Publications by authors named "Timothy N Holt"

16 Publications

  • Page 1 of 1

Investigation of neonatal disorders in New World camelids and factors associated with death during and after hospitalization of affected crias.

J Am Vet Med Assoc 2021 Apr;258(8):892-898

Objective: To assess signalment, clinical findings, and treatments for New World camelids (NWCs) hospitalized for evaluation and treatment of neonatal disorders and investigate associations between these factors and death during and after hospitalization.

Animals: 267 NWCs ≤ 30 days of age.

Procedures: Medical records of a veterinary teaching hospital were retrospectively reviewed to identify NWCs admitted for evaluation and treatment of neonatal disorders between 2000 and 2010. Signalment, physical examination data, diagnostic findings, treatments, and outcomes were recorded. Factors were examined for association with death during hospitalization and the overall hazard of death by use of multivariable logistic regression and Cox proportional hazards analysis, respectively.

Results: The sample comprised alpacas (n = 255) and llamas (12). Median age at admission was 3 days, and median hospitalization time was 2 days; 208 of the 267 (77.9%) neonatal NWCs survived to hospital discharge. Factors associated with increased odds of death during hospitalization included prematurity or dysmaturity, hypothermia, sepsis, toxic changes in neutrophils, and undergoing surgery. The odds of death during hospitalization also increased as anion gap increased. After discharge, 151 of 176 (85.8%) animals had follow-up information available (median follow-up time, 2,932 days); 126 (83%) were alive and 25 (17%) had died. Prematurity or dysmaturity, congenital defects, sepsis, oxygen administration, and undergoing surgery as a neonate were associated with an increased hazard of death; the hazard of death also increased as serum chloride concentration at the time of hospitalization increased.

Conclusions And Clinical Relevance: Results suggested the prognosis for survival during and after hospitalization is good for most NWCs hospitalized because of neonatal disorders.
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http://dx.doi.org/10.2460/javma.258.8.892DOI Listing
April 2021

Repeated measures of PAP at different elevations in beef bulls in Colorado.

Transl Anim Sci 2020 Dec 22;4(Suppl 1):S113-S117. Epub 2020 Dec 22.

Department of Animal Science, Colorado State University, Fort Collins, CO.

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http://dx.doi.org/10.1093/tas/txaa116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754211PMC
December 2020

Evaluation of the sensitivity of pulmonary arterial pressure to elevation using a reaction norm model in Angus Cattle.

J Anim Sci 2020 May;98(5)

Department of Animal Sciences, Colorado State University, Fort Collins, CO.

Pulmonary arterial pressure (PAP) is a diagnostic measure used to determine an individual's susceptibility to developing high-altitude disease. The importance of PAP measures collected at elevations lower than the intended breeding elevation of the bulls (i.e., ≥1,520 m) is unknown. Therefore, the objective of this study was to determine the genetic relationship between PAP measures collected in a range of elevations using reaction norm models. A total of 9,177 PAP and elevation observations on purebred Angus cattle, which averaged 43.49 ± 11.32 mmHg and 1,878.6 ± 296.8 m, respectively, were used in the evaluation. The average age of the individuals in the evaluation was 434.04 ± 115.9 d. A random regression model containing the effects of sex, a linear covariate of age, a quadratic fixed covariate of elevation, and random effects consisting of a contemporary group and a linear regression of PAP on elevation was used for the evaluation of PAP. Two forms of PAP were evaluated with this model. First, to address the non-normality of the data, PAP was raised to the power of -2.6 (ptPAP) based on the results of a Box-Cox analysis. Second, raw PAP (rPAP) phenotypes were evaluated to compare the results to those obtained from the transformed data. For ptPAP, heritability ranged from 0.25 to 0.37 corresponding to elevations of 1,900 and 1,215 m, respectively. For rPAP, heritability ranged from 0.22 to 0.41 corresponding to elevations of 1,700 and 2,495 m, respectively. Generally, lower elevations corresponded to decreased heritabilities while higher elevations corresponded to increased heritability estimates. For ptPAP, genetic correlations ranged from 0.18 (elevation: 1,215 and 2,495 m) to 1.00. For rPAP, genetic correlations ranged from 0.08 (elevation: 1,215 and 2,495 m) to 1.00. In general, the closer the elevations in which PAP was measured, the greater the genetic relationship. The greater the difference in elevation between PAP measures resulted in lower genetic correlations. The rank correlation between expected progeny differences (EPD) for 1,215 and 2,495 m was 0.65 and 0.49 for the ptPAP and rPAP, respectively. These results suggested that PAP measures collected in lower elevations may be used as an indicator of high-altitude adaptability. In the estimation of EPD to rank sires for their suitability for use in high-elevation production systems, it is important to account for the relationships among varied altitudes.
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http://dx.doi.org/10.1093/jas/skaa129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228678PMC
May 2020

Laparoscopic ovariohysterectomy in goats.

J Am Vet Med Assoc 2019 Jan;254(2):275-281

OBJECTIVE To describe a minimally invasive 3-portal laparoscopic approach for elective ovariohysterectomy and the outcome of that procedure in a population of goats. DESIGN Descriptive clinical study. ANIMALS 16 healthy client-owned goats. PROCEDURES Food but not water was withheld from all goats for 24 hours before the procedure. Goats were anesthetized and positioned in dorsal recumbency. Three laparoscopic portals were created in the caudoventral portion of the abdomen, and the abdomen was insufflated to a maximum pressure of 10 mm Hg. A blunt-tip vessel sealer and divider device was used to transect the left and right mesovarium and mesometrium and uterus, and the resected tissue was removed from the abdomen. After hemostasis was verified, the portals were closed in a routine manner and anesthesia was discontinued. Goats were discharged from the hospital 24 hours after the procedure, and owners were contacted by telephone or email to obtain short- and long-term follow-up information by use of standardized questions. RESULTS All procedures were performed by a surgeon and assistant surgeon. The procedure was not complex and was easily learned. No intraoperative complications were reported, and only 1 goat required rescue analgesia post-operatively. No other postoperative complications were recorded. Median surgery time was 43 minutes (range, 20 to 65 minutes). All owners were satisfied with the outcome of the procedure, and several perceived that the procedure improved goat behavior. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that laparoscopic ovariohysterectomy was a viable alternative for elective sterilization of female goats.
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http://dx.doi.org/10.2460/javma.254.2.275DOI Listing
January 2019

Evaluation of moderate to high elevation effects on pulmonary arterial pressure measures in Angus cattle1.

J Anim Sci 2018 Sep;96(9):3599-3605

Department of Animal Sciences, Colorado State University, Fort Collins, CO.

Altitude-induced pulmonary hypertension is a disease once thought to only occur at extremely high elevations (>1,600 m), but recently, it has been observed at moderate elevations of 1,200 to 1,600 m. Pulmonary arterial pressure (PAP) has been used as an indicator of tolerance to high altitude in mountainous beef production systems for over 30 yr. The trait is typically measured on yearling bulls and heifers with values ≤ 41 mmHg being favorable. These observations were historically only considered valid when they were recorded at elevations ≥ 1,600 m; however, if observations from lower (i.e., moderate) elevations were reliable indicators, a greater number of cattle records could be used in genetic improvement programs for high-altitude beef systems. The objectives of this study were to evaluate the relationship between PAP and elevation, as well as to determine whether PAP measures obtained at moderate elevations (ME) less than 1,600 m have a genetic relationship with PAP observations obtained at high elevations (HE) 1,600 m or greater. Elevation and PAP data from purebred Angus cattle (n = 14,665) from 349 contemporary groups were used in the analyses. Elevation and PAP averaged 1,887 ± 1.8 m and 43.0 ± 0.1 mm Hg, respectively. A univariate model containing the effects of sex, age, elevation category (HE vs. ME), elevation (continuous), and elevation category by elevation interaction along with a random direct genetic effect was utilized to determine the relationship between PAP and elevation. In this model, all main effects were found to be significant contributors of variation in PAP (P < 0.001). The interaction between elevation category and elevation was not a significant contributor to variability of PAP (P > 0.05). A bivariate animal model was then used to evaluate the relationship between PAP observations obtained between HE and ME groups. Heritability estimates for these 2 groups were 0.34 ± 0.03 and 0.29 ± 0.09, respectively, and their genetic correlation was 0.83 ± 0.15. Even though this is a strong genetic relationship, results of this study support the hypothesis that PAP observations collected at HE and ME are not perfectly, genetically related. Results suggest that PAP measures collected from 1,219 to 1,600 m may be useful as a correlated trait in a multitrait genetic evaluation to produce EPD useful for selection of animals with reduced susceptibility to pulmonary hypertension.
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http://dx.doi.org/10.1093/jas/sky262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127772PMC
September 2018

Laparoscopic inguinal hernioplasty in a ram.

J Am Vet Med Assoc 2015 May;246(10):1118-21

Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

Case Description: A 4-month-old Hampshire ram underwent open right inguinal herniorrhaphy and unilateral castration following herniation that developed after a kick injury. Seven months later, the ram was reevaluated because of scrotal swelling of 1 month's duration as well as suspected left inguinal hernia.

Clinical Findings: The ram had marked scrotal swelling. Palpation of the left testicle revealed no abnormalities. Ultrasonographic examination revealed heterogenous tissue within the cranial and medial portions of the scrotum with pronounced accumulation of hypoechoic fluid at the scrotal apex. Examination findings indicated left-sided indirect inguinal herniation of omentum.

Treatment And Outcome: To preserve fertility, left inguinal hernioplasty without castration was performed. The ram was anesthetized and placed in dorsal recumbency, and laparoscopic abdominal evaluation revealed omental entrapment within the left inguinal ring. The omentum was removed, and a polypropylene mesh was secured over the internal inguinal ring with an articulating hernia stapler. Following mesh placement, a dorsally based peritoneal flap was elevated and secured over the mesh repair. The ram recovered well from surgery; there was no repeated herniation following the surgical correction, and the ram was able to breed successfully without complication.

Clinical Relevance: Laparoscopic mesh hernioplasty can be successful in rams with inguinal hernias when preservation of fertility is preferred.
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http://dx.doi.org/10.2460/javma.246.10.1118DOI Listing
May 2015

Increased prevalence of EPAS1 variant in cattle with high-altitude pulmonary hypertension.

Nat Commun 2015 Apr 15;6:6863. Epub 2015 Apr 15.

Department of Pediatrics, Division of Medical Genetics and Genomic Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.

High-altitude pulmonary hypertension (HAPH) has heritable features and is a major cause of death in cattle in the Rocky Mountains, USA. Although multiple genes are likely involved in the genesis of HAPH, to date no major gene variant has been identified. Using whole-exome sequencing, we report the high association of an EPAS1 (HIF2α) double variant in the oxygen degradation domain of EPAS1 in Angus cattle with HAPH, mean pulmonary artery pressure >50 mm Hg in two independent herds. Expression analysis shows upregulation of 26 of 27 HIF2α target genes in EPAS1 carriers with HAPH. Of interest, this variant appears to be prevalent in lowland cattle, in which 41% of a herd of 32 are carriers, but the variant may only have a phenotype when the animal is hypoxemic at altitude. The EPAS1 variant will be a tool to determine the cells and signalling pathways leading to HAPH.
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http://dx.doi.org/10.1038/ncomms7863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399003PMC
April 2015

Myosin heavy chain 15 is associated with bovine pulmonary arterial pressure.

Pulm Circ 2014 Sep;4(3):496-503

Medical Research Council, National Institute for Medical Research, Mill Hill, London, United Kingdom ; Division of Medicine, University College London, London, United Kingdom.

Bovine pulmonary hypertension, brisket disease, causes significant morbidity and mortality at elevations above 2,000 m. Mean pulmonary arterial pressure (mPAP) is moderately heritable, with inheritance estimated to lie within a few major genes. Invasive mPAP measurement is currently the only tool available to identify cattle at risk of hypoxia-induced pulmonary hypertension. A genetic test could allow selection of cattle suitable for high altitude without the need for invasive testing. In this study we evaluated three candidate genes (myosin heavy chain 15 [MYH15], NADH dehydrogenase flavoprotein 2, and FK binding protein 1A) for association with mPAP in 166 yearling Angus bulls grazing at 2,182 m. The T allele (rs29016420) of MYH15 was linked to lower mPAP in a dominant manner (CC 47.2 ± 1.6 mmHg [mean ± standard error of the mean]; CT/TT 42.8 ± 0.7 mmHg; P = 0.02). The proportions of cattle with MYH15 CC, CT, and TT genotypes were 55%, 41%, and 4%, respectively. Given the high frequency of the deleterious allele, it is likely that the relative contribution of MYH15 polymorphisms to pulmonary hypertension is small, supporting previous predictions that the disease is polygenic. We evaluated allelic frequency of MYH15 in the Himalayan yak (Bos grunniens), a closely related species adapted to high altitude, and found 100% prevalence of T allele homozygosity. In summary, we identified a polymorphism in MYH15 significantly associated with mPAP. This finding may aid selection of cattle suitable for high altitude and contribute to understanding human hypoxia-induced pulmonary hypertension.
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http://dx.doi.org/10.1086/677364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278609PMC
September 2014

An investigation into beef calf mortality on five high-altitude ranches that selected sires with low pulmonary arterial pressures for over 20 years.

J Vet Diagn Invest 2013 Mar;25(2):210-8

Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523-1678, USA.

Producer reports from ranches over 2,438 meters in southwest Colorado suggest that the mortality of preweaned beef calves may be substantially higher than the national average despite the selection of low pulmonary pressure herd sires for over 20 years. Diagnostic investigations of this death loss problem have been limited due to the extensive mountainous terrain over which these calves are grazed with their dams. The objective of the current study was to determine the causes of calf mortality on 5 high-altitude ranches in Colorado that have been selectively breeding sires with low pulmonary pressure (<45 mmHg) for over 20 years. Calves were followed from branding (6 weeks of age) in the spring to weaning in the fall (7 months of age). Clinical signs were recorded, and blood samples were taken from sick calves. Postmortem examinations were performed, and select tissue samples were submitted for aerobic culture and/or histopathology. On the principal study ranch, 9.6% (59/612) of the calves that were branded in the spring either died or were presumed dead by weaning in the fall. In total, 28 necropsies were performed: 14 calves (50%) had lesions consistent with pulmonary hypertension and right-sided heart failure, and 14 calves (50%) died from bronchopneumonia. Remodeling of the pulmonary arterial system, indicative of pulmonary hypertension, was evident in the former and to varying degrees in the latter. There is a need to better characterize the additional risk factors that complicate pulmonary arterial pressure testing of herd sires as a strategy to control pulmonary hypertension.
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http://dx.doi.org/10.1177/1040638713478608DOI Listing
March 2013

High-altitude pulmonary hypertension in cattle (brisket disease): Candidate genes and gene expression profiling of peripheral blood mononuclear cells.

Pulm Circ 2011 Oct-Dec;1(4):462-9

Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.

High-altitude pulmonary hypertension (HAPH) is a consequence of chronic alveolar hypoxia, leading to hypoxic vasoconstriction and remodeling of the pulmonary circulation. Brisket disease in cattle is a naturally occurring animal model of hypoxic pulmonary hypertension. Genetically susceptible cattle develop severe pulmonary hypertension and right heart failure at altitudes >7,000 ft. No information currently exists regarding the identity of the pathways and gene(s) responsible for HAPH or influencing severity. We hypothesized that initial insights into the pathogenesis of the disease could be discovered by a strategy of (1) sequencing of functional candidates revealed by single nucleotide polymorphism (SNP) analysis and (2) gene expression profiling of affected cattle compared with altitude-matched normal controls, with gene set enrichment analysis (GSEA) and Ingenuity pathway analysis (IPA). We isolated blood from a single herd of Black Angus cattle of both genders, aged 12-18 months, by jugular vein puncture. Mean pulmonary arterial pressures were 85.6±13 mmHg STD in the 10 affected and 35.3±1.2 mmHg STD in the 10 resistant cattle, P<0.001. From peripheral blood mononuclear cells, DNA was hybridized to an Affymetrix 10K Gene Chip SNP, and RNA was used to probe an Affymetrix Bovine genome array. SNP loci were remapped using the Btau 4.0 bovine genome assembly. mRNA data was analyzed by the Partek software package to identify sets of genes with an expression that was statistically different between the two groups. GSEA and IPA were conducted on the refined expression data to identify key cellular pathways and to generate networks and conduct functional analyses of the pathways and networks. Ten SNPs were identified by allelelic association and four candidate genes were sequenced in the cohort. Neither endothelial nitric oxide synthetase, NADH dehydrogenase, TG-interacting factor-2 nor BMPR2 were different among affected and resistant cattle. A 60-gene mRNA signature was identified that differentiated affected from unaffected cattle. Forty-six genes were overexpressed in the affected and 14 genes were downregulated in the affected cattle by at least 20%. GSEA and Ingenuity analysis identified respiratory diseases, inflammatory diseases and pathways as the top diseases and disorders (P<5.14×10(-14)), cell development and cell signaling as the top cellular functions (P<1.20×10(-08)), and IL6, TREM, PPAR, NFkB cell signaling (P<8.69×10(-09)) as the top canonical pathways associated with this gene signature. This study provides insights into differences in RNA expression in HAPH at a molecular level, and eliminates four functional gene candidates. Further studies are needed to validate and refine these preliminary findings and to determine the role of transcribed genes in the development of HAPH.
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http://dx.doi.org/10.4103/2045-8932.93545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3329076PMC
August 2012

Inadvertent transvaginal administration of sodium phosphate enemas in 2 alpaca crias.

J Vet Emerg Crit Care (San Antonio) 2010 Dec;20(6):623-7

Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USA.

Objective: To describe the clinical presentation and resultant metabolic disturbances following retroperitoneal administration of hyperphosphate enemas in alpaca crias.

Case Or Series Summary: Two crias presented to the Colorado State University Veterinary Teaching Hospital after inadvertent transvaginal retroperitoneal hyperphosphate enema administration. The first cria developed an acute onset of neurologic signs, severe hypernatremia, and died soon after presentation. The second cria developed severe hyperphosphatemia, hypocalcemia, and acidemia. The metabolic derangements normalized within 24 hours of intensive treatment with calcium supplementation and IV crystalloid fluid diuresis. The cria was discharged after 1 week in the hospital.

New Or Unique Information Provided: This report provides a description of electrolyte disturbances secondary to inadvertent transvaginal retroperitoneal administration of hyperphosphate enemas in 2 crias and attendant clinical signs of these disturbances. Management of hyperphosphatemia and hypocalcemia in 1 cria via aggressive fluid therapy with calcium supplementation led to a rapid and sustained normalization of phosphorus, calcium, and acid-base balance.
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http://dx.doi.org/10.1111/j.1476-4431.2010.00583.xDOI Listing
December 2010

Hepatic encephalopathy in two goat kids with common paternity.

J Vet Diagn Invest 2008 Nov;20(6):807-11

Colorado State University, Fort Collins, CO 80523-1619, USA.

Two juvenile, intact, female mixed-breed goats from a common sire were presented for periodic neurologic deficits, seizures, and a generalized loss of body condition that occurred over a 4-6-week period. On physical examination, both goats were thin, obtunded, blind, and ataxic. Laboratory diagnostics revealed increased serum bile acids (95 micromol/l; reference interval: 0-50 micromol/l) in one of the goats. Both goats exhibited progressive physical and mental deterioration, and were eventually euthanized. Upon necropsy, no significant macroscopic lesions were noted. Microscopic examination, however, demonstrated hepatocellular atrophy and anomalies in the hepatic microvasculature, including duplication of hepatic arteries, small-to-indistinct portal veins, and oval cell hyperplasia. In addition, spongiform change was microscopically identified throughout the parenchyma of the brain, most notably within the white matter and along the junction of gray and white matter. The diagnosis of congenital portal vein hypoperfusion (suggestive of a portosystemic shunt) with resultant hepatic encephalopathy was proposed in each case based on the characteristic microscopic lesions in conjunction with the signalment and history of the goats. The observation that the affected kids were sired by the same buck suggests a hereditary basis for the condition in these animals as well.
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http://dx.doi.org/10.1177/104063870802000617DOI Listing
November 2008

Pulmonary arterial pressure testing for high mountain disease in cattle.

Vet Clin North Am Food Anim Pract 2007 Nov;23(3):575-96, vii

Department of Clinical Sciences, College of Veterinary Medicine and Biological Sciences, Colorado State University, Fort Collins, CO 80523, USA.

High mountain or brisket disease is an economically costly disease of cattle raised at elevations greater than 1500 m (5000 ft). It appears that no one breed is resistant to the effects of high-altitude hypoxia. Some breeds, and pedigrees within breeds, appear to be more naturally resistant to the effects of high altitude. Multiple factors contribute to the variance in pulmonary arterial pressure in cattle, including breed, gender, body condition, concurrent illness, environmental conditions, elevation, and genetics. Pulmonary arterial pressure testing is an effective diagnostic and management tool used to identify clinically affected and high-risk animals. The procedure can be performed in the field and is an economically valuable method for the selection and breeding management of beef cattle raised at high altitude.
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http://dx.doi.org/10.1016/j.cvfa.2007.08.001DOI Listing
November 2007

Trichophytobezoar duodenal obstruction in New World camelids.

Vet Surg 2005 Sep-Oct;34(5):524-9

Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.

Objective: To describe clinical findings, surgical treatment, and outcome associated with trichophytobezoar duodenal obstruction in New World camelids.

Study Design: Retrospective study.

Animals: Alpacas (7) and 1 llama.

Methods: Historical and clinical data were obtained from the medical records of New World camelids with a diagnosis of trichophytobezoar duodenal obstruction confirmed by surgical exploration or necropsy.

Results: Seven camelids were <1 year old. Abnormal clinical findings included anorexia, reduced fecal output, recumbency, colic, abdominal distension, regurgitation, decreased serum chloride concentration, increased serum bicarbonate concentration, and/or elevated first gastric compartment chloride concentration. Survey abdominal radiographs obtained (4 animals) revealed gastric distension (4) and/or visualization of the obstruction (2). Diagnosis was confirmed at necropsy (1) or surgery (7). Right paracostal celiotomy was performed on all animals and duodenotomy (3) or retropulsion of the trichophytobezoar combined with third compartment gastrotomy (4) was used to remove the obstruction. Six animals survived to discharge and 5 were healthy at follow-up, 8-20 months later. The remaining discharged alpaca was healthy at 12 months but subsequently died of unrelated causes.

Conclusions: Diagnosis of trichophytobezoar duodenal obstruction should be considered in juvenile New World camelids with abdominal distension and hypochloremic metabolic alkalosis. Right paracostal celiotomy can be used for access to the descending duodenum and third gastric compartment for surgical relief of obstruction.

Clinical Relevance: Duodenal obstruction from bezoars should be considered in New World camelids <1year of age with abdominal distension and hypochloremic metabolic alkalosis. Surgical relief of the obstruction by right paracostal celiotomy has a good prognosis.
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http://dx.doi.org/10.1111/j.1532-950X.2005.00079.xDOI Listing
December 2005

Abdominal emergencies in cattle.

Vet Clin North Am Food Anim Pract 2005 Nov;21(3):655-96, vi

Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.

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http://dx.doi.org/10.1016/j.cvfa.2005.06.003DOI Listing
November 2005
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