A philosophy and approach to teaching the epidemiology of food-borne, waterborne, and zoonotic diseases

Faculty members from veterinary colleges that teach courses on food-borne, waterborne, and zoonotic diseases to non-veterinary students face unique challenges. The diversity of students' backgrounds, skills, and goals and the public nature of the science require some ingenuity in combining good science with the ability to communicate clearly in a variety of public forums. Drawing on pedagogical theory, the nature of the material, and the diverse abilities of the students, we have put together an effective teaching package for non-veterinary courses on these subjects, which includes a range of methods from outbreak investigations to town hall meetings and food diaries.     

Subacute atropine toxicity in a pygmy sperm whale, Kogia breviceps.

Atropine, an anticholinergic agent commonly used in human and veterinary medicine, is reported to cause toxicity associated with its antimuscarinic action. A juvenile pygmy sperm whale, Kogia breviceps, was treated with atropine in an attempt to relieve symptoms similar to pyloric stenosis, as has been used in humans. Two doses of 0.01 mg/kg were given i.m., 12 hr apart, followed by three doses of 0.005 mg/kg i.m. s.i.d. over the next 3 days. Symptoms associated with atropine toxicity developed gradually and included hyperexcitability, a generalized ascending paralysis of body musculature, shallow, rapid respiration, vomiting, aspiration of seawater, and pulmonary edema. Treatment with physostigmine salicylate (two doses of 2 mg i.m., I hr apart) was effective in counteracting the paralysis, as well as other symptoms, beginning in as little as 17 min after the first dose, and the whale was back to swimming on its own after 8 hr. All overt symptoms of atropine toxicity were gone in about 24 hr, but there were other possible sequella that lasted much longer.     

Effects of atracurium on intraocular pressure, eye position, and blood pressure in eucapnic and hypocapnic isoflurane-anesthetized dogs

OBJECTIVE: To determine effects of atracurium on intraocular pressure (IOP), eye position, and arterial blood pressure in eucapnic and hypocapnic dogs anesthetized with isoflurane. ANIMALS: 16 dogs. PROCEDURE: Ventilation during anesthesia was controlled to maintain Paco2 at 38 to 44 mm Hg in group- I dogs (n = 8) and 26 to 32 mm Hg in group-II dogs (8). Baseline measurements for IOP, systolic, diastolic, and mean arterial blood pressure, central venous pressure (CVP), and heart rate (HR) were recorded. Responses to peroneal nerve stimulation were monitored by use of a force-displacement transducer. Atracurium (0.2 mg/kg) was administered i.v. and measurements were repeated at 1, 2, 3, and 5 minutes and at 5-minute intervals thereafter for 60 minutes. RESULTS: Atracurium did not affect IOP, HR, or CVP Group II had higher CVP than group I, but IOP was not different. There was no immediate effect of atracurium on arterial blood pressure. Arterial blood pressure increased gradually over time in both groups. Thirty seconds after administration of atracurium, the eye rotated from a ventromedial position to a central position and remained centrally positioned until 100% recovery of a train-of-four twitch response. The time to 100% recovery was 53.1 +/- 5.3 minutes for group I and 46.3 +/- 9.2 minutes for group II. CONCLUSIONS AND CLINICAL RELEVANCE: Atracurium did not affect IOP or arterial blood pressure in isoflurane-anesthetized dogs. Hyperventilation did not affect IOP or the duration of effect of atracurium.     

Outcome of surgical correction of meconium impactions in 8 foals

Meconium impactions are only rarely refractory to medical therapy. The purpose of this paper is to examine the outcome of 8 foals that required an exploratory celiotomy to correct a meconium impaction. Between 1984 and 1992, 24 foals were referred with a primary diagnosis of meconium impaction. All foals were treated medically prior to and following referral. Of the 24 foals, 8 had impactions requiring surgical intervention. Exploratory celiotomies were performed, and the impaction was reduced manually or by enterotomy. Follow up information was available on 7 foals. All survived surgery and were discharged. Four of the 8 foals matured and raced. Two foals were euthanatized due to extensive serosal adhesions and one foal was euthanatized due to an unrelated orthopedic condition. Our results support the decision for an exploratory surgery only after aggressive medical therapy has failed. Several treatment options have been developed in recent years that have reduced the number of foals that may require surgery.     

Infarctive purpura hemorrhagica in five horses

Five horses were examined because of signs of muscle stiffness, colic, or both. All 5 had been exposed to Streptococcus equi within 3 weeks prior to examination or had high serum titers of antibodies against the M protein of S equi. Horses had signs of unrelenting colic-like pain and focal areas of muscle swelling. Four horses were euthanatized. The fifth responded to treatment with penicillin and dexamethasone; after 3 weeks of treatment with dexamethasone, prednisolone was administered for an additional 10 weeks. Common hematologic and serum biochemical abnormalities included neutrophilia with a left shift and toxic changes, hyperproteinemia, hypoalbuminemia, and high serum creatine kinase and aspartate transferase activities. Necropsy revealed extensive infarction of the skeletal musculature, skin, gastrointestinal tract, pancreas, and lungs. Histologic lesions included leukocytoclastic vasculitis in numerous tissues and acute coagulative necrosis resembling infarction. These horses appeared to have a severe form of purpura hemorrhagica resembling Henoch-Sch?nlein purpura in humans and characterized by infarction of skeletal muscles. Early recognition of focal muscle swelling, abdominal discomfort, neutrophilia, hypoalbuminemia, and high serum creatine kinase activity combined with antimicrobial and corticosteroid treatment may enhance the likelihood of a successful outcome.     

Successful drug development despite adverse preclinical findings part 1: processes to address issues and most important findings

Unexpected adverse preclinical findings (APFs) are not infrequently encountered during drug development. Such APFs can be functional disturbances such as QT prolongation, morphological toxicity or carcinogenicity. The latter is of particular concern in conjunction with equivocal genotoxicity results. The toxicologic pathologist plays an important role in recognizing these effects, in helping to characterize them, to evaluate their risk for man, and in proposing measures to mitigate the risk particularly in early clinical trials. A careful scientific evaluation is crucial while termination of the development of a potentially useful drug must be avoided. This first part of the review discusses processes to address unexpected APFs and provides an overview over typical APFs in particular classes of drugs. If the mode of action (MoA) by which a drug candidate produces an APF is known, this supports evaluation of its relevance for humans. Tailor-made mechanistic studies, when needed, must be planned carefully to test one or several hypotheses regarding the potential MoA and to provide further data for risk evaluation. Safety considerations are based on exposure at no-observed-adverse-effect levels (NOAEL) of the most sensitive and relevant animal species and guide dose escalation in clinical trials. The availability of early markers of toxicity for monitoring of humans adds further safety to clinical studies. Risk evaluation is concluded by a weight of evidence analysis (WoE) with an array of parameters including drug use, medical need and alternatives on the market. In the second part of this review relevant examples of APFs will be discussed in more detail.     

Physiologic VDD versus nonphysiologic VVI pacing in canine 3rd-degree atrioventricular block

Historically, ventricular demand, nonphysiologic (VVI) pacing has been the most commonly used modality to treat 3rd-degree atrioventricular (AV) block. The goal of this study was to determine the feasibility of using a commercial, single-lead, physiologic (VDD) pacemaker in dogs with 3rd-degree AV block. Furthermore, we hoped to characterize and identify differences in the radiographic, echocardiographic, neurohormonal, and quality of life consequences of physiologic versus nonphysiologic pacing. We evaluated 10 dogs during a 12-week crossover study. Acutely, rate-matched physiologic pacing reduced pulmonary capillary wedge pressure by 19% compared with nonphysiologic pacing. VDD pacing significantly reduced left atrial size normalized to body weight, left atrial-to-aortic root ratio, and left ventricular end-systolic dimension and increased fractional shortening, aortic Doppler velocity, cardiac output, and stroke volume compared with VVI pacing. Variable rate VDD pacing resulted in a significantly slower heart rate (HR) during echocardiography than fixed-rate (100 bpm) VVI pacing. AV synchronous pacing reduced circulating N-terminal proatrial natriuretic peptide (ANP), norepinephrine (NOR), and epinephrine (EPI) concentrations compared with asynchronous pacing. There were no significant differences in systemic blood pressure, thoracic radiographs, or owner-perceived quality of life. The median percentage of AV synchronous pacing during the VDD modality was 99.8% (range, 1.2 to 99.9%). This study confirms the potential to achieve physiologic pacing with a commercial, single-lead system in dogs. VDD pacing improved hemodynamics and neurohormonal profiles over asynchronous pacing although the long-term clinical benefits of these changes remain to be determined.     

Spike glycoprotein cleavage recognition site analysis of infectious bronchitis virus.

The spike glycoprotein of infectious bronchitis virus (IBV), a coronavirus, is translated as a precursor protein (So), then cleaved into two subunits (S1 and S2) by host cell serine proteases. In this study, we compared the cleavage recognition site of 55 IBV isolates to determine if the cleavage recognition site sequence, which consists of five basic amino acid residues, correlates with host cell range, serotype, geographic origin, and pathogenicity as it does in orthomyxoviruses and paramyxoviruses. The most common cleavage recognition site observed (33 of 55 viruses) was Arg-Arg-Ser-Arg-Arg, representing at least 11 different serotypes. Thus, cleavage recognition site does not appear to correlate with serotype. We also determined that cleavage recognition site sequence does not correlate with pathogenicity because attenuated and pathogenic isolates (different passages of the same virus) contain identical cleavage recognition site sequences. In addition, nephropathogenic strains had the same cleavage recognition site sequence as many nonnephropathogenic isolates. Cleavage recognition site sequence does correlate with viruses in different geographic regions, which may be an important characteristic to examine in epidemiologic studies. An IBV monoclonal antibody neutralization-resistant mutant (NR 18) had an unusual substitution of Ile for Arg at the fourth position, giving the sequence Arg-Arg-Ser-Ile-Arg, which likely prevents cleavage and, thus, destroys the conformationally dependent monoclonal antibody binding epitope. Six residues on the amino-terminal side of the cleavage recognition site are conserved in 31% of the isolates and consist of only one or two basic amino acids. Thus, the number of basic residues around the cleavage recognition site does not appear to correlate with increased cleavability, host cell range, and increased virulence as it does with envelope glycoproteins in orthomyxoviruses and paramyxoviruses.