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Biomedical subjects

T D Watson

Publications and source records attributed to T D Watson.

At least 37 records · Page 2Linked to original sources

High density lipoprotein metabolism in the horse (Equus caballus).

1. Apolipoprotein A-I dependent lecithin:cholesterol acyl transferase (LCAT) activity was identified in equine lipoprotein deficient plasma (LPDP). 2. LCAT activity showed no breed or sex variation, and was unaltered postprandially. 3. There was no significant cholesteryl ester transfer activity in equine LPDP. 4. Hydrophobic interaction chromatography on phenyl sepharose failed to unmask transfer activity or identify an inhibitor of cholesteryl ester transfer. 5. In 12 Shetland ponies, plasma high density lipoprotein (HDL) concentrations were positively correlated with those of triglyceride, but not with the activities of LCAT, lipoprotein lipase or hepatic lipase.

Animals↗

Effects of pregnancy and lactation on plasma lipid and lipoprotein concentrations, lipoprotein composition and post-heparin lipase activities in Shetland pony mares.

The incidence of hyperlipaemia in ponies is highest in mares in late gestation and then early in lactation. Plasma lipid and lipoprotein concentrations were measured to establish the metabolic basis for this and the lipoprotein composition of six healthy Shetland ponies was analysed before pregnancy, in the last six weeks of gestation and one month after foaling. In the pregnant ponies, the concentrations of cholesterol and triglyceride were significantly increased (both P < 0.05) because of increased concentrations of high density lipoproteins (HDL) and very low density lipoproteins (VLDL), respectively (both P < 0.05). The VLDL were significantly enriched in triglyceride and depleted of protein (P < 0.05 in each case), with the majority of cholesterol in the free rather than esterified form. These changes appeared to reflect increased hepatic triglyceride synthesis and VLDL secretion because the activities of lipoprotein lipase and hepatic lipase, the enzymes responsible for the catabolism of VLDL and their remnants, were unaltered. After foaling, the concentrations of triglyceride and VLDL decreased significantly (both P < 0.05) because of increased lipoprotein lipase activity consistent with the induction of the enzyme in mammary tissue to provide for milk fat synthesis. Plasma cholesterol and HDL concentrations remained high and non-esterified fatty acid concentrations were significantly increased (P < 0.05). The VLDL remained enriched in triglyceride but had normal cholesterol and protein compositions, although the mass of phospholipids was reduced. The changes in plasma VLDL concentration and composition found in the pregnant ponies mimicked those previously reported in ponies with hyperlipaemia and suggested a metabolic basis for the incidence of the disease in late gestation.

Animals↗

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.

Alkaline Phosphatase↗

Post-prandial lipoprotein metabolism in nephrotic syndrome.

Post-prandial lipaemia was investigated in a group of nine subjects with nephrotic syndrome by following the concentrations of triglyceride and retinyl palmitate in the d < 1.006 g ml-1 fraction of plasma after a standard oral fat load containing vitamin A. Lipoprotein lipase and hepatic triglyceride lipase activities were measured in post-heparin plasma. Subjects with other renal disease but insignificant proteinuria acted as controls. The time course of the lipaemic response was similar in both groups although individual patients demonstrated a prolonged lipaemia. Overall, there were no significant differences in the rise in triglyceride at 6 h (nephrotic--median 2.53 mmol l-1; range 0.87-4.76 vs. control 1.88; 0.38-4.12, P = 0.34), the peak concentration of retinyl palmitate (nephrotic 0.87 mg dl-1; 0.27-2.16 vs. control 0.65; 0.24-1.89, P = 0.97) or the areas under the curve from 0-24 h for triglyceride (nephrotic 10.5 mmol. h l-1; 2.9-43.6 vs. control 9.7; 4.3-27.0, P = 1.0) or retinyl palmitate (5.5 mg.h dl-1; 1.0-23.4 vs. 4.3; 1.5-12.4, P = 0.7). At baseline, the particles in the d < 1.006 g ml-1 fraction of plasma from nephrotic subjects had a higher free cholesterol:phospholipid ratio but this difference was no longer apparent 6 h after the test meal. There were no differences in total heparin-releasable lipase, lipoprotein lipase or hepatic triglyceride lipase activities between the two groups. These data suggest that impaired clearance of chylomicrons is not a major contributor to nephrotic hyperlipidaemia in man.

Adult↗

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.

Animals↗

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)

Animals↗

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.

Animals↗

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.

Animals↗

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.

Animals↗

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.

Animals↗

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.

Angiomatosis↗

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.

Adult↗

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.

Adolescent↗

Preanesthetic care. Intoxication and trauma.

On the basis of the above discussion, a number of useful guidelines appear for the anesthetic management of alcohol and drug abusers. 1. Because of the decreased ability of intoxicated patients to withstand hemorrhage, blood replacement therapy should probably be instituted earlier than in the nonintoxicated patient. 2. Because the chronic alcoholic may actually be iso-osmotically overhydrated, fluid therapy must be planned with care. 3. Because of the tendency to hypoglycemia, glucose should be added to the fluid management regimen. 4. Because of the enzyme induction effect of chronic ETOH ingestion, anesthetic agents that are in part metabolized (methoxyflurane, halothane, fluroxene) are perhaps best avoided. Increased ability to metabolize anesthetic agents appears to be associated with toxicity. 5. Because ETOH is a CNS depressant and has been shown to have amnesia-inducing properties, supplementation of nitrous oxide-relaxant technique with narcotics or other depressant drugs should be reduced, if not eliminated. 6. Because acutely intoxicated individuals are more prone to hypothermia, their core temperature should be monitored intraoperatively. All intravenous fluids should be warmed and a warming blanket should be employed, if necessary, to maintain body temperature. 7. Because of the sympathomimetic effect of many of the drugs, pulse and blood pressure can be misleading in the assessment of blood loss.

Alcoholic Intoxication↗

A new single-position supine approach to sciatic-femoral nerve block.

To overcome the disadvantages of other methods, the authors have devised a procedure for below-the-knee operations, involving a new technic of sciatic-femoral nerve block. The technic has so far been successful without use of adjuvant agents in 90 percent of over 100 patients so handled.

Anesthesia, Intravenous↗