Electrophysiological correlates of categorization: P300 amplitude as index of target similarity.

Two experiments examined event-related potentials (ERPs) and behavioral correlates of categorizing stimuli varying in perceptual similarity to targets. Participants performed a target-detection task in which non-target stimuli varied in target similarity but occurred with equivalent probability. The stimuli were variations of a schematic human face comprised of eight distinct features: two eyes, two eyebrows, one nose, one mouth, and two ears. Non-target stimuli that were perceptually similar to targets produced larger P300-like neurophysiological responses than did other non-target stimuli. These effects emerged whether participants' target was relatively complex (eight features) or quite simple (zero features). Accordingly, the presence of many constituent elements of a test stimulus does not appear necessary to trigger increases in categorical processing of non-targets that are similar to a target. The data further suggest that the P300 amplitude may be used as a good index of perceptual similarity between target and non-target stimuli.

Objective benefit of nifedipine in the treatment of Raynaud's phenomenon. Double-blind controlled study.

To compare the effects of the calcium channel antagonist, nifedipine, with that of placebo, a randomized double-blind crossover study was performed in 11 patients with moderate to severe Raynaud's phenomenon. Digital skin temperature recovery time was measured after immersing the patient's hand in ice water for 20 seconds. Patients were randomly assigned to receiving either nifedipine or placebo for one week, followed by the crossover phase. Skin temperature recovery time was also measured in 21 normal volunteers. The mean time to recovery for patients taking nifedipine was 28.5 +/- 20.8 minutes versus 44.9 +/- 18.9 minutes for patients receiving placebo (p less than 0.05 by analysis of variance with repeated measures). The mean time to recovery for the normal volunteers was 11.3 +/- 7.2 minutes versus 40.2 +/- 19.9 minutes for the patients (p less than 0.01 by the Student t test). Nine of the 11 patients noted improvement of symptoms during treatment with nifedipine. It is concluded that nifedipine is an effective, well-tolerated treatment for Raynaud's phenomenon.

Echocardiographic evaluation of the St. Jude medical prosthetic valve.

M-mode and two-dimensional echocardiographic studies were performed on 19 patients with 25 normally functioning St. Jude Medical prosthetic cardiac valves, in an attempt to define the normal echocardiographic appearance of this new cardiac prosthesis. Satisfactory M-mode echocardiograms were obtained in 17 of the 19 patients, and satisfactory two-dimensional studies were obtained in all. M-mode measurements included the diameter of the orifice ring, leaflet separation, and the opening and closing slopes of the leaflets. The values obtained compared favorably with direct measurements from the prosthesis and were reasonably reproducible. Two-dimensional imaging revealed characteristic systolic and diastolic patterns and provided direct visualization of valvular motion. Echocardiographic evaluation of the prosthesis can be facilitated if it is positioned at implantation so that the open leaflets are perpendicular to the echocardiographic plane of the long axis of the ventricle.

Use of oral and intravenous fat tolerance tests to assess plasma chylomicron clearance in dogs.

The reduced clearance of chylomicrons from plasma results in an exaggerated post prandial lipaemia and fasting hypertriglyceridaemia. This study evaluated whether oral and intravenous fat tolerance tests are appropriate for the in vivo analysis of chylomicron clearance in dogs. Plasma and chylomicron triglyceride concentrations were measured in eight beagles after the administration of a cream-based meal of 2.35 g fat kg-1 bodyweight. The changes in each parameter were determined chiefly by the activity of lipoprotein lipase, which was measured in plasma collected after the intravenous injection of heparin and did not appear to be influenced by intestinal fat absorption. The inclusion of retinyl palmitate in the meal provided additional information on the metabolic fate of chylomicron remnants. After the intravenous injection of 0.1 g Intralipid kg-1 bodyweight, there was an initial linear decay in plasma triglyceride concentrations that represented the maximal elimination rate K1. This was followed by a second exponential component so that the plasma triglyceride concentration returned to baseline by 60 minutes. Lipoprotein lipase was the major determinant of K1 and the area under the curve of plasma triglycerides.

Plasma lipids, lipoproteins and post-heparin lipases in ponies with hyperlipaemia.

The metabolic origins of equine hyperlipaemia were investigated by analysing the concentration and composition of plasma lipoproteins in 18 ponies with the condition. The mean concentrations of cholesterol, triglyceride and very low density lipoproteins (VLDL) were increased by 4-, 52- and 19-fold, respectively, compared with a control group of 18 healthy ponies. These increases were due to the appearance of a buoyant VLDL fraction (VLDL1) not present in healthy ponies. The mean diameter of VLDL1 particles was 44% greater than control VLDL, and the particles were enriched in triglyceride and free cholesterol and depleted of cholesteryl esters, phospholipid and protein. The apolipoprotein (apo) B-100 content of VLDL1 was reduced and the ratio of apoB-100 to apoB-48 particles was 1:1, compared with 2:1 in control VLDL. The VLDL1 was also enriched in apoE, but had normal complements of apoC-II and apoC-III. The conventional VLDL (called VLDL2), LDL and HDL fractions were moderately enriched with triglyceride, and HDL contained increased amounts of apoE, apoC-II and apoC-III. The activities of lipoprotein lipase and hepatic lipase, the enzymes responsible for the catabolism of VLDL and their remnants, were increased by 2- and 3-fold, respectively, in response to the increased concentrations of their substrates. The composition of VLDL1 suggested that the liver was maximising the secretion of triglyceride by producing larger number of VLDL particles that accommodated a greater mass of triglyceride by having apoB-48 rather than apoB-100 as their structural protein. Plasma free fatty acid (FFA) concentrations were elevated in 17 of the 18 ponies, suggesting that increased FFA flux might be the stimulus for hepatic triglyceride synthesis and VLDL secretion. We conclude that overproduction, rather than defective catabolism, of VLDL was the cause of the hyperlipidaemia and that lipid lowering agents which reduce VLDL synthesis, by decreasing adipose lipolysis and FFA flux, are candidates for the management of hyperlipaemia.

The isolation, characterisation and quantification of the equine plasma lipoproteins.

Plasma lipoproteins were isolated from eight Thoroughbred horses and eight Shetland ponies on the basis of particle size by gel filtration chromatography and according to density using rate-zonal ultracentrifugation. Three major classes corresponding to very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) were identified and characterised by their lipid and apolipoprotein compositions. The particle size distributions of each class were determined by electron microscopy and non-denaturing polyacrylamide gradient gel electrophoresis. HDL was found to dominate the equine lipoprotein spectrum, accounting for 61 per cent of the total plasma lipoprotein mass (VLDL 24 per cent, LDL 15 per cent). The VLDL class was isolated as a single population of particles that were triglyceride rich and cholesterol, phospholipid and protein poor. Equine LDL was characteristically cholesterol rich and was found to be polydisperse comprising three subfractions that were discrete with respect to particle size and lipid composition. The HDL class was composed of homogeneous particles that were typically protein rich. Apolipoprotein (apo) B was the major protein of VLDL and LDL, and presented two components on polyacrylamide gel electrophoresis with molecular weights in the region of human apoB-100 and a third in VLDL similar to that of apoB-48. ApoA-I was the predominant protein in equine HDL. Although there were no breed differences in the physical or chemical properties of each lipoprotein class, the Shetland ponies had higher plasma triglyceride and VLDL concentrations than their Thoroughbred counterparts.

The clinical and metabolic effects of rapid weight loss in obese pet cats and the influence of supplemental oral L-carnitine.

The efficacy, safety, and metabolic consequences of rapid weight loss in privately owned obese cats by means of a canned weight-reduction diet and the influence of orally administered L-carnitine on rate of weight loss, routine clinical evaluations, hepatic ultrasonography, plasma amino acid profiles, and carnitine analytes were evaluated. A double-blinded placebo-controlled design was used with cats randomly divided into 2 groups: Group 1 (n = 14) received L-carnitine (250 mg PO q24h) in aqueous solution and group 2 (n = 10) received an identical-appearing water placebo. Median obesity (body condition scores and percentage ideal body weight) in each group was 25%. Caloric intake was restricted to 60% of maintenance energy requirements (60 kcal/kg) for targeted ideal weight. The reducing formula was readily accepted by all cats. Significant weight loss was achieved by week 18 in each group without adverse effects (group 1 = 23.7%, group 2 = 19.6%). Cats receiving carnitine lost weight at a significantly faster rate (P < .05). Significant increases in carnitine values developed in each group (P < .02). However, significantly higher concentrations of all carnitine moieties and a greater percentage of acetylcarnitine developed in cats of group 1 (P < .01). The dietary formula and described reducing strategy can safely achieve a 20% weight reduction within 18 weeks in obese cats. An aqueous solution of L-carnitine (250 mg PO q12h) was at least partially absorbed, was nontoxic, and significantly increased plasma carnitine analyte concentrations as well as rate of weight loss.

Selective measurement of lipoprotein lipase and hepatic triglyceride lipase in heparinized plasma from horses.

Affinity chromatography on heparin sepharose was used to identify 2 lipolytic enzymes in heparinized plasma from horses. One enzyme was typical of hepatic triglyceride lipase (HTGL), because it was resistant to inactivation by high concentrations of NaCl, and it did not require the addition of serum for activity. The other enzyme was identified as lipoprotein lipase (LPL), because of its inactivation at NaCl concentrations in excess of 0.2M, and its dependency on addition of serum as a source of apolipoprotein C-II activator. The enzymes were purified by 347-(HTGL) and 442- (LPL) fold, with yields of 54 and 58%, respectively. The partially purified enzymes were used to design incubation conditions that gave optimal activities for each enzyme in vitro. A selective assay was then developed for direct measurement of LPL and HTGL activities in heparinized plasma from horses. Analysis of HTGL took advantage of the almost complete inactivation of LPL when serum cofactor was excluded from the assay at the NaCl concentration that gave optimal HTGL activity. Prior incubation of heparinized plasma with sodium dodecyl sulfate to inhibit HTGL was necessary for measurement of LPL, because HTGL retained 67% of its activity at the NaCl concentration required for optimal LPL activity. Activity of each enzyme was measured in heparinized plasma from 12 Shetland ponies. The mean activity +/- SD for LPL was 3.22 +/- 1.04 mumol of fatty acids/ml of heparinized plasma/h (mumol of FA/ml/h. The mean activity for HTGL was 4.9 +/- 1.56 mumol of FA/ml/h. The performance of the assay was assessed by replicate analysis of pools of each enzyme with high and low activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of methods for analyzing plasma lipoprotein concentrations and associated enzyme activities and their use to measure the effects of pregnancy and lactation in cats.

Methods available for measurement of plasma lipoprotein-cholesterol concentrations and activities of lipoprotein lipase, hepatic lipase, lecithin:cholesterol acyl transferase (LCAT), and cholesteryl ester transfer protein were adapted for use in cats. A combined ultracentrifugation/precipitation procedure was used to isolate very low-density lipoproteins (VLDL), then to separate low-density lipoproteins (LDL) from high-density lipoproteins (HDL). The reagent used, 92 mM heparin-manganese chloride, provided complete precipitation of LDL with only trace and insignificant contamination by HDL. Efforts to selectively measure lipoprotein lipase activity in plasma, collected after IV injection of heparin, by inhibiting hepatic lipase with sodium dodecyl sulfate were unsuccessful, and the activity of this enzyme was calculated as the difference between total and hepatic lipase activities. The latter was measured in the presence of high salt concentration to inhibit lipoprotein lipase. Cholesterol esterifying activity was identified in feline plasma and was typical of LCAT, in that it was dependent on apolipoprotein A-I as a cofactor. The intra-assay and interassay coefficients of variation for measurement of lipoprotein lipase, hepatic lipase, and LCAT activities were 18.4, 4.6, and 7.2%, and 20.4, 10.7, and 5.3%, respectively. Appreciable cholesteryl ester transfer protein activity was not detected in either undiluted or diluted plasma. These methods were subsequently used to investigate the effects of pregnancy and lactation on lipoprotein metabolism in a group of 10 queens. Plasma concentrations of cholesterol and triglycerides were unaltered during pregnancy, but the concentrations of VLDL-cholesterol increased and those of HDL-cholesterol decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of age and sex on plasma lipid and lipoprotein concentrations and associated enzyme activities in cats.

OBJECTIVE: To determine effects of age and sex on plasma lipid and lipoprotein metabolism in cats. ANIMALS: 33 kittens and 16 adolescent, 23 adult, and 10 senior cats. PROCEDURE: Plasma concentrations of cholesterol, triglyceride, and lipoprotein-cholesterol and activities of lipoprotein lipase, hepatic lipase, and lecithin:cholesterol acyl transferase (LCAT) were measured and compared within and among groups. RESULTS: Plasma cholesterol and triglyceride concentrations were significantly higher in 5- and 7-week-old kittens, compared with the same kittens after weaning and cats in the other age groups. Cholesterol concentration was significantly less in 20-week-old kittens, compared with adolescent and adult cats. Lipid and lipoprotein-cholesterol concentrations were not significantly different among the adolescent, adult, and senior groups, nor did sex influence lipid and lipoprotein-cholesterol concentrations in these groups. Activities of lipoprotein and hepatic lipases were significantly less in senior cats, compared with the other groups. Activity of LCAT was highest in 20-week-old kittens and was greater in sexually intact adult and adolescent females, compared with their male counterparts. After castration, activities of hepatic lipase and LCAT significantly decreased in adolescent male cats. CONCLUSIONS AND CLINICAL RELEVANCE: The upper limits of reference ranges for plasma cholesterol and triglyceride concentrations should be increased for kittens < 8 weeks of age. Low cholesterol concentrations in adolescent cats likely reflect high tissue demands for growth and steroidogenesis. Decrease in lipoprotein and hepatic lipase activity in senior cats could predispose this age group to hypertriglyceridemia, particularly in insulin-resistant cats or those fed a high fat diet.

Pharmacokinetics of heparin and its pharmacodynamic effect on plasma lipoprotein lipase activity and coagulation in healthy horses.

We evaluated the pharmacokinetics of IV administered sodium heparin and the pharmacodynamic effect of heparin on lipoprotein lipase (LPL) activity. Horses were allotted to 3 groups. Plasma samples were obtained from each horse before and at various times for 6 hours after heparin administration for determination of heparin concentration, LPL activity, and activated partial thromboplastin time (APTT). The disposition of heparin was dose dependent. The area under the plasma heparin concentration vs time curve (AUC) increased more than proportionally with dose, indicating that heparin elimination was nonlinear. Total clearance of heparin was similar after the 40 and 80 IU/kg of body weight dosages, averaging 0.45 and 0.36 IU/kg/min, respectively. However, after administration of the 120 IU/kg dose, clearance was significantly less than that after the 40 IU/kg dose. The half-life of heparin averaged 53, 70, and 136 minutes after 40, 80, and 120 IU/kg, respectively, with significant differences observed between the low and high doses. In contrast to heparin, the area under the plasma concentration vs time curve for LPL activity increased less than proportionally with dose. Maximal LPL activity observed was independent of dose, averaging 4.8 mumol of free fatty acids/ml/h. The APTT was significantly prolonged for 120 minutes after administration of the 40 IU/kg dose. Correlation coefficients for LPL activity vs either plasma heparin concentration or APTT were less than 0.7, indicating that neither laboratory measure can be used to accurately predict plasma LPL activity.

Effects of detomidine on equine oesophageal function as studied by contrast radiography.

The effects of sedation with detomidine on oesophageal function were assessed by contrast radiography in 10 healthy adult thoroughbred horses. Barium swallows were monitored by means of image intensification, first without sedation and then after the intravenous administration of detomidine at doses of 10 and 20 micrograms/kg bodyweight. The transit time of contrast agent to the oesophageal hiatus was recorded and each swallow was scored for markers of oesophageal dysfunction. Analysis of the data indicated that there were highly significant dose dependent increases in the transit time, the retention of barium within the longitudinal mucosal folds, and retrograde peristalsis and pooling of contrast agent within the oesophagus at both the thoracic inlet and caudal to the base of the heart. The degree of gastrooesophageal reflux was not affected at either dosage. These changes in oesophageal function were similar to those recorded from cases of grass sickness and indicate that care should be taken in the interpretation of studies of swallowing in animals that have been given detomidine before a radiographic examination.

Juvenile bovine angiomatosis: a syndrome of young cattle.

This report describes the clinical and pathological features associated with angiomatous lesions in two calves. In the first case, a single mass located in the atrioventricular ring of the heart was responsible for congestive cardiac failure. The mass was composed of numerous vascular cavities filled with blood and lined by a single layer of well differentiated endothelial cells. The second case had multiple blood-filled cutaneous masses which were confirmed as benign vascular tumours by histological examination of a biopsy specimen. The calf was later euthanased after profuse and uncontrollable haemorrhage from one of the lesions. At necropsy, additional tumours were found in the liver, spleen, kidneys, spinal canal and attached to the pleura, omentum and mesentery. It is proposed that these two cases are representatives of solitary and multiple forms of a syndrome which should be called juvenile bovine angiomatosis.

Equine hyperlipaemia in the United Kingdom: clinical features and blood biochemistry of 18 cases.

The background, clinical signs, blood biochemistry and management of 18 cases of equine hyperlipaemia are described. Eleven of the animals were Shetland ponies, four were Welsh mountain ponies or their crosses, one was a fell pony and two were riding ponies of mixed breeding. Their average age was nine years. Fourteen of the cases were mares, of which nine were in foal and two were lactating; the remainder were geldings. Underlying or concurrent diseases were identified in only six animals, but in one other animal the hyperlipaemia appeared to have been precipitated by stress, and in another by undernutrition to prevent laminitis. Twelve of the animals were considered obese. There was no age, seasonal, or geographic bias to the distribution of cases. Plasma triglyceride concentrations were increased by between five- and 80-fold, and ranged from 4.7 to 78.8 mmol/litre. There was biochemical evidence of hepatic damage in 17 cases, of renal insufficiency in 15, and pancreatic pathology in three cases. Four animals were euthanased without therapy. The others were treated with oral glucose solutions, which were supplemented with injections of insulin and heparin in four cases, and insulin alone in two cases. Eight of the treated animals died, to give an overall mortality of 67 per cent. The outcome of the treatment was unrelated to the degree of hypertriglyceridaemia, to the presence and severity of hepatic, renal or pancreatic pathology or to the therapeutic regimen.

Aortic valvular dysplasia in a calf.

Aortic valvular dysplasia, a congenital abnormality not previously reported in cattle, was diagnosed in a calf with a pulsating mass at the base of its neck, an enlarged area of cardiac dullness and a loud (grade IV/V) systolic cardiac murmur. Electrocardiography and thoracic radiography demonstrated that the left atrium and ventricle were enlarged. Dysplasia of two aortic valve cusps and post stenotic dilatation of the ascending aorta were identified by echocardiography and confirmed post mortem.

An investigation of the relationships between body condition and plasma lipid and lipoprotein concentrations in 24 donkeys.

Obese donkeys are susceptible to a hyperlipaemic crisis characterised by high plasma triglyceride concentrations. In this study, the relationships between the body condition of 24 donkeys and their basal lipid metabolism were investigated. Plasma cholesterol, triglyceride and lipoprotein cholesterol concentrations were measured in healthy donkeys classified according to their body condition as thin, ideal or obese. There were significant differences between the groups in the concentrations of triglyceride and very low density lipoprotein (VLDL), which increased in concentration with body condition (P less than 0.05). Cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) concentrations were similar in all the groups. Triglyceride and VLDL concentrations were positively correlated with body weight (r = 0.82) and plasma free fatty acid concentration (r = 0.48). There were no significant differences in basal plasma concentrations of insulin or cortisol. These results suggest that obesity in donkeys is associated with changes in lipid and lipoprotein metabolism that might predispose the animals to hyperlipaemia.

Transient hyperlipidaemia and anaemia in kittens.

Severe fasting hypertriglyceridaemia (5 to 126 mmol/litre) and anaemia (packed cell volume < 11 per cent) was observed in 12 litters of kittens around the time of weaning; the entire litter was usually affected, with significant mortality. Lipid analysis revealed marked increases in chylomicrons and moderate increases in very low density lipoproteins. Supportive measures for the treatment of anaemia and weaning on to a low fat diet resulted in rapid resolution of the clinical signs, anaemia and hypertriglyceridaemia. On recovery, plasma was collected from kittens from five of the affected litters, plus a number of closely related cats and unrelated cats living in the same environment. The lipoprotein lipase (LPL) activity was mildly but significantly lower in the previously affected kittens, their parents and unaffected siblings, than in the unrelated cats. The cats had normal apolipoprotein C-II function, normal heparin binding activity and no evidence of a circulating inhibitor to LPL. They did not have the LPL gene mutation reported previously in LPL-deficient cats from New Zealand.

Effects of feeding regimens on bodyweight, composition and condition score in cats following ovariohysterectomy.

The effects of ovariohysterectomy on bodyweight, composition and condition score were evaluated in 49 cats that were fed ad libitum and 11 cats that had their food allowances controlled with the aim of maintaining a stable bodyweight. In cats fed ad libitum, bodyweight increased by an average of 31 per cent in the 12 months following ovariohysterectomy compared with 3.1 per cent over the 12 months before surgery, and this was largely due to increased body fat content. There was no difference in weight gain between cats fed dry or canned foods, but weight gain was inversely related to age and bodyweight at the time of neutering. Mean bodyweight increased by 7.5 per cent in the controlled feeding group, compared with 3.6 per cent over the 12 months before surgery, and individual bodyweights were maintained to within 10 per cent of pre-neutering values in nine cats. The other two cats experienced substantial weight gain (+20 per cent and +36 per cent), despite being fed only 40 kcal/kg/day. There were no significant changes in body composition of cats with controlled dietary allowances and their condition scores were significantly lower than those of cats fed ad libitum. The results confirm a link between ovariohysterectomy and the development of obesity in cats with free access to food, and indicate that substantial reductions in energy intake are required to prevent weight gain in such cats.