Pituitary responsiveness to GnRH, hypothalamic content of GnRH and pituitary LH and FSH concentrations immediately preceding puberty in gilts

To determine whether pituitary concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) or hypothalamic content of gonadotropin releasing hormone (GnRH) change before puberty, 40 prepubertal gilts averaging 7 mo of age were slaughtered before or on the second, third or fourth day after relocation and boar exposure. Some gilts responded to relocation and boar exposure as indicated by swollen vulvae, turgid uteri and enlarged ovarian follicles at the time of slaughter. Pituitary concentrations of LH and FSH and hypothalamic content of GnRH were similar between gilts that responded to relocation and boar exposure and gilts that did not respond. In addition, boar exposure and relocation had no effect on pituitary concentrations of LH and FSH or on hypothalamic content of GnRH. To determine whether pituitary responsiveness to GnRH changes before puberty, a third experiment was conducted in which 72 gilts were injected with 400 micrograms of GnRH either before or on the second, third or fourth day after relocation and boar exposure. In gilts that subsequently responded (i.e., ovulated) as a result of relocation and boar exposure, pituitary responsiveness to GnRH was reduced as compared with gilts that failed to ovulate after relocation and boar exposure. Peak concentrations of serum LH after GnRH injection were 4.6 +/- 1.3 vs 9.8 +/- .8 ng/ml for responders vs nonresponders. Peak serum FSH after GnRH injection was also lower for responders than for nonresponders (29.5 +/- 4.2 vs 41.2 +/- 2.4 ng/ml). When compared with controls, relocation and boar exposure did not significantly affect GnRH-induced release of LH and FSH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Management Options for the Aged Breeding Stallion with Declining Testicular Function

In our experience, the testicular dysfunction that develops in aged stallions is typically progressive, contributing to a gradual deterioration in sperm output and quality over 2-4 years. As the ability to produce sufficient numbers of normal sperm in ejaculates declines, so do pregnancy rates until the stallion eventually becomes so subfertile that it is no longer commercially feasible to continue breeding. However, more intensive breeding management can sometimes result in pregnancy rates (per cycle and per season) that are sufficient to justify breeding of the aged stallion to a diminishing number of mares during the period of declining fertility.     

Adenohypophyseal Function in Dogs with Primary Hypothyroidism and Nonthyroidal Illness

Background: A recent study of dogs with induced primary hypothyroidism (PH) demonstrated that thyroid hormone deficiency leads to loss of thyrotropin (TSH) hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement with large vacuolated "thyroid deficiency" cells that double-stained for growth hormone (GH) and TSH, indicative of transdifferentiation of somatotropes to thyrosomatropes.
Hypothesis: Similar functional changes in adenohypophyseal function occur in dogs with spontaneous PH as do in dogs with induced PH, but not in dogs with nonthyroidal illness (NTI).
Animals: Fourteen dogs with spontaneous PH and 13 dogs with NTI.
Methods: Adenohypophyseal function was investigated by combined intravenous administration of 4 hypophysiotropic releasing hormones (4RH test), followed by measurement of plasma concentrations of ACTH, GH, luteinizing hormone (LH), prolactin (PRL), and TSH. In the PH dogs this test was repeated after 4 and 12 weeks of thyroxine treatment.
Results: In 6 PH dogs, the basal TSH concentration was within the reference range. In the PH dogs, the TSH concentrations did not increase with the 4RH test. However, TSH concentrations increased significantly in the NTI dogs. Basal and stimulated GH and PRL concentrations indicated reversible hypersomatotropism and hyperprolactinemia in the PH dogs, but not in the NTI dogs. Basal and stimulated LH and ACTH concentrations did not differ between groups.
Conclusions and Clinical Importance: Dogs with spontaneous PH hypersecrete GH but have little or no TSH hypersecretion. Development of hyperprolactinemia (and possible galactorrhea) in dogs with PH seems to occur only in sexually intact bitches. In this group of dogs with NTI, basal and stimulated plasma adenohypophyseal hormone concentrations were not altered.     

Comparison of Insulin and Glucose Metabolism in Horses with Pituitary Pars Intermedia Dysfunction Treated Versus Not Treated with Pergolide

Equine pituitary pars intermedia dysfunction (PPID) is known to alter glucose/insulin metabolism. This study evaluated changes in parameters relating to glucose/insulin metabolism and determined whether there is a difference between pergolide-treated and untreated animals. We hypothesized that glucose/insulin dynamics in PPID horses receiving pergolide would be different than those in untreated horses. A total of 38 horses with diagnoses of PPID were included in the study (average age: 24 years). A total of 25 horses were untreated; 13 horses were treated with pergolide (>3 months). Parameters relating to glucose/insulin metabolism were determined in all horses, as follows: adrenocorticotropin-releasing hormone (ACTH), insulin, fructosamine, triglyceride, glucose, modified insulin-to-glucose ratio (MIRG), and reciprocal of the square root of insulin (RISQI). A combined glucose-insulin test (CGIT) was performed in 23 horses as not all owners agreed to the testing. Treated animals showed a tendency to have lower ACTH, but results were not significant. All animals had fructosamine levels exceeding reference values (mean value 314 ± 32 μmol/L; reference range: <280 μmol/L). There were no statistically significant differences between insulin, glucose, ACTH, triglycerides concentrations, RISQI/MIRG calculations, and CGIT results of pergolide-treated PPID and those of untreated horses. Five horses (13.2%) had combined hyperglycemia/hyperinsulinemia, whereas 7 horses (18.4%) displayed hyperglycemia, and 3 horses (7.9%) showed hyperinsulinemia alone. Forty percent of the horses with altered glucose/insulin metabolism were treated with pergolide. Based on RISQI and MIRG calculations, 19 animals displayed changes in glucose/insulin metabolism. Fourteen of twenty-three horses (61%) showed signs of insulin resistance in CGIT results. In conclusion, PPID horses frequently show alterations in glucose/insulin metabolism, but no significant differences were found between treated and untreated animals. Changes in insulin/glucose dynamics may not be a useful indicator of response to pergolide treatment.     

ABCB1-1Δ Polymorphism Can Predict Hematologic Toxicity in Dogs Treated with Vincristine

Background: Dogs that harbor the naturally occurring ABCB1-1Δ polymorphism experience increased susceptibility to avermectin-induced neurological toxicosis as a result of deficient P-glycoprotein function. Whether or not the ABCB1-1Δ polymorphism affects susceptibility to toxicity of other P-glycoprotein substrate drugs has not been studied.
Hypothesis: Dogs that possess the ABCB1-1Δ mutation are more likely to develop hematologic toxicity associated with vincristine than ABCB1 wild-type dogs.
Animals: Thirty-four dogs diagnosed with lymphoma were included in this study.
Methods: Cheek swab samples were obtained from dogs diagnosed with lymphoma that were to be treated with vincristine. DNA was extracted from cheek swabs and the ABCB1 genotype was determined. Hematologic adverse drug reactions were recorded for each dog and graded according to the Veterinary Comparative Oncology Group's criteria for adverse event reporting (Consensus Document). In order to avoid possible bias, ABCB1 genotype results for a particular patient were not disclosed to oncologists until an initial adverse event report had been submitted.
Results: Dogs heterozygous or homozygous for the ABCB1-1Δ mutation were significantly more likely to develop hematologic toxicity, specifically neutropenia ( P = .0005) and thrombocytopenia ( P = .0001), after treatment with vincristine than ABCB1 wild-type dogs.
Conclusions and Clinical Implications: At currently recommended dosages (0.5–0.7 mg/M²), vincristine is likely to cause hematologic toxicity in dogs with the ABCB1-1Δ mutation, resulting in treatment delays and unacceptable morbidity and mortality. Assessing the ABCB1-1Δ genotype before vincristine administration and decreasing the dosage may prevent toxicity and treatment delays resulting from neutropenia or thrombocytopenia.     

Cross-Sectional Imaging Characteristics of Pituitary Adenomas, Invasive Adenomas and Adenocarcinomas in Dogs: 33 Cases (1988–2006)

Background: Pituitary tumors in dogs can be adenomas, invasive adenomas, or adenocarcinomas. In people, invasive adenomas and pituitary adenocarcinomas carry a worse prognosis than adenomas.
Hypothesis/Objective: To identify differentiating features on cross-sectional imaging in dogs with pituitary adenomas, invasive adenomas, and adenocarcinomas.
Animals: Thirty-three dogs that had computed tomography (CT) or magnetic resonance imaging (MRI) performed and a necropsy diagnosis of pituitary adenoma ( n = 20), invasive adenoma ( n = 11), or adenocarcinoma ( n = 2).
Methods: Medical records were retrospectively reviewed for signalment, history, and diagnosis. CT and MR images were reviewed for characteristics of pituitary tumors.
Results: Mean (± standard deviation) age for dogs with pituitary adenomas (10.6 ± 2.9 years) was greater than that of those with invasive adenomas (8.3 ± 2.7 years, P = .04). Eighteen out of 20 (90%) dogs with adenomas had contrast-enhancing masses. Thirteen out of 20 (65%) had homogeneous enhancement. Mean adenoma height was 1.2 ± 0.7 cm. Eight out of 20 (40%) adenomas were round and 8/20 (40%) compressed surrounding brain. Eleven out of 11 dogs (100%) with invasive adenomas had contrast-enhancing masses. Seven out of 11 (64%) masses were homogeneous. Mean invasive adenoma height was 1.8 ± 0.7 cm, which was significantly greater than adenomas ( P = .03). Mass shape varied from round to oval to irregular. Six out of 11 (55%) masses compressed surrounding brain. Clinical and imaging features were variable for 2 dogs with adenocarcinomas.
Conclusions and Clinical Relevance: Invasive adenoma should be suspected if a dog with a pituitary tumor is <7.7 years of age and has a mass >1.9 cm in vertical height. Adenocarcinomas are uncommon and metastatic lesions were not seen with imaging.     

Synchrony of Ovulation and Follicular Dynamics in Merino Ewes Treated with GnRH in the Breeding and Non-breeding Seasons

The effect of gonadotropin releasing hormone (GnRH) treatment on the time of ovulation and the occurrence of follicular dominance during the non-breeding and breeding seasons (experiment 1), and on fertility after artificial insemination (AI) in the non-breeding season (experiment 2), was examined in Merino ewes. Oestrus was synchronized in 40 nulliparous ewes (experiment 1; n = 20, in the non-breeding and breeding seasons) and in 79 multiparous ewes (experiment 2) using intravaginal sponges and pregnant mare serum gonadotropin. Thirty six hours after sponge removal (SR), half the ewes were injected (i.m.) with 40 microg of synthetic GnRH and the remainder used as controls. GnRH improved the synchrony of ovulation compared with the controls in the breeding (SD = 2.8 vs 5.7 days, p = 0.04) but not the non-breeding season (SD = 3.8 vs 4.4 days, p = 0.69), with ewes ovulating from 42 to 54 h (mean 50.4 +/- 4.08 h) and 42-60 h (mean 54.4 +/- 5.47 h) after SR for GnRH and control, respectively. For both treated and control ewes, ovulation occurred earlier in the non-breeding than the breeding season (50.1 vs 54.6 h; p = 0.002). GnRH had no effect on follicular dominance, as assessed by divergence (D: the time the ovulatory follicle exceeded the average size of the other non-ovulating follicles) or on the interval from D to ovulation (IDO). However, follicular dynamics differed between seasons. The mean follicle diameter increased at a faster rate up to 36 h after SR in the non-breeding compared with the breeding season and then rapidly declined, compared with a later peak (42 h after SR) in mean follicular size during the breeding season. IDO was shorter in the non-breeding than in the breeding season (26.7 +/- 4.30 h vs 39.6 +/- 4.53 h; p = 0.05). In experiment 2, ewes (n = 38 GnRH-treated, n = 40 controls) were inseminated in the uterus by laparoscopy 42 h or 48 h after SR with frozen-thawed sperm. The fertility of ewes treated with GnRH (nine of 39, 23%) was not different to the controls (eight of 38, 21%; p = 0.01). In conclusion the application of GnRH improved synchronization of ovulation but did not improve fertility rates after AI.     

Combined GnRH and PGF2α Application in Cows with Endometritis Puerperalis Treated with Antibiotics

The investigations were carried out on a total of 70 cows with puerperal endometritis. In addition to intrauterine antibiotic treatment, 30 experimental animals were administered 20 μg GnRH analogue, buserelin, between days 10 and 12 post‐partum followed by 500 μg PGF_2α analogue, cloprostenol, 10 days later. Forty control cows were treated only with intrauterine antibiotics. Blood samples for progesterone determination were collected from the tail vein twice weekly until day 70 post‐partum. The first rise in progesterone level above 3.18 nmol/l occurred significantly earlier in the experimental than in control cows (21.6 ± 9.2 versus 27.8 ± 12.3 days; p ≤ 0.05). The duration of the first cycle post‐partum was 15.0 ± 4.3 days in experimental and 19.7 ± 7.3 days in control animals (p ≤ 0.05). However, no significant differences were observed in the occurrence of first oestrus post‐partum. The involution of the uterus was improved after hormone treatment. At day 42 post‐partum, completion of uterine involution was found in 93.3% of hormone‐treated cows and in 82.5% of those treated with antibiotic only (p ≤ 0.05). Clinical recovery was 96.6% in the experimental and 82.5% in the control group (p ≤ 0.05). First service pregnancy rate was significantly better in hormone‐treated than control cows (51.7 versus 36.4%; p ≤ 0.05). Total pregnancy rate and insemination index values were not significantly improved following GnRH and PGF_2α treatment. The average service period was 89.8 ± 21.2 days in cows after hormone treatment, and 112.6 ± 24.5 days in control cows. The difference was statistically significant (p ≤ 0.05). These results indicate, that the sequential GnRH and PGF_2α application in cows with puerperal endometritis positively affected ovarian function and uterine involution, resulting in improved fertility performance.     

Acute Reactions in Dogs Treated with Doxorubicin: Increased Frequency with the Use of a Generic Formulation

During a 4-month period, 34 dogs with tumors received a total of 60 doses of a single generic formulation of doxorubicin; 13 acute drug reactions were observed in these 34 dogs, and no acute reactions were observed after replacing the product with the proprietary brand. These reactions were characterized by one or more of the following signs: pruritus; head-shaking; urticaria; erythema of the pinnal, axillary, or inguinal regions; vocalization; vomiting; hyperemic or pale mucous membranes; high heart rate; and high respiratory rate. We propose that a component unique to generic doxorubicin was responsible for the unusually high number of acute drug reactions observed.     

Serum Pancreatic Lipase Immunoreactivity Concentrations in Dogs Treated with Potassium Bromide and/or Phenobarbital

Potassium bromide, phenobarbital, or a combination of both is commonly used in the treatment of canine epilepsy. Several cases of clinical pancreatitis have been reported in dogs after treatment with potassium bromide, but the risk of elevated serum canine pancreatic lipase immunoreactivity concentrations in dogs treated with potassium bromide and/or phenobarbital has not previously been evaluated in a large group of dogs. This study suggests an increased risk for elevated serum canine pancreatic lipase immunoreactivity concentrations and possibly pancreatitis in dogs treated with potassium bromide or phenobarbital alone or in combination.     

Effects of Cyclosporin A on Blood Pressure, Baroreceptor Reflex and Renal Function in Dogs

The objective of this study is to investigate the effect of cyclosporin A (CsA) on baroreceptor reflex and renal function. Fifteen male mongrel dogs weighing 13-18 kg were divided into three groups and were treated orally as follows: group 1, enalapril 0.5 mg/kg per day for 10 days; group 2, CsA 20 mg/kg per day for 7 days; group 3, enalapril 0.5 mg/kg per day for 3 days combined with CsA 20 mg/kg per day for 7 more days. Measurements of blood pressure and of baroreflex response to sodium nitroprusside (SNP) and phenylephrine (PE) and renal function studies were performed on the days before and after receiving drugs. In group 1, both systolic arterial pressure (SAP) and mean arterial pressure (MAP) were unaltered, while diastolic arterial pressure (DAP) was reduced significantly. In group 2, all pressures (SAP, MAP and DAP) increased significantly. Group 3 showed no change in blood pressure. Studies of baroreceptor reflex showed that only dogs in group 2 had decreased sensitivity to PE without changing the setpoint. No change of the reflex was found in other groups. Renal function studies were unaltered in all groups. The data indicate that CsA increased blood pressure, which may be due to decreased baroreceptor reflex sensitivity mediated via activation of the renin-angiotensin-aldosterone system.     

Partial Laryngectomy in the Dog I. Healing and Swallowing Function in Normal Dogs

Laryngeal paralysis was created in normal dogs by sectioning the recurrent laryngeal nerves. The dogs were treated with bilateral vocal fold resection and unilateral partial arytenoidectomy, and sacrificed from 6 hours to 28 days following surgery. Swallowing abnormalities were not found in any of the dogs. Healing by granulation-epithelialization was complete by 14 days.     

Urinary Catecholamine and Metanephrine to Creatinine Ratios in Dogs with Hyperadrenocorticism or Pheochromocytoma,and in Healthy Dogs

Background: Urinary catecholamines and metanephrines are used for the diagnosis of pheochromocytoma (PHEO) in dogs. Hyperadrenocorticism (HAC) is an important differential diagnosis for PHEO. Objectives: To measure urinary catecholamines and metanephrines in dogs with HAC. Animals: Fourteen dogs with HAC, 7 dogs with PHEO, and 10 healthy dogs. Methods: Prospective clinical trial. Urine was collected during initial work‐up in the hospital; in dogs with HAC an additional sample was taken at home 1 week after discharge. Parameters were measured using high‐pressure liquid chromatography and expressed as ratios to urinary creatinine concentration. Results: Dogs with HAC had significantly higher urinary epinephrine, norepinephrine and normetanephrine to creatinine ratios than healthy dogs. Urinary epinephrine, norepinephrine, and metanephrine to creatinine ratios did not differ between dogs with HAC and dogs with PHEO, whereas the urinary normetanephrine to creatinine ratio was significantly higher (P= .011) in dogs with PHEO (414, 157.0–925.0, median, range versus (117.5, 53.0–323.0). Using a cut‐off ratio of 4 times the highest normetanephrine to creatinine ratio measured in controls, there was no overlap between dogs with HAC and dogs with PHEO. The variables determined in urine samples collected at home did not differ from those collected in the hospital. Conclusion and Clinical Importance: Dogs with HAC might have increased concentrations of urinary catecholamines and normetanephrine. A high concentration of urinary normetanephrine (4 times normal), is highly suggestive of PHEO.     

Pathological Conditions of the Reproductive Organs of Male Stray Dogs in the Tropics: Prevalence, Risk Factors, Morphological Findings and Testosterone Concentrations

The objective of this study was to estimate the prevalence of and risk factors for pathological conditions of the reproductive organs in stray dogs under tropical conditions. Three hundred and eighteen dogs were examined post-mortem in the period from 1 July 2002 to 30 June 2003. Before killing, a blood sample (from the cephalic vein) for testosterone assay was taken. Pathological conditions of the reproductive organs were found in 135 of the dogs (42.5%) and in 175 of the testes (64.8%). The most frequent pathologies found were testicular degeneration, cryptorchidism, testicular hypoplasia and testicular tumours (in 15.1%, 6.6%, 6.6% and 5.4% of the dogs and 15.1, 4.6, 6.0 and 3.5 of the testes, respectively). Transmissible venereal tumour (TVT) was seen in 5.4% of the dogs. Testicular degeneration was more common in old dogs and underweight dogs (p < 0.05). Testicular tumours were 14.3 times more common in cryptorchid dogs. Age was another important factor for the development of testicular tumours (p < 0.05). Lower levels of testosterone concentration (p < 0.05) were observed in dogs with advanced testicular degeneration (0.7 +/- 0.8 nM), dogs with hypoplastic testicles (0.8 +/- 0.9 nM) and dogs with one degenerated and one retained testis or with bilateral cryptorchidism (1.2 +/- 0.9 nM) compared to dogs with one or two normal testes (7.0 +/- 5.5 nM). Testicular volume and weight were significantly lower in degenerated, hypoplastic and retained testes compared with the contralateral normal testis. Some spermatogenic activity was found in three of the retained testes, producing oligozoospermic smears with a high percentage of sperm abnormalities. No comparable epidemiological data about male pathological conditions of the reproductive organs in the dog is available. The prevalence found in this study, yet, appears high.     

Gastric Conduit Urinary Diversion in Normal Dogs Part I, Upper Urinary Tract Structure, Function, and Sepsis

The urinary bladder of 10 clinically normal dogs was excised and the ureters were implanted into an isolated, vagotomized gastric segment derived from the fundic region of the stomach. The gastric segment was closed to form a conduit. Continence was maintained with a modified Kock "nipple valve" created from an isolated segment of ileum. Four dogs were euthanatized by day 30 because of complications related to the early onset of renal failure and electrolyte alterations. Six dogs were euthanatized on day 150. Ureteral dilatation, hydronephrosis, and decreased endogenous creatinine clearance rates were measured in all dogs at the end of the survival period. Pyelonephritis was diagnosed histologically in seven dogs. Positive renal cultures were obtained from seven dogs at necropsy. It was concluded that gastric conduit urinary diversion is unsatisfactory for long-term or short-term clinical use in dogs.