The responsibilities of veterinary educators in responding to emerging needs in veterinary medicine.

It is an unfortunate fact that not only has veterinary education failed to adapt in the face of likely future needs, but it has also failed to respond to societal changes that have already taken place and that have affected the requirements for veterinary services and veterinary capability. The responsibility is primarily that of educators, although vision and foresight require a co-ordinated approach involving national and international veterinary organisations. Once it is accepted by all parties that change is essential, the implementation will fail unless there is a unified programme involving the schools and colleges, the accrediting agencies, the licensing authorities, governments, the professional organisations and corporate veterinary medicine. All have a role to play, and any one can readily block progress. A unified approach is an absolute requirement. The developed countries must take a leading role, but the issues are global, and ways must be found to facilitate change in all parts of the world. Disease knows no boundaries, and any strategy is only as strong as its weakest link.

Is our divided profession a profession in decline?

Richard Halliwell is concerned by criticisms of the veterinary profession in the recent select committee report on a new Veterinary Surgeons Act. He fears that a lack of leadership and division within the veterinary profession may have contributed to loss of influence, and makes some suggestions for putting that right.

Stress in new graduates: can the profession do more to help?

Richard Halliwell and colleagues believe that it can, on the basis of a survey they conducted to assess the incidence of poor mental health and wellbeing in recent veterinary graduates, and workplace factors that might be associated with this.

The effects of endoparasitism on the immune response to orally administered antigen in cats.

The aim of the study was to assess whether infection with Toxocara cati (T. cati) facilitates the induction of immunoglobulin (Ig) E or other antibody responses to a specific antigen administered with food in kittens. Two groups of 10 cats each, either experimentally infected with T. cati or parasite-free, were dosed with human serum albumin (HSA) added daily to their food from day 7 to 28 inclusive. Levels of HSA-specific IgE, IgG, IgA and IgM were assessed in the serum by enzyme-linked immunosorbent assay (ELISA) in both groups of cats at weeks 0, 2, 4 and 8. Although weak, an IgE response was detected in most of the cats 1 week after exposure to HSA. However, HSA-specific IgG and IgA could only be detected from the third week after exposure to HSA. The group of parasitized cats had significantly higher levels of HSA-specific antibodies of the IgG and IgA at weeks 4 and 8 (p<0.05 by Mann-Whitney) and IgE isotypes at weeks 2 and 4 (p<0.05 by analysis of variance (ANOVA)) than did the group of parasite-free cats. Specific IgM antibody was not detected in the sera of any of the 20 cats. These findings are supportive of a role of T. cati infection in enhancing the IgE response to orally administered antigens, and hence possibly, in genetically susceptible individuals, in the development of food hypersensitivity.

Reducing the suicide rate among veterinary surgeons: how the profession can help.

A short communication on page 415 of this issue of The Veterinary Record draws attention to the high suicide rate among members of the veterinary profession. In this article, Professor Richard Halliwell, who has recently chaired a series of meetings on this matter at the Royal College of Veterinary Surgeons, and Mr Brian Hoskin, chairman of the Veterinary Benevolent Fund, describe some of the support mechanisms available to veterinary surgeons and discuss what more might be done.

Immunoglobulin levels in dogs after total-body irradiation and bone marrow transplantation.

The influence of total-body irradiation (TBI) and autologous or allogeneic bone marrow transplantation on serum immunoglobulin subclasses was determined in a dog model. Only IgG1 levels decreased after low-dose (+/- 4.5 Gy) TBI, but levels of all immunoglobulin classes fell after high-dose TBI (8.5 GyX1 or 2X6.0 Gy). After autologous bone marrow transplantation IgM levels were the first and IgE levels were the last to return to normal. After successful allogeneic bone marrow transplantation prolonged low IgM and IgE levels were found but IgA levels increased rapidly to over 150% of pretreatment values. A comparison of dogs with or without clinical signs or graft-versus-host disease (GVHD), revealed no differences in IgM levels. Dogs with GVHD had higher IgA but lower IgE levels. Dogs that rejected their allogeneic bone marrow cells showed significant early rises in IgE and IgA levels in comparison with dogs with GVHD. These results differ from the observations made on Ig levels in human bone marrow transplant patients. No significant differences in phytohemagglutinin stimulation tests were found between dogs with or without GVHD or dogs receiving an autologous transplant for the first four months after TBI and transplantation. An early primary or secondary involvement of humoral immunity in GVHD and graft rejection in dogs is postulated.

Dermal collagen degradation and phagocytosis. Occurrence in a horse with hyperextensible fragile skin.

A 2-year-old female horse had large areas of hyperextensible, fragile skin that were interspersed with areas of normal skin. Affected skin tore easily and contained reduced amounts of dermal collagen. Collagen fibers were fragmented and disorganized, and in trichrome-stained sections, many fibers had abnormal red-stained centers. Electron microscopy showed that many collagen fibers had discrete foci of degradation in which the fibrils were fragmented, loosely packed, and widely separated by granular material. Collagen fibril fragments were present in secondary lysosomes in dermal fibroblasts, but there were no degranulated mast cells or inflammatory cells in these areas. This suggested that a noninflammatory degradation and phagocytosis of collagen had occurred in the areas of hyperextensible fragile skin in this horse. Unaffected skin had no signs of collagen degradation or phagocytosis; uniformly cylindrical collagen fibrils were densely packed into morphologically normal fibers.

Total hemolytic complement values in normal and diseased dog populations.

The optimum conditions for handling and storage of canine sera for total hemolytic complement assays were assessed. Sera from 113 normal dogs and 217 clinical admissions to the University of Pennsylvania Veterinary Hospital were assayed for total hemolytic complement levels. Normal sera had a mean value of 185 CH50 units. Sera from animals with systemic lupus erythematosus and hemorrhagic gastroenteritis, had significantly lower mean levels of complement than the normal group. Sera from dogs with generalized demodectic mange, tumors, various inflammatory diseases, hypothyroidism, seborrhea, and rheumatoid arthritis had values significantly higher than the normal population.

A new era in veterinary immunology.

The importance of the creation of a new international journal of "Veterinary Immunology and Immunopathology" is apparent following the emergence of veterinary immunology as an identifiable discipline and the vital part played by investigations of animal models of immunological diseases of man. The journal will contain papers on basic immunology of domestic animals and on the many disease processes that result in domestic and laboratory animals from immunologic defects. It should thus have a wide appeal to workers in all immunologically related disciplines. Papers will be refereed by members of an international editorial advisory board.

Allergen-specific IgE and IgGd antibodies in atopic and normal dogs.

Intradermal skin tests (IDSTs) were performed on 65 atopic and 24 normal dogs. The levels of allergen-specific IgE and IgGd antibodies were determined in serum samples by enzyme-linked immunosorbent assay (ELISA) using the same 12 allergens that were used in the IDST on normal dogs. The correlation between the levels of IgE and IgGd to Dermatophagoides farinae (DF) and Dermatophagoides pteronyssinus (DP) was examined. The sensitivity, specificity and positive and negative predictive values of allergen-specific IgE and IgGd levels in the total dog population were also compared. Results were consistent and reproducible for 9/12 allergens, but in the case of house dust, flea and Alternaria tenuis, a less discriminating standard curve and the fact that the negative control gave positive results, suggests non-specific binding and that these allergens are complex and should not be employed without further purification. A high percentage of atopic dogs had positive IDSTs and detectable IgE and IgGd antibodies to DF, DP and house dust. Similar results were obtained in the normal dog population. There were significant correlations between allergen-specific IgE and IgGd levels to DF and DP. However, in contrast to IgE, allergen-specific IgGd in normal dogs was higher than in atopic dogs. Furthermore, a high percentage of the atopic population had detectable IgGd to unrelated allergens, despite negative IDSTs. Overall, the negative predictive values were similar for both IgE and IgGd. Sensitivities were higher in the allergen-specific IgGd assays, but the specificities and positive predictive values were higher in the allergen-specific IgE assays. In conclusion, the concordance of IDSTs with ELISA results to DF and DP in normal dogs without clinical signs implied the possible heterogeneity of IgE in dogs. The presence of IgGd directed against apparently irrelevant allergens in atopic patients and the high levels of IgGd in normal dogs to the most common allergens, DF and DP, implied an uncertain role of IgGd in canine atopic disease. Therefore, the detection of allergen-specific IgE is a more useful adjunct to the diagnosis of atopic disease in the dog than IgGd.

The ACVD task force on canine atopic dermatitis (III): the role of antibodies in canine atopic dermatitis.

Although an important pathogenic role for IgE is established in the case of allergic asthma and rhinitis in man, its role in atopic dermatitis is less clear. There are many studies where allergists and immunologists have provided evidence in favour of such a role, whereas dermatologists are less than convinced. In dogs, however, there is an abundance of clinical evidence implying that atopic dermatitis is antigen driven, and recent studies suggest that there may be a role for IgE, not only in the effector pathway, but also in antigen capture. Although an IgG response often accompanies an IgE response in dogs with atopic dermatitis, there is little evidence in support of a pathogenic role in respect of the former isotype.

The ACVD task force on canine atopic dermatitis (XI): the relationship between arthropod hypersensitivity and atopic dermatitis in the dog.

The relationship between arthropod allergen hypersensitivity and the development of canine atopic dermatitis (AD) is unclear. It has been shown that dogs with AD are more likely to exhibit positive intradermal reactivity to flea allergens than non-pruritic dogs from the same flea-endemic geographic region. Also, dogs in a flea endemic region are four times more likely to suffer from flea allergy dermatitis (FAD) and AD than from FAD alone. These results provide indirect evidence to support the hypothesis that, in the canine species, atopy predisposes to the development of hypersensitivity to flea allergens and eventually to FAD. A causal relationship between insects other than fleas and canine AD has not been identified with certainty.

Feline immunoglobulin E: induction of antigen-specific antibody in normal cats and levels in spontaneously allergic cats.

Sera from 10 cats with symptoms consistent with atopy, from 15 normal household cats and from 11 laboratory maintained cats were assessed for allergen-specific IgE and IgG to Dermatophagoides farinae (DF) by enzyme-linked immunosorbent assay (ELISA). In addition, 10 normal cats were immunised with DF and intradermal skin tests (IDST) were performed weekly. Sera from the latter were also assessed for DF-specific IgE by ELISA and using Prausnitz-Küstner (PK) tests. Although DF-specific IgE was detectable in all the atopic cats, there was no significant difference between the levels in this group and in the clinically normal household cats. However levels in both these groups were significantly higher than those in the laboratory maintained cats. Detectable DF-specific IgE was induced in all of the 10 cats, but the levels were not correlated with the development of positive IDSTs, nor with the level of IgE as assessed by PK tests. These findings are consistent with a possible heterogeneity of IgE antibody in cats.

Production and characterisation of polyclonal antisera against feline IgE.

Cats, naturally or experimentally infected with Toxocara cati were immunised with dinitrophenylated ascaris antigen (DNP-Asc). All cats developed immediate skin reactivity to DNP coupled to bovine serum albumin (DNP-BSA) and the sera of the nine cats had a heat labile homocytotropic antibody detectable by homologous Prausnitz-Küstner (PK) tests. Reagin-rich fractions were prepared from these sera and used for the preparation of polyclonal antisera in rabbits. Resultant antisera were passed through a immunoabsorbent column of Sepharose 4B coupled to heated normal cat serum. An immunoabsorbent column prepared with the resultant antisera removed the PK reactivity from the cat sera, and the activity was recovered following acid elution. The antiserum failed to detect any recognised immunoglobulin in cat sera, but precipitated with a heat labile protein with gamma-1 electrophoretic mobility in the sera of parasited cats. These findings support the contention that the antisera are specific for feline IgE.

IgE and IgG antibodies to flea antigen in differing dog populations.

A radioimmunoassay was developed for the detection of IgG and IgE canine antibodies against partially purified flea antigen. Low background levels were found in flea naive dogs, but high levels of both IgE and IgG antibodies were found in many sera from dogs with clinical flea hypersensitivity. In sera from non-allergic dogs exposed chronically to fleas, IgE levels differed little from background, and levels of IgG anti-flea antibodies were much lower than those from the flea allergic group. The results suggest that chronic flea exposure may result in partial or complete tolerance rather than hyposensitization in the commonly accepted sense.

The induction and kinetics of an anti-DNP IgE response in dogs.

Twenty-eight dogs immunized to dinitrophenol-ascaris (DNP-ASC) at birth and then three times at two week intervals produced serum anti-DNP antibody. The IgM response was detected one week after primary immunization and lasted for up to five weeks. The IgE and IgG antibody response in general was not present until week three but persisted through the immunization schedule. Although variation in the level and duration of the antibody response was detected between individual dogs, each dog did have a response that included all three isotypes examined.

The role of basophils in the immunopathogenesis of hypersensitivity to fleas (Ctenocephalides felis) in dogs.

Biopsies taken of skin test sites from 10 dogs allergic to fleas were fixed in Karnovsky's fixative and embedded in methacrylate. One micron sections were stained with acid Giemsa for identification of basophils. This cell was identified in most biopsies taken at intervals from 1 hour to 48 hours post-injection. The proportion was highest between 4 hours and 18 hours and had substantially fallen by 48 hours. The highest number of basophils recorded as a percentage of the inflammatory infiltrate was 22.1%, with biopsies from 7 of the 10 dogs showing in excess of 10% basophils at some point. The results suggest that cutaneous basophil hypersensitivity may play an immunopathogenic role in flea-bite hypersensitivity in dogs.

Identification of anti-idiotypic antibody in dogs.

There is general agreement that idiotype/anti-idiotype (id/anti-id) networks are important mechanisms of immune regulation, based primarily on studies conducted using inbred laboratory animals. To determine if anti-idiotypic antibody (anti-id) could be induced during an immune response in outbred dogs, the dogs were immunized to the hapten-carrier combination dinitrophenol-ascaris (DNP-ASC) and subsequently immunized with autologous antibody in complete Freund's adjuvant (CFA). Auto-anti-id was detected in three of five dogs during the DNP-ASC response. A cross-reactive anti-id was detected in dogs immunized with autologous antibody when a mouse monoclonal antibody was used as the id. These experiments further suggest that the regulation of the immune response via network interaction, as first illucidated in inbred animals, may occur in dogs.

Local and systemic antibody production in horses affected with chronic obstructive pulmonary disease.

An enzyme-linked immunosorbent assay (ELISA) was used to quantify isotype-specific antibody to Micropolyspora faeni and to Aspergillus fumigatus in the sera and bronchoalveolar lavage fluid (BALF) of normal horses, horses with chronic obstructive pulmonary disease (COPD) and horses with other chronic respiratory diseases. Elevated antibody levels were not detected in the sera of affected horses. However, both IgE and IgA antibody to both allergens was significantly elevated in BALF in COPD affected horses sampled both when symptomatic and asymptomatic. Elevated levels were also found in animals that developed a chronic cough after an acute onset with symptoms compatible with a respiratory virus infection. In one animal a ten fold increase in IgE antibody to the two allergens developed after an interval of 7 weeks. These findings are supportive of a central role of local IgE antibody to mould allergens in the immunopathogenesis of COPD, and also suggest that respiratory viral infection may predispose to the development of COPD in some horses.

Quantification of histamine in plasma and pulmonary fluids from horses with chronic obstructive pulmonary disease, before and after 'natural (hay and straw) challenges'.

A commercial radioimmunoassay kit was used to quantify histamine concentrations of plasma, bronchoalveolar lavage fluid (BALF) and pulmonary epithelial lining fluid (PELF) of normal horses and horses with chronic obstructive pulmonary disease (COPD), before and after 'natural (hay and straw) challenge' (NC). There were no significant changes in the concentrations of histamine in plasma or BALF at 0.5 or 5 h after NC, but the PELF histamine concentration of COPD affected horses was significantly increased at 5 h, but not at 0.5 h, following NC. As the histamine concentrations of whole BALF lysates were significantly correlated with the numbers of metachromatically staining cells, presumed to be mast cells and/or basophils, these findings support involvement of a late phase, IgE mediated, hypersensitivity reaction in the pathogenesis of equine COPD.