Vagus Nerve Stimulator Placement in Dogs: Surgical Implantation Technique, Complications, Long-Term Follow-Up, and Practical Considerations.

OBJECTIVE: To describe a modified implantation procedure of a vagus nerve stimulation (VNS) device in dogs and to report short- and long-term complications. STUDY DESIGN: Descriptive, experimental study. ANIMALS: Healthy, adult Beagle dogs (n = 10). METHODS: A VNS Therapy(®) System was implanted in the left cervical region of anesthetized dogs. During and within 48 hours after surgery, electrocardiography (ECG) and impedance testing of the system were performed. Dogs were monitored daily and the impedance of the system was determined regularly until VNS devices were surgically removed 3 years after implantation. RESULTS: The implantation procedure was successful in all dogs without intraoperative complications. ECG monitoring and impedance tests were within normal limits during and within 48 hours after surgery. Postoperative seroma formation was common (70%). One dog developed an irreversible Horner's syndrome leading to removal of the device 5 months after implantation. Another dog developed trauma-induced damage of the lead requiring surgical revision. The device could be safely removed in all dogs; however, electrodes were left in place to avoid nerve damage. At removal, the anchor tether was dislodged in 40% of dogs and the lead was twisted in 50% of dogs. CONCLUSION: Implantation of a VNS Therapy(®) System is safe and feasible in dogs; however, seroma formation, twisting of the lead, and dislodgement of the anchor tether were common. Practical improvements in the technique include stable device placement, use of a compression bandage, and exercise restriction. Regular evaluation of lead impedance is important, as altered values can indicate serious complications.

The influence of sex hormones on seizures in dogs and humans.

Epilepsy is the most common chronic neurological disorder in both humans and dogs. The effect of sex hormones on seizures is well documented in human medicine. Catamenial epilepsy is defined as an increase in frequency and severity of seizures during certain periods of the menstrual cycle. Oestradiol increases seizure activity and progesterone is believed to exhibit a protective effect. The role of androgens is controversial and there is a lack of research focusing on androgens and epilepsy. Indeed, little is known about the influence of sex hormones on epilepsy in dogs. Sterilisation is believed to improve seizure control, but no systematic research has been conducted in this field. This review provides an overview of the current literature on the influence of sex hormones on seizures in humans. The literature on idiopathic epilepsy in dogs was assessed to identify potential risk factors related to sex and sterilisation status. In general, there appears to be an over-representation of male dogs with idiopathic epilepsy but no explanation for this difference in prevalence between sexes has been reported. In addition, no reliable conclusions can be drawn on the effect of sterilisation due to the lack of focused research and robust scientific evidence.

Idiopathic head tremor in English bulldogs.

Idiopathic head tremor (IHT) syndrome is a recognized but poorly characterized movement disorder in English bulldogs (EBs). The data analyzed were collected via a detailed online questionnaire and video recordings. Thirty-eight percent of the population demonstrated IHT. The first presentation was early in life. There was no sex or neutered status predisposition. The condition disappeared with time in 50% of the cases. The direction of the head movement was vertical or horizontal. The number of episodes per day and the duration of the episodes were greatly variable. The majority of episodes occurred at rest. Most of the episodes were unpredictable. And there was no alteration of the mental status for most dogs during the episodes. Stress has been reported as a suspected trigger factor. IHT in EBs can be considered an idiopathic paroxysmal movement disorder.

Idiopathic sterile inflammation of the epidural fat and epaxial muscles causing paraplegia in a mixed-breed dog.

CASE DESCRIPTION: A 4-year-old sexually intact male mixed-breed dog was evaluated because of clinical signs of acute-onset pelvic limb ataxia, rapidly progressing to paraplegia with severe spinal hyperesthesia. CLINICAL FINDINGS: General physical examination revealed pyrexia, tachycardia, and tachypnea. Neurologic examination demonstrated severe spinal hyperesthesia and paraplegia with decreased nociception. Magnetic resonance imaging revealed extradural spinal cord compression at T13-L1 and hyperintense lesions on T1- and T2-weighted images in the epaxial musculature and epidural space. TREATMENT AND OUTCOME: Decompressive surgery, consisting of a continuous dorsal laminectomy, with copious lavage of the vertebral canal was performed. Cultures of blood, urine, and surgical site samples were negative. Histologic examination results for samples obtained during surgery demonstrated suppurative myositis and steatitis. These findings confirmed a diagnosis of sterile idiopathic inflammation of the epidural fat and epaxial muscles with spinal cord compression. The dog's neurologic status started to improve 1 week after surgery. After surgery, the dog received supportive care including antimicrobials and NSAIDs. The dog was ambulatory 1 month after surgery and was fully ambulatory despite signs of mild bilateral pelvic limb ataxia 3 years after surgery. CLINICAL RELEVANCE: Although idiopathic sterile inflammation of adipose tissue, referred to as panniculitis, more commonly affects subcutaneous tissue, its presence in the vertebral canal is rare. Specific MRI findings described in this report may help in reaching a presumptive diagnosis of this neurologic disorder. A definitive diagnosis and successful long-term outcome in affected patients can be achieved by decompressive surgery and histologic examination of surgical biopsy samples.

Intervertebral disk width in dogs with and without clinical signs of disk associated cervical spondylomyelopathy.

BACKGROUND: Disk-associated cervical spondylomyelopathy (DA-CSM) is a multifactorial neurological disorder in which progressive caudal cervical spinal cord compression is mainly caused by one or more intervertebral disk protrusions. The Doberman pinscher breed seems predisposed for this condition. The underlying cause and pathophysiology of DA-CSM are currently unknown. Recently, wider intervertebral disks have been put forward as a risk factor for development of clinically relevant DA-CSM. However, little is known about other factors affecting intervertebral disk width. Therefore the aim of this study was to assess the association between intervertebral disk width, measured on magnetic resonance imaging (MRI), and clinical status, age, gender and intervertebral disk location in dogs with and without clinical signs of DA-CSM. METHODS: Doberman pinschers with clinical signs of DA-CSM (N=17),clinically normal Doberman pinschers (N=20), and clinically normal English Foxhounds (N=17), underwent MRI of the cervical vertebral column. On sagittal T2-weighted images, intervertebral disk width was measured from C2-C3 to C6-C7. Intra -and interobserver agreement were assessed on a subset of 20 of the 54 imaging studies. RESULTS: Intervertebral disk width was not significantly different between Doberman pinschers with clinical signs of DA-CSM, clinically normal Doberman pinschers or clinically normal English Foxhounds (p=0.43). Intervertebral disk width was positively associated with increasing age (p=0.029). Each monthly increase in age resulted in an increase of disk width by 0.0057 mm. Intervertebral disk width was not significantly affected by gender (p=0.056), but was significantly influenced by intervertebral disk location (p <0.0001). The assessed measurements were associated with a good intra -and interobserver agreement. CONCLUSIONS: The present study does not provide evidence that wider intervertebral disks are associated with clinical status in dogs with and without DA-CSM. Instead, it seems that cervical intervertebral disk width in dogs is positively associated with increase in age.

Evolution of clinical signs and predictors of outcome after conservative medical treatment for disk-associated cervical spondylomyelopathy in dogs.

OBJECTIVE: To evaluate the evolution of clinical signs and their correlation with results of magnetic resonance imaging (MRI) and transcranial magnetic stimulation (TMS) and to assess potential prognostic variables after conservative medical treatment for disk-associated cervical spondylomyelopathy (DA-CSM) in dogs. DESIGN: Prospective cohort study. ANIMALS: 21 client-owned dogs with DA-CSM. PROCEDURES: After neurologic grading, dogs underwent low-field MRI and TMS with measurement of onset latencies and peak-to-peak amplitudes from the extensor carpi radialis and cranial tibial muscles. Dimensions calculated from MRI images were remaining spinal cord area, spinal cord compression ratio, vertebral occupying ratio, vertebral canal height-to-body height ratio, vertebral canal height-to-body length ratio, and vertebral canal compromise ratio. Intraparenchymal signal intensity changes were graded. Dogs were reevaluated 1, 3, 6, 12, and 24 months after initial diagnosis. RESULTS: Outcome was successful in 8 of 21 dogs. Negative outcomes were characterized by rapid progression of clinical signs. All dogs with more severe clinical signs of DA-CSM 1 month after diagnosis had unsuccessful outcomes. Outcome was associated with the remaining spinal cord area and vertebral canal compromise ratio. Prognosis was not associated with severity of clinical signs or results of TMS. There were no significant correlations among clinical signs, MRI findings, and TMS results. CONCLUSIONS AND CLINICAL RELEVANCE: Conservative medical treatment of DA-CSM was associated with a guarded prognosis. Selected MRI variables and clinical evolution 1 month after diagnosis can be considered prognostic indicators. The lack of correlation among clinical signs, results of diagnostic imaging, and results of electrophysiologic evaluation in dogs with DA-CSM warrants further investigation.

Morphometric dimensions of the caudal cervical vertebral column in clinically normal Doberman Pinschers, English Foxhounds and Doberman Pinschers with clinical signs of disk-associated cervical spondylomyelopathy.

Client-owned, clinically normal Doberman Pinschers (n=20), English Foxhounds (n=17), and Doberman Pinschers with clinical signs of disk-associated cervical spondylomyelopathy (DA-CSM) (n=17) were prospectively studied. All dogs underwent magnetic resonance imaging (MRI) of the cervical vertebral column. To evaluate vertebral canal stenosis, the canal occupying ratios of the spinal cord and cerebrospinal fluid (CSF)-column were calculated from C5 to C7. To evaluate the degree of spinal cord compression and the amount of canal compromise, the compression ratio, remaining spinal cord and CSF-column area, and vertebral canal and dorsoventral vertebral canal compromise ratios were calculated at the site of most severe compression. For each canal occupying ratio, there was a significant higher value (implicating less space available for the spinal cord in the vertebral canal) at the level of C7 for clinically affected Doberman Pinschers compared with clinically normal English Foxhounds. The remaining spinal cord area was significantly smaller in dogs with clinically relevant spinal cord compression compared to dogs with clinically irrelevant spinal cord compression. Relative stenosis of the caudal cervical vertebral canal occurred more often in Doberman Pinschers with DA-CSM compared to English Foxhounds and a critical degree of spinal cord compression should be reached to result in clinical signs.

Reference values and clinical application of magnetic peripheral nerve stimulation in cats.

Magnetic stimulation of radial (RN) and sciatic (SN) nerves was performed bilaterally in 40 healthy cats. Reference values for onset latency and peak-to-peak amplitude of magnetic motor evoked potentials (MMEPs) were obtained and compared with values of electric motor evoked potentials (EMEPs) in 10/40 cats. Onset latencies and peak-to-peak amplitudes of the MMEPs of three cats with polyneuropathy (PNP) were compared to the reference values. Magnetic motor evoked responses were easily recorded in all normal cats. Significant differences were found in onset latencies between MMEPs and EMEPs, but peak-to-peak amplitudes were equal. The MMEPs of three cats with PNP can be seen as outliers in comparison to the reference values. MMEPs from the RN and SN were easily obtained and reproducible in normal cats. The technique could represent a useful adjunct in the assessment of peripheral nerve disorders.

Magnetic resonance imaging vertebral canal and body ratios in Doberman Pinschers with and without disk-associated cervical spondylomyelopathy and clinically normal English Foxhounds.

OBJECTIVE: To determine magnetic resonance imaging (MRI) vertebral ratio values representing vertebral canal height, vertebral canal shape, and vertebral body shape in Doberman Pinschers with and without disk-associated cervical spondylomyelopathy (DACSM) and clinically normal English Foxhounds. ANIMALS: Doberman Pinschers with (n = 18) and without (20) DACSM and clinically normal English Foxhounds (18). PROCEDURES: All dogs underwent low-field MRI of the cervical vertebral column. From 5 specific measurements made at C3 through C7, 4 linear vertebral ratios were calculated and assessed for correlation: vertebral canal height-to-body height ratio (CBHR), vertebral canal height-to-body length ratio (CBLR), caudal canal height-to-cranial canal height ratio (CCHR), and vertebral body length-to-height ratio (BLHR). The CBHR and CBLR described vertebral canal height, CCHR described vertebral canal shape, and BLHR described vertebral body shape. A midvertebral canal-occupying ratio (mVCOR) for the spinal cord was calculated at C5. RESULTS; Compared with both groups of unaffected dogs, CBHR, CBLR, and BLHR for Doberman Pinschers with DACSM were significantly smaller. The C7 CCHR was significantly larger in DACSM-affected Doberman Pinschers, compared with clinically normal English Foxhounds. Ratios did not differ significantly between unaffected Doberman Pinschers and clinically normal English Foxhounds. Correlation coefficients between CBHR, CBLR, and mVCOR were low and not significant. CONCLUSIONS AND CLINICAL RELEVANCE: Doberman Pinschers with DACSM had significantly smaller vertebral canal heights and more square-shaped vertebral bodies, compared with unaffected Doberman Pinschers, combined with a funnel-shaped vertebral canal at C7. Breed-specific differences were not evident. Linear MRI vertebral canal-to-body ratios do not appear to predict relative vertebral canal stenosis.

Radiographic vertebral canal and vertebral body ratios in Doberman Pinschers with and without clinical signs of caudal cervical spondylomyelopathy.

OBJECTIVE: To determine radiographic vertebral ratio values representing vertebral canal stenosis in Doberman Pinschers with and without clinical signs of caudal cervical spondylomyelopathy (CCSM). ANIMALS: Doberman Pinschers with (n = 81) and without (39) signs of CCSM. PROCEDURES: All dogs underwent lateral survey radiography of the cervical vertebral column. Five specific measurements were made at C3 through C7, and from those data, 3 ratios were calculated and analyzed for use in diagnosis of CSSM: canal height-to-vertebral body height ratio (CBHR), canal height-to-vertebral body length ratio (CBLR), and caudal vertebral canal height-to-cranial vertebral canal height ratio (CCHR). The CBHR and CBLR were considered indicators of vertebral canal stenosis, and CCHR described vertebral canal shape. RESULTS: Compared with Doberman Pinschers without CCSM, mean CBHR and CBLR values were significantly smaller for Doberman Pinschers with CCSM; for CBHR, this difference was evident at each assessed vertebra. The CCHR value for C7 was significantly larger in dogs with CCSM. Receiver operating characteristic statistics did not identify a threshold point that had combined high sensitivity and specificity sufficient to differentiate between Doberman Pinschers with and without CCSM. CONCLUSIONS AND CLINICAL RELEVANCE: Doberman Pinschers with CCSM had vertebral canal stenosis combined with a funnel-shaped vertebral canal at C7 significantly more often than did Doberman Pinschers without CCSM. Despite these significant differences, no reliable threshold ratio values were identified to differentiate groups of dogs.

Intraobserver, interobserver, and intermethod agreement for results of myelography, computed tomography-myelography, and low-field magnetic resonance imaging in dogs with disk-associated wobbler syndrome.

OBJECTIVE: To determine intraobserver, interobserver, and intermethod agreement for results of myelography, computed tomography-myelography (CTM), and low-field magnetic resonance imaging (MRI) in dogs with disk-associated wobbler syndrome (DAWS). DESIGN: Prospective cross-sectional study. ANIMALS: 22 dogs with DAWS. PROCEDURES: All dogs underwent myelography, CTM, and low-field MRI. Each imaging study was interpreted twice by 4 observers who were blinded to signalment and clinical information of the patients. The following variables were assessed by all 3 techniques: number, site, and direction of spinal cord compressions; narrowed intervertebral disk spaces; vertebral body abnormalities; spondylosis deformans; and abnormal articular facets. Intervertebral foraminal stenosis was assessed on CTM and MRI images. Intraobserver, interobserver, and intermethod agreement were calculated by κ and weighted κ statistics. RESULTS: There was very good to good intraobserver agreement for most variables assessed by myelography and only moderate intraobserver agreement for most variables assessed by CTM and low-field MRI. There was moderate to fair interobserver and intermethod agreement for most variables assessed by the 3 diagnostic techniques. There was very good or good intraobserver, interobserver, or intermethod agreement for the site and direction of the worst spinal cord compression as assessed by all the imaging modalities; abnormal articular facets and intervertebral foraminal stenosis were the least reliably assessed variables, with poor interobserver agreement regardless of imaging modality used. CONCLUSIONS AND CLINICAL RELEVANCE: There was considerable variation in image interpretation among observers and between use of various imaging modalities; these imaging techniques should be considered complementary in assessment of dogs with DAWS.

Surgical treatment of disk-associated wobbler syndrome by a distractable vertebral titanium cage in seven dogs.

OBJECTIVE: To evaluate a distractable titanium cage for the treatment of disk-associated wobbler syndrome (DAWS). STUDY DESIGN: Prospective study. ANIMALS: Dogs (n = 7) with DAWS. METHODS: After total discectomy of C5-C6 and C6-C7, the median part of the vertebral body of C6 was removed with preservation of the lateral walls and dorsal cortex. The removed cancellous bone was collected. The implant was placed in the bony defect of C6. After placement, the titanium cage was distracted and affixed by 4 screws. Finally, the implant was filled and covered with cancellous bone. Dogs had follow-up examinations at 1, 3, 6, 12, and 24 months. Six months after surgery, cervical radiographs and computed tomography (CT) were performed. RESULTS: Although no intraoperative complications occurred, correct placement of the cage was technically challenging. Revision surgery was necessary in 2 dogs because of implant loosening and aggravation of vertebral tilting. All dogs improved after discharge from the hospital. In 1 dog, recurrence of clinical signs caused by articular facet proliferation at an adjacent intervertebral disk space occurred. Radiographs at 6 months demonstrated cage subsidence in 4 dogs. In all dogs, CT was suggestive for fusion of the bone graft with the vertebral body. CONCLUSIONS: Although results are promising, technical adaptations will be necessary to make this specific surgical technique, designed for humans, suitable for routine use in dogs.

Intraobserver and interobserver agreement for results of low-field magnetic resonance imaging in dogs with and without clinical signs of disk-associated wobbler syndrome.

OBJECTIVE: To determine interobserver and intraobserver agreement for results of low-field magnetic resonance imaging (MRI) in dogs with and without disk-associated wobbler syndrome (DAWS). DESIGN: Validation study. ANIMALS: 21 dogs with and 23 dogs without clinical signs of DAWS. PROCEDURES: For each dog, MRI of the cervical vertebral column was performed. The MRI studies were presented in a randomized sequence to 4 board-certified radiologists blinded to clinical status. Observers assessed degree of disk degeneration, disk-associated and dorsal compression, alterations in intraspinal signal intensity (ISI), vertebral body abnormalities, and new bone formation and categorized each study as originating from a clinically affected or clinically normal dog. Interobserver agreement was calculated for 44 initial measurements for each observer. Intraobserver agreement was calculated for 11 replicate measurements for each observer. RESULTS: There was good interobserver agreement for ratings of disk degeneration and vertebral body abnormalities and moderate interobserver agreement for ratings of disk-associated compression, dorsal compression, alterations in ISI, new bone formation, and suspected clinical status. There was very good intraobserver agreement for ratings of disk degeneration, disk-associated compression, alterations in ISI, vertebral body abnormalities, and suspected clinical status. There was good intraobserver agreement for ratings of dorsal compression and new bone formation. Two of 21 clinically affected dogs were erroneously categorized as clinically normal, and 4 of 23 clinically normal dogs were erroneously categorized as clinically affected. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that variability exists among observers with regard to results of MRI in dogs with DAWS and that MRI could lead to false-positive and false-negative assessments.

Transcranial magnetic stimulation in Doberman Pinschers with clinically relevant and clinically irrelevant spinal cord compression on magnetic resonance imaging.

OBJECTIVE: To evaluate the use of transcranial magnetic stimulation for differentiating between clinically relevant and clinically irrelevant cervical spinal cord compression on magnetic resonance imaging (MRI). DESIGN: Validation study. ANIMALS: Clinically normal Doberman Pinschers without (n = 11) and with (6) spinal cord compression on MRI and 16 Doberman Pinschers with disk-associated wobbler syndrome (DAWS). PROCEDURES: After dogs were sedated, transcranial magnetic motor evoked potentials were recorded from the extensor carpi radialis muscle (ECRM) and cranial tibial muscle (CTM). Onset latencies and peak-to-peak amplitudes were measured. Magnetic resonance imaging was performed to identify spinal cord compression. RESULTS: There were significant differences in ECRM and CTM onset latencies between Doberman Pinschers with DAWS and each of the 2 groups of clinically normal dogs, but there were no significant differences in ECRM and CTM onset latencies between the 2 groups of clinically normal dogs. There were significant differences in CTM peak-to-peak amplitudes between Doberman Pinschers with DAWS and each of the 2 groups of clinically normal dogs, but there were no significant differences in ECRM peak-to-peak amplitudes among groups or in CTM peak-to-peak amplitudes between the 2 groups of clinically normal dogs. There was a significant correlation between severity of spinal cord compression and ECRM onset latency, CTM onset latency, and CTM peak-to-peak amplitude. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that transcranial magnetic stimulation may be a useful diagnostic tool to differentiate between clinically relevant and clinically irrelevant spinal cord compression identified on MRI alone.

Low-field magnetic resonance imaging findings of the caudal portion of the cervical region in clinically normal Doberman Pinschers and Foxhounds.

OBJECTIVE: To determine the spectrum and frequency of abnormalities for low-field magnetic resonance imaging (MRI) examinations of clinically normal Doberman Pinschers and Foxhounds. ANIMALS: 37 clinically normal dogs (20 Doberman Pinschers and 17 Foxhounds). PROCEDURES: For each dog, MRI of the cervical vertebrae (sagittal, dorsal, and transverse T1- and T2-weighted images) was performed. Variables assessed were intervertebral disk degeneration, disk-associated compression, compression of the dorsal portion of the spinal cord, vertebral body abnormalities, and changes in intraparenchymal signal intensity. Associations between these variables and age, breed, sex, and location of the assessed intervertebral disk spaces were evaluated. RESULTS: Severe MRI abnormalities were detected in 17 dogs, including complete disk degeneration (n = 4 dogs), spinal cord compression (3), or both (10). Vertebral body abnormalities were detected in 8 dogs, and hyperintense signal intensity was detected in 2 dogs. Severity of disk degeneration and disk-associated compression was significantly associated with increased age. There was a significant association between disk degeneration, disk-associated compression, and compression of the dorsal aspect of the spinal cord and location of the assessed intervertebral disk space, with the intervertebral disk spaces in the caudal portion of the cervical region being more severely affected. CONCLUSIONS AND CLINICAL RELEVANCE: Abnormalities were commonly seen on MRI examinations of the caudal portion of the cervical vertebral column and spinal cord of clinically normal Doberman Pinchers and Foxhounds. Such lesions were probably part of the typical spinal cord degeneration associated with the aging process of dogs.

Agreement and repeatability of linear vertebral body and canal measurements using computed tomography (CT) and low field magnetic resonance imaging (MRI).

OBJECTIVE: To evaluate agreement and repeatability of vertebral column measurements using computed tomography (CT) and magnetic resonance imaging (MRI). STUDY DESIGN: Retrospective observational study. ANIMALS; Dogs (n=18) with disc associated wobbler syndrome; Dog cadavers (n=3). METHODS: Five measurements of the 5th cervical vertebra were performed: vertebral body length (VBL), vertebral canal height (VCH), vertebral body height (VBH), vertebral canal width (VCW), and vertebral body width (VBW). Measurements were performed independently twice by 2 observers. Bland-Altman plots were created to evaluate agreement. Cadaveric vertebrae with soft tissue removed had the same variables and actual dimensions measured. RESULTS: The largest discrepancy between CT and MRI measurement was for VBL (mean difference+/-SD=1.262 mm+/-1.245; P<.001), with the difference for all the other variables being acceptable. The 1st measurement was significantly higher than the 2nd only for VBL using CT (mean difference=0.476 mm+/-1.120; P=.009), with all other variables having acceptable differences. Mean difference for all measurements between 2 observers was small, except for VBL using CT (mean difference=0.762 mm+/-1.042; P<.001). Only the difference for VBL between CT and cadaver specimens was statistically significant. CONCLUSIONS: Our results suggest high repeatability and good agreement for most vertebral measurements of interest. VBL measurement using CT was considered problematic. CLINICAL RELEVANCE: Provided limitations are understood, linear measurements of vertebral dimensions from CT and MRI images can be used clinically.

Role of progestin-induced mammary-derived growth hormone in the pathogenesis of cystic endometrial hyperplasia in the bitch.

Endogenous progesterone and synthetic progestins may induce hypersecretion of growth hormone (GH) of mammary origin, hyperplastic ductular changes in the mammary gland, and the development of cystic endometrial hyperplasia (CEH) in dogs. It was investigated whether progestin-induced mammary GH plays a role in the pathogenesis of CEH in the bitch. During 1 year, bitches with surgically excised mammary glands and healthy control bitches received medroxyprogesterone acetate (MPA). Before and after MPA treatment, uterine and mammary tissues were collected for histological, immunohistochemical, and RT-PCR examination. After MPA administration, the mammary tissue in the control dogs had differentiated into lobulo-alveolar structures and CEH was present in all uteri of both dog groups. In the MPA-exposed mammary tissue of the control dogs, GH could only be demonstrated immunohistochemically in proliferating epithelium. After treatment with MPA the dogs of both groups had immunohistochemically demonstrable GH in the cytoplasm of hyperplastic glandular uterine epithelial cells. RT-PCR analysis of the mammary gland tissue after MPA administration demonstrated a significant higher GH gene, and lower GHR gene expression than before treatment. In the uterus, the expression of the gene encoding for GH was significantly increased in the mastectomized dogs, whereas in the control dogs the expression of the gene encoding for insulin-like growth factor-I had significantly increased with MPA administration. MPA treatment significantly down regulated PR gene expression in the uterus in both dog groups. These results indicate that progestin-induced GH of mammary origin is not an essential component in the development of CEH in the bitch.

Effects of growth hormone secretagogues on the release of adenohypophyseal hormones in young and old healthy dogs.

The effects of three growth hormone secretagogues (GHSs), ghrelin, growth hormone-releasing peptide-6 (GHRP-6), and growth hormone-releasing hormone (GHRH), on the release of adenohypophyseal hormones, growth hormone (GH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), luteinising hormone (LH), prolactin (PRL) and on cortisol were investigated in young and old healthy Beagle dogs. Ghrelin proved to be the most potent GHS in young dogs, whereas in old dogs GHRH administration was associated with the highest plasma GH concentrations. The mean plasma GH response after administration of ghrelin was significantly lower in the old dogs compared with the young dogs. The mean plasma GH concentration after GHRH and GHRP-6 administration was lower in the old dogs compared with the young dogs, but this difference did not reach statistical significance. In both age groups, the GHSs were specific for GH release as they did not cause significant elevations in the plasma concentrations of ACTH, cortisol, TSH, LH, and PRL. It is concluded that in young dogs, ghrelin is a more powerful stimulator of GH release than either GHRH or GHRP-6. Ageing is associated with a decrease in GH-releasing capacity of ghrelin, whereas this decline is considerably lower for GHRH or GHRP-6.