Nasal tumor with widespread cutaneous metastases in a Golden Retriever.

An intact, 8-year-old, male Golden Retriever dog was presented for evaluation of a nasal mass and approximately 30 firm, raised, variably ulcerated dermal and subcutaneous masses. Histopathology of both nasal and multiple skin masses revealed multiple nonencapsulated, infiltrative masses comprising clusters, anastomosing trabeculae, and packets of neoplastic, round to ovoid, hyperchromatic cells with marked nuclear molding. Surrounding the neoplastic cells was a marked stromal response in which many of the spindle-shaped cells expressed muscle-specific actin and had ultrastructural features consistent with myofibroblasts. A literature search indicates that this is the first report in a peer-reviewed journal of cutaneous metastasis of a nasal neuroendocrine tumor in any domestic animal species.

Benefit-risk assessment of vitamin D supplementation.

UNLABELLED: Current intake recommendations of 200 to 600 IU vitamin D per day may be insufficient for important disease outcomes reduced by vitamin D. INTRODUCTION: This study assessed the benefit of higher-dose and higher achieved 25-hydroxyvitamin D levels [25(OH)D] versus any associated risk. METHODS AND RESULTS: Based on double-blind randomized control trials (RCTs), eight for falls (n = 2426) and 12 for non-vertebral fractures (n = 42,279), there was a significant dose-response relationship between higher-dose and higher achieved 25(OH)D and greater fall and fracture prevention. Optimal benefits were observed at the highest dose tested to date for 700 to 1000 IU vitamin D per day or mean 25(OH)D between 75 and 110 nmol/l (30-44 ng/ml). Prospective cohort data on cardiovascular health and colorectal cancer prevention suggested increased benefits with the highest categories of 25(OH)D evaluated (median between 75 and 110 nmol/l). In 25 RCTs, mean serum calcium levels were not related to oral vitamin D up to 100,000 IU per day or achieved 25(OH)D up to 643 nmol/l. Mean levels of 75 to 110 nmol/l were reached in most RCTs with 1,800 to 4,000 IU vitamin D per day without risk. CONCLUSION: Our analysis suggests that mean serum 25(OH)D levels of about 75 to 110 nmol/l provide optimal benefits for all investigated endpoints without increasing health risks. These levels can be best obtained with oral doses in the range of 1,800 to 4,000 IU vitamin D per day; further work is needed, including subject and environment factors, to better define the doses that will achieve optimal blood levels in the large majority of the population.

Dietary supplements: how they are used and regulated.

Overall use of nutrient and botanical dietary supplements (DS) has increased for years across all major categories. Many DS are simply taken as part of a healthy lifestyle, but some are used to reduce risk of or modulate risk factors for specific chronic diseases, such as heart disease (vitamin E, folic acid, garlic), cancer (selenium, vitamin E, garlic) and certain birth defects (folic acid). Other DS are used for short-term benefits such as sleep management (valerian, melatonin) and enhanced physical performance (pyruvate, creatine). DS are regulated under food law, but with certain provisions that apply only to DS. Thus, DS are eligible for Food and Drug Administration (FDA)-authorized health claims under the Nutrition and Labeling Education Act (NLEA). Health claims have already been authorized for folic acid and calcium, but not for several others. In 1994, when the Dietary Supplement Health and Education Act (DSHEA) was passed, it expanded and clarified the definition of DS, specified additional requirements for safety and provided for four types of claims of nutritional support. These include prevention of classic nutritional deficiencies, structure or function (S/F) effects, mechanisms for S/F effects and general well-being. Although S/F effects result from both foods and drugs, representation that a product will treat, cure, mitigate or diagnose a disease is reserved for drugs. Therefore, the wording of S/F claims for DS has become a difficult issue in the proposed DS labeling regulations.

Computed tomographic characteristics of multilobular tumor of bone involving the cranium in 7 dogs and zygomatic arch in 2 dogs.

Computed tomography (CT) images of nine dogs with a multilobular tumor of bone of the head were reviewed. The CT characteristics of the neoplasms involving the calvarium (n = 7) were rounded, well defined with a fine granular, nonhomogeneous bone opacity usually in the occipital region. Cranial vault invasion (5 of 7) was commonly found with a significant portion of the mass within the vault. The neoplasms involving the zygomatic arch (n = 2) were also generally rounded and well defined but with a more coarse granular appearance. The common CT findings were best seen when the images were viewed in a bone window.

Low-field magnetic resonance imaging of early subchondral cyst-like lesions in induced cranial cruciate ligament deficient dogs.

Six healthy adult male mongrel dogs underwent cranial cruciate ligament transection in the left stifle. Survey radiography of both stifles and low-field (0.064 T) MRI of the left stifle were performed preoperatively and at 2, 6, and 12 weeks postoperatively. Focal changes in signal intensity were seen with MRI in the subchondral bone of the medial tibial condyle at 2 and 6 weeks postoperatively. At 12 weeks postoperative, a cyst-like lesion was detected using MRI in the subchondral bone of the medial tibial condyle in 4 of 6 dogs and a less defined lesion at this site in the remaining 2 dogs. The cyst-like lesion was spherical in shape and showed typical characteristics of fluid with low signal intensity on T1-weighted images, high signal intensity on T2-weighted images and high signal intensity on inversion recovery images. The lesion was seen in the subchondral bone of the caudal medial and/or middle region of the tibial plateau slightly cranial to the insertion of the caudal cruciate ligament. No subchondral cysts were seen in the tibia on radiographs. Histopathologically, the tibia was characterized by a loose myxomatous phase of early subchondral cyst formation.

Vitamins and minerals: efficacy and safety.

Safety and efficacy are crucial but separate issues for vitamin and mineral supplements. Misinterpretation of "safe and adequate" to mean "safety limit" would impose restrictions on vitamin and mineral intakes that are not needed to ensure safety. Substantial evidence indicates that intakes greater than the recommended dietary allowances (RDAs) of certain vitamins and minerals such as calcium, folic acid, vitamin E, selenium, and chromium reduce the risk of certain diseases for some people. Limitation of intakes to the RDAs would preclude reductions in disease risk from these nutrients. The margin of safety between the usual dietary intake and the intake that would produce adverse effects varies greatly among the different nutrients. Very high intakes of vitamins A and D, niacin, pyridoxine, and selenium have produced adverse effects. Many widely discussed putative adverse effects of vitamin C, vitamin E, and trivalent chromium have little factual basis. There is no evidence of adverse effects from beta-carotene supplements except in current heavy smokers.

A retrospective study of canine hip dysplasia in 116 military working dogs. Part I: Angle measurements and orthopedic foundation for animals (OFA) grading.

The progression of hip dysplasia was investigated in 116 military working dogs. Serial pelvic radiographs were graded for degree of dysplasia and degenerative joint disease (DJD). Norberg angles, angles of inclination, and joint space widths were measured. There was a significant correlation between the Norberg angle and the degree of dysplasia (p less than 0.0001). Angles of inclination and joint space width measurements did not demonstrate a correlation to canine hip dysplasia. Dysplastic dogs had a significant estimated risk for development of DJD compared to normal dogs (p less than 0.0001; odds ratio of 70.2). Dogs with normal hip conformation at 24 months of age or older did not develop moderate nor severe DJD.

A retrospective study of canine hip dysplasia in 116 military working dogs. Part II: Clinical signs and performance data.

The progression of hip dysplasia was investigated in 116 military working dogs. Medical records were reviewed for any clinical history of hind-limb lameness. Pelvic radiographs were studied for evidence and degree of hip dysplasia, degenerative joint disease, or both. The number of months each dog worked was determined. Each dog's age at termination from service and cause of death (or euthanasia) were recorded. The mean months of work for normal and dysplastic dogs were evaluated using the Student's t-test. No significant difference was found in the total number of months worked between normal and dysplastic dogs (p greater than 0.05).

Applications of antioxidants in physiologically functional foods: safety aspects.

Intense public and scientific debate exists over whether the intake of some nutrients above the recommended dietary allowances may provide benefits beyond their traditional functions. However, excessive intakes of nutrients are well documented to cause adverse effects. This review focuses on methods that may be useful for identifying chronic intakes that result in adverse effects and for identifying intakes that provide a reasonable margin of safety from these effects. Groups responsible for nutrition and health policy must establish effective criteria for establishing safety limits, for validating end points, and determination of data acceptability. These criteria are needed to minimize toxicity while maximizing potential health benefits of exaggerated nutrient intake.

Brain stem auditory-evoked response abnormalities in 14 dogs with confirmed central nervous system lesions.

Abnormal brain stem auditory-evoked responses (BAER) were recorded on 14 dogs with brain lesions confirmed by necropsy (n = 13) or magnetic resonance imaging and surgical biopsy (n = 1). Lesions included brain stem or cerebellar tumors (6 dogs), brain stem trauma (1 dog), forebrain tumors (3 dogs), hydrocephalus (2 dogs), granulomatous meningoencephalitis (1 dog), and meningoencephalitis (1 dog). Five affected dogs were comatose at the time of recording. BAER abnormalities could be classified as (1) absence of some or all of waves I to V, (2) increased latencies, with wave V being most frequently affected, or (3) a reduction in the amplitude ratio of waves V/I.

Marginal zinc status does not exacerbate pancreatic carcinogenesis associated with dietary soybean trypsin inhibitor concentrate in rats.

Although the etiology of pancreatic cancer is largely unknown, diet-associated factors may play a role. Male Sprague-Dawley rats (14 d of age) were given a single injection of either saline or azaserine and were weaned (21 d) to diets with either adequate (30 micrograms/g) or low (9 micrograms/g) zinc, with or without 1.0 g/100 g active trypsin inhibitor in the form of soybean trypsin inhibitor concentrate. Experimental diets were fed for 14 wk. Regardless of dietary zinc status, diets with soybean trypsin inhibitor concentrate caused hyperplasia and/or hypertrophy of the pancreas. Pancreatic zinc content was not different among groups. Low dietary zinc levels did not affect total body growth rate or serum zinc concentration. Tibia zinc was also used as an indicator of zinc status. Tibia zinc concentration was lower in rats fed diets low in zinc relative to adequate zinc diets. Azaserine-induced acidophilic foci were larger and more numerous when soybean trypsin inhibitor concentrate was present in the diet regardless of dietary zinc level. Thus, low zinc does not exacerbate the soybean trypsin inhibitor concentrate effects that promote pancreatic cancer.

Prolonged acetaminophen ingestion by mice fed a methionine-limited diet does not affect iron-induced liver lipid peroxidation or S-adenosylmethionine.

This study determined whether acetaminophen (ACAP)-induced glutathione depletion was associated with liver lipid peroxide formation, or the concentrations of liver S-adenosylmethionine and S-adenosylhomocysteine in mice fed diets with L-methionine below or at the requirement level (0.25 or 0.5%) for 7 wk. Iron dextran (281 mg/kg body wt) or saline was administered for 2 d before measurement of lipid peroxide formation. Chronic dietary ACAP (0.5%) in mice fed 0.25% methionine caused a failure to maintain body weight even though food intake was similar to intake by all other treatment groups. Liver GSH (measured as nonprotein sulfhydryl concentration) and cysteine concentrations were depleted by ACAP and by ACAP plus iron. Liver lipid peroxide formation was increased by iron but was not altered additionally by ACAP ingestion. Liver glutathione peroxidase activity was increased by methionine in controls, whereas glutathione S-transferase activity was increased by ACAP ingestion in mice fed 0.5% methionine compared with controls. Liver S-adenosylmethionine and nuclear 5-methyldeoxycytidine concentrations were not affected by dietary ACAP or methionine. Liver S-adenosylhomocysteine levels were lower in mice fed ACAP and 0.25% methionine compared with mice fed ACAP and 0.5% methionine. In conclusion, chronic ACAP did not increase the susceptibility of mice to liver lipid peroxidation or alter the availability of methyl groups for methylation reactions.

Effects of dietary soya bean trypsin inhibitor concentrate on initiation and growth of putative preneoplastic lesions in the pancreas of the rat.

Two studies evaluated the effects of soya bean trypsin inhibitor concentrate (STIC) on early stages of pancreatic carcinogenesis in Wistar rats. In experiment 1, the effects of a 3-month administration of diets containing 3.7% STIC were compared with the effects of administration of diets containing 20% corn oil, in rats pretreated with a single azaserine injection sufficient to initiate putative preneoplastic atypical acinar cell foci. Experiment 2 investigated the capacity of STIC to initiate pancreatic carcinogenesis. Diets containing 3.7% STIC were fed for 4 wk, then diets containing either 5 or 20% corn oil were fed for 3 months. Pancreases were quantitatively evaluated for foci. All groups of azaserine-initiated rats had large numbers of atypical acinar cell foci per cm3 of pancreas. Of these, the group fed 3.7% STIC had pancreatic foci that occupied a significantly greater (P less than 0.01) percentage volume of pancreas than did groups fed 20% corn oil or control diets, which contained 5% corn oil and no added trypsin inhibitor. Very few or no foci were observed in all other groups of either experiment 1 or 2. STIC had a much greater effect on the growth of azaserine-induced lesions than did corn oil. STIC alone did not appear to initiate pancreatic lesions.

Residue trypsin inhibitor: data needs for risk assessment.

Trypsin inhibitor (TI) occurs naturally in many foods from plants, notably soybean protein products. Heat treatment inactivates TI and improves nutritional quality, but residual TI activity of 5 to 20% remains after typical commercial treatments. Chronic feeding of TI or products that contain TI can inhibit trypsin and chymotrypsin, stimulate their secretion, cause hypertrophy and hyperplasia of the pancreas, and lead to adenomas and carcinomas of the exocrine pancreas. In the rat, TI promotes pancreatic carcinogenesis initiated by azaserine. Data needed for possible risk assessment on TI would include 2-year bioassays from animals treated with TI and fed diets carefully controlled for type and amount of fat (which also promotes pancreatic carcinogenesis). The effects of TI on protein nutrition would have to be considered when identifying the maximum tolerated dose. Major reductions in human dietary TI exposure may not be feasible because of the multiple sources of TI, the substantial promotion by other factors such as fat, and the adverse effects of excessive heat on food products. For risk assessment of TI in a particular food, other promotors and the feasibility of decreasing TI intake must be considered.

Metastatic thyroid solid-follicular carcinoma in the cervical portion of the spine of a dog.

A metastatic thyroid solid-follicular carcinoma in the cervical portion of the spine was responsible for severe tetraparesis in a dog. Myelography revealed an extradural compressive lesion dorsal and to the right of the midline of C3. Histologic examination was used to diagnose the mass as a solid-follicular thyroid carcinoma. The primary tumor was not evident on cervical palpation or radiography. A dorsal laminectomy centered over C3 was performed, and all visible tumor was removed from the spine. The owner declined any further treatment for the dog.

A symmetric axis-based method for measuring the projected femoral angle of inclination in dogs.

A new, simple and more consistent method for measuring the projected angle of inclination of the canine femoral neck was devised and tested. This method, based on the principles of symmetric axis (symax) shape analysis, was compared with three other techniques currently in use. Diplomates of the ACVR or ACVS and senior veterinary students were asked to perform measurements of the angle of inclination using the four methods, record their results, and answer several questions about the techniques. Although greater precision was not evident when performed by diplomates, descriptive statistics and a significant difference among the student-derived variances of the four methods demonstrated that the symax-based measurements were most consistent.