K C Smith

Royal Veterinary College, Londinium, England, United Kingdom

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Publications (66)107.07 Total impact

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    ABSTRACT: Background Dogs with congenital portosystemic shunts (CPSS) have hypoplasia of the intrahepatic portal veins. Surgical CPSS attenuation results in the development of the intrahepatic portal vasculature, the precise mechanism for which is unknown, although new vessel formation by angiogenesis is suspected.HypothesisThat the degree of portal vascular development and the increase in portal vascularization after CPSS attenuation is significantly associated with hepatic vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) gene expression and serum VEGF concentration.AnimalsClient-owned dogs with CPSS undergoing surgical treatment. Forty-nine dogs were included in the gene expression data and 35 in the serum VEGF data.Materials and Methods Dogs surgically treated by partial or complete CPSS attenuation were prospectively recruited. Relative gene expression of VEGF and VEGFR2 was measured in liver biopsy samples taken at initial and follow-up surgery using quantitative polymerase chain reaction. Serum VEGF concentration was measured before and after CPSS attenuation using a canine specific ELISA. Statistical significance was set at the 5% level (P ≤ .05).ResultsThere was a significant increase in the mRNA expression of VEGFR2 after partial attenuation (P = .006). Dogs that could tolerate complete attenuation had significantly greater VEGFR2 mRNA expression than those that only tolerated partial attenuation (P = .037). Serum VEGF concentration was significantly increased at 24 (P < .001) and 48 (P = .003) hours after attenuation.Conclusions and Clinical ImportanceThese findings suggest that intrahepatic angiogenesis is likely to occur after the surgical attenuation of CPSS in dogs, and contributes to the development of the intrahepatic vasculature postoperatively.
    Journal of Veterinary Internal Medicine 08/2014; · 2.06 Impact Factor
  • Journal of Veterinary Internal Medicine 06/2014; · 2.06 Impact Factor
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    ABSTRACT: Screening for expression of the high affinity receptor for IgE by reverse transcriptase PCR, revealed that almost all canine mast cell tumors expressed FcɛRIα mRNA, supporting the rationale for developing anti-neoplastic treatments based on molecules that could target this receptor. Use of cytotoxic cytokines to trigger an apoptotic signal is one strategy for inducing cell death in malignant mast cells. The coding sequences for canine IgE and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were identified through genome analyses. Selected regions of the coding sequences for these genes were cloned and compared to the predicted genome sequences. The Fc region of canine IgE, death domain of canine TRAIL and an IgE Fc: TRAIL fusion construct were generated and epitope-tagged proteins expressed, using a eukaryotic expression system. Specific binding of recombinant canine IgE Fc-containing proteins to recombinant human FcɛRIα and to a canine mast cell tumor line expressing FcɛRIα (C2), but not one failing to express FcɛRIα (MCLA), was demonstrated. Specific binding of the IgE:TRAIL fusion protein was not abrogated by the TRAIL moiety. These results are proof of principle that canine IgE targeting to FcɛRIα can be used as a platform for selective delivery of therapies to FcɛRIα-expressing cells, potentially enhancing their therapeutic index and efficacy.
    Veterinary Immunology and Immunopathology 01/2014; · 1.88 Impact Factor
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    ABSTRACT: Wellbeing (positive mental health) and mental ill-health of veterinary students from a single UK school were quantified using validated psychological scales. Attitudes towards mental ill-health and suicide were also assessed. Results were compared with published data from the UK general population and veterinary profession. Of the total student population (N=1068), 509 (48 per cent) completed a questionnaire. Just over half (54 per cent) of the respondents had ever experienced mental ill-health, with the majority reporting a first occurrence before veterinary school. Student wellbeing was significantly poorer (p<0.0001) than general population estimates, but not significantly different (p=0.2) from veterinary profession estimates. Degree of mental distress in students was significantly higher than in the general population (p<0.0001). Despite the majority (94 per cent) agreeing that 'Anyone can suffer from mental health problems', students were significantly more likely than members of the general population to agree that 'If I were suffering from mental health problems, I wouldn't want people knowing about it' (p<0.0001). Students were more likely to have thought about suicide, but less likely to have made an attempt (p<0.001; p=0.005), than members of the general population. The possibility of non-response bias must be considered when interpreting findings. However, strong similarities between results from this study population and the UK veterinary profession, as well as other veterinary student populations internationally, suggest no substantial school-level bias.
    The Veterinary record. 08/2013;
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    ABSTRACT: REASONS FOR PERFORMING STUDY: Many studies of respiratory disease in racehorses have focused on a combination of increased tracheal mucus and airway neutrophilia. Examination of each component separately should provide further insight into this condition. OBJECTIVES: To identify infectious risk factors for endoscopically-visible tracheal mucus in National Hunt racehorses. STUDY DESIGN: A 2-year prospective longitudinal study. METHODS: Monthly quantitative bacteriological examinations of tracheal wash samples and viral serological examinations were conducted. Risk factors for 'small amounts of mucus' (mucus score = 1/3) and 'increased mucus' (score >2/3) were identified. RESULTS: There were increased odds of small amounts of mucus when both S.zooepidemicus and non-haemolytic streptococci (NHS) were isolated (OR 2.6; 95%CI: 1.5-4.6; p<0.001) but not when either species was isolated in the absence of the other. Increased odds of increased mucus were associated with the isolation of either S.zooepidemicus (OR 5.6; 95% CI: 1.2-25.9; p = 0.03) or NHS (OR 3.7; 95% CI: 1.2-11.6; p = 0.02), with an increased effect when both were isolated together (OR 12.5; 95% CI: 3.7-41.6; p<0.001). Approximately 6-fold increased odds of small amounts of mucus were associated with the first 3 months in training (OR 6.3; 95% CI: 2.0-19.4; p<0.001) and 3-fold increased odds of increased mucus associated with the first 6 months in training (OR 2.9; 95% CI: 1.3-6.4; p = 0.01). Coughing at exercise and increased serous nasal discharge were specific but insensitive indicators of increased mucus. CONCLUSIONS: Associations with S.zooepidemicus corroborate previous research, but an independent effect of NHS has not been reported previously. The possibility that there are individual pathogenic species within this group should be considered. Further work is required to identify S.zooepidemicus subtypes and NHS species associated with disease. Closer monitoring of the respiratory health of horses entering training for the first time is likely to be valuable.
    Equine Veterinary Journal 06/2013; · 2.29 Impact Factor
  • The Veterinary record. 05/2013;
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    ABSTRACT: Histopathological changes are reported in the livers of cats with congenital portosystemic shunts (CPSS) before and after surgical attenuation. Medical records, portovenograms and liver biopsies from cats treated surgically for CPSS were reviewed. Biopsies were graded for histopathological features characteristic of CPSS. Of 40 cats with CPSS included in the study, all had portal vein hypoplasia and arteriolar hyperplasia at initial surgery, 20 (50 per cent) had hepatocyte swelling with microvesicular vacuolar change, 17 (42.5 per cent) had fibrosis, 12 (30 per cent) had hepatocyte swelling with macrovesicular vacuolar change, 8 (20 per cent) had biliary hyperplasia and 2 (5 per cent) had haemosiderin within Küpffer cells. Cats with macrovesicular vacuolar change were significantly older than cats without (P = 0.001), with median ages of 18.5 months and 8.5 months, respectively. Twenty-five cats had partial attenuation of the CPSS at initial surgery, and 16 of these had follow-up biopsy samples. There were no significant differences in the histopathological features of biopsies before and after partial attenuation. From first to second surgery, there was a significant improvement in intrahepatic vasculature on portovenography both before (P = 0.001) and after (P = 0.039) temporary complete attenuation. Following partial CPSS attenuation, there was no significant change in histopathological features despite an improvement in intrahepatic vasculature on portovenography.
    The Veterinary record. 01/2013;
  • S L Priestnall, K C Smith
    The Veterinary Journal 03/2012; 191(3):271-2. · 2.42 Impact Factor
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    ABSTRACT: Surgical attenuation of a congenital portosystemic shunt (CPSS) results in increased liver mass, development of intrahepatic portal vasculature and improved liver function. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. The aim of this study was to investigate the role of VEGF and its receptor in the hepatic response to CPSS surgery. The study included 99 dogs with CPSS treated with either partial or complete suture attenuation. Forty-four dogs with partial attenuation underwent a second surgery for complete attenuation. The expression of VEGF and VEGF receptor 2 (VEGFR2) in biopsy samples of liver was assessed by immunohistochemistry with rabbit anti-human VEGF polyclonal antibody and mouse anti-human VEGFR2 monoclonal antibody. Expression of these molecules was graded. The proportion of samples expressing VEGF was significantly greater in samples from dogs with CPSS compared with control samples (P=0.04) and the proportion of samples expressing VEGFR2 was significantly greater in control samples compared with samples from dogs with CPSS (P=0.04). VEGF labelling grade decreased significantly (P=0.038) and VEGFR2 increased significantly (P=0.046) between first and second surgery. The decrease in VEGF may reflect transient expression, preferential expression of other factors, reperfusion of existing vessels and/or increased angiogenesis before surgery in the form of arterialization and subsequent reduction due to improved portal blood flow. Partial suture attenuation was associated with a degree of 'normalization' of VEGF and VEGFR2 expression when compared with the control samples. Further investigation is needed to provide more information on the hepatic response to CPSS surgery.
    Journal of comparative pathology 10/2011; 147(1):55-61. · 1.73 Impact Factor
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    K C Smith
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    ABSTRACT: Respiratory disease is an important cause of wastage in the Thoroughbred industry and is a cause of welfare problems in all types of horse. This review concerns developments in our understanding of equine respiratory disease since 1998 and illustrates how strategic funding from the Horserace Betting Levy Board has contributed to this understanding.
    Equine Veterinary Journal 07/2011; 43(4):388-92. · 2.29 Impact Factor
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    ABSTRACT: CD11c serves as a marker for human and murine dendritic cells (DCs) and cells expressing this marker have been shown to have similar morphological and functional characteristics in the canine immune system. The aim of this study was to quantify CD11c(+) cells in the duodenum, ileum and colon of healthy dogs and dogs with inflammatory bowel disease (IBD). Endoscopic biopsies from the duodenum (n=12 cases), ileum (n=8 cases) and colon (n=12 cases) were obtained from dogs diagnosed with IBD. Intestinal tissue from 10 healthy beagle dogs was used as control. Immunofluorescence microscopy was carried out using an anti-canine CD11c monoclonal antibody. Labelled cells were recorded as cells per 120,000 μm(2). The canine chronic enteropathy clinical activity index (CCECAI) was calculated for all dogs with IBD. In addition, sections from all dogs with IBD were evaluated according to the guidelines of the World Small Animal Veterinary Association Gastrointestinal Standardization Group. The number of CD11c(+) cells in the duodenum, ileum and colon of dogs with IBD was significantly reduced compared with controls (P<0.01, P<0.01 and P<0.05, respectively). There was a significant negative correlation between the number of CD11c(+) cells in the colon of dogs with IBD and the CCECAI (P=0.044, r(2)=-0.558). Chronic inflammation in canine IBD appears to involve an imbalance in the intestinal DC population. Future studies will determine whether reduced expression of CD11c could be a useful marker for the diagnosis and monitoring of canine IBD.
    Journal of comparative pathology 05/2011; 145(4):359-66. · 1.73 Impact Factor
  • The Veterinary record. 04/2011; 168(17):458.
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    ABSTRACT: Rates of airway inflammation in young racehorses decrease with time but it is not clear whether this is associated with increasing age or time exposed to the training environment. The structure of the British National Hunt (NH) population allowed closer examination of this relationship. To compare rates of inflammatory airway disease diagnosed by tracheal sampling (trIAD), and its components, in NH racehorses by age and training history and with published rates in young racehorses. A prospective, longitudinal study was conducted on 5 NH yards over 2 years. Period sample prevalences of nasal discharge, tracheal mucus, airway neutrophilia and trIAD (defined by a combination of tracheal mucus and airway neutrophilia) were estimated and compared between horses with different ages and time in training. Horses new to training had twice the odds of visible tracheal mucus as ex-flat trained horses (OR 2.0; 95% CI: 1.4-2.8; P<0.001) but no significantly increased odds of airway neutrophilia (OR 1.3; 95% CI: 0.8-1.9; P = 0.3) and inconclusive evidence of increased odds of trIAD (OR 1.8; CI: 0.9-3.5; P = 0.08). However, a lower median time in training was significantly associated with the presence of visible mucus (P<0.001), increased mucus (P = 0.005) and trIAD (P = 0.03). No disease measure varied significantly with age. Tracheal mucus and trIAD, but not neutrophilia detected in tracheal wash samples, were less prevalent in horses that had been exposed to the training environment for longer, explaining previously reported associations with age. Neutrophil proportion in tracheal wash samples is not as useful a clinical tool as measures of visible tracheal mucus for identifying horses requiring treatment or changes in management. The inclusion of tracheal wash neutrophils in the assessment of equine airways, or at least their relative weighting in definitions of trIAD, should be re-evaluated.
    Equine Veterinary Journal 03/2011; 43(6):750-5. · 2.29 Impact Factor
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    ABSTRACT: The aim of this study was to describe and report the prevalence of conditions found at necropsy examination of UK donkeys. Records from 1,444 donkeys over a 7-year period were included in the analysis. Sixty-one categories of post-mortem finding were identified from 9,744 observations. The four most prevalent conditions noted were dental disorder (78.7%), vascular disease other than aneurysm (60.9%), arthritis (55.4%) and foot disorder (44.8%). Gastric ulceration was found in 42% of the donkeys and gastrointestinal impaction in 18.6%. The most frequent combination of two post-mortem findings in the same animal was arthritis and dental disorder. The most common disorders were associated with age, body weight and/or body condition post mortem and, for some disorders, gender. For many of the post-mortem findings, crude associations were found between the presence of one finding and the odds of also having certain other post-mortem findings. This study is the first to summarize all conditions noted at necropsy examination for a large group of donkeys. The findings increase knowledge of diseases and conditions of this species and may be useful when investigating the relevance of various pathological conditions in the live animal.
    Journal of Comparative Pathology 02/2011; 144(2-3):145-156. · 1.38 Impact Factor
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    ABSTRACT: Neoplastic diseases are typically diagnosed by biopsy and histopathological evaluation. The pathology report is key in determining prognosis, therapeutic decisions, and overall case management and therefore requires diagnostic accuracy, completeness, and clarity. Successful management relies on collaboration between clinical veterinarians, oncologists, and pathologists. To date there has been no standardized approach or guideline for the submission, trimming, margin evaluation, or reporting of neoplastic biopsy specimens in veterinary medicine. To address this issue, a committee consisting of veterinary pathologists and oncologists was established under the auspices of the American College of Veterinary Pathologists Oncology Committee. These consensus guidelines were subsequently reviewed and endorsed by a large international group of veterinary pathologists. These recommended guidelines are not mandated but rather exist to help clinicians and veterinary pathologists optimally handle neoplastic biopsy samples. Many of these guidelines represent the collective experience of the committee members and consensus group when assessing neoplastic lesions from veterinary patients but have not met the rigors of definitive scientific study and investigation. These questions of technique, analysis, and evaluation should be put through formal scrutiny in rigorous clinical studies in the near future so that more definitive guidelines can be derived.
    Veterinary Pathology 01/2011; 48(1):19-31. · 1.93 Impact Factor
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    ABSTRACT: The aim of this study was to describe and report the prevalence of conditions found at necropsy examination of UK donkeys. Records from 1,444 donkeys over a 7-year period were included in the analysis. Sixty-one categories of post-mortem finding were identified from 9,744 observations. The four most prevalent conditions noted were dental disorder (78.7%), vascular disease other than aneurysm (60.9%), arthritis (55.4%) and foot disorder (44.8%). Gastric ulceration was found in 42% of the donkeys and gastrointestinal impaction in 18.6%. The most frequent combination of two post-mortem findings in the same animal was arthritis and dental disorder. The most common disorders were associated with age, body weight and/or body condition post mortem and, for some disorders, gender. For many of the post-mortem findings, crude associations were found between the presence of one finding and the odds of also having certain other post-mortem findings. This study is the first to summarize all conditions noted at necropsy examination for a large group of donkeys. The findings increase knowledge of diseases and conditions of this species and may be useful when investigating the relevance of various pathological conditions in the live animal.
    Journal of comparative pathology 09/2010; 144(2-3):145-56. · 1.73 Impact Factor
  • Equine Veterinary Education. 01/2010; 18(1):8 - 10.
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    ABSTRACT: A 11-year-old, female, spayed greyhound was presented with a haemorrhagic discharge from the vulva. Clinical examination, vaginoscopy and a computed tomography scan showed an irregular egg-sized mass in the region of the cervix and uterine stump. An endoscopic grab biopsy (incisional) suggested a malignant mesenchymal tumour. Following this, surgical excision of the cranial vagina, cervix and the uterine remnant was performed. The final diagnosis of haemangiosarcoma was based on histological examination of the larger excisional biopsy specimen and was confirmed by positive immunolabelling of the neoplastic endothelial cells for the von Willebrand factor.
    Journal of Small Animal Practice 09/2009; 50(9):488-91. · 1.18 Impact Factor
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    ABSTRACT: Between 1990 and 1993, 16 cats were referred with acute onset blindness or intraocular haemorrhage. Blood pressure assessment, using the Doppler ultrasonic recording technique in 11 of the cats, proved these cases to be hypertensive. Fifteen cats underwent further investigation, revealing 13 with some degree of renal impairment and one as hyperthyroid. Five underwent cardiac ultrasound and all showed evidence of cardiac hypertrophy. The eyes from four of the cats were examined histologically and showed serous or haemorrhagic retinal detachments with varying degrees of retinal degeneration and a range of ocular hypertensive vascular changes. Two cats had full post mortem examinations which revealed evidence of renal and thyroid pathology.
    Journal of Small Animal Practice 06/2008; 35(12):604 - 611. · 1.18 Impact Factor
  • The Veterinary record 05/2008; 162(17):558-61. · 1.80 Impact Factor

Publication Stats

558 Citations
107.07 Total Impact Points

Institutions

  • 2011–2014
    • Royal Veterinary College
      • • Department of Pathology and Infectious Diseases
      • • Department of Veterinary Clinical Sciences
      Londinium, England, United Kingdom
  • 1994–2011
    • Animal Health Trust
      Newmarket, England, United Kingdom
  • 2009
    • University of Florida
      • Department of Infectious Diseases and Pathology
      Gainesville, FL, United States
  • 2006
    • University of Oxford
      • Department of Statistics
      Oxford, ENG, United Kingdom