25 and 50 pounds, and 7.6% were greater than 50 pounds. Gender was recorded in 393 dogs: 217 female dogs and 176 male dogs. CONCLUSIONS: As previously reported, SARD is most common in middle-aged to older dogs. Smaller dogs of less than 25 pounds appear overrepresented, while large/giant breed dogs of greater than 50 pounds are infrequently diagnosed. In this study, there was no statistical significance between female and male dogs.

Objective Measures of Swallowing Function Applied to the Dysphagia Population: A One Year Experience.

Quantitative, reliable measures of swallowing physiology can be made from an modified barium swallowing study. These quantitative measures have not been previously employed to study large dysphagic patient populations. The present retrospective study of 139 consecutive patients with dysphagia seen in a university tertiary voice and swallowing clinic sought to use objective measures of swallowing physiology to (1) quantify the most prevalent deficits seen in the patient population, (2) identify commonly associated diagnoses and describe the most prevalent swallowing deficits, and (3) determine any correlation between objective deficits and Eating Assessment Tool (EAT-10) scores and body mass index. Poor pharyngeal constriction (34.5 %) and airway protection deficits (65.5 %) were the most common swallowing abnormalities. Reflux-related dysphagia (36 %), nonspecific pharyngeal dysphagia (24 %), Parkinson disease (16 %), esophageal abnormality (13 %), and brain insult (10 %) were the most common diagnoses. Poor pharyngeal constriction was significantly associated with an esophageal motility abnormality (p < 0.001) and central neurologic insult. In general, dysphagia symptoms as determined by the EAT-10 did not correlate with swallowing function abnormalities. This preliminary study indicates that reflux disease is common in patients with dysphagia and that associated esophageal abnormalities are common in dysphagic populations and may be associated with specific pharyngeal swallowing abnormalities. However, symptom scores from the EAT-10 did not correspond to swallowing pathophysiology.

Quantitative Measures of Swallowing Deficits in Patients With Parkinson's Disease.

OBJECTIVE: Dysphagia and associated aspiration pneumonia are commonly reported sequelae of Parkinson's disease (PD). Previous studies of swallowing in patients with PD have described prolonged pharyngeal transit time, delayed onset of pharyngeal transit, cricopharyngeal (CP) achalasia, reduced pharyngeal constriction, and slowed hyolaryngeal elevation. These studies were completed using inconsistent evaluation methodology, reliance on qualitative analysis, and a lack of a large control group, resulting in concerns regarding diagnostic precision. The purpose of this study was to investigate swallowing function in patients with PD using a norm-referenced, quantitative approach. METHODS: This retrospective study includes 34 patients with a diagnosis of PD referred to a multidisciplinary voice and swallowing clinic. Modified barium swallow studies were performed using quantitative measures of pharyngeal transit time, hyoid displacement, CP sphincter opening, area of the pharynx at maximal constriction, and timing of laryngeal vestibule closure relative to bolus arrival at the CP sphincter. RESULTS: Reduced pharyngeal constriction was found in 30.4%, and a delay in airway closure relative to arrival of the bolus at the CP sphincter was the most common abnormality, present in 62% of patients. Previously reported findings of prolonged pharyngeal transit, poor hyoid elevation, and CP achalasia were not identified as prominent features.

Voice, speech, and laryngeal features of primary Sjögren's syndrome.

OBJECTIVE: This study examined voice, speech, and laryngeal characteristics in primary Sjögren's syndrome (pSS). METHODS: Eleven patients (10 female, 1 male; mean [SD] age = 57 [14] years) from The University of Utah Division of Rheumatology provided connected speech and sustained vowel samples. Analyses included the Multi-Dimensional Voice Profile, the Analysis of Dysphonia in Speech and Voice, and dysphonia severity, speech clarity, and videolaryngostroboscopy ratings. RESULTS: Shimmer, amplitude perturbation quotient, and average fundamental frequency differed significantly from normative values (P < .01). Cepstral Spectral Index of Dysphonia values indicated mild-to-moderate dysphonia in connected speech (mean [SD] = 20.26 [8.36]) and sustained vowels (mean [SD] = 16.91 [11.08]). Ratings of dysphonia severity and speech clarity using 10-cm visual analog scales suggested mild-to-moderate dysphonia in connected speech (mean [SD] = 2.11 [1.72]) and sustained vowels (mean [SD] = 3.13 [2.20]) and mildly reduced speech clarity (mean [SD] = 1.46 [1.36]). Videolaryngostroboscopic ratings indicated mild-to-moderate dryness and mild reductions in overall laryngeal function. Voice Handicap Index scores indicated mild-to-moderate voice symptoms (mean [SD] = 43 [23]). CONCLUSION: Individuals with pSS may experience dysphonia and articulatory imprecision, typically in the mild-to-moderate range. These findings have implications for diagnostic and referral practices in pSS.

Comparing nebulized water versus saline after laryngeal desiccation challenge in Sjögren's Syndrome.

OBJECTIVES/HYPOTHESIS: This study examined the effects of a laryngeal desiccation challenge and two nebulized hydration treatments on phonation threshold pressure (PTP), vocal effort, and throat dryness in patients with chronic airway dryness. STUDY DESIGN: Double-blind, within-subjects crossover design. METHODS: Eleven individuals with Primary Sjögren's Syndrome received a 15-minute laryngeal desiccation challenge (breathing dry air-<1% relative humidity-transorally), followed by nebulized isotonic saline or nebulized water treatments (3 mL) on 2 consecutive weeks. PTP, as well as self-perceived vocal effort, mouth, and throat dryness were assessed before and after the desiccation challenge, and at 5, 35, and 65 minutes after the nebulized treatment. RESULTS: The laryngeal desiccation challenge produced statistically significant increases in PTP, vocal effort, and mouth and throat dryness (P < 0.05). Nebulized saline produced greater-but not statistically significant-treatment effects than water. PTP was more correlated with throat dryness than vocal effort. CONCLUSION: Patients with chronic airway dryness experienced phonatory changes following dry air exposure. Nebulized isotonic saline may offset this effect. Future research should explore dose-response relationships among dry air exposure, nebulized treatments, voice change, and self-perceived throat dryness.