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Biomedical subjects

G R Thompson

Publications and source records attributed to G R Thompson.

At least 181 records · Page 10Linked to original sources

Reduction of blood viscosity following plasma exchange.

The effect of plasma exchange with plasma protein fraction on blood viscosity was determined in seven hyperlipoproteinaemic patients with coronary or peripheral vascular disease. This resulted in decreases in whole blood viscosity of 83% and 30% respectively at the lowest and highest shear rates studied, and decreases of 21% and 59% in plasma viscosity and fibrinogen. Serum cholesterol and triglyceride were reduced by 66% and 48% respectively. Sequential studies in two patients showed that blood viscosity returned to near-basal values by the 6th day. These findings suggest that plasma exchange may result in short-term enhancement of blood flow in vessels where low shear rates predominate.

Adolescent↗

Metabolism of apolipoprotein B-containing lipoproteins in familial hypercholesterolaemia: effects of plasma exchange.

The turnover of apolipoprotein B (apo B) in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) was investigated in 2 homozygous and 3 heterozygous patients with familial hypercholesterolaemia. The effects of a marked reduction in plasma LDL concentration, brought about by plasma exchange, upon apo B turnover were studied in 4 patients. Specific activity-time curves for the the plasma apo B after intravenous radioactive VLDL before plasma exchange indicated that in the heterozygotes all IDL-apo B was derived from VLDL and all LDL-apo B was derived from IDL, but the curves from the homozygotes showed that a significant fraction of the LDL in the plasma was not derived from IDL. Plasma exchange did not increase the rates of synthesis of LDL-apo B or VLDL-apo B and had no significant effect on the precursor--product relationship between IDL-apo B and LDL-apo B in heterozygous or homozygous patients. These findings provide no support for the hypothesis that apo B synthesis is controlled by the plasma LDL.

Apolipoproteins↗

Reversible abnormalities of low density lipoprotein composition in familial hypercholesterolaemia.

Low density lipoprotein (LDL) composition was analysed in twenty-one patients with familial hypercholesterolaemia, including six homozygotes. By comparison with nineteen controls the patients' LDL had an increased ratio of cholesterol:phospholipid and a decreased ratio of lecithin:sphingomyelin; these changes were more marked in homozygotes than in heterozygotes. Treatment of sevel patients with plasma exchange temporarily resulted in near-normalization of the composition of their LDL. These results suggest that abnormalities of LDL composition in familial hypercholesterolaemia are secondary to hypocatabolism of LDL, which prolongs the half-life of LDL and thus increases the mean age of the population of particles circulating in plasma.

Blood Transfusion↗

Effect of hyperlipidaemia on pulmonary diffusing capacity for carbon monoxide.

There is conflicting evidence on the effect of hyperlipidaemia on pulmonary diffusing capacity for carbon monoxide (DLCO or TLCO) in man. We have measured the carbon monoxide transfer factor per unit alveolar volume (TLCO/VA or KCO) by the single breath method in 25 patients with hyperlipidaemia, and in three normal subjects before and after infusions of an intravenous fat emulsion, Intralipid. Non-smokers with hyperlipidaemia had normal levels of TLCO/VA, whereas some of the smokers showed a slight reduction. In neither group was there any correlation of TLCO/VA with serum triglyceride or cholesterol concentrations. A reduction in triglyceride concentrations of up to five-fold produced by plasma exchange (three studies in two patients) or by dietary manipulation (one patient) had no significant effect on the levels of TLCO/VA. Intralipid infusion in three normal subjects caused a four- to five-fold increase in serum triglyceride concentration but had no effect on TLCO/VA. We conclude that moderate degrees of hyperlipidaemia have no effect on pulmonary diffusion.

Adult↗

Septic bursitis.

In 12 cases of septic bursitis seen during 11 years, 11 patients were men and one patient was a woman, with a mean age of 51.3 years. The olecranon bursa was involved in nine cases. Staphylococcus aureus was grown from nine of ten culture-positive fluids. Bursal fluid WBC counts ranged from 1,550/cu mm to 165,000/cu mm, associated with low glucose levels in two cases, but not in three. Treatment with antibiotics and needle aspiration or surgical drainage was successful.

Adult↗

Familial occurrence of hyperuricemia, gout, and medullary cystic disease.

We observed hyperuricemia, acute gouty arthritis, and renal medullary cystic disease in three members of a family over two generations. Two of these individuals were women who developed gout by age 20 years. Two teenage sons of one of these patients had severe hyperuricemia, which appeared due to underexcretion of uric acid. To our knowledge the occurrence of hyperuricemia, gout, and renal medullary cystic disease has not been reported previously.

Adolescent↗

Testicular effects of cyclohexylamine hydrochloride in the rat.

Testicular effects of cyclohexylamine hydrochloride (CHA) were investigated in Wistar and Sprague-Dawley rats. Groups of 25 rats were fed diets containing 6000, 2000 and 600 ppm CHA for 90 days and in addition ad lib., pair-fed and paired-weight control groups were used to assess the role of reduced food intake in the development of testicular lesions. Rats fed diets containing 6000 and 2000 ppm CHA showed significant decreases in food consumption, body weight and body weight gain. However, significant increases in the incidence of testicular lesions were found only in those animals fed 6000 ppm CHA. Absence of a similar incidence of lesions in either the paired-weight of pair-fed control groups indicated that inanition was not primarily responsible for the development of the lesions. The toxicological significane of these findings is discussed.

Animals↗

Accentuation of ethanol-induced fatty liver by phenobarbitone.

1. Four groups of rats received a liquid formula diet, given alone (control), or supplemented with either ethanol or phenobarbitone, or both together. 2. The ethanol-treated group showed a fall in plasma triglyceride and a rise in liver triglyceride, as compared with the control rats. 3. The phenobarbitone-treated group showed a marked rise in plasma triglyceride but not in liver triglyceride. 4. The group receiving both ethanol and phenobarbitone also showed a rise in plasma triglyceride, but this was accompanied by a striking increase in liver triglyceride. 5. These results suggest that ethanol and phenobarbitone each stimulate triglyceride synthesis but that in addition ethanol has an inhibitory effect on hepatic triglyceride secretion.

Animals↗

Non-stedy-state studies of low-density-liproprotein turnover in familial hypercholesterolaemia.

1. The non-steady-state turnover of low-density lipoprotein (LDL), labelled in its apoprotein moiety (apo-B) with 131I, was determined in four patients with familial hypercholesterolaemia, three of them homozygotes. 2. The fractional and absolute catabolic rates (FCR and ACR) of LDL-apo-B were determined by relating the excretion of radioactivity, measured in urine in vitro and by whole-body counter in vivo, to plasma radioactivity and to LDL specific radioactivity respectively. 3. The FCR remained relatively constant, even after marked reduction of LDL pool size by means of plasma exchange. This confirms the existence of an intrinsic defect in LDL catabolism in familial hypercholesterolaemia. 4. LDL-apo-B synthesis, determined by summing the ACR and the daily increment in plasma LDL, was much higher in the three homozygotes than in the one heterozygote, in whom the synthetic rate was normal. 5. These results illustrate the usefulness of combining plasma exchange and whole-body radioactivy counting as a means of examining the relationship between the turnover and pool size of a 131I-labelled protein, such as LDL.

Adolescent↗

Effects of intravenous phospholipid on low density lipoprotein turnover in man.

The mechanism of the rise in plasma low density lipoprotein (LDL) levels following intravenous administration of a triglyceride-phospholipid emulsion (Intralipid) has been investigated by measuring LDL turnover in eight healthy subjects. The plasma half-life, and the absolute and fractional catabolic rates of LDL protein (apo-LDL) were unaffected by intragastric Intralipid, whereas apo-LDL half-life was prolonged and its fractional catabolic rate was decreased by intravenous Intralipid. Similar changes were observed after intravenous administration of the egg phospholipid constituent of Intralipid. Accompanying increases in the oleate: linoleate ratio of both high and low density lipoprotein cholesterol esters were secondary to phospholipid exchange between infused and endogenous lecithin. These results suggest that the increased concentration of LDL in plasma following intravenous administration of egg phospholipid-containing emulsions was due, at least in part, to a decrease in the fractional catabolic rate of apo-LDL. The data further suggest a possible relationship between apo-LDL catabolism and the fatty acid composition of LDL.

Apoproteins↗

The metabolism in vivo and in vitro of plasma low-density lipoprotein from a subject with inherited hypercholesterolaemia.

1. The metabolism in vivo and in vitro of an abnormal low-density lipoprotein (LDL) obtained from a patient with an inherited form of hypercholesterolaemia was compared with that of LDL obtained from a normal subject. 2. The rates of turnover of the apoprotein of the two types of LDL in a normal subject, and their uptake and catabolism by normal lymphocytes in vitro, were similar. 3. It is concluded that the abnormal behaviour of the patient's LDL may not be due to an abnormality in the apoprotein component.

Acacia↗

Contrasting effects on plasma lipoproteins of intravenous versus oral administration of a triglyceride-phospholipid emulsion.

The effect of fat on plasma lipoproteins was compared when administered by the oral and intravenous routes to healthy control subjects on a low fat diet for 5-6 weeks. During this time each subject underwent two 5 day periods of fat supplementation with a soya bean triglyceride-egg yolk phospholipid emulsion (Intralipid), once via intragastric tube, once intravenously. Changes in plasma lipoproteins were assessed by measurement of their lipid and protein content. Intragastric fat administration significantly decreased the level of very low density lipoprotein (VLDL), whereas intravenous fat administration caused a significant rise in low density lipoprotein (LDL). Morphological evidence of persistence of exogenous phospholipid in plasma following intravenous fat administration was confirmed by alterations in the fatty acid composition of lecithin in the d 1.006-1.063 fraction of plasma. In vitro studies showed that exchange readily occurred between Intralipid and LDL lecithin, causing the latter to assume a more saturated pattern. It is concluded that the occurrence of similar changes in vivo could explain the rise in low density lipoprotein following intravenous fat, possibly by influencing the catabolic rate of the apoprotein. Hydrolysis of ingested phospholipids during absorption presumably explains why none of these changes occurred after oral fat supplementation, and would seem to be an important regulatory function of the small intestine in relation to plasma lipoprotein metabolism.

Administration, Oral↗

Plasma exchange in the management of homozygous familial hypercholesterolaemia.

Two young women with homozygous familial hypercholesterolaemia and coronary and aortic atheroma were treated by repeated plasma exchange, using a continuous-flow blood-cell separator, for 4 and 8 months. A pronounced reduction in plasma cholesterol and low-density lipoprotein (L.D.L.) concentrations was achieved by exchanging each patient's plasma with cholesterol-free plasma protein fraction (B.P.), at 3-weekly intervals on an outpatient basis. By pre-labelling the patients' cholesterol with 14-C and comparing the specific activity of the cholesterol in adipose tissue with that in plasma, evidence was obtained of an influx of tissue cholesterol into plasma after each exchange. There was no side-effects and both patients lost their angina. Plasma exchange offers a new and practical approach to the long-term management of this lethal disorder and may also provide information about the possible reversibility of human atheroma.

Adult↗

Versatile unit for filling gelatin capsules with drugs or chemicals.

A new, inexpensive device was developed for making individually prepared capsules that can be administered to experimental animals. The device was designed for accurate and rapid production of large numbers of various capsule sizes and drug dosages. During 12 months of usage, 21 capsules were prepared weekly for each of 44 dogs (924 total capsules) in approximately 2.5 work-hours/week. Each capsule contained a precise amount of drug to administer a specific dosage to each individual dog. No difficulties were encountered in the manufacture or utilization of this device, and it can be operated by untrained personnel.

Animals↗

Effects of delta-9-tetrahydrocannabinol administered subcutaneously to rabbits for 28 days.

Subcutaneous (s.c.) administration of delta-9-tetrahydrocannabinol (delta-9-THC) to rabbits produced dose-related cumulative toxicity. Five groups of three New Zealand albino rabbits each received 28 daily treatments with isotonic saline, sesame oil of 15.9, 45.0 or 153.4 mg/kg/day of delta-9-THC dissolved in sesame oil. Dose-related dermal responses included erythema, edema, ulceration and nodule formation. Some of the granulomatous nodules contained an oily substance and exhibited liquefactive necrosis. The severities of erythema and ulceration were generally maximal during the first week of treatment, but edema and nodule formation were most severe after days 12 and 14, respectively. All rabbits survived treatment, but body weights, liver weights and liver glycogen levels were decreased in a dose-related manner. Maximal body weight effects occurred after day 19. Hemochemical changes occurred only in rabbits treated with 153.4 mg/kg/day and included decreased blood sugar and alkaline phosphatase, and increased serum potassium. Hematology parameters were normal throughout the treatment period. No drug-related pathological lesions occurred in internal organs. The cumulative body weight changes, significantly decreased hepatic glycogen levels and reduced blood sugar and alkaline phosphatase values may have indicated drug-induced metabolic changes.

Animals↗