Summer 1998 Edition

1998 ACVIM Forum

The C.G.S. Symposium - The C.G.S. sponsored a half-day symposium on ischemia/re-perfusion injury of the gastrointestinal tract. Session speakers included Dr. Neil Granger of the Louisiana State University Medical Center in Shreveport, and Dr. Rustin Moore of the Louisiana State University Veterinary School in Baton Rouge. Their joint presentation provided an overview of the pathophysiology of the syndrome, the role of nitric oxide in I/R injury pathogenesis, and unique features of the syndrome in the feline and equine intestine. The Society thanks Schering-Plough for financial support of the symposium.

The Liver Study Group - The L.S.G. sponsored a half-day symposium on the physiology and pathophysiology of bile salts in hepatobiliary disease. Session speakers included Dr. Alan Hofmann of the University of California-San Diego Medical School, and Dr. David Williams of the Texas A & M University Veterinary School in College Station. The speakers provided an overview of the chemistry, metabolism, and toxicology of ursodeoxycholate, and the diagnostic application of serum bile acid measurement in dogs and cats. Their presentations were followed by a panel discussion (John Cullen, Sharon Center, Anne Chiapella) on the medical management of chronic hepatic diseases in dogs and cats.

Research Abstract Awards - Several research awards were presented at the C.G.S. luncheon meeting, and at the ACVIM Forum Plenary Session. Dr. Lynda Melendez was awarded the C.G.S. Resident Research Abstract Award for her abstract presentation "Conservative Therapy of Esophageal Strictures Using Balloon Catheter Dilation". Dr. David Twedt accepted the award on behalf of Dr. Melendez. Dr. Stan Marks was awarded the C.G.S. Faculty Research Abstract Award for his abstract presentation "Critical Appraisal of Methods to Diagnose Clostridium perfringens-associated Diarrhea in Dogs". These Iams Company-sponsored awards consist of a plaque and $500 cash award. The C.G.S. extends its sincere gratitude to Dr. Greg Reinhart of the Iams Company for helping the Society to sponsor these awards. Another gastroenterology abstract was recognized for merit in the ACVIM Resident Research Abstract competition. Dr. Erika dePapp received one of these Pfizer-sponsored awards for her research abstract presentation "Relationship between Plasma Lactate Concentration, Gastric Necrosis, and Survival in Dogs with Gastric Dilatation/Volvulus". Congratulations to all Research Abstract Award winners. Thanks are also extended to Ralston Purina for their financial support of the membership luncheon meeting.

Research Grant Award - Dr. Jennifer Nadeau and her collaborators, Drs. Frank Andrews and Robert Argenzio, are the recipients of the 1998 C.G.S. Research Grant Award for their grant submission "Pathogenesis of acid injury in the equine stomach". The investigators propose to study the effects of volatile short chain fatty acids on gastric mucosal short circuit current in Ussing chamber experiments. Congratulations to the award winners, and special thanks to the 12 other grant applicants. The competition for funding was especially keen this year, and there were many more deserving grant applications than available funding. Special thanks also to our Immediate Past President, Dr. David A. Williams, for organizing the grant review process.

1998 Digestive Disease Week

Current Topics in Comparative Gastroenterology - The PhD, MD/PhD and DVM Task Force of the AGA once again sponsored a Clinical Symposium on Current Topics in Comparative Gastroenterology at the AGA annual meeting in New Orleans. The program, entitled Viral Hepatitis and Hepatic Carcinogenesis, featured speakers John Cullen ("Animal Models of Hepatitis B Virus Infection") of the North Carolina State University School of Veterinary Medicine, and Bud Tennant ("Woodchuck Hepatitis Virus Infection: Role in Hepatocarcinogenesis") of the Cornell University School of Veterinary Medicine. The meeting was chaired by Society members Colin Burrows and Robert Washabau.

Interesting Research Abstracts

Moayyedi P, Braunholtz, Liptrot, et al.: Can pets act as a vector for Helicobacter pylori transmission? (Abstract #G0943) - Investigators from the University of Leeds obtained demographic data and pet ownership information from 8,306 subjects in a prospective study of H. pylori infection. Dog and cat ownership, either in childhood or adulthood, was not associated with H. pylori infection when controlling for markers of socio-economic status.

Editor's Comment - This study confirms the findings of several previous studies (summarized by Fox, J.G. in Aliment. Pharmacol. Ther. 1995; 9: 93-103) that pet owners are not necessarily at increased risk for Helicobacter pylori infection. The study controlled for socio-economic status because pet ownership is often highly associated with higher socio-economic groupings.

Neiger R, Stoffel M, Burnens A, et al.: Scanning electron microscopy of different gastric Helicobacter-like organisms in dogs. (Abstract #G4295) - This study from the University of Bern was designed to characterize morphological differences in H. felis, H. heilmannii, H. bizzozeronii, and H. salomonis using scanning EM methodology. The investigators showed that presence and location of periplasmic fibrils could be used to differentiate these four Helicobacter species in biopsy, but not culture, specimens.

Editor's Comment - The authors have previously reported (J. Clin. Microbiol. 1998; 36: 624-627) that pet cats are frequently colonized by H. heilmannii without a significant correlation between infection and degree of gastritis. The authors have now shown that morphologic criteria may be used to differentiate some of the Helicobacter species. Molecular and biochemical characteristics will continue to be used in the identification and speciation of these organisms, but scanning EM may be a useful diagnostic tool in the absence of these techniques. The present study also confirms the previous findings of Utriainen et al. (Morphologic diversity of cultured canine gastric Helicobacter spp., Comp. Immun. Microbiol. Infect. Dis. 1997; 20: 285-297) who showed scanning EM differences between H. felis, H. bizzozeronii, and Flexispira organisms.

Cattoli G, Kusters JG, Zanoni RG, et al.: Characterization of canine gastrospirilla. (Abstract # G0353) - This multi-center study (Utrecht, Amsterdam, Bologna, and Milan) revealed the presence of Helicobacter-like organisms in the stomach of a small number (23/25) of dogs. Ribosomal RNA (16S) analysis revealed infection with H. heilmannii or H. felis. H. felis, but not H. heilmannii, organisms were positive for the vacA and cagA virulence factors; both H. felis and H. heilmannii organisms were positive for the iceA virulence factor.

Editor's Comment - The study confirms the previous findings of Happonen et al. (Occurrence and topographical mapping of gastric Helicobacter-like organisms, J. Vet. Med. 1996; 43: 306-315), but, unlike the previous study, there was no mention of histologic changes associated with infection. As with other isolates of H. felis and H. heilmannii, infection in this study was associated with the expression of certain virulence factors.

Meining A, Kroher G, and Stolte M.: Animal reservoirs in the transmission of Helicobacter heilmannii: results of a questionnaire-based study. (Abstract #G0916) - In this study from Bayreuth, 202 patients with histologically confirmed Helicobacter heilmannii gastritis were asked if they had regular contact with other animal species. Logistic regression analysis showed that contact with pigs (O.R. = 4.99), cats (O.R. = 1.71) and dogs (O.R. = 1.46) leads to a significant risk of H. heilmannii infection. The investigators concluded that pigs, cats, and dogs appear to be reservoirs in the transmission of H. heilmannii.

Editor's Comment - Isolated cases of zoonotic transmission of H. heilmanniii have been reported previously (Thomson MA. Canine-human transmission of Gastrospirillum hominis, Lancet 1994; 343: 1605-1607; Lavelle JP et al. Acute gastritis associated with spiral organisms from cats, Dig Dis Sci 1994; 39: 744-750). Additional studies will be needed to define the routes of natural infection in humans and animals.

Fox JG, Shen Z, Feng F, et al.: Hepatobiliary Helicobacter species identified from patients with primary sclerosing cholangitis. (Abstract #G4009) - Jim Fox and his colleagues at M.I.T. found Helicobacter spp. by PCR amplification and Southern hybridization in 5 of 8 human PSC patients. A 1200 base pair PCR amplification product homologous to the 16S rRNA sequence of H. rodentium, H. rappini, and H. pullorum was found in two of these patients. The authors suggested that additional studies should be performed to ascertain where Helicobacter organisms play a role in human hepatobiliary disease.

Editor's Comment - The investigators have previously isolated H. canis from the liver of a dog with multifocal necrotizing hepatitis (Fox JG, et al., J. Clin. Microbiol. 1996; 34: 2479-2482). These findings, which are still very preliminary, suggest that Helicobacter infection may contribute to the pathogenesis of chronic, inflammatory hepatobiliary disease in animals and humans.

Sakamoto S, Adams MG, and Sarna SK.: G-protein activated contractions in normal and inflamed canine ileum. (Abstract # G3406) - Using an ethanol/acetic acid infusion model of canine ileitis, Sarna and his colleagues showed that the cholinergic (ACh) and nitronergic (NO) stimulation of L-type calcium channels, phospholipase C, and G proteins are all down regulated during inflammation.

Editor's Comment - In several pivotal studies (J. Pharmacol. Exp. Therap. 1996; 279: 207-213; Am. J. Physiol. 269: G913-924; Gastroenterology 1991; 100: 954-962), Sarna and his colleagues have shown that experimental canine IBD is a motility disorder, e.g., clinical signs are related to the occurrence of giant migrating contractions in the distal ileum and colon. The biochemical and molecular perturbations of experimental IBD are now being investigated. Similar studies in spontaneous canine and feline IBD are desperately needed.

Schuurkes J, Meulemans A, Briejer M, et al.: The enterokinetic R093877 normalizes opioid-delayed fecal pellet propulsion in the isolated guinea pig distal colon. (Abstract #G3427) - Investigators from Janssen Pharmaceutical showed that R093877 accelerates fecal pellet propulsion in the guinea pig distal colon, even if propulsion is inhibited by a peripheral µ-opioid receptor agonist (e.g., loperamide). The R093877 effects were shown to be mediated by 5-HT₄ receptors.

Editor's Comment - The investigators have previously documented similar R093877 effects in the canine and feline colon. R093877 stimulates canine colonic contractile patterns (Gastroenterology 1997; 112: A704), and enhances defecation frequency in conscious cats (Gastroenterology 1997; 112: A705a). The drug could develop into a clinically useful distal G.I. prokinetic agent, but it does have proximal prokinetic properties, as well (Gastroenterology 1997; 112: A705b).

Shibata C, Sasaki I, Naito H, et al.: The herbal medicine, dai-kenchu-to, stimulates upper G.I. motility in conscious dogs via cholinergic and 5-HT₃ receptors. (Abstract #G3437) - In this study from Tohoku University School of Medicine in Sendai, dogs were equipped with strain gauge transducers in the upper gastrointestinal tract, and the effects of intra-gastric dai-kenchu-to (dried ginger rhizome, ginseng root, zanthoxylum fruit) on G.I. motility were examined. DKT stimulated motility through cholinergic and 5-HT₃ receptors, with specific herbal effects at different sites.

Editor's Comment - Herbs and spices anyone? Interesting finding, but the experimental paradigm did not include an analysis of gastric emptying or intestinal transit. Additional studies will be needed before it may be concluded that dai-kenchu-to is an effective gastrointestinal prokinetic agent in the dog. Hmmmmm...........wonder what it does in a muscle bath?

Koch KL, Xu L, Wilson R, et al.: Effect of gastric electrical stimulation on gastric contractions, myoelectrical activity, and emptying during post-operative ileus in dogs. . (Abstract #G3211) - Small bowel manipulation was used to induce post-operative ileus in dogs in this study reported from the Hershey Medical Center. Electrical pacing of the gastric corpus was induced with 5.0 mA, 330 microsecond pulses with a 20 cycle/minute stimulation frequency. Gastric electrical stimulation was shown to improve myoelectrical and contractile activity and gastric emptying at 4, but not 24, hours of post-operative ileus.

Editor's Comment - These studies largely confirm the findings of Keith Kelly and colleagues at the Mayo Clinic in the late 1970's and early 1980's (Am. J. Physiol. 1972; 222: 588-594; Gastroenterology 1983; 84: 383-387). Question: Will this there ever become a useful clinical modality?

The AGA Post-Graduate Course on "Controversies and Clinical Challenges in Pancreatic Diseases" - Dr. Joerg Steiner of Texas A & M University offers the following summary from his attendance at the Post-Graduate Course:

"It has been 13 years since an AGA postgraduate course was focused solely on exocrine pancreatic disorders. The postgraduate course was held two days before Digestive Disease Week in New Orleans, and brought together 52 world-renowned faculty and several thousand attending gastroenterologists. I will try to summarize some of the new and exciting knowledge presented at this course, but I will also add new information from some of the pancreatology abstracts presented at the DDW.

Pancreatitis remains one of the most important G.I. disorders in humans accounting for 302,000 hospital discharges in 1993 in the USA alone. About three quarters of these cases are acute and one quarter are chronic. However, one should take into account that many cases of acute pancreatitis are not severe enough to warrant hospital admission of the patient, and others are so severe that the patient will succumb to the disease and will therefore not be captured by a hospital discharge statistic. Comparing these data with data from other developed countries would suggest an overall incidence of pancreatitis of 24.1 cases/100,000 population. This number compares to an overall incidence of pancreatic cancer between 7.4 cases per 100,000 population (Wales) and 11.1 cases per 100,000 population (African-Americans in the USA).

There are several accepted risk factors for pancreatitis in humans. Gallstones appear to cause 40-50% of all pancreatitis cases in humans. Alcohol consumption appears to be another important risk factor. Other, less important risk factors are obesity, hyperlipidemia, various drugs, AIDS, and immune-mediated disease. In comparison, 60-80% of all chronic pancreatitis cases are caused by alcohol consumption. Other causes and risk factors include gallstones, smoking, malnutrition, and hereditary factors. However, 20-30% of chronic pancreatitis cases remain idiopathic. The biggest advance in pancreatitis etiology and pathophysiology research has been in the field of hereditary pancreatitis. About 1% of chronic pancreatitis cases in the USA are hereditary. So far, the disease has been linked to at least two different mutations of the protrypsinogen gene. The most important mutation appears to be the one leading to a replacement of the arginine in position 117 with a histidine (R117H) residue. This mutation appears to be of major importance because the R117 is necessary in order for prematurely activated trypsin to fit into the active site of other trypsin molecules. This mutation is therefore believed to dramatically limit the effectiveness of an important defense mechanism against pancreatitis. Another mutation causing a similar clinical syndrome is N21I (a mutation leading to a replacement of asparagine in position 21 with isoleucine), but this syndrome has not been studied as well. Another major advance has been the recognition of the importance of inflammatory mediators in the progression from local pancreatic inflammation to systemic organ dysfunction. After recognizing the failure of protease inhibitor treatment to modulate established pancreatitis, H. Rinderknecht postulated ten years ago that factors other than digestive enzymes were involved in the perpetuation of pancreatitis. Rinderknecht further postulated that deterioration of pancreatitis patients was mainly due to the failure to combat cytokines released from neutrophils and macrophages. After a decade of research, TNF, IL-1, IL-2, IL-6, IL-8, IL-10, NO, INF-, INF-, PAF, and oxygen free radicals have been shown to play an important role in disease progression. Recent studies suggest that PAF plays a central role in this progression, and that PAF antagonists such as lexipafant (all PAF antagonists end in -pafant for PAF ANTagonists) may be the most promising therapeutic agents for the treatment of acute pancreatitis. Several small studies have shown a significant decrease in mortality in pancreatitis patients treated with lexipafant. Results of a large (> 1000 patients) multicenter study should be available by the end of 1998. It will be interesting to see the results of this study, especially in light of a recent International Journal of Pancreatology paper which reported that lexipafant did not influence morbidity or histologic changes in a rat model of pancreatitis. The other important concept in the treatment of acute pancreatitis is the importance of early nutritional support in patients with acute pancreatitis. An Italian study had found a beneficial effect of early enteral feeding of acute pancreatitis patients. These results were taken one step further by Clement Imrie and colleagues at the Royal Infirmary in Glasgow. He fed 27 acute pancreatitis patients via nasogastric tube within 48 hours of presentation and found a beneficial effect in 24 of the 27 patients.

Obviously, there has been remarkable progress in imaging techniques of the exocrine pancreas in human medicine. Endoscopic retrograde cholangiopancreatography (ERCP) and contrast-enhanced computed tomography are standard diagnostic imaging tools in patients suspected of having pancreatitis. However, controversy remains whether ERCP should be reserved for a subset of patients in order to prevent serious ERCP-related complications. Endoscopic ultrasonography is another imaging technique pancreatologists at most institutions now use routinely in patients suspected of having exocrine pancreatic disorders. The latest development in this arena is a three dimensional endoscopic-ultrasonographic system which was presented in a research abstract. The images provided by this technology are of outstanding clarity. One would hope that endoscopic ultrasonography will be explored in veterinary patients with exocrine pancreatic and other disorders.

There was also some interesting data about the treatment of EPI. While several previous studies have found no difference between the efficacy of conventional pancreatic enzymes and enteric-coated capsules, one of the abstracts showed that total trypsin delivery to the small intestine was higher with conventional enzymes.

Most of the material on pancreatic adenocarcinoma (AC) is not really applicable to veterinary patients. But, it seems interesting to note that even human pancreatic surgeons are not united in whether pancreatic surgery is useful in the treatment of patients with pancreatic AC. One of the speakers who is in favor of pancreatic surgery qualified his support by adding that only surgical teams performing more than 50 surgical procedures per year would achieve results which would be acceptable. Translated into the veterinary community this would argue against the use of pancreatic surgery for veterinary patients with pancreatic AC altogether. Also, many chemotherapeutic protocols, involving monotherapies as well as combination therapies, have been compared to the standard 5-fluorouracil monotherapy. However, none have been shown to be superior to 5-fluorouracil monotherapy. Some new data would suggest that gemcitabine may be superior to 5-FU, but further studies are needed to confirm these findings.

In summary, a lot of exciting pancreatology data were presented at the AGA post-graduate course and in the Scienfic Sessions of Digestive Disease Week. "Vive la pancreatology" - Jörg Steiner

New Web Site Listings

The Society's Web Site has been operational for several months now. Interested Web enthusiasts may obtain important Society information about C.G.S. membership, grant and membership applications, articles of incorporation, Society resources, and related Societies (e.g., American Gastroenterology Association, American Physiological Society, Conference of Research Workers in Animal Disease). Please visit the C.G.S. Web Page at:

Society Newsletters, including this Newsletter, will be published in the Society Web Page.

Society-sponsored and Society-endorsed Endoscopy Courses

The Society sponsors an endoscopy course at the North American Veterinary Conference in Orlando, Florida. NAVC is usually held in the second or third week of January. In addition to the Society-sponsored course at the NAVC, the Society also endorses a number of other endoscopy courses as a service to specialists and generalists in practice. Courses currently endorsed by the Society include the programs at Virginia Tech University (Dr. Mike Leib, contact person), Washington State University (Dr. Cheryl Dhein, contact person), and the international VECCS meeting (Drs. Mike Matz and Lesley King, contact persons). Please let me (washabau@vet.upenn.edu) know if there are other courses worthy of Society endorsement.

Endoscopy Guidelines

The Society is currently developing a set of guidelines for the indication, instrumentation, and performance of gastrointestinal endoscopy in the dog, cat, and horse. Society guidelines will help to promote practice standards and to provide recommendations to specialists and generalists in practice. The following Society members have volunteered to help write these guidelines: Frank Andrews, Colin Burrows, Al Jergens, Mike Leib, Al Merritt, Diane Levitan, David Rolfe, Bob Sherding, Kenny Simpson, and Mike Willard. Guidelines will include information on indications, instrumentation, upper G.I. endoscopy, lower G.I. endoscopy, biopsy, large animal vs. small animal, and PEG tubes. Please let me know if there are others interested in this endeavor.

Funded Research Projects

In addition to the project funded at the University of Tennessee ("Pathogenesis of acid injury in the equine stomach", Jennifer Nadeau and Frank Andrews), the Society has funded a number of other research projects in comparative gastroenterology and gastrointestinal physiology. Promoting gastrointestinal research is one of the major goals of the Society. More information on Society- funded research projects may be found in the Society Web Site.

Society Meetings

Summaries of upcoming and past Society meetings will be maintained in the Society Web Site.

Position Announcements

The Society will maintain an active list of academic, industry, and private practice positions in gastroenterology and gastrointestinal physiology. The first position announcement is for the Waltham Lectureship in Small Animal Clinical Nutrition and Gastroenterology at the University of Liverpool (visit the Web Site for further details).

Thank You from Carolein Rutgers

A Get Well card was sent to Carolein Rutgers via Colin Burrows following Carolein's recent illness. Carolein writes back (to Colin): "Many thanks for the Get Well card, signed by so many of the CGS members, which you organized for me during the recent ACVIM Forum in San Diego. It was a great and pleasant surprise to receive it. Thank you very much indeed! Please pass my thanks to the other CGS members, if that would be possible. It is so nice to be remembered like that!"

Editor's Note - Great hearing from you, Carolein. Continued best wishes for a speedy recovery.

Society Elections

The Society must elect a Secretary-Treasurer, At-Large Director, and President-Elect this summer. A ballot will be included in the summer mailing, along with the Newsletter and updated Membership Directory. Don't forget to vote!

Meeting Announcements

The American Motility Society will hold its biennial meeting August 19-23 in Philadelphia. For information about the program, please contact the Office of Continuing Medical Education at Jefferson Medical College (215-955-6992). For more information about the Society or membership, please contact: National Headquarters, Ms. Patricia A. McFadden, 6900 Grove Road, Thorofare, New Jersey 08086; (609) 848-0105 office; (609) 848-5274 FAX; E-Mail:ams@slackinc.com. A hyperlink to the AMS Web Site can also be found within the CGS Web Site.

Society Newsletter

Due to the underwhelming response for requests for volunteers at the May business meeting, I will be "volunteering" several Society members for Newsletter-writing in the very near future. Stay tuned, friends and colleagues!

Web page master: David A. Schneider