RESUMEN
For conservation science to effectively inform management, research must focus on creating the scientific knowledge required to solve conservation problems. We identified research questions that, if answered, would increase the effectiveness of conservation and natural resource management practice and policy in Oceania's small-island developing states. We asked conservation professionals from academia, governmental, and nongovernmental organizations across the region to propose such questions and then identify which were of high priority in an online survey. We compared the high-priority questions with research questions identified globally and for other regions. Of 270 questions proposed by respondents, 38 were considered high priority, including: What are the highest priority areas for conservation in the face of increasing resource demand and climate change? How should marine protected areas be networked to account for connectivity and climate change? What are the most effective fisheries management policies that contribute to sustainable coral reef fisheries? High-priority questions related to the particular challenges of undertaking conservation on small-island developing states and the need for a research agenda that is responsive to the sociocultural context of Oceania. Research priorities for Oceania relative to elsewhere were broadly similar but differed in specific issues relevant to particular conservation contexts. These differences emphasize the importance of involving local practitioners in the identification of research priorities. Priorities were reasonably well aligned among sectoral groups. Only a few questions were widely considered answered, which may indicate a smaller-than-expected knowledge-action gap. We believe these questions can be used to strengthen research collaborations between scientists and practitioners working to further conservation and natural resource management in this region.
Asunto(s)
Biodiversidad , Conservación de los Recursos Naturales , Islas , Recursos Naturales , OceaníaRESUMEN
BACKGROUND: The term 'metabolically healthy obese (MHO)' is distinguished using body mass index (BMI), yet BMI is a poor index of adiposity. Some epidemiological data suggest that MHO carries a lower risk of cardiovascular disease (CVD) or mortality than being normal weight yet metabolically unhealthy. OBJECTIVES: We aimed to undertake a detailed phenotyping of individuals with MHO by using imaging techniques to examine ectopic fat (visceral and liver fat deposition) and myocardial function. We hypothesised that metabolically unhealthy individuals (irrespective of BMI) would have adverse levels of ectopic fat and myocardial dysfunction compared with MHO individuals. SUBJECTS: Individuals were categorised as non-obese or obese (BMI ⩾30 kg m(-2)) and as metabolically healthy or unhealthy according to the presence or absence of metabolic syndrome. METHODS: Sixty-seven individuals (mean±s.d.: age 49±11 years) underwent measurement of (i) visceral, subcutaneous and liver fat using magnetic resonance imaging and proton magnetic resonance spectroscopy, (ii) components of metabolic syndrome, (iii) cardiorespiratory fitness and (iv) indices of systolic and diastolic function using tissue Doppler echocardiography. RESULTS: Cardiorespiratory fitness was similar between all groups; abdominal and visceral fat was highest in the obese groups. Compared with age- and BMI-matched metabolically healthy counterparts, the unhealthy (lean or obese) individuals had higher liver fat and decreased early diastolic strain rate, early diastolic tissue velocity and systolic strain indicative of subclinical systolic and diastolic dysfunction. The magnitude of dysfunction correlated with the number of components of metabolic syndrome but not with BMI or with the degree of ectopic (visceral or liver) fat deposition. CONCLUSIONS: Myocardial dysfunction appears to be related to poor metabolic health rather than simply BMI or fat mass. These data may partly explain the epidemiological evidence on CVD risk relating to the different obesity phenotypes.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Hiperlipidemias/fisiopatología , Síndrome Metabólico/fisiopatología , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Obesidad/fisiopatología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/fisiopatología , Estudios Transversales , Inglaterra/epidemiología , Femenino , Humanos , Hiperlipidemias/epidemiología , Resistencia a la Insulina , Espectroscopía de Resonancia Magnética , Masculino , Síndrome Metabólico/complicaciones , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Obesidad/complicaciones , Obesidad/epidemiología , Fenotipo , Estudios Prospectivos , Factores de RiesgoRESUMEN
Clostridium perfringens type D causes enterotoxemia in sheep and goats. The disease is mediated by epsilon toxin (ETX), which affects the cerebrovascular endothelium, increasing vascular permeability and leading to cerebral edema. In the present study, we compared the distribution and severity of the cerebrovascular changes induced in lambs by C. perfringens type D strain CN1020, its isogenic etx null mutant, and the ETX-producing complemented mutant. We also applied histochemical and immunohistochemical markers to further characterize the brain lesions induced by ETX. Both ETX-producing strains induced extensive cerebrovascular damage that did not differ significantly between each other in nature, neuroanatomic distribution, or severity. By contrast, lambs inoculated with the etx mutant or sterile, nontoxic culture medium did not develop detectable brain lesions, confirming that the neuropathologic effects observed in these infections are dependent on ETX production. Lambs treated with the wild-type and complemented strains showed perivascular and mural vascular edema, as well as serum albumin extravasation, particularly severe in the cerebral white matter, midbrain, medulla oblongata, and cerebellum. Brains of animals inoculated with the ETX-producing strains showed decreased expression of glial fibrillary acidic protein and increased expression of aquaporin-4 in the end-feet processes of the astrocytes around blood vessels. Early axonal injury was demonstrated with anti-amyloid precursor protein immunohistochemistry. Perivascular accumulation of macrophages/microglia with intracytoplasmic albumin globules was also observed in these animals. This study demonstrates that ETX is responsible for the major cerebrovascular changes in C. perfringens type D-induced disease.
Asunto(s)
Encéfalo/patología , Clostridium perfringens/patogenicidad , Enterotoxemia/patología , Enfermedades de las Ovejas/patología , Animales , Acuaporina 4/análisis , Encéfalo/irrigación sanguínea , Química Encefálica , Clostridium perfringens/genética , Enterotoxemia/microbiología , Proteína Ácida Fibrilar de la Glía/análisis , Ovinos , Enfermedades de las Ovejas/microbiologíaRESUMEN
High density mineralised protrusions (HDMP) from the tidemark mineralising front into hyaline articular cartilage (HAC) were first described in Thoroughbred racehorse fetlock joints and later in Icelandic horse hock joints. We now report them in human material. Whole femoral heads removed at operation for joint replacement or from dissection room cadavers were imaged using magnetic resonance imaging (MRI) dual echo steady state at 0.23 mm resolution, then 26-µm resolution high contrast X-ray microtomography, sectioned and embedded in polymethylmethacrylate, blocks cut and polished and re-imaged with 6-µm resolution X-ray microtomography. Tissue mineralisation density was imaged using backscattered electron SEM (BSE SEM) at 20 kV with uncoated samples. HAC histology was studied by BSE SEM after staining block faces with ammonium triiodide solution. HDMP arise via the extrusion of an unknown mineralisable matrix into clefts in HAC, a process of acellular dystrophic calcification. Their formation may be an extension of a crack self-healing mechanism found in bone and articular calcified cartilage. Mineral concentration exceeds that of articular calcified cartilage and is not uniform. It is probable that they have not been reported previously because they are removed by decalcification with standard protocols. Mineral phase morphology frequently shows the agglomeration of many fine particles into larger concretions. HDMP are surrounded by HAC, are brittle, and show fault lines within them. Dense fragments found within damaged HAC could make a significant contribution to joint destruction. At least larger HDMP can be detected with the best MRI imaging ex vivo.
Asunto(s)
Calcinosis/patología , Cartílago Articular/patología , Osteoartritis/patología , Cadáver , Femenino , Pinzamiento Femoroacetabular , Cabeza Femoral/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Microtomografía por Rayos XRESUMEN
Recent conservation planning studies have presented approaches for integrating spatially referenced social (SRS) data with a view to improving the feasibility of conservation action. We reviewed the growing conservation literature on SRS data, focusing on elicited or stated preferences derived through social survey methods such as choice experiments and public participation geographic information systems. Elicited SRS data includes the spatial distribution of willingness to sell, willingness to pay, willingness to act, and assessments of social and cultural values. We developed a typology for assessing elicited SRS data uncertainty which describes how social survey uncertainty propagates when projected spatially and the importance of accounting for spatial uncertainty such as scale effects and data quality. These uncertainties will propagate when elicited SRS data is integrated with biophysical data for conservation planning and may have important consequences for assessing the feasibility of conservation actions. To explore this issue further, we conducted a systematic review of the elicited SRS data literature. We found that social survey uncertainty was commonly tested for, but that these uncertainties were ignored when projected spatially. Based on these results we developed a framework which will help researchers and practitioners estimate social survey uncertainty and use these quantitative estimates to systematically address uncertainty within an analysis. This is important when using SRS data in conservation applications because decisions need to be made irrespective of data quality and well characterized uncertainty can be incorporated into decision theoretic approaches.
Asunto(s)
Participación de la Comunidad , Conservación de los Recursos Naturales , Análisis Espacial , Técnicas de Planificación , IncertidumbreRESUMEN
Clostridium perfringens type D causes disease in sheep, goats, and other ruminants. Type D isolates produce, at minimum, alpha and epsilon (ETX) toxins, but some express up to five different toxins, raising questions about which toxins are necessary for the virulence of these bacteria. We evaluated the contribution of ETX to C. perfringens type D pathogenicity in an intraduodenal challenge model in sheep, goats, and mice using a virulent C. perfringens type D wild-type strain (WT), an isogenic ETX null mutant (etx mutant), and a strain where the etx mutation has been reversed (etx complemented). All sheep and goats, and most mice, challenged with the WT isolate developed acute clinical disease followed by death in most cases. Sheep developed various gross and/or histological changes that included edema of brain, lungs, and heart as well as hydropericardium. Goats developed various effects, including necrotizing colitis, pulmonary edema, and hydropericardium. No significant gross or histological abnormalities were observed in any mice infected with the WT strain. All sheep, goats, and mice challenged with the isogenic etx mutant remained clinically healthy for ≥24 h, and no gross or histological abnormalities were observed in those animals. Complementation of etx knockout restored virulence; most goats, sheep, and mice receiving this complemented mutant developed clinical and pathological changes similar to those observed in WT-infected animals. These results indicate that ETX is necessary for type D isolates to induce disease, supporting a key role for this toxin in type D disease pathogenesis.
Asunto(s)
Toxinas Bacterianas/metabolismo , Infecciones por Clostridium/patología , Clostridium perfringens/patogenicidad , Cabras/microbiología , Ovinos/microbiología , Animales , Toxinas Bacterianas/genética , Clostridium perfringens/genética , Clostridium perfringens/metabolismo , Femenino , Técnicas de Inactivación de Genes , Genes Bacterianos , Prueba de Complementación Genética , Intestinos/microbiología , Estimación de Kaplan-Meier , Masculino , Ratones , Viabilidad Microbiana , Mutación , Plásmidos/genética , Plásmidos/metabolismo , VirulenciaRESUMEN
Rapid genomic scanning methods are required to identify expressed sequences and we report an efficient, sensitive and specific approach which relies upon hybridization of an amplified, labeled cDNA library to digested cosmid DNA. We identified expressed sequences within a cosmid in the glycerol kinase (GK) "critical region" of Xp21 that had impressive similarity to prokaryotic GKs. We used this genomic sequence information to clone the human hepatic GK cDNA. Independent confirmation of the identity of this gene was obtained by functional complementation of GK deficient E. coli mutants with a construct containing the complete human X-linked GK coding sequence.
Asunto(s)
Glicerol Quinasa/genética , Hígado/enzimología , Cromosoma X , Secuencia de Aminoácidos , Bacillus subtilis/enzimología , Bacillus subtilis/genética , Secuencia de Bases , Mapeo Cromosómico , Clonación Molecular , Cósmidos , Escherichia coli/enzimología , Escherichia coli/genética , Biblioteca de Genes , Humanos , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos , Reacción en Cadena de la Polimerasa , Homología de Secuencia de AminoácidoRESUMEN
OBJECTIVES: To assess the inter-rater agreement of corneal cytology findings in canine ulcerative keratitis by veterinary surgeons of different training levels and the agreement of corneal cytology with culture. MATERIALS AND METHODS: Dogs with progressive ulcerative keratitis were prospectively recruited for corneal cytology and culture. Corneal cytology slides were reviewed by veterinary surgeons of different training levels (three general practitioners, three ophthalmologists and three pathologists). The inter-rater agreement of cytology findings and agreement of cytology with culture was assessed using the kappa measure of agreement. RESULTS: The study included 145 corneal cytology samples from 143 dogs (145 eyes) with progressive ulcerative keratitis. Positive cultures were obtained from 81 of 145 (56%) eyes. The most commonly isolated pathogens were Streptococcus canis, Pseudomonas aeruginosa and Staphylococcus pseudintermedius. The results demonstrated increased inter-rater agreement of corneal cytology and increased agreement with culture with increased ocular pathology expertise (pathologists > ophthalmologists > general practitioners). CLINICAL SIGNIFICANCE: This study provides important information about the diagnostic value of corneal cytology in canine ulcerative keratitis and the most common pathogens involved in such cases in the UK. Based on the results of this study, cytology findings should be interpreted in conjunction with the expertise of the observer. For maximal pathogen identification, both cytology and culture should be considered.
Asunto(s)
Úlcera de la Córnea , Enfermedades de los Perros , Animales , Córnea/patología , Úlcera de la Córnea/diagnóstico , Úlcera de la Córnea/patología , Úlcera de la Córnea/veterinaria , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/patología , PerrosRESUMEN
BACKGROUND: Tumor proliferation in human intracranial meningiomas can be defined by the reactivity of the monoclonal antibody MIB-1 to the Ki-67 antigen. Vascular endothelial growth factor (VEGF), a pro-angiogenic factor, is a predictive marker for survival of dogs with intracranial meningiomas. HYPOTHESIS: Ki-67 is expressed in canine intracranial meningiomas and is associated with VEGF expression. Ki-67 expression is a prognostic marker for patient outcome. ANIMALS: Seventy client-owned dogs with WHO grade I intracranial meningiomas. METHODS: Retrospective study assessing the degree of immunostaining for Ki-67 by MIB-1 and VEGF expression in intracranial meningioma tissue from dogs. MIB-1 Labeling Index (LI) was calculated with Image J NIH-software. Extent, intensity, and distribution of VEGF-expression was assessed semiquantitatively. Cross tabulations with Fisher's exact tests and nonparametric Spearman's rank correlations were performed to identify associations between VEGF expression and MIB-1 LI. Fifteen dogs underwent postsurgical radiotherapy and were included in survival analysis. The effect of MIB-1 LI on survival was examined by Kaplan-Meier and Cox proportional hazards regression procedures. RESULTS: Ki-67 staining was positive in 91% (64/70) and VEGF expression was detected in 96% (67/70). There was no significant association between VEGF expression and MIB-1 LI. MIB-1 LI was not associated with survival. CONCLUSIONS AND CLINICAL IMPORTANCE: MIB-1 antibody can be used to document cell proliferation in intracranial meningiomas in dogs, but does not predict outcome. No association between VEGF as a marker of angiogenesis and tumor proliferation was found. Angiogenesis might be a more important predictor of meningioma activity in dogs than is Ki-67.
Asunto(s)
Enfermedades de los Perros/metabolismo , Regulación Neoplásica de la Expresión Génica/fisiología , Antígeno Ki-67/metabolismo , Meningioma/veterinaria , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Perros , Antígeno Ki-67/genética , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
OBJECTIVES: To assess the effectiveness of three commonly used methods of controlling dental plaque accumulation within a general practice setting. MATERIALS AND METHODS: A blinded study, block randomising dogs at recruitment to receive one of three treatments to start after a routine scale and polish procedure: once daily tooth brushing using a toothbrush and veterinary toothpaste, once daily administration of a single dental hygiene chew or a prescription dental diet. Blinded scoring of plaque accumulation, both coverage and thickness, was performed at the end of the 6-week study. RESULTS: A total of 22 dogs completed the study, which simultaneously assessed the effectiveness of the three means of plaque control. Daily tooth brushing was shown to be more than three times as effective at controlling plaque accumulation compared to using a daily dental chew or dental diet. The dental plaque scores for the diet and dental chews were not significantly different from one another and there was much greater variability in the mouth scores for these two groups of dogs compared to the tooth brushing group. CLINICAL SIGNIFICANCE: The study design has been shown to be an effective means of assessing plaque accumulation over a 6-week period using a clean mouth model. Secondly, this study adds to the evidence which shows that daily tooth brushing is the most effective single method of reducing plaque accumulation and optimising dogs' oral health.
Asunto(s)
Placa Dental/veterinaria , Gingivitis/veterinaria , Animales , Enfermedades de los Perros , Perros , Estudios Prospectivos , Método Simple Ciego , Cepillado Dental/veterinariaRESUMEN
We investigate muscle fiber composition, fiber-specific glycolytic and oxidative enzyme capacity and nitric oxide synthase (NOS) expression in skeletal muscle of patients with type 1 diabetes (T1D) compared to individuals with normal glucose tolerance (NGT). Vastus lateralis muscle was obtained by percutaneous biopsy from 7 T1D patients and 10 healthy controls with similar characteristics. Using cytophotometry, muscle fiber composition and fiber type-specific glycolytic and oxidative enzyme activities were measured in slow oxidative (SO), fast oxidative glycolytic (FOG) and fast glycolytic (FG) fibers. In addition, NOS 1-3 protein expression was mea-sured. The glycolytic fiber fraction was 1.4 fold higher, whereas FOG and SO fiber fractions were significantly reduced by 13.5% and 6.2% in skeletal muscle from T1D patients. Glycolytic enzyme activities and fiber-specific ratio of glycolytic relative to oxidative enzyme activity were significantly higher in all fiber types of T1D patients and correlated with HbA (1c). Expression of NOS1-3 isoforms was reduced in skeletal muscle of T1D subjects. Increased glycolytic enzyme activity in muscle of T1D patients is most likely due to both a higher number of fast glycolytic fibers and a shift towards increased glycolytic metabolism in all fiber types. Alterations in muscle fiber distribution and enzyme activities seem to be due to impaired long-term glycemic control.
Asunto(s)
Diabetes Mellitus Tipo 1/enzimología , Diabetes Mellitus Tipo 1/genética , Fibras Musculares Esqueléticas/enzimología , Músculo Esquelético/enzimología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo , Adulto , Biopsia , Diabetes Mellitus Tipo 1/patología , Femenino , Perfilación de la Expresión Génica , Glucólisis , Humanos , Masculino , Fibras Musculares Esqueléticas/patología , Músculo Esquelético/patología , Consumo de Oxígeno , Aptitud Física , Valores de Referencia , Población Blanca , Adulto JovenRESUMEN
The medical records and magnetic resonance images of 33 dogs with surgically confirmed Hansen type I cervical intervertebral disc disease were reviewed. Fourteen of the dogs were chondrodystrophic and 19 were not chondrodystrophic. The most common clinical sign was neck pain, which affected 28 of the dogs, and 23 of the dogs were able to walk. Fifteen of the dogs had developed clinical signs acutely, within the previous 24 hours. On cross-sectional images the median area of spinal cord compression was 26 per cent (range 11 to 71 per cent) of the normal spinal cord area. The degree of spinal cord compression was significantly associated with the dogs' presurgical neurological status but not with their postsurgical neurological status. The dogs with an acute onset of clinical signs had more severe neurological dysfunction before surgery, but their condition improved more as a result of surgery.
Asunto(s)
Vértebras Cervicales/patología , Enfermedades de los Perros/diagnóstico , Desplazamiento del Disco Intervertebral/veterinaria , Imagen por Resonancia Magnética/veterinaria , Compresión de la Médula Espinal/veterinaria , Animales , Perros , Femenino , Desplazamiento del Disco Intervertebral/diagnóstico , Masculino , Pronóstico , Estudios Retrospectivos , Compresión de la Médula Espinal/diagnósticoRESUMEN
OBJECTIVES: To investigate the correlation between the magnetic resonance imaging findings and subsequent surgical findings for a series of dogs presenting with suspected pharyngeal stick injuries to the Animal Health Trust, Newmarket, between 1995 and 2004. METHODS: Magnetic resonance imaging findings were reviewed for patients undergoing a scan of the pharyngeal or cervical area for suspected foreign bodies during the years 1995 to 2004. RESULTS: Case signalment, history and clinical signs were similar to those reported in previous studies. Magnetic resonance imaging demonstrated foreign material in six of seven cases where this was present. There was good correlation between diagnosis of a foreign body at magnetic resonance imaging and subsequent surgical identification. CLINICAL SIGNIFICANCE: Compared with other imaging modalities, magnetic resonance imaging is very helpful for this type of injury, especially in chronic cases where radiographic evidence of a foreign body is unlikely. It is a valuable aid in the diagnosis of pharyngeal penetration injury and in surgical planning.
Asunto(s)
Perros/lesiones , Cuerpos Extraños/veterinaria , Imagen por Resonancia Magnética/veterinaria , Faringe/lesiones , Faringe/cirugía , Heridas Penetrantes/veterinaria , Animales , Femenino , Cuerpos Extraños/diagnóstico , Imagen por Resonancia Magnética/métodos , Masculino , Resultado del Tratamiento , Heridas Penetrantes/diagnóstico , Heridas Penetrantes/cirugíaRESUMEN
A six-month-old, female, domestic shorthair cat was presented with a history of failure to grow and bilateral corneal opacity caused by corneal oedema. Congenital hyposomatotropism and possible secondary hypothyroidism were diagnosed on the basis of fasting serum levels of insulin-like growth factor-1 and thyroxine levels, respectively. These endocrinopathies are rare in the cat and have not been reported to cause ocular signs. The cat died during investigation of these diseases, and histopathological examination of the eyes showed significantly reduced corneal endothelial cell density and number of corneal epithelial cell layers when compared with age-matched healthy control corneas. These changes were implicated in the development of the corneal oedema.
Asunto(s)
Enfermedades de los Gatos/congénito , Edema Corneal/veterinaria , Enanismo Hipofisario/veterinaria , Animales , Enfermedades de los Gatos/diagnóstico , Gatos , Edema Corneal/congénito , Edema Corneal/etiología , Edema Corneal/patología , Enanismo Hipofisario/complicaciones , Enanismo Hipofisario/congénito , Femenino , Inmunohistoquímica/veterinaria , Factor I del Crecimiento Similar a la Insulina/metabolismo , Tiroxina/sangreRESUMEN
OBJECTIVES: To determine the survival of 54 cats with histologically confirmed feline oral squamous cell carcinoma (FOSCC) treated in UK general practice and to determine factors predictive for survival. METHODS: Cases were identified from consecutive samples submitted for histological diagnosis. Observational and survival data were collated retrospectively from submitting practices. Immunohistochemical analysis of cyclooxygenase (COX) expression variables was available using previously published data. Kaplan-Meier product limit estimation for overall survival and Cox proportional hazards regression for potential explanatory variables were performed. RESULTS: The overall median survival time was 44 days [95 per cent confidence interval (CI): 31-79] and 1 year survival was 9.5 per cent. Variables associated with survival were whether the cat was pedigree [hazard ratio (HR)=8.17, 95 per cent CI: 1.96-34.12], whether the cat received non-steroidal anti-inflammatory drug (NSAID) therapy after diagnosis (HR=0.46, 95 per cent CI: 0.21-0.98) and whether the COX-1 staining distribution was patchy rather than diffuse (HR=0.25, 95 per cent CI: 0.08-0.014). CLINICAL SIGNIFICANCE: This study suggests that although the prognosis for inoperable FOSCC remains poor, palliative treatments may offer a survival advantage that compares favourably with more aggressive treatment methods. Further work is needed to evaluate NSAID therapy in this disease, in particular to determine whether the potential survival advantage is because of an analgesic or anticancer effect or both. COX-1 distribution patterns may have a role as a prognostic indicator in this disease.
Asunto(s)
Carcinoma de Células Escamosas/veterinaria , Enfermedades de los Gatos/epidemiología , Neoplasias de la Boca/veterinaria , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/epidemiología , Enfermedades de los Gatos/etiología , Enfermedades de los Gatos/mortalidad , Enfermedades de los Gatos/terapia , Gatos , Medicina Familiar y Comunitaria , Femenino , Masculino , Neoplasias de la Boca/epidemiología , Pautas de la Práctica en Medicina , Modelos de Riesgos Proporcionales , Registros/veterinaria , Estudios Retrospectivos , Análisis de Supervivencia , Reino Unido/epidemiología , Medicina VeterinariaRESUMEN
This paper considers the different approaches to post-authorisation safety monitoring of veterinary medicinal products that is essential to ensure confidence in their safety. Most safety testing is undertaken prior to granting of a marketing authorisation and is generally on a small scale. Field trials are usually much larger, but still involve relatively low numbers of animals compared to the number to which authorised products are administered. Safety testing is generally aimed at detecting common events; the numbers of animals used in the tests are too small for detection of all but the most common reactions. The efficiency of the tests depends on the frequency and severity of the adverse reaction and the ability to associate the adverse event with the product. The latter is affected by the period of time between administration and the event, as well as by its underlying frequency. Adverse reaction surveillance is critical in monitoring the safety of a marketed product. Most is entirely passive and so reporting rates are likely to underestimate true incidence. It is relatively efficient for rare, serious adverse effects and for those with a low underlying frequency in the population, but it is less useful when there is long period between administration and the event, or where the event has a relatively high underlying frequency. Greater emphasis should be placed on active surveillance after production registration. Detailed epidemiological investigations, including cohort, case control and cross-sectional designs, offer the only approaches that provide more information on the association between a product and events that have a high underlying frequency in the population or where there is a long period between administration and the adverse event. The relative merits of different approaches are discussed, with particular reference to our recently published study of the temporal association between canine vaccination and non-specific signs of ill health and plans to undertake studies of associations with feline injection site sarcoma. Emphasis is placed on the need for clearly stated hypotheses and the consideration of equivalence, rather than significance testing when considering safety studies.
Asunto(s)
Sistemas de Registro de Reacción Adversa a Medicamentos , Vigilancia de Productos Comercializados , Vacunas/efectos adversos , Animales , Bases de Datos Factuales , Seguridad , Factores de TiempoRESUMEN
This study demonstrated immunohistochemically the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in feline oral squamous cell carcinoma (FOSCC), with primary polyclonal antibodies raised against human epitopes. COX-2 immunolabelling was intracytoplasmic and, in some neoplastic cells, perinuclear; it was demonstrated in a small proportion (< or = 1%) of neoplastic cells and its intensity was usually mild to moderate. In contrast, all neoplastic tissues showed extensive nuclear and cytoplasmic COX-1 immunolabelling. Cytoplasmic COX-1 immunolabelling was less intense than nuclear labelling in neoplastic tissue. In the adjacent histologically normal oral mucosa, COX-2 immunolabelling was absent. The cytoplasmic and nuclear intensity and distribution of COX-1 immunolabelling was significantly higher in neoplastic tissue than in adjacent normal oral mucosa. The results indicate that COX-1 and COX-2 are overexpressed in FOSCC, but the clinical and pathophysiological significance of this finding remains to be determined.
Asunto(s)
Carcinoma de Células Escamosas/enzimología , Carcinoma de Células Escamosas/veterinaria , Enfermedades de los Gatos/enzimología , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/metabolismo , Neoplasias de la Boca/enzimología , Neoplasias de la Boca/veterinaria , Animales , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Enfermedades de los Gatos/genética , Enfermedades de los Gatos/patología , Gatos , Ciclooxigenasa 1/genética , Ciclooxigenasa 2/genética , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/genética , Inmunohistoquímica , Mucosa Bucal/enzimología , Mucosa Bucal/patología , Neoplasias de la Boca/genética , Neoplasias de la Boca/patologíaRESUMEN
Eleven dogs diagnosed with refractory idiopathic epilepsy were treated orally with gabapentin for a minimum of three months at an initial dose of 10 mg/kg every eight hours. They were all experiencing episodes of generalised tonic-clonic seizures and had been treated chronically with a combination of phenobarbital and potassium bromide at doses sufficient to reach acceptable therapeutic serum levels without causing significant side effects. In each dog, the number of seizures per week, the average duration of the seizures and the number of days on which seizures occurred were compared for the three months before and after they were treated with gabapentin. A minimum 50 per cent reduction in the number of seizures per week was interpreted as a positive response to gabapentin, and six of the dogs showed a positive response. After the addition of gabapentin, both the number of seizures per week (P= 0.005) and the number of days with any seizures in a one-week period (P=0.03) were significantly reduced. Mild side effects of ataxia and sedation were observed in five of the dogs, but they were not severe enough to warrant the treatment being discontinued during the trial.
Asunto(s)
Aminas/uso terapéutico , Anticonvulsivantes/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Epilepsia/veterinaria , Convulsiones/veterinaria , Ácido gamma-Aminobutírico/uso terapéutico , Aminas/efectos adversos , Animales , Anticonvulsivantes/efectos adversos , Ácidos Ciclohexanocarboxílicos/efectos adversos , Enfermedades de los Perros/epidemiología , Perros , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Femenino , Gabapentina , Masculino , Convulsiones/tratamiento farmacológico , Convulsiones/epidemiología , Resultado del Tratamiento , Ácido gamma-Aminobutírico/efectos adversosRESUMEN
OBJECTIVES: To determine whether there is an association between the degree of transverse spinal cord compression detected by magnetic resonance imaging following thoracolumbar Hansen type 1 intervertebral disc disease in dogs and their presenting and postsurgical neurological status. METHODS: Medical records of 67 dogs with surgically confirmed Hansen type 1 intervertebral disc disease (2000 to 2004) were reviewed to obtain the rate of onset of disease, duration of clinical signs and presurgical and postsurgical neurological grade. Percentage of spinal cord compression was determined on transverse T2-weighted magnetic resonance images. Linear regression was used to examine the association between spinal cord compression and each of the above variables. Chi-squared tests were used to examine associations among postsurgical outcome and presurgical variables. RESULTS: Eighty-five per cent (57 of 67) of dogs were chondrodystrophoid. Mean spinal cord compression was 53 per cent (sd=219.7, range 14.3 to 84.9 per cent). There was no association between the degree of spinal cord compression and the neurological grade at presentation, rate of onset of disease, duration of clinical signs or postsurgical outcome, with no difference between chondrodystrophoid and non-chondrodystrophoid dogs. CLINICAL SIGNIFICANCE: The degree of spinal cord compression documented with magnetic resonance imaging in dogs with thoracolumbar Hansen type 1 intervertebral disc disease was not associated with the severity of neurological signs and was not a prognostic indicator in this study.
Asunto(s)
Enfermedades de los Perros/patología , Desplazamiento del Disco Intervertebral/veterinaria , Imagen por Resonancia Magnética/veterinaria , Compresión de la Médula Espinal/veterinaria , Vértebras Torácicas , Animales , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/etiología , Perros , Inglaterra/epidemiología , Desplazamiento del Disco Intervertebral/patología , Registros Médicos , Linaje , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Compresión de la Médula Espinal/patologíaRESUMEN
Canine tonsillar squamous cell carcinoma is an aggressive disease with a poor prognosis. A retrospective study was undertaken of all dogs that were presented between January 1999 and January 2004 to the Animal Health Trust for the treatment of tonsillar squamous cell carcinoma. Five cases were identified, and their median survival time was 211 days (95 per cent confidence interval 80 to 352) with two of the five dogs remaining alive at the end of the study, 826 and 1628 days from diagnosis with no clinical signs of disease. The protocol was well tolerated with only one of the five dogs showing toxicity associated with carboplatin and all dogs that started radiotherapy completing it. Compared with results of previous studies, these cases suggest that surgical cytoreduction followed by coarse fractionated radiotherapy together with carboplatin may be a useful way to treat this tumour. Carboplatin alone caused partial remission in the two cases where it was used as neo-adjunctive therapy.