犬瘟热自然病例脱髓性脑病发生的机理

为了进一步调查脑组织的髓鞘脱失与神经胶质细胞等成份的关系,用12只犬瘟热自然病例通过病理组织学和免疫组织化学染色法进行了本试验.结果表明:髓鞘脱失部位的脑组织伴有明显的血液循环障碍,即淤血、水肿、血栓形成和弥漫性血管内凝血;少突胶质细胞发生代谢紊乱和凋亡;用抗犬瘟热病毒(CDV)抗体染色,星状胶质细胞呈现强阳性反应;用抗GFAP染色,纤维性星状胶质细胞在脱髓区呈较强阳性反应,用TUNEL染色可检出发生凋亡的星状胶质细胞;一些室管膜细胞也被CDV感染,许多含有包涵体币口凋亡的室管膜细胞在脑室壁被发现;少数神经元变性和皱缩,其核发生浓缩.据此认为,脑组织的髓鞘脱失主要与血液循环障碍和少突胶质细胞的代谢紊乱及凋亡有关;脑组织的髓鞘脱失是许多病因共同作用的结果,并非是一种病因所致.     

Investigation of thyroid function in dogs treated with the tyrosine kinase inhibitor toceranib

Tyrosine kinase inhibitors are widely utilized in veterinary oncology for the treatment of mast cell and solid tumours. In man, these drugs are associated with thyroid dysfunction: however, to date only one study has investigated this in dogs. The aim of this study was to prospectively assess thyroid function in a group of dogs with cancer receiving toceranib. Thirty‐four dogs were prospectively enrolled at two referral hospitals into two groups; those receiving toceranib with prednisolone and those receiving toceranib alone. Total thyroxine (TT4) and thyroid stimulating hormone (TSH) was monitored at regular time points during treatment. Follow‐up data was available for 19 dogs. Overall, 12 incidences of elevated TSH occurred but none of these dogs had concurrent low TT4 concentrations. There was a significant difference in median TSH at week six compared with baseline. Hypothyroidism was not diagnosed in any patient during the study period. Patient drop‐out was higher than anticipated which prevented the assessment of longer term toceranib administration on thyroid function. Toceranib therapy was not associated with hypothyroidism in this study but did result in elevations in TSH which confirms what has been previously reported. Toceranib should be considered to cause thyroid dysfunction in dogs and monitoring is advised.     

Safety of orally administered,USP‐compliant levothyroxine sodium tablets in dogs

The safety of synthetic levothyroxine sodium tablets (Thyro‐Tabs® Canine; LLOYD , Inc.) in dogs was evaluated in a randomized, sham‐dose controlled, parallel‐group study. Young, healthy, euthyroid Beagle dogs were randomized into four groups (four females and four males per group) and received single daily doses of 0×, 2× (0.044 mg/kg), 6× (0.132 mg/kg), or 10× (0.22 mg/kg) the labeled starting dose of 0.022 mg kg^?1 day^?1 for 182 days. Every 2 weeks, physical examinations, electrocardiology examinations, and sample collections for thyroid panel, hematology, serum biochemistry, coagulation panel, and urinalysis were performed. At the end of the study, the dogs were euthanized and full necropsies performed. The most overt finding was the expected dose‐dependent increase in serum concentrations of total and free thyroxine with dose‐dependent suppression of the hypothalamic–pituitary–thyroid axis as evidenced by decreased serum thyroid‐stimulating hormone concentrations, decreased thyroid+parathyroid/body weight ratios, and a trend for decreased pituitary weight/brain weight ratios. Clinical signs of thyrotoxicosis (excitation, tachypnea, tachycardia) in the treated dogs were sporadic with no dose–response relationship. Other findings statistically associated with levothyroxine treatment were generally mild and not clinically important. In summary, doses of levothyroxine sodium up to 10× the labeled starting dose were well tolerated in healthy dogs.     

Hypothyroid dogs treated with intravenous levothyroxine

The purpose of this retrospective study was to report clinical and clinicopathologic findings, response to treatment, and outcome of hypothyroid dogs treated with levothyroxine intravenously (IV). Seven levothyroxine IV treated hypothyroid dogs and 799 other hypothyroid dogs examined during the same period were included. Rottweiler dogs were overrepresented in the group of levothyroxine IV-treated hypothyroid dogs compared with other hypothyroid dogs (P < .0001). Common physical examination abnormalities were obese or overweight body condition (5 dogs), mental dullness (5 dogs), and nonpitting edema (4 dogs). Anemia (4 dogs) and hypercholesterolemia (5) were common, although 1 dog had neither. Concurrent disease (most commonly infection) was observed in 5 dogs. Glucocorticoids and nonsteroidal antiinflammatory drugs had been administered to 2 dogs before examination. Surgery was performed in 2 dogs before treatment with levothyroxine IV. Four of the 7 dogs received 4-5 microg/kg of levothyroxine IV. Subjective improvement in mentation or ambulation (6 of 7 dogs) and systolic hypotension (2 of 2 dogs) occurred within 30 hours of levothyroxine IV administration. Six of the 7 dogs responded well to therapy and were discharged from the hospital. It was concluded that physical examination and clinicopathologic findings of dogs with a hypothyroid crisis are nonspecific, although Rottweiler dogs may be at increased risk. Concurrent disorder, such as infection, concurrent administration of thyroid hormone-altering medication, and surgery, may be associated with development of a hypothyroid crisis. Resolution of abnormal mentation, ambulation, and systolic hypotension should be expected within 30 hours. Prognosis is good in most treated dogs.     

ERG findings in three hypothyroid adult dogs with and without levothyroxine treatment

Purpose To evaluate the effects of levothyroxine (LTh) on the electroretinogram (ERG) of adult dogs. Material and methods Binocular, full field photopic and scotopic ERGs were recorded from an anesthetized Maltese Bichon cross (MB), a Yorkshire Terrier (YT) and a Shetland Sheepdog (SS) affected with hypothyroidism and treated with a daily dose of LTh at 20 µg/kg. The photopic ERGs were evoked to 12 different intensities ranging from 0.81 to –2.19 log cd.s/m² and presented under photopic conditions in order to assess (from the derived luminance-response curves) Vmax and b : a amplitude ratio parameters. Photopic flicker ERGs were obtained at 30 Hz. The scotopic ERGs (intensity: –3.09 log cd.s/m²) were recorded while the retina was dark-adapting and after 32 min of dark adaptation. This procedure was performed on two separate sessions: following a 3-day interruption of LTh treatment (S1) and following 30 days without interruption of LTh treatment (S2). Results The mean photopic a-wave peak times were 9.8 ms at S1 and 5.0 ms at S2, respectively. The mean photopic b-wave peak times were 23.3 ms at S1 and 11.5 ms at S2, respectively, and the mean scotopic b-wave peak times (after 32 min of dark adaptation) were 45.2 ms at S1 and 26.0 ms at S2, respectively. No other significant ERG changes were observed. Conclusion Our results indicate that a dose of 20 µg/kg of LTh given to adult dogs was accompanied by a marked peak time shortening of both photopic and scotopic ERGs, without affecting other ERG parameters.     

Serum insulin-like growth factor type 1 concentrations in healthy dogs and dogs with spontaneous primary hypothyroidism

Circulating insulin-like growth factor type 1 (IGF-1) concentrations in dogs have been correlated with standard breed bodyweight (SBBW or breed size). Thyroid and somatotropic functions, which have common effects and regulatory mechanisms, were investigated in hypothyroid dogs. IGF-1 was measured in 495 adult healthy dogs (N) and in 220 primary hypothyroid dogs (HOT) with clinical and biological signs of primary hypothyroidism. IGF-1 was determined as a function of SBBW (kg): ≤15 (group A); 1540 (group D). In HOT dogs, median fT4 and c-TSH values were 9pmol/L and 1.5ng/mL, respectively. A significant correlation between bodyweight (BW) and IGF-1 was observed in both HOT and N dogs. The median IGF-1 value (ng/mL) was significantly higher (P<0.01) in HOT dogs compared to N in groups B, C and D (230 vs. 182; 316 vs. 230; 606 vs. 306 respectively). In conclusion, IGF-1 concentration should be interpreted in the context of SBBW in dogs and increases in spontaneous primary hypothyroidism. However, it remains unclear if this association is directly due to hypothyroidism or is the result of the weight gain accompanying hypothyroidism.     

Post‐radiotherapy hypothyroidism in dogs treated for thyroid carcinomas

Hypothyroidism is a common adverse event after head and neck radiotherapy in human medicine, but uncommonly reported in canine patients. Records of 21 dogs with histologically or cytologically confirmed thyroid carcinoma receiving definitive or hypofractionated radiotherapy were reviewed. Nine cases received 48 Gy in 12 fractions, 10 received 36 Gy in 4 fractions and 2 received 32 Gy in 4 fractions. Seventeen cases had radiotherapy in a post‐operative setting. Ten cases developed hypothyroidism (47.6%) after radiotherapy. The development of hypothyroidism was not associated with the radiotherapy protocol used. Median time to diagnosis of hypothyroidism was 6 months (range, 1–13 months). Hypothyroidism is a common side effect following radiotherapy for thyroid carcinomas. Monitoring of thyroid function following radiotherapy is recommended. No specific risk factors have been identified.     

Identification and preservation of the parathyroid gland during total thyroidectomy in dogs with bilateral thyroid carcinoma: a report of six cases

Simultaneous removal of bilateral thyroid tumors was performed while preserving the parathyroid gland in six dogs. At least one external parathyroid gland was identified in all dogs. In five cases, the external parathyroid gland and its blood supply were preserved intact. In one dog, the vessels supplying the external parathyroid gland had been invaded by the tumor, and the gland was thus removed and reimplanted into the sternohyoid muscle. That dog required postoperative treatment with oral calcium gluconate and vitamin D₃. Local tumor recurrence was not observed in any of the cases. The mean survival time was 920 days. We found that the external parathyroid gland could be identified and preserved in most dogs undergoing total thyroidectomy.     

Clodronate treatment of vitamin D-induced hypercalcemia in dogs

Objective: To determine the effects of clodronate on vitamin D₃‐induced hypercalcemia in dogs. Design: Prospective experimental study. Settings: University research laboratory. Animals: Fourteen healthy intact adult male and female mixed breed dogs. Interventions: Dogs received 7.5 mg of vitamin D₃/kg of body weight once orally and were randomly assigned to 2 groups of 7 dogs each. Dogs in the saline control group were given intravenous infusions of 150 mL 0.9% NaCl solution 24 hours after vitamin D₃ administration. Dogs in the clodronate group were given an infusion of 4 mg/kg of clodronate in 150 mL 0.9% NaCl solution 24 hours after vitamin D₃ administration. Measurements and main results: Clinical signs of vitamin D₃ toxicosis were evaluated 48 hours after ingestion of vitamin D₃. Dogs that were given clodronate had significantly lower serum calcium (Ca), phosphorus (P), urea, and Ca × P values than dogs in the control group on days 4, 7, and 12 after administration. Additionally, alkaline phosphatase activity was significantly lower in the clodronate group compared with dogs in the control group on days 4 and 7. Conclusions: Parenteral administration of clodronate, a biphosphonate compound and osteoclastic activity inhibitor, may be a useful therapy when administered within the first 24 hours after ingestion of toxic doses of vitamin D₃.     

Preliminary study of plasma vascular endothelial growth factor (VEGF) during low- and high-dose radiation therapy of dogs with spontaneous tumors

High plasma vascular endothelial growth factor (VEGF) concentrations are associated with radiation resistance and poor prognosis. After an exposure to ionizing radiation in cell culture an early phase and a late phase of increased VEGF have been documented. The activation was dependent on the radiation dose. Therefore, the purpose of this study was to measure baseline plasma VEGF and changes in VEGF over the course of fractionated radiation therapy in dogs with spontaneous tumors. Dogs with tumors had a significantly higher pretreatment plasma VEGF than did dogs without tumors. Immediately after irradiation no increased plasma VEGF was observed. Over the course of radiation therapy there was an increased plasma VEGF in dogs treated with low doses per fraction/high total dose, whereas plasma VEGF remained stable in dogs irradiated with high doses per fraction/low total dose. The regulatory mechanisms are very complex, and therefore the value of plasma VEGF measurements as an indirect marker of angiogenesis induced by radiotherapy is limited.