Use of Body Surface Area (BSA)-Based Dosages to Calculate Chemotherapeutic Drug Dose in Dogs: I. Potential Problems with Current BSA Formulae

The dose of most cancer chemotherapeutic drugs administered to dogs is calculated on the basis of estimated body surface area (BSA); however, results of some chemotherapy trials have revealed that this dosing method increases toxicosis in small dogs. The current formula used to estimate BSA in dogs may be inaccurate or the assumption that BSA correlates with chemotherapeutic drug exposure may be unfounded. Results presented in this review suggest that canine BSA estimates may be inaccurate because the values for the constant (K) and exponent (a) in the formulae (BSA = K.W^a) are incorrect or because a linear parameter such as body length is lacking from the formulae. Results that suggest the relationship between BSA and the physiologic/pharmacologic factors that influence drug exposure may not be closely correlated are also presented. Studies are warranted to determine whether there are dosing methods that normalize chemotherapeutic drug toxicity in dogs.     

Computer applications. An overview

Applications are programs that are designed for specific tasks. They may be written by the ultimate user or by commercial programmers. Personally written software offers the benefit of a custom solution and adaptability to changing conditions but at a very high cost. Vendor software is cheaper, but more general in nature. It may be difficult for some practitioners to find commercial software that exactly duplicates their operation, and adaptations will add expense. Software maintenance may not be available or it may mean additional cost. Veterinarians can profit from practice management packages, computer-aided diagnostics, educational software, and other programs. Computers must solve the users' problems or they are worthless. With appropriate applications, they represent one of the most cost-effective instruments in the practice.     

Invited review: Amino acid bioavailability and digestibility in pig feed ingredients: terminology and application

In this review, the terminology that is used to describe the bioavailability and ileal digestibility of AA in pig feed ingredients is defined. Aspects of the methodology to establish bioavailability and ileal digestibility values also are discussed, and recommendations about the use of these values are provided. Two main factors can contribute to differences between bioavailability and ileal digestibility of AA. First, some AA, such as Lys, may be absorbed in chemical complexes that preclude their use for metabolism. Second, fermentation in the upper gut may result in a net loss or gain of AA to the animal. In addition, dietary effects on the efficiency of using bioavailable AA intake for tissue growth or milk production should be considered and may be attributed to endogenous AA losses in the hindgut and the metabolic costs associated with endogenous gut protein synthesis and losses. Ileal digestibility values may be expressed as apparent ileal digestibility (AID), standardized ileal digestibility (SID), or true ileal digestibility (TID). These terms are used to specify how ileal endogenous AA losses are reflected in digestibility values. Ileal endogenous AA losses may be separated into basal losses, which are not influenced by feed ingredient composition, and specific losses, which are induced by feed ingredient characteristics such as levels and types of fiber and antinutritional factors. Values for AID are established when total ileal outflow of AA (i.e., the sum of endogenous losses and nondigested dietary AA) is related to dietary AA intake. A concern with the use of AID values is that these are not additive in mixtures of feed ingredients. This concern may be overcome by correcting AID values for defined basal endogenous losses of AA, which yields SID values. Furthermore, if the AID values are corrected for basal and specific endogenous losses, then values for TID are calculated. However, reliable procedures to routinely measure specific endogenous losses are not yet available. It is recommended that basal ileal endogenous losses of AA should be measured in digestibility experiments using a defined protein-free diet and that these losses are reported with observed AID and SID values. It is suggested that SID values should be used for feed formulation, at least until more information on TID values becomes available.     

Lymph node cytology

In clinical practice, animals with lymphadenopathy are eminently suitable candidates for cytology sample collection by FNAB from several enlarged nodes; or, if surgical biopsies are made, imprint smears from the tissue may yield diagnostically useful information to supplement the histological findings. Cytology may reveal the lesion to be reactive, inflammatory, or neoplastic. Cytologically, reactive nodes will contain increased numbers of plasma cells, possibly with some inflammatory cells, along with the resident lymphoid population. If inflammation is present, neutrophils and macrophages also will be found and the type of inflammation may be classified. Any infectious agent such as fungal hyphae, yeasts, bacteria, and protozoa also may be demonstrated. Aspirates may be cultured directly onto blood agar plates or transported in nutrient broth for culture at a referral laboratory. In chronic dermatopathic nodes, a mixed inflammatory cell infiltrate is expected, and in pruritic skin disorders, eosinophils usually are plentiful in node aspirates. Increased numbers of eosinophils also may be found in dogs that are microfilaremic with heartworm infection. Background debris of hemosiderin and melanin pigment and other fine particles may occur in some chronic inflammatory lymphadenopathies. Metastatic lesions are identified by the presence of foreign neoplastic cells, but this diagnosis may be missed in early metastatic spread or if the aspirate is not sufficiently cellular. A cytological guide to the classification of the more common diffuse canine lymphomas is provided but full characterization of the lymphoma type may require histology and immunocytochemistry. In practice, a simple differential Romanowsky stain such as Diff Quik is suitable for most purposes. Supplementary stains using 1 per cent toluidine blue may increase the detection of mast cells. Aspirates also may be transferred into suitable media for transport to a referral diagnostic laboratory for cytocentrifugation or further tests such as electron microscopy, immunocytochemistry, flow cytometry, and culture. Although definitive diagnosis by histopathology and other tests still may be required, in many routine cases, diagnoses can be achieved expediently in clinical practice by aspiration cytology.     

Using simple models to review the application and implications of different approaches used to simulate transmission of pathogens among aquatic animals

Disease is an important issue affecting aquatic animal populations. Aquatic pathogens may be transmitted in ways that could result in qualitatively different impacts to those of terrestrial diseases. I analyse simple SIR epidemic models with different functions to describe transmission. Four forms of transmission are applied: density-dependent, density-independent, non-linear density-dependent and constant infection pressure; the first two are similar to terrestrial systems, the second two are based on specifically aquatic modes of transmission. Observed diseases and existing models are reviewed in terms of these simple forms. The significance of mode of transmission to host populations, to strategies to prevent or control diseases, and to wild-farm interactions are analysed. Different diseases are simulated by different transmission models, for example furunculosis depends on host density, while spread of phocine distemper virus is density-independent, and sea lice infestation pressure may result from open transmission processes that are not dependent on local infested hosts. Appropriate transmission model may also depend on the scale of interest (inter- or intra-population). These different models result in very different responses to intervention strategies, for example culling may be effective for controlling density-dependent disease but may be counter-productive when pathogens depend on open recruitment. It is therefore important for management that appropriate models (whether existing or novel) be selected and this paper aims to provide a basic framework for cataloguing and management of aquatic diseases.     

Common rodent procedures.

Rodents are commonly owned exotic animal pets that may be seen by veterinary practitioners. Although most owners presenting their animals do care about their pets, they may not be aware of the diagnostic possibilities and challenges that can be offered by rodents to the veterinarian. Understanding clinical anatomy, proper hand-ling technique, realistic management of emergency presentations,correct and feasible diagnostic sampling, anesthesia, and humane euthanasia procedures is important to enhancing the doctor-client-patient relationship, especially when financial constraints may be imposed by the owner.     

Equine recurrent airway obstruction and insect bite hypersensitivity: understanding the diseases and uncovering possible new therapeutic approaches

Recurrent airway obstruction (RAO) and insect bite hypersensitivity (IBH) are allergic conditions that are commonly encountered in the horse. Whilst complete allergen avoidance is an effective management strategy for both diseases, this may not be achievable in all cases and treatment options are therefore required. The inflammatory response is the main therapeutic target for glucocorticoids given to horses with RAO and severe cases of IBH, whilst the bronchodilators used in RAO primarily target airway smooth muscle. Such drugs are effective in most but not all individuals and there may be unwanted adverse effects. This article will review how knowledge of drug action and the pathogenesis of RAO and IBH can be utilised to identify potential targets for novel therapeutic agents that, in the longer term, may be safer and/or more effective in managing the allergic horse.     

Diagnostic techniques in the investigation of shoulder lameness

Methods of investigating horses with suspected shoulder lameness are described and discussed. The gait of shoulder lameness is characterised and compared with that of lower forelimb lameness. If lameness is slight, differentiation may be difficult, but if moderate, upper forelimb lameness usually results in shortening of the cranial phase of the stride and a low limb flight. Clinically, it may not be possible to differentiate between shoulder and elbow lameness without intra-articular anaesthesia. Practical aspects of intra-articular anaesthesia of the shoulder joint are reviewed. Synovial fluid must be retrieved to ensure that the needle is intra-articular. Up to 60 mins may elapse after injection of local anaesthetic before significant improvement occurs. Lameness is often improved rather than eliminated. A technique for standing radiography of the shoulder is described and the limitations of assessing a joint only by lateral projections are highlighted. There may be difficulties in positioning weanling foals and yearlings, resulting in superimposition of the shoulder joint, cervical and thoracic vertebra and ribs. It is concluded that a combination of a thorough clinical examination, faradism, local anaesthesia, synovial fluid analysis and radiography usually enables an accurate diagnosis to be reached.     

Fungal diseases of amphibians: an overview.

Clinicians should be familiar with the most common fungal diseases of amphibians. Because lesions in mycotic diseases are nonspecific, a diagnosis cannot be established solely on the basis of clinical presentation. Bacterial, mycobacterial, chlamydial, and parasitic infections, and toxic or environmental conditions may mimic mycotic disease to various extents. Furthermore, mycoses may be masked by overwhelming secondary bacterial infection and therefore remain undiagnosed. Skin scrapings, impression smears, biopsies, and fungal culture are all useful tools in confirming or dismissing a diagnosis of mycosis. Whenever possible, an effort should be made to forward samples and biopsies for culture to appropriate laboratories. Providing the laboratory with a tentative etiologic diagnosis may allow for specific selection of more specific agars and culture conditions and maximize the chances of recovering the fungus from lesions. Identification to species level should also be encouraged, if progress is to be made in the understanding of mycoses in amphibians. The morphology of an isolate should be consistent with the microscopic features of the fungus in histological sections of affected tissues, if it is to be firmly incriminated as the cause of disease. A complete necropsy should be conducted on animals that die or are found dead, and, ideally, isolates from confirmed cases of fungal infection should be deposited in scientific collections, so that they are available for later studies. In addendum, readers should be aware that there is recent evidence to suggest that at least some published cases of amphibian basidiobolomycosis were in fact cases of chytridiomycosis [38], and therefore the validity of basidiobolomycosis as a disease entity in amphibians may be revisited in the years to come.     

The molecular basis for bidirectional communication between the immune and neuroendocrine systems

IL-2 has analgesic effects in both central and peripheral nervous systems. There are two distinct domains in IL-2 molecule mediating immunologic and analgesic activity, respectively. The analgesic domain of IL-2 may be composed of the 44th Phe, 45th Tyr, 107th Tyr, and 117th Phe residues that are located closely in the tertiary structure of IL-2. The analgesic activity may be mediated through the analgesic domain interaction with opioid receptor.In addition to peptides, cytokines may directly bind to peptide receptors, other than their specific cytokine receptors themselves. Conversely, peptides may also interact with cytokine receptors. Thus, peptide neurotransmitters and hormones may serve as endogenous regulators of the immune system, and cytokines may also serve as neurotransmitters. Multiple actions might be mediated by interactions between distinct domains of bioactive molecules with different receptors.     

Imaging suppurative infections of the central nervous system in horses

Suppurative infections are typically caused by pyogenic bacteria, and are characterised by the formation of purulent exudates (pus). These infections may occur anywhere in the body and are particularly life‐threatening when pertaining to the central nervous system (CNS). Suppurative infections of the CNS may be due to trauma, local extension of disease, and haematogenous spread. In horses, suppurative infections are an important cause of morbidity and mortality, but only infrequently involve the CNS. The gross morphology of suppurative inflammation is described as phlegmon, abscess and empyema, with each form having characteristic morphological features that may be identified during advanced imaging of the CNS. In horses with known or suspected suppurative infection of the CNS, imaging may be performed to reduce diagnostic uncertainty, determine prognosis, or to describe the character and extent of the disease to guide case management.     

Behavioral problems of geriatric dogs and cats

Dogs and cats that have been perfectly acceptable pets for many years may develop behavioral problems with old age. Most often these problems develop in animals that have never been very well behaved but have been tolerated by the owners until the problem has somehow exacerbated secondary to some other geriatric problem. The behavioral problems of old dogs most likely to be encountered by the practitioner are those of deaf dogs, dogs that house-soil because of renal, cardiovascular or gastrointestinal problems, and dogs that are aggressive because of a change in the number of animals or humans in the household or that are aggressive secondary to a chronic painful condition such as arthritis. Common feline problems may concern changes in the cat's environment. The treatment of behavioral problems of old animals is similar to the treatment of the problems of young animals, except that the physical limitations and disabilities of the old, usually ill, animal must be considered. Owners should be advised of the behavioral problems that may occur secondary to degenerative diseases and also be persuaded to keep social and environmental changes to a minimum in an old animal's life.     

Reproductive management of captive parrots.

Studies of the behavior of Amazon parrots throughout a reproductive trial indicate that activities such as food gathering, which may occupy large fractions of the activity budget of wild parrots, occupy little time in captivity. This may be one factor contributing to the large percentage of time during which Amazon parrots are generally inactive in typical captive conditions. The extent of inactivity in captive Amazons creates an open time niche wherein enrichment devices might play a role in improving their well being. Studies of the reproductive endocrinology and the behavior of parrots suggest that hand rearing may impair adult fertility and nest box use. Hand rearing may also cause adult Cockatiels to lay eggs on cage floors rather than in nest boxes. However, the use of nest boxes with oversized nest entrances can be very effective in alleviating chronic floor laying in Cockatiels. Another egg-laying problem in Cockatiels, unwanted egg laying, can be prevented by the use of long-acting formulations of the superactive GnRH agonist, leuprolide acetate, which presumably [figure: see text] acts in birds, as in mammals, by down-regulating pituitary GnRH receptors. Manipulations to limit the increases in prolactin normally seen during incubation in poultry can significantly increase egg production. As clutch size in Cockatiels may also be limited by rising prolactin levels, such manipulations may be effective in stimulating egg production in parrots. An alternative approach for increasing flock egg production is to place foster eggs in nests of Cockatiel pairs that are slow to lay. This technique stimulates males to increase their nest-oriented behavior and, subsequently, may stimulate egg laying in some females that might not otherwise have laid eggs. The parental phases of reproduction in Amazon parrots are often a time of heightened aggressiveness towards humans, but low levels of serum testosterone in males during that time suggest that this particular interspecies aggressiveness may not be dependent on elevated testosterone levels. Occasional human handling during the nestling stage may produce a degree of tameness comparable with hand-reared chicks, yet not impair adult reproductive performance. Such handling may also alter the immune status of captive parrots, and possibly reduce the serum corticosterone response to handling. If so, occasional human handling during the nestling stage could improve the adaptation of parrots to captivity.     

Learning strategies and the social brain: Missing elements in the link between developmental stress,song and cognition?

Bird songs may advertise aspects of cognition because song learning and learning speed in cognitive tasks are both affected by early‐life environments. However, such relationships remain ambiguous in the literature. Here, I discuss 2 lines of research that may help to demystify links between song learning and cognition. First, learning strategies should be considered when assessing performance to ensure that individual differences in learning ability are not masked by individual differences in learning strategies. Second, song characteristics should be associated with social behavior because songs have a social purpose and, consequently, should be strongly related at functional and neural levels. Finally, if song learning and cognitive abilities are correlated because they develop concurrently and/or share or compete for the same resources, I discuss ways glucocorticoids may link early‐life stress, song learning and cognitive ability, focusing particularly on oxidative stress as a potential mechanism.     

Metabolism of endogenous and exogenous anabolic agents in cattle

The endogenous anabolic agents, estradiol-17 beta, progesterone and testosterone are steroids that are quickly metabolized by the liver and are not very active when administered orally. Estradiol-17 beta is excreted by the bovine in bile as free estradiol-17 alpha, and by swine, in urine, as glucuronides and sulfates. In ruminants, the primary metabolite of progesterone is pregnandiol and that of testosterone is epitestosterone. In horses, the metabolites of these compounds are primarily 17 ketosteroids. Esters of the endogenous anabolic agents are rapidly hydrolyzed and the nonesterified forms follow the same biotransformation pathways as the natural compounds biosynthesized by the animal. The exogenous anabolic agents, such as trenbolone acetate, zeranol and diethylstilbestrol, may be active by the oral route and are less readily metabolized in the liver than the endogenous anabolics. Their metabolic pathways may be complex and lead to excreted forms after glucuronide conjugation. With respect to biochemical mechanism of action, it can be assumed that the anabolics act like all steroids by way of intracellular receptors. Biotransformations could lead to more reactive molecules that may bind themselves to normal constituents of the organism. Bound metabolites are generally formed later than free metabolites, and are considered less toxic with a lower level of bioavailability.     

Lungworm infection in three loggerhead sea turtles, Caretta caretta

Although lungworms are known to infect many mammalian species and a few are known to infect snakes, lizards, and birds, previously none were known to infect chelonians. This study documents the first three known cases of lungworms in loggerhead sea turtles, Caretta caretta. It is unlikely that the lungworms were the primary cause of illness in any of the cases, and they may be only contributory or even incidental. Changes observed in the two cases that died included tracheal and bronchial epithelial hyperplasia and goblet cell hyperplasia. Lesions caused directly by the parasites seem to be restricted to the upper respiratory tree (trachea and main bronchi), but changes in the lungs themselves may be caused by the debris produced by the worms. Although neither case was successfully treated for the lungworms prior to death, it would appear that oxfendazole may be an effective treatment and has been used in the third case that is still undergoing rehabilitation.     

Definition of apparent, true, and standardized ileal digestibility of amino acids in pigs

Measures of ileal digestibility (ID) are used routinely as estimates of amino acid (AA) bio-availability in pig feed ingredients. Values for ID may be expressed as apparent (AID), standardized (SID), or true (TID). Values for AID are calculated by deducting the total ileal outflow of AA (the sum of endogenous losses (IAA_end) and non-digested dietary AA) from dietary AA intake. The IAA_end may be separated into basal losses, which are not influenced by feed ingredient composition, and specific losses induced by feed ingredient characteristics such as anti-nutritional factors and dietary fiber. If the AID values are corrected for total IAA_end, then values for TID are calculated. Lack of additivity of AID values in feed formulation may be overcome by correcting AID values for basal IAA_end only, which yields SID values. Until reliable procedures for the routine measurement of specific IAA_end become available, it is suggested that SID values are used for feed formulation. It is advisable that basal IAA_end are measured in digestibility experiments and that these losses are reported with SID values.     

Use of local and axial pattern flaps for reconstruction of the hard and soft palate

There are numerous conditions that may result in defects of the hard and soft palate. Reconstruction of these defects may be difficult due to anatomical limitations and limited tissue availability. The majority of palate defects, even when large, may be closed using local and/or axial pattern flaps, while other more advanced techniques such as free tissue transfer and prosthetic implants are required in a smaller number of cases. This article describes the use of local and axial pattern flaps in the reconstruction of the hard and soft palate.     

Inbreeding and genetic diversity in dogs: results from DNA analysis

This review assesses evidence from DNA analysis to determine whether there is sufficient genetic diversity within breeds to ensure that populations are sustainable in the absence of cross breeding and to determine whether genetic diversity is declining. On average, dog breeds currently retain approximately 87% of the available domestic canine genetic diversity. Requirements that breeding stock must be 'clear' for all genetic disorders may firstly place undue genetic pressure on animals tested as being 'clear' of known genetic disorders, secondly may contribute to loss of diversity and thirdly may result in the dissemination of new recessive disorders for which no genetic tests are available. Global exchange of genetic material may hasten the loss of alleles and this practice should be discussed in relation to the current effective population size of a breed and its expected future popularity. Genomic data do not always support the results from pedigree analysis and possible reasons for this are discussed.     

The importance of safety signals in animal handling and training

This review considers the importance of safety for various species of domestic animals and explains how the need for safety may motivate them to offer a variety of unwelcome responses. We argue that the value of safety to animals is often overlooked by trainers and handlers. As a result, animal owners, handlers, trainers, and veterinarians are regularly injured, and training may fail. Reinforced responses that increase the animal's perceived sense of safety but simultaneously endanger the safety of handlers or trainers may lead to the inadvertent training of dangerous responses. This review offers suggestions about how safety can be used effectively and humanely as a resource in operant training. Training calmness in the presence of a specific stimulus that is associated with safety may deserve closer attention. The ethics of creating the need for safety in domestic animals as part of a training regime are discussed. It emerges that the highly prized attribute of so-called trust in animal–trainer dyads may, at least sometimes, be a manifestation of trainers acting as safety signals. Similarly, animals said to have confidence in and regard for their handlers may value the relative safety they afford.