Current Role at Stanford

My research focuses on the proteins of the human immune system that vary greatly between individuals and populations. These differences, the consequence of natural selection, not only modulate the immune response to infection and cancer, but also influence the success of reproduction and therapeutic transplantation of cells, tissues and organs.

Honors & Awards

  • Christopher M Smith Research Award, UC Davis (2008 and 2009)
  • Deans Fellowship, Stanford University (June 2010)

Education & Certifications

  • BVM&S, Edinburgh University, Veterinary Medicine (2005)
  • PhD, Edinburgh University, Immunology and Immunogenetics (2016)
  • Board Ceritifcation, ACVIM (2009)
  • Residency, University of California, Davis (2009)
  • Internship, Ontario Veterinary College, University of Guelph (2006)

Service, Volunteer and Community Work

  • Stanford University Undergraduate Standards and Policies Sub-Committee, Stanford University (2013)

    Rhodes and Marshall Scholarship panel


    Stanford, CA


All Publications

  • Deciphering the KIR system at super-resolution for NK and T cell biology. Immunology Béziat, V., Hilton, H., Norman, P. J., Traherne, J. A. 2016


    Killer-cell immunoglobulin-like receptors (KIRs) are components of two fundamental biological systems essential for human health and survival. Firstly, they contribute to host immune response, both innate and adaptive, through their expression by natural killer (NK) cells and T cells. Secondly, KIR play a key role in regulating placentation, and hence reproductive success. Analogous to the diversity of their HLA class I ligands, KIR are extremely polymorphic. In this review, we describe recent developments, fuelled by methodological advances, which are helping to decipher the KIR system in terms of haplotypes, polymorphisms, expression patterns and their ligand interactions. These developments are delivering deeper insight into the relevance of KIR in immune system function, evolution and disease. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/imm.12684

    View details for PubMedID 27779741

  • Class I HLA haplotypes form two schools that educate NK cells in different ways. Science immunology Horowitz, A., Djaoud, Z., Nemat-Gorgani, N., Blokhuis, J., Hilton, H. G., Béziat, V., Malmberg, K. J., Norman, P. J., Guethlein, L. A., Parham, P. 2016; 1 (3)


    Natural killer (NK) cells are lymphocytes having vital functions in innate and adaptive immunity, as well as placental reproduction. Controlling education and functional activity of human NK cells are various receptors that recognize HLA class I on the surface of tissue cells. Epitopes of polymorphic HLA-A,-B and -C are recognized by equally diverse killer cell immunoglobulin-like receptors (KIR). In addition, a peptide cleaved from the leader sequence of HLA-A,-B or -C must bind to HLA-E for it to become a ligand for the conserved CD94:NKG2A receptor. Methionine/threonine dimorphism at position -21 of the leader sequence divides HLA-B allotypes into a majority having -21T that do not supply HLA-E binding peptides and a minority having -21M, that do. Genetic analysis of human populations worldwide shows how haplotypes with -21M HLA-B rarely encode the KIR ligands: Bw4(+)HLA-B and C2(+)HLA-C KIR. Thus there are two fundamental forms of HLA haplotype: one preferentially supplying CD94:NKG2A ligands, the other preferentially supplying KIR ligands. -21 HLA-B dimorphism divides the human population into three groups: M/M, M/T and T/T. Mass cytometry and assays of immune function, shows how M/M and M/T individuals have CD94:NKG2A(+) NK cells which are better educated, phenotypically more diverse and functionally more potent than those in T/T individuals. Fundamental new insights are given to genetic control of NK cell immunity and the evolution that has limited the number of NK cell receptor ligands encoded by an HLA haplotype. These finding suggest new ways to dissect the numerous clinical associations with HLA class I.

    View details for DOI 10.1126/sciimmunol.aag1672

    View details for PubMedID 27868107

  • A Distinctive Cytoplasmic Tail Contributes to Low Surface Expression and Intracellular Retention of the Patr-AL MHC Class I Molecule JOURNAL OF IMMUNOLOGY Goyos, A., Guethlein, L. A., Horowitz, A., Hilton, H. G., Gleimer, M., Brodsky, F. M., Parham, P. 2015; 195 (8): 3725-3736


    Chimpanzees have orthologs of the six fixed, functional human MHC class I genes. But, in addition, the chimpanzee has a seventh functional gene, Patr-AL, which is not polymorphic but contributes substantially to population diversity by its presence on only 50% of MHC haplotypes. The ancestral AL gene emerged long before the separation of human and chimpanzee ancestors and then subsequently and specifically lost function during human evolution, but was maintained in chimpanzees. Patr-AL is an alloantigen that participates in negative and positive selection of the T cell repertoire. The three-dimensional structure and the peptide-binding repertoire of Patr-AL and HLA-A*02 are surprisingly similar. In contrast, the expression of these two molecules is very different, as shown using specific mAbs and polyclonal Abs made against Patr-AL. Peripheral blood cells and B cell lines express low levels of Patr-AL at the cell surface. Higher levels are seen for 221-cell transfectants expressing Patr-AL, but in these cells a large majority of Patr-AL molecules are retained in the early compartments of the secretory pathway: mainly the endoplasmic reticulum, but also cis-Golgi. Replacing the cytoplasmic tail of Patr-AL with that of HLA-A*02 increased the cell-surface expression of Patr-AL substantially. Four substitutions distinguish the Patr-AL and HLA-A*02 cytoplasmic tails. Systematic mutagenesis showed that each substitution contributes changes in cell-surface expression. The combination of residues present in Patr-AL appears unique, but each individual residue is present in other primate MHC class I molecules, notably MHC-E, the most ancient of the functional human MHC class I molecules.

    View details for DOI 10.4049/jimmunol.1500397

    View details for Web of Science ID 000362968100027

    View details for PubMedID 26371256

  • Polymorphic HLA-C Receptors Balance the Functional Characteristics of KIR Haplotypes JOURNAL OF IMMUNOLOGY Hilton, H. G., Guethlein, L. A., Goyos, A., Nemat-Gorgani, N., Bushnell, D. A., Norman, P. J., Parham, P. 2015; 195 (7): 3160-3170


    The human killer cell Ig-like receptor (KIR) locus comprises two groups of KIR haplotypes, termed A and B. These are present in all human populations but with different relative frequencies, suggesting they have different functional properties that underlie their balancing selection. We studied the genomic organization and functional properties of the alleles of the inhibitory and activating HLA-C receptors encoded by KIR haplotypes. Because every HLA-C allotype functions as a ligand for KIR, the interactions between KIR and HLA-C dominate the HLA class I-mediated regulation of human NK cells. The C2 epitope is recognized by inhibitory KIR2DL1 and activating KIR2DS1, whereas the C1 epitope is recognized by inhibitory KIR2DL2 and KIR2DL3. This study shows that the KIR2DL1, KIR2DS1, and KIR2DL2/3 alleles form distinctive phylogenetic clades that associate with specific KIR haplotypes. KIR A haplotypes are characterized by KIR2DL1 alleles that encode strong inhibitory C2 receptors and KIR2DL3 alleles encoding weak inhibitory C1 receptors. In striking contrast, KIR B haplotypes are characterized by KIR2DL1 alleles that encode weak inhibitory C2 receptors and KIR2DL2 alleles encoding strong inhibitory C1 receptors. The wide-ranging properties of KIR allotypes arise from substitutions throughout the KIR molecule. Such substitutions can influence cell surface expression, as well as the avidity and specificity for HLA-C ligands. Consistent with the crucial role of inhibitory HLA-C receptors in self-recognition, as well as NK cell education and response, most KIR haplotypes have both a functional C1 and C2 receptor, despite the considerable variation that occurs in ligand recognition and surface expression.

    View details for DOI 10.4049/jimmunol.1501358

    View details for Web of Science ID 000361741200022

    View details for PubMedID 26311903

  • The production of KIR-Fc fusion proteins and their use in a multiplex HLA class I binding assay JOURNAL OF IMMUNOLOGICAL METHODS Hilton, H. G., Moesta, A. K., Guethlein, L. A., Blokhuis, J., Parham, P., Norman, P. J. 2015; 425: 79-87


    Soluble recombinant proteins that comprise the extracellular part of a surface expressed receptor attached to the Fc region of an IgG antibody have facilitated the determination of ligand specificity for an array of immune system receptors. Among such receptors is the family of killer cell immunoglobulin-like receptors (KIR) that recognize HLA class I ligands. These receptors, expressed on natural killer (NK) cells and T cells, play important roles in both immune defense and placental development in early pregnancy. Here we describe a method for the production of two domain KIR-Fc fusion proteins using baculovirus infected insect cells. This method is more scalable than traditional mammalian cell expression systems and produces efficiently folded proteins that carry posttranslational modifications found in native KIR. We also describe a multiplex binding assay using the Luminex platform that determines the avidity and specificity of two domain KIR-Fc for a panel of microbeads, each coated with one of 97 HLA class I allotypes. This assay is simple to perform, and represents a major improvement over the assays used previously, which were limited in the number of KIR and HLA class I combinations that could be assayed at any one time. The results obtained from this assay can be used to predict the response of NK cell and T cells when their KIR recognize HLA class I.

    View details for DOI 10.1016/j.jim.2015.06.012

    View details for Web of Science ID 000363819600011

  • Co-evolution of MHC class I and variable NK cell receptors in placental mammals IMMUNOLOGICAL REVIEWS Guethlein, L. A., Norman, P. J., Hilton, H. H., Parham, P. 2015; 267 (1): 259-282

    View details for DOI 10.1111/imr.12326

    View details for Web of Science ID 000360082000017

  • The Use of Recombinant Tissue Plasminogen Activator (rTPA) in The Treatment of Fibrinous Pleuropneumonia in Horses: 25 Cases (2007-2012) JOURNAL OF VETERINARY INTERNAL MEDICINE Tomlinson, J. E., Byrne, E., Pusterla, N., Magdesian, K. G., HILTON, H. G., McGorum, B., Davis, E., Schoster, A., ARROYO, L., Dunkel, B., Carslake, H., Boston, R. C., Johnson, A. L. 2015; 29 (5): 1403-1409


    Information about treatment protocols, adverse effects and outcomes with intrapleural recombinant tissue plasminogen activator (rTPA) use in horses with fibrinous pleuropneumonia is limited.Describe factors that contribute to clinical response and survival of horses treated with rTPA intrapleurally.Horses with bacterial pneumonia and fibrinous pleural effusion diagnosed by ultrasonography, that were treated with rTPA intrapleurally.Retrospective multicenter case series from 2007-2012. Signalment, history, clinical and laboratory evaluation, treatment, and outcome obtained from medical records. Regression analysis used to identify associations between treatments and outcomes.Thirty three hemithoraces were treated in 25 horses, with 55 separate treatments. Recombinant tissue plasminogen activator (375-20,000 μg/hemithorax) was administered 1-4 times. Sonographically visible reduction in fibrin mat thickness, loculations, fluid depth, or some combination of these was seen in 32/49 (65%) treatments. Response to at least 1 treatment was seen in 17/20 (85%) horses with sonographic follow-up evaluation after every treatment. Earlier onset of rTPA treatment associated with increased survival odds. No association was found between cumulative rTPA dose or number of rTPA doses and survival, development of complications, duration of hospitalization or total charges. Clinical evidence of hypocoagulability or bleeding was not observed. Eighteen horses (72%) survived to discharge.Treatment with rTPA appeared safe and resulted in variable changes in fibrin quantity and organization within the pleural space. Recombinant tissue plasminogen activator could be a useful adjunct to standard treatment of fibrinous pleuropneumonia, but optimal case selection and dosing regimen remain to be elucidated.

    View details for DOI 10.1111/jvim.13594

    View details for Web of Science ID 000360916700020

    View details for PubMedID 26256909

  • Loss and Gain of Natural Killer Cell Receptor Function in an African Hunter-Gatherer Population PLOS Genetics Hilton, H. G., Norman, P. J., Nemat-Gorgani, N., Goyos, A., Hollenbach, J. A., Henn, B. M., Gignoux, C. R., Guethlein, L. A., Parham, P. 2015
  • Co-evolution of Human Leukocyte Antigen (HLA) Class I Ligands with Killer-Cell Immunoglobulin-Like Receptors (KIR) in a Genetically Diverse Population of Sub-Saharan Africans PLOS GENETICS Norman, P. J., Hollenbach, J. A., Nemat-Gorgani, N., Guethlein, L. A., Hilton, H. G., Pando, M. J., Koram, K. A., Riley, E. M., Abi-Rached, L., Parham, P. 2013; 9 (10)


    Interactions between HLA class I molecules and killer-cell immunoglobulin-like receptors (KIR) control natural killer cell (NK) functions in immunity and reproduction. Encoded by genes on different chromosomes, these polymorphic ligands and receptors correlate highly with disease resistance and susceptibility. Although studied at low-resolution in many populations, high-resolution analysis of combinatorial diversity of HLA class I and KIR is limited to Asian and Amerindian populations with low genetic diversity. At the other end of the spectrum is the West African population investigated here: we studied 235 individuals, including 104 mother-child pairs, from the Ga-Adangbe of Ghana. This population has a rich diversity of 175 KIR variants forming 208 KIR haplotypes, and 81 HLA-A, -B and -C variants forming 190 HLA class I haplotypes. Each individual we studied has a unique compound genotype of HLA class I and KIR, forming 1-14 functional ligand-receptor interactions. Maintaining this exceptionally high polymorphism is balancing selection. The centromeric region of the KIR locus, encoding HLA-C receptors, is highly diverse whereas the telomeric region encoding Bw4-specific KIR3DL1, lacks diversity in Africans. Present in the Ga-Adangbe are high frequencies of Bw4-bearing HLA-B*53:01 and Bw4-lacking HLA-B*35:01, which otherwise are identical. Balancing selection at key residues maintains numerous HLA-B allotypes having and lacking Bw4, and also those of stronger and weaker interaction with LILRB1, a KIR-related receptor. Correspondingly, there is a balance at key residues of KIR3DL1 that modulate its level of cell-surface expression. Thus, capacity to interact with NK cells synergizes with peptide binding diversity to drive HLA-B allele frequency distribution. These features of KIR and HLA are consistent with ongoing co-evolution and selection imposed by a pathogen endemic to West Africa. Because of the prevalence of malaria in the Ga-Adangbe and previous associations of cerebral malaria with HLA-B*53:01 and KIR, Plasmodium falciparum is a candidate pathogen.

    View details for DOI 10.1371/journal.pgen.1003938

    View details for Web of Science ID 000330367200087

    View details for PubMedID 24204327

  • Direct binding to antigen-coated beads refines the specificity and cross-reactivity of four monoclonal antibodies that recognize polymorphic epitopes of HLA class I molecules TISSUE ANTIGENS HILTON, H. G., Parham, P. 2013; 81 (4): 212-220


    Monoclonal antibodies with specificity for human leukocyte antigen (HLA) class I determinants of HLA were originally characterized using serological assays in which the targets were cells expressing three to six HLA class I variants. Because of this complexity, the specificities of the antibodies were defined indirectly by correlation. Here we use a direct binding assay, in which the targets are synthetic beads coated with 1 of 111 HLA class I variants, representing the full range of HLA-A, -B and -C variation. We studied one monoclonal antibody with monomorphic specificity (W6/32) and four with polymorphic specificity (MA2.1, PA2.1, BB7.2 and BB7.1) and compared the results with those obtained previously. W6/32 reacted with all HLA class I variants. MA2.1 not only exhibits high specificity for HLA-A*02, -B*57 and -B*58, but also exhibited cross-reactivity with HLA-A*11 and -B*15:16. At low concentration (1 µg/ml), PA2.1 and BB7.2 were both specific for HLA-A*02 and -A*69, and at high concentration (50 µg/ml) exhibited significant cross-reactions with HLA-A*68, -A*23 and -A*24. BB7.1 exhibits specificity for HLA-B*07 and -B*42, as previously described, but reacts equally well with HLA-B*81, a rare allotype defined some 16 years after the description of BB7.1. The results obtained with cell-based and bead-based assays are consistent and, in combination with amino acid sequence comparison, increase understanding of the polymorphic epitopes recognized by the MA2.1, PA2.1, BB7.2 and BB7.1 antibodies. Comparison of two overlapping but distinctive bead sets from two sources gave similar results, but the overall levels of binding were significantly different. Several weaker reactions were observed with only one of the bead sets.

    View details for DOI 10.1111/tan.12095

    View details for Web of Science ID 000316628100004

    View details for PubMedID 23510417

  • Mutation at positively selected positions in the binding site for HLA-C shows that KIR2DL1 is a more refined but less adaptable NK cell receptor than KIR2DL3. Journal of immunology Hilton, H. G., Vago, L., Older Aguilar, A. M., Moesta, A. K., Graef, T., Abi-Rached, L., Norman, P. J., Guethlein, L. A., Fleischhauer, K., Parham, P. 2012; 189 (3): 1418-1430


    Through recognition of HLA class I, killer cell Ig-like receptors (KIR) modulate NK cell functions in human immunity and reproduction. Although a minority of HLA-A and -B allotypes are KIR ligands, HLA-C allotypes dominate this regulation, because they all carry either the C1 epitope recognized by KIR2DL2/3 or the C2 epitope recognized by KIR2DL1. The C1 epitope and C1-specific KIR evolved first, followed several million years later by the C2 epitope and C2-specific KIR. Strong, varying selection pressure on NK cell functions drove the diversification and divergence of hominid KIR, with six positions in the HLA class I binding site of KIR being targets for positive diversifying selection. Introducing each naturally occurring residue at these positions into KIR2DL1 and KIR2DL3 produced 38 point mutants that were tested for binding to 95 HLA- A, -B, and -C allotypes. Modulating specificity for HLA-C is position 44, whereas positions 71 and 131 control cross-reactivity with HLA-A*11:02. Dominating avidity modulation is position 70, with lesser contributions from positions 68 and 182. KIR2DL3 has lower avidity and broader specificity than KIR2DL1. Mutation could increase the avidity and change the specificity of KIR2DL3, whereas KIR2DL1 specificity was resistant to mutation, and its avidity could only be lowered. The contrasting inflexibility of KIR2DL1 and adaptability of KIR2DL3 fit with C2-specific KIR having evolved from C1-specific KIR, and not vice versa. Substitutions restricted to activating KIR all reduced the avidity of KIR2DL1 and KIR2DL3, further evidence that activating KIR function often becomes subject to selective attenuation.

    View details for DOI 10.4049/jimmunol.1100431

    View details for PubMedID 22772445

  • Review: Immunogenetics of human placentation PLACENTA Parham, P., Norman, P. J., Abi-Rached, L., HILTON, H. G., Guethlein, L. A. 2012; 33: S71-S80


    Natural killer (NK) cells are a population of lymphocytes that function in both immune defense and reproduction. Diversifying NK cell phenotype and function are interactions between NK cell receptors and major histocompatibility complex (MHC) class I ligands. As a consequence of strong and variable selection these ligand-receptor systems are polymorphic, rapidly evolving, and considerably species-specific. Counterparts to the human system of HLA class I ligands and killer cell immunoglobulin-like receptors (KIR) are present only in apes and Old World monkeys. HLA-C, the dominant ligand for human KIR and the only polymorphic HLA class I expressed by trophoblast, is further restricted to humans and great apes. Even then, the human system appears qualitatively different from that of chimpanzees, in that it has evolved a genetic balance between particular groups of receptors and ligands that favor reproductive success and other groups of receptors and ligands that have been correlated with disordered placentation. Human populations that have survived successive episodes of epidemic disease and population bottlenecks maintain a breadth of diversity for KIR and HLA class I, implying that loss of such diversity disfavors long-term survival of a human population.

    View details for DOI 10.1016/j.placenta.2011.11.020

    View details for Web of Science ID 000301868000014

    View details for PubMedID 22177321

  • Distribution of Flunixin Meglumine and Firocoxib into Aqueous Humor of Horses JOURNAL OF VETERINARY INTERNAL MEDICINE Hilton, H. G., Magdesian, K. G., Groth, A. D., Knych, H., Stanley, S. D., Hollingsworth, R. 2011; 25 (5): 1127-1133


    Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used systemically for the treatment of inflammatory ocular disease in horses. However, little information exists regarding the ocular penetration of this class of drugs in the horse.To determine the distribution of orally administered flunixin meglumine and firocoxib into the aqueous humor of horses.Fifteen healthy adult horses with no evidence of ophthalmic disease.Horses were randomly assigned to a control group and 2 treatment groups of equal sizes (n = 5). Horses assigned to the treatment groups received an NSAID (flunixin meglumine, 1.1 mg/kg PO q24h or firocoxib, 0.1 mg/kg PO q24h for 7 days). Horses in the control group received no medications. Concentrations of flunixin meglumine and firocoxib in serum and aqueous humor and prostaglandin (PG) E(2) in aqueous humor were determined on days 1, 3, and 5 and aqueous : serum ratios were calculated.Firocoxib penetrated the aqueous humor to a significantly greater extent than did flunixin meglumine at days 3 and 5. Aqueous : serum ratios were 3.59 ± 3.32 and 11.99 ± 4.62% for flunixin meglumine and firocoxib, respectively. Ocular PGE(2) concentrations showed no differences at any time point among study groups.Both flunixin meglumine and firocoxib penetrated into the aqueous humor of horses. This study suggests that orally administered firocoxib penetrates the aqueous humor better than orally administered flunixin meglumine at label dosages in the absence of ocular inflammation. Firocoxib should be considered for the treatment of inflammatory ophthalmic lesions in horses at risk for the development of adverse effects associated with nonselective NSAID administration.

    View details for DOI 10.1111/j.1939-1676.2011.0763.x

    View details for Web of Science ID 000295092800022

    View details for PubMedID 21781166

  • Expression of cyclooxygenase genes in the jejunum of horses during low-flow ischemia and reperfusion AMERICAN JOURNAL OF VETERINARY RESEARCH Hilton, H., Nieto, J. E., Moore, P. E., Harmon, F. A., Naydan, D. K., Snyder, J. R. 2011; 72 (5): 681-686


    To determine expression of cyclooxygenase (COX) genes 1 and 2 (also called prostaglandin-endoperoxide synthases 1 and 2) and stability of housekeeping gene expression during low-flow ischemia and reperfusion in the jejunum of horses.5 healthy adult horses.Horses were anesthetized, and two 30-cm segments of jejunum were surgically exteriorized. Blood flow was maintained at baseline (untreated) values in 1 (control) segment and was decreased to 20% of baseline (low-flow ischemia) for 75 minutes, followed by 75 minutes of reperfusion, in the other (experimental) segment. Biopsy samples were collected from experimental segments at baseline (T0), after 75 minutes of ischemia (T1), and after 75 minutes of reperfusion (T2); samples were collected from control segments at T0 and T2. Horses were euthanized 24 hours after induction of ischemia (T3), and additional samples were collected. Samples were evaluated histologically. Total RNA was extracted; expression of COX genes and stability of 8 housekeeping genes were determined via quantitative real-time PCR assays.COX-1 and COX-2 genes were constitutively expressed in baseline samples. Low-flow ischemia resulted in significant upregulation of COX-2 gene expression at each subsequent time point, compared with baseline values. The most stably expressed reference genes were ?-actin and hypoxanthine phosphoribosyltransferase, whereas glyceraldehyde 3-phosphate dehydrogenase and ?-2 microglobulin were the least stably expressed.Low-flow ischemia resulted in upregulation of COX-2 gene expression in the jejunum of horses. Housekeeping genes traditionally used as internal standards may not be stable in this tissue during arterial low-flow ischemia and reperfusion.

    View details for Web of Science ID 000290191300013

    View details for PubMedID 21529221

  • Repetitive Stimulation of the Common Peroneal Nerve as a Diagnostic Aid for Botulism in Foals JOURNAL OF VETERINARY INTERNAL MEDICINE Aleman, M., Williams, D. C., JORGE, N. E., Magdesian, K. G., Brosnan, R. J., Feary, D. J., HILTON, H. G., Kozikowski, T. A., Higgins, J. K., Madigan, J. E., LeCouteur, R. A. 2011; 25 (2): 365-372


    Botulism is a potentially fatal paralytic disorder for which definitive diagnosis is difficult. Objectives: To determine if repetitive stimulation of the common peroneal nerve will aid in the diagnosis of botulism in foals.Four control and 3 affected foals.Validation of the test in healthy foals for its comparison in foals with suspected botulism. Controls were anesthetized and affected foals were sedated to avoid risks of anesthesia. The common peroneal nerve was chosen for its superficial location and easy access. Stimulating electrodes were placed along the common peroneal nerve. For recording, the active and reference electrodes were positioned over the midpoint and distal end of the extensor digitorum longus muscle, respectively. Repeated supramaximal stimulation of the nerve was performed utilizing a range of frequencies (1-50 Hz). Data analysis consisted of measuring the amplitude and area under the curve for each M wave and converting these values into percentages of decrement or increment based on the comparison of subsequent potentials to the initial one (baseline) within each set.A decremental response was seen at all frequencies in control foals. Decremental responses also were observed in affected foals at low frequencies. An incremental response was seen in all affected foals at 50 Hz.Decreased baseline M wave amplitudes with incremental responses at high rates are supportive of botulism. Repetitive nerve stimulation is a safe, simple, fast, and noninvasive technique that can aid in the diagnosis of suspected botulism in foals.

    View details for DOI 10.1111/j.1939-1676.2011.0682.x

    View details for Web of Science ID 000288073800026

    View details for PubMedID 21314725

  • Standing Lateral Thoracotomy in Horses: Indications, Complications, and Outcomes VETERINARY SURGERY Hilton, H., Aleman, M., Madigan, J., Nieto, J. 2010; 39 (7): 847-855


    To describe the indications for, complications arising from, and outcome of horses that had standing lateral thoracotomy for pleural or pericardial disease.Case series.Horses (n=16).Medical records (January 1990-December 2008) of sedated standing horses that had lateral thoracotomy were reviewed. Clinical and surgical findings, perioperative and short-term complications were recorded. Long-term (>6 months) outcome was determined through telephone conversations with owners and veterinarians.Mean (±SD) horse age was 6.6±5.3 years (range, 1-15 years). Thoracotomy was most commonly for treatment of recurrent or chronic pleural infection (94%). Anaerobic bacteria were frequently isolated from pleural effusion associated with pleuropneumonia (63%). Right lateral intercostal thoracotomy was performed in 13 horses (82%); intercostal muscle myectomy in 5 horses; and rib resection in 1. Perioperative complications were hemipneumothorax (2 horses) and short-term complications included cellulitis and abscessation of the thoracotomy site (6 horses). Fourteen (88%) horses survived to discharge and 46% of horses that survived returned to their previous level of athletic activity.Lateral thoracotomy is well tolerated by standing sedated horses with minimal perioperative and short-term complications.Standing lateral thoracotomy should be considered for the treatment of complicated pleuropneumonia in horses.

    View details for DOI 10.1111/j.1532-950X.2010.00713.x

    View details for Web of Science ID 000282380400009

    View details for PubMedID 20673275

  • Evaluation of the humoral immune response and fecal shedding in weanling foals following oral and intra-rectal administration of an avirulent live vaccine of Lawsonia intracellularis VETERINARY JOURNAL Pusterla, N., Hilton, H., Wattanaphansak, S., Collier, J. R., Mapes, S. M., Stenbom, R. M., Gebhart, C. 2009; 182 (3): 458-462


    Equine proliferative enteropathy (EPE) caused by Lawsonia intracellularis has recently been recognized as an emerging disease in foals. Whilst the clinical entity, diagnostic evaluation and treatment of affected foals have been well established and described, preventive measures for EPE have remained largely unaddressed. The objectives of this study were to investigate the humoral immune response and onset and duration of fecal shedding in foals after oral and intra-rectal administration of a modified-live vaccine of L. intracellularis. Foals were vaccinated twice, 3 weeks apart, via oral drenching after pre-medication with a proton-pump inhibitor (omeprazole; group 1), intra-rectally (group 2) or orally without any pre-medication (group 3). The health status of the foals was monitored daily, with feces and serum collected at regular intervals for Polymerase Chain Reaction (PCR) and serology. All foals remained healthy and no adverse vaccine reactions were observed. Fecal shedding lasted from 1 to 12 days and was mainly detected in foals receiving the intra-rectal vaccine 11-15 days following the first vaccine administration. Serological responses were measured in the majority of the vaccinated foals. All foals vaccinated intra-rectally seroconverted after the first vaccine, compared to 50% and 0% of foals in groups 1 and 3, respectively. Pre-medication with omeprazole prior to oral vaccination in group 1 foals led to an earlier and stronger detectable humoral response compared to non pre-medicated foals.

    View details for DOI 10.1016/j.tvjl.2008.08.016

    View details for Web of Science ID 000272760000015

    View details for PubMedID 18835201

  • Intrapleural fibrinolytic therapy in the management of septic pleuropneumonia in a horse VETERINARY RECORD Hilton, H., Pusterla, N. 2009; 164 (18): 558-559

    View details for Web of Science ID 000266119500012

    View details for PubMedID 19411687

  • Successful Treatment of Invasive Pulmonary Aspergillosis in a Neonatal Foal JOURNAL OF VETERINARY INTERNAL MEDICINE Hilton, H., Galuppo, L., Puchalski, S. M., Johnson, L., Robinson, K., Mohr, F. C., MAHER, O., Pusterla, N. 2009; 23 (2): 375-378


    Equine temporohyoid osteoarthropathy is characterized by progressive osseous proliferation of the temporohyoid articulation and surrounding structures. The diagnosis has generally been made using radiography and endoscopy of the guttural pouch. Recently, computed tomography (CT) has been used in the diagnosis of temporohyoid osteoarthropathy. This study was performed to determine the CT imaging characteristics of temporohyoid osteoarthropathy and to compare these to radiographic and endoscopic findings. CT scans from 16 horses with a final diagnosis of temporohyoid osteoarthropathy were reviewed. Five horses that had undergone CT scan for reasons other than temporohyoid osteoarthropathy were included as controls. Qualitative and quantitative data were used to describe the magnitude of the CT findings. Osseous proliferation of the stylohyoid bone and temporohyoid articulation was found to be a consistent feature of temporohyoid osteoarthropathy. Thickening of the ceratohyoid bone and proliferation of its articulation with the stylohyoid bone was frequently identified and this finding may have surgical implications. Horses with neurologic deficits had increased stylohyoid width that was significantly different than the subclinically affected side. CT evaluation also allowed the identification of subclinical bilateral disease in horses thought to be unilaterally affected based on clinical examination.

    View details for DOI 10.1111/j.1740-8261.2009.01508.x

    View details for Web of Science ID 000263760700003

    View details for PubMedID 19400460

  • Evaluation of four topical preparations for the treatment of cannon hyperkeratosis in a horse VETERINARY DERMATOLOGY Hilton, H., Affolter, V. K., White, S. D. 2008; 19 (6): 385-390


    The response to treatment with four topical preparations was evaluated in an 11-year-old Morgan horse mare with histologically confirmed quadrilateral cannon hyperkeratosis. Each limb was treated for 30 days with 0.1% tacrolimus ointment, 0.1% adapalene gel, 0.2% phytosphingosine spray or a water-based emollient. Response to treatment was evaluated both histologically and visually. A water-based emollient and 0.1% tacrolimus ointment produced encouraging clinical responses. Pre-treatment histopathology identified marked, mostly compact, hyperkeratosis and follicular hyperkeratosis, most prominent in the infundibular area. Following treatment, histopathology identified a mild reduction in follicular keratin production and stratum corneum thickness.

    View details for DOI 10.1111/j.1365-3164.2008.00715.x

    View details for Web of Science ID 000261334400008

    View details for PubMedID 19055613

  • Rhabdomyolysis associated with Anaplasma phagocytophilum infection in a horse JOURNAL OF VETERINARY INTERNAL MEDICINE Hilton, H., Madigan, J. E., Aleman, M. 2008; 22 (4): 1061-1064
  • Hand-assisted laparoscopic nephrectomy in a standing horse for the management of renal cell carcinoma EQUINE VETERINARY EDUCATION HILTON, H. G., Aleman, M., MAHER, O., Peterson, T. S., Whitcomb, M. B., Galuppo, L. D. 2008; 20 (5): 239-244
  • Ultrasound-guided balloon thrombectomy for treatment of aorto-iliac-femoral thrombosis in a horse JOURNAL OF VETERINARY INTERNAL MEDICINE Hilton, H., Aleman, M., Textor, J., Nieto, J., Pevec, W. 2008; 22 (3): 679-683
  • Hand-assisted laparoscopic nephrectomy in a standing horse for the management of renal cell carcinoma Equine Veterinary Education Hilton HG, Aleman M, Maher O, Peterson TS, Whitcomb MB, Galuppo LD 2008; 20 (5): 239-244