Polioencephalomalacia and Heart Failure Secondary to Presumptive Thiamine Deficiency, Hepatic Lipidosis, and Starvation in 2 Abandoned Siamese Cats.

Two 4-year-old spayed female Siamese cats were seized by the British Columbia Society for the Prevention of Cruelty to Animals after confinement to an abandoned housing unit without food for 9 weeks. One cat was found dead, and the second was euthanized within 24 hours due to neurologic deterioration despite therapy. Polioencephalomalacia of the caudal colliculus, hepatic lipidosis, cachexia, and congestive heart failure with cardiomyocyte atrophy were identified in both cats through postmortem examination and attributed to a prolonged period of starvation. Brain lesions were likely the result of thiamine deficiency (Chastek paralysis), which can be associated with both malnutrition and liver disease. This case highlights the importance of thiamine supplementation during realimentation of cats with hepatic lipidosis. Heart failure resulting from cachexia may have contributed to the death of the first cat and the morbidity of the second cat.

Liver pathology associated with increased mortality in turkey breeder and meat turkey flocks.

Between 2006 and 2011 a series of disease conditions characterized by raised mortality and liver disorders occurred in turkey breeder flocks and in meat turkey flocks in Germany. The flocks were between 12 and 23 wk of age, and mostly hens were affected. Clinical signs were nonspecific and accompanied by mortality varying between 1% and 7%. Affected birds displayed swollen livers that were marbled with black and red spots and yellowish areas. The pericardium was filled with an amber fluid, and the coronary groove was extensively filled with fat. Spleens were swollen, and a serous fluid that seemed to leak from the liver was present in the body cavity. Histopathological findings in all but one case included fatty degeneration of hepatocytes with parenchymal collapse and associated hemorrhages. Some animals showed cholangitis and hepatitis with intranuclear inclusion bodies. In three cases with breeders, electron microscopy detected virus particles that were between 23 and 30 nm and similar to parvo- or picornavirus. In addition, picornavirus RNA was detected in the livers of one meat turkey flock. Investigations by PCR for circovirus, polyomavirus parvovirus, and aviadenovirus yielded negative results in all cases, but an aviadenovirus was isolated from livers twice and a reovirus from the intestines once. Supplementation with vitamin E and selenium seemed to improve the situation. The most likely diagnosis is lipidosis, a metabolic disorder with complex etiology, which has rarely been described in turkeys.

Ataxia with loss of Purkinje cells in a mouse model for Refsum disease.

Refsum disease is caused by a deficiency of phytanoyl-CoA hydroxylase (PHYH), the first enzyme of the peroxisomal alpha-oxidation system, resulting in the accumulation of the branched-chain fatty acid phytanic acid. The main clinical symptoms are polyneuropathy, cerebellar ataxia, and retinitis pigmentosa. To study the pathogenesis of Refsum disease, we generated and characterized a Phyh knockout mouse. We studied the pathological effects of phytanic acid accumulation in Phyh(-/-) mice fed a diet supplemented with phytol, the precursor of phytanic acid. Phytanic acid accumulation caused a reduction in body weight, hepatic steatosis, and testicular atrophy with loss of spermatogonia. Phenotype assessment using the SHIRPA protocol and subsequent automated gait analysis using the CatWalk system revealed unsteady gait with strongly reduced paw print area for both fore- and hindpaws and reduced base of support for the hindpaws. Histochemical analyses in the CNS showed astrocytosis and up-regulation of calcium-binding proteins. In addition, a loss of Purkinje cells in the cerebellum was observed. No demyelination was present in the CNS. Motor nerve conduction velocity measurements revealed a peripheral neuropathy. Our results show that, in the mouse, high phytanic acid levels cause a peripheral neuropathy and ataxia with loss of Purkinje cells. These findings provide important insights in the pathophysiology of Refsum disease.

Spinosad insecticide: subchronic and chronic toxicity and lack of carcinogenicity in CD-1 mice.

The potential toxicologic and oncogenic effects of spinosad, a natural fermentation product with insecticidal properties, were investigated. The 13-week toxicity study consisted of groups of 10 CD-1 mice/sex provided diets containing 0, 0.005, 0.015, 0.045, or 0.12% spinosad (Study 1). The 0.12% group was terminated on Test Day 44 due to mortality and overt clinical signs of toxicity. An 18-month chronic oncogenicity study consisted of groups of 50 CD-1 mice/sex provided diets containing 0, 0.0025, 0.008, or 0.036% spinosad (Study 2). Two interim groups of 10 mice/sex/group were terminated after 3 and 12 months. Females given 0.036% were terminated on Day 455 due to markedly lower body weights and feed consumption, as well as excessive mortality. Because of the early termination of the female high-dose group, additional groups of 10 male and female mice (12-month interim necrospy) and 50 male and female mice (18-month necropsy) were provided diets containing 0, 0.0008, or 0.024% spinosad (Study 3) to fully assess potential chronic toxicity and oncogenicity. Standard toxicologic parameters were evaluated consistent with existing regulatory guidelines. The primary effect in the 13-week and 18-month studies was intracellular vacuolation of histiocytic and epithelial cells in numerous tissues and organs at doses of > or = 0.015%. The histological vacuolation corresponded to ultrastructural lysosomal lamellar inclusion bodies. This alteration was consistent with phospholipidosis, a condition that results from accumulation of polar lipids in lysosomes. Lesions with no apparent direct relation to vacuolation were hyperplasia of the glandular mucosa of the stomach, skeletal muscle myopathy, bone marrow necrosis, and anemia with associated splenic hematopoiesis. The incidence of tumors in mice given spinosad was not increased relative to controls at any dose level. The no observed effect level for the 13-week study was 0.005% (6 mg/kg/day) spinosad, and for the chronic toxicity/oncogenicity study was 0.008% (11 mg/kg/day) spinosad for male and female CD-1 mice.

Symptomatic vitamin E deficiency diagnosed after histological recognition of myometrial lipofuscinosis.

We report a 44-year-old woman in whom intestinal bypass for obesity at age 23 resulted in chronic malabsorption. After hysterectomy for menorrhagia due to atypical endometrial hyperplasia, the finding of myometrial lipofuscinosis led to a demonstration of vitamin E deficiency. Vitamin E supplementation led to an unexpected improvement in the unsteadiness of gait and slurring of speech of which she had also complained. We suggest that supplementation with vitamin E should be routine in all patients with persistent severe steatorrhoea.

A retrospective study of 77 cats with severe hepatic lipidosis: 1975-1990.

The physical, clinicopathologic, and survival rates of 77 cats with severe spontaneous hepatic lipidosis are detailed in this report. Cats were subdivided into groups designated as idiopathic lipidosis if no other disease process was recognized, or secondary lipidosis if another disease process was diagnosed. Cats were also subdivided into groups designated as survivors or nonsurvivors on the basis of successful recuperation at 4 months after initial diagnosis. Differences between disease and survival groups were evaluated for significance. Overall, more female cats and middle-aged cats were affected. Presenting complaints of vomiting, anorexia, weakness, and weight loss were common. Physical assessment of most cats showed obvious hepatomegaly, jaundice, dehydration, and a weight loss > or = 25% of usual body weight. Neurobehavioral signs indicative of hepatic encephalopathy, other than ptyalism and depression, were rare. Clinicopathologic features are characterized by hyperbilirubinemia and increased activities of serum ALT, AST, and ALP, with only small if any increase in gamma GT activity. Clinical features distinguishing cats with hepatic lipidosis from those with other serious cholestatic disorders include absence of hyperglobulinemia and low gamma GT activity relative to ALP activity. Although coagulation tests were abnormal in 45% of cats tested (n = 44), few cats showed clinical bleeding tendencies. Most cats received prophylactic vitamin K1 therapy. Forty two cats received aggressive nutritional and supportive care and of these 55% survived. Cats with idiopathic disease were significantly younger, had significantly higher ALP activity and bilirubin concentration, and had a slightly better survival rate than cats with secondary lipidosis. Low PCV, hypokalemia, and an older age were significantly related to nonsurvival. Because of the variety of diets and food supplements used in case management, the influence of nutritional factors on survival could not be evaluated.

Histopathologic lesions in sea otters exposed to crude oil.

Following the Exxon Valdez oil spill in Prince William Sound, Alaska, sea otters (Enhydra lutris) that appeared to be contaminated with oil, that were in danger of becoming contaminated, or that were behaving abnormally were captured and taken to rehabilitation centers. Exposure to oil was assessed by visual examination when otters arrived at the centers. Degree of oil exposure was graded according to the following criteria: oil covering greater than 60% of the body--heavily contaminated; oil covering 30-60% of the body--moderately contaminated; oil covering less than 30% of the body or light sheen on fur--lightly contaminated. If there was no oil visible, otters were considered uncontaminated. Tissues from 51 oil-contaminated sea otters (14 males, 37 females) and from six uncontaminated sea otters (three males, three females) that died in rehabilitation centers were examined histologically. Among oil-contaminated sea otters, 19/46 had interstitial pulmonary emphysema, 13/40 had gastric erosion and hemorrhage, 11/47 had centrilobular hepatic necrosis, 14/47 had periportal to diffuse hepatic lipidosis, and 10/42 had renal tubular lipidosis. Of the uncontaminated sea otters, 1/6 had gastric erosion and hemorrhage and 1/6 had diffuse hepatic lipidosis. Histologic examinations were performed on tissues from five sea otters (three males, two females) found dead with external oil present 15 to 16 days after the spill. Periportal hepatic lipidosis and renal tubular lipidosis were found in 3/5, and interstitial pulmonary emphysema was found in 1/5. Tissues from six apparently normal sea otters (four males, two females) collected from an area not affected by an oil spill were examined histologically, and none of these lesions were found. We conclude that interstitial pulmonary emphysema, centrilobular hepatic necrosis, and hepatic and renal lipidosis of sea otters were associated with exposure to crude oil. Gastric erosion and hemorrhage may have been associated with stress of captivity and/or oil exposure.

Effects of dietary saturated fat on erucic acid induced myocardial lipidosis in rats.

Male Sprague-Dawley rats were fed for one week diets containing 20% by weight fat/oil mixtures with different levels of erucic acid (22:1n-9) (approximately 2.5 or 9%) and total saturated fatty acids (approximately 8 or 35%). Corn oil and high erucic acid rapeseed (HEAR) oil were fed as controls. The same hearts were evaluated histologically using oil red O staining and chemically for cardiac triacylglycerol (TAG) and 22:1n-9 content in cardiac TAG to compare the three methods for assessing lipid accumulation in rat hearts. Rats fed corn oil showed trace myocardial lipidosis by staining, and a cardiac TAG content of 3.6 mg/g wet weight in the absence of dietary 22:1n-9. An increase in dietary 22:1n-9 resulted in significantly increased myocardial lipidosis as assessed histologically and by an accumulation of 22:1n-9 in heart lipids; there was no increase in cardiac TAG except when HEAR oil was fed. An increase in saturated fatty acids showed no changes in myocardial lipid content assessed histologically, the content of cardiac TAG or the 22:1n-9 content of TAG at either 2.5 or 9% dietary 22:1n-9. The histological staining method was more significantly correlated to 22:1n-9 in cardiac TAG (r = 0.49; P less than 0.001) than to total cardiac TAG (r = 0.40; P less than 0.05). The 22:1n-9 content was highest in cardiac TAG and free fatty acids. Among the cardiac phospholipids, the highest incorporation was observed into phosphatidylserine, followed by sphingomyelin. With the addition of saturated fat, the fatty acid composition showed decreased accumulation of 22:1n-9 and increased levels of arachidonic and docosahexaenoic acids in most cardiac phospholipids, despite decreased dietary concentrations of their precursor fatty acids, linoleic and linolenic acids.

Treatment of idiopathic hepatic lipidosis in cats: 11 cases (1986-1987).

Idiopathic hepatic lipidosis was diagnosed in 11 cats. Cats were treated by delivery of balanced nutrients supplemented with L-carnitine via a surgically placed gastrostomy tube. Feeding through the gastrostomy tube was initiated in the hospital and was continued at home in all cats. The mean duration of gastrostomy tube feeding was 48 days (range, 22 to 98 days). Vomiting associated with feeding (3 cats) and localized cellulitis at the gastrostomy site (2 cats) were the most frequent complications. Vomiting was controlled by reducing the volume of food administered at each feeding or by administration of metoclopramide. Cellulitis was treated successfully by parenteral administration of antibiotics and local wound cleansing. Seven of 11 cats (65%) survived and have remained clinically healthy for 15 to 29 months (mean, 20 months) since diagnosis. The other 4 cats died of peritonitis (n = 1), pneumonia (n = 1), hepatic encephalopathy (n = 1), or cardiopulmonary arrest (n = 1) between 0 and 10 days after surgery.

Testing a short-term feeding trial to assess compositional and histopathological changes in hearts of rats fed vegetable oils.

Male, female and castrated rats, three wk of age, were fed a low-fat diet for 14 wk followed by high-fat diets (20% by weight) for one wk containing graded levels of erucic acid from 1 to 50%, to evaluate the effect of short-term feeding and interaction of male sex hormones on formation of heart lesions. Some rats within each group were returned to the low-fat diet for one wk after the test period. For comparison, one group of three-wk-old male rats was fed the high fat 50% erucic acid diet for 15 wk. Erucic acid depressed growth rate and food consumption and increased cardiac lipidosis and triglycerides proportional to the erucic acid content of the diet. There were no sex differences, and the effects disappeared once rats were returned to the low-fat diet for one week. There was a significance (P less than 0.05) in the incidence of myocardial necrosis among male rats fed increased levels of erucic acid for one week, but the response was not linear to the increase in dietary erucic acid. Furthermore, the response was much less than in males fed the 50% erucic acid diet continually for 15 weeks. These results suggest that the short-term model is not a suitable substitute for the long-term feeding trial to test the cardiopathogenicity of a vegetable oil. The significantly lower incidence in myocardial lesions in female and castrated male rats compared with male rats suggests involvement of sex hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Mineral oil (follicular) lipidosis: II. Histologic studies of spleen, liver, lymph nodes, and bone marrow.

Tissues obtained from 600 routine autopsies were studied. Mineral oil lipidosis was present in the spleen (76 per cent), liver (45 per cent), bone marrow (26 per cent), and lymph nodes; more than 50 per cent of the lymph nodes from the mesentery, porta hepatis, and mediastinum were affected. Mineral oil and its metabolic products produce a nonfibrogenic reaction in these tissues. The differential diagnosis of mineral oil lipidosis in lymph nodes with reaction to radiopaque oils and Whipple's disease is discussed. The presence of mineral oil in para-aortic (42 per cent) and internal iliac (15 per cent) lymph nodes could result in false-positive readings after lymphangiography.

Morphologic effects of dietary plant and animal lipids rich in docosenoic acids on heart and skeletal muscle of cynomolgus monkeys.

Cynomolgi (Macaca fascicularis) were fed diets containing 25% rapeseed oil (RSO), partially hydrogenated herring oil (PHHO), or a 3:1 mixture of lard and corn oil as control for 4 months. The RSO contained approximately 25% of the fatty acids as erucic acid; the PHHO contained a similar concentration of mainly cetoleic acid. The control diet did not include such fatty acids. At the time of necropsy, the RSO- and PHHO-fed monkeys showed myocardial and skeletal muscle lipidosis. Foci of mononuclear cell infiltration, although infrequent, occurred in all three groups and were thought to be nonspecific. The only significant intergroup difference in serum biochemical or hematologic parameters was an increase in serum glutamic-oxaloacetic transaminase activity in both RSO and PHHO groups. Ultrastructural studies confirmed the presence of lipidosis in cardiac and skeletal muscle and revealed mild mitochondrial degeneration, causing a depression of the P/O ratio of the RSO group and a State III respiratory rate depression of the PHHO group. The difference in the exposure/life span ratio represented by this experiment may account for the absence of clear intergroup differences such as are reported in rats used in similar studies, but a true species difference in regard to dietary oils containing docosenoic acids has to be considered as well.

[Infantile generalized ceroid-Lipofuscinosis (type Hagberg-Santavuori). A new case and a retrospective study of two observations (author's transl)]. / La céroïdo-lipofuscinose infantile généralisée (type Hagberg-Santavuori). A propos d'une nouvelle observation et de I'étude rétrospective de deux autres cas

Three post mortem studies of cases of infantile generalized ceroid-lipofuscinosis are reported: two of them were published under other classifications but our retrospective study warrants their inclusion in the infantile group of ceroid-lipofuscinosis. The children died at the respective ages of 4, 5 8/12 and 8 years and this allows interesting morphological comparisons: 1 degree there is an increasingly severe loss of cortical neurons, of Purkinje cells and of neurons in the griseum pontis with age. Intracytoplasmic inclusions mainly of a granular osmiophilic nature were found in all other neurons and glial cells; 2 degrees the involvement of the visceral organs is especially striking and permits an easier diagnosis under light microscopy, unlike the late infantile and juvenile forms of ceroid-lipofuscinosis. Electron microscopy supports the observation by Anzil et al. (1975) concerning the relative pleiomorphism of the inclusions; 3 degree the diffuse accumulation of inclusions in the skin and its appendages ensures a rapid diagnosis by skin biopsy.

Cardiac lesions in rats fed rapeseed oils.

Fully refined rapeseed oils containing different amounts of erucic acid (1.6%, 4.3% and 22.3%) were fed, at 20% by weight of diet, to weanling male and female Sprague-Dawley rats for periods up to 112 days. Transient myocardial lipidosis characterized by accumulation of fat droplets in myocardial fibers was marked in male and female rats fed oxidized and unoxidized rapeseed oil containing 22.3% erucic acid, moderate with rapeseed oil containing 4.3% erucic acid and very slight in rats fed rapeseed oil containing 1.6% erucic acid. Peak intensity of myocardial lipidosis occurred at three to seven days and regressed thereafter. Focal myocardial necrosis and fibrosis occurred in male rats fed rapeseed oils containing different levels of erucic acid for 112 days. The incidence of myocardial necrosis and fibrosis was markedly lower in female rats, and the incidence of these lesions in either sex was not affected by the state of oxidation of these oils. In a second experiment, male rats were fed diets containing crude, partially refined or fully refined rapeseed oils. There was no correlation between the number of foci of myocardial necrosis and fibrosis and the state of refinement of the oils, but there were generally fewer lesions in rats fed those oils having the lowest levels of erucic acid.

Morphological effects of rapeseed oil in rats. I. Short-term studies.

Light microscopy of paraffin embedded and frozen sections, supplemented with electron microscopy, was performed on the heart muscle of young rats fed rapeseed oil in short-term experiments. It was confirmed that high levels of rapeseed oil, which contains erucic acid, produce severe lipoidosis of the heart muscle fibres within 10 days. An attempt was made to find out the lowest level of erucic acid in the rat diet to give rise to pathological fatty accumulation. Several frozen sections from each heart or serial sections in combination with electron microscopy were used for this evaluation. The level found to give rise to pathological fatty accumulation was about 2% by weight (w/w), while rats fed 1% erucic acid showed normal myocardium. No direct proof that erucic acid is of importance in human pathophysiology has hitherto been presented. It is concluded, however, that the similarity in reaction among the many species of experimental animals tested by different workers, as well as the basic metabolic disturbances demonstrated, are in strong favour of a similar effect in man.

Morphological effects of rapeseed oil in rats. II. Long-term studies.

In long-term studies covering up to 160 days young Sprague-Dawley rats were fed diets containing 40 cal% of fat. The fat component consisted of either conventional rapeseed oil, or Canadian rapeseed oil low in erucic acid, or arachis oil. Myocardial fatty accumulation was demonstrated in light microscopic studies throughout the experiments in rats fed conventional rapeseed oil, but the number of fat droplets decreased with time. The controls fed arachis oil showed no fatty accumulation. In the rats fed conventional rapeseed oil focal myocardial lesions appeared after 40 days on the diet. These consisted of histiocytic infiltration, occurrence of macrophages, myolysis, proliferation of fibroblasts and finally scarring. Such foci were found widely spread in the myocardium of these rats. In the experimental groups given Canadian rapeseed oil from the cultivar Oro no histiocytic foci or scarring were observed. Small myocardial lesions were occasionally found in the control rats. These latter findings were observed on serial sections. It was concluded that this type of lesion is a "normal" finding. The number and size of the foci observed in animals fed conventional rapeseed oil (10% and 2% (w/w) erucic acid in the diet) indicate, however, that they have to be considered pathological under such circumstances. The pathogenesis of the myocardial alteration is discussed and it is concluded that the long-chain fatty acids are responsible. No direct proof has been presented that the described events are of importance in human pathophysiology, However, several circumstances pointing in this direction are discussed. It is concluded that on the basis of our present knowledge a pathological effect of erucic acid and its homologues in man cannot be excluded.

Morphological effects of rapeseed oil in rats. III. Studies in germ-free rats.

The morphological effects on the myocardium of feeding rapeseed oil were compared in conventional and germ-free rats in short-term experiments (10 days). It was concluded that the fatty accumulation in the heart muscle cells occurring in rats fed rapeseed oil was not influenced by the presence or absence of a normal intestinal flora. In long-term experiments (80 days) under similar conditions, the myocardial effects of feeding germ-free rats with conventional rapeseed oil, rapeseed oil from the Canadian cultivar Oro very low in erucic acid, or arachis oil were studied in serial sections. Severe myocardial lesions developed in the group of rats fed conventional rapeseed oil, while in the other two groups the myocardium was completely normal. These results give no support to the theory that other factors than C22:1 acids in rapeseed oil are responsible for the myocardial lesions.