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Abstract Background In order to perform at top levels, elite athletes have to both protect and risk their health at the same time. Adolescent elite athletes have the additional challenge of coping with substantial physical, psychological and social transformations. The contradictory phenomenon of protecting and risking the adolescent athletes' health in sports challenges the development of health promotion and protection strategies. The GOAL Study (German Young Olympic Athletes' Lifestyle and Health Management Study) analyzes the individual and organizational management of health in adolescent elite sports. Methods/design We combine quantitative and qualitative approaches in a mixed-method study. This allows us to gather a broad range of representative information on squad athletes from all Olympic disciplines as well as in-depth information on four selected Olympic disciplines (artistic gymnastics, biathlon, handball and wrestling). Within the quantitative section we attempt to identify the young athletes' health and nutrition behavior, their subjective health state and their lay health representations, health-related social networks, and structures of medical attendance. 1138 national team level athletes born between 1992 and 1995 from 51 Olympic disciplines responded to the questionnaire (response rate: 61,75%). The qualitative section investigates the meaning and relevance of health and nutrition within the athletes' sports specific surroundings, the impact of biographic backgrounds on individual health behavior, and sports specific cultures of health, nutrition and risk. We interviewed 24 athletes and 28 coaching and medical experts, and carried out 14 multi-day participant observations at training sessions and competitions. Conclusions The studies' results will serve as the basis for developing tailored health promotion strategies to be in cooperation with German elite sports associations.

Thirteen American Hereford cattle were reported blind with presumed onset when ~12-mo-old. All blind cattle shared a common ancestor through both the maternal and paternal pedigrees, suggesting a recessive genetic origin. Given the pedigree relationships and novel phenotype, we characterized the ophthalmo-pathologic changes associated with blindness and identified the responsible gene variant. Ophthalmologic examinations of 5 blind cattle revealed retinal degeneration. Histologically, 2 blind cattle had loss of the retinal photoreceptor layer. Whole-genome sequencing (WGS) of 7 blind cattle and 9 unaffected relatives revealed a 1-bp frameshift deletion in ceroid lipofuscinosis neuronal 3 ( CLN3 ; chr25 g.26043843del) for which the blind cattle were homozygous and their parents heterozygous. The identified variant in exon 16 of 17 is predicted to truncate the encoded protein (p. Pro369Argfs*8) battenin, which is involved in lysosomal function necessary for photoreceptor layer maintenance. Of 462 cattle genotyped, only blind cattle were homozygous for the deletion. A query of WGS data of > 5,800 animals further revealed that the variant was only observed in related Hereford cattle. Mutations in CLN3 are associated with human juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten disease, which results in early-onset retinal degeneration and lesions similar to those observed in our cases. Our data support the frameshift variant of CLN3 as causative of blindness in these Hereford cattle, and provide additional evidence of the role of this gene in retinal lesions, possibly as a model for human non-syndromic JNCL., Competing Interests: Declaration of conflicting interestsFunding was provided in part by the American Hereford Association. The funders assisted with sample acquisition and pedigree evaluation. The experimental design and analyses of data were independent of the funding agency.

Objective: To describe a protocol for corneal ulcer monitoring utilizing daily fluorescein staining and evaluation of owner-acquired anterior segment images., Animal Studied: Nine client-owned small animal patients (eight dogs, one cat) diagnosed with superficial corneal ulcers at the University of Georgia Veterinary Capitalize Hospital., Procedure(s): In addition to routine ulcer therapy, patients were discharged with supplies to perform daily fluorescein staining including a Quikvue® cobalt blue light camera adapter. Fluorescein staining was performed daily, photographs and/or videos were acquired at home by the patient's owner(s), and images were analyzed daily by trained personnel. In-house examinations were performed weekly and within 24 h after the ulcer had appeared healed on photographs., Results: All (9/9) owners were able to take interpretable photographs. The majority (6/9) of patients had images successfully detailing their ulcer healing progress. One (1/9) patient appeared healed on images, but on subsequent examination had persistent ulceration covered by third eyelid elevation. Two (2/9) patients had persistent ulceration, consistent on both images and examination, but exited the study prematurely prior to ulcer healing., Conclusions: Remote fluorescein staining and image evaluation can be considered as an adjunct for monitoring ulcer healing but should not be used alone or as a substitute for ophthalmic examinations. Ulcers under the third eyelid have potential to be missed on image evaluation alone., (© 2023 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

This article describes the history and infrastructure associated with canine breed-related eye screening and certification by Diplomates of the American College of Veterinary Ophthalmologists. Some of the common or otherwise particularly problematic specific inherited ophthalmic conditions are discussed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

With the continued rise of interest and need for veterinary specialists, information regarding optimal selection criteria for successful residency candidates has been lacking in veterinary medicine. A 28-question online survey was developed to determine prioritized resident selection criteria, the importance of formal interviews, and residency supervisor satisfaction with the current selection process. This survey was sent to all programs listed by the Veterinary Internship and Residency Matching Program (VIRMP) for the 2019-2020 program year. Overall, the most important aspects of the residency application process were (1) letters of recommendation, (2) performance during the interview, (3) personal contact/recommendation from a colleague, (4) personal statement, and (5) demonstrated interest in the residency specialty. While measures of academic performance including GPA and veterinary class rank may play a role in sorting of candidates in more competitive specialties, this does not necessarily exclude them from the ranking process. This information should be helpful to candidates and program directors alike in understanding the success of the current residency candidate selection process.

Introduction: Surgical site infections (SSI) increase morbidity, increase treatment costs, and can delay onset of necessary adjunctive therapy. The goal of this retrospective study was to determine the incidence of and risk factors of SSI after enucleation in dogs., Methods: Medical records were searched at one veterinary teaching hospital and identified 280 dogs that underwent enucleation and had an adequate follow-up to assess SSI. Multiple preoperative (e.g., reason for enucleation), peri-operative (e.g., surgical approach and surgeon experience level), and post-operative (e.g., use of post-operative antibiotics or anti-inflammatory medications) variables were assessed as risk factors for development of SSI., Results: The incidence of SSI after enucleation was 5%, and no risk factors for SSI were identified. Dogs that received cephalexin as a prophylactic post-operative antibiotic were statistically more likely to develop SSI versus those that received a different post-operative antibiotic ( p = 0.045). However, the clinical significance of this finding is unclear as administration of prophylactic post-operative antibiotics overall did not reduce the risk of SSI in the population evaluated here., Discussion: No risk factors were identified to guide clinical decision-making for prevention of SSI. Additionally, the results do not support the use of prophylactic antibiotics after enucleation in dogs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dacanay, Barber, Diehl and Myrna.)

The purpose of this study was to identify motivations for fourth-year veterinary students to choose future career paths based on post-graduation employment or post-graduation education. Approximately 500 students from four institutions were invited to participate in an online survey. Surveys were based on the cognitive evaluation theory, a minitheory within the self-determination macrotheory framework developed by Deci and Ryan. Intrinsic motivational factors were categorized by autonomy, competence, and relatedness, and extrinsic motivators were categorized by environmental and interpersonal factors. Students pursuing post-graduation education have intrinsic motivators that aligned with competence and were extrinsically motivated by a mentor, while students interested in post-graduation employment had intrinsic motivators that were more focused on autonomy with extrinsic motivational influences of debt/finances and geographic location.

Objective: To compare single and triplicate applanation tonometry values across previous intraocular pressure (IOP) studies in dogs., Animals: 116 ophthalmologically normal dogs., Procedures: Triplicate IOP readings (n = 1432) from studies evaluating effect of anesthetic protocols were analyzed to estimate a range of probable differences between averaged triplicate and first, averaged and lowest, and first and lowest IOPs. The decrease in variability with triplicate measurements and the magnitude of effects on statistical power were quantified., Results: The 2.5th to 97.5th interpercentile range for differences of averaged triplicate values minus first IOP readings was -3 to 2.7 mm Hg; for averaged minus lowest: 0 to 3.7 mm Hg; for first minus lowest: 0 to 5 mm Hg. The 95% prediction interval for differences in study group means (n = 160 groups, n = 5 to 11 eyes per group) based on averaged minus first measurements was -1.0 to 0.9 mm Hg with associated SDs reduced by 4% on average. Analysis of previous studies using averaged instead of first IOP values resulted in minimal decreases in SEs of 3-9% (0.03 to 0.09 mm Hg). Of 11 comparisons found significant with averaged data, 2 (18%) were found nonsignificant with first measurements. Of 96 comparisons found nonsignificant with averaged data, 3 (3%) were found significant with first measurements., Clinical Relevance: With applanation tonometry in ophthalmologically normal dogs, no clinically meaningful difference was found between the first, lowest, or averaged triplicate IOP measurements, but the first reading has a larger variance and hence will result in lower statistical power.

Background: Little is published regarding topical NSAID effect on corneal healing in dogs. This retrospective cohort study aimed to compare healing times and complications in dogs with spontaneous chronic corneal epithelial defects (SCCED) treated with and without topical non-steroidal anti-inflammatory drugs (NSAID)., Methods: Medical records of 66 dogs (71 eyes) diagnosed with SCCED between 2008 and 2019 were included. Eyes were divided into: (1) those receiving topical NSAIDs (n = 33) versus (2) those not receiving topical NSAID (n = 38). Follow-up until healed, such as comfortable eye, negative fluorescein stain was required. Use of topical or systemic anti-inflammatories outside of NSAID or presence of ocular disorders or systemic endocrinopathies that may contribute to delayed healing resulted in study exclusion., Results: Healing times were significantly longer in eyes that received topical NSAID (p = 0.008), however, the use of more topical medications for treatment was also associated with longer healing times (p = 0.001). The majority of eyes in the NSAID group received multiple medications, compared to the non-NSAID group, so it was not possible to separate the effects of NSAID from a number of medications. Complications occurred in three eyes of three dogs within the NSAID group., Conclusions: In these canine SCCED eyes, the use of more topical medications, including NSAID, was associated with significantly delayed healing time., (© 2021 British Veterinary Association.)

Objective: To determine the effect of xylazine on intracranial pressure (ICP) in standing compared to isoflurane-anesthetized horses., Design: Prospective, crossover study design., Setting: University Teaching Hospital., Animals: Six adult horses donated to the University. Horses were determined to be healthy via physical examination, complete blood count, and neurological evaluation., Interventions: Horses were anesthetized, maintained on isoflurane in oxygen in left lateral recumbency, and ventilated to normocapnia. Horses were instrumented for intraparenchymal measurement of ICP, invasive blood pressure, pulse oximetry, and end tidal gas analyzer. Xylazine 1 mg/kg was administered IV and ICP, systolic arterial pressure, mean arterial pressure (MAP), diastolic arterial pressure, and heart rate were recorded and cerebral perfusion pressure (CPP) was calculated for the following 15 minutes. Twenty-four to 36 hours following anesthetic recovery, xylazine 1 mg/kg was administered IV and ICP, heart rate, and Doppler blood pressure (BPdop) on the tail were monitored for 15 minutes., Measurements and Main Results: There was a decrease in ICP following administration of xylazine in anesthetized horses (P < 0.003) but not standing horses (P = 0.227). There was an increase in systolic arterial pressure, MAP, diastolic arterial pressure (P < 0.001), and BPdop (P = 0.001) following administration of xylazine. As a result, CPP increased in anesthetized horses (P < 0.03). There was a negative association between ICP and MAP in anesthetized horses (P = 0.007) but not ICP and BPdop conscious horses (P = 0.379)., Conclusions: Administration of xylazine to anesthetized horses resulted in an increased CPP due to decreased ICP with concurrent increased MAP. Administration of xylazine to standing horses did not result in a change in ICP. However, with the increase in BPdop found in awake horses, it is likely that CPP would also increase in awake horses following xylazine administration., (© Veterinary Emergency and Critical Care Society 2021.)

Objective: To determine whether an association exists between direct intracranial pressure (ICP) measurement and ultrasonographic measurement of optic nerve sheath diameter (ONSD) in anesthetized and standing horses., Design: Cross-sectional study performed on a convenience sample of healthy adult horses., Setting: University teaching hospital., Animals: Eight adult horses donated to the University. Enrolled horses were free of abnormalities on physical examination, CBC, neurological evaluation, and ophthalmological examination., Measurements and Main Results: Horses were anesthetized in lateral recumbency for placement of an ICP transducer. Three head positions (neutral, elevated, and lowered) were used to alter ICP. ICP and ONSD in 2 directions (D1 and D2) were recorded at 5 and 10 minutes after position change to elevated and lowered. ICP and ONSD measurements were repeated in standing sedated horses 24-36 hours after recovery from anesthesia. Linear regressions were performed with ICP as the dependent variable and ONSD as the independent variable by head position and times. Linear regressions were also performed for change from neutral under anesthesia, with ONSD as the independent variable and ICP as the dependent variable, by head position and times. Significance was set at P < 0.05. There was a moderate association between ICP and ONSD in horses with head lowered at 5 and 10 minutes (R 2 values = 63%-78%) and weak association in head elevated at 10 minutes (R 2 values = 56%-63%). There was a weak association between change from neutral ICP and change from neutral ONSD in the elevated anesthetized position at 10 minutes for summed D1 + D2 (R 2  = 33%)., Conclusions: Consistent associations between direct ICP and ONSD in anesthetized or standing horses were not observed. This inconsistency limits the clinically utility of transpalpebral ultrasonographic ONSD measurement for ICP monitoring in horses., (© Veterinary Emergency and Critical Care Society 2021.)

Pigmentary uveitis (PU), also known as Golden Retriever Pigmentary Uveitis (GRPU), is a common ocular condition of Golden Retrievers that has severe, vision-threatening ocular complications and can require surgical intervention. In order to ensure consistency in the diagnosis of GRPU between examiners, a specified set of diagnostic criteria must be applied. This is critical to ensure owners, breeders, and veterinary ophthalmologists maintain confidence in the ocular certification process. Therefore, current and former members of the American College of Veterinary Ophthalmologists' Genetics Committee came together to draft this Viewpoint Article on the challenges of diagnosis and treatment of Golden Retriever Pigmentary Uveitis for veterinary ophthalmologists, Golden Retriever owners, and Golden Retriever breeders., (© 2020 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

Objectives: To evaluate two visual aid devices in blind dogs., Materials and Methods: Transit time and number of collisions through a maze were recorded for 12 chronically and irreversibly blind dogs. Each dog repeated the maze while fitted with a BlindSight® echolocation device, or Muffin's Halo® physical barrier. They then repeated another maze test after a 30-day device acclimation period at home., Results: All dogs had fewer collisions when wearing the halo device versus their baseline with no device. Dogs ≤11.8 kg had fewer collisions when acclimated to the halo versus their baseline with no device or when acclimated to the BlindSight®. For dogs >11.8 kg, maze completion time was faster when acclimated to the BlindSight® versus their baseline with no device or when acclimated to a halo. Owner surveys indicated no noticeable improvement in quality of life or dog navigation at home with either device., Clinical Significance: This study demonstrates the utility of commercially available visual aid devices in aiding blind dogs' navigation and may help veterinarians make recommendations to owners of blind dogs regarding the purchase of these devices., (© 2020 British Small Animal Veterinary Association.)

Objective: To assess and compare retention, application characteristics, and patient tolerance of nine bandage contact lens types from four manufacturers., Animals Studied: Six research Beagles were used in this pilot study., Procedure: Five bandage contact lens types from two veterinary brands and four bandage contact lens types from two human brands were evaluated in six research Beagles. Placement ease, the dogs' contact lens tolerance, and contact lens retention time for up to 14 days were recorded. Statistical analysis with a linear mixed model was performed., Results: Veterinary contact lenses had an average retention time of 0.4 days (range 0-7 days, with an average of 10% and 3% retained ≥1 and ≥7 days, respectively), while human contact lenses had a significantly (P < 0.0001) longer average retention time of 5.2 days (range 0-14 days, with an average of 83% and 37.5% retained ≥1 and ≥7 days, respectively). Specifically, Johnson and Johnson Vision Care Acuvue® Oasys™ with Hydraclear™ Plus lenses were retained significantly longer than all veterinary lenses, and Bausch and Lomb PureVision® 2 lenses were retained significantly longer than Keragenix HydroBlues™ 18 and AnimaLens™ HRT 78 18 mm lenses., Conclusion: Although all bandage contact lenses were easy to use and well tolerated by the dogs, the human lenses were retained significantly better and longer than the veterinary lenses. Additionally, human lenses were retained significantly better and longer than veterinary lenses of similar measurements. This suggests factors other than measurement and associated fit may determine contact lens retention time., (© 2019 American College of Veterinary Ophthalmologists.)

Objective: Identify dogs that required removal of an eye that had previously undergone a parotid duct transposition (PDT) and secondly to characterize demographics, surgical technique, and outcomes associated with it., Procedure: An online survey was distributed to American College of Veterinary Ophthalmologists (ACVO) and Veterinary Ophthalmology (VOPH) listservs asking members to report the breed, reason for eye removal, time between surgeries, surgical technique, complications, and additional therapy instituted for dogs requiring removal of an eye subsequent to PDT surgery., Results: Sixteen dogs fit the inclusion criteria. Small breeds (<15 kg) made up 80% of the study population. Time between surgeries was <6 months (1/16), 6 to 12 months (7/16), and ≥1 year (8/16). Reasons for eye removal included: advancing corneal disease (6/16), discomfort (6/16), reaction to saliva (4/16), decreased saliva production (2/16), glaucoma (1/16), orbital neoplasia (1/16), and endophthalmitis (1/16). Surgical techniques included: transection of the parotid duct without ligation (2/16), ligation (9/16), and reversal of the PDT with reimplantation into the mouth (5/16). Complications reported were two dogs who underwent duct ligation experienced prolonged dilation of the duct that resolved with medical therapy (1/2) or without additional therapy (1/2)., Conclusion: Ligation of or reversal of the PDT with reimplantation into the mouth are appropriate adjunctive surgical techniques when removing an eye that previously underwent PDT surgery. Two dogs with nonfunctional PDT had complication-free eye removal with transection without ligation. Prolonged dilation of the duct is possible after eye removal with duct ligation and may resolve with time or medical management., (© 2019 American College of Veterinary Ophthalmologists.)

The primary purpose of this study was to identify themes that are consistent across veterinary internship applicants' personal statements and that are correlated with the statements' perceived overall quality. A secondary purpose was to investigate the reliability in personal statement quality scoring among six experienced internship candidate evaluators. One hundred applications to the University of Georgia Small Animal Rotating Internship program were evaluated. Each evaluator wrote a description of what he or she values in personal statements and his or her beliefs about content and presentation in high- and low-quality statements. After statement de-identification, each evaluator reviewed 15 randomly selected personal statements from internship applicants and assigned each a score ranging from 1 to 4 according to the following criteria: 1 = would not rank for an internship; 2 = would rank in the bottom third; 3 = would rank in the middle third; and 4 = would rank in the top third. A subset of these scored personal statements was chosen for qualitative analysis. A qualitative document analysis using grounded theory was performed for both the evaluators' descriptions of preferences in personal statements and the subset of personal statements. Agreement among evaluators' assigned scores was slight (Fleiss's κ = 0.11). Analysis of the evaluator statements and the scored candidate statements indicated that important factors in a personal statement include the applicant's ability to articulate experiences, to convey maturity, to demonstrate understanding of what an internship entails, and to describe reasons for pursuing an internship.

Objective: To compare the effect of propofol and ketamine/diazepam for induction following premedication on intraocular pressure (IOP) in healthy dogs., Study Design: Prospective, quasi-experimental, unmasked, longitudinal., Animals: A total of 61 client-owned dogs., Methods: Dogs were anesthetized twice with a 4 week washout period. Premedication with dexmedetomidine (5 μg kg -1 ) and hydromorphone (0.1 mg kg -1 ) intramuscularly was followed by either propofol (4 mg kg -1 ) or ketamine (5 mg kg -1 ) and diazepam (0.25 mg kg -1 ) intravenously for induction and inhaled isoflurane for maintenance. IOP was measured by applanation tonometry using TonoPen-XL before premedication and after 5, 10, 20 and 30 minutes. IOP was measured again immediately after induction and after 3, 5, 10, 15, 20, 30 and 40 minutes. Data were analyzed using one- or two-way repeated measures ANOVA., Results: No difference was found between right and left IOP (p = 0.45), and data from both the eyes of each dog were averaged and considered as one set of data. Following premedication, IOP was significantly lower at all time points than at baseline when animals were grouped together, mean difference -1.6 ± 0.2 mmHg (p < 0.05). IOP increased immediately (12.2 ± 2.4 mmHg before versus 17.1 ± 3.8 mmHg after) and at 3, 5 (p < 0.001), 10 and 40 minutes (p = 0.009 and 0.045, respectively) after propofol administration. For ketamine/diazepam, IOP was increased immediately post-induction (13.0 ± 2.7 mmHg before versus 14.7 ± 2.8 mmHg after) and at 3, 5 (p < 0.001), 30 and 40 minutes (p = 0.010 and 0.037, respectively)., Conclusions and Clinical Relevance: Sedation with hydromorphone and dexmedetomidine significantly decreased IOP in normal dogs and may be an appropriate choice for dogs that cannot tolerate acute increases in IOP. However, IOP increased significantly after both induction protocols, abolishing the effect of premedication., (Copyright © 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To describe the clinical presentations of patients diagnosed with ocular adnexal or orbital squamous cell carcinoma (SCC), which possess features similar to feline restrictive orbital myofibroblastic sarcoma (FROMS)., Procedures: A retrospective review of adnexal and/or orbital SCC was performed. Cases were collected from the University of Georgia College of Veterinary Medicine and the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) (1990-2016). Data included signalment, ophthalmic clinical signs, nonophthalmic history and clinical signs, clinician suspicion of FROMS, advanced imaging results, and subsequent histopathologic diagnosis. FROMS cases from the COPLOW over the same time span were reviewed and compared statistically to the SCC cases with a significance threshold of 0.05., Results: Nineteen cases (20 eyes) were identified with adnexal SCC with features similar to FROMS, including keratitis and eyelid/third eyelid restriction and/or thickening. There were no statistically significant differences between clinical findings in the SCC cases and the identified and compared FROMS cases (57 cases; 67 eyes), except for exophthalmos and/or resistance to retropulsion, which was less common in SCC cases (20%) than in FROMS cases (47.8%) (P = 0.027); and clinical or imaged presence of an overt eyelid or orbital mass, which was more common in the SCC cases (30%) than in the FROMS cases (4.5%) (P = 0.0010)., Conclusions: SCC with adnexal involvement has many features similar to FROMS. In addition to FROMS, SCC should be considered a differential diagnosis in cats with restrictive adnexal or orbital signs and corneal changes., (© 2017 American College of Veterinary Ophthalmologists.)

Objective: To compare Schirmer tear test I (STTI) values collected in normal horses with and without an auriculopalpebral nerve block., Procedure: Schirmer tear test I values were measured in 20 clinically normal horses (38 eyes) with a median age of 12 years. The order of eyes tested was randomized. Within 24-48 h, at the same time of day, tear measurements were collected again after administration of an auriculopalpebral nerve block. Each block was performed a minimum of 5 min prior to each STT I. A repeated-measures model was used to analyze differences between STT I values in eyes with and without nerve blocks incorporating within horse correlation between eyes. The mixed-model included fixed factors of treatment and eye and a random intercept for each horse. An unstructured covariance structure was used., Results: On average, STT I values measured in eyes after auriculopalpebral nerve blocks were 0.55 mm/min greater than those without nerve blocks. This difference was not statistically significant (P = 0.5268)., Conclusions: There was no effect of auriculopalpebral nerve block on STT I values in normal horses., (© 2016 American College of Veterinary Ophthalmologists.)

This article covers considerations and techniques of eye removal surgeries in exotic pets. After issues including surgical indications, anesthesia, patient preparation, and instrumentation are explored, surgical techniques are described. Enucleation/exenteration and modified evisceration are discussed, with species-specific nuances of small mammals, birds, reptiles, snakes, amphibians, and fish highlighted., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: While a positive margin after an attempt at breast conservation therapy (BCT) is a reason for concern, there is more controversy regarding close margins. When re-excisions are performed, there is often no residual disease in the new specimen, calling into question the need for the procedure. We sought to examine the incidence of residual disease after re-excision for close margins and to identify predictive factors that may better select patients for re-excision., Methods: Our IRB-approved prospective breast cancer database was queried for all breast cancer patients who underwent a re-excision lumpectomy for either close or positive margins after an attempt at BCT. Close margins are defined as < or =2 mm for invasive carcinoma and < or =3 mm for DCIS. Clinicopathologic features were correlated with the presence of residual disease in the re-excision specimen., Results: Three hundred three patients (32%) underwent re-operation for either close (173) or positive (130) margins. Overall, 33% had residual disease identified, 42% of DCIS patients and 29% of patients with invasive disease, nearly identical to patients with positive margins. For patients with DCIS, only younger age was significantly related to residual disease. For patients with invasive cancer, only multifocality was significantly associated with residual disease (OR 3.64 [1.26-10.48]). However, patients without multifocality still had a substantial risk of residual disease., Discussion: The presence of residual disease appears equal between re-excisions for close and positive margins. No subset of patients with either DCIS or invasive cancer could be identified with a substantially lower risk of residual disease.

Bias in referral patterns and variations in multi-disciplinary management may impact breast conservation therapy (BCT) rates between hospitals. Retrospective studies of BCT rates are limited by their inability to differentiate indicated mastectomies versus those chosen by the patient. Our prospective breast cancer data base was queried for patients with invasive breast cancer who underwent surgical therapy at the University of Michigan over a 3-year period. Demographics, stage and histology were recorded along with the reason mastectomy was performed, categorized as "by need" (contraindication to BCT) or "by choice." Multivariate analysis was used to identify factors significantly associated with mastectomy by choice. BCT was associated with tumor size, histology and nodal status, but not older age, either by choice or by need. Of the 34% of patients initially felt to be poor candidates for BCT, it was absolutely contraindicated in 44%, while 56% were thought to have a tumor-to-breast size ratio too large for successful BCT. Of this latter group, 80% underwent neo-adjuvant chemotherapy in an attempt to downstage the primary tumor and perform BCT, which was successful in over half the patients. For the patients initially thought to be good candidates for BCT, only 15% chose to undergo mastectomy, while 5% eventually required mastectomy due to failed attempts to achieve negative margins. Overall, the BCT rate was 63%, however without the use of neo-adjuvant chemotherapy, the BCT rate would have been only 53%. At a tertiary referral center, BCT rates are driven more by contraindications than patient choice, and may be heavily skewed towards mastectomy due to referral patterns. In addition to tumor factors such as stage and histology, BCT rate can be dramatically impacted by neo-adjuvant chemotherapy or genetic counseling. Examining BCT rates alone as a measure of quality, therefore, is not an appropriate standard across institutions serving diverse populations.

Background: Recent data have implicated tumor necrosis factor (ligand) superfamily, member 4 (TNFSF4) gene variation in myocardial infarction in women; however, no prospective data are available on either incident arterial or venous disorders., Methods: We evaluated 2 previously characterized TNFSF4 gene variants (-921C>T and dbSNP rs3850641) with a) incident arterial events using a prospective case-cohort design with 344 incident CVD cases and 2254 control participants, all white, drawn from the Women's Health Study cohort with 10 years of follow-up, and b) venous thromboembolism (VTE) risk using a nested, matched case-control design of 108 white male pairs (drawn from the Physicians' Health Study cohort) and a case-cohort design of white female participants consisting of 125 cases and 2269 controls (drawn from the Women's Health Study cohort), analyzed separately., Results: Genotype distributions were in Hardy-Weinberg equilibrium. Results from a marker-by-marker regression analysis, adjusting for traditional risk factors, showed a significant association of -921C>T with an increased risk of VTE in women (additive: odds ratio 1.86; 95% CI 1.17-2.92, P = 0.008) in women. Furthermore, using a haplotype-based regression analysis, haplotype C-G was associated with a reduced risk of VTE relative to the referent haplotype, C-A (odds ratio 0.50; 95% CI 0.27-0.92; P = 0.02). In contrast, we found little evidence for an association of the variants/haplotypes with risk of VTE in men or CVD risk in women (as previously reported)., Conclusions: Our present findings, if corroborated in other prospective investigations, suggest that the TNFSF4 variants tested may be useful indicators for assessing the risk of venous thromboembolism.

Recent data have implicated a haplotype of the purinergic receptor P2Y, G-protein coupled, 12 gene (P2RY12), as potential risk determinant for atherothrombosis. However, to date, no prospective, genetic-epidemiological data are available. Using DNA samples collected at baseline in a prospective cohort of 14,916 initially healthy American men, we examined the possible association of P2RY12 genetic variants, in particular a haplotype H2 (constituted by dbSNP rs10935838, rs2046934, rs5853517, and rs6809699) amongst 708 white males who subsequently developed a thromboembolic event (incident myocardial infarction (MI), ischemic stroke, or deep venous thromboembolism/pulmonary embolism (DVT/PE)) and amongst an equal number of age- and smoking-matched white males who remained free of reported vascular disease during follow-up (controls). The P2RY12 gene variants tested were in linkage disequilibrium. The haplotype H2 distribution was significantly different between the DVT/PE cases (12%) and their matched controls (21%), p-permuted=0.02. In an adjusted conditional logistic regression analysis, the haplotype H2 was significantly associated with a lower risk of incident DVT/PE as compared to the reference haplotype H1 (odds ratio=0.50, 95% CI=0.27-0.93, p=0.028). However, we found no evidence for an association of the P2RY12 variants or the haplotype H2 with incident MI or ischemic stroke. The present investigation provides evidence for an association of the P2RY12 haplotype H2 with lower risk of DVT/PE; however these findings require replication in other well-designed studies.

Introduction: Sentinel lymph node (SLN) biopsy using blue dye and radioisotope often results in the removal of multiple SLNs. We sought to determine whether there is a point where the surgeon can terminate the procedure without sacrificing accuracy., Methods: One thousand one hundred ninety-seven patients from University of Michigan and the Mayo Clinic undergoing SLN biopsy formed the study population. Surgeons removed all SLNs until counts within the axilla were less than 10% of the highest node ex vivo and recorded the order in which they were removed., Results: The mean number of SLNs removed per patient was 2.5 (range 1-9). Approximately 42% of patients had three or more lymph nodes removed, while 19% had four or more lymph nodes removed. Eighteen percent of patients (132/725) at University of Michigan and 22% (103/472) at Mayo Clinic had a positive SLN. Ninety-eight percent (231/235) of patients with lymph node metastases were identified by the 3rd SLN while 100% were identified by the 4th SLN., Conclusion: Among patients undergoing SLN biopsy for breast cancer, the only positive SLN is rarely identified in the 4th or higher node. Terminating the procedure at the 4th node may lower the cost of the procedure and reduce morbidity.

Case Description: A great horned owl of estimated age < 1 year that was captured by wildlife rehabilitators was evaluated because of suspected cataracts., Clinical Findings: Nuclear and incomplete cortical cataracts were evident in both eyes. Ocular ultrasonography revealed no evidence of retinal detachment, and electroretinography revealed normal retinal function., Treatment and Outcome: For visual rehabilitation, cataract surgery was planned and intraocular lens design was determined on the basis of values obtained from the schematic eye, which is a mathematical model representing a normal eye for a species. Cataract surgery and intraocular lens placement were performed in both eyes. After surgery, refraction was within -0.75 diopters in the right eye and -0.25 diopters in the left eye. Visual rehabilitation was evident on the basis of improved tracking and feeding behavior, and the owl was eventually released into the wild., Clinical Relevance: In raptors with substantial visual compromise, euthanasia or placement in a teaching facility is a typical outcome because release of such a bird is unacceptable. Successful intraocular lens implantation for visual rehabilitation and successful release into the wild are achievable.

Objective: Recent data have shown an association between polymorphisms of prostaglandin-endoperoxide synthase-2 gene (PTGS2; alias COX-2), and prostaglandin-E receptor-2 gene (PTGER2) and risk of atherothrombotic disorders., Methods: We evaluated two PTGS2 (rs20417, rs689470), and three PTGER2 (rs708494/uS5, rs708495/uS7, and chr14: 50 764 013/uS10) gene polymorphisms among 600 Caucasian male participants of the Physicians' Health Study with incident myocardial infarction (MI) or ischemic stroke and 600 age- and smoking-matched controls who remained free of all reported cardiovascular disease., Results: Genotype distributions were in Hardy-Weinberg equilibrium in the control groups. Genotype and allele distribution were similar between cases and controls. The polymorphisms tested were in linkage disequilibrium. Results from the adjusted haplotype-based conditional logistic regression analysis showed a modest association of the PTGER2 2-1-1 haplotype with reduced risk of MI (odds ratio = 0.50, 95% CI; CI = 0.26-0.97, P = 0.04), and the 2-2-1 haplotype with reduced risk of ischemic stroke (odds ratio = 0.68, 95% CI = 0.47-0.99, P = 0.048). In contrast to prior data, we found no evidence for an association of the PTGS2 polymorphisms/haplotypes tested with risk of incident MI nor with ischemic stroke. However, we found suggestive evidence for an association of specific PTGER2 haplotypes with reduced risk of these outcomes., Conclusion: Although these prospective data implicate the potential involvement of prostaglandin-E receptor-2 gene variation in atherothrombosis, external validation of our findings is needed.

Objectives: An exonic polymorphism (Y402H) in the complement factor H (CFH) gene, which locates within the binding sites for heparin and C-reactive protein, has recently been described and hypothesized to play an important role in atherothrombosis., Methods: We, therefore, evaluated the CFH genetic variant Y402H amongst 685 Caucasian individuals who subsequently developed arterial or venous thrombotic event (incident myocardial infarction (MI), ischaemic stroke, or venous thromboembolism) and amongst 685 age- and smoking-matched Caucasian individuals who remained free of reported vascular disease during follow-up (controls) within the Physicians' Health Study cohort., Results: Genotype distribution for the polymorphism tested was in Hardy-Weinberg equilibrium in the control group. In contrast to expected results, we found no association of Y402H polymorphism with risk of atherothrombosis (adjusted: myocardial infarction, OR=1.09, 95%CI 0.88-1.36, p=0.43; ischaemic stroke, OR=1.11, 95%CI 0.81-1.54, p=0.52; venous thromboembolism, OR=1.41, 95%CI 0.88-2.24, p=0.15), nor with baseline plasma C-reactive protein levels [median (interquartile range) mg/L: YY, 1.39 (0.70-2.60); YH, 1.10 (0.57-2.16); HH, 1.00 (0.48-1.79); p=0.14]., Conclusions: In this large, prospective cohort of apparently healthy Caucasian men, we found no association of the complement factor H Y402H gene polymorphism with risk of incident thromboembolic events, nor with baseline levels of C-reactive protein.

The effect on intraocular pressure (IOP) from dogs pulling against a collar or a harness was evaluated in 51 eyes of 26 dogs. The force each dog generated while pulling against a collar or a harness was measured. Intraocular pressure measurements were obtained during application of corresponding pressures via collars or harnesses. Intraocular pressure increased significantly from baseline when pressure was applied via a collar but not via a harness. Based on the results of the study, dogs with weak or thin corneas, glaucoma, or conditions for which an increase in IOP could be harmful should wear a harness instead of a collar, especially during exercise or activity.

The purpose of this study was to evaluate the effect of surface topographic features that mimic the corneal epithelial basement membrane on cell migration. We used electron-beam and X-ray lithography and reactive ion etching to pattern silicon wafers with pitches (groove width plus ridge width) of nano- and microscale dimensions (pitches ranged from 400 to 4000 nm). Additionally, polyurethane patterned surfaces were created by replication molding techniques to allow for real-time imaging of migrating cells. Individual SV40-transformed human corneal epithelial cells frequently aligned with respect to the underlying surface patterns and migrated almost exclusively along grooves and ridges of all pitches. Direction of migration of individual cells on smooth surfaces was random. In cell dispersion assays, colonies of cells migrated out from initially circular zones predominantly along grooves and ridges, although there was some migration perpendicular to the ridges. On smooth surfaces, cells migrated radially, equally in all directions, maintaining circular colony shapes. We conclude that substratum features resembling the native basement membrane modulate corneal epithelial cell migration. These findings have relevance to the maintenance of corneal homeostasis and wound healing, as well as to the evolution of strategies in tissue engineering, corneal prosthesis development, and cell culture material fabrication., ((c) 2005 Wiley Periodicals, Inc.)

Objective: To evaluate the usefulness of high-resolution ultrasonography (HRUS) for measurements of anterior segment structures in canine eyes., Animals: 4 clinically normal Beagles., Procedure: Images were obtained from 8 eyes with a handheld 20-MHz transducer. Eleven anterior segment structures on each image were measured 5 times by 2 independent observers. Coefficients of variation (CVs) for measurements were used to assess intraobserver reliability. Interobserver reliability was assessed by comparing measurements obtained by the 2 observers from the same images. Five images were sequentially obtained from 2 locations (ie, superior and temporal) to evaluate image reproducibility. Anterior segment structures were measured once on each image; image reproducibility was assessed by use of the CV for each parameter measured. Imaging location was assessed by comparison of CV for measurements from each location., Results: CVs were < 10% for observer A for all measurements except the ciliary cleft area (11.63%). The CVs were > 10% for observer B for measurements of the angle recess area (18.51%) and ciliary cleft width (17.44%) and area (16.01%). Significant differences in measurements between observers were found for 5 of 11 anterior segment structures. Imaging the superior aspect of the globe provided the most reproducible images, although image reproducibility was still somewhat variable, with the highest and lowest CVs for measurements of 33.01% and 11.32%, respectively, in the superior position., Conclusions and Clinical Relevance: High-resolution ultrasound images can be used to reliably measure various anterior segment structures. Clinically relevant findings in the anterior segment of canine eyes may be detectable by use of HRUS.

The recent development of a 20-MHz, high-frequency ultrasound probe has allowed tissue to be visualized at resolutions of 20 to 80 microm, which is similar to a low-power histologic view. This high degree of resolution, however, limits tissue penetration to 5 to 10 mm, which is ideal for examination of the anterior segment of the eye. The detail provided by high-resolution ultrasound readily permits the clinician to distinguish between various anterior segment entities that may appear similar but are treated quite differently, such as anterior uveal tumors, iridociliary cysts, and iris bombé. High-frequency ultrasound is also a valuable aid in creating a surgical plan for treatment of ocular disorders in which the cornea is opaque, such as feline corneal sequestrum and tumor invasion into the cornea. Other applications of this technology include elucidation of the pathogenesis of glaucoma in veterinary patients and evaluation of regions of the lens that are difficult to examine directly.

Significant advances have recently been achieved in the development of topical glaucoma medications. The primary advantage of a topical preparation is the reduced incidence of adverse systemic effects attributable to a given drug compared to its systemically administered counterpart. However, the strong protective barrier of the eye forces topical ophthalmic preparations to be highly concentrated and in some cases, they have the potential to produce unwanted systemic effects, particularly in smaller animals. Oral carbonic anhydrase inhibitors are commonly associated with adverse effects in both humans and animals. Two recently developed topical carbonic anhydrase inhibitors, dorzolamide and brinzolamide, have shown promise in reducing intraocular pressure in animals and systemic side effects are apparently limited with their use. The topical alpha2-agonist apraclonidine, on the other hand, effectively reduces intraocular pressure in cats and dogs, but in its currently available form is likely to induce unwanted systemic effects. Latanoprost is a topical prostaglandin F2alpha analog that has proven effective in reducing intraocular pressure in dogs and horses, but while systemic side effects have not yet been reported, this topical preparation may exacerbate pre-existing or concurrent ocular inflammatory disease.

Hyperthermia above a critical threshold results in multisystemic changes that include neurological manifestations of heat stroke. It is unknown if the latter represents an intrinsic thermal sensitivity of the CNS or whether injury is secondary to physiological responses of non-CNS origin. To address this issue, the present work examined functional, structural, and biochemical changes in the CNS of dogs subjected to a thermal dosage immediately below that which induces disseminated intravascular coagulation with secondary multiple organ injury. The experimental approach is previously reported, inducing a 42.5 degrees C, 90 min, whole body hyperthermia while preventing other physiological responses to treatment, including respiratory alkalosis and significant reductions in mean arterial pressure. Functional analyses included neurologic examinations and brainstem auditory evoked potential recordings in the post-treatment interval in both hyperthermic and euthermic control populations. Biochemical and structural analyses examined the expression of 70-kDa heat shock proteins, cytokines, markers of astroglial and microglial injury/activation, evidence of vascular endothelial damage, and evidence of neuronal and axonal injury in brain between 0.5 h and 8 days from the end of the treatment. The only significant change associated with treatment was induction of the major inducible 70-kDa heat shock protein, this being most prominent in the cerebellum with maximal expression at 6 h and a return to baseline by 8 days.Collectively, from these results we suggest that the canine brain is intrinsically resistant to sublethal hyperthermia such that when CNS lesions occur, they do so in the presence of other physiological derangements.

Objective: To determine the effect of 0.005% latanoprost solution on intraocular pressure (IOP) of eyes of clinically normal horses and establish the frequency of adverse effects of drug administration., Animals: 20 adult clinically normal horses., Procedure: IOP was recorded (7, 9, and 11 AM; 3, 5, and 7 PM) on days 1 and 2 (baseline), days 3 to 7 (treatment), and days 8 to 9 (follow-up). Latanoprost was administered to 1 randomly assigned eye of each horse every 24 hours during the treatment period, following the 7 AM IOP recording. Pupil size and the presence or absence of conjunctival hyperemia, epiphora, blepharospasm, blepharedema, and aqueous flare were recorded prior to IOP measurement., Results: IOP was reduced from baseline by a mean value of 1.03 mm Hg (5%) in males and 3.01 mm Hg (17%) in females during the treatment period. Miosis developed in all treated eyes and was moderate to marked in 77% of horses, with the peak effect observed 4 to 8 hours after drug administration. Conjunctival hyperemia, epiphora, blepharospasm, and blepharedema were present in 100, 57, 42, and 12% of treated eyes, respectively, 2 to 24 hours following drug administration. Aqueous flare was not observed at any time point., Conclusions and Clinical Relevance: Although IOP was reduced with every 24-hour dosing of latanoprost, the frequency of prostaglandin-induced adverse events was high. Because recurrent uveitis appears to be a risk factor for glaucoma in horses, topical administration of latanoprost may potentiate prostaglandin-mediated inflammatory disease in affected horses.

Use of hyperthermia in the treatment of cancer and viral infection has received renewed interest. However, the in vivo relationship between hyperthermia and direct versus indirect effects upon hemostasis are incompletely defined, although we do know that disseminated intravascular coagulation (DIC) is a common sequel to heat stroke. The purpose of the present study was to more precisely define the relationship between hyperthermia and derangements of hemostasis, thereby providing a guideline for the development of safe hyperthermia treatment regimens. The present investigation examined the in vivo effects of high-grade whole-body hyperthermia (WBH) (42.5 degrees C, 90 min) on hemostasis in a canine model. Induction of hyperthermia via extracorporeal circulation of heated blood (ECC-WBH) caused thrombocytopenia, increased plasma fibrin degradation products (FDPs), prolonged clotting times, increased serum liver enzymes, and evidence of spontaneous bleeding. However, when WBH was induced by peritoneal lavage (PL-WBH), transient thrombocytopenia was the only significant alteration. Temporal correlation between hemostatic alterations and elevations in serum alanine aminotransferase (ALT) levels in the ECC-WBH treatment group suggested that liver injury is responsible, at least in part, for the coagulopathy associated with high-grade hyperthermia and that in the absence of liver injury, identical degrees of hyperthermia cause only incidental decreases in platelet numbers., (Copyright 2000 Wiley-Liss, Inc.)