Ferrets

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EXOTIC PET MEDICINE II

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FERRETS Karen Rosenthal, DVM, MS

During the last decade, the European ferret (Mustela putarius Jura) has become a popular household pet in the United States.5 In 1990, it was estimated that there were at least 7 million pet ferrets in the United States.6°Coinciding with an increase in the popularity of this animal has been a great proliferation in our knowledge of the diseases of ferrets. Before 1980, the majority of information about ferrets was directed at or coming from laboratory research. Since the early 1980s, there has been a large increase of veterinary literature describing the medical problems of pet ferrets. It is obvious from these papers that the pet ferret has diseases that differ from those of the laboratory ferret. This article concentrates on the common conditions of pet ferrets and currently recommended treatments. It is not intended as a complete review of all diseases that occur in ferrets. If more detailed information on laboratory ferrets or more in-depth anatomic or physiologic data is desired, there are numerous references throughout this article from which to find that information. TAXONOMY AND HISTORY

The domestic ferret (Mustela putarius Jura) belongs to the order Carnivora and is in the family Mustelidae. Related species include weasels, stoats, mink, and ermines. The pet ferret and the wild North American black-footed ferret (Mustela nigripes) are two distinctly different species. The population of the black-footed ferret has been decimated as a result of habitat and prey destruction and is limited to small colonies in the western United States.52 Recently, there has been some success in increasing the size of this population.

From The Animal Medical Center, New York, New York

VETERINARY CLINICS OF NORTH AMERICA: SMALL AN IMAL PRACTICE VOLUME 24 • NUMBER 1 • JANUARY 1994

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M. putorius furo has been domesticated for over 2000 years. Aristotle is said to have mentioned ferrets in his writin~s. 23 Until recently, ferrets were mainly known as either hunting animals or laboratory subjects. Currently, ferrets are primarily recognized by the general public as pets, but they are well known in the scientific community because of their value as a research animal. A few of the research disciplines using ferrets include endodontic research/ 8 gastroenterology,37 cardiology, virology, and toxicology,S0 and studies of human influenza,62 sexual differentiation/ vision/9 brain function/ 5 and the human guinea worm. 6 In a review of ferrets and zoonotic diseases, the only disease in which there is documentation of transmission of disease from ferrets to humans is viral influenza.47

ANATOMY The anatomy of the ferret does not differ significantly from other carnivores.5 This discussion reviews the unique aspects of ferret anatomy which are clinically relevant. For a more detailed description of ferret anatomy, the reader is referred to another source. 1 The ferret is a long, thin animal with short limbs. Male ferrets can be twice as large as female ferrets, even when neutered.52 Ferrets have poorly developed sweat glands and are prone to heat prostration.52 The vertebral column is very flexible with large vertebra. The vertebral formula is C7, T15, LS, 53, Cdl8. 1 The skull and associated musculature are developed for strength and shearing action. Unlike other carnivores, ferrets have only three premolars.1 The permanent dentition of the ferret is 2 (13/3, Cl / 1, Pm3/ 3, Ml/2}=34. The trachea of the ferret is unusually long, There are 60 to 70 Cshaped hyaline tracheal rings. 1 This feature has enhanced the ferret's value as a subject for respiratory-associated research. The ferret has a single central ascending artery instead of the more common bilateral carotid arteries.52 The ferret gastrointestinal system lacks a cecum, appendix, and teniae coli.5 The large intestine appears as one long tube with no gross distinction between the ileum and the colon and, therefore, no ileocolonic sphincter.52 The urogenital anatomy of both females and males is similar to other carnivores. There is some controversy as to whether male ferrets have a prostate gland and bulbourethral gland.51 • 52

HUSBANDRY Because ferrets live in three distinctly different situations (pet, research, hunting), it is important to discuss their husbandry in relation to how they are kept. Emphasis here is placed on the pet environment, as

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very few ferrets are used for hunting in the United States. There are many good in-depth reference sources for husbandry of the laboratory ferret. z. 19, 55, 66

Housing

Pet ferrets are kept in a variety of settings. Ferrets are sometimes treated like pet dogs and cats and allowed unsupervised free roam of the household. This is to be discouraged (see the section on gastrointestinal (GI) diseases). Ferrets can be kept in cages, aquariums, or pens while the owners are not home. Although aquariums are popular be- · cause they are easily made escape-proof, they are usually a poor choice for ferret housing. Tanks prevent exercise and have poor air circulation, which contributes to an increase in respiratory disease.19 Ferrets need cages and pens large enough for exercise if they are to be confined for long periods. A "den" area should be provided within the cage.61 In suburban or rural areas, ferrets are sometimes housed outdoors. Care must be taken to protect these outside ferrets from predators and weather extremes, especially heat. Ferrets can be trained to use a litter pan, and one should always be available. Diet

Numerous recommendations concerning ferret nutrition have been made. 5• 50 Like most carnivores, a diet high in protein and fat but low in fiber is best suited to the ferret's digestive tract.5 Dietary needs can be met by feeding a high-quality cat or kitten chow or one of several commercial ferret diets. Soft, moist and canned cat food should be avoided because of an increased risk of dental calculus formation. 32 One study showed that ferrets allowed free access to food will eat nine to ten small meals a day. 42 The ferret's diet can be supplemented with a limited amount of meats, vegetables, and fruits. Although ferrets are carnivores, some enjoy eating a small amount of fruits and vegetables. Any foodstuffs other than a balanced commercial diet should be kept to a minimum. Dietary changes are sometimes suggested based on medical conditions. A ferret with an insulinoma should be fed frequently and discouraged from eating high-sugar meals. Owners of ferrets with gastroenteritis may be advised to make temporary dietary changes to help alleviate diarrhea. PREVENTATIVE HEALTH CARE

Preventative health care for pet ferrets begins at an early age with their first vaccination. Owners should be encouraged to bring in their

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ferrets for annual veterinary examinations. During these visits, it is important to educate the dient about common dis'eases of ferrets. As ferrets grow into midd~e age (3 to 4 years of age), some veterinarians recommend twice-yearly examinations to screen for such common diseases as insulinoma, adrenal gland disease, heart disease, and lymphosarcoma? During these visits, routine blood tests can be done, including complete blood count (CBC), biochemical profile, and blood glucose and insulin concentrations. Also, survey thoracic and abdominal radiographs can be taken. It is recommended that p et ferrets be given a series of canine distemper virus vaccine injections derived from an egg-propagated modified live canine distemper virus. It is important that the correct canine distemper vaccine be administered. Killed distemper vaccines derived from canine cell lines may not induce an effective response and have been implicated in clinical distemper disease. 5 Ferrets should be given their first canine distemper vaccination at 6 to 8 weeks of age and subsequent vaccinations every 3 to 4 weeks until the age of 16 weeks. Ferrets then require yearly boosters. Ferrets should also receive a subcutaneous inactivated rabies virus vaccine. Based on serologic studies, ferrets can get their first vaccination at 3 months of age and should then receive an annual booster.60 An inactivated rabies virus vaccine should always be used. One reported case of ferret rabies virus infection may have been due to vaccination w ith a modified live vaccine.36 Although the USDA granted approval for ferrets to receive an inactivated rabies virus vaccine in 1990,6° veterinarians need to check local government regulations regarding the legality of vaccinating ferrets for rabies virus. The value of preventative health care at home should be strongly emphasized during visits to the veterinarian. Owners are instructed not to leave tempting potential gastrointestinal foreign bodies such as rubber and plastic objects in reach of ferrets. Alsb, -i.twners are shown how to restrain their ferrets by scruffing the nape '"of the neck. This restraint method can be used for grooming or giving oral medications at home. The clinical signs of common diseases that ferrets can develop as they age are discussed. A client handout will help greatly in this regard. Female ferrets are induced ovulators and usually remain in heat until bred. If the ferret is not bred and remains in heat, she may develop estrogen-induced bone marrow depression, resulting in a fatal, nomegenerative anemia and thrombocytopenia. Owners of intact females should be educated on this condition and advised to spay their ferret if she will not be used as a breeding animal. Most ferrets bred by commercial breeders and sold in pet stores are neutered and descented at 3 to 4 weeks of age. Ferrets sold through private breeders are usually sexually intact.

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CLINICAL TECHNIQUES Restraint

Many of the procedures performed in ferrets depend on proper restraint for successful completion. Manual restraint is easily accomplished and, in our practice, is adequate for most procedures. Ferrets are grasped by the nape of the neck and suspended. This method both relaxes and immobilizes the ferret, and many procedures can be performed with the ferret held in this manner. When more secure restraint is necessary, the ferret can be grasped both at the nape of the neck and around the hips to secure the hindlimbs. When the ferret must be totally immobilized, anesthesia is used. Venipuncture

Blood is most easily collected from the jugular vein, vena cava, or heart. The jugular veins are found by wetting or shaving the hair on the neck. The ferret is held with its body on a table and its neck, head, and front limbs extending off the table. The head and neck are extended upward while the front limbs are held down. A 25-ga needle attached to a 1- or 3-mL syringe is used for venipuncture. In the author's practice, successful venipuncture via the vena cava is often used in unanesthetized ferrets. Ferrets are placed in dorsal recumbency with the hindlimbs held at the hips, the forelimbs pulled caudally over the thorax, and the head restrained. The site of needle entry is in the notch between the first rib and manubrium of the sternum. A 25-ga needle attached to a 3-mL syringe, held at a 45-degree angle to the skin, is directed towards the contralateral hip. The needle is inserted almost to the hub. As the needle and syringe are slowly removed, the plunger is pulled back until blood fills the syringe. Heart venipuncture is used mainly in a laboratory setting and usually as a terminal procedure. This method is not recommended for pet ferrets. Ferrets can be given Nutri-cal (EVSCO Pharmaceuticals, Buena, NJ) to eat to distract them while blood is being drawn. Some ferrets are not easily held for venipuncture, and anesthesia must be used for restraint. In the author's practice, isoflurane anesthesia is used for this procedure. If a small amount of blood is desired, the lateral saphenous vein or cephalic vein can be used. A small-gauge needle (28V2 ga) attached to a low dose insulin syringe should be used. A needle of this size will enter the vein easily without collapsing it. Injections

Injections are given to ferrets in the same manner as they are in dogs and cats. Intramuscular injections are best given in the semitendenous

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and semimembranous muscles or in the lumbar muscles. Subcutaneous injections are most easily given along the dorsum, where the skin can be tented. Small volymes of intravenous injections are usually placed directly into the lateral saphenous or cephalic vein. In the author's practice, an intravenous catheter in the jugular, saphenous, or cephalic vein facilitates the injection of large volumes of medication. For most injections, scruffing the neck will sufficiently immobilize the ferret. Distracting the ferret with Nutri-cal while giving the injection is also useful. Physical Examination

The physical examination of the ferret is the same as that of the dog and cat. Restraint is usually limited to neck scruffing and is used only when necessary. Before handling the ferret, it should be observed for activity and general body condition. While it is scruffed by the neck, it usually will yawn numerous times, allowing a visual examination of the oral cavity. The oral cavity is examined for dental calculus build-up, broken teeth, and exposed pulp cavities. It is not uncommon for ferrets to have ceruminous aural discharge, which should be examined for mites. Ferret lymph nodes (i.e., submandibular, axillary, popliteal, inguinal) are palpated for abnormalities. Auscultation of the heart and lungs is performed over the entire thorax. Heart murmurs often can be localized within the thoracic cavity. The ferret's abdomen is easily palpated to note any abnormalities. In female ferrets, the size of the vulva should be assessed as a tool for early diagnosis of hyperadrenocorticism. The haircoat should be examined for thinning, which may be associated with hyperadrenocorticism. Aspiration of Masses

Masses and other tissues are aspirated in ferrets similar to other animals. The most common areas to aspirate in ferrets include lymph nodes, the spleen, abscesses, skin masses, and the bone marrow. Except for bone marrow aspiration, the ferret can be manually immobilized by scruffing the neck for most of these procedures. Percutaneous aspiration of the spleen is commonly performed in ferrets owing to the great number of ferrets with splenomegaly. The ferret is held by the nape of the neck and the spleen is palpated with one hand. With the spleen located and immobilized, the ferret is placed in dorsal recumbency and the spleen is aspirated with a 25-g needle attached to a 3-mL syringe. If the ferret is difficult to restrain, gas anesthesia can be used. Anesthesia

General anesthesia is easily accomplished in ferrets. In the author's practice, anesthesia is induced with either a face mask or a tank. During

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short anesthetic periods, a face mask is used, but for longer procedures, an endotracheal tube is placed. Either isoflurane or halothane gas anesthesia is used. Isoflurane is preferred when the ferret is ill or when quick recovery times are important. While the ferret is under anesthesia, it is monitored by a four-lead electrocardiograph and, sometimes, a breathing monitor. A circulating-water heating pad is placed beneath the ferret. Injectable anaesthetics are also used in ferrets. Like most drug dosages for ferrets, we use published drug dosage guidelines for cats to determine a dose. Catheter

Intravenous catheters are used routinely in the author's practice during lengthy surgeries or for very sick ferrets. Catheters are placed in the jugular, saphenous, or cephalic vein. All intravenous catheter placement is done under isoflurane anesthesia. Successful catheter placement is aided by immobilization of the ferret with anesthesia, shaving the hair over the catheter placement site, using very small gauge catheters (24- to 25~ga), and using a 20-g needle to pre-puncture the skin to make an entry site for the catheter apparatus. This will save the catheter from damage. COMMON DISEASES IN PET FERRETS

The following discussion is not meant to be a comprehensive listing and description of ferret diseases. The diseases mentioned are included because they are very common (i.e., insulinoma), have not been well described elsewhere (i.e., adrenal gland disease), or are diseases of importance (i.e., rabies). Table 1 lists the most important differential diagnoses for some of the more common complaints. Gastrointestinal Diseases

Dental Disease

Ferrets are prone to various dental problems. The incidence of dental calculus formation and periodontal disease is increased in ferrets fed soft moist or canned cat food diets. However, even ferrets fed dry food can develop this calculus.32 This disease has the same appearance as it does in other mammals, although it most closely resembles calculus formation in humans.32 A build-up of calculus on the teeth leads to tooth decay and eventual tooth loss. The application of antitartar toothpaste to the teeth and subsequent rubbing of the ferret's gums will help retard the formation of calculus.46 In the author's practice, most ferrets older than 1 year have dental tartar, and scaling of the teeth during the physical examination helps to decrease the amount of calculus present. It is common to see older ferrets with numerous missing teeth.

Table 1. MOST IMPORTANT DIFFERENTIAL DIAGNOSIS FOR COMMON PRESENTING SIGNS Signs

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Differential Diagnosis

Abdominal mass

Gl foreign body'"' Neoplasia Polycystic kidneys Splenomegaly

Alopecia

Dermatomycosis External parasites Hyperadrenocorticism Hyperestrogenism Mast cell tumor Seasonal variation (on tail only)

Chronic wasting disease

Aleutian disease Chronic Gl foreign body Dental disease Gastroenteritis Internal parasites Megaesophagus Mycotic disease Neoplasia Proliferative bowel disease

Diarrhea

Dietary indiscretion Gastroenteritis Gl foreign body Internal parasites Proliferative bowel disease

Hypersalivation

Gastroenteritis Gl foreign body Hypoglycemia (insulinoma)

Neurologic signs

Canine distemper virus lnsulinoma Neoplasia Proliferative bowel disease Rabies virus Toxins Trauma

Pruritus

External parasites Hyperadrenocorticism Mast cell tumor

Respiratory disease

Bacterial pneumonia Canine distemper virus Cardiomyopathy Heartworm disease Influenza virus Neoplasia

Swollen vulva

Estrus Hyperadrenocorticism Hyperestrogenism Ovarian remnant Vaginitis

Vomiting/regurgitation

Esophageal obstruction Gastroenteritis Gl obstruction lnsulinoma Megaesophagus Metabolic disease

Weakness

Aleutian disease Cardiomyopathy Hyperestrogenism/anemia lnsulinoma Lymphosarcoma Metabolic disease

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Ferrets commonly break off the tip of their canine teeth, especially the upper canines. If the dental pulp is exposed, it can be painful, can cause anorexia, and can lead to the loss of the tooth. A root canal is recommended for a tooth with exposed dental pulp.41 Like dogs and cats, ferrets can develop tooth root abscesses. This is usually noticed by the owner as a swelling over the zygomatic arch area. The ferret may be anorectic. Some of the swellings may have a draining tract. If a draining tract is not present, the ferret is anesthetized, and a dental probe is used to find the abscess cavity. The inside of the mouth is explored, and the involved tooth is extracted. The soft tissue is flushed and left open to drain, and the animal is placed on antibiotics. The area normally heals without incident. Foreign Body Obstruction

Foreign body obstruction of the GI tract is very common in young ferrets. 10' 35' 55 Although young ferrets are more prone to this disease due to their inquisitive nature, it also occurs in older animals. Ferrets that roam freely through their environment are more likely to develop this problem. In a retrospective study of GI obstruction in ferrets, sponges and rubber objects were the most common foreign bodies.55 GI obstruction due to trichobezoars is more common in older ferrets. Foreign bodies can be entrapped in the stomach, pylorus, or small intestine. The signs of a GI foreign body in ferrets are slightly deceiving, because vomiting may not be prominent part of the history.55 If a GI foreign body is suspected, the owners should be asked to search their hous~ for any missing or chewed objects. Commonly, ferrets with GI obstructions are brought to the veterinarian with the complaint of partial or total anorexia and possibly diarrhea. If the problem has been prolonged, weight loss is usually present. Ptyalism and pawing at the mouth and, possibly, signs of nausea are sometimes reported. Owing to the long, slender body of the ferret, it is relatively easy to palpate a foreign object in the ferret's GI system. Abdominal palpation may elicit signs of discomfort, especially if peritonitis is present. Radiographs are very useful in determining if and where a foreign object is in the GI tract. In the author's experience, many GI foreign bodies are detected on radiographs without the use of a barium series. Radiographically, the presence of a large amount of gas in the GI tract, a fluid- or gas-filled stomach, or a detectable radio-opaque object in the GI tract are suggestive of a foreign body. Some objects, especially trichobezoars, may pass through the GI tract with the use of feline hairball laxatives. If the foreign body is in the stomach, it can sometimes be retrieved by endoscopy. However, most foreign bodies must be removed surgically via an enterotomy or gastrotomy. Peritonitis or perforation of the gut wall may be present although in the author's experience, this is not common. Surgical removal and postoperative care are similar to that for the dog or cat.55 Gastroenteritis

Gastroenteritis is a multifaceted disease in ferrets with numerous possible etiologies that have yet to be totally elucidated. In young ferrets,

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primary causes of gastroenteritis include GI foreign bodies, proliferative bowel disease, and internal parasitism. In older ferrets, other reasons need to be considered for gastroenteritis. An infectious-cause of gastritis and gastroduodenal ulcers in ferrets has been postulated to be Helicobacter mustelae.25 Helicobacter-like organisms can be found in both young and old ferrets with chronic active gastritis. 3° Ferrets as young as 5 to 6 weeks can be colonized with this bacteria. In one study, 100% of adult ferrets were colonized by this organism.25 Clinical signs of gastroduodenal ulcers include anorexia, lethargy, teeth grinding, ptyalism, and melena. Diagnosis of this disease is difficult, but it is facilitated by endoscopy, an upper GI barium series, and tissue biopsies.35 Treatment is dependent on the severity of the disease. Supportive care may include fluid replacement therapy, iron supplementation, and enteral nutritional suppprt. Antibiotics (amoxicillin 20 mg/kg q8-12hrs SQ, PO; metronidazole 20 mg/kg q12hrs PO), bismuth subsalicylate (Pepto-Bismol 0.25 mL/kg q4-6hrs PO), cimetidine (10 mg/kg q8hrs PO or IV bolus) and sucralfate (1/8 of a 1-g tablet q6hrs PO) are given for a minimum of 7 to 10 days. 22' 35 In humans, the prevalence of a chronic H. pylorus infection has been associated with gastric carcinoma.25 One report of pyloric adenocarcinoma in a ferret did not have a demonstrated infection with H. mustelae.58 Eosinophilic gastroenteritis is seen infrequently in ferrets. Recently, a condition of eosinophilic gastroenteritis was described in six ferrets. 26 All ferrets showed signs of a nonspecific gastroenteritis, including chronic weight loss, anorexia, and diarrhea. Five of the ferrets had eosinophilia on hemograms. No infectious agents were found, and treatment, if performed, was not described.26 A similar case was successfully treated with ivermectin at 0.4 mg/kg subcutaneously.35 Physical palpation of ferrets with eosinophilic gastroenteritis can reveal thickened intestines and enlarged mesenteric lymph nodes. 56 The diagnosis of this disease is facilitated by a CBC and biopsy specimens of the Gltr~et and associated lymph nodes. Histopathologic examination can reveal eosinophilic infiltration of the stomach and small intestine.56 Some veterinarians recommend therapy with prednisone starting at 1.25 to 2.5 mg/kg orally daily and tapering the dose weekly.56 . Internal Parasites

Like other animals, ferrets are susceptible to infections from internal parasites. These parasites include Toxascaris leonia, Toxocara cati, Ancylostoma sp, Dipylidium caninum, Giardia spp, and coccidia.5 ' 2 1 In clinical practice, these parasites are found far less frequently in ferrets than in dogs and cats.35 Of these parasites, coccidia are most common. In the author's practice, coccidia are mainly seen in young, newly acquired ferrets and are especially common after a stressful event. Coccidia can cause severe diarrhea, which can lead to dehydration, metabolic imbalance, and even death. Ferrets can develop a rectal prolapse associated with a coccidial infection. Treatment of coccidiosis can be accomplished by sulfa drugs such as sulfadimethozine at 50 mg/kg orally once and

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then 25 mg/kg orally every 24 hours for 9 days. 35 Rectal prolapse can be treated by placement of a temporary pursestring suture. However, the prolapse usually resolves without treatment once the coccidia are cleared. Treatment of nematodiasis is accomplished with ivermectin at a dose of 0.2 to 0.4 mg/kg subcutaneously, which is repeated in 2 weeks. Megaesophagus

Megaesophagus is an uncommon but frustrating disease in ferrets. It has been seen most frequently in middle-aged to older ferrets. Owners

report either an acute onset or a chronic course of regurgitation. The disease is progressive, and aspiration pneumonia is usually the cause of death. Megaesophagus is diagnosed by clinical signs and imaging techniques such as a barium swallow, fluoroscopy or esophageal endoscopy. Many possible causes of this disease have been investigated, including lead poisoning, myasthenia gravis, hypothyroidism, Addison's disease, and esophageal nerve damage, but the exact etiology is unknown. Treatment includes supportive care, antibiotics, and small, elevated feedings. In the author's experience, this is a terminal disease. Proliferative Bowel Disease

Proliferative bowel disease occurs primarily in younger ferrets (less than 14 months of age). Presenting signs of this disease include chronic diarrhea, hematochezia, anorexia, weight loss, lethargy, and rectal prolapse.43 Some ferrets develop neurologic signs such as ataxia, head tilt, or tremors. 35• 43 Proliferative bowel disease often begins as an acute colitis with tenesmus and green diarrhea flecked with blood. The exact cause is unknown, but Campylobacter-type organisms have been seen microscopically in cultures from some ferrets with this disease. 16• 43 It can be associated with stress.16 Although the disease is associated with the colon, it has been recognized to affect the small bowel.35 Typical lesions include mucosal thickening and hyperplasia of the glandular epithelium.24 Diagnosis is based on clinical signs, response to treatment, and tissue biopsies. Chloramphenicol (50 mg/kg q12hrs) administered for 2 to 3 weeks is the first-line drug of choice in treating this disease. In debilitated ferrets, hospitalization with supportive care is necessary. Rarely, ferrets may become progressively weak, emaciated, and die, even with supportive care.43 Cardiovascular/Respiratory Disease Cardiomyopathy

Heart disease is seen in middle-age to older ferrets. Most ferrets are diagnosed with either hypertrophic or dilated cardiomyopathy. The dilated form appears to be more commonly associated with overt disease in the author's practice. Clinical signs of cardiomyopathy in ferrets in-

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elude respiratory distress, cyanotic mucous membranes, inappetance, exercise intolerance, and abdominal enlargement"'(ascites). Physical findings may include _a heart murmur, muffled heart and lung sounds, and moist rales. Diagnosis of this disease is facilitated by radiography, electrocardiography, and echocardiography. Therapy depends on the type of heart disease present, following the principles of canine and feline cardiology. If heart failure is severe, oxygen therapy is recommended. Pleural centesis is attempted, if indicated. Long-term management of dilated cardiomyopathy includes diuretics (furosemide, 2.0 mg/ kg q12hrs), digoxin (0.01 mg/kg q24hrs), and vasodilators (i.e., enalapril, 0.5 mg/kg q48hrs). Therapy includes a low salt diet and moderation of exercise. Ferrets are monitored frequently with electrocardiography, echocardiography, radiography, and assays of serum digoxin concentrations. In the author's experience, if cardiomyopathy is diagnosed at an early stage and if the treatment protocol is followed, ferrets can have a good quality of life for months or years. Heartworm

Heartworm disease in ferrets is rarely reported but should be considered as part of a diagnostic differential when ferrets develop signs of thoracic disease.53 Ferrets that live in or originate from heartworm endemic areas are most susceptible. Clinical signs include coughing, dyspnea, lethargy, pulmonary congestion, and ascites.28 Dirofilaria immitis adult worms may be found in the right ventricle, cranial vena cava, or pulmonary artery. Peripheral microfilaremia is uncommon.28• 53 Although it is reported that D. immitis infection is fatal, there is a treatment protocol that includes thiacetarsamide sodium at 0.22 mL/kg intravenously twice daily for 2 daysY Experimentally, ivermectin given at 0.1 mg/ kg prevents maturation of third-stage D. immitis larvae. This can be used as preventative treatment in ferrets in endemic areas. 28 Influenza Virus

Ferrets are prone to the same influenza viruses that affect humans. Ferrets can develop this disease after a person in the household has been sick with the flu. 5 Clinical signs are predominantly limited to an upper respiratory tract infection, with nasal discharge, fever, listlessness, and anorexia. Pneumonia may evolve but is rarely fatal. 57 The clinical course is usually 7 to 14 days. 28 Treatment includes supportive care, antihistamines, cough suppressants, and prophylactic antibiotics. Preventive measures include separation of susceptible ferrets from ferrets or humans affected with influenza. Genitourinary Tract Diseases Cystic/Polycystic Kidneys

Solitary renal cysts are typically an incidental finding in ferrets. These may be palpable or found at surgery when an abdominal explora-

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tory is being performed for other reasons. Polycystic kidneys usually have a more diffuse involvement with cysts in other organs, especially in the liver. 22 Polycystic kidneys usually palpate abnormally on physical examination. Occasionally, a ferret may present in terminal renal failure due to severe polycystic disease. Renal cysts may be developmental, hereditary, or acquired. 22

Hyperestrogenism

Hyperestrogenism in ferrets is not as common as it was in the past. This is primarily due to the practice of neutering ferrets before they are sold to the public. Ferrets are induced ovulators, and unless they are bred or mechanically induced, they can remain in estrus for extended periods. Hyperestrogenism develops in intact females subsequentto prolonged estrus.51 The high circulating concentration of estrogen can cause bone marrow depression.65 Myeloid, erythroid, and megakaryocyte cell lines are suppressed, resulting in nonregenerative anemia and thrombocytopenia.4 If not treated in the early stages, ferrets will die. 51 Signs of hyperestrogenism include pale mucous membranes, weakness, alopecia, and vulvar enlargement. Ferrets in the later stages of this disease show anorexia, lethargy, melena, and petechiationY Experimentally, clinical signs of hyperestrogenism are not evident until the packed cell volume (PCV) is below 20% and/or the platelet count is below 50,000 103 /mm3 •4 Definitive treatment for this disease is ovariohysterectomy. Treatment is dependent on clinical signs and the stage of the disease. In early estrus, a complete blood count, reticulocyte count, and platelet count should be taken. If results are normal, the ferret is a fair surgical candidate for ovariohysterectomy. Occasionally, evidence of bone marrow suppression may not be apparent on test results, and postoperative hemorrhage may occur. If results are equivocal, a bone marrow aspirate can be taken to examine for evidence of suppression. If test results show evidence of anemia or thrombocytopenia, the ferret can be given human chorionic gonadotropin (hCG) to induce ovulation. One study showed that 100 IU of hCG was an optimal dose to induce ovulation and terminate estrus.51 Two injections may be needed to completely induce the anestrous phase of the estrous cycle in these ferrets. Supportive therapy can be given simultaneously, including supplemental iron, B vitamins, and anabolic steroids. Once the ferret is in anestrus, the blood tests are repeated. If test results are normal, the ferret is then spayed. Ferrets with severe anemia and thrombocytopenia have an extremely poor prognosis. Blood transfusions and, possibly, bone marrow transfusions should be considered. Determination of the packed cell volume (PCV) is useful for prognosis. A PCV greater than 20% is usually a good prognostic indicator. A PCV between 14% and 20% carries a guarded prognosis, and less than 14% carries a very poor prognosis. Tamoxifen, an antiestrogenic drug used in humans, has estrogenic effects in ferrets, and is therefore contraindicated.4

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Ovarian Remnant

An ovarian remnant may be suspected in ·;! neutered female ferret with signs of estrus (i.e., swollen vulva). Ovarian remnants produce estrogen and, therefore, cause signs of estrus. Ovarian remnants usually respond to injections of hCG, and the swollen vulva decreases in size. Female ferrets with hyperadrenocorticism often have a swollen vulva; however, in these ferrets, treatment with hCG is not effective. Signs of an ovarian remnant often appear when the ferret is over 1 year of age and the ferret has not previously shown signs of estrus. The incidence of ovarian remnants in ferrets may be higher than in other mammals due to the practice of neutering ferrets at an early age and possibly leaving pieces of the ovary behind. A remnant, if present, is removed during an abdominal exploratory surgery. Renal/Cystic Calculi and Urolithiasis

Ferrets may develop urolithiasis. It appears to be more common in male ferrets. Clinical signs of urolithiasis include hematuria, stranguria, incontinence, polyuria, and lethargy. 22 Complete urinary blockage can occur. Diagnosis is based on history and results of hematologic examination, urinalysis, radiography, and abdominal ultrasonography. Radiographically opaque calculi are easily identified. In practice, cystic calculi appear to be more common than renal calculi. Treatment is similar to that in other mammals with this disease. Medical supportive care includes antibiotics, fluids, and urinary catheters.Z2 In practice, urinary catheters can be very difficult to place in ferrets. Surgery is usually required to remove the calculi. Stones can recur. It is not known if longterm dietary manipulation will decrease stone reformation. Most diets intended to decrease stone formation in dogs and cats are lower in protein than is desired for ferrets. It is not known if long-term use of these diets is safe for ferrets. Also, it is unknown ·H the same theories about feline urologic syndrome apply to ferrets and if the same logic behind the diet manipulation advocated for that syndrome in cats would be useful in ferrets. Skin Diseases

External Parasites

Ferrets are susceptible to external parasitic infestations similar to those of other mammals.9 Fleas (Ctenocephalides spp) can attack ferrets, causing mild to intense pruritusY Diagnosis includes finding fleas or flea excrement on the ferret. Fleas are usually found on the dorsum, especially near the nape of the neck. It is not unusual to have other pets in the house infested with fleas. Treatment involves removing the fleas and flea eggs from the ferret's environment. Methods of environmental flea control are the same for ferrets as for other household pets. Feline products are safe for use with ferrets.

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Ferrets can contract sarcoptic mange (Sarcoptes scabiei). Affected ferrets either show signs of a generalized whole-body form or a more specific, very pruritic form confined to the toes and nail beds.64 The generalized form is characterized by generalized alopecia and intense pruritis. The localized form is characterized by swollen feet, scabs, and possible nail loss. 64 Treatment includes ivermectin (0.4 mg/kg SQ, repeated in 2 weeks), shampoos/ soaks to reduce the prurih.ts, and antibiotics for secondary bacterial dermatitis. Ear mites (Otodectes cyanotis) are a common problem ih Jerrets. 21 Diagnosis is made after visualization of the mite. Signs may be absent or may include mild pruritus and brown cerumen in the external ear canal.64 Treatments can include topical ear parasiticides but ivermectin (0.4 mg/kg SQ, repeated in 2 weeks) given by injection or massaged into the ear works well. The author has found that some ferrets have brown cerumen in the external ear canal even with a negative examination for mites. In these cases, the ear canal is cleaned, and mite treatment is considered if tl1e ferret is symptomatic. Mast Cell Tumors

Mast cell tumors on ferrets are very common, but there are few reports in the literature of these neoplasms.63 They appear intermittently on the skin and can cause pruritus and alopecia.63 Usually, the tumors are small, tan or erythematous, slightly raised, circumscribed skin masses. A black, crusty exudate is often present, and owners may mistake the tumor for a wound that does not heal. These tumors can be hidden under the hair, and the author finds it useful to brush the hair against its grain to find the tumors on the skin. It is not uncommon to find these tumors along the neck and dorsum. Many mast cell tumors in ferrets follow a benign course as compared to the expected behavior of these skin tumors in other species.33 Usually, surgical excision is curative. In practice, mast cell tumors are found on many ferrets with an insulinoma. This is probably coincidentat because both conditions are very common in middle-aged to older ferrets. Nonetheless, the author recommends that any ferret diagnosed with a mast cell tumor should have preoperative testing of blood glucose and insulin concentrations. Mycotic Diseases

Fungal infections are suspected in ferrets with persistent draining tracts and skin eruptions that are unresponsive to antibiotics. They are usually accompanied by other signs such as pneumonia, chronic weight loss, and lethargy. Blastomycosis has been reported in the ferret. 44 Cryptococcosis has been described in ferrets and may even be considered part of a differential for meningoencephalitis.2° Recently, three ferrets were described with coccidioidomycosis (Coccidioides immitis). These ferrets either died or were euthanizedP

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Neurologic Diseases Canine Distemper Virus

Canine distemper virus, a paramyxovirus, causes almost 100% fatality in ferrets. 28 The virus may be transmitted by direct contact, fomites, or aerosolization of urine, feces, or nasal exudate.Z8 This disease has been associated with ferret shows and the intermingling of ferrets that have not been properly vaccinated. Early clinical signs include anorexia, pyrexia, chin dermatitis, photophobia, nasal and ocular discharge, and brown crusts around the face. Later clinical signs include bronchopneumonia, central nervous system signs, and death.28 Footpads swell and become hyperkeratotic.5 If the ferret survives the acute phase, central nervous system signs such as tremors, convulsions, and coma ensue.5 Histologically, eosinophilic viral inclusion bodies are both intracytoplasmic and intranuclear.28 Supportive care can be implemented, but treatment is not recommended.28 Prevention is by routine vaccination with a modified live virus vaccine of chick cell origin (see the section on Preventative Health Care). It is important to prevent contact with unvaccinated ferrets and dogs. Rabies Virus

There have been several cases of ferret rabies reported in the United States.28 The signs in experimentally infected ferrets include anxiety, lethargy, posterior paresis, and other central nervous system signs.28 Owing to governmental regulations, even ferrets vaccinated against rabies virus may still need to be sacrificed if they have bitten a human. Organomegaly/Neoplasia Adrenal Cortical Disease

A common disorder seen in middle-aged to older ferrets is adrenal cortical disease. The major presenting signs of this disease are alopecia and, in females, a swollen vulva. There are a number of reports in the literature of hyperadrenocorticism, including a recent retrospective of 50 cases.29• 59 The cortical region of the adrenal gland is affected, apparently resulting in an excess production of some adrenal steroids. The author sees more female ferrets with this disease than male ferrets. Clinical signs seen with this disease include alopecia, pruritus, swollen vulva in females, and a return to sexual behavior in neutered ferrets. Alopecia may involve only the tail or encompass the entire body. Occasionally, owners report the presence of these signs throughout the spring and summer and the cessation of these signs without treatment in the autumn. The next spring the signs recur but then do not dissipate in the autumn. Approximately one third of ferrets with hyperadrenocorticism have palpably enlarged adrenal glands. Hematologic test results are usually

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within normal limits. ACTH stimulation tests for cortisol concentration fall within the normal range for ferrets. An enlarged adrenal gland may be detected on abdominal ultrasound. However, diagnosis of adrenal cortical disease usually is based on clinical signs with confirmation at surgery. It is important to recognize that hyperadrenocorticism in ferrets is not the typical Cushing's disease or Cushing's syndrome seen in dogs. Signs normally associated with Cushing's disease in dogs, such as calcinosis cutis, polyuria/polydipsia (PU/PD), polyphagia, muscle weakness, lethargy, or increased panting are rarely seen. 14 Cortisol production is rarely elevated. Consequently, the typical effects of Cushing's disease, including thin skin, pot belly appearance, elevated alkaline phosphatase, neutrophilia, lymphopenia, and pulmonary thromboembolic events, are rarely seen. 14 The disease is treated most effectively by surgical removal of the abnormal adrenal gland. Various techniques for adrenalectomy are described for ferrets. 15• 54 Usually, only the left adrenal gland is affected, but in approximately 10% of the ferrets with hyperadrenocorticism, both adrenal glands are diseased. With bilateral adrenal involvement, the author recommends removing the larger gland and performing a subtotal adrenalectomy on the remaining gland. Once surgical removal of the gland(s) is accomplished, the disease is unlikely to recur, as metastasis is very rare. Postoperatively, the swollen vulva regresses in days, but alopecia may take months to resolve. If nonsurgical treatment is desired, a protocol for the use of lysodren has been published.34 The long-term effectiveness of this treatment regimen is equivocal. Histopathologic results reveal evidence of hyperplasia, adenoma, or adenocarcinoma in the cortical region of the adrenal gland. Pancreatic Beta Cell Tumors

Although pancreatic beta cell tumors (insulinomas) are the most common disease seen in older ferrets in the author's practice, it has been infrequently reported in the literature_~?· 34• 40• 48 The onset of this disease is usually insidious, and owners may not realize that their ferret is sick until it is severely hypoglycemic. Pancreatic beta cell tumors produce an inappropriately large amount of insulin in relation to the blood glucose concentration. Diagnosis is based on clinical signs of hypoglycemia, including episodes of severe weakness, lethargy, ptyalism, and nausea combined with low blood glucose and high blood insulin concentrations. Rarely, ferrets may become comatose or have seizures caused by the hypoglycemia. Ferrets may first show weakness in the rear legs with signs resembling intervertebral disk disease. These are the same signs of hypoglycemia described in six ferrets with islet cell tumors.48 This disease is so common in the author's practice that any ferret with lethargy, hypoglycemia, and/ or weakness is suspected of having an insulinoma until proven otherwise. A blood glucose concentration of 60 mg/ dL or less is suspicious of an insulinoma. Although an insulin value over 350 pmol/L associated with a low blood glucose concentration is suggestive

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of an insulinoma, insulin concentrations may be normal. The amended insulin:glucose ratio does not appear useful in ferrets, possibly as a result of the inaccuracy of some insulin measurements in ferrets. 48 The CBC and biochemistry-profile are usually within the normal range except for a low blood glucose and occasionally elevated alanine aminotransferase (ALT) value. Radiography and abdominal ultrasonography are not useful in diagnosing this disease but are used to screen for metastasis. When this disease has been diagnosed, ferrets should be examined for mast cell tumors and adrenal gland abnormalities, as both these conditions are common in ferrets with pancreatic beta cell tumors. Treatment is designed to increase the blood glucose concentration. This can be accomplished medically by such drugs as prednisone and diazoxide and surgically by removal of pancreatic tissue. Prednisone increases blood glucose concentration by promoting gluconeogenesis and inhibiting glucose uptake peripherally.34 Ferrets are started on a dose of 0.5 to 1.0 mg/ kg/ day of prednisone divided BID. This dose can be gradually increased to a maximum of 4.0 mg/ kg/ day divided twice daily. Ferrets may become resistant to the hyperglycemic effects of prednisone. Diazoxide can be added into the treatment regimen either early or later in the clinical course. Diazoxide inhibits insulin release and cellular uptake of glucose. 34 Diazoxide is started at a dose of 10 mg/ kg/ day divided twice daily. The dose can be increased to a maximum of 60 mg/kg/ day divided twice daily. Owners are instructed to feed their ferrets frequent meals, to always have food available, and to discontinue feeding high-sugar foods (such as semi-moist cat foods). Owners are also instructed to place a high-sugar liquid (i.e., Karo syrup) on their ferret's gums when there is a hypoglycemic crisis. Surgical treatment involves a partial pancreatectomy and/ or pancreatic nodule removal. Surgical therapy is usually a debulking procedure, which decreases the amount of insulin produced. During the surgery, the abdomen is fully explored. A liver biopSf 1s performed to screen for metastases. If the spleen is enlarged or' any abnormal lymph nodes are present, these are also biopsied or removed. Results of the histopathologic examination of the pancreas may reveal hyperplasia, adenoma, or adenocarcinoma.34 Immunocytochemical results confirm that insulin immunoreactivity is prominent in the insulinomasP Prognosis of pancreatic beta cell tumors depends on the age of the ferret, the presence of metastasis, and whether medical or surgical treatment is pursued. The owner needs to be aware that this disease can be managed but is usually chronic and ultimately fatal. The pancreatic tumor has usually micrometastasied throughout the pancreas and/ or liver when clinical signs are first apparentP Surgical treatment may or may not increase the lifespan of these ferrets. However, surgery may decrease the need for medical treatment for a number of months and lessen the severity of clinical signs. Rarely, ferrets have shown a complete clinical recovery after surgical excision of pancreatic nodules. In the author's experience, the best prognosis is in younger ferrets without tumor metastasis and very early diagnosis of the disease. Ferrets with the worst prognosis are older ferrets with metastasis and late diagnosis of the

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disease. Seizure activity or a coma does not necessitate a poor prognosis. The author has seen seizuring or comatose ferrets do well after surgical treatment. One ferret that continued to seizure while receiving a 12% dextrose intravenous solution lived for another 18 months after surgical debulking of its pancreas. Lymphosarcoma

Lymphosarcoma (LSA) is a common neoplasm of ferrets. 13 Ferrets with LSA can be separated into two groups: peripubescent and adult ferretsY Ferrets less than 1 year of age tend to develop acute disease with thymic enlargement. In adult ferrets, LSA follows a more chronic course associated with lymphadenopathyP In older ferrets, it is not unusual to diagnosis lymphosarcoma after enlarged lymph nodes are incidentally palpated by the clinician during a physical examination. LSA should be considered in a ferret with nonspecific signs of anorexia, weight loss, and lethargy. Ferrets with mediastinal masses may have thoracic disease signs similar to heart failure. The prognosis for a ferret with LSA depends on disease progression at the time of diagnosis and its response to treatment. Before treatment is attempted, CBC, biochemical profile, radiographs, bone marrow aspirations, and biopsies are submitted for a definitive diagnosis and to stage the disease. Treatment for this disease varies between clinicians. The author's current chemotherapy protocol recommendations closely resemble those published for dogs with LSN9 (Table 2). During the chemotherapy protocol, the CBC and biochemical profile should be monitored at least biweekly or even weekly. A recent report described the use of combination doxorubicin and radiation therapy along with high-dose vincristine to induce clinical remission.38 The author has found that the Table 2. CHEMOTHERAPY PROTOCOL FOR LYMPHOSARCOMA Week

2 3 4-6 8 10 12 14

Drug

Dose

Vincristine 0.07 mg/kg, IV Asparaginase 400 IV/kg, IP Prednisone 1 mg/kg, PO, SID Cyclophosphamide 10 mg/kg, sa Prednisone 1 mg/kg, PO, SID Doxorubicin 1 mg/kg, IV Prednisone 1 mg/kg, PO, SID As weeks 1-3 above but discontinue asparaginase 0.07 mg/kg, IV Vincristine Prednisone 1 mg/kg, PO, SID Cyclophosphamide 10 mg/kg, sa Prednisone 1 mg/kg, PO, SID Vincristine 0.07 mg/kg, IV Prednisone 1 mg/kg, PO, SID Methotrexate 0.5 mg/kg, IV Prednisone 1 mg/kg, PO, SID

Protocol is continued in sequence biweekly after week 14. Prednisone is given daily throughout the protocol.

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more aggressive the treatment (i.e., intravenous drugs), the more likely the treatment will afford some degree of succesg: In many respects, this disease resembles. the viral-induced malignant lymphomas found in other species. However, no viral etiology has yet been establishedY Other Neoplasias

Many other neoplasias are described in ferrets. A recent article describes over 95 different types of neoplasia in ferretsY Primary neoplasms have been identified in all organ systems except the respiratory tract and central nervous systemY Primary renal neoplasms in ferrets are reported to be rare. 3 Leiomyosarcomas are reported to be found in the abdomen, thorax, female reproductive tract and subcutaneous tissue. 8 Numerous reports of squamous cell carcinomas are noted in ferrets. 31 Aleutian Disease

Aleutian disease is a parvovirus infection first described in mink.s Mink die from this disease as a result of renal failure caused by immune complex-mediated glomerulonephrosis.s Aleutian disease in ferrets is characterized by a chronic wasting syndrome and immune complex formation with spontaneous hypergammaglobulinemia, vasculitis, and lymphoplasmacytic perivascular infiltrates. 13 The most consistent physical findings in ferrets infected with this virus are lymphadenopathy and splenic enlargements, 28 Typical histopathologic lesions of this disease include bile duct proliferation and plasmacytic and lymphocytic infiltrates of the liver, spleen, and lymph nodes.28 The diagnosis of Aleutian disease is facilitated by demonstrating hypergammaglobulinemia and positive serology in a chronically sick ferret. Ser;t.tm samples can be submitted to the Research Animal Diagnostic Laboratory of the Department of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, for determination of serum antibody titers. Clinically normal ferrets with positive titers do not necessarily develop clinical signs. There is no treatments Splenomegaly

Splenomegaly is a common finding on physical examination of a middle aged to older ferret, although it can be present in ferrets at any age. It is not necessarily associated with disease. Frequently, the clinician will find an enlarged spleen incidentally during a yearly health examination or when the ferret comes to the hospital for another problem. Typically, the clinician will palpate a nonpainful, larger-than-normal spleen that has smooth round borders. Infrequently, a nodular or irregular-shaped spleen is present. This is most likely associated with neoplasia and not splenomegaly. An enlarged spleen is easily aspirated percutaneously for cytologic examination. If an aspirate is nondiagnostic or a

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larger tissue sample is desired, an abdominal exploratory surgery is done. A CBC, platelet count, biochemistry profile, bone marrow aspiration, radiographs, and abdominal ultrasound are supportive tests to determine if the splenomegaly is benign. With benign splenomegaly, the hematologic results are within normal limits for ferrets. True hypersplenism is uncommon. The cause of benign splenomegaly is not known. Rarely, spleens become so large that they apply pressure to other abdominal organs. The ferret may become uncomfortable and possibly even anorectic. In these animals, the spleen should be removed. References 1. An NQ, Evans HE: Anatomy of the ferret. In Fox JG (ed): Biology and Diseases of the Ferret. Philadelphia, Lea & Febiger, 1988, pp 14-65 2. Baum MJ: The ferret as a model for studying the sexual differentiation of behavioral and reproductive function. J Exp Zool4[suppl):213-214, 1990 3. Bell RC, Moeller RB: Transitional cell carcinoma of the renal pelvis in a ferret. Lab Anim Sci 40:537-538, 1990 4. Bernard SL, Leathers CW, Brobst OF, eta!: Estrogen-induced bone marrow depression in ferrets. Am J Vet Res 44:657-661, 1982 5. Besch-Williford CL: Biology and medicine of the ferret. Vet Clin North Am Small Anim Pract 17:1155-1183, 1987 6. Broderson JR, Eberhard ML, Welch BG, eta!: Spinal dracunculiasis in an experimentally infected ferret. Lab Anim Sci 41:180-182, 1991 7. Brown SA: Preventative health program for the domestic ferret. Journal of Small Exotic Animal Medicine 1:6-11, 1991 8. Brunnert SR, Herron AJ, Altman NH: Leiomyosarcoma in a domestic ferret: Morphologic and immunocytochemical diagnosis. Lab Anim Sci 40:208-210, 1990 9. Burke TJ: Skin disorders of rodents, rabbits, and ferrets. In Kirk RW, Bonagura JD (eds): Current Veterinary Therapy XI. Philadelphia, WB Saunders, 1992, pp 1170-1175 10. Caligiuri R, Belhih JR, Collins BR, et a!: Medical and surgical management of esophageal foreign body in a ferret. JAm Vet Med Assoc 195:969-971, 1989 11. Dillberger JE, Altman NH: Neoplasia in ferrets: Eleven cases with a review. J Comp Pathol100:161-176, 1989 12. DuVal-Hudelson KA: Coccidioidomycosis in three european ferrets. J Zoo Wild! Med 21:353- 357, 1990 13. Erdman SE, Moore FM, Rose R, et al: Malignant lymphoma in ferrets: clinical and pathological findings in 19 cases. J Comp Pathol106:37-47, 1992 14. Feldman EC, Nelson RW: Hyperadrenocorticism. In: Canine and Feline Endocrinology. Philadelphia, WB Saunders, 1987, pp 137-194 15. Filion DL, Hoar RM: Adrenalectomy in the ferret. Lab Anim Sci 35:294-295, 1985 16. Finkler MR: Ferret Colitis. In Kirk RW, Bonagura JD (eds): Current Veterinary Therapy XI. Philadelphia, WB Saunders, 1992, pp 1180- 1181 17. Fix AS, Harms CA: Immunocytochemistry of pancreatic endocrine tumors in three domestic ferrets (Mustela putorius furo). Vet Pathol 27:199-201, 1990 18. Fouad A, Walton R, Rittman B: Induced periapical lesions in ferret canines: histologic and radiographic evaluation. Endodontics and Dental Traumatology 8:56-62, 1992 19. Fox JG: Housing and management. In Biology and Diseases of the Ferret. Philadelphia, Lea & Febiger, 1988, pp 153-158 20. Fox JG: Mycotic diseases. In Biology and Diseases of the Ferret. Philadelphia, Lea & Febiger, 1988, pp 248-254 21. Fox JG: Parasitic diseases. In Biology and Diseases of the Ferret. Philadelphia, Lea & Febiger, 1988, pp 235-247 22. Fox JG: Systemic diseases. In Biology and Diseasess of the Ferret. Philadelphia, Lea & Febiger, 1988, pp 255-273

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23. Fox JG: Taxonomy, history, and use. In Biology and Diseases of the Ferret. Philadelphia, Lea & Febiger, 1988, pp 3-13 24. Fox JG, Murphy JC, Otto G, et al: Proliferative colitis in ferrets: Epithelial dysplasia and translocation. Vet-Pathol26:515-517, 1989 25. Fox JG, Otto G, Murphy JC, et al: Gastric colonization of the ferret with Helicobacter species: Natural and experimental infections. Rev Infect Dis 13(suppl8):S671-680, 1991 26. Fox JG, Palley LS, Rose R: Eosinophilic gastroenteritis with Splendore-Hoeppli material in the ferret (Mustela putorius furo). Vet Path6129:21-26, 1992 27. Fox JG, Pearson RC, Gorham JR: Diseases associated with reproduction. In Fox JG (ed): Biology and Diseases of the Ferret. Philadelphia, Lea & Febiger, 1988, pp 186-196 28. Fox JG, Pearson RC, Gorham JR: Viral and chlamydia] diseases. In Fox JG (ed): Biology and Diseases of Ferrets. Philadelphia, Lea & Febiger, 1988, pp 217-234 29. Fox JG, Pequet-Goad ME, Garibaldi BA, et al: Hyperadrenocorticism in a ferret. J Am Vet Med Assoc 191:343-344, 1987 30. Gottfried MR, Washington K, Harrell LJ: Helicobacter pylori-like microorganisms and chronic active gastritis in ferrets. Am J Gastroenterol85:813-818, 1990 31. Hamilton T A, Morrison WB: Bleomycin chemotherapy for metastatic squamous cell carcinoma in a ferret. JAm Vet Med Assoc 198:107-108, 1991 32. Harper OS, Mann PH, Regner S: Measurement of dietary and dentrifice effects upon calculus accumulation rates in the domestic ferret. J Dent Res 69:447-450, 1990 33. Harvey HJ: Principles of cancer surgery. In Ettinger SJ (ed): Textbook of Veterinary Internal Medicine. Philadelphia, WB Saunders, 1983, pp 405-416 34. Hillyer EV: Ferret endocrinology. In Kirk RW (eds): Current Veterinary Therapy XI. Philadelphia, WB Saunders, 1992, pp 1185- 1188 35. Hillyer EV: Gastrointestinal diseases of ferrets. Journal of Small Exotic Animal Medicine 2:44-45, 1992 36. Hoover JP, Baldwin CA, Rupprecht CE: Serologic response of domestic ferrets (Mustela putorius furo) to canine distemper and rabies virus vaccines. J Am Vet Med Assoc 194:234-238, 1989 37. Hudson M, Piasecki C, Sankey EA, et al: A ferret model of acute multifocal gastrointestinal infarction. Gastroenterology 102:1591- 1596, 1992 38. Hutson CA, Kopit MJ, Walder EJ: Combination doxorubicin and orthovoltage radiation therapy, single-agent doxorubicin, and high-dose vincristine for salvage therapy of ferret lymphosarcoma. JAm Anim Hosp Assoc 28:365-368, 1992 39. Jackson CA, Hickey TL: Use of ferrets in studies of the visual system. Lab Anim Sci 35:211-215, 1985 40. Jergens AE, Shaw DP: Hyperinsulinism and hypoglycemia associated with pancreatic islet cell tumor in a ferret. JAm Vet Med Assoc 194:269-271, 1~89 41. Johnson-Delaney CA, Nelson WB: A rapid procedure for filiing fractured canine teeth of ferrets. Journal of Small Exotic Animal Medicine 1:100-102, 1992 42. Kaufman LW: Foraging cost and meal patterns in ferrets. Physiol Behav 25:139-141, 1980 43. Krueger KL, Murphy JC, Fox JG: Treatment of proliferative colitis in ferrets. JAm Vet Med Assoc 194:1435-1436, 1989 44. Lenhard A: Blastomycosis in a ferret. JAm Vet Med Assoc 186:70, 1985 45. Lockard BI: The forebrain of the ferret. Lab Anim Sci 35:216-228, 1985 46. Mann PH, Harper OS, Regnier S: Reduction of calculus accumulation in domestic ferrets with two dentrifices containing pyrophosphate. J Dent Res 69:451-453, 1990 47. Marini RP, Adkins JA, Fox JG: Proven or potential zoonotic diseases of ferrets. J Am Vet Med Assoc 195:990-994, 1989 48. Marini RP, Ryden EB, Rosenblad WD, et al: Functional islet cell tumor in six ferrets. J Am Vet Med Assoc 202:430- 433, 1993 49. Matus RE: Chemotherapy of lymphoma and leukemia. In Kirk RW (ed): Current Veterinary Therapy X. Philadelphia, WB Saunders, 1989, pp 482-488 50. McLain DE, Thomas JA, Fox JG: Nutrition. In Fox JG (ed): Biology and Diseases of the Ferret. Philadelphia, Lea & Febiger, 1988, pp 135- 152 51. Mead RA, Joseph MM, Neirinckx S: Optimal dose of human chorionic gonadotropin for inducing ovulation in the ferret. Zoo Bioi 7:263- 267, 1988 52. Moody KD, Bowman TA, Lang CM: Laboratory management of the ferret for biomedical research. Lab Anim Sci 35:272- 279, 1985

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53. Moreland AF, Battles AH, Nease JH: Dirofilariasis in a ferret. J Am Vet Med Assoc 188:864, 1986 54. Mullen HS: Surgical treatment of ferrets. In Proceedings of the 27th Annual Meeting of the American College of Veterinary Surgeons, Miami, FL, 1992 55. Mullen HS, Scavelli TD, Quesenberry KE, et al: Gastrointestinal foreign body in ferrets: 25 cases (1986-1990). JAm Anim Hosp f\ssoc 28:13-19, 1992 56. Palley LS, Fox JG: Eosinophilic gastroenteritis in the ferret. In Kirk RW, Bonagura JD (eds): Current Veterinary Therapy XI. Philadelphia, WB Saunders, 1992, pp 1182-1184 57. Renegar KB: Influenza virus infections and immunity: A review of human and animal models. Lab Anim Sci 42:222-232, 1992 58. Rice LE, Stahl SJ, McLeod CG: Pyloric adenocarcinoma in a ferret. J Am Vet Med Assoc 200:1117-1118, 1992 59. Rosenthal KL: Hyperadrenocorticism associated with adrenocortical tumor or nodular hyperplasia in ferrets: 50 cases (1987- 1991). JAm Vet Med Assoc 203:271- 275, 1993 60. Rupprecht CE, Gilbert J, Pitts R, et al: Evaluation of an inactivated rabies virus vaccine in domestic ferrets. JAm Vet Med Assoc 196:1614-1616, 1990 61. Ryland LM, Gorham JR: The ferret and its diseases. J Am Vet Med Assoc 173:11541158, 1978 62. Smith H, Sweet C: Lessons for human influenza from pathogenicity studies in ferrets. Rev Infect Dis 10:56-75, 1988 63. Stauber E, Robinette J, Basaraba R, et al: Mast cell tumors in three ferrets. J Am Vet Med Assoc 196:766- 767, 1990 64. Timm KI: Pruritus in rabbits, rodents, and ferrets. Vet Clin North Am Small Anim Pract 18:1077-1091, 1988 65. Williams ES, Thome ET, Kwiatkowski DR, et al: Comparative vaginal cytology of the estrous cycle of black-footed ferrets (Mustela nigripes), siberian polecats (M. eversmanni), and domestic ferrets (M. putorius furo). J Vet Diagn Invest 4:38-44, 1992 66. Willis LS, Barrow MV: The ferret (Mustela putorius furo L.) as a laboratory animal. Lab Anim Sci 21:712-716, 1971

Address reprint requests to Karen Rosenthal, DVM, MS The Animal Medical Center 510 East 62 Street New York, NY 10021