Journal of Veterinary Internal Medicine最新文献

Background: Seasonal pasture myopathy (SPM) is a highly fatal form of nonexertional rhabdomyolysis that occurs in pastured horses in the United States during autumn or spring. In Europe, a similar condition, atypical myopathy (AM), is common. Recently, a defect of lipid metabolism, multiple acyl-CoA dehydrogenase deficiency (MADD), has been identified in horses with AM.

Objective: To determine if SPM in the United States is caused by MADD.

Animals: Six horses diagnosed with SPM based on history, clinical signs, and serum creatine kinase activity, or postmortem findings.

Methods: Retrospective descriptive study. Submissions to the Neuromuscular Diagnostic Laboratory at the University of Minnesota were reviewed between April 2009 and January 2010 to identify cases of SPM. Inclusion criteria were pastured, presenting with acute nonexertional rhabdomyolysis, and serum, urine, or muscle samples available for analysis. Horses were evaluated for MADD by urine organic acids, serum acylcarnitines, muscle carnitine, or histopathology.

Results: Six horses had clinical signs and, where performed (4/6 horses), postmortem findings consistent with SPM. Affected muscle (4/4) showed degeneration with intramyofiber lipid accumulation, decreased free carnitine concentration, and increased carnitine esters. Serum acylcarnitine profiles (3/3) showed increases in short- and medium-chain acylcarnitines and urinary organic acid profiles (3/3) revealed increased ethylmalonic and methylsuccinic acid levels, and glycine conjugates, consistent with equine MADD.

Conclusions and clinical importance: Similar to AM, the biochemical defect causing SPM is MADD, which causes defective muscular lipid metabolism and excessive myofiber lipid content. Diagnosis can be made by assessing serum acylcarnitine and urine organic acid profiles.

Background: STAT1 and STAT3 are important signaling molecules in disorders of systemic inflammation and are likely to be involved in laminitis, as laminar and systemic inflammation have been well documented in experimental models of laminitis.

Hypothesis: The STAT1 and STAT3 activation (via phosphorylation of tyrosine and serine moieties) is occurring in the laminar tissue during the developmental and onset of lameness time points in both the black walnut extract (BWE) and carbohydrate overload (CHO) models of laminitis.

Animals: Archived laminar tissue from horses.

Methods: Experimental studies of induced laminitis (BWE and CHO administration) in horses were conducted and laminar tissue samples archived. Western hybridization was performed to determine concentrations of Tyr- and Ser-phosphorylated STAT1 and STAT3 from these archived samples. The RT-qPCR was also performed to assess mRNA concentrations of target genes of STAT1 and STAT3.

Results: Increases (P < .05) in phosphorylation of tyrosine705 and serine727 of STAT3, demonstrated by band intensity ratios, are present in laminar tissue from both the BWE and CHO models at the DEV and OG1 time points. No change in phosphorylation of tyrosine701 or serine727 of STAT1 was present in the laminar tissue from either the BWE or the CHO models. The SOCS3 mRNA concentrations were increased at the onset of lameness in both the CHO and BWE models.

Conclusions and clinical relevance: The STAT3 activation likely plays a role in equine laminitis, similar to its reported involvement in organ injury/failure in human sepsis. Regulation of JAK-STAT, through STAT3 inhibitors, might serve as potential therapeutic target for controlling the inflammatory response in the septic horse.

Background: Pituitary pars intermedia dysfunction (PPID) is common in older horses.

Objectives: To determine diagnosis frequency, prognostic factors, long-term survival, and owner satisfaction with treatment.

Animals: Medical records from horses diagnosed with PPID, 1993-2004.

Methods: A retrospective cohort design with data collected from the Veterinary Medical Data Base (VMDB) and a cohort of 3 VTHs. Proportional accessions, annual incidence, and demographics were compared for all accessions. During the same period, a subset of medical records (n = 44) was extracted and owners (n = 34) contacted to obtain long-term follow-up information.

Results: Diagnoses of PPID were reported for 217 horses that presented to VTHs and were reported to the VMDB. Proportional diagnosis increased from 0.25/1,000 in 1993 to 3.72/1,000 in 2002. For 44 horses included in the follow-up study, the most commons signs were hirsutism (84%) and laminitis (50%). Of 34 horse owners contacted, the average time from onset of signs to diagnosis was 180 days. Improvement in ≥ 1 signs, 2 months after diagnosis, was reported by 9/22 (41%) of horse owners. Clinical signs and clinicopathologic data were not associated with survival, and 50% of horses were alive 4.6 years after diagnosis. Cause of death among horses (15/20; 85%) was euthanasia, and 11/15 (73%) were euthanized because of conditions associated with PPID. Most horse owners (28/29; 97%) said they would treat a second horse for PPID.

Conclusion and clinical importance: PPID was diagnosed with increasing frequency, and 50% of horses survived 4.5 years after diagnosis. Owners were satisfied with their horses' quality of life and would treat a second horse if diagnosed.

Background: Gastroesophageal reflux (GER) is the presence of gastric contents proximal to the stomach. Pathologic consequences secondary to GER are termed gastroesophageal reflux disease (GERD).

Objectives: The purpose of this study was to determine the prevalence of GER and GERD in premature calves by endoscopic examination.

Animals: Ten healthy and 51 premature calves were included in the study. All premature calves also had respiratory distress syndrome.

Methods: Esophagoscopy of premature calves was conducted by fiber optic endoscopy. Abnormalities such as increased saliva, hyperemia, hemorrhage, petechiae, presence of abomasal content in the esophagus, and relaxation of the lower esophageal sphincter (LES) were evaluated by endoscopy.

Results: The prevalence of GERD and GER in the premature calves was 55 and 67%, respectively. Hyperemia and hyperemia with hemorrhage or petechiation of the esophageal mucosa were determined by endoscopic examination. Hyperemia was commonly observed in the distal esophageal mucosa, although a few hyperemic areas also were observed in other portions of the esophagus. In addition to these abnormalities, LES relaxation, abomasal fluid in the distal esophagus, abomasal content in the esophagus, and increased saliva also were observed in premature calves with GER.

Conclusions: The prevalence of both GER (67%) and GERD (55%) in premature calves was high in the study. Endoscopy provides a practical, rapid, noninvasive, and reasonably accurate method for determining the presence of GER and GERD in premature calves.

Background: External beam radiation therapy can be used to treat pelvic tumors in dogs, but its utility is limited by lack of efficacy data and associated late complications.

Hypothesis/objectives: The objective of this study was to assess local tumor control, overall survival, and toxicosis after intensity-modulated and image-guided radiation therapy (IM/IGRT) for treatment of genitourinary carcinomas (CGUC) in dogs.

Animals: 21 client-owned dogs.

Methods: A retrospective study was performed. Medical records of dogs for which there was intent to treat with a course of definitive-intent IM/IGRT for CGUC between 2008 and 2011 were reviewed. Descriptive and actuarial statistics comprised the data analysis.

Results: Primary tumors were located in the prostate (10), urinary bladder (9), or urethra (2). The total radiation dose ranged from 54-58 Gy, delivered in 20 daily fractions. Grade 1 and 2 acute gastrointestinal toxicoses developed in 33 and 5% of dogs, respectively. Grade 1 and 2 acute genitourinary and grade 1 acute integumentary toxicoses were documented in 5, 5, and 20% of dogs, respectively. Four dogs experienced late grade 3 gastrointestinal or genitourinary toxicosis. The subjective response rate was 60%. The median event-free survival was 317 days; the overall median survival time was 654 days. Neither local tumor control nor overall survival was statistically dependent upon location of the primary tumor.

Conclusions and clinical importance: IM/IGRT is generally well-tolerated and provides an effective option for locoregional control of CGUC. As compared with previous reports in the veterinary literature, inclusion of IM/IGRT in multimodal treatment protocols for CGUC can result in superior survival times; controlled prospective evaluation is warranted.

Adverse drug reactions (ADRs) can be dose dependent or idiosyncratic. Most idiosyncratic reactions are believed to be immune-mediated; such drug hypersensitivities and allergies are unpredictable. Cutaneous reactions are the most common presentation of drug allergies. In veterinary medicine it can be difficult to assess the true prevalence of adverse drug reactions, although reports available suggest that they occur quite commonly. There are multiple theories that attempt to explain how drug allergies occur, because the pathogenesis is not yet well understood. These include the (pro)-hapten hypothesis, the Danger Theory, the pi concept, and the viral reactivation theory. Cutaneous drug allergies in veterinary medicine can have a variety of clinical manifestations, ranging from pruritus to often fatal toxic epidermal necrolysis. Diagnosis can be challenging, as the reactions are highly pleomorphic and may be mistaken for other dermatologic diseases. One must rely heavily on history and physical examination to rule out other possibilities. Dechallenge of the drug, histopathology, and other diagnostic tests can help to confirm the diagnosis. New diagnostic tools are beginning to be used, such as antibody or cellular testing, and may be used more in the future. There is much yet to learn about drug allergies, which makes future research vitally important. Treatment of drug allergies involves supportive care, and additional treatments, such as immunosuppressive medications, depend on the manifestation of the disease. Of utmost importance is to avoid the use of the incriminating drug in future treatment of the patient, as subsequent reactions can be worse, and ultimately can prove fatal.

Background: Horses are extremely susceptible to ionophore intoxication. Although numerous reports are available regarding monensin, little is known about lasalocid toxicity.

Objectives: To describe accidental lasalocid poisoning on a farm in Belgium.

Animals: Eighty-one horses, of which 14 demonstrated clinical signs from day 0-21 after being fed a new concentrate batch. One horse died on day 20 and another on day 27.

Methods: The most severe cases (n = 7), admitted to the clinic on day 29-46, underwent cardiac examination and blood biochemical analysis, including determination of plasma cardiac troponin I (cTnI) at admission and during follow-up. On day 57-70, cardiac examination, cTnI determination or both were undertaken on 72 remaining horses.

Results: Short-term effects of lasalocid intoxication included inappetance, lethargy, sweating, and muscular weakness. All 7 horses admitted to the clinic demonstrated signs of myocardial degeneration such as increased cTnI, dysrhythmia and reduced myocardial contractility. Four horses developed ataxia on day 40-50. Five horses died or were euthanized on day 30-370, 2 horses recovered fully and returned to previous athletic use. None of the 72 remaining horses exhibited clinical signs between day 57-70, but 34 had dysrhythmia and 13 had increased cTnI concentrations. After a period of rest, all horses returned to their previous work. Lasalocid was detected in hepatic tissue of 2 necropsied horses.

Conclusions and clinical importance: Lasalocid intoxication induced myocardial and neurological damage. Although uncommon, this should be included as differential diagnosis for unexplained inappetance, signs of depression, cardiomyopathy, and ataxia in horses.

Background: Tolfenamic acid (TA) is an NSAID currently under investigation as an anticancer agent in humans. TA induces proteosome-dependent degradation of transcription factors Sp 1, 3, and 4. These proteins are known to be overexpressed in many human cancers.

Hypothesis: To evaluate the protein expression of Sps in canine tissue, and efficacy of TA against several canine tumor cell lines.

Methods: Six canine cell lines (2 osteosarcoma, 2 mammary carcinoma, 2 melanoma) were evaluated. Protein levels of Sp 1-4 and their downstream targets were evaluated using Western Blots. Cell survival and TUNEL assays were performed on cell lines, and Sp1 expression was evaluated on histologic samples from archived canine cases.

Animals: Six immortalized canine cancer cell lines derived from dogs were used. Archived tissue samples were also used.

Results: Sps were highly expressed in all 6 cell lines and variably expressed in histologic tissues. TA decreased expression of Sps 1-4 in all cell lines. All of the downstream targets of Sps were inhibited in the cell lines. Variable Sp1 expression was identified in all histologic samples examined. TA significantly inhibited cell survival in all cell lines in a dose dependant fashion. The number of cells undergoing apoptosis was significantly increased (P < .05) in all cell lines after exposure to TA in a dose-dependent fashion. CONCLUSIONS, AND CLINICAL IMPORTANCE: Tolfenamic acid is a potential anticancer NSAID and further investigation is needed to determine its usefulness in a clinical setting.

Background: Pepsinogens are proenzymes secreted by gastric chief cells. In humans, their serum concentrations reflect gastric mucosal morphological and functional status.

Objectives: To evaluate serum canine pepsinogen-A (cPG-A), C-reactive protein (CRP), and canine pancreatic lipase immunoreactivity (cPLI) concentrations in dogs with gastric dilatation-volvulus (GDV).

Animals: Sixty-six dogs presented with GDV and 79 healthy controls.

Methods: Blood was collected prospectively, and records retrospectively reviewed.

Results: Median cPG-A concentration was higher in GDV dogs (median, 397 μg/L; range, 37-5,410) compared to controls (median, cPG-A 304 μg/L; range, 18-848; P = .07). Mortality rate in GDV dogs was 22.7%. In nonsurvivors of GDV, median cPG-A was higher compared to survivors (median, 746 μg/L; range, 128-5,409 versus median, 346; range, 36-1,575, respectively; P = .003). The proportion of dogs with increased cPG-A increased with gastric wall damage score (P = .007). An ROC analysis of cPG-A as a predictor of death showed an area under the curve (AUC) of 0.75, higher than lactate (AUC 0.66), and corresponded to a sensitivity and specificity of 53% and 88%, respectively. CRP was increased in 48 dogs (75%), cPLI was >200 μg/L in 26 dogs (39.4%) and >400 μg/L in 12 dogs (18.2%) but both analytes had no association with outcome.

Conclusions: Presurgical cPG-A concentration was positively and significantly associated with gastric wall lesion severity, but, based on ROC analysis, it was only a moderate outcome predictor. CRP and cPLI were commonly increased in dogs with GDV.

Background: Atypical myopathy (AM) is an acute, fatal rhabdomyolysis in grazing horses that mainly affects skeletal muscles. Postmortem examinations have shown that myocardial damage also occurs. Limited information is available on the effect of AM on cardiac function in affected and surviving horses.

Objectives: To describe electrocardiographic and echocardiographic changes associated with AM in the acute stage of the disease and after follow-up.

Animals: Horses (n = 12) diagnosed with AM in which cardiac ultrasound examination and ECG recording were available.

Methods: All horses underwent clinical examinations, serum biochemistry, electrocardiography, and echocardiography. Four surviving horses underwent the same examinations after 2-10 weeks.

Results: All but 1 horse had increased cardiac troponin I concentrations and 10 horses had ventricular premature depolarizations (VPDs). All horses had prolonged corrected QT (QT(cf) ) intervals on the day of admission and abnormal myocardial wall motion on echocardiography. One of the surviving horses still had VPDs and prolonged QT(cf) at follow-up after 10 weeks.

Conclusions and clinical importance: The AM results in characteristic electrocardiographic and echocardiographic changes and may be associated with increased cardiac troponin I concentrations and VPDs. In survivors, abnormal cardiac function still may be found at follow-up after 10 weeks. Additional research in a larger group of horses is necessary to identify the long-term effects of AM on cardiac function.