Biology of PrPsc accumulation in two natural scrapie-infected sheep flocks.

Sheep scrapie is a prion disease that requires interaction of exogenous prions with host prion protein (PrP) supporting prion formation. Disease is associated with deposition of a host-generated conformational variant of PrP, PrPsc, in a variety of tissues, including brain, resulting in fatal spongiform encephalopathy. Efficiency of PrPsc formation is determined by polymorphisms in the PrP-coding sequence. This article adds to previous data of natural sheep scrapie, concentrating on the effect of host genotype and age on PrPsc accumulation patterns during preclinical and clinical disease. Two entire scrapie-infected, predominantly Suffolk-cross, sheep flocks euthanized for regulatory purposes were genotyped and analyzed for PrPsc deposition in various tissues using single- and dual-label immunohistochemistry. Scrapie, as defined by PrPsc deposition, occurred in 13/80 sheep. Preclinical disease was evident in nearly 70% of infected sheep, ranging in age from 14 months to 7 years. PrPsc accumulated systemically in the nervous tissue, various lymphoid tissues, both alimentary tract related and non-alimentary tract related, and the placenta. Clinical neurological illness was always associated with spongiform encephalopathy and PrPsc deposition in the brain. Only 6 of 9 sheep with preclinical scrapie had PrPsc deposition in the brain but widespread PrPsc deposition in peripheral lymphoid tissue, supporting previous data showing peripheral PrPsc accumulation preceding deposition in the brain. PrPsc colocalized with a marker for follicular dendritic cells throughout the lymphoid system. PrPsc also accumulated in the peripheral nervous system, particularly the nervous supply of the gastrointestinal tract. Abundant PrPsc was evident in trophoblast cells of placentomes but not in the endometrium, myometrium, or associated nervous plexus. PrPsc deposits were not observed in the mammary parenchyma or bone marrow. Scrapie susceptibility was defined genetically by PrP codon 171: PrPsc deposition was restricted to PrP genotype AA136RR154QQ171 in 12/13 cases or AV136RR154QQ171 in 1/13 cases. The earliest accumulation was observed in the single VRQ/ARQ heterozygous animal, consistent with the reported high scrapie susceptibility and brief incubation period observed in breeds with predominance of the V136R154Q171 allele. Disease occurred within, as well as independent of, mother-daughter lines, suggesting both maternal and nonmaternal transmission in the flocks.     

Multiple organ dysfunction syndrome in humans and dogs

Objective: To describe the clinical appearance and theories on the pathogenesis of multiple organ dysfunction syndrome (MODS) in humans, and to review the evidence suggesting that a similar syndrome occurs in critically ill dogs. Human‐based studies: Currently, there are a multitude of publications describing the pathogenesis and clinical course of MODS in humans. Providing much of the basis for on‐going research and the development of clinical applications, a consensus statement made by the American College of Chest Physicians and Society of Critical Care Medicine defined parameters that had guided and shaped much of what is known about MODS. Veterinary‐based studies: To date, there are few publications describing MODS in dogs and much of what is known has been derived from case reports and reviews of various critical illnesses in dogs. While a similar syndrome of multiple organ dysfunction likely exists in dogs, a consensus statement defining clinical parameters has not been made. Data sources: Veterinary and human literature review. Conclusions: The development of MODS in human critical illness is widely recognized and major strides have been made in the understanding of this complex syndrome. Scoring schemes applied to human MODS patients have established that with increasing numbers of failing organs, there is a worse prognosis. As a similar finding likely exists in dogs, an awareness of MODS is vital to veterinary critical care clinicians and a consensus definition of MODS in dogs is warranted.     

Influence of fire regimes on lodgepole pine stand age and density across the Yellowstone National Park (USA) landscape

A probabilistic spatial model was created based on empirical data to examine the influence of different fire regimes on stand structure of lodgepole pine (Pinus contorta var. latifolia) forests across a >500,000-ha landscape in Yellowstone National Park, Wyoming, USA. We asked how variation in the frequency of large fire events affects (1) the mean and annual variability of age and tree density (defined by postfire sapling density and subsequent stand density) of lodgepole pine stands and (2) the spatial pattern of stand age and density across the landscape. The model incorporates spatial and temporal variation in fire and serotiny in predicting postfire sapling densities of lodgepole pine. Empirical self-thinning and in-filling curves alter initital postfire sapling densities over decades to centuries. In response to a six-fold increase in the probability of large fires (0.003 to 0.018 year⁻¹), mean stand age declined from 291 to 121 years. Mean stand density did not increase appreciably at high elevations (1,029 to 1,249 stems ha⁻¹) where serotiny was low and postfire sapling density was relatively low (1,252 to 2,203 stems ha⁻¹). At low elevations, where prefire serotiny and postfire lodgepole pine density are high, mean stand densities increased from 2,807 to 7,664 stems ha⁻¹. Spatially, the patterns of stand age became more simplified across the landscape, yet patterns of stand density became more complex. In response to more frequent stand replacing fires, very high annual variability in postfire sapling density is expected, with higher means and greater variation in stand density across lodgepole pine landscapes, especially in the few decades following large fires.     

Nd:YAG laser-assisted modified Forssell's procedure for treatment of cribbing (crib-biting) in horses

OBJECTIVE: To report an neodymium:yttrium-aluminum garnet (Nd:YAG) laser-assisted modified Forssell's surgical technique and outcome for treatment of cribbing (crib-biting) in horses. STUDY DESIGN: Retrospective clinical study. ANIMALS: Ten adult horses with stereotypic cribbing behavior. METHODS: Data were obtained from medical records and telephone conversations with owners, trainers, and veterinarians. Surgical technique involved an approximately 34-cm ventral median skin incision starting rostral to the larynx and extending caudally. A 10-cm section of the ventral branch of the spinal accessory nerve was removed, using an Nd:YAG laser at 25 W and continuous pulse with a contact, sculpted-fiber tip. After neurectomy, approximately 34-cm sections of the paired omohyoideus and sternothyrohyoideus muscles were removed starting 2 cm rostral to the ventral aspect of the larynx, at the basihyoid bone, using the Nd:YAG laser. RESULTS: Median horse age was 7 years (range, 1 to 11 years). Median surgical time was 90 minutes (range, 75 to 130 minutes). Long-term outcome (range, 7 to 72 months) was available for all horses. None of the horses had cribbing behavior after surgery, and all returned to their previous use. Four horses had complications (two of which were unrelated to the surgical site), but all recovered fully. CONCLUSION: The successful outcome we obtained is better than reported previously using a modified Forssell's technique. CLINICAL RELEVANCE: Surgical treatment for cribbing by Nd: YAG laser-assisted myectomy and neurectomy resulted in an excellent prognosis for resolution of the stereotypical behavior with minimal complications.     

Comparison of effects of dexamethasone and the leukotriene D4 receptor antagonist L-708,738 on lung function and airway cytologic findings in horses with recurrent airway obstruction

OBJECTIVE: To evaluate whether the leukotriene (LT) D4 receptor antagonist L-708,738 is therapeutically beneficial in treating horses with recurrent airway obstruction (heaves). ANIMALS: 12 adult horses with heaves and healthy lung lobes from 20 slaughtered horses. PROCEDURE: Lung lobes were used for smooth muscle tension and radioligand binding studies. Horses with heaves were given a placebo for 14 days and administered L-708,738 (n = 6; 2.5 mg/kg PO, q 12 h) or dexamethasone (6; 0.04 mg/kg, IV, q 24 h) from days 14 to 28. Pulmonary function was measured weekly for 36 days, and bronchoalveolar cells were collected on days 0,14, and 29 for cytologic examination. RESULTS: Nanomolar concentrations of L-708,738 were effective at antagonizing LTD4-induced bronchoconstriction and LTD4-receptor binding in lung lobes. Mean peak and trough L708,738 plasma concentrations during the treatment period were 1.54 and 0.28 microM, respectively. On days 21 and 29, lung mechanics were significantly improved in the dexamethasone-treated horses but not in the L-708,738-treated horses. Neither dexamethasone nor L-708,738 had a significant effect on cytologic findings. CONCLUSIONS AND CLINICAL RELEVANCE: L-708,738 was bioavailable after oral administration and sustained concentrations in plasma during the dosing period that exceeded in vitro efficacy values. However, airway function did not improve, suggesting that either drug concentrations in the lungs were subtherapeutic or that cysteinyl LT may not be important mediators of airway inflammation in heaves. Results provide the first evidence of cysteinyl LT1 receptors in airways of horses.     

Regional and zonal variations in the sulfation patterns of chondroitin sulfate in normal equine corneal stroma

OBJECTIVE: To determine regional and zonal variation in sulfation patterns of chondroitin sulfate in normal equine corneal stroma. SAMPLE POPULATION: 22 normal eyes from 11 horses. PROCEDURE: Corneas were collected within 24 hours of death from equine necropsy specimens. After papain-chondroitinase digestion of corneal tissue, disaccharides deltaDi4S and deltaDi6S were quantified by use of capillary zone electrophoresis in the superficial, middle, and deep zones of central and peripheral regions of the cornea. RESULTS: For the 2 regions combined, deltaDi6S/deltaDi4S values were significantly lower in the deep and middle zones, compared with that of the superficial zone. In the central region, deep and middle zones had significantly lower deltaDi6S/deltaDi4S values than the superficial zone did. In the peripheral region, the deep zone had significantly lower deltaDi6S/deltaDi4S values, compared with superficial and middle zones. In the deep zone, the peripheral region had significantly lower deltaDi6S/deltaDi4S values than the central region did. CONCLUSIONS AND CLINICAL RELEVANCE: Distribution of deltaDi6S/deltaDi4S values follows a gradient across the healthy equine cornea, being smallest in the deep and middle zones of the central region and the deep zone of the peripheral region. Regional and zonal differences in the distribution of stromal deltaDi6S and deltaDi4S may influence the role of glycosaminoglycans in health, disease, and wound repair of the equine cornea.     

Open versus closed bilateral anal sacculectomy for treatment of non-neoplastic anal sac disease in dogs: 95 cases (1969-1994)

OBJECTIVE: To determine complications associated with anal sacculectomy in dogs with non-neoplastic anal sac disease and compare complication rates for open versus closed techniques. DESIGN: Retrospective study. ANIMALS: 95 dogs. PROCEDURE: Medical records were reviewed for information on signalment, history, physical examination findings, type of anal sac disease, surgical technique (closed, standard open [surgery performed prior to 19801, or modified open [surgery performed after 19801), and postoperative complications. RESULTS: In 57 dogs, a closed technique was used, and in 38, an open technique was used. Only 3 dogs developed short-term complications (excessive drainage, scooting and inflammation, and seroma formation), and 14 developed long-term complications (continued licking of the surgery site, fecal incontinence, fistulation, and stricture formation). Development of postoperative complications was significantly associated with surgical technique. Dogs that underwent standard open sacculectomy prior to 1980 were 13.67 times as likely to have a long-term complication as were dogs that underwent closed sacculectomy. Weight of the dog, type of anal sac disease, age at the time of surgery, and whether the wound was closed surgically were not significantly associated with whether dogs developed postoperative complications. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that anal sacculectomy is a safe and effective treatment for non-neoplastic anal sac disease in dogs and is associated with a low rate of complications. The standard open technique was associated with the greatest number of complications, whereas complication rates for the closed and modified open techniques were similar to each other.     

Tremorgenic mycotoxicosis in four dogs from a single household

Mycotoxins are fungal metabolites that induce undesirable effects. The effects of these mycotoxins vary depending on the chemical structure of the toxin and degree of toxicity. Mycotoxins that induce muscle tremors, ataxia, and convulsions are termed tremorgenic mycotoxins. Our report documents the clinical course of 4 dogs from a single household that were simultaneously affected by tremorgenic mycotoxins. Diagnosis of tremorgenic mycotoxicosis was confirmed by stomach content analysis from 1 of the dogs. The mycotoxins identified were penitrem A and roquefortine, which are both produced by Penicillium spp. Treatment goals following tremorgenic mycotoxin ingestion include minimizing absorption, controlling tremors and seizures with methocarbamol and pentobarbital sodium administration, and providing supportive care. Two of the affected dogs required ventilatory support. With early aggressive treatment, prognosis is good and recovery is complete without sequelae. It is helpful for the clinician to be familiar with the typical clinical signs at the time of admission, treatment, and clinical course of dogs with tremorgenic mycotoxicosis.