Pharmacokinetics of paroxetine, a selective serotonin reuptake inhibitor, in Grey parrots (Psittacus erithacus erithacus): influence of pharmaceutical formulation and length of dosing.

Paroxetine, a selective serotonin reuptake inhibitor, may be beneficial in the treatment of behavioural disorders in pet birds. The lack of pharmacokinetic data and clinical trials currently limits the use of this drug in clinical avian practice. This paper evaluates the pharmacokinetic properties and potential side effects of single and repeated dosing of paroxetine in Grey parrots (Psittacus erithacus erithacus). Paroxetine pharmacokinetics were studied after single i.v. and single oral dosing, and after repeated oral administration during 1 month. Plasma paroxetine concentrations were determined by liquid chromatography-tandem mass spectrometry. No undesirable side effects were observed during the study. Pharmacokinetic analysis revealed a quick distribution and rapid elimination after i.v. administration. Oral administration of paroxetine HCl dissolved in water resulted in a relatively slow absorption (T(max)=5.9±2.6 h) and a low bioavailability (31±15%). Repeated administration resulted in higher rate of absorption, most likely due to a saturation of the cytochrome P450-mediated first-pass metabolism. This study shows that oral administration of paroxetine HCl (4 mg/kg twice daily) in parrots results in plasma concentrations within the therapeutic range recommended for the treatment of depressions in humans. Further studies are needed to demonstrate the clinical efficacy of this dosage regimen in parrots with behavioural disorders.

Ethanol poisoning as a differential diagnosis in a hunter's dog with tetraplegia.

A 4.5-month-old German pointer was presented with tetraplegia. Based on the physical examination, a tentative diagnosis of idiopathic polyneuropathy or synaptic disorder was made. Later that day additional information from the owner revealed that the dog might have ingested sloe berries that had been used to make sloe gin. Ethanol poisoning was added to the differential diagnosis. The dog's locomotion recovered in the course of 24 hours. Faecal analysis revealed that the animal had ingested at least 127 gin-saturated sloe berries and it was estimated that the blood ethanol concentration would have been at least 0.75 per thousand. The aetiology, diagnosis, and treatment of ethanol poisoning in dogs is reviewed.

[Numbers of dogs, cats, birds, and exotic animals in veterinary practices in the Netherlands 1994-2005 and possible consequences for the veterinary curriculum]. / Aanbod van honden, katten, vogels en bijzondere dieren in de Nederlandse diergeneeskundige praktijk in 1994 en 2005 en consequenties voor het veterinaire curriculum.

The species of pets owned in the Netherlands are constantly changing, and it is important that veterinary practitioners have information about the number and species of pets presented in veterinary practice. Using the same methodology as in 1994, we determined the relative importance of the various pet species in 2005 and compared these data with those for 1994. The most notable findings were a 25% increase in the number of birds and exotic animals seen in small and large animal practices (from about 10% to about 12.5%), a doubling of the number of birds and tripling of the number of pigeons seen in mixed practices, a doubling of the number of reptiles seen in small animal practices, and a 10-fold increase in the number of fish seen in veterinary practices in general. There was a significant decrease in the proportion of cats (from 46% to 40.7%) and an increase in the proportion of dogs (from 44% to 46.7%). These trends in veterinary practice consultations did not parallel those seen in pet ownership. The increase in the number of birds (especially pigeons), reptiles, and fish seen in veterinary practice emphasizes the need to pay attention to these species in the standard companion animal curriculum.

Giant cell tumor of the bone in a scarlet macaw (Ara macao).

A 6-mo-old female scarlet macaw (Ara macao) was presented after a 2-mo period of anorexia and weakness. The bird was reluctant to fly 1 wk before referral due to a painful left wing. Physical examination revealed a firm swelling around the left shoulder. On radiographs, the diaphysis and proximal metaphysis of the left scapula were radiolucent. Computer tomography revealed an osteolytic process, suggestive of a bone tumor, affecting the left scapula. Cytology of a fine needle aspiration biopsy of the mass showed erythrocytes, a proliferation of spindle-shaped mesenchymal cells, and multinucleated giant cells (osteoclasts) suggestive of a giant cell tumor. The left wing, including the scapula, was amputated. The bird showed a fast recovery but died 1 hr later. Findings during the pathological examination were compatible with shock due to blood loss. The shoulder process was characterized as a giant cell tumor. To our knowledge, this is the first complete report of a giant cell tumor of the bone in a bird.

The role of luteinizing hormone in the pathogenesis of hyperadrenocorticism in neutered ferrets.

Four studies were performed to test the hypothesis that gonadotrophic hormones, and particularly luteinizing hormone (LH) play a role in the pathogenesis of ferrets: (I) adrenal glands of ferrets with hyperadrenocorticism were studied immunohistochemically to detect LH-receptors (LH-R); (II) gonadotrophin-releasing hormone (GnRH) stimulation tests were performed in 10 neutered ferrets, with measurement of androstenedione, 17alpha-hydroxyprogesterone and cortisol as endpoints; (III) GnRH stimulation tests were performed in 15 ferrets of which 8 had hyperadrenocorticism, via puncture of the vena cava under anesthesia; and (IV) urinary corticoid/creatinine (C/C) ratios were measured at 2-week intervals for 1 year in the same ferrets as used in study II. Clear cells in hyperplastic or neoplastic adrenal glands of hyperadrenocorticoid ferrets stained positive with the LH-R antibody. Plasma androstenedione and 17alpha-hydroxyprogesterone concentrations increased after stimulation with GnRH in 7 out of 8 hyperadrenocorticoid ferrets but in only 1 out of 7 healthy ferrets. Hyperadrenocorticoid ferrets had elevated urinary C/C ratios during the breeding season. The observations support the hypothesis that gonadotrophic hormones play a role in the pathogenesis of hyperadrenocorticism in ferrets. This condition may be defined as a disease resulting from the expression of LH-R on sex steroid-producing adrenocortical cells.

Plasma bile acid concentrations in response to feeding in peregrine falcons (Falco peregrinus).

A significant post-prandial increase of plasma bile acid concentration (PBAC) was observed in peregrine falcons (Falco peregrinus). In order to avoid physiological food-induced elevations in PBAC, which can complicate interpretation of plasma chemistry results in birds of prey, it is recommended that blood samples be obtained after a fasting period of at least 24 hours.

Surgical management of digital gryposis syndrome in a goshawk (Accipiter gentilis gentilis).

Digital gryposis syndrome is an acquired abnormal curvature of the digits due to an unknown etiology. Past medical therapeutic efforts have had limited success, with occasional reports of spontaneous recoveries. Unilateral digital flexor tendon hypertension was identified as the cause of the presenting signs in the goshawk reported in this paper. Tenectomy was performed on the flexor perforatus digiti III, flexor perforans et perforatus digiti III, and flexor perforatus digiti IV tendons. A foot cast fashioned from elastic bandaging tape, epoxy, and aluminum wire was applied for 4 weeks. Fourteen weeks after the operation, the goshawk exhibited a normal stance and good coordination.

No evidence for diurnal variation in the responsiveness of the pituitary-adrenocortical axis of the pigeon (Columba livia domestica) to stimulation with adrenocorticotrophin and vasopressin.

The responsiveness of the pituitary-adrenocortical axis of the pigeon (Columba livia domestica) to intravenous administration of high and low doses of adrenocorticotrophic hormone (ACTH) and following arginine vasopressin (AVP) was investigated at two different moments of the diurnal rhythm. Administrations of ACTH and AVP were performed at the moment of low plasma corticosterone concentration and during high plasma corticosterone concentration. Plasma corticosterone concentrations following administration of AVP and ACTH did not change with the time of the day. It is concluded that for the assessment of pituitary adrenocortical function in pigeons the pituitary adrenocortical stimulation tests with AVP and ACTH can be used at any time of day.

Diurnal rhythms of plasma corticosterone concentrations in racing pigeons (Columba livia domestica) exposed to different light regimens, and the influence of frequent blood sampling.

The effects of two different light regimens and the frequency of blood sampling on the diurnal plasma corticosterone concentrations in racing pigeons (Columba livia domestica) were investigated. The daily light regimens tested were a period of light during the day (DL; lights on 0515-2215) and shifting of the light period by 12 hours (SL; lights on 1715-1015). In the first experiment, the influence of the frequency of blood sampling was investigated by comparing plasma corticosterone concentrations at 28-hr intervals for several days and at 4-hr intervals during one day. Sampling at 4-hr intervals resulted in significantly higher corticosterone concentrations in plasma than sampling at 28-hr intervals. Within both groups, the plasma corticosterone concentrations at the first and last sampling times did not differ significantly. Concentrations of plasma corticosterone were always highest during the dark period, and the corticosterone rhythm in the SL experiment was strictly in phase with the altered light/dark schedule.

Sensitivity of the hypothalamic-pituitary-adrenal system of pigeons (Columba livia domestica) to suppression by dexamethasone, cortisol, and prednisolone.

The sensitivity of the hypothalamic-pituitary-adrenal system in pigeons (Columba livia domestica) to glucocorticoid feedback was studied after single intravenous administration of dexamethasone (500, 100, 50, 10, 5, 1, 0.5, and 0.1 micrograms/kg), cortisol (15,000, 3000, 1500, 300, 150, 30, 15, and 3 micrograms/kg), and prednisolone (3500, 700, 350, 70, 35, 7, 3.5, 0.7, and 0.35 micrograms/kg). Dose responses, the threshold doses, and the onset of maximum suppression were determined by measuring plasma corticosterone concentrations around the expected peak of plasma corticosterone in pigeons kept on a shifted-light regimen. At 52 hr following the highest dose of dexamethasone, and at 48 hr following the highest doses of cortisol and prednisolone, plasma corticosterone concentrations were similar to the initial values and to the control values. Following the minimum doses that resulted in suppression of the normal diurnal variation in plasma corticosterone concentration (0.5 microgram dexamethasone/kg, 15 micrograms cortisol/kg, and 0.7 microgram prednisolone/kg), plasma corticosterone concentrations were similar to values of the control group and to initial values within 24 hr. The onset of suppression of plasma corticosterone concentrations was between 30 and 60 min following 1 microgram dexamethasone/kg, 7 micrograms prednisolone/kg, or 30 micrograms cortisol/kg. Suppression was greatest at 60 min following prednisolone and cortisol administration, and at 90 min following dexamethasone administration. It is concluded that the hypothalamic-pituitary-adrenal system of pigeons reacts to exogenous glucocorticoids by early delayed feedback, is more sensitive to suppression by glucocorticoids than that of mammals, and is suppressed for the longest time by dexamethasone. These observations indicate that some of the side effects of glucocorticoid therapy are likely to be at least as frequent and as severe in birds as in mammals.

Severe leukopenia and liver necrosis in young African grey parrots (Psittacus erithacus erithacus) infected with psittacine circovirus.

This paper describes the signs, clinical pathology, and postmortem findings in 14 young African grey parrots (Psittacus erithacus erithacus) that were naturally infected with psittacine beak and feather disease (PBFD) virus (psittacine circovirus). All but two of the parrots had severe leukopenia at clinical presentation. Two other parrots also had severe anemia. All birds died within 3 wk after presentation. Postmortem examination documented liver necrosis in 11 of 14 birds and secondary bacterial or fungal infections in 9 of 14 birds. Tests for Chlamydia psittaci, polyomavirus, and Salmonella sp. were negative. PBFD viral infection could be demonstrated in all birds by polymerase chain reaction. Supporting evidence of PBFD viral infection was gathered by histologic examination of the bursa of Fabricius, electron microscopy, and DNA in situ hybridization. Electron microscopic examination of both the bursa of Fabricius and liver revealed virus particles resembling circovirus. DNA in situ hybridization of six liver tissue samples confirmed the presence of PBFD virus and excluded the presence of avian polyomavirus. Our findings suggest that a specific presentation of peracute PBFD viral infection, characterized by severe leukopenia, anemia, or pancytopenia and liver necrosis in the absence of feather and beak abnormalities, may occur in young African grey parrots.

Urinary glucocorticoid excretion in the diagnosis of hyperadrenocorticism in ferrets.

Hyperadrenocorticism in ferrets is usually associated with unaltered plasma concentrations of cortisol and adrenocorticotropic hormone (ACTH), although the urinary corticoid/creatinine ratio (UCCR) is commonly elevated. In this study the urinary glucocorticoid excretion was investigated in healthy ferrets and in ferrets with hyperadrenocorticism under different circumstances. In healthy ferrets and in one ferret with hyperadrenocorticism, approximately 10% of plasma cortisol and its metabolites was excreted in the urine. High-performance liquid chromatography (HPLC) revealed one third of the urinary corticoids to be unconjugated cortisol; the other peaks mainly represented cortisol conjugates and metabolites. In 21 healthy sexually intact ferrets, the UCCR started to increase by the end of March and declined to initial values halfway the breeding season (June). In healthy neutered ferrets there was no significant seasonal influence on the UCCR. In two neutered ferrets with hyperadrenocorticism the UCCR was increased, primarily during the breeding season. In 27 of 31 privately owned ferrets with hyperadrenocorticism, the UCCR was higher than the upper limit of the reference range (2.1 x 10(-6)). In 12 of 14 healthy neutered ferrets dexamethasone administration decreased the UCCR by more than 50%, whereas in only 1 of the 28 hyperadrenocorticoid ferrets did the UCCR decrease by more than 50%. We conclude that the UCCR in ferrets primarily reflects cortisol excretion. In healthy sexually intact ferrets and in ferrets with hyperadrenocorticism the UCCR increases during the breeding season. The increased UCCR in hyperadrenocorticoid ferrets is resistant to suppression by dexamethasone, indicating ACTH-independent cortisol production.

Morphology of the pituitary gland in ferrets (Mustela putorius furo) with hyperadrenocorticism.

Pituitary tumours are the cause of hyperadrenocorticism in a variety of species, but the role of the pituitary gland in hyperadrenocorticism in ferrets is not known. In this species, the disease is mediated by the action of excess gonadotrophins on the adrenal cortex and is characterized by an excessive secretion of sex steroids. In this study, the pituitary gland of four healthy control ferrets, intact or neutered, and 10 neutered ferrets with hyperadrenocorticism was examined histologically following immunohistochemical labelling for adrenocorticotrophic hormone, alpha-melanocyte-stimulating hormone, growth hormone, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and prolactin. Immunohistochemistry revealed that somatotrophs, thyrotrophs and lactotrophs were the most abundant cell types of the pars distalis of the pituitary gland in the healthy ferrets. The distribution of corticotrophs was similar to that in the dog and man. In ferrets, as in dogs, the melanotrophic cell was almost the only cell type of the pars intermedia. Gonadotrophs were found in the pars distalis of neutered, but not intact ferrets. All the ferrets with hyperadrenocorticism had unilateral or bilateral alterations of the adrenal gland. In addition, in the pituitary gland of two of these ferrets a tumour was detected. These tumours were not immunolabelled by antibodies against any of the pituitary hormones, and had characteristics of the clinically non-functional gonadotroph tumours seen in man. In some of the other ferrets low pituitary immunoreactivity for gonadotrophic hormones was detected, which may have been due to the feedback of autonomous steroid secretion by the neoplastic transformation of the adrenal cortex. It is concluded that initially high concentrations of gonadotrophins resulting from castration may initiate hyperactivity of the adrenal cortex. The low incidence of pituitary tumours and the low density of gonadotrophin-positive cells in non-affected pituitary tissue in this study suggest that persistent hyperadrenocorticism is not dependent on persistent gonadotrophic stimulation.

Electrocardiogram of the racing pigeon (Columba livia domestica).

Using standard limb leads electrocardiograms (ECGs) were recorded in 60 pigeons. The greatest amplitude of the P wave was observed in lead II in the majority of ECGs. The predominant pattern of the P wave was positive in leads I and II, biphasic (-/+) in lead III, negative in aVR, biphasic (+/-) in aVL and positive in aVF. A Ta wave was observed in 50 out of 60 tracings. Wenckebach's phenomenon was observed in three different pigeons. In lead I the QRS pattern was rs or qs. In leads II, III and aVF the waveform was rS or QS. In leads aVR and aVL this pattern was R or qR. The highest voltage was observed in lead II. ST elevation and ST slurring were common findings. The T wave was always discordant, except for lead I, where the T wave was isoelectric. Reference values for electrocardiographic parameters were established.

I plasma concentrations of adrenocorticotrophic hormone and alpha-melanocyte-stimulating hormone in ferrets (Mustela putorius furo) with hyperadrenocorticism.

OBJECTIVE: To determine plasma concentrations of adrenocorticotrophic hormone (ACTH) and alpha-melanocyte stimulating-hormone (alpha-MSH) in healthy ferrets and ferrets with hyperadrenocorticism. ANIMALS: 16 healthy, neutered, privately owned ferrets, 28 healthy laboratory ferrets (21 sexually intact and 7 neutered), and 28 ferrets with hyperadrenocorticism. PROCEDURES: Healthy ferrets were used for determination of reference plasma concentrations of ACTH and a-MSH. Diagnosis of hyperadrenocorticism was made on the basis of history, clinical signs, urinary corticoid-to-creatinine ratios, ultrasonography of the adrenal glands, and macroscopic or microscopic evaluation of the adrenal glands. Blood samples were collected during isoflurane anesthesia. Plasma concentrations of ACTH and alpha-MSH were measured by radioimmunoassay. RESULTS: Plasma concentrations of ACTH in 23 healthy neutered ferrets during the breeding season ranged from 4 to 145 ng/L (median, 50 ng/L). Plasma concentrations of alpha-MSH in 44 healthy neutered or sexually intact ferrets during the breeding season ranged from < 5 to 617 ng/L (median, 37 ng/L). Reference values (the central 95% of the values) for ACTH and alpha-MSH were 13 to 100 ng/L and 8 to 180 ng/L, respectively. Plasma concentrations of ACTH and alpha-MSH in ferrets with hyperadrenocorticism ranged from 1 to 265 ng/L (median, 45 ng/L) and 10 to 148 ng/L (median, 46 ng/L), respectively. These values were not significantly different from those of healthy ferrets. Plasma ACTH concentrations of sexually intact female ferrets in estrus were significantly higher than those of neutered females. CONCLUSIONS AND CLINICAL RELEVANCE: Ferrets with hyperadrenocorticism did not have detectable abnormalities in plasma concentrations of ACTH or alpha-MSH. The findings suggest that hyperadrenocorticism in ferrets is an ACTH and alpha-MSH-independent condition.

Four methods for general anaesthesia in the rabbit: a comparative study.

The efficacy and safety of pentobarbitone, ketamine/xylazine, fentanyl/fluanisone/diazepam, and halothane/nitrous oxide anaesthesia were compared in 4 groups of six New Zealand White rabbits. Heart and respiratory rates, body temperature, reflexes, blood pressure and blood gases were measured. Pentobarbitone appeared to be unsuitable for anaesthesia in rabbits, as 5 of the 6 rabbits to whom it was administered, required artificial respiration or died. The combinations of ketamine/xylazine and fentanyl-fluanisone/diazepam both produced unpredictable levels of anaesthesia together with a substantial decline in arterial blood pressure and PO2. Despite a severe drop in blood pressure (up to 37.5%), anaesthesia with halothane and nitrous oxide was found to be superior to the other anaesthetic agents.

A comparison of two methods to establish the prevalence of lead shot ingestion in mallards (Anas platyrhynchos) from The Netherlands.

Two collection methods for screening the mallard (Anas platyrhynchos) population in the Netherlands for the ingestion of spent lead shot were compared. One method consisted of examination of gizzards from mallards shot by hunters (n = 2,859) and the other method consisted of examination of gizzards from mallards caught in duck traps (n = 865). The 95% confidence interval of lead shot ingestion in the mallard population estimated by the first method was 1.7 to 2.9% and by the second method 1.1 to 3.1%. These values were not significantly different. From the numbers of lead pellets embedded in the gizzard wall in hunter-killed and trapped mallards it was estimated that at least 22 to 68% of the trapped ducks had been hit by lead shot previously, but survived. Furthermore, this study shows that it is reasonable to assume that a substantial part of the pellets which are identified (in this study and other studies) as ingested, may well have been shot into the gizzard lumen at some time before the birds were actually killed. To avoid lead poisoning in mallards and in raptors depredating waterfowl hit by lead shot, a change to steel shot is advocated.

Plasma chemistry reference values in ostriches.

Reference values for 18 plasma chemical variables in blue neck ostriches (Struthio camelus australis, n = 60, age 24-36 mo) were established for use in veterinary clinical practice using nonparametric statistics. The following values were established for the percentiles P2.5 and P97.5: sodium 147-157 mmol/L, calcium 2.4-4.8 mmol/L, inorganic phosphate 1.3-2.3 mmol/L, chloride 94-105 mmol/L, glucose 10.3-13.7 mmol/L, urea 0.5-0.8 mmol/L, uric acid 351-649 mumol/L, bile acids 8-33 mumol/L, total protein 39-56 g/L, albumin-globulin ratio 0.45-0.59, osmolality 304-330 mOsm/kg, alkaline phosphate 69-217 IU/L, aspartate aminotransferase 243-418 IU/L, gamma-glutamyltransferase 0-1 IU/L, creatine kinase 1648-4894 IU/L, glutamate dehydrogenase 8-17 IU/L, and lactate dehydrogenase 860-2236 IU/L. The plasma calcium concentration was significantly (P < 0.001; r = 0.74) related to the total protein concentration and an adjustment-formula for calcium was derived: adjusted Ca (mmol/L) = Ca (mmol/L)--0.09 TP (g/L) + 4.4. The influence of blood sample treatment on the plasma potassium concentration as seen in other avian species was demonstrated in a separate experiment, emphasizing the need to separate plasma and cells immediately after collection in avian blood samples.

Correlation between age at neutering and age at onset of hyperadrenocorticism in ferrets.

OBJECTIVE: To determine prevalence of hyperadrenocorticism in ferrets in The Netherlands and evaluate age, sex, and age at neutering in affected ferrets. DESIGN: Prevalence survey and retrospective study. ANIMALS: 50 ferrets with hyperadrenocorticism and 1,267 ferrets without hyperadrenocorticism. PROCEDURE: A questionnaire was sent to 1,400 members of a ferret-owners organization in The Netherlands; 492 (35%) owners returned the questionnaire, providing usable data on 1,274 ferrets. Seven of these ferrets developed hyperadrenocorticism during the survey period; medical records for these ferrets and 43 ferrets with confirmed hyperadrenocorticism were reviewed. Hyperadrenocorticism was confirmed by histologic examination of an excised adrenal gland (92% of ferrets) or clinical improvement after excision. RESULTS: Prevalence of hyperadrenocorticism in the survey population was 0.55%. Sex was not associated with prevalence of disease. Median time interval between neutering and diagnosis of hyperadrenocorticism was 3.5 years. A significant linear correlation between age at neutering and age at time of diagnosis was detected. CONCLUSIONS AND CLINICAL RELEVANCE: Age at neutering may be associated with age at development of hyperadrenocorticism in ferrets.