I was pleased to once again attend the AKC Canine Health Foundation Parent Club Conference. Here's a synopsis of the presentations:
Bloat and Multiple Organ Failure: Elizabeth Rozanski, Tufts
Management of bloat has advanced since the early days when prognosis was grim and treatment options were basically passing a tube or if possible, surgery. Survival increased with the introduction of large volume of IV fluids and prompt surgical treatment (that is, going to surgery within an hour of presentation---once fluids have taken effect--- rather than waiting for the dog to stabilize or improve before surgery). A huge improvement in long term survival came with the introduction of various types of stomach tacking (gastropexy). When promptly treated, 80-85% of dogs survive. Much research has focused on what causes bloat, but mostly it has shown that our initial ideas were probably wrong. 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, but with exceptions), 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.
Cost of surgery ranges from about $2000 to $8000, depending on area, time of day, and type of practice. Because of the high cost, and the often pessimistic prognosis given by veterinarians, as many as 25% of dogs with bloat are euthanized without surgery. It's often hard to decide based on current diagnostic criteria which dogs have a poor prognosis. Lactate levels are sometimes used to predict outcome but should not be used to decide euthanasia versus surgery. Stomach tacking during surgery should always be
performed.
Sometimes dogs survive the surgery but die within days of other organ failure, mostly affecting the lungs, liver, kidney and GI tract. Blood clotting abnormalities can be a confusing problem, as some dogs have a bleeding tendency early on but others may clot too much following surgery. Although counterintuitive, it may be beneficial to treat with heparin even early in the course of therapy. Rozanski's group is studying the use of a clotting test called the thromboelastograph (TEG) that can detect 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.
Epilepsy: William Thomas, University of Tennessee
About 1-2% of all dogs suffer from epilepsy. Of these, about 60% suffer from status (seizures lasting over 5 minutes) or cluster (multiple seizures in short period) seizures. These dogs have a significantly reduced average lifespan. Most dogs with epilepsy are diagnosed between 1 and 5 years of age. Other causes, such as stroke, tumor, encephalitis and fungal infection can also cause seizures.
Epilepsy is more common in some breeds, including Beagle, Belgian Shepherds, Bernese Mountain Dog, Dalmatian, Golden Retriever, German Shepherd, Vizsla, Border Collie, English Springer Spaniel, Irish Wolfhound, Keeshond, Labrador Retriever and Standard Poodle. 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.
Inherited Cardiomyopathies: Kathryn Meurs, North Carolina State University
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.
Arrhythmogenic 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 heart beat 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.
But---and this was not part of the presentation--- some Boxer and Dobe breeders wonder how useful a DNA test is if it essentially gives a large percentage of false positive and false negatives.
Applying Physical Therapy Techniques to Dogs: Janet Van Dyke, Canine Rehabilitation Institute
We've always been told to cage rest our dogs following orthopedic surgery. But as anyone who has had such surgery themselves knows, the current standard of treatment is to start physical therapy immediately. Resting the affected area delays or even 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 is 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 treatment, no differences in success were found. None of the current surgical treatments for CCL repair can prevent osteoarthritis. Conservative (non-surgical) 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 disc disease, cage rest and surgery have long been the standard of care. 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 amputation. But with newer prosthetics, dogs can use all four limbs. Van Dyke even gave an example of one dog that had lost all four feet to frostbite, that was now running on his 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 that had broken its neck when hit by a car. Initially it could only move its rear feet. It required stimulation, passive movement, walking fully suspended from a sling, walking on a sling on an underwater treadmill, attaching elastic bands to its legs to assist it walking on the underwater treadmill, swimming in a pool, wearing orthotics that allowed a pre-dialed range of motion that was gradually increased, until two months later, "Lucky" was walking and even running!
Canine rehabilitation is becoming more popular, but watch out for people claiming to do rehab without credentials. 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.
Regenerative Medicine for Soft Tissue Injuries: Sherman Canapp, Veterinary Orthopedic and Sports Medicine Group
Surgery and physical therapy don't always fix things. 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.
First, you must have a definitive diagnosis. You can't treat "front end lameness" without knowing what's causing it. Diagnostic procedures may include radiographs, MRI, ultrasound and arthroscopy. 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.
Then you need stem cells. You can get them from bone marrow or adipose tissues, with the latter much easier, safer and are comfortable to harvest (basically a strip of fat tissue is taken from the area just behind the sternum while the dog is under anesthesia). The cells may be processed in-house or sent off. Be very picky about who does it.
You could also use platelet rich plasma, which seems to hasten 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. You can't just inject them in the bloodstream or general area.
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 (even Border Collie agility!) within 6 months.
Infection & Immunity: Adam Birkenheuer, North Carolina State University
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 able to be replicated.
Hemangiosarcoma: Jaime Modiano, University of Minnesota
I should preface this by saying that Jaime Modiano is the single most devoted researcher of canine hemangiosarcoma (HSA). He works with a number of other researchers who also regularly report to CHF. So most of the work here is highly collaborative. He and his collaborators also work on other canine and human cancers, including osteosarcoma, lymphoma and melanoma--so first, the news on them:
Osteosarcoma: They have recently identified molecular subtypes of osteosarcoma that will enable better predictions of patient response to therapy. One subgroup has a median survival time of 3 months, whereas the other has a median survival of 14 months. You cannot tell these groups apart by any physical features, only by their genetic microenvironment. Patents have been submitted to make this test, which would take a few days to get back results, available in clinical practice.
Lymphoma: Treating dogs with lymphoma also gives widely varied results. Traditionally, veterinarians have classified the prognosis of B cell lymphomas as "bad" and T cell lymphomas as "terrible." But really cell type is not predictive, as there are long and short term survivors in both groups. Using a four-gene signature test, veterinarians could 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 aspirant. (This test could potentially be combined with a new test developed by another CHF-funded researcher, Matthew Breen, that can determine best therapy for B-cell lymphomas).
Hemangiosarcoma (HSA): Modiano terms it "the tumor from hell." By the time it's detected, it's too late. HSA can occur in any breed at any age, but is more common in large breeds, older (8-10 years) dogs and in certain breeds. First described in the 1950s, it was only treated with surgery. By the 1980s, chemotherapy was also being used and considered helpful with surgery.
Risk increases with age, but no age-related stratification by breed. So whatever the breed disposition is, it's for the disease, not the age at which it strikes. We still don't know the cause of HSA, but an hereditary risk factor is assumed based on breed predilections, and has been confirmed at a genetic level in Goldens. A recently published paper citing environmental and lifestyle factors has significant biases and is based on anecdotal findings.
HSA is classically described as a tumor of the endothelial cells, but that's probably not correct. Perhaps it is instead a tumor of the blood forming cells. It may be formed in the bone marrow and the tumor develops wherever it happens to land, be it the spleen, heart or elsewhere. This means removing the spleen to prevent splenic HSA won't help; it will just develop elsewhere.
Modiano's groups found a subgroup of endothelial precursor cells present in the blood of Goldens with HSA. Modiano believes these cells are the same no matter the breed, and no matter the site of the HSA tumor. This could provide a blood test for HSA. 1) It could help decide whether a splenic tumor was a hemangiosarcoma or a hemangioma without surgery. 2) It could provide early detection of HSA. But still must decide how to deal with the possibility of false positives and false negatives. See
http://cancer.landofpuregold.com/the-pdfs/cancerdiagnostics.pdf for a discussion of use and misuse of screening tests. A patent has been awarded but they still need a partner for distribution. A clinical trial is ongoing.
Beyond detection, how do we fight the tumor? One study has been published that used a toxin to kill HSA stem cells. A clinical trial is ongoing but too soon to know results.
They are also looking at hereditary traits that may contribute to HSA in Golden Retrievers. 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 .
Cytogenic Landscape of Canine Cancer: Matthew Breen, North Carolina State University
Cancer is the leading cause of death in pet dogs. 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 TUMOURS: 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.
In humans, aberrations in the chromosomes of tumor cells have been shown to help identify cancers, assist in localizing cancer-associated genes and select best treatment. Dogs appear to share many of these same cytogenomic changes. Breen's lab is studying cytogenomic changes in canine lymphoma, leukemia, osteosarcoma, histiocytic neoplasia, urogenital carcinoma, intracranial malignancies, hemangiosarcoma and melanoma.
Lymphoma: Breen developed a predictive test for response to certain therapies for dogswith lymphomas several years ago, but is still trying to get it on the market.
Mast cell tumors: Generally graded 1, 2 and 3, with grade 1 being good news, grade 3 bad news, and grade 2 who knows? Now a test can give more guidance as o whether a grade 2 tumor will act like a grade 1 versus a grade 3. If you have a dog with a grade 2 mast cell tumor in the last three years, its biopsy specimen may still be available at the testing facility. Please contact the Breen lab ([email protected]) as they would like access to it, especially if you have updated information on the tumor's grade.
Hemangiosarcoma: HSA ells are hard to work with because the cells are usually mixed in with normal cells. But analyses show three different clusters of cytogenonic 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. T 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! All samples and information will be merged with the data from the Modiano lab.
Other tests forthcoming 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.
"Without all the money and resources, none of this work can be
done without samples from your dogs---even though it is often difficult at such a grief-stricken time." --Breen.
Other talks: Cytokines and nutrition, focus areas in GI research, modeling biomechanical forces after CCL surgery, genetics primer, breeding and genetics discussion panel and canine cognition.
The Canine Cognition talk by Brian Hare was of course the most interesting. 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?
It's not interesting that dogs can learn a lot of words, says Hare. What's interesting is that at least some can use the exclusionary principle to learn them. In other words, tell a dog to find the "blablah" and if a new toy is among other toys all of which he already knows, if he can bring you the new one, and ID it as he blahblah, then he's used this exclusionary logic to deduce the name of the new toy. Some dogs, and human infants, can do this. No other species.
Dogs can follow pointing and gaze directions. Chimps can't. Foxes and wolves can, but only if hand raised.
Hare is working on a battery of tests that can predict working (guide or military) dog success, or help better place shelter dogs. Some dogs look for help when they can't reach a goal, others don't. One subtype is better for certain jobs than others. For trainers, test results could help diagnose why a dog has a harder time learning a particular task; maybe scores low in memory, or gesture interpretation, or high in cunning.
You can test your dog at www.dognition.com (for a fee, although a couple of sample tests are available for free). Tests are based upon scientifically verified protocols. Not only will you receive a report based on your dogs test scores for memory, empathy, cunning, communication and reason categories, but your dog's data will be entered into a huge database (more than 68,000 so far!) dogs that will enable breed differences to possibly emerge.
I have just signed up Pepe. I'll let you know how it goes...If I can get him to come.
Bloat and Multiple Organ Failure: Elizabeth Rozanski, Tufts
Management of bloat has advanced since the early days when prognosis was grim and treatment options were basically passing a tube or if possible, surgery. Survival increased with the introduction of large volume of IV fluids and prompt surgical treatment (that is, going to surgery within an hour of presentation---once fluids have taken effect--- rather than waiting for the dog to stabilize or improve before surgery). A huge improvement in long term survival came with the introduction of various types of stomach tacking (gastropexy). When promptly treated, 80-85% of dogs survive. Much research has focused on what causes bloat, but mostly it has shown that our initial ideas were probably wrong. 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, but with exceptions), 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.
Cost of surgery ranges from about $2000 to $8000, depending on area, time of day, and type of practice. Because of the high cost, and the often pessimistic prognosis given by veterinarians, as many as 25% of dogs with bloat are euthanized without surgery. It's often hard to decide based on current diagnostic criteria which dogs have a poor prognosis. Lactate levels are sometimes used to predict outcome but should not be used to decide euthanasia versus surgery. Stomach tacking during surgery should always be
performed.
Sometimes dogs survive the surgery but die within days of other organ failure, mostly affecting the lungs, liver, kidney and GI tract. Blood clotting abnormalities can be a confusing problem, as some dogs have a bleeding tendency early on but others may clot too much following surgery. Although counterintuitive, it may be beneficial to treat with heparin even early in the course of therapy. Rozanski's group is studying the use of a clotting test called the thromboelastograph (TEG) that can detect 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.
Epilepsy: William Thomas, University of Tennessee
About 1-2% of all dogs suffer from epilepsy. Of these, about 60% suffer from status (seizures lasting over 5 minutes) or cluster (multiple seizures in short period) seizures. These dogs have a significantly reduced average lifespan. Most dogs with epilepsy are diagnosed between 1 and 5 years of age. Other causes, such as stroke, tumor, encephalitis and fungal infection can also cause seizures.
Epilepsy is more common in some breeds, including Beagle, Belgian Shepherds, Bernese Mountain Dog, Dalmatian, Golden Retriever, German Shepherd, Vizsla, Border Collie, English Springer Spaniel, Irish Wolfhound, Keeshond, Labrador Retriever and Standard Poodle. 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.
Inherited Cardiomyopathies: Kathryn Meurs, North Carolina State University
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.
Arrhythmogenic 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 heart beat 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.
But---and this was not part of the presentation--- some Boxer and Dobe breeders wonder how useful a DNA test is if it essentially gives a large percentage of false positive and false negatives.
Applying Physical Therapy Techniques to Dogs: Janet Van Dyke, Canine Rehabilitation Institute
We've always been told to cage rest our dogs following orthopedic surgery. But as anyone who has had such surgery themselves knows, the current standard of treatment is to start physical therapy immediately. Resting the affected area delays or even 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 is 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 treatment, no differences in success were found. None of the current surgical treatments for CCL repair can prevent osteoarthritis. Conservative (non-surgical) 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 disc disease, cage rest and surgery have long been the standard of care. 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 amputation. But with newer prosthetics, dogs can use all four limbs. Van Dyke even gave an example of one dog that had lost all four feet to frostbite, that was now running on his 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 that had broken its neck when hit by a car. Initially it could only move its rear feet. It required stimulation, passive movement, walking fully suspended from a sling, walking on a sling on an underwater treadmill, attaching elastic bands to its legs to assist it walking on the underwater treadmill, swimming in a pool, wearing orthotics that allowed a pre-dialed range of motion that was gradually increased, until two months later, "Lucky" was walking and even running!
Canine rehabilitation is becoming more popular, but watch out for people claiming to do rehab without credentials. 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.
Regenerative Medicine for Soft Tissue Injuries: Sherman Canapp, Veterinary Orthopedic and Sports Medicine Group
Surgery and physical therapy don't always fix things. 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.
First, you must have a definitive diagnosis. You can't treat "front end lameness" without knowing what's causing it. Diagnostic procedures may include radiographs, MRI, ultrasound and arthroscopy. 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.
Then you need stem cells. You can get them from bone marrow or adipose tissues, with the latter much easier, safer and are comfortable to harvest (basically a strip of fat tissue is taken from the area just behind the sternum while the dog is under anesthesia). The cells may be processed in-house or sent off. Be very picky about who does it.
You could also use platelet rich plasma, which seems to hasten 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. You can't just inject them in the bloodstream or general area.
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 (even Border Collie agility!) within 6 months.
Infection & Immunity: Adam Birkenheuer, North Carolina State University
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 able to be replicated.
Hemangiosarcoma: Jaime Modiano, University of Minnesota
I should preface this by saying that Jaime Modiano is the single most devoted researcher of canine hemangiosarcoma (HSA). He works with a number of other researchers who also regularly report to CHF. So most of the work here is highly collaborative. He and his collaborators also work on other canine and human cancers, including osteosarcoma, lymphoma and melanoma--so first, the news on them:
Osteosarcoma: They have recently identified molecular subtypes of osteosarcoma that will enable better predictions of patient response to therapy. One subgroup has a median survival time of 3 months, whereas the other has a median survival of 14 months. You cannot tell these groups apart by any physical features, only by their genetic microenvironment. Patents have been submitted to make this test, which would take a few days to get back results, available in clinical practice.
Lymphoma: Treating dogs with lymphoma also gives widely varied results. Traditionally, veterinarians have classified the prognosis of B cell lymphomas as "bad" and T cell lymphomas as "terrible." But really cell type is not predictive, as there are long and short term survivors in both groups. Using a four-gene signature test, veterinarians could 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 aspirant. (This test could potentially be combined with a new test developed by another CHF-funded researcher, Matthew Breen, that can determine best therapy for B-cell lymphomas).
Hemangiosarcoma (HSA): Modiano terms it "the tumor from hell." By the time it's detected, it's too late. HSA can occur in any breed at any age, but is more common in large breeds, older (8-10 years) dogs and in certain breeds. First described in the 1950s, it was only treated with surgery. By the 1980s, chemotherapy was also being used and considered helpful with surgery.
Risk increases with age, but no age-related stratification by breed. So whatever the breed disposition is, it's for the disease, not the age at which it strikes. We still don't know the cause of HSA, but an hereditary risk factor is assumed based on breed predilections, and has been confirmed at a genetic level in Goldens. A recently published paper citing environmental and lifestyle factors has significant biases and is based on anecdotal findings.
HSA is classically described as a tumor of the endothelial cells, but that's probably not correct. Perhaps it is instead a tumor of the blood forming cells. It may be formed in the bone marrow and the tumor develops wherever it happens to land, be it the spleen, heart or elsewhere. This means removing the spleen to prevent splenic HSA won't help; it will just develop elsewhere.
Modiano's groups found a subgroup of endothelial precursor cells present in the blood of Goldens with HSA. Modiano believes these cells are the same no matter the breed, and no matter the site of the HSA tumor. This could provide a blood test for HSA. 1) It could help decide whether a splenic tumor was a hemangiosarcoma or a hemangioma without surgery. 2) It could provide early detection of HSA. But still must decide how to deal with the possibility of false positives and false negatives. See
http://cancer.landofpuregold.com/the-pdfs/cancerdiagnostics.pdf for a discussion of use and misuse of screening tests. A patent has been awarded but they still need a partner for distribution. A clinical trial is ongoing.
Beyond detection, how do we fight the tumor? One study has been published that used a toxin to kill HSA stem cells. A clinical trial is ongoing but too soon to know results.
They are also looking at hereditary traits that may contribute to HSA in Golden Retrievers. 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 .
Cytogenic Landscape of Canine Cancer: Matthew Breen, North Carolina State University
Cancer is the leading cause of death in pet dogs. 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 TUMOURS: 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.
In humans, aberrations in the chromosomes of tumor cells have been shown to help identify cancers, assist in localizing cancer-associated genes and select best treatment. Dogs appear to share many of these same cytogenomic changes. Breen's lab is studying cytogenomic changes in canine lymphoma, leukemia, osteosarcoma, histiocytic neoplasia, urogenital carcinoma, intracranial malignancies, hemangiosarcoma and melanoma.
Lymphoma: Breen developed a predictive test for response to certain therapies for dogswith lymphomas several years ago, but is still trying to get it on the market.
Mast cell tumors: Generally graded 1, 2 and 3, with grade 1 being good news, grade 3 bad news, and grade 2 who knows? Now a test can give more guidance as o whether a grade 2 tumor will act like a grade 1 versus a grade 3. If you have a dog with a grade 2 mast cell tumor in the last three years, its biopsy specimen may still be available at the testing facility. Please contact the Breen lab ([email protected]) as they would like access to it, especially if you have updated information on the tumor's grade.
Hemangiosarcoma: HSA ells are hard to work with because the cells are usually mixed in with normal cells. But analyses show three different clusters of cytogenonic 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. T 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! All samples and information will be merged with the data from the Modiano lab.
Other tests forthcoming 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.
"Without all the money and resources, none of this work can be
done without samples from your dogs---even though it is often difficult at such a grief-stricken time." --Breen.
Other talks: Cytokines and nutrition, focus areas in GI research, modeling biomechanical forces after CCL surgery, genetics primer, breeding and genetics discussion panel and canine cognition.
The Canine Cognition talk by Brian Hare was of course the most interesting. 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?
It's not interesting that dogs can learn a lot of words, says Hare. What's interesting is that at least some can use the exclusionary principle to learn them. In other words, tell a dog to find the "blablah" and if a new toy is among other toys all of which he already knows, if he can bring you the new one, and ID it as he blahblah, then he's used this exclusionary logic to deduce the name of the new toy. Some dogs, and human infants, can do this. No other species.
Dogs can follow pointing and gaze directions. Chimps can't. Foxes and wolves can, but only if hand raised.
Hare is working on a battery of tests that can predict working (guide or military) dog success, or help better place shelter dogs. Some dogs look for help when they can't reach a goal, others don't. One subtype is better for certain jobs than others. For trainers, test results could help diagnose why a dog has a harder time learning a particular task; maybe scores low in memory, or gesture interpretation, or high in cunning.
You can test your dog at www.dognition.com (for a fee, although a couple of sample tests are available for free). Tests are based upon scientifically verified protocols. Not only will you receive a report based on your dogs test scores for memory, empathy, cunning, communication and reason categories, but your dog's data will be entered into a huge database (more than 68,000 so far!) dogs that will enable breed differences to possibly emerge.
I have just signed up Pepe. I'll let you know how it goes...If I can get him to come.
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