bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased prostaglandin E2 levels in the airway of patients with eosinophilic bronchitis
Authors: Sastre B. , Fernández‐Nieto M. , Mollá R. , López E. , Lahoz C. , Sastre J. , Del Pozo V. , Quirce S.
Published: October 2007

Background:  Eosinophilic bronchitis is a common cause of chronic cough, which like asthma is characterized by sputum eosinophilia, but unlike asthma there is no variable airflow obstruction or airway hyperresponsiveness. We tested the hypothesis that the different airway function in patients with eosinophilic bronchitis and asthma could be caused by an imbalance in the production of bronchoconstrictor (LTC4) and bronchoprotective (prostaglandin E2; PGE2) lipid mediators.

Methods:  We measured cytokines levels, proinflammatory mediators and eicosanoids concentration in sputum from 13 subjects with nonasthmatic eosinophilic bronchitis, 13 subjects with asthma, and 11 healthy control subjects. Cytokines mRNA levels were measured by real time PCR, proinflammatory mediators, PGE2, and LTC4 were measured by enzyme immunoassays.

Results:  The median sputum eosinophil count was not statistically different in patients with asthma (7.95%) and eosinophilic bronchitis (15.29%). The levels of mRNA specific to interleukin‐5 (IL‐5), IL‐4, IL‐10, IL‐13, interferon γ (IFN‐γ), IL‐2, vascular endothelial growth factor and transforming growth factor β were similar in both conditions. In addition, no differences were found between asthma and eosinophilic bronchitis in proinflammatory cytokines, such as IL‐8, IFN‐γ and tumor necrosis factor α (TNF‐α) levels. Sputum cysteinyl‐leukotrienes concentration was raised both in eosinophilic bronchitis and asthma patients. We found that induced sputum PGE2 concentrations were significantly increased in subjects with eosinophilic bronchitis (838.3 ± 612 pg/ml) when compared with asthmatic (7.54 ± 2.14 pg/ml) and healthy subjects (4 ± 1.3 pg/ml).

Conclusion:  This data suggest that the difference in airway function observed in subjects with eosinophilic bronchitis and asthma could be due to differences in PGE2 production in the airways.
Growth and weight gain of prepubertal children after cardiac transplantation
Authors: Peterson Renuka E. , Perens Gregory S. , Alejos Juan C. , Wetzel Glenn T. , Chang Ruey‐Kang R.
Published: October 2007

Abstract:  This study evaluated changes in growth parameters after pediatric heart transplantation and identified factors associated with the changes after pediatric heart transplantation (OHT). We retrospectively evaluated the somatic growth of 46 children <11 yr of age who underwent OHT for changes in weight, height, and BMI. The patient age range was 3.5 months to 10.7 yr. Gain in Z score for weight and BMI was significant at six months post‐OHT (mean weight Z score changed from −1.1 to −0.1 and mean BMI Z score changed from −0.1 to 1.3; p < 0.001). After six months post‐OHT, there was no further significant change in weight or BMI Z score. Height Z score did not show significant change from pre‐OHT at six months, one yr, or two yr post‐OHT. Eight patients (17%) became overweight during the two‐yr follow‐up period as evidenced by a BMI Z score > 2. Multivariate analysis showed length of steroid treatment as a predictor for negative height Z score change, and age at transplant as a predictor for positive height Z score change. Post‐OHT, weight significantly increases without proportional increases in height, resulting in a significant proportion of these children becoming obese. Length of steroid therapy is negatively related to the “catch‐up” linear growth following OHT.
Prevention of pediatric graft coronary artery disease: Atorvastatin
Authors: Chin Clifford , Lukito Sophia S. , Shek Jennifer , Bernstein Daniel , Perry Stanton B.
Published: October 2007

Abstract:  Graft coronary artery disease is a significant cause of late graft failure and death after cardiac transplantation. HMG‐coenzyme A reductase inhibitors have been used safely in children but their preventative effects against GCAD are not well known. We investigated whether atorvastatin when initiated early could prevent against the development of pediatric GCAD. Pediatric patients (transplanted between October 28, 1992 and July 9, 2004) were stratified into two groups based on whether or not they received atorvastatin early after transplant. Angiograms were reviewed by a single observer blinded to the treatment strategies and clinical outcomes. Actuarial survival method and the Mantel‐Cox test were used to assess statistical significance. Freedom from GCAD was higher among those treated with atorvastatin early in the post‐transplant course. One, three, and five‐yr freedom from GCAD was significantly greater in the early treatment group (97%, 93%, and 93% respectively) compared with the control group (72%, 65%, and 60% respectively, p < 0.005). The early treatment group was also noted for fewer rejection episodes in the first post‐transplant year. The use of atorvastatin when initiated early in the post‐transplant course appears protective against graft coronary artery disease.
Safety and pharmacokinetics of daclizumab in pediatric renal transplant recipients
Authors: Pescovitz Mark D. , Knechtle Stuart , Alexander Steven R. , Colombani Paul , Nevins Tom , Nieforth Keith , Bouw M. René
Published: October 2007

Abstract:  This study examined the safety and pharmacokinetics/pharmacodynamics of daclizumab in combination with mycophenolate mofetil (or azathioprine), corticosteroids, and cyclosporine or tacrolimus, in 61 pediatric renal allograft recipients in three age groups: less than or equal to five yr (n = 18), 6–12 yr (n = 18), and 13–17 yr (n = 25). The dosing regimen was daclizumab 1.0 mg/kg before transplantation, followed by four biweekly doses. The pharmacokinetics of daclizumab were described using NONMEM software. Median (range) estimated trough daclizumab levels achieved on day 56 (before dose 5) were 3.88 μg/mL (2.48–8.78), 4.54 μg/mL (1.79–18.7), and 4.94 μg/mL (0.05–10.6) in the less than or equal to five yr (n = 15), 6–12 yr (n = 17), and 13–17 yr (n = 22) age groups, respectively. Steady‐state median (range) daclizumab exposures were 2040 mg · h/mL (1585–3778), 2757 mg · h/mL (1873–3494) and 3297 mg · h/mL (1705–6453), respectively. Saturation of the IL‐2R occurred rapidly and was maintained for greater than or equal to three months after transplantation. Daclizumab was generally well‐tolerated with no acute allergic or anaphylactic reactions, deaths or malignancies during the study. The proportion of patients who developed acute rejection at six and 12 months was 8.5% and 16.7%, respectively. This study shows that adding daclizumab at 1 mg/kg to standard immunosuppressive therapy provides safe and effective IL‐2R blockade.
Effects of 4‐chloro‐2,6‐bis‐(2‐hydroxyl‐benzyl)‐phenol on Healing of Skin Wounds and Growth of Bacteria
Authors: Oryan A. , Khalafi‐Nezhad A. , Toloo N. , Soltani Rad M. N.
Published: October 2007

In this investigation, the effects of synthesized 4‐chloro‐2,6‐bis‐(2‐hydroxyl‐benzyl)‐phenol (CBHBP) on cutaneous wound healing and growth of some of the wound contaminating microorganisms were studied. The antibacterial effects of this compound were then evaluated on Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli) and Klebsiella spp., using solid dilution method. It was demonstrated that CBHBP has a significant antimicrobial activity against S. aureus but it is not effective in the case of other microorganisms studied in this experiment. The effect of local administration of CBHBP on healing of a standard full‐thickness 2 cm skin incision of skeletally mature rats was evaluated. Histological changes together with mechanical properties and dry weight content of the healing tissues at the site of the lesions were assessed in treated and untreated animals. It was observed that the injured area of the treated animals was more organized and showed more fibroblasts and less inflammatory cells. Much better maturation criteria in treated tissues were observed in comparison with those of the untreated ones which contained numerous polymorphonuclear inflammatory cells after 14 days post‐injury. Many infiltrated macrophages and lymphocytes were present even 28 days after injury induction in the haphazardly organized dermis and also in subcutaneous tissues of the untreated animals. The percentage dry weight content of the treated lesions at 14 days post‐injury was remarkably higher than those of the untreated animals. The results of biomechanical tensile testing showed that the ultimate tensile strength and stress of the injured skin of the treated animals were higher than those of the untreated ones. From these results, it could be concluded that CBHBP can be effective on wound healing and may be considered as a treatment regimen after evaluating its mechanism of action as well as testing its contraindications.
Proliferation of Pulmonary Artery Smooth Muscle Cells in the Development of Ascites Syndrome in Broilers Induced by Low Ambient Temperature
Authors: Wang J. , Qiao J. , Zhao L. H. , Li K. , Wang H. , Xu T. , Tian Y. , Gao M. , Wang X.
Published: October 2007

Pulmonary vascular remodelling, mainly characterized by arterial medial thickening, is an important pathological feature of broiler ascites syndrome (AS). Since vascular smooth muscle cells (VSMC) form the major cellular component of arterial medial layer, we speculate that VSMC proliferation is one of the causes of pulmonary arterial medial thickening in ascitic broilers. Hence, the present study was designed to investigate the role of VSMC proliferation in pulmonary vascular remodelling in development of AS induced by low ambient temperature. Broilers in control group (22 ± 1.5°C) and low temperature group (11 ± 2°C) were sampled every week at 15–50 days of age. Proliferative indexes of VSMC in pulmonary arteries were assessed with proliferating cell nuclear antigen, and the relative medial thickness (RMT) and relative wall area (RWA), as indexes of pulmonary vascular remodelling, were examined by computer‐image analysing system. The results showed that the high incidence (18.75%) of AS was induced by low temperature, and a significantly increased VSMC proliferation was observed in pulmonary arteries in the low temperature group at 22–50 days of age (P < 0.05). In addition, RMT and RWA in pulmonary arteries were significantly elevated in the low temperature group from 36 days of age (P < 0.05), indicating that pulmonary vascular remodelling occurred following VSMC proliferation in AS. Our data suggest that proliferation of VSMC may facilitate pulmonary vascular remodelling and have a pivotal role in AS induced by low ambient temperature.
Identification and Antimicrobial Susceptibility of Bacteria and Yeasts Isolated from Healthy Dogs and Dogs with Otitis Externa
Authors: Lyskova P. , Vydrzalova M. , Mazurova J.
Published: October 2007

The bacterial and fungal flora of the external ear canal of dogs with otitis externa and of healthy dogs were studied. The most frequently isolated microorganism from otitic ears wasStaphylococcus intermedius(58.8%), followed byMalassezia pachydermatis(30.9%),Streptococcus canis(29.9%),Proteusspp. (14.4%) andEscherichia coli(10.3%). A statistical analysis of our results showed that the prevalence of these microorganisms is significant in dogs with otitis externa. Furthermore, the antimicrobial susceptibility patterns of isolated strains were determined. Majority of all bacterial isolates were most susceptible to gentamicin.Malassezia pachydermatis, the most prevalent yeast in this study, showed an excellent level of susceptibility to all antifungal agents tested.
A Case of Intravascular Lymphoma with Mixed Lineage Antigen Expression in a Cat
Authors: Henrich M. , Huisinga M. , Bauer N. , Reinacher M.
Published: October 2007

A 3‐year‐old neutered male British shorthair cat was presented to the Clinic for Small Animal Medicine, Internal Medicine and Clinical Pathology, at the Justus‐Liebig‐University Giessen with a short history of lethargy, severe dyspnoea, fever, anaemia, thrombocytopenia and hyperbilirubinaemia. In blood smears and lymph node aspirates, large pleomorphic lymphatic blasts were detected. On necropsy splenic infarcts and moderate hydrothorax as well as moderate ascites could be observed. Histological examination revealed large numbers of lymphoid blasts within the lumen of the vessels of the lung, lymph nodes, the liver, the chorioid coat of the eyes, in meningeal vessels, arteries and veins of the brain, and within the larger splenic vessels. Neoplastic cells immunohistochemically stained positive for CD45R and CD3. Based on these findings, an intravascular lymphoma was diagnosed.
Extending rural and remote medicine with a new type of health worker: Physician assistants
Authors: O'Connor Teresa M. , Hooker Roderick S.
Published: October 2007

The purpose of this paper was to demonstrate that the medical workforce shortage is an international phenomenon and to review one of the strategies developed in the USA in the late 1960s: the physician assistant model of health service provision. The authors consider whether this model could provide one strategy to help address the medical workforce shortage in Australia. A systematic review of the literature about medical workforce shortages, strategies used to address the medical workforce shortage, and the physician assistant role was undertaken. Literature used for the review covered the period 1967–2006. Physician assistants provide safe, high‐quality and cost‐effective primary care services under the direction of a doctor and respond to workforce shortages in rural and remote areas, family practice medicine and hospital settings. This model of health care provision has been adopted in several other developed countries, including England, Scotland, the Netherlands and Canada. The physician assistant concept might provide Australia with a novel strategy for addressing its medical workforce shortage, particularly in rural and remote settings.
Recruitment and retention of rural general practitioners: A marketing approach reveals new possibilities
Authors: Hemphill Elizabeth , Dunn Steve , Barich Hayley , Infante Rebecca
Published: October 2007

Objective:  This paper repositions the challenge of attracting and retaining rural GPs in a marketing context as a new focus for future research and policy development.

Design:  Case study with mixed design of surveys of GPs and medical students and depth interviews with GPs, medical students, regional‐division administrators and GP recruitment agents.

Setting:  GP recruitment and retention in the Limestone Coast region of South Australia.

Participants:  Twenty‐seven Limestone Coast (LC) GPs; random sample of medical students from Adelaide University, Adelaide University Rural Health Society and Flinders University; snowball sampling two adjacent rural regions (20 GPs); and administrators from LC and adjacent regions and GP recruitment agencies in Adelaide.

Main outcome measures:  Drawing from marketing theory, creative suggestion of ‘promotion of the practice and not the region’ offers a means of GP recruitment and retention for structured succession planning for rural general practices.

Results:  Structural attempts to broaden the GP market with overseas recruitment have done little for improving full‐time equivalent GP levels. Market segmentation and market orientation offer a new emphasis on value exchange between the corporation (the practice), customer (GPs) and competition (all practices) to influence future mobility.

Conclusion:  A marketing orientation to the GP challenge emphasises individual's perceptions of value, GP expectations and practice offerings. Failure to acknowledge benefits of this marketing approach means that solutions such as those developed in the Limestone Coast region are unlikely. Research is now required to define GP satisfaction and value for long‐term viability of general practices.
Primary health care in the Kimberley: Is the doctor shortage much bigger than we think?
Authors: Roach Sally , Atkinson David , Waters Andrew , Jefferies Felicity
Published: October 2007

Objective:  This study describes the extent to which general practitioners in the Kimberley region are available for doctor‐provided primary care and relates primary care availability to need and standardised population.

Design:  Data collection and analysis was based on government statistics and interviews with general practitioners, local managers and regional employers and organisations.

Results:  A shortfall of 20.6 full time general practitioner positions was identified and this was aggravated by a significant number of unfilled positions in the areas of greatest need. Overall the region had only half the primary care general practitioners needed. The Shire of Halls Creek at the time of survey had less than a quarter of the doctors required based on this analysis.

Conclusion:  Steps to increase the Australian medical workforce have begun but resources to recruit, support and sustain this workforce are required. Aboriginal health workers and locally trained nurses competently provide much of the primary care but need greater resources to support the available medical care.
Physiotherapy in rural and regional Australia
Authors: Williams Elizabeth , D'Amore Wendy , McMeeken Joan
Published: October 2007

Objective:  To inform rural physiotherapy recruitment and retention strategies by describing physiotherapists in the Shepparton region: reasons for career choice, education and physiotherapy professional issues.

Design:  Survey.

Setting:  Health service providers.

Participants:  Practising and non‐practising physiotherapists.

Main outcome measure:  Survey responses.

Results:  Survey response rate 79%. Eighty four physiotherapists (79 practicing and 5 non‐practicing; 80% female) clustered in main regional centres responded. Two‐thirds worked part‐time with most in the public sector (70%), with one third holding more than one position. One‐third considered themselves generalists and one‐third specialists. Physiotherapy was first career choice for 83% who made this decision between 14 and 19 years old (16.8–2.5 years) because of contact with a physiotherapist. Professional issues challenging physiotherapists in a rural location are compounded by lack of career path, professional support, access to professional development and postgraduate education. Additional issues are the costs and time to attend courses and conferences, travel/distance, and inadequate resources. Positive elements of rural practice were part‐time employment opportunities, independence as primary health providers, practice variety and community recognition.

Conclusion:  Rural physiotherapy recruitment and retention strategies must address resource shortcomings by developing career paths, access to postgraduate education and support. Enhancing workforce capacity could enable more students to have meaningful rural experience to assist recruitment. Strategies highlighting existing positive features of rural practice, reinforced with tangible rewards and recognition of physiotherapists’ contribution to the health care of Australians are recommended.
OATP1B1 POLYMORPHISM IS A MAJOR DETERMINANT OF SERUM BILIRUBIN LEVEL BUT NOT ASSOCIATED WITH RIFAMPICIN‐MEDIATED BILIRUBIN ELEVATION
Authors: Zhang Wei , He Yi‐Jing , Gan Zhou , Fan Lan , Li Qing , Wang An , Liu Zhao‐Qian , Deng Sheng , Huang Yuan‐Fei , Xu Lin‐Yong , Zhou Hong‐Hao
Published: October 2007

Elevated serum bilirubin levels are caused mainly by liver diseases, haematolysis, genetic defects and drug intake. Unconjugated bilirubin (UCB) is taken up into hepatocytes by human organic anion transporting polypeptide 1B1 (OATP1B1; encoded for by the SLCO1B1 gene). The present study was performed to determine the association between SLCO1B1 gene polymorphisms and serum bilirubin levels in vivo. Moreover, the effects of administration of low‐dose rifampicin on serum bilirubin levels in different SLCO1B1 genotypes was examined.

Serum bilirubin levels were examined in 42 healthy volunteers who had been analysed for SLCO1B1 genotype (seven, 13, 14 and eight with SLCO1B1 genotypes *1a/*1a, *1b/*1b, *1b/*15 and *15/*15, respectively). Among them, 24 subjects (seven, seven, eight and two with SLCO1B1 genotypes *1a/*1a, *1b/*1b, *1b/*15 and *15/*15, respectively) were selected to participate in an open‐label, two‐phase clinical trial. Each was given 450 mg rifampicin orally once daily at 2000 hours for 5 consecutive days. Serum bilirubin concentrations at 0800 hours on the 1st and 6th days were compared between the different SLCO1B1 genotypes.

In the 42 volunteers, the mean (±SD) serum UCB in both SLCO1B1*1b/*15 and *15/*15 groups was significantly higher than that in the SLCO1B1*1b/*1b group (11.07 ± 2.31, 13.01 ± 3.87 and 8.21 ± 2.68 µmol/L, respectively; P = 0.009 and P < 0.001). Total bilirum (T.BIL) in both the SLCO1B1*1b/*15 and *15/*15 groups was significantly higher than that in the SLCO1B1*1b/*1b group (16.69 ± 4.09, 20.71 ± 5.12 and 13.06 ± 5.12 µmol/L, respectively; P = 0.029 and P < 0.001). The direct bilirubin (D.BIL) in the SLCO1B1*15/*15 group was significantly higher than that in the SLCO1B1*1b/*1b group (7.69 ± 1.81 vs 4.85 ± 1.81 µmol/L, respectively; P = 0.001). Rifampicin significantly increased UCB, T.BIL and D.BIL concentrations in 24 healthy volunteers (17.68 ± 5.96 vs 13.95 ± 4.44 µmol/L (P = 0.040), 5.72 ± 2.01 vs 4.35 ± 1.50 µmol/L (P = 0.028) and 12.00 ± 4.26 vs 9.61 ± 3.15 µmol/L (P = 0.035), respectively). However, the extent of the increase in serum bilirubin caused by 450 mg rifampicin for 5 days was not affected by SLCO1B1 genotype.

Genetic polymorphism in SLCO1B1 is a major determinant of interindividual variability in the serum bilirubin level. SLCO1B1*15 carriers had higher baseline serum UCB, T.BIL and D.BIL levels compared with subjects with the SLCO1B1*1a/*1a and SLCO1B1*1b/*1b genotypes. SLCO1B1*15/*15 homozygotes are more susceptible to hyperbilirubinaemia. Serum bilirubin levels could be increased by low‐dose rifampicin administration, but the extent of the increase was not associated with SLCO1B1 genotype.
Shared signals –‘alarm calls’ from plants increase apparency to herbivores and their enemies in nature
Authors: Halitschke Rayko , Stenberg Johan A. , Kessler Danny , Kessler André , Baldwin Ian T.
Published: October 2007

The attraction of natural enemies of herbivores by volatile organic compounds as an induced indirect defence has been studied in several plant systems. The evidence for their defensive function originates mainly from laboratory studies with trained parasitoids and predators; the defensive function of these emissions for plants in natural settings has been rarely demonstrated. In native populations and laboratory Y‐tube choice experiments with transgenic Nicotiana attenuata plants unable to release particular volatiles, we demonstrate that predatory bugs use terpenoids and green leaf volatiles (GLVs) to locate their prey on herbivore‐attacked plants. By attracting predators with volatile signals, this native plant reduces its herbivore load – demonstrating the defensive function of herbivore‐induced volatile emissions. However, plants producing GLVs are also damaged more by flea beetles. The implications of these conflicting ecological effects for the evolution of induced volatile emissions and for the development of sustainable agricultural practices are discussed.
Genes encoding the candidate enzyme for anaerobic activation of n‐alkanes in the denitrifying bacterium, strain HxN1
Authors: Grundmann Olav , Behrends Astrid , Rabus Ralf , Amann Judith , Halder Thomas , Heider Johann , Widdel Friedrich
Published: October 2007

Strain HxN1, a member of the Betaproteobacteria, can grow anaerobically by denitrification with n‐alkanes. n‐Alkanes are apparently activated by subterminal carbon addition to fumarate yielding (1‐methylalkyl)succinates, the postulated enzyme being (1‐methylalkyl)succinate synthase (Mas). Genes encoding this enzyme (mas) were searched for via proteins that were specifically formed in n‐hexane‐grown cells (in comparison with caproate‐grown cells), as revealed by two‐dimensional gel electrophoresis. Partial amino acid sequencing and subsequent probe development for hybridization of restricted DNA led to the identification of a gene cluster. Deduced proteins are similar to the subunits of benzylsuccinate synthase (Bss), the toluene‐activating enzyme in other anaerobic bacteria and its activase. The tentative (1‐methylalkyl)succinate synthase is presumably a heterotrimer (MasDEC) which, like benzylsuccinate synthase, contains a motif (in MasD, the large subunit) characteristic of glycyl radical‐bearing sites. Based on amino acid sequence comparison, the tentative (1‐methylalkyl)succinate synthase branches outside of the phylogenetic cluster of benzylsuccinate synthases from different organisms and represents a separate line of descent within glycyl radical enzymes. n‐Hexane‐induced co‐transcription of the mas genes and additional genes of an apparent operon was demonstrated by Northern hybridization experiments.
The NHS Bowel Cancer Screening Programme – a realistic approach with additional benefits
Authors: West N. J. , Poullis A. P. , Leicester R. J.
Published: October 2007

Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer death in the UK with 36 100 new cases diagnosed each year in England and Wales and 55% of all patients presenting with lymph node metastases at the time of diagnosis. Early detection, before the development of symptoms, may be an effective way of reducing mortality and it is this which a screening programme seeks to address. The NHS Bowel Cancer Screening Programme (NHS BCSP) commenced in April 2006 and invites men and women aged 60–69 to participate via submission of a faecal occult blood test every 2 years; those with a positive result will be offered colonoscopy as the next investigation of choice. This article will explore the background to the programme, including the financial considerations behind it and the implication that this has had on colonoscopy standards and training in the UK. The chosen programme is not the most effective neither in terms of survival benefit nor cost effectiveness but is a compromise within a financially strained health care system. Endoscopy standards because of its introduction have, however, considerably improved in terms of patient experience, safety and improved practice.
Goniodysgenesis associated with primary glaucoma in an adult European Short‐haired cat
Authors: Trost Katrin , Peiffer Robert L. , Nell Barbara
Published: October 2007

A 9.5‐year‐old, male castrated European Short‐haired (ESH) cat was presented with bilateral glaucoma associated with pectinate ligament dysplasia and an open iridocorneal angle (ICA) upon gonioscopy. The right eye (OD) was avisual and slightly enlarged; the left eye (OS) was still visual. Intraocular pressure (IOP) had been controlled with medical therapy over a 1.5 year‐period in both eyes (OU). Eventually IOP could not be adequately controlled medically and the painful and blind right eye was enucleated and transscleral diode laser cyclophotocoagulation was performed twice in the left eye with less than optimal results and progressive loss of vision. Histopathology of the right eye showed goniodysgenesis characterized by failure of differentiation of the pectinate ligament, which existed as a solid sheet of uveal tissue at the entrance of a hypoplastic ciliary cleft, which contained loose mucoid mesenchymal tissue. The trabecular meshwork was hypoplastic and the scleral venous plexus could not be identified. Other findings of chronic glaucoma were inner retinal atrophy, optic nerve atrophy with disc cupping, scleral thinning, peripheral corneal vascularization and pigmentation, and mild focal iridal mononuclear inflammatory cell infiltrate.
Variation in intraocular pressure following application of tropicamide in three different dog breeds
Authors: Taylor Nicole R. , Zele Andrew J. , Vingrys Algis J. , Stanley Robin G.
Published: October 2007

Objective  To record intraocular pressure (IOP) of three different dog breeds following administration of one drop of 1% tropicamide.

Animals  Three dog breeds – Golden Retrievers (n = 20), Siberian Huskies (n = 20) and English Cocker Spaniels (n = 36) – were studied.

Procedure  IOPs were measured using a Tonopen following corneal anesthesia with a single drop of 0.5% proxymetacaine. A drop of 0.5% tropicamide was then administered bilaterally and a second IOP measurement was taken 30 min later (postdilation). The difference between the two measurements was considered as the effect of mydriasis on IOP.

Results  Dogs had an average IOP of 14.9 ± 3.2 mmHg, with 95% confidence limits ranging from 8 to 22 mmHg. There were significant differences between breeds (P < 0.006) with Siberian Huskies having higher IOPs (17.2 ± 3.7 mmHg) than the other breeds (Spaniels: 14.2 ± 2.8 mmHg, P < 0.01; Retrievers: 14 ± 1.9 mmHg, P < 0.001). The majority (60%) of dogs displayed 5 mmHg or less in IOP change postmydriasis. Siberian Huskies showed the highest IOP levels, and also had the greatest variability with dilation.

Conclusions and clinical relevance  Interbreed variability in effect of tropicamide of canine IOP is evident.
Immunocytochemical localization of smooth muscle actin‐containing cells in the trabecular meshwork of glaucomatous and nonglaucomatous dogs
Authors: Hassel Brant , Samuelson Don A. , Lewis Patricia A. , Gelatt Kirk N.
Published: October 2007

Purpose  It has been recently demonstrated that trabecular meshwork (TM) cells within the canine iridocorneal angle (ICA) contain smooth muscle actin (smA) and possess contractile abilities that probably alter aqueous outflow. As the number of trabecular meshwork cells in glaucomatous canine eyes have been found to be less than those in age‐matched nonglaucomatous eyes, we hypothesize that the sub‐population of TM cells that contain smooth muscle actin will also decline with age. We also hypothesize that a greater loss of these cells will be observed in glaucomatous eyes than in nonglaucomatous eyes of the same age. In the present study the ICA of 17 glaucomatous and eight nonglaucomatous eyes were examined for the presence of smA‐containing TM cells.

Material and methods  Five‐micron sagittal sections of each whole globe were immunolocalized for smooth muscle actin. Positive and negative controls were performed concomitantly.

Results  Labeling was observed in the meshwork of 10 out of the 17 glaucomatous eyes, distributed across all of the age groups represented, including eyes with primary and secondary glaucoma. Smooth muscle actin labeling was observed in the TM of 7 out of 14 eyes with closed‐angle glaucoma. Positive immunoreaction was observed in 3/3 eyes with open ICAs. Labeling of smooth muscle actin was observed in the anterior part of the meshwork in only 4 of the 17 glaucomatous eyes, each having had secondary glaucoma. There were no eyes in which label was observed exclusively in the anterior portion of the meshwork. Labeling was most consistently observed in the outer, posterior uveal TM and the inner, posterior corneoscleral TM. All of the eight nonglaucomatous eyes showed greater labeling in both area and intensity than the glaucomatous eyes of the same age.

Conclusion  It was concluded that smooth muscle actin‐cell loss is associated with age in canine eyes and that this loss is more severe in glaucomatous eyes.
Endothelin‐1, nitric oxide, and glutamate in the normal and glaucomatous dog eye
Authors: Källberg Maria E. , Brooks Dennis E. , Gelatt Kirk N. , Garcia‐Sanchez Gustavo A. , Szabo Nancy J. , Lambrou George N.
Published: October 2007

Purpose To document differences in the levels of the endothelin‐1 peptide, nitric oxide, and glutamate in aqueous humor and vitreous in the dog eye with spontaneous glaucoma compared to the normal dog eye.

Methods Samples of aqueous humor and vitreous from enucleated normal eyes (n = 21) of 14 dogs and glaucomatous eyes (n = 8) of eight dogs were collected. Levels of endothelin‐1, nitric oxide, and glutamate were measured by enzyme immunoassay.

Results Endothelin‐1 aqueous humor levels (mean ± SD) increased significantly from 3.05 (± 1.66) pg/mL for the normal eyes to 6.22 (± 2.83) pg/mL for the glaucomatous eyes (P = 0.0054). The increase in vitreous from 1.83 (± 1.66) pg/mL for the normal eyes to 2.86 (± 1.31) pg/mL for the glaucomatous eyes was not significant (P = 0.0840). Nitric oxide levels (mean ± SD) increased significantly in aqueous humor from 4.12 (± 2.64) µM for the normal eyes to 12.95 (± 14.42) µM for the glaucomatous eyes (P = 0.0141). The vitreous levels increased from 4.86 (± 3.92) µM for the normal eyes to 15.33 (± 16.22) µM for the glaucomatous eyes (P = 0.0179). Glutamate levels (mean ± SD) decreased nonsignificantly in aqueous humor from 2.35 (± 3.84) µM for the normal eyes to 1.61 (± 0.74) µM for the glaucomatous eyes (P = 0.9377) and in vitreous from 1.37 (± 1.89) µM for the normal eyes to 1.02 (± 1.11) µM for the glaucomatous eyes (P = 0.3303).

Conclusion Endothelin‐1 and nitric oxide increased in aqueous humor and vitreous of dogs with spontaneous glaucoma while the changes in glutamate varied.
Cloning of caninemyocilincDNA and molecular analysis of themyocilingene in Shiba Inu dogs
Authors: Kato Kumiko , Sasaki Nobuo , Matsunaga Satoru , Nishimura Ryohei , Ogawa Hiroyuki
Published: October 2007

Objective To identify caninemyocilincDNA and compare its sequence in glaucomatous and nonglaucomatous Shiba Inu dogs with closed and open iridocorneal angles (ICAs).

Procedures Total RNA was extracted from the ciliary body of the eyes of a healthy Beagle, and the caninemyocilingene was cloned and sequenced. Of the Shiba Inu dogs tested, five were glaucomatous with closed ICA, three were nonglaucomatous with open ICA, and two were nonglaucomatous with closed ICA. The genomic DNA of these dogs was extracted from peripheral blood leukocytes. The exons of the caninemyocilingene were amplified using the polymerase chain reaction (PCR), and sequenced. The frequency of mutation in caninemyocilinDNA was verified in these dogs by using themyocilincDNA of a Beagle.

Results The caninemyocilincDNA was 1452 bp long and contained the entire open reading frame encoding 483 amino acids. A leucine zipper‐like motif and olfactomedin‐like domain were conserved in the amino acid residues. The presence of sequence variants in the genomic DNA of Shiba Inu dogs was independent of the occurrence of glaucoma and ICA grading.

Conclusions MyocilinRNA was detected in the ciliary body and trabecular meshwork (TM) of a Beagle. Themyocilinsequence of Shiba Inu dogs suggests thatmyocilinmutations are unlikely to play a significant role in the pathogenesis of primary closed‐angle glaucoma in this breed. However, several mutations in themyocilingene in exon 1 of Shiba Inu dogs may predispose them to an obstruction in the anterior aqueous outflow.
Microvessel loss, vascular damage and glutamate redistribution in the retinas of dogs with primary glaucoma
Authors: Alyahya Khaleel , Chen Chu‐Te , Mangan Brendan G. , Gionfriddo Juliet R. , Legare Marie E. , Dubielzig Richard R. , Madl James E.
Published: October 2007

Objective Vascular damage and ischemia‐like changes in glutamate distribution occur in primary glaucoma (PG) in dogs. We measured the microvessel density in PG retinas to determine whether microvessel loss may induce ischemia and glutamate redistribution.

Animals studied Sections from 12 control and 33 glaucomatous dog retinas.

Procedures Vessels in retinas were identified by staining withGriffonia simplicifoliaisolectin B4 or immunohistochemical staining for laminin or glutamate. Damage to regions of the inner nuclear layer (INL) was classified as mild (< 10% damaged neurons), moderate (≥ 10% damaged neurons, INL ≥ 2 cells thick) or severe (INL < 2 cells thick).

Results Glutamate redistribution was found in some mildly damaged regions and increased as damage increased. Regions with increased glutamate redistribution and increased damage had lower densities of microvessels in plastic sections. However, neuronal damage and glutamate redistribution were seen even in areas adjacent to the remaining microvessels. Microvessel loss in damaged regions was confirmed in paraffin sections with lectin staining and immunohistochemical localization of laminin. The density of larger vessels was not decreased in PG, but larger vessels often had thickened walls, cuffing with leukocytes, and leakage of albumin.

Conclusions Microvessel loss may occur in regions of glutamate redistribution and neuronal damage in PG retinas. Larger vessels were often damaged. The redistribution of glutamate is associated with a loss of microvessels, even in mildly damaged regions. However, neuronal damage and glutamate redistribution may occur close to remaining microvessels, suggesting microvessel loss was not the sole factor inducing these changes.
Measurement of retinal nerve fiber layer thickness in normal and glaucomatous Cocker Spaniels by scanning laser polarimetry
Authors: García‐Sánchez Gustavo A. , Gil‐Carrasco Félix , Román Jesús Jiménez , Brooks Dennis E. , Álvarez‐Clau Ana , Hosgood Giselle , Iwabe Simone , Moreno‐Mendoza Norma A.
Published: October 2007

Objective To measure changes in the thickness of the retinal nerve fiber layer in normal and early glaucomatous dogs with scanning laser polarimetry.

Animals studied A total of 45 eyes, 32 normal and 13 glaucomatous eyes, of American Cocker Spaniels with primary glaucoma were used. All eyes were evaluated through a complete neuro‐ophthalmic examination, tonometry, gonioscopy, slit‐lamp biomicroscopy, and indirect ophthalmoscopy prior to enucleation.

Methods The retinal nerve fiber layer thickness was measured in anesthetized animals with scanning laser polarimetry (Nerve fiber analyzer, GDx; Laser Diagnostic Technologies, LTD, San Diego, CA, USA). Glaucomatous eyes retained some vision at the time of this study.

Results The mean ± SD of the retinal nerve fiber layer thickness was 141.69 ± 18 µm for normal dogs and 105.08 ± 23.86 µm for visual glaucomatous dogs. The average retinal nerve fiber layer thickness in the superior and inferior retinal quadrants was 148.03 ± 8.5 and 141.06 ± 8.73 µm, respectively, for normal dogs, and 106.61 ± 25.77 and 107.08 ± 24.99 µm in the superior and inferior retinal quadrants, respectively, for glaucomatous dogs. The superior to nasal retinal nerve fiber layer thickness ratio was 1.45 for normal dogs and 1.26 for visual glaucomatous dogs.

Conclusions Using scanning laser polarimetry it was possible to detect changes in retinal nerve fiber layer thickness in glaucomatous dogs at early stages of the disease. Therefore, this instrument has the potential to improve the clinical management of canine glaucoma by detecting progressive changes to the retinal nerve fiber layer.
Ganglion cell death in glaucoma: from mice to men
Authors: Nickells Robert W.
Published: October 2007

Glaucoma results from the degeneration of retinal ganglion cells and their axons. Over the last 20 years several important advancements have been made in our understanding of the molecular pathology of this disease, particularly through the development of rat models of experimental glaucoma and the characterization of a spontaneous secondary form of glaucoma in DBA/2 substrains of inbred mice. One of these advances is the observation that ganglion cells die by apoptosis, an intrinsic molecular pathway of programmed cell death. An important aspect of this cell death process is the concept that these cells actually undergo compartmentalized self‐destruction. Importantly, genetic evidence now suggests that axons die independently of the apoptotic program that executes the cell body or soma. This review briefly summarizes some of the most significant developments in glaucoma research, with respect to the process of ganglion cell degeneration.
Pharmacokinetics of topically applied ciprofloxacin in equine tears
Authors: Hendrix Diane V. H. , Stuffle Jamie L. , Cox Sherry K.
Published: October 2007

Objective  To evaluate the pharmacokinetics of topically applied ciprofloxacin 0.3% ophthalmic solution in tears of healthy horses.

Animal studied  Twenty healthy, adult, mixed‐breed horses.

Procedures  Twenty study horses were confirmed free of ophthalmic disease by complete ophthalmic examination. Seventy microliters of 0.3% ciprofloxacin (Ciloxan™) was placed in the ventral cul‐de‐sac of each eye using a microliter syringe and 19‐g cannula. Population kinetics were carried out by sampling the tear film from the lower cul‐de‐sac of each eye with tear test strips at 5, 10, 15 and 30 min and 1, 2, 4 and 6 h post administration for a total of five samples at each time‐point. Sample collection time was 15 s. Concentrations of ciprofloxacin were determined using high performance liquid chromatography.

Results  Mean (±SD) of the Schirmer tear test results from all eyes was 23.4 ± 4.8 mm wetting in 1 min. Mean concentration of ciprofloxacin in the tears at 5 min post administration was 498.4 ± 266.8 µg/g. Mean concentration rapidly declined and began to plateau at 30 min. The mean tear concentrations of ciprofloxacin at 30 min and at 1, 2, 4 and 6 h were 66.6 ± 56.0, 60.25 ± 55.7, 42.25 ± 30.9, 36.25 ± 32.0, and 45.5 ± 46.5 µg/g, respectively.

Conclusions  The pharmacokinetics of ciprofloxacin in normal horses are similar to those in rabbits and humans. Topical application of ciprofloxacin resulted in a mean tear concentration of ciprofloxacin that remained above the MIC90 levels for most pathogenic bacteria for 6 h post administration.
Comparative ocular anatomy of the western lowland gorilla
Authors: Knapp Stefanie , McCulley James P. , Alvarado Thomas P. , Hogan R. Nick
Published: October 2007

Objective  To examine the lowland gorilla (Gorilla gorilla gorilla) eye and determine similarities to and differences between the mountain gorilla (Gorilla gorilla beringei) and the human eye. In addition, we compare our findings of G. g. gorilla to previous reports on the eye of this subspecies.

Procedures  A 13‐year‐old deceased male lowland gorilla and a 34‐year‐old deceased female lowland gorilla were included in the study. Gross and microscopic examinations of the formalin‐fixed right eyeball of each gorilla were carried out.

Results  Globe dimensions of G. g. gorilla were similar to G. g. beringei and to humans. The limbal conjunctival epithelium and the choroid were densely pigmented. However, the distribution of the conjunctival pigment ring was different to that of G. g. beringei and the melanocytes of the choroid were unusually round. There were deep crypts in the anterior border layer of the iris, and the epithelium of the pars plana was uniquely irregular. Vertical corneal diameter was observed to be equal or greater than horizontal diameter in G. g. gorilla, which is in contrast to humans and to previous findings for G. g. beringei. Corneal thickness was closer to that of humans than to G. g. beringei. Posterior lens capsule thickness was noticeably greater than that of humans.

Conclusions  Although some variation between the ocular anatomy of G. g. gorilla and G. g. beringei does exist, the gross and microscopic findings closely resemble each other in these two subspecies. In addition, the eye of Gorilla appears remarkably similar to the human eye. However, comparison of measurements with those in humans is somewhat limited because formalin‐fixation can introduce tissue shrinkage and artifact.
Clinical and electroretinographic characteristics of congenital stationary night blindness in the Appaloosa and the association with the leopard complex
Authors: Sandmeyer Lynne S. , Breaux Carrie B. , Archer Sheila , Grahn Bruce H.
Published: October 2007

Objective To determine the prevalence of congenital stationary night blindness (CSNB) in Appaloosa horses in western Canada, investigate the association with the leopard complex of white spotting patterns, and further characterize the clinical and electroretinographic aspects of CSNB in the Appaloosa.

Animals studied Three groups of 10 Appaloosas were studied based on coat patterns suggestive of LpLp, Lplp, and lplp genotype.

Procedures Neurophthalmic examination, slit‐lamp biomicroscopy, indirect ophthalmoscopy, measurement of corneal diameter, streak retinoscopy, scotopic and photopic full‐field and flicker ERGs and oscillatory potentials (OPs) were completed bilaterally.

Results All horses in the LpLp group were affected by CSNB, while none in the Lplp or lplp groups was affected. The LpLp and Lplp groups had significantly smaller vertical and horizontal corneal diameters than the lplp group had. Median refractive error was zero for all groups. Scotopic ERGs in the LpLp (CSNB‐affected) group were consistent with previous descriptions. The CSNB‐affected horses had significantly longer photopic a‐wave implicit times, greater a‐wave amplitudes, and lower b‐wave amplitudes than the Lplp and lplp (normal) groups did. No differences were present in photopic flicker amplitude or implicit times. Scotopic flickers in the CSNB‐affected horses were markedly reduced in amplitude and abnormal in appearance. No differences were noted in OP implicit times; however, amplitudes of some OPs were reduced in CSNB‐affected horses. There were no differences in scotopic and photopic or flicker ERGs or OPs between the normal groups.

Conclusions CSNB was present in one‐third of horses studied and there was a significant association between CSNB and the inheritance of two Lp alleles. ERG abnormalities support the hypothesis that CSNB is caused by a defect in neural transmission through the rod pathway involving the inner nuclear layer.
Comparison of the rebound tonometer (TonoVet®) with the applanation tonometer (TonoPen XL®) in normal Eurasian Eagle owls (Bubo bubo)
Authors: Jeong Man‐Bok , Kim Young‐Jun , Yi Na‐Young , Park Shin‐Ae , Kim Won‐Tae , Kim Se‐Eun , Chae Je‐Min , Kim Jong‐Taek , Lee Hang , Seo Kang‐Moon
Published: October 2007

Objective To examine the feasibility and accuracy of a handheld rebound tonometer, TonoVet®, and to compare the intraocular pressure (IOP) readings of the TonoVet®with those of an applanation tonometer, TonoPen XL®, in normal Eurasian Eagle owls.

Animals studied Ten clinically normal Eurasian Eagle owls (20 eyes).

Procedures Complete ocular examinations, using slit‐lamp biomicroscopy and indirect ophthalmoscopy, were conducted on each raptor. The IOP was measured bilaterally using a rebound tonometer followed by a topical anesthetic agent after 1 min. The TonoPen XL®tonometer was applied in both eyes 30 s following topical anesthesia.

Results The mean ± SD IOP obtained by rebound tonometer was 10.45 ± 1.64 mmHg (range 7–14 mmHg), and by applanation tonometer was 9.35 ± 1.81 mmHg (range 6–12 mmHg). There was a significant difference (P = 0.001) in the IOP obtained from both tonometers. The linear regression equation describing the relationship between both devices wasy = 0.669x + 4.194 (x = TonoPen XL®andy = TonoVet®). The determination coefficient (r2) wasr2 = 0.550.

Conclusions The results suggest that readings from the rebound tonometer significantly overestimated those from the applanation tonometer and that the rebound tonometer was tolerated well because of the rapid and minimal stress‐inducing method of tonometry in the Eurasian Eagle owls, even without topical anesthesia. Further studies comparing TonoVet®with manometric measurements may be necessary to employ rebound tonometer for routine clinical use in Eurasian Eagle owls.
Photodynamic therapy: basic principles and potential uses for the veterinary ophthalmologist
Authors: Giuliano Elizabeth A. , Ota Juri , Tucker Sheryl A.
Published: October 2007

Photodynamic therapy (PDT) involves the use of photochemical reactions mediated through the interaction of photosensitizing agents, light and oxygen. PDT, while now commonly used in physician ophthalmology and oncology, is uncommonly used for the veterinary ophthalmic patient. It is an emerging new therapy in veterinary ophthalmology for the treatment of periocular tumors. This article reviews the basic principles of PDT to provide the veterinary ophthalmologic community with a succinct reference for this emerging treatment modality in our field.