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Glucose tolerance decreases with age. For determining the cause of this decrease, 67 elderly and 21 young (70.1 +/- 0.7 vs. 23.7 +/- 0.8 years) participants ingested a mixed meal and received an intravenous injection of glucose. Fasting glucose and the glycemic response above basal were higher in the elderly than in the young participants after either meal ingestion (P < 0.001) or glucose injection (P < 0.01). Insulin action (Si), measured with the meal and intravenous glucose tolerance test models, was highly correlated (r = 0.72; P < 0.001) and lower (P

Abstract: Support for a patient in the aftermath of a potentially traumatic event is enhanced when clinicians understand the normal reactions that may occur during the traumatization process. This article discusses recommendations from international and national guidelines as well as best practices from the medical and psychiatric literature to help guide clinicians providing care for acutely traumatized patients., (Copyright © 2021 American Academy of Physician Assistants.)

For more than two decades, the UCSC Genome Browser database (https://genome.ucsc.edu) has provided high-quality genomics data visualization and genome annotations to the research community. As the field of genomics grows and more data become available, new modes of display are required to accommodate new technologies. New features released this past year include a Hi-C heatmap display, a phased family trio display for VCF files, and various track visualization improvements. Striving to keep data up-to-date, new updates to gene annotations include GENCODE Genes, NCBI RefSeq Genes, and Ensembl Genes. New data tracks added for human and mouse genomes include the ENCODE registry of candidate cis-regulatory elements, promoters from the Eukaryotic Promoter Database, and NCBI RefSeq Select and Matched Annotation from NCBI and EMBL-EBI (MANE). Within weeks of learning about the outbreak of coronavirus, UCSC released a genome browser, with detailed annotation tracks, for the SARS-CoV-2 RNA reference assembly., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The University of California Santa Cruz Genome Browser website (https://genome.ucsc.edu) enters its 20th year of providing high-quality genomics data visualization and genome annotations to the research community. In the past year, we have added a new option to our web BLAT tool that allows search against all genomes, a single-cell expression viewer (https://cells.ucsc.edu), a 'lollipop' plot display mode for high-density variation data, a RESTful API for data extraction and a custom-track backup feature. New datasets include Tabula Muris single-cell expression data, GeneHancer regulatory annotations, The Cancer Genome Atlas Pan-Cancer variants, Genome Reference Consortium Patch sequences, new ENCODE transcription factor binding site peaks and clusters, the Database of Genomic Variants Gold Standard Variants, Genomenon Mastermind variants and three new multi-species alignment tracks., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Study Design: An observational study., Objective: The aim of this study was to evaluate the impact of a health plan's prior authorization (PA) programs for low back pain (LBP) in a non-Medicare population by assessing changes in pre-surgical nonoperative care; lumbar fusion trends; and overall back surgery rates compared with another health plan with a similar program and national benchmarks. The PA programs require mandatory physiatrist consultation before surgical evaluation, with subsequent additional LBP surgery PA., Summary of Background Data: LBP is prevalent and concern exists that spinal fusion is overutilized for LBP., Methods: Annual rates of lumbar fusion trended over 6 years, and analysis of changes in standardized costs for LBP-related services among a 501-member subset who underwent lumbar fusion before and after program implementations, during the period January 1, 2008, through December 31, 2013, among commercial members aged 18 and 65 years enrolled in a health maintenance organization with commercial membership averaging >500,000 annually., Results: After initiation of the physiatrist PA in December 2010, lumbar fusions decreased from 76.27/100,000 in 2010 to 62.63/100,000 in 2011 with subsequent increases to 64.24/100,000 and 73.84/100,000 in years 2012 and 2013. For members who had lumbar fusion, per-member, pre-surgical costs increased by $2,233 with the physiatrist PA and an additional $1,370 with implementation of the LBP surgery PA (March 2013). Spinal injections and inpatient admissions were the greatest contributors to the overall increase in costs. The physiatrist and LBP surgery PA programs were also associated with lengthening of LBP episodes ending in surgery by 309 and 198 days., Conclusion: Mandatory referral to a physiatrist before surgical evaluation did not result in persistent reduction in lumbar fusions. Instead, these programs were associated with the unintended consequence of increased costs from more nonoperative care for only a transitory change in the lumbar fusion rate, likely from delays due to the introduction of both PA programs., Level of Evidence: 3.

Objective: To determine the effect of once daily topical 0.3% naltrexone (NTX) on tear production, tear film breakup time (TFBUT), and corneal sensitivity in dogs with uncontrolled keratoconjunctivitis sicca (KCS)., Animals Studied: Sixteen dogs with uncontrolled KCS., Procedures: A randomized placebo-controlled trial was performed in 16 dogs with topical 0.3% NTX once daily or topical saline solution drops once daily. A baseline was obtained at week 0 for tear production (Schirmer tear test 1 and 2-STT1, STT2), TFBUT, and corneal sensitivity. STT1, STT2, and TFBUT were then subsequently measured at weeks 1, 2, and 4 while on NTX or saline drops. Corneal sensitivity measures were repeated at week 4. The drops were subsequently discontinued and all parameters rechecked at week 5., Results: There was no statistically significant difference in tear parameters or corneal sensitivity between the NTX-treated and the saline-treated groups., Conclusion: Topical 0.3% NTX given as a once daily dose over 4 weeks did not alter tear production, tear film stability, or corneal sensitivity in dogs with uncontrolled KCS., (© 2015 American College of Veterinary Ophthalmologists.)

Study Design: Prospective, nonrandomized study of children with congenital scoliosis., Objective: To determine the outcomes of children with congenital scoliosis using SRS-22., Summary of Background Data: Outcome measures in children with congenital scoliosis are unreported. Novel treatments such as VEPTR (vertical expandable prosthetic titanium rib) must show positive patient-reported outcomes during treatment because improvement in pulmonary function has not been demonstrated., Methods: Patients with congenital scoliosis were prospectively enrolled and divided into 3 groups: children under observation (OBSERVATION), children who had surgery (SURGICAL), and children treated with VEPTR (VEPTR). The SRS-22 questionnaire reports 6 domains: Total, Function, Mental Health, Image, Satisfaction, and Pain. SRS-22 questionnaires were prospectively collected from 184 OBSERVATION patients, 27 SURGICAL patients, and 22 VEPTR patients. Because of repeated measurement on each patient, the observations cannot be assumed to be independent. To account for this dependence, linear mixed models were used., Results: OBSERVATION scores were near normal in all domains. Initial postoperative scores for Function and Pain decreased for the SURGICAL group and subsequently Total, Function, Image, and Satisfaction scores increased. Initial postoperative VEPTR scores in Mental Health and Pain decreased and Total, Function, and Image scores increased during subsequent visits., Conclusion: Children with congenital scoliosis had SRS-22 scores that compare favorably with scores reported in the literature for adolescent idiopathic scoliosis. For SURGICAL and VEPTR patients with congenital scoliosis, SRS-22 Total, Function, and Image scores increased over time. Function, Image, and Pain require focus in children with congenital scoliosis. This is the first study that documents improvement in outcomes of VEPTR patients while in treatment., Level of Evidence: 2.

Objective: To determine the effect of topical naltrexone 0.3% on tear production, corneal sensitivity, and tear film stability in normal brachycephalic dogs., Animals Studied: Twenty-two normal brachycephalic dogs., Procedures: Measurements of tear production (Schirmer tear test I and II), intraocular pressure (IOP), central corneal sensitivity (CS), and tear film breakup time (TFBUT) were collected at time 0, 1, and 24 h after administration of either naltrexone (NTX) 0.3% or placebo (SV). Naltrexone or SV was then administered once daily for 1 week, and the above measurements were repeated at 7 days, then again 7 days after discontinuing medication. Owners scored the degree of comfort, redness, rubbing, squinting, and tearing. Serum was collected at time 0, 1, 24 h, and 7 days to determine systemic concentrations., Results: Owners reported no significant change in the degree of comfort, redness, rubbing, squinting, or tearing. Naltrexone was detected in serum of all treated dogs 1-h postadministration (average: 908 pg/mL, range: 319-1570 pg/mL) and in two dogs at the 1-week time point. Naltrexone was not detected at the 24-h time point. There was no significant effect of NTX on STT1, STT2, IOP, CS, or TFBUT., Conclusions: Naltrexone 0.3% is well tolerated and safe when applied topically to the eye once daily. Naltrexone 0.3% did not show any significant effects on corneal parameters as measured in this study. At once, daily dosing NTX is systemically absorbed; however, the degree of systemic absorption is not likely to be clinically significant., (© 2013 American College of Veterinary Ophthalmologists.)

Purpose: To evaluate the corneal changes immediately after diamond burr debridement of superficial corneal wounds in dogs. Spontaneous chronic corneal epithelial defects (SCCEDs) are the most common form of canine recurrent corneal ulcers. The diamond burr has been used in the management of corneal lesions in humans since 1983. Recently, it has been successfully used in the treatment of SCCEDs in dogs; however, little has been documented as to its mechanism of action., Methods: Five adult female research dogs euthanized for reasons unrelated to the study were included, providing 10 normal eyes. An excimer laser spatula was used for epithelial removal after delineation with an 8 mm punch biopsy trephine. Diamond burr debridement was performed for 30 and 45 s in five eyes each (groups 1 and 2 respectively). The procedure was performed on the ventral half of the experimental defect as well as ventral normal cornea, immediately after euthanasia, and prior to enucleation. Samples were processed routinely for histologic evaluation and stained with periodic acid-Schiff., Results: No stromal defects could be identified under light microscopy. In experimental corneal wounds, multi-focal areas remained covered by the epithelial basement membrane (BM) after diamond burr treatment in both groups (group 1 = 48% ± 16SD, group 2 = 26% ± 12SD). Removal of BM on group 2 was significantly higher than group 1 (P < 0.05). CONCLUSIONS : The diamond burr allows a safe method of debridement and does not create defects beyond the epithelial BM in corneal wounds in normal dogs. Evaluation of the diamond burr debridement in cases of SCCEDs is warranted., (© 2011 American College of Veterinary Ophthalmologists.)

Purpose: Oxidative stress plays a major role in the pathogenesis of many neurodegenerative diseases. It has also been implicated as part of the pathogenic mechanisms in the development of glaucoma. Alpha-luminol has shown profound anti-inflammatory and antioxidant effects in both experimental animal and human clinical studies. The purpose of this pilot study was to investigate for the first time the ocular penetration of topical alpha-luminol., Methods: Nine animals were divided into three treated groups (three animals each; one drop OU/n = 18), each group receiving a different concentration of the eyedrop (0.5%, 1.5%, 2.5%). Aqueous humor and peripheral blood samples were obtained from each rabbit at three different timepoints (20 min, 4 h and 12 h). Samples were analyzed by means of high performance liquid chromatography and mass spectrometry; median values were compared., Results: Alpha-luminol was found in the aqueous humor in all treated groups at all timepoints. At the 2nd and 3rd timepoints (4 h and 12 h), aqueous humor levels decreased significantly (P < 0.05) for two of the three dosages tested and it was not detectable in some eyes. The highest aqueous humor concentration of the drug was 272 ng/mL after 20 min (0.0217% of one drop, 2.5% group). Alpha-luminol was found in the vitreous in two animals, one in the 1.5% and another in the 2.5% group (16.4 and 21.5 ng/mL, respectively), at 12 h., Conclusions: Topically administered alpha-luminol readily penetrates into the anterior chamber and can penetrate into the vitreous chamber. Further investigation is warranted to better understand the intraocular pharmacokinetics of alpha-luminol., (© 2011 American College of Veterinary Ophthalmologists.)

Toxoplasma gondii, Bartonella henselae and feline herpesvirus-1 (FHV-1) have been implicated as causative agents in feline uveitis. The usefulness of serum and aqueous humor (AH) antibody testing for these agents is limited as antibodies can be detected in both healthy cats and cats with uveitis. Very few studies using polymerase chain reaction (PCR) assays to amplify organism DNA from samples from cats with uveitis have been performed. In this study, assays to detect T gondii antibodies, feline leukemia virus antigen, feline immunodeficiency virus antibody, and Bartonella species antibodies were performed on serum and PCR assays for amplification of T gondii, Bartonella species, and FHV-1 DNA were performed on blood and AH samples from 104 cats with endogenous uveitis and 19 healthy cats. Results suggest the addition of the PCR assay to the diagnostic work-up for cats with uveitis will increase the detection of T gondii and FHV-1; however, the diagnostic usefulness of these additional data is not clear., (Copyright © 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

This report describes a long-horned cowfish, which was diagnosed with buphthalmia and lens sub-luxation in the right eye, conditions that progressed to complete anterior lens luxation and secondary keratoconus. Three months after the initial evaluation, a pigmented mass was observed protruding from the vitreous. An enucleation was performed under general anesthesia. Ocular histopathology revealed an iridociliary melanoma. Reports of intraocular melanomas are extremely rare in fish. To the authors' knowledge, this is the first report of an iridociliary melanoma that led to buphthalmia, lens luxation, and keratoconus in a fish. Histological findings of lens luxation are also demonstrated. Due to the presence of a complex suspensory apparatus involving the teleost lens, this report speculates that lens luxation is a more devastating disease process in teleosts than in mammals.

Background: Administration of tetracyclines or fluoroquinolones is associated with improvement in clinical and laboratory abnormalities in cats infected with Mycoplasma haemofelis. No treatment protocol has consistently eliminated the organism, and antimicrobial susceptibility may vary among M. haemofelis isolates. Continued search for effective therapies is warranted., Hypothesis: Marbofloxacin administered at the onset of clinical illness will be safe and effective for the treatment of M. haemofelis., Animals: Fourteen young adult, laboratory-reared cats housed together in a specific pathogen-free facility., Methods: Twelve cats were inoculated IV with 2.0 mL of blood from 2 M. haemofelis positive cats. Clinical parameters were assessed daily. CBC and hemoplasma polymerase chain reaction (PCR) assay were performed before inoculation, weekly for 1-3 weeks postinoculation (PI) and twice weekly 3-6 weeks PI. Treatment with marbofloxacin (2.75 mg/kg PO daily for 14 days) was initiated in 6 randomly selected cats when PCV was <30% or fever was >102.5 degrees F (39.2 degrees C). Cats that were PCR positive on day 7 of therapy were treated for 28 days. Cats that were PCR negative on day 42 PI were treated with 20 mg/kg methylprednisolone acetate IM on day 50 PI., Results: Significant differences between groups on some days after inoculation included higher PCV and red blood cell counts, lower mean cell volume, and higher mean cell hemoglobin content in marbofloxacin-treated cats. No differences in PCR assay results were noted between groups., Conclusions and Clinical Importance: Marbofloxacin was safe and resulted in more rapid hematologic improvement in M. haemofelis-infected cats, but did not change clinical scores and did not consistently eliminate infection.

Objective: To evaluate the efficacy of twice-daily ophthalmic application of 0.5% cidofovir solution in cats with experimentally induced primary ocular feline herpesvirus-1 (FHV-1) infection., Animals: Twelve 6-month-old sexually intact male cats., Procedures: Cats were randomly assigned to either a treatment or control group. Ocular infection with FHV-1 was induced (day 0) in all cats via inoculation of both eyes with 10(4) plaque-forming units of a plaque-purified FHV-1 field strain. Twice daily for 10 days beginning on day 4 after virus inoculation, the treatment group received 1 drop of 0.5% cidofovir in 1% carboxymethylcellulose in both eyes, and the control group received 1 drop of 1% carboxymethylcellulose in both eyes. A standardized scoring method was used to evaluate clinical signs of FHV-1 infection in each cat once daily for 24 days. The amount of ocular viral shedding was assessed by use of a quantitative real-time PCR procedure every 3 days during the study period. Clinical scores and viral quantification were averaged over the pretreatment (days 0 to 3), treatment (days 4 to 14), and posttreatment (days 15 to 24) periods for each cat., Results: During the treatment period, clinical scores and amount of viral ocular shedding were significantly lower in the treatment group, compared with findings in the control group., Conclusions and Clinical Relevance: Twice-daily application of 0.5% cidofovir solution in both eyes significantly decreased the amount of viral shedding and the severity of clinical disease in cats with experimentally induced ocular FHV-1 infection.

Bartonella henselae has been implicated as a causative agent of chronic uveitis in people and in some cats. The objective of this study was to determine whether Bartonella species seroprevalence or titer magnitude varies among cats with uveitis, cats without ocular diseases recorded and healthy cats, while controlling for age and risk of flea exposure based on state of residence. There was no difference in seroprevalence rates or titer magnitude between cats with uveitis and cats with non-ocular diseases. Healthy cats were more likely to be seropositive for Bartonella species than cats with uveitis. The median Bartonella species titer was 1:64 for all groups, although healthy cats were more likely to have higher titers than cats with uveitis and cats with non-ocular disease. The results suggest that serum antibody tests alone cannot be used to document clinical uveitis associated with Bartonella species infection.

A 2-month-old, male alpaca had a 1-month history of mucoid ocular discharge from the left eye. Signalment, history and clinical findings were suggestive of a congenital nasolacrimal outflow obstruction. A dacryocystorhinogram confirmed bilateral nasolacrimal duct atresia, which involved the distal half of both nasolacrimal ducts. In order to establish alternative outflow, a conjunctivomaxillosinusotomy and conjunctivorhinostomy were performed on the right and left eye, respectively. The surgical openings remain patent after 11 months, and there have been no clinical signs of nasolacrimal disease.

Objective: This paper aims to determine if abnormalities of the retinal pigment epithelium (RPE) and retinal inflammation occur in primary glaucoma., Procedure: Twenty-three canine globes with primary glaucoma, goniodysgenesis, and elevated intraocular pressure were evaluated. Sections from 6 control and 23 glaucomatous canine globes were stained with hematoxylin and eosin, Griffonia simplicifolia isolectin B4, or immunohistochemically stained for CD3 or albumin. The retinal sections were evaluated with light microscopy for morphological and immunohistochemical evidence of pigmentary changes and inflammation., Results: Abnormal pigmented cells including displaced RPE cells and macrophages (identified by lectin binding) were found in the neuroretinas and vitreous bodies of glaucomatous eyes. Other abnormalities included hypertrophy of RPE cells and loss of RPE continuity. Regions of neuroretina with more displaced pigment had fewer remaining neurons. Signs of retinal inflammation found in glaucomatous eyes included infiltration with leukocytes, retinal swelling, and albumin leakage from vessels. Accumulation of perivascular CD3-positive T lymphocytes also occurred in glaucomatous retinas. Chronic glaucomatous retinas had increased pigmentary changes, fewer neutrophils, and less swelling than acute glaucomatous retinas., Conclusions: Disruption of the RPE, increased permeability of the vascular endothelium, accumulation of inflammatory cells, and retinal swelling or thinning occur in canine primary glaucoma. The displacement of pigment and accumulation of inflammatory cells in the neuroretina suggests that inflammation may be an important contributor to retinal damage.

Objective: To use PCR assays to determine the prevalence of feline herpesvirus 1 (FHV-1), Chlamydophila felis, and Mycoplasma spp DNA in conjunctival cells collected from cats with and without conjunctivitis; to compare results of conventional and real-time fluorogenic PCR assays for amplification of FHV-1 DNA; and to determine whether copy numbers of FHV-1 DNA are correlated with conjunctivitis., Animals: 55 cats with active conjunctivitis, 39 healthy cats that never had conjunctivitis, and 32 cats with a history of conjunctivitis that had been resolved for at least 3 months., Procedures: Samples were obtained by rolling cotton-tipped applicators on the ventral conjunctiva of awake cats treated topically with proparacaine. The DNA was extracted from the swab specimens and assessed in PCR assays to detect DNA of FHV-1 (fluorogenic PCR assay and conventional PCR assay), Mycoplasma spp (conventional PCR assay), and C felis (conventional PCR assay)., Results: Overall prevalence rates of FHV-1, C felis, and Mycoplasma spp as assessed by the conventional PCR assays were 6.7%, 3.2%, and 9.6%, respectively. Percentage concordance between conventional PCR and fluorogenic PCR assays for FHV-1 was 92.5%. There were no significant differences among the 3 groups of cats for the mean copy number of FHV-1 divided by the copy number of glyceraldehyde-3-phosphate dehydrogenase., Conclusions and Clinical Relevance: Mycoplasma spp were the most prevalent organism detected and was associated with conjunctivitis. This study could not confirm that there are increased copy numbers of FHV-1 DNA in cats with conjunctivitis, compared with the copy numbers for cats without conjunctivitis.

Background: The completion of several genome projects showed that most genes have not yet been characterized, especially in multicellular organisms. Although most genes have unknown functions, a large collection of data is available describing their transcriptional activities under many different experimental conditions. In many cases, the coregulatation of a set of genes across a set of conditions can be used to infer roles for genes of unknown function., Results: We developed a search engine, the Multiple-Species Gene Recommender (MSGR), which scans gene expression datasets from multiple organisms to identify genes that participate in a genetic pathway. The MSGR takes a query consisting of a list of genes that function together in a genetic pathway from one of six organisms: Homo sapiens, Drosophila melanogaster, Caenorhabditis elegans, Saccharomyces cerevisiae, Arabidopsis thaliana, and Helicobacter pylori. Using a probabilistic method to merge searches, the MSGR identifies genes that are significantly coregulated with the query genes in one or more of those organisms. The MSGR achieves its highest accuracy for many human pathways when searches are combined across species. We describe specific examples in which new genes were identified to be involved in a neuromuscular signaling pathway and a cell-adhesion pathway., Conclusion: The search engine can scan large collections of gene expression data for new genes that are significantly coregulated with a pathway of interest. By integrating searches across organisms, the MSGR can identify pathway members whose coregulation is either ancient or newly evolved.

Objective: To F whether vessels in the ocular fundus changed over the lifetime of Beagles and whether any changes were substantial enough to likely preclude positive identification of individual dogs by use of their retinal vascular patterns., Animals: 18 Beagles., Procedures: Fundic photographs of both eyes of 18 Beagles taken at 1 or 3, 5, and 7 or 9 years of age were digitalized. Photographs were analyzed by use of 2 software programs. One was used to determine vessel numbers and widths and the other to determine the locations of the 3 largest vessels. Measurements were compared over time periods in the life of each dog. Only observations made at baseline (1 or 3 years of age) and again at 5 and 9 years of age were included in the statistical analysis, as these points were common to all dogs., Results: No significant changes in numbers or locations of the blood vessels were detected over time. Widths of the vessels decreased significantly as the dogs aged., Conclusions and Clinical Relevance: The ocular fundus of Beagles changed over each dog's lifetime in that the retinal blood vessels became smaller but did not change in number or location. Results suggest that digitalized retinal images can likely be used to identify dogs over their lifetimes.

Two Great Horned owls were presented to the Colorado State University Veterinary Teaching Hospital for evaluation of corneal lesions. Each bird had a corneal ulcer and bullous keratopathy. Following unsuccessful attempts at medical and surgical management, the corneal defects in each bird were treated with penetrating keratoplasties and conjunctival pedicle grafts. In each bird the cornea healed well and regained approximately its normal shape. Both birds fully recovered and have been released into the wild.

Objective: To determine whether taurine and glutamate contents are reduced in damaged photoreceptors in dogs with primary glaucoma (PG) in a manner consistent with an ischemia-like release of both of these amino acids from damaged cells., Sample Population: Retinas from 6 dogs with PG and 3 control dogs., Procedure: Serial, semithin sections of each canine retina were stained with toluidine blue to identify damaged photoreceptors or via immunogold techniques to quantify taurine and glutamate content in retinal cells., Results: Regions with a thin outer nuclear layer and pathologic nuclear changes in photoreceptors were evident in retinas of dogs with PG. The density of immunostaining for taurine in damaged photoreceptors was significantly reduced to (mean +/- SEM) 37.5 +/- 2.6% of the density in adjacent undamaged photoreceptors. Photoreceptors with decreased taurine immunostaining also had decreased glutamate immunostaining, consistent with ischemia-like release of both of these amino acids from damaged cells. Immunostaining for glutamate, but not taurine, was increased in presumptive radial glial cells (i.e., Miller cells) in damaged regions, consistent with an ischemia-induced redistribution of amino acids in dogs with PG., Conclusions and Clinical Relevance: Retinal damage in dogs with PG includes ischemia-like losses of taurine and glutamate from photoreceptors and accumulation of glutamate, but not taurine, in nearby Müller cells. These changes are consistent with glutamate release and depletion of intracellular taurine in damaged regions, perhaps contributing to progressive damage in these areas.

Objectives: The aim of this study was to determine the relation between functional measures of peripheral arterial disease (PAD) severity with both disease-specific and generic self-reported health-related quality-of-life (HR-QOL) measures, as well as the relation between the two types of HR-QOL measures., Methods: This was a cross-sectional observation of participants from the community and primary care or vascular surgery clinics in an academic Veterans Administration medical center. Eighty patients with symptomatic Fontaine stage II PAD provided physiologic measures and self-response questionnaires. Objective measures included the ankle-brachial index (ABI), time to maximum claudication pain on a graded exercise test, and a 6-minute floor-walking distance. Self-reports included the Walking Impairment Questionnaire (WIQ), a disease-specific HR-QOL measure and the Medical Outcomes Study (MOS) Short-Form 36 (SF-36), a generic HR-QOL measure., Results: Patients (mean age 70 +/- 8 [+/- SD] and 85% men) exhibited moderate-to-severe PAD by objective measures of ABI (0.65 +/- 0.19) and time in minutes to maximal claudication on a graded exercise test (7:54 +/- 4:58). Significant correlations were found between these measures and the WIQ distance, MOS-Physical Function, and MOS-Role Limitations due to physical dysfunction. The SF-36 and the WIQ subscales were significantly correlated., Conclusion: In older PAD patients with intermittent claudication, objective measures of disease severity are correlated with a self-reported, disease-specific and generic HR-QOL.

Objective: To determine whether retinal damage in dogs with primary glaucoma (PG) is consistent with ischemia-induced glutamate toxicosis., Sample Population: Retinal tissue sections from 25 dogs with PG and 12 normotensive control dogs., Procedure: Retinal sections from control and glaucomatous dogs were stained for morphometric and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) analyses to determine whether retinal damage was consistent with glutamate toxicosis. Immunohistochemical analysis was performed to detect ischemia-like loss of glutamate from neurons in damaged areas., Results: In severely damaged glaucomatous retinas, all neurosensory layers had focal regions that were thin or disrupted. There was less thinning of the outer nuclear layer (ONL) and inner nuclear layer (INL) in moderately damaged retinas than in severely damaged retinas. Acute signs of damage in the INL included cells with dark, condensed chromatin and lightly stained cytoplasm interspersed with a few TUNEL-positive cells, which was consistent with glutamate toxicosis. Glutamate immunoreactivity was reduced in thin areas and in damaged cells of the INL and ONL, which was consistent with glutamate release in damaged areas. Glutamate immunoreactivity was increased in putative Müller cells in damaged areas, which also was consistent with glutamate release., Conclusions and Clinical Relevance: Retinal damage in dogs with PG differs in intensity in focal areas. Damage in affected regions resembles damage induced by glutamate. Glutamate is lost from damaged neurons and accumulates in Müller cells, which is consistent with increased glutamate release contributing to the damage. Glutamate antagonists may protect INL cells in dogs with glaucoma.

Objective: Distinguishing between pituitary-dependent Cushing's syndrome (CS) and occult ectopic ACTH syndrome can be extremely difficult. Bilateral inferior petrosal sinus sampling has been shown to have the highest diagnostic accuracy in this subtype evaluation. Internal jugular vein sampling (IJVS) has been reported as a potentially safer invasive alternative, but data are limited. Our objective was to compare the sensitivity and specificity of bilateral IJVS and bilateral inferior petrosal sinus sampling (IPSS) in patients with ACTH-dependent CS., Design: We prospectively collected blood samples from the inferior petrosal sinus and internal jugular vein of consecutive patients with ACTH-dependent CS., Patients: The study group included 35 patients: 32 with pituitary-dependent CS (positive immunohistochemical findings for ACTH pituitary tumour or biochemical cure after pituitary surgery) and three with histologically proven ectopic ACTH syndrome., Measurements: Inferior petrosal sinus sampling and bilateral IJVS were performed simultaneously before and after administration of corticotropin-releasing hormone (CRH), and ratios of central-to-peripheral ACTH concentrations were calculated., Results: The basal IJVS central-to-peripheral ACTH ratios were diagnostic for pituitary-dependent CS (> 2) in 15 patients (46.9%), as were basal inferior petrosal sinus sampling central-to-peripheral ACTH ratios in 29 patients (90.6%). The post-CRH IJVS central-to-peripheral ACTH ratios were diagnostic for pituitary-dependent disease (> 3) in 24 patients (75%), as were post-CRH inferior petrosal sinus sampling central-to-peripheral ACTH ratios in 28 patients (87.5%). In the three patients with ectopic ACTH CS, the IJVS and inferior petrosal sinus sampling pre- and post-CRH ACTH ratios were correctly negative. The overall sensitivity of combined pre- or post-CRH was 81.3% for IJVS and 93.8% for inferior petrosal sinus sampling. Because of the difference between mean ratios in the two techniques, new criteria for IJVS were mathematically calculated: a pre-CRH central-to-peripheral ACTH ratio of 1.59 and a post-CRH central-to-peripheral ACTH ratio of 2.47 maximized sensitivity and specificity when both of these are equally taken into consideration., Conclusion: In conclusion, IJVS is not superior to inferior petrosal sinus sampling for establishing the cause of ACTH-dependent CS. When new criteria of basal (> 1.6) and post-CRH (> 2.5) central-to-peripheral ACTH gradients were applied to ACTH ratios from IJVS, the sensitivity of this test was maximized. However, confirmatory inferior petrosal sinus sampling is recommended when there is a lack of a central-to-peripheral ACTH gradient and when there is only a gradient above the cut-off on basal (pre-CRH) sampling.

It is generally considered that thyroid dermopathy and acropachy almost always occur with Graves' ophthalmopathy and that these two extrathyroidal manifestations are indicators of severe autoimmune disease and hence of more severe ophthalmopathy. However, documentation of these anecdotal impressions is needed. We assessed the presence of optic neuropathy and frequency of orbital decompression in 2 referral cohorts: 40 patients with acropachy and dermopathy (acropachy group) and 138 patients with Graves' dermopathy and no acropachy (dermopathy group). We compared those cohorts with a cohort of 114 patients who had ophthalmopathy without dermopathy and acropachy (control group). We considered optic neuropathy and the need for orbital decompression to be indicators of severe Graves' ophthalmopathy. The frequency of orbital decompression was significantly higher in the dermopathy group than in the control group (odds ratio, 3.55) and even higher in the acropachy group (odds ratios: 20.68 for acropachy group compared with control group; 5.83 for acropachy group compared with dermopathy group). The same trend occurred with optic neuropathy but was not statistically significant (alpha = 0.05; p = 0.07). Five patients were exceptions: they had definite Graves' dermopathy without clinically obvious ophthalmopathy. In conclusion, dermopathy and acropachy appear to be markers of severe ophthalmopathy. Occasionally, however, Graves' dermopathy occurs without clinical ophthalmopathy.

A young female Akita presented for ocular and nasal lesions. Examination showed bilateral 360 degree limbal masses that extended onto the peripheral cornea. In addition, intranasal granulomatous masses were observed by rhinoscopy. Histopathologic examination with immunohistochemical staining showed that these masses were almost identical and were classified as an idiopathic, T-cell rich, granulomatous inflammation. The dog responded well to anti-inflammatory medication and the disease remains in remission 2 years after the initial presentation.

Ultrasound biomicroscopy was performed on enucleated feline globes as a model for use in vivo. Quantitative measurements were obtained from the anterior segment using a 50-MHz transducer. Mean values from 26 feline globes were axial corneal thickness, 0.74 mm; anterior chamber depth, 4.20 mm; distance from the first ciliary process to the limbus, 3.17 mm; angle recess, 0.38 mm; angle opening distance, 1.05 mm; iris base width 0.38 mm; iris middle width 0.52 mm; iris tip width 0.13 mm, and iris-lens overlap, 0.69 mm. Distinctive features of the feline anterior segment include a relatively wide iridocorneal angle and deep anterior chamber.

This study identified correlates of attendance to a community-based exercise program in an African American church congregation. After medical clearance, 48 participants completed measures of social support, health-related quality of life, depression, exercise self-efficacy, and exercise motivation and then participated in an exercise program for 6 months (attendance rate = 27%). Age, a sense of affiliation as a motivator to exercise, and weekly caloric expenditure derived from yard work were positively associated with program attendance, and full- or part-time employment was negatively associated with attendance. The authors concluded that exercise adherence is a complicated phenomenon that is influenced by a variety of environmental, personal, and social factors. Social factors, in particular, may be important in promoting adherence to an exercise program in African Americans.

Introduction: An increased number of circulating platelet-monocyte aggregates (PMAs) is present in patients with all clinical classes of chronic venous insufficiency (CVI). The purpose of this study was to determine whether patients with CVI maintain elevated levels of PMAs following complete surgical correction of chronic venous insufficiency., Methods: Patients with superficial venous insufficiency and a normal deep venous system documented by duplex scan were included in the study. Venous blood was drawn from a superficial vein in the leg and an antecubital vein prior to vein stripping and again six weeks postoperatively. Control subjects without evidence of venous disease had blood drawn from an antecubital vein. Whole blood flow cytometry was used to analyze the samples for the presence of platelet-monocyte aggregates following incubation with buffer or 0.5 microM adenosine diphosphate (ADP)., Results: Postoperative duplex scanning demonstrated elimination of venous reflux in the superficial venous system and normal deep vein physiology in all nine patients. Preoperatively, patients with CVI had significantly elevated levels of circulating PMAs in both arm and leg samples without stimulation by an agonist compared to controls (15.2+/-1.1 and 14.3+/-1.3 vs 7.4+/-0.3 for controls, p<0.02 for each), and after stimulation by 0.5 microM ADP (33.7+/-4.7 and 34.3+/-5.2 vs 12.5+/-3.8 for controls, p<0.04 for each). There was no significant change in the number of PMAs in either patient arm or leg blood samples six weeks following correction of venous reflux by removal of the diseased veins., Conclusions: Complete correction of chronic venous insufficiency did not diminish the elevated circulating levels of platelet-monocyte aggregates. We conclude that the presence of an increased number of PMAs identified in patients with CVI is not secondary to the presence of venous reflux, but may be involved with the primary etiology of chronic venous insufficiency. This finding also suggests that a stimulus other than venous hypertension may be important in triggering the leukocyte activation seen in patients with chronic venous disease.

It is uncertain whether more extensive primary surgery and increasing use of radioiodine remnant ablation (RRA) for papillary thyroid carcinoma (PTC) have resulted in improved rates of cause-specific mortality (CSM) and tumor recurrence (TR). Details of the initial presentation, therapy, and outcome of 2444 PTC patients consecutively treated during 1940-1999 were recorded in a computerized database. Patients were followed for more than 43,000 patient-years. The 25-year rates for CSM and TR were 5% and 14%, respectively. Temporal trends were analyzed for six decades. During the six decades, the proportion with initial MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size) scores <6 were 77%, 82%, 84%, 86%, 85%, and 82%, respectively (p = 0.06). Lobectomy accounted for 70% of initial procedures during 1940-1949 and 22% during 1950-1959; during 1960-1999 bilateral lobar resection (BLR) accounted for 91% of surgeries (p <0.001). RRA after BLR was performed during 1950-1969 in 3% but increased to 18%, 57%, and 46% in successive decades (p <0.001). The 40-year rates for CSM and TR during 1940-1949 were significantly higher (p = 0.002) than during 1950-1999. During the last 50 years the 10-year CSM and TR rates for the 2286 cases did not significantly change with successive decades. Moreover, the 10-year rates for CSM and TR were not significantly improved during the last five decades of the study, either for the 1917 MACIS <6 patients or the 369 MACIS < 6 patients. Increasing use of RRA has not apparently improved the already excellent outcome, achieved before 1970, in low risk (MACIS <6) PTC patients managed by near-total thyroidectomy and conservative nodal excision.

Objectives: To determine the cognitive and demographic factors that affect the performance of a predominantly African-American population in the use of a computerized version of the Center for Epidemiologic Studies Depression Scale (CES-D)., Design: Cross-sectional., Setting: University Medical Center and Veterans Affairs Medical Center in Baltimore, Maryland., Participants: Forty-three healthy community-dwelling adults from a predominantly African-American Apostolic church; mean age +/- standard deviation 57 +/- 14 (range 29-83)., Measurements: Cognitive measurements (Mini-Mental State Examination, digits span, word list learning, letter number sequencing, executive interview, and clock-drawing task), education level, computer experience, and age. The CES-D was administered on three occasions: a paper form CES-D once and a computerized version twice. Time to completion the computer CES-D (Time 1), differential in time to completion of both computer tests (delta-time) and scores of the CES-D with both forms of administration were recorded., Results: There was no difference between the scores from the paper and the computer CES-D or between the two computer forms. Computer experience predicted Time 1 (partial correlation R = 15%, P =.017) and delta-time (partial correlation R = 10%, P =.048). Age, education, and cognitive function did not affect performance., Conclusion: Computerized assessment techniques are valid and unaffected by age, education level, or cognitive factors in healthy individuals.

Ciliary block (malignant) glaucoma is caused by the posterior flow of aqueous humor into or behind the vitreous. It is a rare complication of anterior segment surgery in humans. This is a report of ciliary block glaucoma occurring as a postoperative complication of cataract surgery in a llama. Medical management was ineffective in lowering intraocular pressure (IOP). Posterior capsulotomy and anterior hyaloid disruption with a 22-gauge needle, in addition to medical management maintained IOP in the normal range until anterior vitrectomy could be performed. After vitrectomy, glaucoma resolved and medical treatment was no longer necessary.

The clinical work-up, diagnosis and follow-up of an 8-year-old, female-spayed Shih Tzu with diffuse, granulomatous meningoencephalomyelitis (GME)-causing visual deficits is reported. The use of cytosine arabinoside as an alternative treatment for GME is discussed.

Tachyzoites of Toxoplasma gondii have been found in the milk of sheep, goats, cows and mice and infection by ingestion of raw goat milk has been documented in humans. Lactational transmission from infected cats to their kittens is suspected but the organism has not been detected in the milk. The purpose of this study was to demonstrate the presence of T. gondii in the milk of experimentally infected cats. Pregnant specific pathogen free cats were inoculated orally with T. gondii at various times prior to parturition. Feces were examined for oocyst shedding after sugar solution centrifugation. Milk was collected for polymerase chain reaction (PCR) and bioassay in mice. T. gondii was detected in the milk of five of six cats by either bioassay or PCR.

Objective: To evaluate composition of aqueous humor obtained from normal eyes of llamas (Lama glama) and alpacas (Lama pacos)., Sample Population: Aqueous humor obtained from 10 male llamas and 10 male alpacas., Procedure: All animals had normal eyes, as determined by ocular examination. Aqueous humor samples were obtained via paracentesis of the anterior chamber of animals that were heavily sedated. Chemical analysis included measurement of concentrations of sodium, potassium, magnesium, chloride, bicarbonate, phosphorus, and glucose as well as osmolality and pH., Results: With the exception of potassium concentrations, values for aqueous humor composition did not differ significantly between llamas and alpacas. Mean +/- SD values for llamas and alpacas, respectively, were: sodium, 154.7 +/- 2.1 and 152.7 +/- 2.1 mEq/L; potassium, 5.3 +/- 0.4 and 4.6 +/- 0.4 mEq/L; magnesium, 1.8 +/- 0.1 and 1.7 +/- 0.1 mg/dl; chloride, 130.0 +/- 1.6 and 127.0 +/- 3.3 mEq/L; bicarbonate, 19.2 +/- 1.5 and 20.2 +/- 2.3 mEq/L; phosphorous, 2.7 +/- 0.3 and 2.5 +/- 0.4 mg/dl; glucose, 80.3 +/- 3.9 and 80.8 +/- 7.3 mg/dl; total protein, 29.0 +/- 8.6 and 31.5 +/- 10.1 mg/dl; and osmolality, 305.8 +/- 11.8 and 306.2 +/- 4.9 mOsm. The pH ranged from 7.5 to 8.0 for both species. Potassium concentrations were significantly higher in llamas than alpacas., Conclusions and Clinical Relevance: Except for potassium, composition of aqueous humor did not differ significantly between llamas and alpacas. Aqueous humor composition of llamas and alpacas is similar to that of other species that have been examined.

Objective: To describe ocular findings in kittens with congenital or early neonatal infection by Toxoplasma gondii and to determine if there are detectable differences in disease caused by three strains., Animals Studied: Six adult female cats and the offspring from seven litters., Methods: Four kittens from uninfected specific pathogen-free (SPF) queens and 21 kittens from SPF queens inoculated at various times late in gestation with Mozart, Maggie, or ME-49 strain of T. gondii were used. Ocular examinations were performed on queens prior to and after delivery, and on kittens weekly to bi-weekly for up to 27 weeks. Whole blood for serology was collected from all kittens at 5(1/2) to 8 weeks of age and again at 12 weeks of age or later., Results: No kittens from noninfected queens developed ocular lesions or antibody to T. gondii. Three of the 24 kittens from infected queens died or were euthanized early in the study. Chorioretinitis was detected in 15 of 21 living kittens from infected queens. Two developed concurrent anterior uveitis that resolved within 1 week. Posterior segment lesions varied ophthalmoscopically between strains. Of 21 kittens from T. gondii-infected queens, six developed positive antibody titers to T. gondii during the study. All seropositive kittens were born to queens infected with Mozart strain of T. gondii., Conclusion: Results of this study suggest that ocular toxoplasmosis can occur without other evidence of clinical illness in kittens infected in utero or in the neonatal period, and that T. gondii strains may have varying degrees of ocular pathogenicity in cats.

Patients with peripheral arterial disease (PAD) and intermittent claudication often have coronary artery disease (CAD) and other comorbid medical problems. There is a paucity of information on the impact of coexistent medical conditions on exercise capacity and functional status in patients with PAD. This study examined the impact of CAD, diabetes, cigarette smoking, prior peripheral surgical revascularization and other medical conditions on claudication pain times and peak oxygen capacity (VO2) during maximal effort treadmill testing in 119 male outpatient volunteers (ankle-brachial index (ABI) of 0.65 +/- 0.2, mean +/- SEM) with a history of Fontaine Stage II PAD. Smoking status was significantly related to ambulatory function. Current smokers had a lower peak VO2 expressed in l/min than either former or never smokers (ANCOVA adjusted for age, p = 0.003). However, after adjustment for body weight, there was only a trend for a difference in peak VO2 between current (13.2 +/- 0.5 ml/kg per min), former (14.2 +/- 0.4 ml/kg per min) and never (15.4 +/- 1.0 ml/kg per min) smokers (ANCOVA, p = 0.10). Current smokers had a shorter time to onset of claudication pain (p = 0.023) and shorter maximal claudication pain times (p = 0.029) than former or never smokers (p = 0.023). The ABI 1 min after cessation of exercise was also lower in smokers compared to former and never smokers (p = 0.018). There were no significant differences in functional performance measures or time to recovery from maximal claudication pain when patients were categorized on the presence or absence of CAD, diabetes, peripheral revascularization, arthritis, hypertension or dyslipidemia. Therefore, smoking adversely affected exercise capacity in these PAD patients, whereas the presence of CAD, diabetes and other medical problems had a relatively minor impact on exercise capacity. In conclusion, the relatively minor impact of comorbid medical conditions on walking ability in patients with PAD reflects the overwhelming limitation in ambulatory function due to the claudication pain.

Objective: The purpose of this study was to determine whether a 6-month exercise rehabilitation program can improve cardiovascular risk factors in patients with peripheral arterial occlusive disease (PAOD)., Methods: Thirty-four patients (mean age, 68 +/- 8 years; range 54-84 years) with PAOD with intermittent claudication (Fontaine stage II) and 14 longitudinal controls of comparable age with stage II PAOD enrolled in an exercise intervention at the University Medical Center and Veterans Affairs Medical Center at Baltimore, Maryland. The main outcome measures were lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol [LDL-C]), fasting glucose, blood pressure, body mass index, treadmill times to onset and maximal claudication pain, cardiopulmonary function (peak oxygen uptake), and ankle/brachial index., Results: With exercise rehabilitation, treadmill times to onset and maximal claudication pain increased by 106% and 64% (P <.0001), whereas peak oxygen uptake increased 7% (P <.05). Exercise rehabilitation lowered total cholesterol and LDL-C levels by 5.2% (P <.005) and 8% (P <.01), respectively. Systolic blood pressure declined by 5.7% (P <.05) with no change in diastolic blood pressure. These changes in cholesterol and LDL-C concentrations were related to their initial values. All other cardiovascular risk factors measured did not change. There was no correlation between improvement of cardiovascular risk factors and functional performance measurements. None of the variables measured changed significantly in the control group., Conclusions: Exercise rehabilitation not only improves functional performance, but also results in favorable alterations in cardiovascular risk factor profile, which is an important element in the management of PAOD.

Objective: The extravasation detection accessory (EDA) is designed for use during contrast-enhanced CT studies performed with a power injector. The EDA detects the changes in soft-tissue impedance that occur with enhanced extravasation and halts the further infusion of contrast material via a feedback circuit to the injector. We tested the sensitivity of this device in a model of contrast extravasation., Materials and Methods: Study subjects had an extravasation of 5% dextrose in water (nonionic contrast equivalent) in one arm and 0.9% sodium chloride solution (ionic contrast equivalent) in the other. An EDA was placed over the site of infusion and connected to a power injector. Injections were performed at 0.25 ml/sec (n = 40), 2.5 ml/sec (n = 62), or 5 ml/sec (n = 20)., Results: At infusion rates of 2.5 and 5 ml/sec, the device halted the injector in every subject after an average volume of 12.5 +/- 1.6 ml was delivered. At 0.25 ml/sec, the device failed to halt the injector in 11 of 20 events. After reprogramming the algorithm, 10 more subjects were tested at the lowest injection rate. The device halted 18 of 20 extravasation events with an average volume of 3.7 +/- 0.5 ml., Conclusion: In our model of contrast extravasation, the EDA halted a power injector with reliability and reproducibility before a large volume of contrast material was delivered. The sensitivity of the device approached, but did not reach, 100%. This device may serve to diminish the morbidity of extravasation events.

OBJECTIVE: To determine the mean intraocular pressure in llamas (Lama glama) and alpacas (Lama pacos) using applanation tonometry.Animals studied: Ten llamas and 10 alpacas.Procedures: Intraocular pressure (IOP) was measured with a Tono-Pentrade mark XL (Mentor Ophthalmics, Inc., Norwell, MA, USA). Three values, with 5% variance, were recorded for each eye. Least-squares means were determined for IOP for each eye of llamas and alpacas. Controlling for age, differences between left and right eye were analyzed using ANOVA. Two age groups were established, less than 5 years and greater than 5 years. The effect of age on IOP within each group was analyzed by linear regression. Probability values of less than 0.05 were considered significant. RESULTS: Comparison of mean IOP between right (n = 20) and left eyes (n = 20), independent of species type, showed no differences in IOPs for llamas and alpacas. Mean IOP declined with increasing age in llamas and alpacas. Mean IOPs for 20 eyes in 10 llamas was 16.96 +/- 3.51 mmHg. Mean IOP for 20 eyes in 10 alpacas was 16.14 +/- 3.74 mmHg. Mean IOP for all eyes (n = 40), independent of species, was 16.55 +/- 3.55 mmHg. The range of IOP in normal llamas and alpacas within 2 SD (95% of the population) was 14.89+/-18.21 mmHg. CONCLUSIONS: There was no significant difference in IOP between alpacas and llamas. Mean IOP in both species decreased with increased age.