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In drug development, assessing the toxicity of candidate compounds is crucial for successfully transitioning from preclinical research to early-stage clinical trials. Drug safety is typically assessed using animal models with a manual histopathological examination of tissue sections to characterize the dose-response relationship of the compound - a time-intensive process prone to inter-observer variability and predominantly involving tedious review of cases without abnormalities. Artificial intelligence (AI) methods in pathology hold promise to accelerate this assessment and enhance reproducibility and objectivity. Here, we introduce TRACE, a model designed for toxicologic liver histopathology assessment capable of tackling a range of diagnostic tasks across multiple scales, including situations where labeled data is limited. TRACE was trained on 15 million histopathology images extracted from 46,734 digitized tissue sections from 157 preclinical studies conducted on Rattus norvegicus. We show that TRACE can perform various downstream toxicology tasks spanning histopathological response assessment, lesion severity scoring, morphological retrieval, and automatic dose-response characterization. In an independent reader study, TRACE was evaluated alongside ten board-certified veterinary pathologists and achieved higher concordance with the consensus opinion than the average of the pathologists. Our study represents a substantial leap over existing computational models in toxicology by offering the first framework for accelerating and automating toxicological pathology assessment, promoting significant progress with faster, more consistent, and reliable diagnostic processes.
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Domestic rabbits (Oryctolagus cuniculus) are commonly kept as pets or bred for laboratory investigation, meat, fur production, or a combination of these purposes. We conducted a retrospective study to assess the prevalence of diseases in domestic rabbits according to purpose. We retrieved results of autopsies, biopsies, and cytologies from 2,583 cases received at 4 diagnostic laboratories in California from 2013-2022. Rabbits were classified as pets (2,241; 86.8%), laboratory animals (92; 3.6%), meat-production animals (60; 2.3%), or multipurpose animals (190; 7.4%). A final diagnosis was reached in 2,360 (91.4%) cases and was classified by system, etiology, and type of process. Pet rabbits had the highest median age (5.9 y; vs. 3 y, 0.67 y, and 0.25 y in meat, multipurpose, and laboratory rabbits, respectively), and most of the neoplasms were diagnosed in this group (872 of the total 896 neoplasms in the study; 97.3%), with tumors of the skin, female reproductive tract, and hematolymphoid system being the most common. Laboratory rabbits had a high prevalence of infectious enterotyphlocolitis (40 of 92; 43.4%), and ~45% of those cases were due to opportunistic colibacillosis. Infectious and parasitic pneumonias were common in meat rabbits (18 of 60; 30%); pneumonic pasteurellosis accounted for >60% of those cases. Infectious cholangiohepatitides were common in multipurpose rabbits (61 of 110; 55.5%), with rabbit hemorrhagic disease representing the most common etiology (82.4% of those cases). Our results demonstrate that purpose of use can predict prevalence of disease in rabbits submitted to diagnostic laboratories.
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Clostridium spiroforme has been associated with spontaneous and antibiotic-associated enteric disease (C. spiroforme-associated enteric disease, CSAED) in rabbits, which is clinically characterized by anorexia, diarrhea, or sudden death. Diagnosis is usually based on gross and microscopic lesions, coupled with finding the characteristic coiled bacteria in intestinal smears. Isolation of C. spiroforme is often challenging, and a PCR protocol has been developed. We reviewed 32 cases of CSAED submitted for autopsy to the Davis, Tulare, and Turlock laboratories of CAHFS between 1992 and 2019. The reported gross findings were soiling of the perineum, tail, and/or hind legs with diarrhea (16 of 32); gastric (16 of 32), small intestinal (6 of 32), cecal (15 of 32), and/or colonic (4 of 32) distention with brown-to-green, watery content; and serosal hemorrhages in the cecum (15 of 32). The most common microscopic finding was necrotizing enteritis (19 of 32), followed by cecal mucosal or submucosal edema (8 of 32), necrotizing or pleocellular typhlitis (6 of 32), necrotizing or heterophilic typhlocolitis (6 of 32), and cecal transmural hemorrhages (5 of 32). In all 32 rabbits, typical helically coiled, gram-positive bacilli were observed in fecal or intestinal smears. C. spiroforme was isolated from the intestinal content of 2 of 24 rabbits and detected by PCR assay in 8 of 8 rabbits.
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Helicosporidium is a genus of nonphotosynthetic, green algae in the family Chlorellaceae, closely related to Prototheca. It is a known pathogen of invertebrates, and its occurrence in vertebrates has not been documented. A captive, 10-month-old, male, albino California kingsnake (Lampropeltis californiae) was submitted for necropsy. Gross examination revealed hemorrhagic laryngitis and a red mottled liver. Histologically, intravascular, intramonocytic/macrophagic and extracellular, eukaryotic organisms were observed in all tissues. These organisms stained positive with Grocott-Gomori methenamine silver and periodic acid-Schiff and were variably acid-fast and gram-positive. Ultrastructural analysis revealed approximately 4 µm vegetative multiplication forms and cysts with 3 parallel ovoid cells and a helically coiled filamentous cell. A polymerase chain reaction with primers targeting Prototheca, amplicon sequencing, and Bayesian phylogenetic analysis confirmed it clustered within Helicosporidium sp. with 100% posterior probability. The genus Helicosporidium was found to nest within the genus Prototheca, forming a clade with Prototheca wickerhamii with 80% posterior probability.
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Neoplasia is one of the main causes of euthanasia in geriatric captive nondomestic felids. However, few studies have examined oral tumors in these animals. We describe here the clinicopathologic features of gingival squamous cell carcinoma (SCC) in 2 lions (Panthera leo) from separate zoologic collections. In both cases, the lions had a history of sialorrhea, bloody oral discharge, and anorexia. Autopsy findings in both lions were similar and were characterized by poorly circumscribed, friable, and bloody gingival masses with grossly apparent invasion of the mandibular bone; a pathologic fracture was observed in 1 case. Histologically, the masses consisted of poorly circumscribed, unencapsulated, densely cellular proliferations of neoplastic epithelial cells arranged in irregular islands, cords, and anastomosing trabeculae with formation of keratin pearls, which, coupled with positive immunohistochemistry for pancytokeratin, were diagnostic for SCC. Although no metastases were found in either animal, both lions were ultimately euthanized because of poor prognosis.
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Carcinoma de Células Escamosas , Neoplasias Gengivais , Leões , Animais , Animais de Zoológico , Carcinoma de Células Escamosas/veterinária , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/diagnóstico , Evolução Fatal , Neoplasias Gengivais/veterinária , Neoplasias Gengivais/patologia , Neoplasias Gengivais/diagnósticoRESUMO
Mannheimia haemolytica-associated abomasitis has been clinically described as a cause of sudden death in lambs, but it is poorly characterized. We describe the pathological features of a severe fibrinonecrotizing abomasitis in 3 lambs that died suddenly. All 3 abomasums had a thickened submucosa due to edema and necrotic areas delimited by bands of degenerate neutrophils with slender nuclei (oat cells) and angiocentric distributions. The overlying mucosa was congested. Myriads of gram-negative coccobacilli were observed within the oat cell bands. M. haemolytica was isolated from the abomasum in all 3 animals and was serotyped as A2 in one of them. Pericarditis and pleuritis were observed in 2 of the lambs. Clostridium spp. were isolated in 1 lamb and detected by immunohistochemistry in the 3 animals, suggesting clostridial co-infection. M. haemolytica should be considered among the differential diagnoses of necrotizing abomasitis in lambs.
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Abomaso , Mannheimia haemolytica , Necrose , Infecções por Pasteurellaceae , Doenças dos Ovinos , Animais , Mannheimia haemolytica/isolamento & purificação , Doenças dos Ovinos/patologia , Doenças dos Ovinos/microbiologia , Ovinos , Abomaso/patologia , Abomaso/microbiologia , Infecções por Pasteurellaceae/veterinária , Infecções por Pasteurellaceae/patologia , Infecções por Pasteurellaceae/microbiologia , Necrose/veterinária , Necrose/patologia , Necrose/microbiologia , Gastropatias/veterinária , Gastropatias/patologia , Gastropatias/microbiologia , Masculino , Feminino , Imuno-Histoquímica/veterináriaRESUMO
Published information about fish botulism is scant. We review here the current literature on fish botulism. Freshwater fish are susceptible to botulism. Only anecdotal evidence exists about possible botulism cases in saltwater fish. With only a few exceptions, the etiology of all cases of fish botulism reported is Clostridium botulinum type E, although fish are sensitive to, and may carry, various C. botulinum types. Clinical signs of botulism in fish include loss of equilibrium and motion, abducted opercula, open mouths, dark pigmentation, and head up/tail down orientation in which attempts to swim result in breaching the surface of the water. Dark pigmentation is thought to be associated with acetylcholine imbalance in botulinum neurotoxin (BoNT)-affected fish. Rarely, but similar to the situation in other animal species, fish can recover from botulism. Fish botulism can cause secondary outbreaks of the disease in birds, as botulism-affected fish stand out from normal fish, and are selectively preyed upon by fish-eating birds, which thus become intoxicated by the BoNT present in sick fish. The source of BoNT in fish has not been definitively confirmed. Fish may ingest C. botulinum spores that then germinate in their digestive tract, but the possibility that fish ingest preformed BoNT from the environment (e.g., dead fish, shellfish, insects) cannot be ruled out. The presumptive diagnosis of botulism in fish is established based on clinical signs, and as in other species, confirmation should be based on detection of BoNT in intestinal content, liver, and/or serum of affected fish.
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Botulismo , Doenças dos Peixes , Peixes , Botulismo/veterinária , Botulismo/diagnóstico , Animais , Doenças dos Peixes/microbiologia , Doenças dos Peixes/diagnóstico , Toxinas Botulínicas , Clostridium botulinum/isolamento & purificaçãoRESUMO
Although bovine respiratory syncytial virus (BRSV) infection has been reported in cattle in Argentina, it has not been associated with pneumonia in Argentina. We report here 5 cases of bovine pneumonia associated with BRSV. Autopsies were performed on 35 beef cattle with gross and/or microscopic lesions of pneumonia from 3 commercial feedlots. Lung samples in 5 of 35 animals were BRSV-positive by reverse-transcription nested PCR. The lungs of 2 of these 5 animals were coinfected with Mannheimia haemolytica, and 1 with bovine viral diarrhea virus 1. Microscopically, the lungs of 3 of the 5 BRSV PCR-positive animals had fibrinosuppurative bronchopneumonia, with or without pleuritis; 2 of the 5 had interstitial pneumonia. We conclude that BRSV is part of the bovine respiratory disease complex in Argentina.
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Complexo Respiratório Bovino , Doenças dos Bovinos , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Bovino , Bovinos , Animais , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/veterinária , Infecções por Vírus Respiratório Sincicial/patologia , Argentina/epidemiologia , Doenças dos Bovinos/patologia , Pulmão/patologiaRESUMO
Enterotoxemia caused by Clostridium perfringens type D usually affects sheep and goats ≥ 2-wk-old. The main clinical signs and lesions of the disease are produced by the epsilon toxin (ETX) elaborated by this microorganism. However, ETX is produced in the form of a mostly inactive prototoxin that requires protease cleavage for activation. It has traditionally been believed that younger animals are not affected by type D enterotoxemia given the low trypsin activity in the intestinal content associated with the trypsin-inhibitory action of colostrum. Two Nigerian dwarf goat kids, 2- and 3-d-old, with a history of acute diarrhea followed by death, were submitted for postmortem examination and diagnostic workup. Autopsy and histopathology revealed mesocolonic edema, necrosuppurative colitis, and protein-rich pulmonary edema. Alpha toxin and ETX were detected in intestinal content, and C. perfringens type D was isolated from the colon of both animals. The isolates encoded the gene for lambda toxin, a protease that has been shown previously to activate ETX in vitro. Type D enterotoxemia has not been reported previously in neonatal kids, to our knowledge, and we suggest that lambda toxin activated the ETX.
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Clostridium perfringens , Doenças dos Ovinos , Ovinos , Animais , Clostridium perfringens/fisiologia , Enterotoxemia/diagnóstico , Enterotoxemia/patologia , Cabras , Tripsina , Peptídeo HidrolasesRESUMO
Accumulative evidence has shown that short non-coding RNAs such as miRNAs can regulate the innate and adaptive immune responses. Aluminium hydroxide is a commonly used adjuvant in human and veterinary vaccines. Despite its extended use, its mechanism of action is not fully understood and very few in vivo studies have been done to enhance understanding at the molecular level. In this work, we took advantage of a previous long-term experiment in which lambs were exposed to three different treatments by parallel subcutaneous inoculations with aluminium-containing commercial vaccines, an equivalent dose of aluminium or mock injections. Spleen samples were used for miRNA-seq. A total of 46 and 16 miRNAs were found differentially expressed when animals inoculated with commercial vaccines or the adjuvant alone were compared with control animals, respectively. Some miRNAs previously related to macrophage polarization were found dysregulated exclusively by the commercial vaccine treatment but not in the aluminium inoculated animals. The dysregulated miRNAs in vaccine group let-7b-5p, miR-29a-3p, miR-27a and miR-101-3p are candidates for further research, since they may play key roles in the immune response induced by aluminium adjuvants added to vaccines. Finally, protein-protein interaction network analysis points towards leucocyte transendothelial migration as a specific mechanism in animals receiving adjuvant only.
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MicroRNAs , Vacinas , Ovinos , Humanos , Animais , MicroRNAs/genética , Baço , Alumínio , Adjuvantes Imunológicos/farmacologia , VacinaçãoRESUMO
Clostridium perfringens type C and Clostridioides difficile are the main enteric clostridial pathogens of swine and are both responsible for neonatal diarrhea in this species. The role of Clostridum perfringes type A is under discussion. History, clinical signs, gross lesions and histological findings are the basis for a presumptive diagnosis of C. perfringens type C or C. difficile infection. Confirmation is based upon detection of beta toxin of C. perfringens type C or toxin A/B of C. difficile, respectively, in intestinal contents or feces. Isolation of C. perfringens type C and/or C. difficile is highly suggestive of infection by these microorganisms but it is not enough to confirm a diagnosis as they may be found in the intestine of some healthy individuals. Diagnosis of C. perfringens type A-associated diarrhea is more challenging because the diagnostic criteria have not been well defined and the specific role of alpha toxin (encoded by all strains of this microorganism) and beta 2 toxin (produced by some type A strains) is not clear. The goal of this paper is to describe the main clostridial enteric diseases of piglets, including etiology, epidemiology, pathogenesis, clinical signs, pathology and diagnosis.
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Clostridioides difficile , Infecções por Clostridium , Doenças dos Suínos , Animais , Suínos , Doenças dos Suínos/diagnóstico , Doenças dos Suínos/patologia , Clostridium , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/veterinária , Infecções por Clostridium/patologia , Clostridium perfringens , Diarreia/veterináriaRESUMO
In animals, salmonellosis is seen typically as enteritis and/or septicemia. Subclinical infection also occurs, and outwardly healthy animals can serve as reservoirs of infection. Reports of salmonellosis in elephants are rare, limited to a few serovars, and the gross and microscopic lesions of enteric salmonellosis in this species have not been described in detail. We present here, in 2 elephants in managed care settings, cases of salmonellosis that resulted from infection by Salmonella enterica serovar Muenchen and S. enterica serovar Montevideo, serovars that have not been described previously as the cause of salmonellosis in elephants, to our knowledge. We also review the literature on salmonellosis in elephants. Animal A, an adult Asian elephant that was euthanized because of gastrointestinal hemorrhage, had multifocal, necrotizing, suppurative enterocolitis, and necrotizing gastritis. Animal B, an adult African elephant with chronic, recurrent colic, followed by death, had necrotizing typhlocolitis. The origin of infection was not determined in either case. The animals came from different facilities and did not have a common feed source. Previously reported cases of salmonellosis in elephants were caused by Salmonella Dublin, Salmonella Typhimurium, or Salmonella Enteritidis. The definitive diagnosis of salmonellosis is made based on compatible gross and microscopic lesions, coupled with the detection of Salmonella spp. in the affected tissues. Effective biosecurity should be adopted to minimize the risk of salmonellosis in elephants in managed care.
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Elefantes , Salmonelose Animal , Animais , Elefantes/microbiologia , Salmonella enterica , Salmonelose Animal/diagnóstico , Salmonella typhimurium , SorogrupoRESUMO
Reproductive failure represents an important cause of economic loss for the equine industry. We reviewed the cases of equine abortion and stillbirth submitted to the California Animal Health and Food Safety Laboratory System, University of California-Davis from 1990 to 2022. A total of 1,774 cases were reviewed. A confirmed cause of abortion was determined in 29.2% of the cases. Abortion or stillbirth was attributed to infectious agents in 18.7% of the cases, with Streptococcus spp., equine herpesvirus 1, and Leptospira spp. being the most prevalent. Noninfectious causes of abortion were established in 10.5% of the cases, with umbilical cord torsion being the most common. In 70.8% of the cases, a definitive cause of abortion could not be established. Our study demonstrated the difficulties in establishing an etiologic diagnosis, even when following a standard diagnostic work-up. New diagnostic approaches are needed to improve the likelihood of reaching a final diagnosis in cases of equine abortion and stillbirth.
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Doenças dos Cavalos , Leptospira , Gravidez , Feminino , Animais , Cavalos , Natimorto/epidemiologia , Natimorto/veterinária , Aborto Animal/diagnóstico , Aborto Animal/epidemiologia , California/epidemiologia , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/epidemiologia , Doenças dos Cavalos/etiologiaRESUMO
Gastrointestinal disorders are among the most common disease processes in captive elephants. Colic is a frequent clinical presentation and may have several infectious and noninfectious causes. Ingestion of sand has been reported in elephants living in enclosures with loose sandy soils. Similar to the situation in horses, sand ingestion can cause intestinal impaction and colic in elephants. Here we describe a case of colonic sand impaction with cecal rupture and peritonitis in an African savanna elephant from a zoologic collection that died after several days of colic. On autopsy, abundant, gritty, sandy material was found within a segment of colon immediately aboral to the cecum. There was a full-thickness tear in the cecal wall, free intestinal contents within the abdominal cavity, and peritonitis. To our knowledge, the postmortem examination of an elephant with sand impaction and cecal rupture has not been reported previously; this condition should be included among the differential diagnoses in elephants with colic. We review the reports of noninfectious causes of gastrointestinal disease in elephants, which include cases of small intestinal and colonic torsion and of intestinal obstruction by fecal boluses.
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Doenças do Ceco , Cólica , Elefantes , Gastroenteropatias , Doenças dos Cavalos , Cavalos , Animais , Doenças dos Cavalos/diagnóstico , Cólica/diagnóstico , Cólica/etiologia , Cólica/veterinária , Doenças do Ceco/veterinária , Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Gastroenteropatias/veterinária , ColoRESUMO
Four Indian ringneck parakeets (Psittacula krameri; syn. ringneck parrots or rose-ringed parakeets) were submitted by 2 private owners for autopsy following a history of dyspnea and death. Gross findings were varied and included thickening of the left caudal thoracic air sac, white spots throughout the liver, mild dilation of the proventriculus, coelomic effusion, splenomegaly, and pulmonary congestion and edema. Microscopically, the submitted parakeets had significant lesions in the lower respiratory tract, including necrotizing bronchitis, parabronchitis, and interstitial pneumonia with numerous syncytia containing eosinophilic intranuclear inclusions. Electron microscopy of the lungs was compatible with a herpesviral infection and Psittacid alphaherpesvirus 5 (PsAHV5) was detected via PCR and sequencing. There has been inconsistent terminology used with Psittacid alphaherpesvirus 3 and PsAHV5; we attempt here to clarify the reported history of these viruses.
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Alphaherpesvirinae , Infecções por Herpesviridae , Papagaios , Psittacula , Animais , Infecções por Herpesviridae/veterinária , PeriquitosRESUMO
Epiploic foramen entrapment (EFE) is a common cause of small intestinal colic in horses and may lead to intestinal strangulation. Strangulating intestinal obstruction impairs the gastrointestinal outflow and can lead to secondary gastric rupture and endotoxemia. Clostridioides difficile can cause enterotyphlocolitis with colic in horses of all ages, and the process is commonly referred to as C. difficile-associated disease (CDAD). Here we report the results of the postmortem examination of a 7-y-old Thoroughbred racehorse with concurrent CDAD, EFE, and gastric rupture that was euthanized following a history of colic over several days. A segment of distal jejunum and proximal ileum had passed through the epiploic foramen, and the intestinal wall was thickened and dark-red. The remaining small intestinal loops were distended and filled with blood-tinged contents. Peritonitis had resulted from escape of gastric contents into the abdominal cavity through a tear in the major curvature of the stomach. Histologically, the incarcerated segment had acute transmural hemorrhage with congestion and mucosal necrosis; neutrophilic infiltrates with fibrin thrombi were in the mucosa of the non-incarcerated small intestinal segments. C. difficile toxins were detected in the small intestinal contents, and C. difficile was isolated from the small intestine, colon, and cecum.
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Clostridioides difficile , Cólica , Doenças dos Cavalos , Ruptura Gástrica , Animais , Clostridioides , Clostridium , Cólica/complicações , Cólica/veterinária , Doenças dos Cavalos/diagnóstico , Cavalos , Ruptura Gástrica/complicações , Ruptura Gástrica/veterináriaRESUMO
Yellow lamb disease is an infrequent disease in sheep for which there is scant literature, and that has been reported in the US, Australia, New Zealand, South Africa and Europe, although anecdotal evidence indicates that it may have also been diagnosed in South America. The disease is produced by some strains of Clostridium perfringens type A that produce unusually high levels of alpha- toxin. Because C. perfringens type A is ubiquitous and is found in the intestine of most clinically healthy sheep, diagnosis of yellow lamb disease is challenging and requires quantitating the amount of this microorganism present in feces and/or intestinal content. Clinically, yellow lamb disease is characterized by depression, anemia, icterus and hemoglobinuria. Occasionally, sudden death may occur. Gross findings include generalized icterus, red urine in the bladder, enlarged, pale, and friable spleen, enlarged liver with an acinar pattern, and dark, swollen kidneys. Microscopically, yellow lamb disease is characterized by centrilobular necrosis of the liver, hemoglobinuria-associated acute tubular injury, splenic congestion, pulmonary congestion and edema. Although there are no vaccines specifically designed to prevent yellow lamb disease, several vaccines against the different types of C. perfringens may afford at least some level of protection against yellow lamb disease.
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A presumptive postmortem diagnosis of oleander (Nerium oleander) poisoning is made based on the histological observation of cardiomyocyte degeneration and necrosis, which is considered to be a reliable diagnostic marker, and can be confirmed via the detection of oleandrin in tissues or fluids. However, cardiac lesions may not be present in every case, and autolysis can often preclude the identification of subtle changes in the cardiomyocytes. Several studies of experimental oleander poisoning have noted the presence of renal lesions in multiple mammalian species, and case studies of accidental exposure have found similar, although more variably severe, renal abnormalities. Kidney pathology in horses with oleander poisoning has been only briefly mentioned. In this study, we reviewed 21 cases of spontaneous oleander poisoning in horses, evaluated the kidneys microscopically, and compared the renal microscopic lesions with those detected in 10 horses that died or were euthanized due to other causes to assess if histological renal changes could serve as an additional diagnostic marker for oleander poisoning in horses. We found that microscopic renal lesions, principally mild to moderate tubular changes such as hyaline cast formation, neutrophilic casts, epithelial attenuation and necrosis, as well as mineralization and congestion, occur in horses with oleander poisoning. Most of these changes match the descriptions of lesions previously noted in other species, although with less frequency and severity. Similar lesions were found in horses that died spontaneously due to different causes or were euthanized. We concluded that microscopic renal lesions may be detected in horses with oleander poisoning but they cannot be used as a diagnostic marker that allows differentiation from other disease processes or causes of death.
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The health system in the Netherlands is one of the best in the world and it is a challenge to keep this affordable and accessible for everyone. A shift from care to lifelong maintenance of health is highly needed, but the drivers of change are missing. Obviously, the involvement of citizens is essential, but to introduce the change the indispensable incentives must be identified. The believe in integrated network care is growing, but it requires a fresh view on the integration of prevention and care, the involvement of the "old players" to create a new governance model, the supporting IT and adequate funding arrangements. In the Tiel region the implementation of the INCA model for integrated care in the primary care setting might make the difference for this journey.
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Assistência Centrada no Paciente , Humanos , Países BaixosRESUMO
The clostridial diseases of horses can be divided into three major groups: enteric/enterotoxic, histotoxic, and neurotoxic. The main enteric/enterotoxic diseases include those produced by Clostridium perfringens type C and Clostridioides difficile, both of which are characterized by enterocolitis. The main histotoxic diseases are gas gangrene, Tyzzer disease, and infectious necrotic hepatitis. Gas gangrene is produced by one or more of the following microorganisms: C. perfringens type A, Clostridium septicum, Paeniclostridium sordellii, and Clostridium novyi type A, and it is characterized by necrotizing cellulitis and/or myositis. Tyzzer disease is produced by Clostridium piliforme and is mainly characterized by multifocal necrotizing hepatitis. Infectious necrotic hepatitis is produced by Clostridium novyi type B and is characterized by focal necrotizing hepatitis. The main neurotoxic clostridial diseases are tetanus and botulism, which are produced by Clostridium tetani and Clostridium botulinum, respectively. Tetanus is characterized by spastic paralysis and botulism by flaccid paralysis. Neither disease present with specific gross or microscopic lesions. The pathogenesis of clostridial diseases involves the production of toxins. Confirming a diagnosis of some of the clostridial diseases of horses is sometimes difficult, mainly because some agents can be present in tissues of normal animals. This paper reviews the main clostridial diseases of horses.