Disclaimer: ScottiePhile provides resources for informational purposes. The materials contained here are not intended to be used for the diagnosis or treatment of health problems or as a substitute for consulting a veterinarian.
A Successful Cure (to Persistent False Pregnancy)
By Carole Owen
Source: The Scotch Bark Newsletter, No other information given.
It didn't seem like the usual time for a pseudo-pregnancy, but Cherry was exhibiting classic signs. She spent all her time nervously lying in the hall by the bedroom door -- this is where her whelping box had been several weeks earlier. There would always be a toy or toys with her, which I'm sure Cherry considered her "babies". If the bedroom door were open, Cherry would dig in the storage boxes under the bed in an attempt to nest. This behavior continued for a month and didn't appear to be lessening.
When I read the report in Dog News, I decided thyroid supplementation was worth a try to see if it could switch Cherry back into her normal mode.
An increase of thyroid levels caused by a dosage of just .1 mg. Soloxine twice daily brought an immediate change in this bitch's behavior. Within a couple of days, Cherry was no longer exhibiting nesting behavior and was no longer nursing toy "babies". (NOTE: This bitch had already been tested for thyroid function on the Michigan State Thyroid Panel, so we were not blindly guessing at thyroid supplementation. She had tested normal, but was low normal, and according to the Dog News article, a prime candidate for this treatment.) I was grateful to have read this article because one option suggested to alleviate the persistence behavior of false pregnancy was a treatment with Prostaglandin F2 alpha. I knew Prostin was a miracle drug since it has resolved pyometra successfully in Cherry a year earlier, letting her go on to have a healthy litter. But I dreaded putting her through a Prostaglandin treatment, if something simpler might work. The Prostin procedure is highly unpleasant because of the massive contractions of the uterus that it causes, something you'd rather save in the last ditch arsenal. The thyroid supplementation worked with Cherry. It couldn't have been less traumatic!
Next time you are plagued with a persistent false pregnancy in one of your females, do check out the possible simple solution of thyroid supplementation with your vet. Dr. Priscilla Stockner, the canine reproductive specialist quoted in the Dog News article, is available for phone consultation at Canine Cryobank, Escondido, CA: phone (616) 739-1091.
Original Doc: bred03.doc
Anipryl, A new approach to managing canine Cushing's disease
By William W. Ruehl, VMC, PhD, DACVP
Deprenyl Animal Health, Inc.
7101 College Boulevard
Overland Park, Kansas 66210
Before 1997, options for the medical management of canine Cushing's disease were limited to human medications which sometimes were associated with adverse events such as adrenal toxicity or cortisol insufficiency. With the introduction of the monoamine oxidase inhibitor Anipryl, practitioners were given a more convenient, patient-friendly medical option, one that features unique modes of action directed at restoring regulation of the hypothalamic-pituitary-adrenal axis. Here, Dr Ruehl compares existing management options and presents sqfety and efficacy data from Anipryl licensing studies.
he previous article focused on the pathobiology of canine Cushing's disease and suggested new ways of looking at this serious geriatric endocrinopathy. An equally important consideration is the medical management of Cushing's. In January 1998, Pfizer Animal Health began marketing Anipryl (selegilinehydrochloride or L-deprenyl hydrochloride), the first and only prescription medication cleared by the U.S. Food and Drug Administration to control the clinical signs associated with uncomplicated canine pituary-dependent hyperadrenocorticism (PCH, or Cushing's disease). *
Anipryl allows veterinarians to medically manage Cushing's disease without causing either adrenal toxicity or insufficiency--side effects that have been associated with other medications.+ Moreover, veterinarians need not be concerned about inducing hypoadrenocorticism or an Addisonian crisis. With Anipryl, no loading dose (induction phase) or extensive ACTH endocrine monitoring tests that require frequent in-hospital visits are necessary, thereby reducing the risks associated with medical intervention, increasing client compliance, and giving practitioners greater peace of mind. Anipryl's safety, clinical efficacy, and convenience mean that now vet erinarians can comfortably and confidently offer clients another option for dogs afflicted with canine Cushing's disease.
TRADITIONAL MANAGEMENT OPTIONS
Traditional medical managementoptions for a dog with Cushing's disease include the adrenolytic agent mitotane or o,p'DDD (Lysodrenâ, Bristol-Myers Squibb Oncology), and the adrenal enzyme inhibitor ketoconazole (Nizoralâ, Janssen Pharmaceutica).
Lysodren, the most commonly used medication, and ketoconazole therapies do result in improvement of the clinical signs of PDH, presumably by decreasing cortisol secretory capacity. However, neither medication addresses the underlying pathophysiology of PDH and, in fact, their use results in further dysregulation of the HPA axis.1-3 While efficacy rates of up to 80% can be expected with either drug, significant adverse effects that may require discontinuation of the medication occur in 25% to 35% of dogs either during induction (dose titration) or long-term maintenance therapy.1,4,5 The potential adverse effects of Lysodren and ketoconazole are well known, and may include gastrointestinal upset, hepatotoxicity, and transient (ketoconazole) or, in rare cases, permanent (Lysodren) hypoadrenocorticism (Addison's disease).1,4-6 In addition, dogs receiving Lysodren should be evaluated with an ACTH response test every 3 to 6 months for life depending upon on how well they respond to the maintenance dosing regimen. Dogs developing Addison's disease require glucocorticoids and mineralocorticoids for life.
*"Uncomplicated indicates that a dog does not have another complicating disease associated with PDH, such as pancreatitis, diabetes mellitus, or pulmonary thromboembolism. In dogs with complicated PDH, it may be necessary to decrease blood cortisol levels more rapidly than is likely with Anipryl so that critical patients can be stabilized.
+Side effects of Anipryl may include vomiting, diarrhea, stereotypical behavior, increased salivation, and pale mucous membranes. Because senior dogs are more prone to other disorders and diseases, routine geriatric exams are recommended.
AN ALTERNATIVE MEDICAL MANAGEMENT OPTION
A new and innovative approach to the medical management of PDH has been added to veterinarians' armamentarium with the introduction of Anipryl (selegiline hydrochloride). Selegiline is widely recognized as a potent, selective, and irreversible inhibitor of monoamine oxidase type B (MAOB), one of the enzymes that degrade dopamine in the brain. By specifically inhibiting MAOB activity, selegiline helps elevate dopamine concentration and availability within the synaptic clefts of dopaminergic neurons.
The compound inhibits MAOB activity by a "suicide reaction," in which a competitive, reversible interaction initially occurs between selegiline and MAOB to form a noncovalent complex. Subsequent oxidation of this inhibitor-enzyme complex is then followed by the formation of an irreversible covalent bond. This unique mode of action promotes normalization of dopamine levels and ultimately helps restore HPA axis regulation (Figure 1). 1
By working at the hypothalamic-pituitary level, selegiline permits medical management of PDH without adrenal toxicity or insufficiency. Furthermore, since Anipryl is nonadrenolytic, it does not inhibit glucocorticoid production, and thus ACTH stimulation testing and routine measurement of serum electrolytes are not necessary.1 However, because the disease affects older dogs, periodic routine evaluations are recommended. The active ingredient of Anipryl is selegiline hydrochloride. Studies in humans show that C14-labeled selegiline binds into brain regions known to be rich in MAOB activity, where it exerts its most important pharmacological effects.7
MODES OF ACTION
Several modes of action may contribute to selegiline's pharmacological effects. The most significant of these involve the effects of selegiline on dopaminergic transmission and dopamine metabolism, particularly through the inhibition of MAOB. Selegiline increases dopamine concentrations in the synaptic cleft by:
Decreasing presynaptic dopamine reuptake, which appears to be reversible even after continuous medication 8, 9
Increasing phenylethamine concentration, another substrate of MAOB, which also potentiates dopamine activity8, 9
Enhancing impulse-mediated releases of catecholamines10, 11
Increasing synthesis of l-amino acid decarboxylase, which, in turn, increases dopamine synthesis1
After detaching from postsynaptic receptor sites, neurotransmitters may be either degraded enzymatically, or they may diffuse to reuptake receptor sites on the presynaptic neuron for uptake by the cell. Investigators have proposed that selegiline inhibits reuptake of dopamine and may increase its synthesis by blocking the presynaptic dopamine autoreceptors that regulate dopamine synthesis. 12 This effectively increases the amount of neurotransmitter available to interact with the postsynaptic cell.
In addition, selegiline decreases production of toxic free radicals and increases their removal through activation of superoxide dismutase and catalase, two enzymes responsible for scavenging and removing free radicals.9
DEFINING THE SAFETY PROFILE
Target animal safety study
A placebo-controlled, blinded pivotal study was conducted to determine the relative safety of Anipryl when administered orally to adult dogs at one, two, three, and six times the recommended initial daily dose of 1 mg/ kg of body weight over a period of six months (183 days).
Fig. 1-By inhibiting MAOB activity, Anipryl promotes normalization of dopamine levels, which, in turn, improves regulation of the HPA axis (thick, dashed arrows).
Twenty purebred male beagles and 20 female beagles, ranging from 2 to 7 years of age, were housed in an environmentally controlled laboratory setting and assigned randomly to one of five treatment groups by age and sex. Groups, containing four males and four females each, were then randomly assigned to one of five treatments (Table 1).
Anipryl was shown to be safe for dogs at the recommended dose of 1.0 mg/kg to the highest labeled dose of 2.0 mg/kg. In the 3 mg/kg and 6 mg/kg (1.5 and 3.0 times the highest recommended label dose) groups, salivation, decreased pupillary response, and decreased body weight were observed. At the 6 mg/kg dose, panting, increased alanine aminotransferase (ALT), dehydration, and stereotypic behaviors such as weaving were noted. Some side effects were seen in all groups including the placebo group. No changes in blood pressure, heart rate, electrocardiogram readings, or ophthalmic exams were observed. For additional information, see the Anipryl package insert.
Two-year placebo-controlled safety study
In a two-year placebo-controlled, fullv blinded safety study, 82 beagle dogs ranging in age from 2.8 to 16.4 years (average age: 11 years) were divided into 41 pairs matched by age, sex, and body weight. One dog in each pair received a single daily dose of Anipryl at 1 mg/kg body weight. The other dog was given an indistinguishable placebo. The dosing continued for more than 2 years.
No significant adverse health effects were observed in dogs of various ages given 1 mg/kg body weight of Anipryl for more than 2 years.
In clinical trials involving 132 dogs, only 5% of dogs experienced adverse events that led to discontinuation of Anipryl administration, dismissal from a study, or a dose reduction.13 These side effects included vomiting, diarrhea, stereotypical behavior, hypersalivation or pale mucous membranes. In addition, no adverse drug interactions between Anipryl and a variety of antibiotics, anthelmintics, ectoparasiticides, heartworm medications, analgesics, or antihistamines were reported after three years of clinical trials. Because senior dogs may require concommitant therapy with several medications, care should be taken in diagnosing, medicating, and monitoring older dogs.
Although no adverse drug interactions were reported in the clinical trials in dogs, it seems prudent to avoid the combination of Anipryl and tricyclic antidepressants and Anipryl and selective serotonin reuptake inhibitors. Concurrent use of Anipryl with ephedrine or potential MAO inhibitors (such as amitraz) is not recommended.
Anipryl is contraindicated in patients with known hypersensitivity to this drug. In humans, selegiline is contraindicated for use with meperidine, and this contraindication is often extended to other opioids.
The effect of Anipryl on breeding, pregnant and lactating bitches, and breeding dogs has not been determined.
A six-month pivotal clinical trial involving 41 veterinary practices and colleges of veterinary medicine throughout the U.S. was one of several studies conducted to assess the efficacy and safety of Anipryl in controlling the clinical signs associated with uncomplicated canine PDH. Fifty-two client-owned dogs with confirmed, spontaneously occurring PDH were dosed once daily with 1 mg/kg body weight of Anipryl. Dogs were evaluated on a monthly basis by both owner and veterinary assessment of clinical signs. At the end of the six-month trial, veterinarians were asked to give a final assessment of the overall improvement of each dog.
In this pivotal study, Anipryl was shown to be effective for the control of clinical signs associated with canine PDH, according to veterinary investigators (Figure 2) and dog owners (Figure 3). In their final evaluation of overall response, veterinarians indicated that:
48% of dogs had improved
35% had slightly improved
A particularly significant (P< .05) improvement was the change observed in abdominal circumference, which decreased by an average of approximately 0.5 inches per month.
Owner satisfaction was demonstrated by the fact that 93% of the owners (25/27) whose dogs were eligible for extended compassionate use elected to continue Anipryl medication, despite the necessary inconvenience associated with participation in any clinical trial.
LDDS TEST RESULTS
As an added measure of efficacy, response to Anipryl was evaluated by comparing LDDS test results obtained before initiation of medication with those obtained after medication. At every time point after Anipryl initiation, the LDDS value for the population was lower than the first enrollment LDDS value.
After one month of medication, the LDDS value declined by an average of 22%, and this reduction was sustained throughout the study. These results indicate that Anipryl helped return the balance of the HPA axis toward normal, and that, at a dose of 1 mg/kg body weight once daily, the improvement was sustained in the population throughout the duration of the trial.
For dogs >30 kg or 66 lb, tablet sizes may be combined as needed to reach the recommended daily dose of 1 mg/kg.
0 10 20 30 40 50 60 70 80
Percent of Dogs Improved+
*Abdominal circumference measurements decreased approximately 0.5 inches per month
+Dogs whose clinical assessment for a particular variable was normal at the start of the study and at all
time points during the study were not included in the assessment
Fig. 2- Percentage of dogs improved (veterinary investigator assessments).
0 10 20 30 40 50 60 70 80 90 100
Percent of Dogs Improved*
*Dogs whose clinical assessment for a particular variable was normal at the start of the study and at all time points during the study were not included in the assessments
Fig. 3-Percentage of dogs improved (pet owner assessments).
ANIPRYL PRODUCT PROFILE*
Restoration of depleted dopamine levels; enhancement of dopaminergic nerve function
Reduction in toxic free radical production; increased removal of toxic free radicals
Enhanced release of other neurotransmitters such as norepinephrine
Monoamine oxidase-type B (MAOB) inhibitor
Selegiline hydrochloride/L-deprenyl hydrochloride
Control of clinical sips associated with uncomplicated PDH or Cushing's disease
Route of administration
Peak blood plasma concentrations
20 to 30 minutes following oral administration of 1 mg/kg body weight
Approximately 79 minutes (range 45.9 to 109.7 minutes) after a single oral dose of 1 mg/kg body weight
Selegiline is metabolized in the liver to l-desmethylselegiline (DES) and l-methamphetamine. Methamphetamine is further metabolized to l-amphetamine. No racemic transformation has been detected.
In clinical trials, Anipryl proved effective in controlling the clinical signs of uncomplicated PDH, according to veterinary investigators and dog owners. At the end of a six-month study, veterinary assessments indicated that 48% of dogs had improved and an additional 35% of the dogs had slightly improved. *
In a two-year blinded safety study, 82 beagle dogs, ranging in age from 2.8 to 16.4 years, were divided into 41 pairs matched as closely as possible by age, sex, and body weight. One dog in each pair received a single daily dose of Anipryl at 1 mg/kg body weight; the other dog, a placebo. Dosing continued every day for more than 2 years. No significant adverse health effects were observed in dogs of various ages given 1 mg/kg body weight of Anipryl for more than 2 years.
In a laboratory safety study, Anipryl was administered orally to healthy adult beagles once daily for six months at doses of 0, 1, 2, 3, or 6 mg/kg (0.5X, IX, 1.5X, and 3X the maximum recommended daily dose of 2.0 mg/kg). The drug was demonstrated to be safe at the recommended dose range of 1.0-2.0 mg/kg. The following statistically significant clinical observations were noted in dogs in the 1.5X and 3X groups: salivation, decreased pupilary response and decreased body weight despite normal to increased feed consumption. Additional reactions seen at the 3X dose included panting, decreased skin elasticity (dehydration) and stereotypic behavior, i.e., weaving (repetitive left to right movement) in the cage. This repetitive movement started several hours after dosing but was no longer present at the time of the next morning dose. There were no changes noted in blood pressure, heart rate, and ECG parameters, nor were there any ophthalmic changes. *
Some dogs may experience side effects, including vomiting, diarrhea, stereotypical behavior, hypersalivation or pale mucous membranes.
It is prudent to avoid a combination of Anipryl and tricyclic antidepressants and Anipryl and selective serotonin reuptake inhibitors.
Concurrent use of Anipryl with ephedrine or potential MAO inhibitors (ainitraz) is not recommended.
If warranted, alternative therapy should be considered if complications of PDH are evident at the time of diagnosis or emerge during Anipryl therapy.
Concurrent use of Anipryl with other therapies for PDH has not been reported.
Close monitoring is recommended as is appropriate for all geriatric patients.
The effect of Anipryl on breeding, pregnant and lactating bitches, and breeding dogs has not been determined.
Should not be used in dogs exhibiting previous hypersensitivity to selegiline
In humans, selegiline is contraindicated for use with meperidine; the contraindication is often extended to other opioids
Tablets in 2 mg, 5 mg, 10 mg, 15 mg, and 30 mg strengths
Packaged in blister-packs of 30 tablets each
Initially, 1 mg/kg body weight/day
If no improvement after 2 months, 2 mg/kg/day
*For additional product profile informatino, see the Anipryl insert
CONVENIENT DOSING AND MONITORING HELP COMPLIANCE
Anipryl is administered orally once a day for the control of clinical signs associated with uncomplicated PDH. The dose is started at 1 mg/kg body weight. The patient should be reevaluated regularly during the first two months of therapy for clinical response. If no improvement in clinical signs is evident after two months, the dose can be increased to a maximum of 2 mg/kg per day. Anipryl is not indicated for the treatment of dogs with iatrogenic Cushing's or ADH.
For maximum convenience and dosage compliance, Anipryl is available in five tablet strengths--2, 5, 10, 15, and 30 mg---each of which is a different shape. Five tablet strengths provide one-tablet-per-day dosing for most dogs (Table 2). The tablets are packaged in blister cards of 30 tablets each, enough for a one-month supply.
Since Anipryl is not toxic to adrenal cells, a stringent schedule of follow-up visits for laboratory testing is not required. Response to therapy should be based on history, physical examination, and resolution of clinical signs associated with uncomplicated PDH.
While clinical signs may improve, blood cortisol levels can still remain above normal. For this reason, treatment success with Anipryl is best evaluated by improvement in clinical signs. However, because dogs with PDH usually are older dogs-and more likely to develop other medical problems-practitioners should establish appropriate schedules for followup with owners and clinic visits to monitor the'dog's general health.
A profile of key product characteristics is given in Table 3.
ANIPRYL GIVES OLD DOGS A NEW LEASE ON LIFE
Anipryl provides practitioners with a new medical management option:
Unlike other medications, Anipryl works at the level of the hypothalamus and is not toxic to the adrenal glands. Anipryl inhibits MAOB and helps restore HPA axis function by promoting normalization of dopamine levels and enhancing dopaminergic nerve function.
Because it works at the level of the hypothalamus, Anipryl allows you to manage Cushing's disease without adrenal toxicity and the fear of potentially inducing hypoadrenocorticism (Addison's disease).
In clinical trials, Anipryl was proven to be effective in controlling the signs of uncomplicated PDH. Veterinary assessments during a six-month study showed that 48% of the dogs improved and an additional 35% improved slightly. In the same trial, 93% of the owners of dogs eligible for compassionate use asked that their animals be allowed to remain on Anipryl at the conclusion of the study.
With Anipryl there is no loading dose (induction phase) nor extensive ACTH endocrine monitoring tests, which reduces the risks associated with medical intervention, increases client comfort and compliance, and gives practi- tioners greater peace of mind.
Anipryl enables you to approach visits with owners of PDH dogs with greater confidence. In situations where dogs are diagnosed with uncomplicated PDH, you can provide assurance that signs associated with Cushing's disease are manageable and that Anipryl can help maintain quality of life for both dogs and owners.
1. Bruyette DS, Ruehl WW, Entriken, TL, et al. Treating canine pituitary-dependent hyperadrenocorticism with L-deprenyl. Vet Med 1997; 92(8):710-724.1
2. Bruyette D. Aging and canine hyperadrenocofticism: Relationship to pathogenesis and potential therapies. Proceedings of the Fourth Canine Geriatric Symposium, sponsored by Deprenyl Animal Health, Inc, in conjunction with the 64th annual meeting of the American Animal Hospital Association, San Diego, CA, 1997.
3. Nelson RW, et al. Effect of o,p'-DDD therapy on endogenous ACTH concentrations in dogs with hypophysis-dependent hyperadrenocorficism. AIVR 1985; 46:1534.
4. Kintzer PP, Peterson ME. Mitotane (o,p'DDD) treatment of 200 dogs with pituitary-dependent hyperadrenocorticism. J Vet Intertn Med 1991; 5:182-190.
5. Bruyette DS, Feldman EC. Ketoconazole and its use in the management of canine Cushing's disease. Compen Cont Ed 1988; 10:1379-1386.
6. Behrend EN. Efficacy of and side effects associated with use of ketoconazole as treatment for canine Cushing's syndrome (Abst). Vet Intern Med 1996; 10(3): 182.
7. Heinonen EH, Lammintausta R. A review of the pharmacology of selegiline. Acta Neurol Scand 1991; 84 (Suppl 136):44-59.
8. Bruyette DS, Ruehl WW, Entriken TL, et al. Management of canine pituitary-dependent hyperadrenocorticism with L-deprenyl - (Anipryl). Vet Clin North Ant Small Anim Pract 1997; 27(2):273-286.
9. Gerlach M, Riederer P, Youdin MH. The mode of action of MAOB inhibitors. In: Szelenyi 1, ed. Inhibitors of Monamine Oxidase B: Pitarttiaeology and Clinical Use in Neurodegenerative Disorders. Basel, Switzerland: BirkhAuser Verlag; 1993:183-201.
10. Knoll J, et al. (-) Deprenyl and (-) 1-phenyl-2-propylaminopentane, [(-) PPAP], act primarily as potent stimulants of action potential-transmitter release coupling in the tatecholarninergic neurons. Life Sci 1996; 58:817-827.
11. Dodman and Shuster. Psychopharmacology of animal behavior disorders. Blackwell Science Inc; 1998:183-201. 12. Mahmood I, Peters, DK, Mason, WD. The pharmacokinetics and absolute bioavailability of selegiline in the dog. Biopharm Drug Dis 1994; 15:653-664.
13. Package insert (USA) for Anipryl tablets (selegiline hydrochloride, L-deprenyl hydrochloride). Pfizer Animal Health; December 1997.
ABOUT THE AUTHOR
William W. Ruehl, VMD, PhD, DACVP, is Vice President of Scientific Affairs for Deprenyl Animal Health, Inc., Overland Park, Kansas. He helped design and direct the clinical and developmental trials for Anipryl. Dr. Ruehl received his VMD degree from the University of Pennsylvania in 1979 and completed an internship there in companion animal medicine and surgery. He was a resident in clinical pathology at the University of California-Davis and earned a PhD degree in comparative pathology from the same institution. Dr. Ruehl is a Diplomate of the American College of Veterinary Pathologists and a member of numerous professional associations including the American Animal Hospital Association, the American College of Veterinary Pathologists, the Animal Veterinary Society for Animal Behavior, and the American Society for Investigative Pathology.
The author thanks Gary Svatos for assistance with the article. Page 11 photo by John Noliendorfs.
Bernadette’s Story: Diabetes, Cataracts, Blindness and Sight Restored
By Susan Morris
Stornoway Scottish Terriers
I’ve owned, bred and shown Scotties for 20 years. Formerly a long-time resident of Idaho, I now live in western WA with my husband of 29 years, Steve. Steve loves the dogs as much as I do and I couldn’t accomplish all I do without him.
I’ve been a member of the Scottish Terrier Club of America since 1984 and am currently active with the STCA’s ScottiePhile project, a compilation of over 200 health articles pertaining to dogs in general, Scotties in particular. I’m also a member of the All Terrier Club of Western Washington; The Scottish Terrier Club (England) and The Scottish Terrier Breeders’ & Exhibitors’ Association.
I don’t breed very often; only when I want my next show prospect, there have only been 7 litters in the past 20 years. Our dogs are pets first, show dogs second. Currently, there are 6 Stornoway Scots in our household, three generations ranging in age from 18 months to 11 years. Black, brindle and wheaten, there’s at least one of each color!
In addition to all things “Scottie,” I love to garden. In spring, summer and fall you’ll find me and the dogs digging in the dirt and in the winter we can be found in the greenhouse.
It is my hope that Bernadette’s story makes a difference for other dogs that are diagnosed with diabetes - by encouraging their owners to see a veterinary ophthalmologist just as soon as the diagnosis is made. Sadly, almost all dogs with diabetes will go blind from diabetic cataracts within 6-9 months of diagnosis, so time is of the essence.
ome birthday present. 2 days before her 11th birthday, Bernadette was diagnosed with diabetes. She’d been slowing down the previous month or so, was drinking lots of water and urinating in equal measure. I naturally thought of Cushing’s Disease, but most alarming was the fact that in spite of a good appetite, she was losing weight. On May 30, 2003, after exams, ex-rays, blood and urine tests, Dr. Roden of South Fork Veterinary Service in Onalaska, WA told me “Bernie” had diabetes.
Bernie spent the next week at Dr. Roden’s office during the daytime, while he monitored what he called an Insulin Curve. Early each morning a blood sample was drawn, then she was fed her morning meal and given an injection of insulin. Every two hours throughout the day blood was drawn to see how her body was responding to the insulin. The goal was to give just enough insulin to keep her blood glucose level between 60 and 120mg/dL. The amount of insulin was slowly increased that week until Bernie’s customized dosage of 8 units twice daily was found to be perfect for her. (Her blood glucose had been 524 mg/dL the week before, by the end of that Insulin Curve it was 102 mg/dL).
I was anxious for the week to be over so Bernie could be at home with us, but I dreaded having to give the insulin shots myself. I didn’t think I could do it, but Dr. Roden patiently taught me to draw the insulin into the tiny syringe, to lift the skin on her neck and poke it in so smoothly she didn’t even feel it.
I’ve learned it’s important to keep a regimented routine for your diabetic dog. Bernie’s insulin, Novolin N, is injected every 12 hours. Dr. Roden prescribed Eukanuba® Glucose Control dry dog food for Bernie. Her daily ration of food (2 cups) is divided throughout the day on a schedule based on what Dr. Roden learned about her response during the Insulin Curve. I feed her 1/3 of her ration at 8 am along with an injection of 8 units of insulin; another 1/3 ration at 10 am and the final 1/3 ration at 8:00 pm when I give her the second injection of 8 units of insulin. I give Bernie one regular strength DermCap with her morning meals. She gets no table scraps or snacks other than occasional raw green vegetables. A week after Bernie’s insulin dosage and feeding schedule was established she had another blood glucose recheck, happily she was steady at 102.
I thought we were doing so well those first few days. But on June 11th Bernie began having trouble seeing. I’d found some great websites about pets and diabetes, so I’d read that blindness can be a side effect of diabetes, but you never really think it could happen to your dog. But it was true, it was happening to my dog – in 5 incredibly short days Bernie was completely blind. I’ll never forget that morning when I lifted her down from the bed and instead of heading down the hall; she walked into the wall, standing like a statue, afraid to move. My shock and fear quickly matched hers. I helped her outside and could tell she was very confused as well. I wonder what she was thinking? “Are all the lights turned off? Is it still night time?”
6-15-03, in another day Bernie would be completely blind
Bernie’s fear and confusion gave way to simply giving up. I suppose she was too afraid of bumping into things to try to find her way around. The only high points in her day seemed to be meal times.
It was so odd, less than a month before this I knew next to nothing about diabetes. Now, here I was dealing with my beloved Bernie needing insulin shots twice a day, and who was completely blind from the disease. It was overwhelming. Websites I found described how easily dogs adapt to blindness; that their other senses take over and you sometimes can’t even tell a dog is blind. Not our Bernie, she’d given up. All she wanted to do was sleep and be near me. It made us so sad to watch this energetic “youngster” of 11 turn into an old dog so quickly. It broke our hearts to watch her favorite Kong Ball roll right by her, unseen, as we tried to find a game she could still enjoy.
I searched my dog books, the internet, ScottiePhile articles, etc. for answers to my many questions. No one was able to tell me exactly why diabetic dogs go blind. What are the mechanisms involved? Was Bernie a candidate for the cataract surgery I found a little information about? Was it terribly expensive, as most websites hinted at? Cost seemed to be the main issue why folks didn’t have it done, so I assumed it must be thousands and thousands of dollars. I needed to understand what was happening to Bernie, but couldn’t find the answers. Even if the surgery was financially out of the question, I still needed to know what our options were. Would surgery be an option indefinately? Maybe I could save enough money in a year…did it matter how long the dog had had cataracts? These were all questions I couldn’t seem to find answers to.
We had to take a business trip to north Idaho at the end of June. We took our camper so we could comfortably take all the dogs with us. I dreaded the week long trip but it turned out to be real blessing. While we were there, I visited with one of the vets who used to take care of my dogs before we moved. Dr. Bloxham hesitated to try to answer all of my questions; he said discoveries and procedures change so quickly in the field of ophthalmology, his information might be wrong, so he encouraged me to talk to veterinary ophthalmologist, Dr. William Yakely of The Animal Eye Clinic, in nearby Spokane, WA.
Right away I called Dr. Yakely’s office and spoke with his assistant who answered many of my questions regarding the cost of the surgery and what I could expect for follow-up care. It wasn’t as bad as I’d expected, she told me it would be from $1400 to $1500 including the surgery, all the medications and follow-ups. Dr. Yakely had an appointment available on Thursday, the day before we were to drive home, so I quickly scheduled the appointment for Bernie.
Thursday couldn’t come fast enough. From the moment Dr. Yakely walked into the exam room I knew we were in good hands. Finally, someone was able to answer all of my questions! He not only talked to me, he drew pictures - this man knew how to explain things!
Dr. Yakely told me the reason diabetic dogs go blind is that the lens in their eye is the one organ that cannot rid itself of excess sugar. The lens fibers become dehydrated in the presence of the trapped sugar. The fibers die and become white – much like our fingernail responds to being hit with a hammer. Hence, the whitish blue color of the cataract.
In response to this insult, the lens swells, causing pain and discomfort to the dog. Then the lens capsule actually tears and protein from the swollen lens is released into the eye. This progresses to Uveitis, an inflammation of the lining of the eye caused by the protein leaking from the swollen lens. Since this protein has never been seen by the body before, always having been enclosed in the lens capsule, the body treats it as an invader. Dry. Yakely said you might as well put a thorn in they dog’s eye, it is that irritating.
The protein leakage from blood vessels blocks the outflow drain and produces secondary glaucoma (a rise in interocular pressure) which damages the rods, cones and optic nerve. (Yes, contrary to popular belief, dogs do have a small percentage of cones and DO see the basic colors!) Once this happens, cataract surgery is of no use. Dog and human alike, the retina is like the film in a camera; the retina translates light rays to the optic nerve so we experience sight.
Dr. Yakely lifted Bernie’s eyelids and showed me how red the sclera (whites) of her eyes were. She had progressed to Uveitis. Whether or not I decided to have the cataract surgery done, we needed to treat her eyes for the Uveitis immediately. He explained that dogs with Uveitis are in pain and they don’t want to do much of anything except keep their eyes closed and sleep. Yes, that’s exactly how she’d been acting.
I worried that with her skewed blood values revealed the month before, Bernie would not be considered a candidate for surgery. Dr. Yakely told me that for a diabetic dog, her blood values weren’t that unusual and that many of his patients were sick dogs. Why, some diabetic dogs also had Cushing’s Disease, and they came through the surgery just fine! His confidence and excitement about what he could do for Bernie was contagious, there was not a moment I worried or doubted the surgery would be a success.
Bless his heart, Dr. Yakely juggled his schedule to squeeze her in on the following Tuesday at 8:00 am. He warned me there was no time to lose, that protein was already leaking from her lens and we didn’t want to wait until it tore - surgery would do no good then.
We came home for a fast weekend to “regroup” before we returned to Idaho the day before her surgery on July 1. We decided we would stay in Idaho until July 8, returning home after the second follow-up.
In the meantime, I was to put Voltaren® Opthalmic Solution in her eyes twice daily until the day of surgery, to arrest the Uveitis. 48 hours before her surgery I put Falcon® Neomycin Polymyxin B Sulfates and Dexamethasone Opthalmic Suspension in her eyes 3 times a day also.
Interestingly, Dr. Yakely said that he’s noticed that while most breeds of diabetic dogs take from 6 to 9 months to go completely blind, terriers breeds seem to go blind very quickly from the time of diagnosis. Some terriers can go blind literally overnight, so he knew it wasn’t my imagination Bernie was blind in 5 days.
Dr. Yakely also showed me a telltale shape in her cataracts, called the “Y Suture”. It looks just like the letter Y superimposed on the cataract, proof that the cataract formed very quickly, dehydrating quickly and folding up on itself in this distinctive shape.
Dr. Yakely told me that in some dogs, blindness was actually from PRA (Progressive Retinal Atrophy) and cataract surgery wouldn’t help them. In many cases a test needs to be done before scheduling cataract surgery called an Electroretinogram, which determines if the retina is indeed functioning. From Bernie’s age and history he felt sure her retina was functioning, and that her blindness was from the diabetes. PRA usually strikes younger dogs and would take longer to cause blindness than 5 days. An ERG will eliminate 50% of candidates for cataract surgery.
He explained to me how cataracts are removed by the procedure known as Phacoemulsification. A tiny incision is made in the eye and a microscopic needle that pulses 30,000 times/second is inserted to fragment the cataract. The cataract is then removed by irrigation and aspiration.
This is the diagram Dr. Yakely used to explain Bernie’s cataract
No replacement of the lens is needed. Dr. Yakely feels the disadvantages of lens implants (more expensive and more chance of complications) outweigh their benefit (good up-close vision immediately). Without lens implants you can expect a return of full range, normal vision after surgery, but up-close (12 inches and closer) vision will be blurry for 6-9 months. After that the dog will compensate and appear to have just as good of vision as with implants.
Dr. Yakely explained in detail what to expect after surgery. Bernie would have to wear a cone on her head (Elizabethan collar) for two full weeks to protect her eyes while they healed. She would have to come back for at least 4 follow-up visits. There would be a strict eye drops/medication regime to follow for many weeks after surgery.
On the morning of the surgery I fed her ½ her normal ration of food at 6:00 am and gave ½ the normal insulin dose at 6:30 am. Once we arrived at The Animal Eye Clinic they began administering eye drops and medications every 15 minutes to prepare her for the surgery. Bernie and I had a small room to ourselves while we waited for the surgery. Between drops I was able to take her for walks outside the office.
The surgery began about 10:30 am and lasted until about 12:30 pm. They brought Bernie to me immediately after the surgery. She was already wearing the Elizabethan collar and I got to hold her while she woke up from the anesthetic. I was amazed how quickly she came around; she was ready to go home by about 2:00 pm. I absentmindedly moved my hand when she had awakened, and was overcome by emotion as she followed the movement! It was too good to be true.
I was told the first night might be the worst, that some dogs were awake all night and very uncomfortable. But Bernie slept all night at the foot of the bed just like always, never moving an inch! Even though I knew Bernie was not feeling great, it was obvious she was glad to see again. I often found her staring intently at me. I’m sure she knew we had helped her.
What Bernie had the most trouble with was the E-collar, it upset her terribly. She wouldn’t walk, drink or eliminate the first 36 hours. The only thing she would do was eat her dog food, which I hand fed to her. I worried she wasn’t drinking water, so I made her meals very soupy. She spent her days mostly sleeping, in a puppy playpen with the floor raised and lined with soft bedding. I offered her drinks of water in a small dish throughout the day, which she seldom drank.
The morning after her surgery we returned for the first follow-up. You can’t believe the thrill of watching Bernie maneuver the obstacle course successfully (they removed the cone for this exercise). What a miracle – the day before she was in a dark world of blindness and this morning she was making her way among orange cones to the end of the hall where I was calling her to me. I don’t know who was more pleased - Bernie, Dr. Yakely or me!
Dr. Yakely said everything looked good. The cloudiness we saw in her eyes was caused from high cholesterol that is common in diabetic dogs. Dr. Yakely said it would clear in about 4 days, which it did, right on schedule. We were to come back on day 7 for the second follow-up appointment.
The first three days were the worst, but on day 5 she woke up a new dog. She was finally willing to walk on a lead with the cone on. I attached her leash to the top edge of the cone, to help her lift it high enough that it didn’t catch on the ground when she walked. She was eliminating more regularly by this time, having resigned herself to the fact that the cone was staying on.
We were on a strict schedule of drops and pills each day for the first two weeks. Voltaren® Opthalmic Solution drops were administered twice daily and Falcon® Neomycin Polymyxin B Sulfates and Dexamethasone Opthalmic Suspension three times daily. She was given Torbutrol tablets for pain the first 3 days and 25 mg Rimadyl daily for 2 weeks.
We went back on July 8 for her 2nd follow-up appointment, one week after her surgery. Again she maneuvered the obstacle course like a pro! Dr. Yakely said he couldn’t be more pleased with the outcome of her surgery. She was doing so well, he wouldn’t have to see her for another 3-4 weeks.
Bernie wearing her Elizabethan Collar
We left for home right after that appointment. I was anxious to get home and watch her rediscover her world. All the dogs were glad when we pulled into the driveway. They were tired of traveling and being away from home for so long. Bernie was delighted to be home and see her favorite things again.
Immediately she wanted to walk down the path that leads to our garden, but it would be another week before she was allowed to do that. She was not supposed to have any exercise, nor could the cone come off, for 14 days.
Those 14 days passed so quickly. Cone or not, her nose was to the ground inside and out, getting reacquainted. She enjoyed exploring her home as if she’d never been here before. After 14 days we took the cone off for an hour or so each day. We had to watch carefully that she didn’t scratch her eyes. In about 4 days it came off for good. At this time the medications decreased too, only two drops per day for the next two weeks.
Back to her favorite pastime, chasing the sprinkler!
It’s been 4 weeks since the surgery and Bernie is gaining strength every day as her activity level increases. She’s walking to the garden and back up the hill once or twice a day and follows me everywhere. She plays fetch with her Kong ball every evening before bedtime. She loves to chase the sprinkler and bark at the squirrels. Her diabetes remains in control with insulin shots morning and night along with a closely monitored diet. All in all, life is back to normal for all of us.
Bernie saw Dr. Yakely on July 31, 2003 - 4 weeks after the surgery. He said everything looked great and that her sutures had almost entirely dissolved. It will be important to continue with eye drops twice daily for several more months and that they will eventually taper down to one drop every other day. Because there may be tiny bits of the lens protein still present in the eye after surgery, it is important to be consistent with the eye drops, which quiet the immune response in her eyes. She will see Dr. Yakely again in 2 months. Until then, we continue to marvel at the happy life she has resumed.
original doc: Diabetes, Cataracts & Blindness.doc
Atypical Cushings: Adrenal Steriod Profiles in the Diagnosis of Adrenal Disease
ADRENAL STEROID PROFILES IN THE DIAGNOSIS OF ADRENAL DISEASE
College of Veterinary Medicine, The University of Tennessee
Source: From: J.W. Oliver, Proc. ACVIM Forum, Dallas, TX, 2002.
The Clinical Diagnostic Service at the University of Tennessee provides adrenal steroid profiletesting. The adrenal hormone profiles are determined in dogs, cats, ferrets and other species that are suspected of having adrenal disease. The profiles provide a more complete evaluation of adrenal function by assessing hormone levels that arise from different parts of the hormone synthesis pathways.
Most tests of adrenal function in animals involve the measurement of the hormone cortisol to determine whether or not the adrenal glands are functioning in a normal fashion. Excessive production of adrenocorticotropic hormone (ACTH) from the pituitary gland results in bilateral enlargement of the adrenals, with excess release of cortisol. Excess release of ACTH from the pituitary is the usual disorder that results in adrenal disease of animals. However, perhaps 20% of adrenal disease is caused by a primary tumor of one of the adrenal glands that spontaneously secretes excess cortisol into the bloodstream. For ferrets, adrenal disease is due to primary adrenal tumors, and hormones other than cortisol are involved. Whether or not an animal (other than ferrets) has adrenal disease is usually determined by stimulating the adrenal glands with synthetic ACTH (ACTH stimulation test), or by suppressing the release of ACTH from the pituitary gland (low dose dexamethasone suppression test). Using the stimulation test, one is looking for excessive release of cortisol from the adrenal glands; and using the suppression test, one is looking at whether or not cortisol levels can be completely suppressed for a prolonged period of time. However, in some individuals, these usual tests of adrenal function give normal results even though the animal has very suggestive clinical signs of adrenal disease. In these latter cases, adrenal steroid profile testing is very helpful to determine if hormones other than cortisol are involved, and causing problems for the animal. Steroid profiles for ferrets will determine whether or not a suspected adrenal tumor is present.
Congenital adrenal hyperplasia is a syndrome that occurs in humans where inherited defects of adrenal hormone synthesis occur, with steroids other than cortisol being secreted in excess. Congenital hyperplasia-like syndrome can occur in animals due to inherited defects of hormone synthesis, tumor presence in the adrenal glands that affects the enzymes involved with adrenal hormone synthesis, or other factors that are ill defined at present. In these atypical cases of adrenal disease, the adrenal steroid profiles are very effective in assessing the status of the adrenal glands. This is because different levels of adrenal hormone synthesis are being examined, and not just the end product of the synthetic pathway (cortisol). Clinical signs are similar in animals that have increased levels of cortisol or the adrenal intermediate hormones. These signs include frequent and excessive urination, temperament changes, thin skin, hair loss, changes in tests of liver function, and frequently, concurrent diabetes. In ferrets, where adrenal tumors are associated with high serum levels of the hormones 17-hydroxyprogesterone, androstenedione and estradiol, clinical signs include the occurrence of hair loss, swollen vulvas, return to male sexual behavior and enlarged prostate glands that cause difficult urination.
The congenital hyperplasia-like syndrome that occurs in animals, where adrenal intermediate hormones are elevated, certainly occurs in both intact and neutered individuals. However, the majority of dogs submitted to the University of Tennessee Clinical Endocrinology Service have been spayed or neutered. This eliminates difficulty with interpretation of results due to presence of similar secretory tissues (adrenals/gonads). Ferrets are nearly always spayed or neutered at a very young age to prevent problems with estrogen toxicity, and odor associated with accessory sex glands. A basal serum sample is all that’s needed for ferret assays. For dogs and cats, it is most meaningful to perform an ACTH stimulation test so that comparisons of both basal and stimulated hormone concentrations can be made. Treatment options should be discussed with a veterinarian.
Canine Cushing's Disease
By William E. Schultz, D.V.M.
First described in humans in 1932 by Dr. Harvey Cushing, the disease was originally thought to be a disorder of only the pituitary gland. Later studies showed "Cushing's Disease" as being caused by multiple factors. Canine Cushing's Disease (CCD) and Canine Cushing's Syndrome (CCS), all types of hyperadrenocorticism, have multiple pathophysiologic origins. The hallmark of the disease process is an overproduction of cortisol by the adrenal glands. Cortisol is a type of steroid produced by the adrenal gland which is necessary for normal body functions. Overproduction of cortisol causes many changes to normal metabolism. Some of the changes are readily apparent and some are very difficult to interpret. Onset is usually subtle with diagnosis often not made until quite late in the disorder. Hopefully, this article will allow some insight which may result in a more rapid diagnosis and earlier therapy.
Veterinary medicine recognized three main types of hyperadrenocorticism
I. Canine Cushing's Disease (CCD)
Pituitary dependent hyperadrenocorticism (PDH) is caused by the presence of a tumor in the pituitary gland. The tumor secretes an increased amount of adrenocorticotrophic hormone (ACTH) causing the adrenal glands (small glands near the kidneys) to increase their output of cortisol. The tumor in the pituitary gland is small and rarely are other signs of the tumor seen. PDH represents 80 to 85% of naturally occurring hyperadrenocorticism in dogs. According to the fourth edition of the Textbook of Veterinary Internal Medicine by Ettinger and Feldman, 1995, the top four affected breeds are Poodles, Dachshunds, Terriers and Beagles. About 75% of dogs with PDH weigh less than 20kg.
II. Iatrogenic Cushing's Syndrome
This type of Cushing's is secondary to use of steroids taken orally or by injection. The most frequent reason for steroid therapy is allergic dermatitis. Chronic usage will eventually cause the adrenal glands to atrophy, allowing the administered steroids to cause the clinical signs of hyperadrenocorticism. Attempts at desensitization and control of dermatitis without steroid usage can totally prevent this form of Cushing's. There is no weight predisposition for Iatrogenic Cushing's Syndrome.
III. Adrenal Gland Tumors
Several types of tumors can grow in the adrenal gland. Both cancerous or benign tumors may be present. The types are beyond the scope of this article, but it is important to know that tumors may be a cause of Canine Cushing's Syndrome. Forty-five to 50% of dogs with adrenocortical tumors weigh greater than 20 kg.
The three types of Cushing's all have one common factor -- the presence of elevated cortisol. Cortisol causes similar signs in all cases and a complete history, physical exam and laboratory test results will usually lead to a diagnosis. The testing is not 100% accurate and therefore it may be necessary to run several tests before a correct diagnosis is accomplished. Factors involved in diagnosis are multiple, and in many cases, only one or two signs may be present, while in other cases, the signs may be overwhelming. Many of the following statistics are from the Textbook of Veterinary Internal Medicine and some may be anecdotal from 22 years of practice.
Age -- usually older than 6 yrs -- 75% are older than 9 yrs for PDH, while dogs with tumors of the adrenal gland tend to be older.
Sex -- 55% to 60% of PDH are female and 60% to 65% of adrenal tumor dogs are female.
Breed -- smaller breeds (listed above) tend to get PDH, while adrenal tumors tend to develop in larger dogs.
History -- this is a disease with a slow onset and clinical problems are few in the initial stages. Frequently, the owner suspects diabetes or other skin related problems.
Physical findings -- increased thirst and increased appetite are very common findings. It is important to note that several signs of Cushing's may be normal behavior traits -- our Golden Retriever would eat any amount of food given as fast as possible, and if not dieted would be enormous. Because many of the dogs with Cushing's have such an excellent appetite, owners are reluctant to think that their dog is ill and tolerate many physical changes before concerns are great enough to have the dog checked.
Increased thirst and increased urine output are common findings. With Cushing's the urine is often very dilute and a simple urine specific gravity may be done as an initial screening test. It is strongly recommended that a refractometer and not urine dip sticks be used to determine the concentration of the urine. As with many of the tests, if this test is normal, but the disease is still questioned, more thorough testing is necessary. Urinary cortisol/creatinine testing is easily done and is a very good initial test, but it is also not specific - if the test is elevated, usually other testing is necessary.
A large distended (potty) abdomen and muscle weakness are seen in many advanced cases. The dog may develop an extremely potty abdomen -- this sign is in as many as 80% to 90% of the cases. Many cases are first seen because the owners think they appear obese, when, in reality, the abdomen looks larger due to muscle weakness and the extremities are actually much thinner from muscle wasting. Weakness, often a presenting sign, may be a sign that develops after treatment. The disease causes an increase in cortisol that helps to keep inflammation out of old arthritic joints -- treatment reduces the unwanted cortisol and may exacerbate signs of joint disease.
Several signs may be present in the skin to lead to a presumptive diagnosis of Cushing's. As many as 100% of the affected dogs will have some type of dermatological signs with up to 80% having alopecia (hair loss). Alopecia is usually evident in the flanks, sides of abdomen and around the anal area. The hair loss usually has bilateral symmetry ( the same on both sides). Poor re-growth of shaved areas, or re-growth with brittle sparse hair must be considered as clinical signs. Thin cool skin and infections like pyoderma or seborrhea may also be present. Calcium deposits in the skin (calcinosis cutis) which may feel firm to the touch may occur in the head and dorsal neck area, ventral abdomen and flanks. These deposits appear slightly raised and may be whitish to light pink with areas being quite small to very large.
Rapid breathing may be noted, but usually no cough is present. The respiratory difficulties may be related to enlargement of the liver putting pressure on the cardiopulmonary areas. Because small breeds may be affected, coughing may be present due to a collapsing trachea.
Many tests may be used to differentiate Cushing's from other endocrine disorders -- urine testing has been noted. Ultrasonography and radiology may image enlarged or calcium containing adrenal glands. Protocol for blood tests taken which use injections of ACTH and/or Dexamethasone can be found in veterinary textbooks. If you suspect Cushing's may be present and only one test has been done, it may be imperative to request further testing. If your veterinarian is not familiar with other testing methods, a veterinary teaching hospital or specialist may be necessary.
PDH cases may be treated with oral medication -- the protocol may vary according to practitioners, but the attempt is made to decrease the output of cortisol by the adrenal gland without completely stopping cortisol production. Timing meals or measuring water intake may be used in determining initial treatment end-point and used as factors to determine the maintenance dose.
Patience must be used during therapy -- each case is different. If initial results are not gratifying, or if the attending veterinarian gets frustrated, it may be necessary to start over with another protocol or another veterinarian.
Iatrogenic Cushing's Syndrome which is caused by excess oral or injectable steroids may often be helped by cessation of the steroid therapy and diet changes. Long term prognosis is poor.
Adrenal tumors, if in only one adrenal gland, may respond to surgical intervention. The possibility that cancerous tumors may have already spread to other organs necessitate a thorough pre-surgical work-up.
William E. Schultz, D.V.M., graduated from Michigan State University School of Veterinary Medicine in spring, 1973. Dr. Schultz has a companion animal practice in Okomos, Michigan.