Cardiac Leiomyosarcoma in a Cat Presenting for Bilateral Renal Neoplasia.

A 10-year-old neutered female domestic longhair cat was presented to a tertiary care veterinary hospital for evaluation of a right renal mass that was identified incidentally on abdominal radiographs and classified further as a sarcoma based on fine needle aspiration cytology. Further diagnostic workup, including ultrasound and cytology, identified a sarcoma in the left kidney. After approximately 1 month of conservative medical management, the clinical condition deteriorated and the cat was humanely destroyed. Post-mortem examination confirmed bilateral renal masses with multifocal infarction and extensive necrosis, and further identified a large mass at the apex of the heart as well as multiple pulmonary nodules. Microscopical examination of the masses identified a population of poorly-differentiated neoplastic spindle cells, consistent with sarcoma. Immunohistochemically, the neoplastic cells expressed smooth muscle actin and muscle-specific actin, but were negative for myoglobin and factor VIII. Phosphotungstic acid-haematoxylin staining was unable to identify cross-striations in the neoplastic cells. Based on these results and the pattern of lesion distribution, the cat was diagnosed with cardiac leiomyosarcoma with pulmonary and bilateral renal metastasis.

Treatment outcomes and prognostic factors of feline splenic mast cell tumors: A multi-institutional retrospective study of 64 cases.

BACKGROUND: Mast cell tumors (MCT) are common splenic tumors in cats, but there is limited information on treatment outcomes of cats with this disease. MATERIALS AND METHODS: This retrospective study evaluated treatment outcomes in 64 cats with splenic MCT. Cats were categorized into the following treatment groups: splenectomy (A, n = 20); splenectomy with chemotherapy (B, n = 20); chemotherapy alone (C, n = 15); or supportive care (D, n = 9). RESULTS: Median tumor specific survival (MTSS) was: 856, 853, 244, 365 days for groups A, B, C, and D, respectively. The MTSS was not significantly different between the 4 groups. However, comparing cats that had splenectomy (A and B) versus those that did not (C and D), the MTSS was 856 and 342 days, respectively (p=0.008). None of the prognostic factors analyzed significantly influenced survival. CONCLUSION: Splenectomy (+/- chemotherapy) significantly prolongs survival in cats with mast cell tumors. The role of chemotherapy remains unknown.

Description of a new octoploid frog species (Anura: Pipidae: Xenopus) from the Democratic Republic of the Congo, with a discussion of the biogeography of African clawed frogs in the Albertine Rift.

We describe a new octoploid species of African clawed frog (Xenopus) from the Lendu Plateau in the northern Albertine Rift of eastern Democratic Republic of the Congo. This species is the sister taxon of Xenopus vestitus (another octoploid), but is distinguished by a unique morphology, vocalization and molecular divergence in mitochondrial and autosomal DNA. Using a comprehensive genetic sample, we provide new information on the species ranges and intra-specific diversity of African clawed frogs from the Albertine Rift, including the details of a small range extension for the critically endangered Xenopus itombwensis and previously uncharacterized variation in Xenopus laevis. We also detail a new method for generating cytogenetic preparations in the field that can be stored at room temperature for up to 3 weeks. While extending our understanding of the extant diversity in the Albertine Rift, this new species highlights components of species diversity in ancestral African clawed frogs that are not represented by known extant descendants.

Establishing clinical utility of pharmacogenetic tests in the post-FDAAA era.

The US Food and Drug Administration (FDA) Amendments Act of 2007, when fully implemented, will offer new sources of evidence and new regulatory mechanisms during the postmarket phase of drug life. If artfully and carefully applied, these new capabilities could help resolve problems that have long impeded the clinical translation of pharmacogenomics.

Glaucoma detection: the content of optometric eye examinations for a presbyopic patient of African racial descent.

AIMS: Standardised patient (SP) methodology is the gold standard for evaluating clinical practice. We investigated the content of optometric eyecare for an early presbyopic SP of African racial descent, an "at-risk" patient group for primary open-angle glaucoma (POAG). METHODS: A trained actor presented unannounced as a 44-year-old patient of African racial descent, complaining of recent near vision difficulties, to 100 community optometrists for an audio-recorded eye examination. The eye examinations were subsequently assessed via a checklist based on evidence-based POAG reviews, clinical guidelines and expert panel opinion. RESULTS: Ninety-five per cent of optometrists carried out optic disc assessment and tonometry, which conforms to the UK College of Optometrists' advice that those patients aged >40 years should receive at least two of the following tests: tonometry, optic disc assessment, visual field testing. Thirty-five per cent of optometrists carried out all of these tests and 6% advised the SP of increased POAG risk in those of African racial descent. CONCLUSION: SP encounters are an effective measure of optometric clinical practice. As in other healthcare disciplines, there are substantial differences between optometrists in the depth of their clinical investigations, challenging the concept of a "standard sight test". There is a need for continuing professional development (CPD) in glaucoma screening, in which the increased risk of POAG in those of African racial descent should be emphasised.

The Pattern Glare Test: a review and determination of normative values.

Pattern glare is characterised by symptoms of visual perceptual distortions and visual stress on viewing striped patterns. People with migraine or Meares-Irlen syndrome (visual stress) are especially prone to pattern glare. The literature on pattern glare is reviewed, and the goal of this study was to develop clinical norms for the Wilkins and Evans Pattern Glare Test. This comprises three test plates of square wave patterns of spatial frequency 0.5, 3 and 12 cycles per degree (cpd). Patients are shown the 0.5 cpd grating and the number of distortions that are reported in response to a list of questions is recorded. This is repeated for the other patterns. People who are prone to pattern glare experience visual perceptual distortions on viewing the 3 cpd grating, and pattern glare can be quantified as either the sum of distortions reported with the 3 cpd pattern or as the difference between the number of distortions with the 3 and 12 cpd gratings, the '3-12 cpd difference'. In study 1, 100 patients consulting an optometrist performed the Pattern Glare Test and the 95th percentile of responses was calculated as the limit of the normal range. The normal range for the number of distortions was found to be <4 on the 3 cpd grating and <2 for the 3-12 cpd difference. Pattern glare was similar in both genders but decreased with age. In study 2, 30 additional participants were given the test in the reverse of the usual testing order and were compared with a sub-group from study 1, matched for age and gender. Participants experienced more distortions with the 12 cpd grating if it was presented after the 3 cpd grating. However, the order did not influence the two key measures of pattern glare. In study 3, 30 further participants who reported a medical diagnosis of migraine were compared with a sub-group of the participants in study 1 who did not report migraine or frequent headaches, matched for age and gender. The migraine group reported more symptoms on viewing all gratings, particularly the 3 cpd grating. The only variable to be significantly different between the groups was the 3-12 cpd difference. In conclusion, people have an abnormal degree of pattern glare if they have a Pattern Glare Test score of >3 on the 3 cpd grating or a score of >1 on the 3-12 cpd difference. The literature suggests that these people are likely to have visual stress in everyday life and may therefore benefit from interventions designed to alleviate visual stress, such as precision tinted lenses.

The inflammatory effect of cardiopulmonary bypass on leukocyte extravasation in vivo.

OBJECTIVE: Extravascular trafficking of leukocytes into organs is thought to play a major role in the pathophysiologic mechanisms of the inflammatory response to cardiopulmonary bypass, yet leukocyte extravasation is difficult to study clinically. Here we have tested the hypothesis that leukocyte emigration into skin blisters can provide a way to monitor the inflammatory effect of cardiopulmonary bypass that allows testing of anti-inflammatory interventions (exemplified by aprotinin). METHODS: Patients undergoing primary elective coronary artery bypass grafting (n = 14) were randomized into 2 equal groups to receive saline infusion during cardiopulmonary bypass (control group) or high-dose aprotinin. Experimental skin blisters (in duplicate) were induced on the forearm by means of topical application of the vesicant cantharidin, and blister fluid was sampled at 5 hours postoperatively. Inflammatory leukocyte subsets in blister fluid were analyzed by means of flow cytometry by using expression of CD11b and CD62L as a phenotypic marker of activation. RESULTS: In the control group of patients, cardiopulmonary bypass surgery triggered a 381% increase in leukocyte extravasation into the skin compared with reference blisters carried out before surgical intervention, with neutrophil (P = .014), monocyte (P = .014), and eosinophil (P = .009) levels all statistically significantly increased. In the aprotinin group there was no statistically significant increase during cardiopulmonary bypass surgery in any inflammatory leukocyte subset. The activation phenotype of extravascular leukocytes was not significantly altered between surgical groups. CONCLUSIONS: This study introduces the cantharidin blister technique as a powerful new research tool for analyzing the inflammatory effect of cardiopulmonary bypass in vivo. It has provided detailed molecular insight into the extravascular leukocyte population during cardiopulmonary bypass. Although aprotinin blocked cardiopulmonary bypass-dependent extravasation of leukocytes, there was no change in their CD11b/CD62L activation status. The cantharidin skin test thus represents a novel research tool for evaluating future anti-inflammatory interventions in cardiothoracic surgery.

Finding a liability-free space in which personalized medicine can bloom.

Personalized medicine uses genetic and other screening tests to predict a patient's response to specific drug and biologic therapies (together "drugs"), with the aim of choosing a treatment that will provide benefits while avoiding drug-related harms. There are two schools of thought on how tort liability may affect personalized medicine, i.e., whether fear of lawsuits will tend to accelerate progress or slow it down. Tort suits include product liability suits against manufacturers and negligence suits against physicians and other providers of health-related services.

Distinguishing product and practice regulation in personalized medicine.

Protecting the public from faulty targeting of medicines, while preserving the crucial distinction between product and practice regulation, may require innovative regulatory approaches and close, ongoing involvement by the medical profession. This article explores four problem areas: validation of clinical claims for tests used in targeting therapies; developing and implementing appropriate restrictions on off-label use; promoting consistent concepts of clinical utility for use in various regulatory, reimbursement, and judicial contexts; and communication of clear information to guide clinicians in appropriate use of targeted therapeutic products. The article suggests an approach for addressing these problems by sharing regulatory activities between the Food and Drug Administration and a newly-created clinical standards board formed within the medical and scientific communities.

Hemoglobin scavenger receptor CD163 mediates interleukin-10 release and heme oxygenase-1 synthesis: antiinflammatory monocyte-macrophage responses in vitro, in resolving skin blisters in vivo, and after cardiopulmonary bypass surgery.

The recently described hemoglobin scavenger receptor CD163 mediates the endocytosis of hemoglobin:haptoglobin (Hb:Hp) complexes and thereby counters Hb-induced oxidative tissue damage after hemolysis. Although CD163 has been indirectly associated with antiinflammatory and atheroprotective activity, no ligand-receptor-effector pathway has yet been described for this receptor. To understand the significance of CD163 and more clearly define downstream pathways linked to inflammatory resolution, we studied the expression and function of CD163 in human monocytes/macrophages using both in vitro and in vivo models. Differentiation of human blood monocytes into macrophages either by in vitro culture or in resolving cantharidin-induced skin blisters led to an equivalent increase (>15x) in CD163 expression. Elevated CD163 levels were also noted on circulating monocytes in cardiac surgical patients during the resolution phase of the systemic inflammatory response to cardiopulmonary bypass surgery. In each case, binding of Hb:Hp to CD163-bearing cells elicited potent interleukin-10 secretion, and this was inhibited by the anti-CD163 antibody RM3/1. Release of interleukin-10, in turn, induced heme oxygenase-1 stress protein synthesis via an autocrine mechanism. Such induction of heme oxygenase-1 was observed in vivo 24 to 48 hours after the onset of cardiopulmonary bypass surgery. These results identify novel antiinflammatory and cytoprotective effector pathways in human monocytes/macrophages related to Hb scavenging and metabolism, which may have relevance in atheroprotection, wound healing, and patient recovery postoperatively.

Tinted spectacles and visually sensitive migraine.

A double-masked randomized controlled study with cross-over design compared the effectiveness of precision ophthalmic tints in the prevention of headache in migraine sufferers. Seventeen patients chose the colour of light that optimally reduced perceptual distortion of text and maximized clarity and comfort. They were later given glasses with spectral filters providing optimal colour under conventional white lighting ('optimal' tint) or glasses that provided a slightly different colour ('control' tint). The tints were supplied in random order, each for 6 weeks, separated by an interval of at least 2 weeks with no tints. Headache diaries showed that the frequency of headaches was marginally lower when the 'optimal' tint was worn, compared with the 'control'. The trial extends to adults with migraine, the results of a previous double-masked study demonstrating, in children with reading difficulty, beneficial effects of precision tints in reducing symptom frequency. In the present study, however, the effects are suggestive rather than conclusive.

Optometric function in visually sensitive migraine before and after treatment with tinted spectacles.

Optometrists frequently encounter patients with migraine and patients and practitioners sometimes suspect that visual stimuli or visual anomalies trigger headaches. There is a lack of evidence-based research on the issue, however. Some patients with migraine may be hypersensitive to visual stimuli, and it has been suggested that individually prescribed coloured filters might be an effective treatment to reduce symptoms from such stimuli. A recent randomised controlled trial showed such a treatment to be effective and the present paper reports on the optometric characteristics of the patients in this study. Twenty-one patients with neurologically diagnosed migraine were compared with 11 controls. No significant differences were found between the two groups with respect to refractive error, ocular pathology, colour vision, contrast sensitivity, accommodative function, strabismus and hyperphoria. The migraine group tended to be a little more exophoric, but by most criteria they were able to compensate for their exophoria as well as the control group. The migraine group were more prone to pattern glare than the controls (p = 0.004). The effects of precision tinted and control tinted lenses were investigated. The only variable to show a consistent and marked improvement with tinted lenses was pattern glare. The most likely mechanism for the benefit from individually prescribed coloured filters in migraine is the alleviation of cortical hyperexcitability (Wilkins et al. 1994) and associated pattern glare.

Hybridization and population genetics of two macaque species in Sulawesi, Indonesia.

This study investigates hybridization and population genetics of two species of macaque monkey in Sulawesi, Indonesia, using molecular markers from mitochondrial, autosomal, and Y-chromosome DNA. Hybridization is the interbreeding of individuals from different parental taxa that are distinguishable by one or more heritable characteristics. Because hybridization can affect population structure of the parental taxa, it is an important consideration for conservation management. On the Indonesian island of Sulawesi an explosive diversification of macaques has occurred; seven of 19 species in the genus Macaca live on this island. The contact zone of the subjects of this study, M. maura and M. tonkeana, is located at the base of the southwestern peninsula of Sulawesi. Land conversion in Sulawesi is occurring at an alarming pace; currently two species of Sulawesi macaque, one of which is M. maura, are classified as endangered species. Results of this study indicate that hybridization among M. maura and M. tonkeana has led to different distributions of molecular variation in mitochondrial DNA and nuclear DNA in the contact zone; mitochondrial DNA shows a sharp transition from M. maura to M. tonkeana haplotypes, but nuclear DNA from the parental taxa is homogenized in a narrow hybrid zone. Similarly, within M. maura divergent mitochondrial DNA haplotypes are geographically structured but population subdivision in the nuclear genome is low or absent. In M. tonkeana, mitochondrial DNA haplotypes are geographically structured and a high level of nuclear DNA population subdivision is present in this species. These results are largely consistent with a macaque behavioral paradigm of female philopatry and obligate male dispersal, suggest that introgression between M. maura and M. tonkeana is restricted to the hybrid zone, and delineate one conservation management unit in M. maura and at least two in M. tonkeana.

A review of the management of 323 consecutive patients seen in a specific learning difficulties clinic.

Visual correlates of specific learning difficulties (SpLD) include: binocular instability, low amplitude of accommodation, and Meares-Irlen Syndrome. Meares-Irlen Syndrome describes asthenopia and perceptual distortions which are alleviated by using individually prescribed coloured filters. Data from 323 consecutive patients seen over a 15 month period in an optometric clinic specialising in SpLD are reviewed. Visual symptoms and headaches were common. 48% of patients were given a conventional optometric intervention (spectacles, orthoptic exercises) and 50% were issued with coloured filters, usually for a trial period. 40% of those who were given orthoptic exercises were later issued with coloured overlays. 32% of those who were issued with coloured overlays were ultimately prescribed Precision Tinted lenses. Approximately half the sample were telephoned more than a year after the last clinical appointment. More than 70% of those who were prescribed Precision Tints were still wearing them daily, and results for this intervention compared favourably with data for non-tinted spectacles. The data suggest that many people with SpLD need optometric care and that the optometrist needs to be skilled in orthoptic techniques and cognisant of recent research on coloured filters.

Randomised double-masked placebo-controlled trial of a treatment for congenital nystagmus.

Several therapies have been developed for congenital nystagmus (CN) but without placebo-controlled trials. We investigated a treatment which combined two therapies that had been advocated by several authors and were reported to improve visual acuity (VA). A placebo treatment was designed to mimic the time, attention, 'high tech' apparatus, and the explanation used in the experimental treatment. To each group, 38 subjects with CN were randomly allocated. Their VA and contrast sensitivity (CS) were assessed three times before undergoing treatment for 6 weeks and then once more. An improvement in VA occurred, however, this was not significantly different in the two groups. The improvement in CS was greater in the experimental than in the control group, but the difference failed to reach significance in most statistical tests. We conclude that putative therapies for CN should be assumed to be placebos until proven otherwise with randomized controlled trials.