Dirofilaria immitis Identified in Galapagos Sea Lions (Zalophus wollebaeki): A Wildlife Health and Conservation Concern.

The Galapagos sea lion (Zalophus wollebaeki), an endemic and endangered pinniped, faces an increasing threat due to infectious diseases related to domestic animals. Dirofilaria immitis, the parasite responsible for canine heartworm disease, is one such threat, as canine infections on the archipelago have been documented. We used a canine heartworm antigen test kit to analyze the blood from 25 juvenile Galapagos sea lions for D. immitis. Two (8%) sea lions tested positive for D. immitis antigen. Using morphologic and genetic assessments, we evaluated 20 filarial-like worms collected from within the heart of an adult male Galapagos sea lion during a previous routine postmortem examination. The intracardiac worms were morphologically consistent with adult D. immitis, and sequence analysis of targeted PCR amplicons confirmed their identity. This is the first report of D. immitis infection in Galapagos sea lions, which could become a major health problem for these pinnipeds. Further studies are necessary to confirm the level of threat from this parasite; however, widespread adoption of routine heartworm testing, prevention, and treatment in the canine population, and the control of mosquitos, could potentially reduce the disease impact on this endangered pinniped species.

Assessment of systemic AAV-microdystrophin gene therapy in the GRMD model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by the absence of dystrophin, a membrane-stabilizing protein encoded by the DMD gene. Although mouse models of DMD provide insight into the potential of a corrective therapy, data from genetically homologous large animals, such as the dystrophin-deficient golden retriever muscular dystrophy (GRMD) model, may more readily translate to humans. To evaluate the clinical translatability of an adeno-associated virus serotype 9 vector (AAV9)-microdystrophin (µDys5) construct, we performed a blinded, placebo-controlled study in which 12 GRMD dogs were divided among four dose groups [control, 1 × 1013 vector genomes per kilogram (vg/kg), 1 × 1014 vg/kg, and 2 × 1014 vg/kg; n = 3 each], treated intravenously at 3 months of age with a canine codon-optimized microdystrophin construct, rAAV9-CK8e-c-µDys5, and followed for 90 days after dosing. All dogs received prednisone (1 milligram/kilogram) for a total of 5 weeks from day -7 through day 28. We observed dose-dependent increases in tissue vector genome copy numbers; µDys5 protein in multiple appendicular muscles, the diaphragm, and heart; limb and respiratory muscle functional improvement; and reduction of histopathologic lesions. As expected, given that a truncated dystrophin protein was generated, phenotypic test results and histopathologic lesions did not fully normalize. All administrations were well tolerated, and adverse events were not seen. These data suggest that systemically administered AAV-microdystrophin may be dosed safely and could provide therapeutic benefit for patients with DMD.

Epigenetic upregulation of Schlafen11 renders WNT- and SHH-activated medulloblastomas sensitive to cisplatin.

BACKGROUND: Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, survival markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response to DNA damaging agents in various cancers, to be one of the top prognostic markers in medulloblastomas. Hence, we explored the expression and functions of SLFN11 in medulloblastoma. METHODS: SLFN11 expression for each subgroup was assessed by immunohistochemistry in 98 medulloblastoma patient samples and by analyzing transcriptomic databases. We genetically or epigenetically modulated SLFN11 expression in medulloblastoma cell lines and determined cytotoxic response to the DNA damaging agents cisplatin and topoisomerase I inhibitor SN-38 in vitro and in vivo. RESULTS: High SLFN11 expressing cases exhibited significantly longer survival than low expressing cases. SLFN11 was highly expressed in the WNT-activated subgroup and in a proportion of the SHH-activated subgroup. While WNT activation was not a direct cause of the high expression of SLFN11, a specific hypomethylation locus on the SLFN11 promoter was significantly correlated with high SLFN11 expression. Overexpression or deletion of SLFN11 made medulloblastoma cells sensitive and resistant to cisplatin and SN-38, respectively. Pharmacological upregulation of SLFN11 by the brain-penetrant histone deacetylase-inhibitor RG2833 markedly increased sensitivity to cisplatin and SN-38 in SLFN11-negative medulloblastoma cells. Intracranial xenograft studies also showed marked sensitivity to cisplatin by SLFN11-overexpression in medulloblastoma cells. CONCLUSIONS: High SLFN11 expression is one factor which renders favorable outcomes in WNT-activated and a subset of SHH-activated medulloblastoma possibly through enhancing response to cisplatin.

Endoscopy Training in Small Animal Internal Medicine: A Survey of Residency Training Programs in North America.

Competency in multiple endoscopic techniques is a major goal of small animal internal medicine (SAIM) residency programs. Training relies predominantly on mentored supervision of procedures performed on patients. Supplementation of this apprenticeship model with classroom sessions and hands-on laboratories can be advantageous to trainees and patients. Few veterinary resources describe supplemental training options, and no single source exists for mentors to consult for program development. The purpose of this study was to describe the supplemental training opportunities currently available to SAIM residents at academic hospitals in the US and Canada and to compare their timing during the residency, resident and faculty time commitment, and perceived helpfulness. Data were collected by an electronic survey distributed to one faculty member per institution. The response rate was 80% (24/30). Most programs (22/24; 92%) offered some form of supplemental training, including classroom sessions (9/24) and hands-on laboratories using physical models (7/24), virtual reality simulators (2/24), and cadaver (2/24) and anesthetized (2/24) dogs. Fifteen programs provided residents with the opportunity to attend external endoscopy workshops. Only three programs required any training prior to residents performing procedures on patients. There was considerable variability in training between programs, precluding statistical comparisons. The survey identified topics for classroom sessions and several inexpensive physical models, rated very or extremely helpful, that would be suitable for programs with limited budgets. A human-based virtual reality simulator was also rated highly by two programs. Comprehensive, external workshops evoked numerous positive comments with perceived value ranging from somewhat to extremely helpful.

RpoN/Sfa2-dependent activation of the Pseudomonas aeruginosa H2-T6SS and its cognate arsenal of antibacterial toxins.

Pseudomonas aeruginosa uses three type six secretion systems (H1-, H2- and H3-T6SS) to manipulate its environment, subvert host cells and for microbial competition. These T6SS machines are loaded with a variety of effectors/toxins, many being associated with a specific VgrG. How P. aeruginosa transcriptionally coordinates the main T6SS clusters and the multiple vgrG islands spread through the genome is unknown. Here we show an unprecedented level of control with RsmA repressing most known T6SS-related genes. Moreover, each of the H2- and H3-T6SS clusters encodes a sigma factor activator (SFA) protein called, Sfa2 and Sfa3, respectively. SFA proteins are enhancer binding proteins necessary for the sigma factor RpoN. Using a combination of RNA-seq, ChIP-seq and molecular biology approaches, we demonstrate that RpoN coordinates the T6SSs of P. aeruginosa by activating the H2-T6SS but repressing the H1- and H3-T6SS. Furthermore, RpoN and Sfa2 control the expression of the H2-T6SS-linked VgrGs and their effector arsenal to enable very effective interbacterial killing. Sfa2 is specific as Sfa3 from the H3-T6SS cannot complement loss of Sfa2. Our study further delineates the regulatory mechanisms that modulate the deployment of an arsenal of T6SS effectors likely enabling P. aeruginosa to adapt to a range of environmental conditions.

Factors associated with clinical interpretation of tracheal wash fluid from dogs with respiratory disease: 281 cases (2012-2017).

BACKGROUND: Clinicians face several dilemmas regarding tracheal washes (TWs) for the diagnosis of respiratory disease, including method and prediction of bacterial growth from cytology results. OBJECTIVE: To compare cytology and culture of endotracheal and transtracheal washes and identify factors associated with discordancy and bacterial growth. ANIMALS: Two hundred forty-five dogs with respiratory disease. METHODS: Retrospective study. Tracheal wash submissions were included if cellularity was sufficient for cytologic interpretation and aerobic cultures were performed. Collection technique, cytology, bacterial growth, and antibiotic history were analyzed. RESULTS: Fewer transtracheal specimens (9/144, 6.3%) were excluded for hypocellularity than endotracheal (28/174, 16.1%); otherwise, results were similar and were combined. Of 281 specimens with cellularity sufficient for interpretation, 97 (34.5%) had bacteria on cytology and 191 (68.0%) had bacterial growth. Cytology positive/culture negative discordancy was uncommon (8/97, 8%). Cytology negative/culture positive discordancy was frequent (102/184, 55.4%), but occurred less often (28/184, 14.2%) when only 1+ growth or greater was considered positive. Oropharyngeal contamination was associated with bacterial growth, but not discordancy. No association was found between antibiotic administration and bacterial growth. CONCLUSIONS AND CLINICAL IMPORTANCE: Endotracheal wash fluid, in particular, should be screened for gross mucus or turbidity to maximize the likelihood of an adequate specimen. Otherwise, endotracheal and transtracheal specimens were similar. Presence of bacteria on cytology was a good predictor of any growth, while their absence was a good predictor of the absence of growth of 1+ or more. Recent antibiotic usage should not discourage TW culture if there is compelling reason to avoid delay.

Expiratory dysfunction in young dogs with golden retriever muscular dystrophy.

Respiratory disease is a leading cause of morbidity in people with Duchenne muscular dystrophy and also occurs in the golden retriever muscular dystrophy (GRMD) model. We have previously shown that adult GRMD dogs have elevated expiratory flow as measured non-invasively during tidal breathing. This abnormality likely results from increased chest and diaphragmatic recoil associated with fibrosis and remodeling. Treatments must reverse pathologic effects on the diaphragm and other respiratory muscles to maximally reduce disease morbidity and mortality. Here, we extended our work in adults to younger GRMD dogs to define parameters that would be helpful in preclinical trials. Tidal breathing spirometry and respiratory inductance plethysmography were performed in GRMD dogs at approximately 3 and 6 months of age, corresponding to approximately 5-10 years in DMD, when clinical trials are often conducted. Expiratory flows were markedly elevated in GRMD versus normal dogs at 6 months. Values increased in GRMD dogs between 3 and 6 months, providing a 3-month window to assess treatment efficacy. These changes in breathing mechanics have not been previously identified at such an early age. Expiratory flow measured during tidal breathing of unsedated young GRMD dogs could be a valuable marker of respiratory mechanics during preclinical trials.

Evaluation of a Human Virtual-Reality Endoscopy Trainer for Teaching Early Endoscopy Skills to Veterinarians.

Competency in flexible endoscopy is a major goal of small animal internal medicine residency training programs. Hands-on laboratories to teach entry-level skills have traditionally used anesthetized laboratory dogs (live dog laboratory [LDL]). Virtual-reality endoscopy trainers (VRET) are used for this purpose in human medicine with the clear benefits of avoiding live animal use, decreasing trainee stress, and allowing repeated, independent training sessions. However, there are currently no commercially available veterinary endoscopy simulators. The purpose of the study was to determine whether a human VRET can be a reasonable alternative to a LDL for teaching early veterinary endoscopy skills. Twelve veterinarians with limited or no endoscopy experience underwent training with a VRET (n = 6) or a LDL (n = 6), performed two recorded esophagogastroduodenoscopies (EGD) on anesthetized dogs for evaluation purposes (outcomes laboratory), and then underwent training with the alternative method. Participants completed questionnaires before any training and following each training session. No significant differences were found between training methods based on: measured parameters from the outcomes laboratory, including duration of time to perform EGD; evaluators' assessment of skills; and, assessment of skills through blinded review of the esophageal portion of EGD recordings. The VRET was less stressful for participants than the LDL (p = .02). All participants found that the VRET was a useful and acceptable alternative to the LDL for training of early endoscopy skills. Based on this limited study, VRET can serve as a reasonable alternative to LDL for teaching endoscopy skills to veterinarians.

Methotrexate Administration to Patients With Presumed Ectopic Pregnancy Leads to Methotrexate Exposure of Intrauterine Pregnancies.

OBJECTIVE: To report clinical experience with methotrexate (MTX) treatment for suspected but not definite ectopic pregnancy (EP). METHODS: This was a retrospective cohort study. All patients treated with MTX for presumed EP between 2000 and 2016 were included. Demographic, clinical, sonographic, and outcome data were collected and analyzed. RESULTS: A total of 820 patients were treated with MTX, 692 (84.4%) of which were lacking definitive features of EP; 155 (22.4%) failed to follow up until complete resolution and were excluded. Retrospective sonographic categorization was applied to 537 patients; of those patients, 393 (73.2%) were categorized as probable EPs, 136 (25.3%) pregnancies of unknown location (PULs), and 8 (1.5%) probable intrauterine pregnancies (IUPs). Sixteen were eventually diagnosed with IUP: 6 from the probable EPs, 9 from the PULs, and 1 from the probable IUP group. Patients with final diagnosis of IUP had higher values of ß-human chorionic gonadotropin as well as lower prevalence of adnexal mass (38% versus 74%; P = .003), higher prevalence of intracavitary fluid (44% versus 9%; P = .0004) and thicker endometrium (17.1 ± 11.8 versus 9.7 ± 5.6; P = .04). None of the sonographic parameters were able to distinguish patients with IUP. One patient of the 16 with IUP was diagnosed with a viable pregnancy, and 7 additional patients had a possible viable pregnancy. None of them elected to continue the pregnancy. CONCLUSIONS: Most patients with suspected EP who are eligible for medical treatment lack definitive sonographic features of EP. Treatment with MTX in such cases should be delayed, as clinically reasonable, to improve the diagnosis and prevent inadvertent administration of MTX to patients with a viable IUP.

Hysteroscopic morcellation: review of the manufacturer and user facility device experience (MAUDE) database.

STUDY OBJECTIVE: To investigate the number and type of adverse events associated with hysteroscopic morcellation of intrauterine disease. DESIGN: Systematic review of Manufacturer and User Device Experience (MAUDE) database from 2005 to June 2014 (Canadian Task Force classification III). SETTING N/A PATIENTS: Women undergoing hysteroscopic surgery for removal of intrauterine polyps or myomas with use of a reciprocating morcellator. INTERVENTIONS: The MAUDE database was searched for the key words "Hysteroscope," "Hysteroscopic reciprocating morcellator," "Interlace," "MyoSure," "Smith & Nephew," and "TRUCLEAR," to identify reported incidences of device malfunction, injury, or death. A total of 119 adverse events were analyzed. Reports were reviewed individually and categorized by date of occurrence, type of morcellation device, type of complication, and a brief description. Each company was contacted to provide an estimate of the number of procedures performed or units sold to date. MEASUREMENTS AND MAIN RESULTS: From 2005 to June 2014, 119 adverse events were reported to the MAUDE database. On the basis of severity, adverse events were categorized as major or minor complications. Major events included intubation/admission to an intensive care unit (n = 14), bowel damage (n = 12), hysterectomy (n = 6), and death (n = 2). Minor events included uterine perforation requiring no other treatment (n = 29), device failure (n = 25), uncomplicated fluid overload (n = 19), postoperative bleeding controlled using noninvasive measures (n = 6), and pelvic infection (n = 4). These events were then categorized according to manufacturer. The number of adverse events reported to the MAUDE database was divided by the total units sold as a surrogate for the estimated number of procedures performed. Understanding the limitation of the numbers used as a numerator and denominator, we concluded that adverse events complicated hysteroscopic morcellation in <0.1% cases. CONCLUSIONS: The suction-based, mechanical energy, rotating tubular cutting system was developed to overcome adverse events that occur during traditional resectoscopy. On the basis of acknowledged limited information from the MAUDE database, it seems that life-threatening complications such as fluid overload, uterine perforation, and bleeding do occur with hysteroscopic morcellation but less frequently than with traditional electrocautery.

In vivo oocyte retrieval in a young woman with ovarian cancer.

BACKGROUND: Oocyte cryopreservation is rapidly becoming an option for single women recently diagnosed with cancer who wish to preserve their fertility. We describe oocyte retrieval in young women with invasive ovarian cancer. CASE: A 23-year-old nulliparous woman had recurrence of a mixed ovarian germ cell tumor after unilateral oophorectomy. Concern of involvement of her remaining ovary and need for postoperative chemotherapy prompted decision to perform controlled ovarian hyperstimulation followed by intraoperative in vivo oocyte retrieval. CONCLUSION: Oocyte cryopreservation through controlled ovarian hyperstimulation leading up to oocyte retrieval at the time of surgical staging for gynecologic malignancies can be coordinated in a timely fashion, affording fertility preservation without significant treatment delay. Greater awareness of this capability may prompt extension of oocyte cryopreservation services to all potential candidates and help mobilize the establishment of referral pathways and multidisciplinary teams of general gynecologists, gynecologic oncologists, and reproductive endocrinologists.

Vaginal erosion of an abdominal cerclage 7 years after laparoscopic placement.

BACKGROUND: With advances in minimally invasive approaches, laparoscopically placed abdominal cerclages are becoming more common. Although not meant to replace vaginally placed cerclages, one potential advantage is reuse in subsequent pregnancies. Their lifespan, potential remote complications, and long-term management remain unexplored. CASE: Reported is a patient with a laparoscopic abdominal cerclage who carried two pregnancies to term. Seven years after initial placement, 3 years after her last delivery, an abscess developed at the cerclage site. Erosion and subsequent expulsion of the cerclage followed. CONCLUSION: The longevity of abdominally placed cerclages is unknown. Placement in the peritoneal cavity reduces suture migration risk, yet tissue degradation may limit the lifespan. Patients with retained abdominal cerclages after completion of childbearing are at risk for remote complications. Closer long-term surveillance on an individual level and a collective level is warranted.

Respiratory dysfunction in unsedated dogs with golden retriever muscular dystrophy.

Golden retriever muscular dystrophy (GRMD) is a well-established model of Duchenne muscular dystrophy. The value of this model would be greatly enhanced with practical tools to monitor progression of respiratory dysfunction during treatment trials. Arterial blood gas analysis, tidal breathing spirometry, and respiratory inductance plethysmography (RIP) were performed to determine if quantifiable abnormalities could be identified in unsedated, untrained, GRMD dogs. Results from 11 dogs with a mild phenotype of GRMD and 11 age-matched carriers were compared. Arterial blood gas analysis was successfully performed in all dogs, spirometry in 21 of 22 (95%) dogs, and RIP in 18 of 20 (90%) dogs. Partial pressure of carbon dioxide and bicarbonate concentration were higher in GRMD dogs. Tidal breathing peak expiratory flows were markedly higher in GRMD dogs. Abnormal abdominal motion was present in 7 of 10 (70%) GRMD dogs. Each technique provided objective, quantifiable measures that will be useful for monitoring respiratory function in GRMD dogs during clinical trials while avoiding the influence of sedation on results. Increased expiratory flows and the pattern of abdominal breathing are novel findings, not reported in people with Duchenne muscular dystrophy, and might be a consequence of hyperinflation.

Cervical lung lobe herniation in dogs identified by fluoroscopy.

This study aimed to determine the frequency of cervical lung lobe herniation (CLLH) in dogs evaluated fluoroscopically and to identify associated characteristics. Reports of diagnostic procedures and patient summaries from 2008 to 2010 were reviewed retrospectively. Signalment, body weight, duration of cough, presence of heart murmur and airway collapse, and radiographic findings were compared between dogs with and without CLLH. Of the 121 dogs that were examined, CLLH occurred in 85 (70%). The extra-thoracic trachea kinked during herniation in 33 (39%) dogs with CLLH. Collapse of the intra-thoracic trachea (assessed fluoroscopically or bronchoscopically) and collapse of major bronchi (assessed fluoroscopically) were strongly associated with CLLH. Although redundant dorsal tracheal membrane on radiographs was associated with CLLH, extra-thoracic tracheal collapse, assessed fluoroscopically or bronchoscopically, was not. No other associations were found. Cervical lung lobe herniation was present in most dogs evaluated during cough and was associated with intra-thoracic large airway collapse, but not duration of cough.

Herniation du lobe pulmonaire cervical chez les chiens identifié par fluoroscopie. Cette étude a visé à déterminer la fréquence de l'herniation du lobe pulmonaire cervical (HLPC) chez les chiens évalués par fluoroscopie et à identifier les caractéristiques connexes. Des rapports des procédures diagnostiques et des sommaires des patients de 2008 à 2010 ont été examinés rétrospectivement. Le signalement, le poids corporel, la durée de la toux, la présence d'un souffle cardiaque et de l'affaissement des voies aériennes ainsi que les constatations radiographiques ont été comparés entre les chiens avec et sans HLPC. Parmi les 121 chiens qui ont été examinés, HLPC s'est produite dans 85 cas (70 %). La trachée extra-thoracique s'est tordue durant l'herniation chez 33 (39 %) des chiens atteints de HLPC. L'affaissement de la trachée intra-thoracique (évalué par fluoroscopie ou bronchoscopie) et l'affaissement des bronches majeures (évalué par fluoroscopie) étaient fortement associés à HLPC. Même si la membrane trachéale dorsale redondante sur les radiographies était associée à HLPC, l'affaissement trachéal extra-thoracique, évalué par fluoroscopie ou bronchoscopie, ne l'était pas. Aucune autre association n'a été trouvée. L'herniation du lobe pulmonaire cervical était présente chez la plupart des chiens évalués durant la toux et était associée à l'affaissement des grandes voies aériennes intra-thoraciques, mais non à la durée de la toux.(Traduit par Isabelle Vallières).

A myristoylated alanine-rich C kinase substrate-related peptide suppresses cytokine mRNA and protein expression in LPS-activated canine neutrophils.

Myristoylated alanine-rich C kinase substrate (MARCKS) is a ubiquitously expressed protein kinase C substrate that has emerged as a potential therapeutic target for the amelioration of mucin secretion and inflammation in patients with chronic obstructive pulmonary disease. MARCKS also plays a key role in regulating the adhesion, migration, and degranulation of neutrophils. Moreover, given its biological role in epithelial and immune cells, we hypothesized that MARCKS may play an integral role in cytokine secretion by neutrophils. Because the amino terminus of MARCKS is highly conserved across vertebrate species, we successfully applied the well-characterized human MARCKS inhibitory peptide, myristoylated N-terminal sequence (MANS), to attenuate the function of MARCKS in isolated canine neutrophils. Pretreatment of canine neutrophils with MANS peptide significantly reduced both mRNA and protein expression in a broad range of LPS-induced cytokines, including IL-8, a chemokine (C-X-C motif) ligand-1 orthologue, and TNF-α, in comparison with untreated cells or those treated with a control peptide. This reduction in cytokine expression was observed even when neutrophils were treated with MANS 2 hours after LPS exposure. The observed reduction in cytokine secretion was not attributable to protein retention or cell death, but was associated with reduced cytokine transcript synthesis. These observations identify MARCKS protein as a promising therapeutic target in the treatment of inflammatory diseases or syndromes attributed to neutrophil influx and inflammatory cytokine production, such as sepsis, acute lung injury, and acute respiratory distress syndrome.

Effect of a combined aspiration and core biopsy technique on quality of core bone marrow specimens.

For cases requiring both a bone marrow aspirate and core biopsy, using the same needle and site (i.e., a combined technique) can decrease time, expense, and discomfort compared with the independent (direct) collection of each specimen. The benefits of the combined approach should not be achieved at the expense of specimen quality. In this study, core bone marrow samples obtained from the proximal humerus of 26 dogs by a combined technique immediately posteuthanasia were compared with core samples obtained directly from the opposite humerus. Both core samples from each dog were compared for relative overall quality. Biopsies were unsuccessful in four dogs using the combined technique and in one dog by the direct technique. Marrow length was shorter and hemorrhage artifact was more common using the combined technique. There were no differences in cellularity, megakaryocyte count, the myeloid/erythroid ratio (M/E ratio), iron stores, or diagnostic quality. Direct core biopsy remains the ideal technique; however, the degree of compromise was small in the samples obtained from the combined technique. For clinical patients, the advantages of the combined technique must continue to be weighed against potential loss of diagnostic sensitivity.

Inflammatory polyps of the nasal turbinates of cats: an argument for designation as feline mesenchymal nasal hamartoma.

Inflammatory polyps of the nasal turbinates (IPNT) in cats are benign growths that are histologically distinct from feline nasopharyngeal polyps. Most cats with IPNT are presented at less than 1 year of age with sneezing, noisy breathing and epistaxis, but without mucoid or mucopurulent nasal discharge. Histologically, IPNT are characterised by the presence of woven bone as part of the proliferating stroma and erythrocyte-filled spaces. These unique histological features are analogous to nasal hamartomas (NH) of children, specifically chondromesenchymal hamartoma (NCMH) and sinonasal fibro-osseous hamartoma (SFOH), which also result in signs of nasal obstruction, sneezing and epistaxis. In our study, clinical and histopathological features in five cats with IPNT were compared with published descriptions of NH in children. We conclude that the terminology 'feline mesenchymal nasal hamartoma' provides a more accurate description of the disease currently termed IPNT, and has the added advantage of being consistent with its human counterpart.

Failure of nebulized irritant, acidic, or hypotonic solutions or external mechanical stimulation of the trachea to consistently induce coughing in healthy, awake dogs.

A useful approach for evaluating antitussive drugs in humans is to determine the sensitivity of the cough reflex to a standard challenge. The purpose of this study was to determine if methods used to induce coughing in humans would be effective when used on awake, untrained, healthy dogs for future application in therapeutic trials involving dogs with spontaneous disease. Methods tested were: mechanically stimulating the trachea by digital compression as well as by vibration from an electric shaver, neck massager, and palm sander (11 dogs), and administering nebulized irritant (3000 µM capsaicin), acidic (1 M citric acid), and hypotonic (deionized water) solutions using face masks (4 dogs). The threshold for success was defined as induction of at least 2 moderate or strong coughs in at least 75% of the dogs. None of the methods tested was successful. Digital compression induced soft (n = 2) or moderate (n = 1) coughing in 3 of 11 dogs tested. Nebulization of citric acid induced 1 soft cough in 1 of 4 dogs. It was concluded that coughing cannot be successfully induced in awake, healthy dogs using methods that are successful in humans. Other strategies must be developed so that cough sensitivity can be objectively and non-invasively measured in dogs for clinical research purposes.

Naturally occurring mutations in the canine CFTR gene.

Naturally occurring cystic fibrosis (CF)-causing mutations in the CFTR gene have not been identified in any nonhuman animal species. Since domestic dogs are known to develop medical conditions associated with atypical CF in humans (e.g., bronchiectasis and pancreatitis), we hypothesized that dogs with these disorders likely have a higher expression rate of CFTR mutations than the at-large population. Temporal temperature-gradient gel electrophoresis (TTGE) was used to screen canine CFTR in 400 animals: 203 dogs diagnosed with pancreatitis, 23 dogs diagnosed with bronchiectasis, and 174 dogs admitted to clinics for any illness (at-large dogs). Twenty-eight dogs were identified with one of four CFTR missense mutations. P1281T and P1464H mutations occur in relatively unconserved residues. R1456W is analogous to the human R1453W mutation, which has approximately 20% of normal CFTR function and is associated with pancreatitis and panbronchiolitis. R812W disrupts a highly conserved protein kinase A recognition site within the regulatory domain. We conclude that naturally occurring CFTR mutations are relatively common in domestic dogs and can be detected with TTGE. No substantive differences in mutation frequency were observed between the at-large, pancreatitis, and bronchiectasis dogs.