Evaluation of dietary histories in cats presenting with chronic gastrointestinal clinical signs to a veterinary teaching hospital

Objectives Although less frequently described than in dogs, it is also well recognised in cats that chronic gastrointestinal (GI) disease can fully respond to dietary changes only. So far, no study has assessed how much dietary information can be obtained during veterinary consultations. Methods We retrospectively evaluated how much dietary information was available when owners presenting their cats to our gastroenterology (GE) and internal medicine (IM) service between October 2017 and January 2020 were questioned during consultations. Because of the larger IM caseload, for each week the first two cats presenting with chronic GI signs were selected for the IM group. Data from 80 cats presenting for first GE consultations were compared with data from 84 cats presenting with chronic GI signs for first IM consultations. Results Referrals comprised 42/80 (53%) GE cats and 53/84 (63%) IM cats. Referral documents mentioned the previously fed diet in 12/42 (29%) GE and 4/53 (8%) IM cats, and response to that previous diet trial was recorded in the referral documents of 4/12 (33%) GE and 3/4 (75%) IM cats. No cat had received more than one previous diet trial. During consultations, owners of 61/80 (76%) GE and 53/84 (63%) IM cats were asked about diet. Irrespective of referral status, previous dietary trials had been performed in 27/61 (44%) GE and 19/53 (36%) IM cats. The specific diet fed at the time of consultation could be named by 37/61 (61%) GE and 11/53 (21%) IM cat owners. Conclusions and relevance Overall dietary information gained from referring veterinarians and owners was often incomplete. Although more information could be gained from owners during GE consultations vs IM consultations, awareness of the importance of diet in cats with GI disease still appears to be low among veterinarians and cat owners. Future studies need to assess if more complete dietary information can be obtained at the time of consultations with a prospective study design

Effects of medical history and clinical factors on serum lipase activity and ultrasonographic evidence of pancreatitis: Analysis of 234 dogs

Background: Lipase measurements and ultrasonographic (US) evidence of pancreatitis correlate poorly. Objectives: Identify explanations for discrepant lipase and pancreatic US results. Animals: Two hundred and thirty-four dogs with gastrointestinal signs. Methods: A retrospective study was conducted, in which lipase activity and US were performed within 30 hours. Medical history, clinical examination results, lipase activity, and US results were recorded. Results: Lipase and US results were weakly correlated (rs = .25, P 2 days, 118 U/L; P = .03; ≤7 days, 334 U/L; >7 days, 99 U/L; P = .004), but US was not significantly more frequently positive. For both cut-offs (>216/≤216 U/L, >355/≤355 U/L; reference range, 24-108 U/L), median disease duration was significantly shorter (3 vs 4 days) with higher lipases. Previous pancreatitis episodes were significantly associated with an US diagnosis of pancreatitis (P = .04), but median lipase activities were not significantly higher (386 U/L vs 153 U/L; P = .06) in these dogs. Pancreatic US was significantly more often positive when the request contained "suspicion of pancreatitis" (P < .001) or "increased lipase" (P = .01). Only changes in pancreatic morphology, echogenicity, and peripancreatic mesentery were significantly associated with a positive US diagnosis, and also had significantly higher lipase activities. Conclusions and clinical importance: Duration of clinical signs before presentation differently affects laboratory and US evidence of pancreatitis. Previous pancreatitis episodes and information given to radiologists influence US results. These findings can be helpful for future studies on pancreatitis in dogs

A Descriptive Study on the Extent of Dietary Information Obtained during Consultations at a Veterinary Teaching Hospital

The majority of dogs with chronic idiopathic gastrointestinal (GI) disease respond to diet. So far, no study has assessed how much dietary information is obtained during consultations. We retrospectively evaluated what dietary information was available from dogs presenting to our Gastroenterology (GE), and Internal Medicine (IM) Service between 10/2017 and 01/2020. Data from 243 dogs presenting for first GE consultations were compared to 239 dogs presenting with chronic GI signs for first IM consultations. Referrals comprised 131 (54%) GE dogs and 112 (47%) IM dogs. Referral documents specified the previously fed diet in 53/131 (40%) GE and 14/112 (13%) IM dogs. No dog had received more than one previous diet trial for chronic GI signs. Irrespective of referral status, diet trials had been performed in 127/199 (64%) GE, and 56/156 (36%) IM dogs. The specific diet fed at the time of consultation could only be named by 106/199 (53%) GE and 40/156 (26%) IM dog owners. Data on response to subsequent newly prescribed diets were available from 86 GE dogs and 88 IM dogs. A positive response to diet was noted in 50/86 (58%) GE and 26/88 (30%) IM dogs. A further 23/35 (66%) GE dogs and 12/21 (57%) IM dogs responded positively to a second diet trial, and 4/9 GE dogs (44%) and 6/7 (86%) IM dogs responded positively to a third diet trial. In conclusion, overall dietary information gained from referring veterinarians and owners was often incomplete. More dietary information could be gained during GE consultations compared to IM consultations for chronic GI signs. A positive response to diet can still be seen after two diet failures. Further studies will help to ascertain if the percentage of diet-responsive GI disease increases when more complete dietary information is obtained at the time of consultations

Prevalence of inflammatory versus neoplastic lesions in dogs with chronic gastrointestinal signs undergoing gastroduodenoscopy: 195 cases (2007–2015)

Objectives: Prevalence of inflammatory enteropathy versus lymphoma in dogs undergoing gastroduodenoscopy has not been evaluated. This retrospective study assessed outcome from 195 client-owned dogs scheduled to undergo upper gastrointestinal endoscopy as the next diagnostic step. Material and methods: Cases were grouped into the following diagnoses according to WSAVA guidelines: lymphoplasmacytic enteritis (LPE), eosinophilic enteritis (EE), mixed-cell enteritis (ME), histologically normal biopsies (N), and lymphoma (L). Clinical signs, and preendoscopic results from laboratory and ultrasonography examinations, were compared among groups. Results: LPE was diagnosed in 133 (68%), EE in 17 (9%), ME in 9 (5%), 32 (16%) dogs had histologically normal biopsies. Four (2%) dogs were diagnosed with lymphoma. Vomiting was the most frequent clinical sign (61%), followed by weight loss (43%), and diarrhea (39%). Vomiting also predominated when looking at individual histological disease categories, however clinical signs did not differ significantly between groups. Dogs with lymphoma were more likely to have ultrasonographic abnormalities, had significantly lower haematocrit, albumin and total protein concentrations compared to dogs with LPE and histologically normal biopsies. Clinical significance: Lymphoma was rarely found in this group of dogs with nonspecific results of pre-endoscopic work-up. Our results provide first reference for clinicians when discussing the possibility of a step-up therapeutic approach (such as multiple dietary trials) with owners before pursuing endoscopy. Understanding the likelihood of finding lymphoma is important in that histologic documentation of inflammatory enteropathy alone has limited therapeutic consequences. Future studies are needed to validate these findings in dogs undergoing combined upper and lower gastrointestinal endoscopy and biopsies

Sticks and Stones, a conserved cell surface ligand for the Type IIa RPTP Lar, regulates neural circuit wiring in Drosophila

Control of tyrosine phosphorylation is an essential element of many cellular processes, including proliferation, differentiation neurite outgrowth, and synaptogenesis. Receptor-like protein-tyrosine phosphatases (RPTPs) have cytoplasmic phosphatase domains and cell adhesion molecule (CAM)-like extracellular domains that interact with cell-surface ligands and/or co-receptors. We identified a new ligand for the Drosophila Lar RPTP, the immunoglobulin superfamily CAM Sticks and Stones (Sns). Lar is orthologous to the three Type IIa mammalian RPTPs, PTPRF (LAR), PTPRD (PTPδ), and PTPRS (PTPσ). Lar and Sns bind to each other in embryos and in vitro. The human Sns ortholog, Nephrin, binds to PTPRD and PTPRF. Genetic interaction studies show that Sns is essential to Lar′s functions in several developmental contexts in the larval and adult nervous systems. In the larval neuromuscular system, Lar and sns transheterozygotes (Lar/sns transhets) have synaptic defects like those seen in Lar mutants and Sns knockdown animals. Lar and Sns reporters are both expressed in motor neurons and not in muscles, so Lar and Sns likely act in cis (in the same neurons). Lar mutants and Lar/sns transhets have identical axon guidance defects in the larval mushroom body in which Kenyon cell axons fail to stop at the midline and do not branch. Pupal Kenyon cell axon guidance is similarly affected, resulting in adult mushroom body defects. Lar is expressed in larval and pupal Kenyon cells, but Sns is not, so Lar-Sns interactions in this system must be in trans (between neurons). Lastly, R7 photoreceptor axons in Lar mutants and Lar/sns transhets fail to innervate the correct M6 layer of the medulla in the optic lobe. Lar acts cell-autonomously in R7s, while Sns is only in lamina and medulla neurons that arborize near the R7 target layer. Therefore, the Lar-Sns interactions that control R7 targeting also occur in trans

Live Dissection of Drosophila Embryos: Streamlined Methods for Screening Mutant Collections by Antibody Staining

Drosophila embryos between stages 14 and 17 of embryonic development can be readily dissected to generate "fillet" preparations. In these preparations, the central nervous system runs down the middle, and is flanked by the body walls. Many different phenotypes have been examined using such preparations. In most cases, the fillets were generated by dissection of antibody-stained fixed whole-mount embryos. These "fixed dissections" have some disadvantages, however. They are time-consuming to execute, and it is difficult to sort mutant (GFP-negative) embryos from stocks in which mutations are maintained over GFP balancer chromosomes. Since 2002, our group has been conducting deficiency and ectopic expression screens to identify ligands for orphan receptors. In order to do this, we developed streamlined protocols for live embryo dissection and antibody staining of collections containing hundreds of balanced lines. We have concluded that it is considerably more efficient to examine phenotypes in large collections of stocks by live dissection than by fixed dissection. Using the protocol described here, a single trained individual can screen up to 10 lines per day for phenotypes, examining 4-7 mutant embryos from each line under a compound microscope. This allows the identification of mutations conferring subtle, low-penetrance phenotypes, since up to 70 hemisegments per line are scored at high magnification with a 40X water-immersion lens

Interactions between a Receptor Tyrosine Phosphatase and a Cell Surface Ligand Regulate Axon Guidance and Glial-Neuronal Communication

We developed a screening method for orphan receptor ligands, in which cell-surface proteins are expressed in Drosophila embryos from GAL4-dependent insertion lines and ligand candidates identified by the presence of ectopic staining with receptor fusion proteins. Stranded at second (Sas) binds to the receptor tyrosine phosphatase Ptp10D in embryos and in vitro. Sas and Ptp10D can interact in trans when expressed in cultured cells. Interactions between Sas and Ptp10D on longitudinal axons are required to prevent them from abnormally crossing the midline. Sas is expressed on both neurons and glia, whereas Ptp10D is restricted to CNS axons. We conducted epistasis experiments by overexpressing Sas in glia and examining how the resulting phenotypes are changed by removal of Ptp10D from neurons. We find that neuronal Ptp10D restrains signaling by overexpressed glial Sas, which would otherwise produce strong glial and axonal phenotypes

Tau Aggregation Inhibitor Therapy : An Exploratory Phase 2 Study in Mild or Moderate Alzheimer's Disease

ACKNOWLEDGMENTS We thank patients and their caregivers for their participation in the study and are indebted to all the investigators involved in the study, particularly Drs. Douglas Fowlie and Donald Mowat for their helpful contributions to the clinical execution of the study in Scotland. We thank Sharon Eastwood, Parexel, for assistance in preparing initial drafts of the manuscript. We acknowledge constructive comments provided by Professors G. Wilcock and S. Gauthier on drafts of the article. CMW, CRH, and JMDS are officers of, and hold beneficial interests in, TauRx Therapeutics. RTS, PB, KK, and DJW are paid consultants to TauRx Therapeutics. The study was financed entirely by TauRx TherapeuticsPeer reviewedPublisher PD

Progression of lipase activity and pancreatic lipase immunoreactivity in dogs hospitalized for acute pancreatitis and correlation with clinical features

Background: Lipase activity and pancreatic lipase immunoreactivity (PLI) have not been compared in dogs hospitalized for acute pancreatitis (AP). Objectives: To describe the progression of lipase activity and PLI, and correlations with clinicopathologic features in dogs with AP. Animals: Thirty-nine dogs with AP based on clinical signs and lipase activity >350 U/L (reference interval [RI], 24-108 U/L). Methods: Retrospective study. Lipase activity (LIPC Roche), PLI (SpecPL), and clinical signs were recorded daily. Admission (d1) data (clinical, laboratory, and ultrasound [US] findings), and clinical signs during hospitalization (d2-d3) were assessed for correlation with lipases. Results: Median (range) duration of clinical signs before presentation was 2 days (1-7 days). Median (range) lipase activity and PLI at d1 were 1070 U/L (range, 357-1500 U/L) and 1111 μg/L (range, 292-1500 μg/L). Strong correlation between assays at d1 (rs 0.96; P < .0001; n = 39), remained equally strong on d2 (rs 0.964; P < .0001; n = 39), and d3 (rs 0.966; P < .0001; n = 22). On d2, lipase activity and PLI were within RI in 13/39 (33%) and 18/39 (46%) of cases. Lipase activities were minimally increased (median, 124 U/L) in 5 dogs with d2 PLI <200 μg/L. On d3, 4 more dogs had normal lipase activity and PLI, and the nature and magnitude of change were always the same for both assays. Clinical signs were not associated with lipases. Only a hyperechoic mesentery, but not an US diagnosis of AP, correlated significantly with lipase activity and PLI. Conclusions and clinical importance: Lipase decreases rapidly to near or within RI within 2 days of treatment in the majority of dogs with AP. Both lipase assays yielded virtually identical results. Mesenteric echogenicity may be an early marker of AP in dogs