Updated Health Notes: 

1. DPCA (Dobermans) have made both a Holter (24. hr. heart monitor device) and an echocardiogram (ultrasound of the heart) done by a board-certified cardiologist mandatory for their CHIC program in an attempt to identify DCM cases earlier and more thoroughly. There are several ongoing research projects for DCM that can ultimately translate into a gene-level test, which is a lot better (more direct, more specific, less expensive) that repeated clinical analyses that is all we now have offered, so I urge all Dane owners with any interest in helping rid this breed of DCM in Danes to contact Stephanie Herbst at TAMU who is currently working on our problem and to consider contributing to the Charitable Trust to help fund research on this deadly disease.  Right now breed surveys are showing between 10-25% of Danes are affected by this terrible problem.

6. SOLVING THE MYSTERIES OF CANINE AGING AND LONGEVITY By Sarah Canterberry, TAMU.
Scientists are working to assess the genes most likely to affect the aging process in the dog. It is a well-known phenomenon that the life expectancy of purebred dogs decreases as the breed size increases. This is the opposite of trends among mammals of different species. For example, mice may be expected to live only a few years while elephants may live as long as 70 years or more. The difference among dogs, researchers at TAMU ( Texas A&M University) College of Veterinary Medicine believe, is due in part to underlying genetic factors. Scientists here are working to assess the genes most likely to be linked to the aging process in an attempt to both increase the lifespan of dogs and improve their quality of life. The initial step in this process was to determine the exact effect size has on canine longevity. Data was collected primarily from internet sources on average height and weight standards, as well as the average life expectancy of pure breed dogs. Preliminary regression analysis of 117 breeds reinforced the longstanding view that as the average size of a dog breed increases, the average life expectancy decreases.

Next chromasomal locations of 54 genes in the dog and the human were compared. Included in this study were 26 genes shows to affect the life expectancy of either humans or mice, as well as 28 genes located in a small region of the human chromosome 4, which has been associated with the ability to reach excessive old age in a human population. Current work is focused in two areas. The first is defining single nucleotide polymorphisms (SNPs, which is called, "SNIPS" in the parlance, Ed. note), in seven genes of particular interest from the sets mentioned above. Analysis of these SNPs across various breed may help identify genes that cause larger dogs to experience a shorter life span in comparison with their smaller counterparts. DNA samples have been collected, in the form of buccal swabs from dogs of different sizes and different life expectancies. These samples will be used to compare the aforementioned genes between these diverse breeds in hopes of discovering genetic factors that contribute to the agin process in the dog. The other primary interest is to discover the effects oxidative stress has on the aging process in various dog breeds. OXIDATIVE STRESS has been shown to affect the aging process in mice, fruit flies, and worms. [ Ed. note: oxidative stress is essentially the result of a normal and natural process of cell function & involves a potentially toxic by-product of cellular metabolism long implicated in cellular damage. Nature never gives that she doesn't also take away? See this link for a review: 
http://www.oxisresearch.com/library/oxidative_stress.shtml ] Studies in humans have also implicated oxidative stress as one of the causative factors in the aging process. By investigating oxidative stress in dogs, researchers hope to discover mechanisms that allow different breeds to overcome oxidative stress. Assessments will be made to determine if there is any correlation between size of the breed that donated the initial skin samples and the reaction of the cells to the oxidative stress
event. 

7. Study Shows Inherited Links to Canine LYMPHOMA. By Jaime Modiano VMD PhD Colorado Health Sciences Center.

The lifetime risk & incidence of lymphoma are different among distinct dog breeds, signaling a unique opportunity to identify heritable factors that could be manipulated to reduce the risk. Lymphoma is one of the more common cancers seen in dogs, occuring about 2 to 5 times as frequently in dogs as in people. It is estimated that approximately 1 of every 15 dogs born today will get lymphoma at some point, most likely between the ages of 8 and 11. Lymphomas are cancers that arise from lymphocytes (white blood cells that fight disease). Normally these cells travel through the body in the blood steam and in another network of thin "tubes" called lymph vessels, which interconnect organs of the lymphoid system (spleen, lymph nodes, thymus). When a lymphocyte becomes cancerous, it divides out of control and produces large numbers of identical cells, which crowd the lymph nodes and make them swell.  Most cases of lymphoma appear as swollen "glands" or lymph nodes that can be seen or felt under the neck, in front of the shoulders, or behind the knee. Occasionally, lymphoma can affect lymph nodes that are not visible or palpable from outside the body, such as those inside the chest or in the abdomen. In these cases, dogs may have difficulty breathing, or they may have digestive problems (diarrhea, vomiting, or a painful abdomen). If left unattended, dogs with lymphoma will generally die within 3 to 4 weeks. Treatment with PREDNISONE (a corticosteroid) alone generally can indue short-lived remissions (usually less than 8 to 12 weeks), but this treatment can make the disease resistant to other treatments. Long-lasting remissions can be achieved for dogs with lymphoma, so the disease is considered treatable. Multi-agent CHEMOTHERAPY can produce remission of 12 to 18 months and occasionaly longer. The goal of treatment for canine patients is to maintain quality of life during their remission, so in most cases, drug doses used to treat dogs will be lower than those used for comparable disease in humans. This minimizes side effects but can still make dogs feel sick and weak during treatment. Other therapies include radiation therapy, and, more recently, bone marrow transplants, although the latter treatment remains experimental and is only available through specialized centers. Some of the more aggressive types of lymphoma are unresponsive to any available treatment. Unfortunately even those lymphomas that respond to treatment eventually recur in most cases. Cures are rare, and most dogs with lymphoma die from causes related to their disease. That shifts the emphasis to research into PREVENTING lymphoma. We do not know precisely what causes lymphoma. In cats, cows, mice, and people there are certain viruses that can lead to lymphoma, but no such viral agents have been identified in dogs. Similarly, no single environmental agent or toxin can be blamed for lymphoma (although some can increase the risk of the disease). Lastly, heritable risk for lymphoma cannot be assigned to a single gene, but indicates involvement and interaction among many genes. Also, the lifetime risk and incidence of lymphoma are different among distinct dog breeds, signaling a unique opportunity to identify heritable factors that could be manipulated to reduce this risk. A recently published study supported in part by the AKC Canine Health Foundation showed that the oldest breeds, including Spitz dogs and small Asian "lap dogs" share a predisposition for excess lymphomas that arise from cells called T-LYMPHOMCYTES suggesting these breeds retain inherited risk factors that arose ancestrally. In contrast, some recently derived European breeds such as Basset Hounds and Cocker Spaniels are predisposed to excess lymphomas that arise from cells called B-LYMPHOCYTES suggesting these tumors may stem from different risk factors....that arose during the process of breed derivation and selection. Retrievers show an approximately equal number of occurrences of lymphomas [ from both types of cell lines] and in Goldens, each of these tumor types arises from unique genetics characteristics. These exciting results provide the first level of insight that will allow scientists to identify heritable factors that influence the risk of lymphomas in both dogs and people. 

OTHER CANCER NEWS: 

LYMPHOMA TESTING: Recent surveys happily indicate that veterinarians are remarkably consistent in their ability to accurately diagnose lymphoma, even using such "old fashioned" methods as physical examination. (AVMA Feb 1505 issue) Cytometry however is more sensitive than mere fingers, with PARR (a canine equivalent of the "clonality assay") faring better than flow cytometry (which only picked up 70% of initial cases). Cytology typically results in a confirmed diagnosis & is recommended for a definitive diagnosis; cytometry is best suited for monitoring the dogs during treatment. CSU (Colorado State University) studies show that PARR detects 85% of confirmed lymphoid malignancies, and can confirm malignancies early than more conventional testing, but all methods have reasonable accuracy, and owners are encouraged to seek a veterinary consultation when finding enlarged lymph nodes on their dogs, as without treatment, lymphoma can progress rapidly and prove fatal. See the CSU site on this new diagnostic (PARR): http://www.cvmbs.colostate.edu/

ADVANCES IN TREATING CANINE CANCER: New treatments for melanoma, osteosarcoma and mast-cell tumors have recently been found. New York's AMC (Animal Medical Center) has recently developed a "DNA vaccine" that shows promise in treating malignant melanoma. Phillip J. Bergman, DVM, PhD, DACVCIM, head of oncology at the AMC, is in charge of clinical trials currently underway. He hopes to see a "melanoma vaccine" available to clinical veterinarians in the next 2-3 years. CSU has under development a technique to treat osteosarcoma called bone-transport osteogenesis, which essentially grows new (good) bone for dogs with bone cancer. Traditional "bone banking" (dog to dog) implant surgery and interoperative irradiation have their uses, but also their drawbacks, and newer "limb-sparing" procedure pioneered by Stephen Withrow DVM of the AMC is using the dog's own bone as a "replacement part" is now seen in wider use. But this other new & sophisticated limb-sparing technique called bone-transport osteogenesis, may prove even more fruitful. This procedure helps minimalize the incidence of infection. It was developed by Nicole Ehrhard VMD, DACVS, and involves shifting small segments of the patient's own local bone into the area where the tumor is excised. And UC-Davis has an experimental oral drug that is helping to prevent further tumor growth in dogs with mast-cell tumors. The drug effectively inhibits a metabolic process that leads to mast cell cancer, where a gene (c-kit) codes for a protein (Kit) that promotes the development and survival of normal mast cells. A mutation in the c-kit gene is at the heart of mast-cell tumors, resulting in uncontrolled growth, and so the drug effectively reverses this process, according to assistant professor and lead researcher, Cheryl A. London, DVM, PhD. Mast cell tumors are a common malignancy, occurring in up to 21% of the canine population. (More information on each RX at the appropriate website.) Furthermore, with the completion of the sequencing of the canine genome, researchers have gained new insight into identifying genes that predispose dogs to cancer. Genes that increase susceptibility to genetic forms of lymphoma, sarcoma and some other cancers have been found. Fifty percent of dogs 10 years or older will develop some form of cancer, however veterinary treatment has improved greatly in the past few years, and so the morbidity and mortality statistics are now much better.

TREATING CANCER PAIN IN COMPANION ANIMALS: There is a series of articles in the current (MAY 2005) Veterinary Medicine on treating pain in cancer patients. This is something to bring to your vet's attention and/or ask him/her to share with you. A conservative estimates assumes at least 50% of veterinary cancer patients experience some level of actual physiologic pain to some degree. In some cases treating the underlying malignancy may alleviate pain, but in others appropriate symptomatic therapy needs to be instituted for the overall welfare and quality of life of the patient in question. The first article in this series stresses that "one essential component of pain recognition is adequate communication with the owner. Owners know their pets better than anyone else." AAHA has published standards for pain assessment as does WHO and the article discusses various ways to accurately assess and monitor pain given there are too few clearly objective parameters. There is a chart (p. 356) that defines the expected level and signs of pain given a particular cancer diagnosis. It also talks about which diagnostic and therapeutic procedures can actually cause pain. The second article goes on to discuss, at length, various methods of treating cancer pain in dogs and cats. First stressed is the most rational way to treat pain is to treat the underlying tumor (i.e. with surgery, radiation, etc.). Secondly the goal in managing all companion animals with cancer should be one of improved overall quality of life, which includes some adequate form of pain management. Surgical options are outlined. Radiation therapy is discussed as well as chemotherapy. Multimodality treatment is outlined and then specific analgesics are also discussed. NSAIDS, particularly COX-2 inhibitors, would form the first tier & have multiple reasons for their efficacy. Opiods are still considered the mainstay of cancer pain therapy in human oncology, and this article asserts there should be no reason to assume a difference exists in veterinary oncology. Alpha-2 agonists, adjuvant drugs, NMDA antagonists, anticonvulsants, tricyclics, aminobisphosphonates, corticosteroids, and even local anesthesia may also all serve a function in control of pain associated with cancer. Charts list (p. 370 & 374) their relative efficacy and potential side-effects. Complementary therapies and rehab strategies are also discussed.

MORE CANCER LINKS:
A study for osteosarcoma that the GDCA is currently participating in: http://www.gdca.org/health/bonecancer.htm

The Veterinary Cancer Registry: 
http://www.vetcancerregistry.com/

A site that lists various research in canine cancer: http://www.smilingblueskies.com/new/studies_in_cancer.html

8. INTERVET has developed the first USDAA approved 3-year vaccines for distemper, adenovirus & parvovirus. It is called CONTINUUM DAP and became available to veterinarians in March 2005. Intervet has traditionally had the vaccines that performed best in many comparison tests. Continuum DAP was supported by challenge studies. Fort Dodge also offers a 3 year vaccine that is supported by a challenge study. Called DURAMUNE ADULT, it provides protections against distemper, parvovirus, adenovirus, hepatitis and parainfluenza and also offers three year immunity. These vaccines rid veterinarians of the issue of liability involved in following three-year vaccination protocols while using 1-year vaccines (in an off-label manner). Dog World has an in-depth article on HOW VACCINES WORK in the upcoming (JULY 2005) issue: pp 14-15. The central message is that splitting vaccines can result in an inadequate response (leaving the dog unprotected) Safety & efficacy, as well as breakthroughs on the horizon are also discussed. 

Three-year duration of immunity in dogs following vaccination against canine adenovirus type-1, canine parvovirus, and canine distemper virus. Gore TC, Lakshmanan N, Duncan KL, Coyne MJ, Lum MA, Sterner FJ. Intervet Inc, 29160 Intervet Lane, PO Box 318, Millsboro, DE 19966, USA. Vet Ther. 2005 Spring;6(1):5-14.

A challenge-of-immunity study was conducted to demonstrate immunity in dogs 3 years after their second vaccination with a new multivalent, modified-live vaccine containing canine adenovirus type 2 (CAV-2), canine parvovirus (CPV), and canine distemper virus (CDV). Twenty-three seronegative pups were vaccinated at 7 and 11 weeks of age. Eighteen seronegative pups, randomized into groups of six dogs, served as challenge controls. Dogs were kept in strict isolation for 3 years following the vaccination and then challenged sequentially with virulent canine adenovirus type 1 (CAV-1), CPV, and CDV. For each viral challenge, a separate group of six control dogs was also challenged. Clinical signs of CAV-1, CPV, and CDV infections were prevented in 100% of vaccinated dogs, demonstrating that the multivalent, modified-live test vaccine provided protection against virulent CAV-1, CPV, and CDV challenge in dogs 7 weeks of age or older for a minimum of 3 years following second vaccination.

9. AAHA has established "senior care" guidelines for older dogs & cats. There has been a lack of standard care in the veterinary field for aging pets, with only 14% of senior pets getting the recommended regular health screenings. Annual blood work for dogs seven years and older is emphasized, and biannual blood work is recommended for pets over ten. The guidelines provide reference material for veterinarians in clinical practice to establish good standards of care. Owners need to discuss their aging pets needs with their attending veterinarian, as a team effort is important in quality of life issues for older pets. For more on AAHA and it's support of veterinary practice and quality animal care, see: http://www.aahanet.org/

10. For those interested in vWD (von Willebrand's Disease), this is very straight forwardly discussed at the BMDCA's website. It is a very practical and layman-friendly article available at http://www.bmdca.org/health/vwd.htm Please note the percentages needed to define a dog as affected (below 20%), expected to clot (above 35%), as a carrier (30-100%), and normals (50-100%). This highlights the need for a gene test, as this current (blood) test is clearly not clear or particularly useful. The GDCA currently has an ongoing request for Great Danes to participate in developing a gene test for vWD that is breed specific: http://www.gdca.org/health/vwd.htm

11. The WCA has some interesting information on HOD, including recent information on the heritability pattern. They are finding this to be an immune-based disease and suspect an autosomal recessive inheritance pattern. For more details, see: http://www.weimclubamerica.org/health/hod.html

12. THYROID DISEASE UPDATE: Here is another compelling reason to follow the OFA enacted "gold standard" for thyroid testing (as originally set by such as Nachreimer & the "white paper" recently generated): FT4D is resistant to changes that are unrelated to the disease state while measures such as T4 are not, & so are not offering an accurate analysis of the state of the dog's thyroid. This study again proves that testing for TgAA, cTSH & FT4D is the best choice as offers the most accurate data on our dogs. See the abstract below for more information: 

"Serum thyroid hormone concentrations and thyroglobulin autoantibodies in trained and non-trained healthy whippets," Cindy van Geffen, Valérie Bavegems, Luc Duchateau, Katrien De Roover and Sylvie Daminet The Veterinary Journal Article in Press, Corrected Proof Abstract:" Numerous factors including non-thyroidal systemic diseases and drug administration can significantly alter canine thyroid function test results. Furthermore, the importance of breed specific variations has probably been underestimated. In this study, total thyroxine (TT4), free thyroxine (FT4), canine endogenous thyroid stimulating hormone (cTSH) serum concentrations and thyroglobulin autoantibodies (TgAA) were determined in a population of healthy whippets and compared to a control group of different breeds. Mean TT4 values were significantly lower in the whippets but no significant differences were seen between whippets and control dogs for FT4 and for cTSH. The prevalence of serum TgAA in the whippets was 2%, and this was not significantly different from the controls. The results suggest a breed variation for TT4, but not for FT4, cTSH and TgAA serum concentrations in whippets. Serum thyroid hormone concentrations were also compared between trained and non-trained whippets and it was concluded that regular training did not seem to have any significant influence."

Recent research (2004) also suggests that NSAIDs can interfere with normal thyroid panel results. This is preliminary, but veterinarians are now recommending that NSAID use be discontinued if possible before doing checks for thyroid function. Using the recommended OFA thyroid panel (FT4D, cTSH, TgAA) can possibly circumvent these problems and will provide the most accurate results on thyroid function. More info here on how to successfully accomplish breed thyroid panels. If checking thyroid for breed status (i.e. seeking OFA Thyroid normals), bitches should ideally be in anestrus, and animals ill or on medications should be checked at another time. See: http://www.gdca.org/health/chic.htm

13. New Test for Heartworm Drug Sensitivity: WSU (Washington State University's Veterinary Clinical Pharmacology Laboratory has developed a gene test for ivermectin/drug sensitivity that owners/veterinarians can use to identify dogs that have the mutation BEFORE administering various drugs that can result in illness and even death in certain dogs. Individuals then can be treated with alternative drugs or with dosage adjustments to protect them. The test identifies those dogs with one copy of the mutant gene, as well as animal with two normal or two copies of the mutant gene. Dogs with one copy of the mutant gene can be at increased risk of toxicity; dogs with two copies are potentially in grave danger of toxicity. Dogs with the wild-type (normal) gene can safely be administered drugs like ivermectin. The dogs with the mutated gene can be sensitive to other medications as well.

The gene has been dubbed MDR1 for Multiple Drug Resistance gene #1, and normally produces a protein that pumps various drugs out of the central nervous system, for example, thus avoiding toxic build up. Dogs with the mutated gene have a frame-shift mutation that results in a stop codon & so produces a nonfunctional protein. Various drugs can then accumulate in the brain & other tissues, resulting in various neurological and gastrointestinal effects typically. The gene is found in many herding breeds & is widespread in several breeds: in collies current studies indicate that less than 1/4 of the population is free of the gene. Ivermectin sensitivity is found scattered throughout a number of breeds, and although it's possible that other mutations are responsible for drug sensitivities in various breeds, WSU will genotype any dog for the MDR1 mutation.

Genotype testing offers owners a new opportunity to protect their pets. Treating individuals according to their individual genotype holds great promise for the future of what is now being called pharmacogenetics. Genotype testing also allows breeders the information to control the expression of various traits & so manage disease and limit the spread of various disease-inducing genes. For more on the service, email: vcpl@vetmed.wsu.edu or visit: http://www.vetmed.wsu.edu/depts-VCPL/

JP Yousha
Chmn., Health & Welfare Committee
Great Dane Club of America
http://www.gdca.org/healthandwelfare.htm
danehealth@gdca.org
432-684-8940 (CT-USA)

Permission to reprint as submitted for educational purposes is given. 
Submitted by JP Yousha, Chair, H&W Committee, GDCA 2004.

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