Meet Me in St. Louis - at the AKC Canine Health Foundation Conference

This article originally appeared in Show Sight magazine.  It is reprinted with permission from the author, Caroline Coile.

Every two years I'm amazed. Because that's when the AKC Canine Health Foundation holds its Parent Club Conference, and that's when I'm always in awe of the scientists and breeders who work every day to make my dogs and your dogs healthier. I wish people who criticize dog shows and breeders could see what money raised by clubs and fanciers is accomplishing. I wish they could see the people share their dogs' histories and DNA for the cause, or work for their clubs' health committees as though it were a full time job. This was the ninth biennial conference, and the eighth I've attended, and I've never failed to leave feeling that the single most important thing we can do as dog enthusiasts is to support canine health research. The thrill of a Best in Show is no compensation for the grief of an untimely death, and the show ring is the smallest part of the time we share with our dogs.  Once again, this year's presentations left me awed and optimistic.

Cancers

The CHF and the Golden Retriever Foundation are jointly funding two projects totaling nearly $1.5 million.

Talks by Mathew Breen (University of North Carolina) and Jaime Modiano (University of Minnesota) gave hope for new tests to help make decisions regarding cancer treatment.  Both labs have developed different tests to predict lymphoma response to therapy. Traditionally, veterinarians have classified the prognosis of B cell lymphomas as "bad" and T cell lymphomas as "terrible."  But actually both groups have long and short term survivors. A test developed in the Modiano lab uses a four-gene signature to predict which dogs will respond to treatment. Samples would initially require a biopsy, but by next spring the technique should only require a fine needle aspirate. The Modiano lab has also developed a test to better predict osteosarcoma response to therapy based on its molecular subtype. Although they look the same clinically, one subgroup has a median survival time of 3 months, whereas the other a median survival of 14 months.

Mast cell tumors are graded 1, 2 and 3, with grade 1 being good news, grade 3 bad news, and grade 2 who knows? The Breen lab has a test can give more guidance on whether a grade 2 tumor will act like a grade 1 versus a grade 3. If you've had a dog with a grade 2 mast cell tumor in the last three years, and have updated information on the tumor's grade, contact info@breenlab.org as the biopsy specimen may still be available for research.

Other tests forthcoming from the Breen lab will 1) predict with 95% accuracy how long your dog with lymphoma will respond to doxorubicin or CHOP treatment; 2) whether it will respond very well or very poorly to single agent doxorubicin; 3) separate lymphoma from histiocytic malignancy in breeds with both; and 4) identify the presence of urogenital carcinoma cells in dog urine.

Hemangiosarcoma (HSA) is a particular focus of the Modiano lab. First described in the 1950s, it's now an all to common diagnosis in large breeds. Surgery and chemotherapy may prolong life, but by the time the cancer is detected it's often too late. Removing the spleen (one of its favorite sites) won't prevent it because HSA is likely a tumor of the blood-forming cells in the bone marrow, so wherever the cells land they form tumors. If there's no spleen HSA will just develop elsewhere. Modiano's group found a subgroup of endothelial precursor cells present in the blood of Goldens with HSA. If these cells also occur in dogs of other breeds with HSA, this will provide a blood test for early detection of HSA and help decide whether a splenic tumor is a hemangiosarcoma (bad news) or hemangioma (good news). A clinical trial is ongoing. Information on participating in trials or submitting DNA from any breed is available at www.modianolab.org/studyInfo/studyInfo_index.shtml and www.cvm.umn.edu/cic/home.html .

The Breen lab has found three different clusters of cytogenomic changes in dogs with HSA. Different breeds have different cytogenomic changes---for example, Australian Shepherds have 5983 genes that are aberrant in HSA---but by comparing five different breeds (Aussies, Berners, GSDs, Flat Coats and Goldens) they found "only" 396 genes shared by all five breeds. To reduce that number further, they're now looking at Dachshunds, PWDs and Briards---but if your breed has high incidence of HSA, please send samples!

Twenty five percent of dogs will develop cancer, and 50% of dog over age 10 will die of cancer. Many cancers have breed predispositions: Lymphoma: Old English Sheep dog, Boxer, Pointer, Golden Retriever, Rottweiler (Also evidence for Basset hound, St. Bernard, Scottish Terrier, Airedale and Bulldog.); Osteosarcoma: Large and giant breeds such as Irish Wolfhound, Scottish Deerhound, Great Dane, Bernese Mountain Dog, St. Bernard, Irish Setter, Golden Retriever, Doberman Pinscher, Rottweiler, Greyhound; Soft tissue tumors: Larger dogs such as Boxer, Bernese Mountain Dog, Airedale Terrier, Great Dane, Saint Bernard, Basset hound, Golden Retriever --- all have twice as many as the general canine population; Hemangiosarcoma: German Shepherd, Bernese Mountain Dog, Golden Retriever, Flat Coated Retriever, Portuguese Water Dog, Labrador Retriever, Boxer, Skye Terrier; Histiocytic sarcoma/malignant histiocytosis: Bernese Mountain Dog, Flat Coated Retriever, Rottweiler, Golden Retriever. Breen's lab is studying cytogenomic changes in canine lymphoma, leukemia, osteosarcoma, histiocytic neoplasia, urogenital carcinoma, intracranial malignancies, hemangiosarcoma and melanoma. If your dog suffers from any of these cancers, the bravest thing you can do is arrange to have a sample sent to his lab. "None of this work can be done without samples from your dogs," says Breen, while acknowledging the difficulty of doing so at an often grief-stricken time.

Orthopedics

The CHF has launched a Canine Athlete Initiative. Go to www.akcchf.org/CanineAthlete to download podcasts on a number of sports topics.

The emphasis this year was on fixing injured dogs. Gina Bertocci (University of Louisville) described a computer-simulation that calculates stresses on stifle ligaments, the movement of the tibia relative to the femur, and contact forces between the femur and menesci in stifles with intact cranial cruciate ligaments and following various CCL repairs, as well as those using a stifle brace instead of surgery. Such simulations will be used to compare the outcomes of various types of CCL surgeries.

Janet Van Dyke's talk on applying physical therapy (PT) techniques to dogs was eye-opening. Van Dyke, from the Canine Rehabilitation Institute, started by pointing out that we've always been told to cage rest our dogs following orthopedic surgery. But the current standard for humans is to start physical therapy immediately. Resting the affected area delays or prevents return to use. In humans, a raging debate continues about surgery versus PT for many conditions, including knee injuries and lower back pain. There's good evidence that PT produces equally good results. We are entering that debate with dogs.

In a study comparing two types of surgical treatment for cranial cruciate ligament repair with conservative (non-surgical) treatment, no differences in success were found. None of the current surgical treatments for CCL repair can prevent osteoarthritis. Conservative treatment may give satisfactory results for many patients and even allow equal return to sporting activities.  Conservative treatment of CCL does not change the instability of the joint, but may let the dog achieve a high level of function with an unstable joint.

In dogs with intervertebral disk disease, cage rest and surgery have long been the standard. But as far back as 1961, a JAVMA article written by a human physical therapist outlined the success he had in treating 82 dogs with IVDD using only nursing care, muscle relaxants, thermotherapy, massage, exercises and stretching, electrical stimulation, and ultrasonic therapy.

Canine rehabilitation also includes the use of prosthetics. Currently, dogs needing any part of a limb, even a foot, amputated end up having their entire limb amputated. But with newer prosthetics, that's not necessary. Van Dyke mentioned a dog that lost all four feet to frostbite, he's now running on four prosthetic feet!

Rehabilitation is not necessarily cheaper than surgery, and certainly more work. But it can accomplish things surgery alone can't. Van Dyke showed the progress of a Lab puppy with a broken neck who could only move his rear feet. With stimulation, passive movement, walking fully suspended from a sling, walking on a sling on an underwater treadmill, attaching elastic bands to his legs to assist when walking on the underwater treadmill, swimming in a pool, wearing orthotics that allowed a pre-dialed range of motion that was gradually increased, "Lucky" was walking and even running in two months!

Human physical therapists have a DPT degree that requires 4-5 year post-graduate training. With additional training, some are now working in veterinary practices. The new American College of Veterinary Sports Medicine and Rehabilitation will drive additional research and progress in this area.

Surgery and physical therapy don't always fix things. Sherman Canapp, of the Veterinary Orthopedic and Sports Medicine Group, spoke about the role of regenerative medicine for soft tissue injuries. Tendons and ligaments are subjected to major stresses during physical activity, and if injured due to repeated microtrauma, heal very slowly because of poor vascularity. Tendon ruptures or avulsions are typically treated by surgery, but core lesions---disruptions within the tendon---usually heal by fibrosis rather than regeneration. Fibrotic tissue is not as elastic and is thus more prone to re-injury. In horses, and now in dogs, use of stem cells or platelet rich plasma has been shown to heal and regenerate tendon core lesions, allowing return to activity without re-injury.

You must have a definitive diagnosis. Not only do you need to know exactly where to put the stem cells, but you must be sure the lameness isn't due to cancer, because stem cells help cancer cells multiple, too. Stem cells are harvested from bone marrow or adipose tissues, with the latter much easier, safer and more comfortable (basically a strip of fat tissue is taken from the area just behind the sternum). The cells may be processed in-house or sent off. Be very picky about who does it. Platelet rich plasma hastens healing when applied directly at the site of injury because of two growth factors within it. Plasma is derived as with any blood draw, and then processed to make it rich in platelets. Again, the laboratory that processes them is important. The cells are then injected right into the injured area using ultrasound to guide.

Canapp presented case studies of dogs with longstanding injuries that had not responded to previous therapies.  The dogs were given combined stem cell and platelet rich plasma injection, followed by physical therapy. Results were apparent within weeks, with full return to function within 6 months.

Bloat

The CHF is launching a Collaborative Bloat Initiative, with a free webinar describing bloat in lay language, continuing education for veterinarians showing gastropexy during spay/neuter, and funding two to three research projects at $250,000 each.

Elizabeth Rozanski, of Tufts University, spoke about bloat and multiple organ failure. As for causes, it doesn't seem to matter if you feed elevated, or twice versus once a day, or soaked kibble, or before or after exercise. It does seem to matter what breed you have (large and deep-chested dogs in general), whether they have close family members that bloated, and whether they tend to be nervous or stressed (as when traveling or being boarded or shown).  It may help to feed large versus small food size, and it may help to avoid weather extremes (sudden temperature changes). And exercise may be useful for promoting gut motility. Using anti-gas pills won't hurt, and may help because one study has shown that at least some of the gas in the bloated stomach is from fermented food, not swallowed air.

Surgery is costly ($2000 to $8000). Because of cost and the often pessimistic prognosis given by veterinarians, as many as 25% of bloating dogs are euthanized without surgery. Lactate levels are sometimes used to predict outcome but should not be used to decide euthanasia versus surgery. When promptly treated, 80-85% of dogs survive.

Sometimes dogs die within days of other organ failure, mostly affecting the lungs, liver, kidney and GI tract. Blood clotting abnormalities can be confusing, as some dogs have a bleeding tendency early on but others may clot too much later. It may be beneficial to treat with heparin even early in the course of therapy. Rozanski's group is studying the use of the thromboelastograph (TEG) clotting test that detects excessive clotting earlier than conventional tests.

Rozanski is a proponent of prophylactic gastropexy (tacking), even suggesting breeders of high-risk breeds may wish to have pet puppies tacked before leaving for their new homes. She also wishes pet insurance companies would provide a "bloat only" policy.

Cardiomyopathy

Kathryn Meurs (North Carolina State University) is known for her research into the genetics of heart disease. Cardiomyopathies are diseases of the heart muscle. The two most common types are Dilated and Arrhythmogenic, which together occur second only to valvular disease in dogs. Arrhymogenic Right Ventricular Cardiomyopathy (ARVC) is common to Boxers and to a lesser extent, Bulldogs. The heart muscle contracts well but microscopically, many of the muscle cells die and are replaced with fat cells, leading to abnormal electrical conduction. Affected dogs have an abnormal heartbeat that may cause them to faint or die suddenly. A genetic mutation has been found in a region of the genome involved in making a protein that sticks cardiac cells together. It seems to be inherited as an autosomal dominant; however, dogs with two copies of the mutation have more abnormal beats per day than with one copy. Usually. Actually, the mutation has about 72% penetrance, meaning that 72% of dogs with the gene will have disease, but 28% of dogs with the same gene will not.

Dilated cardiomyopathy (DCM) is most known in the Doberman Pinscher, but also occurs in many large breeds. However, it may be different kinds of DCM in different breeds. In humans, 24 different genetic mutations can cause DCM. In Dobes, the cardiac mitochondria, which is involved in cell metabolism, is abnormal. In at least some families of Dobes, dogs with a mutation in a mitochondrial gene develop DCM. The gene is an autosomal dominant. About 28% of Dobes with this gene develop DCM, suggesting that as with humans, there may be different genetic causes even within one breed.

DCM in Great Danes is again a different form, appearing to be caused by a sex-linked gene. This again suggests that you can't generalize DCM genetic studies between breeds. You have to start fresh: characterize the disease in your breed; characterize familial patterns; and characterize molecular aspects of the disease.

Realize that a gene test may not be as helpful as you hoped, especially in cases where the mutation has incomplete penetrance. Why do some dogs with the mutation show the disease and not others? Is it diet, daily activities, genetic background? And if you have an unaffected dog that has the mutation, how do you use that information to guide breeding decisions? Add to that the situation where you may have more than one mutation causing DCM in a breed, and you have another concern: Just because your dog "passes" the one available DNA test for DCM, it doesn't mean he may not carry a different gene for DCM. Meurs suggests dogs must still be phenotypically tested with Holter monitors and cardiac ultrasounds. She does not suggest wide-scale removal of dogs with the mutations, but balanced breeding to dogs not carrying the same mutation.

Vaccination

Adam Birkenheuer (North Carolina State University) addressed vaccination issues. Did you know 55,000 people die of rabies worldwide each year? With dogs the major source? And that while you can get exemption letters from your veterinarian saying your dog can't be vaccinated for medical reasons, if your dog bites somebody he will still be treated as an unvaccinated dog.

Approximately 20 vaccines are now available for dogs. The core vaccines (rabies, parvo, CAV-2 and distemper) should be given to all dogs; CAV-1, giardia and corona are NOT recommended; and the others (such as lepto) depend on your dog's particular circumstances. He also did not recommend the rattlesnake vaccine.

We always hear about "new" strains of parvo. There are at least five known variants: CPV-1 (extinct); CPV-2, 2a, 2b and 2c.  CVP-2c, the newest, has been known for over a decade, but is said anecdotally to cause severe disease in vaccinated dogs. But controlled studies have shown cross-protection from existing parvo vaccine.

Interference from maternal antibodies are the most common reason for vaccine failure. But by age 12, and especially 16, weeks about 99% of puppies respond to vaccination appropriately.

In a study of vaccine reactions looking at more than a million (!) dogs, the two main associations found were that the lower the body weight, the more likely an adverse event; and the more vaccines given at once, the more likely an adverse event.

What about vaccination and immune mediated blood problems?  One study showed that dogs with IMHA were more likely to have been vaccinated with one month prior, but this study has not been replicated.

Epilepsy

William Thomas (University of Tennessee) spoke about epilepsy. Different genes may be responsible for epilepsy in different breeds, as supported by research in the Wirehair Dachshund, English Setter, Border Collie and Lagotta Romagnolo. Phenobarbital is the most commonly used drug in dogs, but some newer human drugs such as zonisamide, levetiracetam, gabapentin and pregabalin, or treatments such as vagus nerve stimulation, surgery and acupuncture, may provide more effective seizure control with fewer side effects, although some may be expensive. Even with current treatment, a survey  showed that 95% of owners felt their dogs had good quality of life, 48% felt seizure control was adequate, and 55% felt the cost of advanced diagnostic testing was worth it.

There were other talks, too, on cytokines and nutrition, focus areas in GI research, preventing capsule opacities following lens replacement, modeling biomechanical forces after CCL surgery, a genetics primer, and a breeding and genetics discussion panel.

Eddie Dziuk, of OFA, talked about the importance of DNA banking for clubs. Did you know you can store frozen parts (like dewclaws and tails) in your home freezer (not the defrosting type) for future DNA analysis?  That blood yields the most samples, but even a cheek swab can be kept at home for years and still yield usable DNA? Did you know CHIC will bank DNA (no, not from tails, from blood) they collect at national specialties for half price?

The keynote speaker was Brian Hare, of Duke, who spoke about his work in canine cognition. Do dogs imitate? Navigate? Intentionally deceive? Take short cuts? Know what you can and cannot see? Know what you do and do not know? Understand causal properties like gravity? Understand symbols, like children do?  Think about others' thinking? Do breeds differ? But I'll wait to tell you more about that once I've finished running my dogs through the tests on his www.dognition.com site. So far, my dog appears to rival a sea cucumber in communication skills.