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Biomedical subjects

B Lewis

Publications and source records attributed to B Lewis.

At least 181 records · Page 10Linked to original sources
PubMed1985

An alternative procedure for incorporating radiolabelled cholesteryl ester into human plasma lipoproteins in vitro.

A simple method has been developed for labelling human plasma lipoproteins to high specific radioactivity with radioactive cholesteryl esters in vitro. After isolation by preparative ultracentrifugation, the selected lipoprotein was incubated for 30 min at 4 degrees C in human serum (d greater than 1.215) that had been prelabelled with [4-14C]cholesteryl oleate or [1,2-3H]cholesteryl linoleate, and was then re-isolated by ultracentrifugation. All major lipoprotein classes were labelled by the procedure. Specific radioactivities of up to 18 d.p.m. . pmol-1 (46 d.p.m. . ng-1) were achieved. When radiolabelled high-density lipoprotein was infused intravenously, the radioactive cholesteryl ester behaved in vivo indistinguishably from endogenous cholesteryl esters produced by the lecithin (phosphatidylcholine): cholesterol acyltransferase reaction.

Carbon Radioisotopes↗
PubMed1985

Relationship between changes in plasma lipoprotein concentrations and fecal steroid excretion in man during consumption of four experimental diets.

Limited information is available on the mechanism by which changes in nutrient intake influence plasma lipids. We compared the effects on plasma lipoprotein levels of 3 dietary modifications involving changes in total fat intake (27-40% of calories), cholesterol intake (100-250 mg/1000 kcal), the dietary polyunsaturated to saturated fatty acid ratio (0.3-1.0) and intake of vegetable-derived fiber and protein. On these 3 diets, plasma low density lipoprotein was reduced by 26-34%. Fecal bile acid excretion was similar on all diets (363-379 mg/day). There was no alteration in fecal bile acid output associated with an increase in polyunsaturated or total fat intake. Sterol balance became significantly more negative during consumption of only 1 of the 3 cholesterol-lowering diets. The observed reduction in plasma cholesterol levels was not associated with an increase in fecal bile acid output suggesting that diet-induced changes in circulating cholesterol are not maintained by an increase in sterol turnover but may reflect alterations in hepatic cholesterol and lipoprotein synthesis.

Adult↗
PubMed1985

Plasma cholesterol response to a change in dietary fat intake: a collaborative twin study.

The rise of plasma cholesterol in response to an increase from 8 to 22.3% in saturated fatty acid of total intake was studied by comparing the concordance of change in pairs of young English and Italian monozygotic (33 pairs) and dizygotic (22 pairs) twins. LDL and total cholesterol rose about 0.6 mmol/l. All methods of analyses showed a marked genetic component influencing total and LDL cholesterol level. However, the genetic component of the increase in LDL and total cholesterol levels was small in Italy and absent in England. These results suggest that the response of plasma cholesterol to this dietary change is largely determined by environmental factors rather than inheritance.

Adolescent↗
PubMed1985

Randomised controlled trial of the treatment of hyperlipidaemia on progression of atherosclerosis.

Two types of end-point measurement are presently available in clinical trials of the effect of treatment of hyperlipidaemia on cardiovascular disease; these are the incidence of clinical events and the arteriographic assessment of progression or regression of atherosclerosis. These approaches are briefly reviewed. In the present trial, 25 hyperlipidaemic men with symptomatic femoral atherosclerosis underwent biplanar femoral arteriography at baseline. They were then randomised into treatment and usual-care groups; treatment was individualized, comprising a lipid-lowering diet with cholestyramine, nicotinic acid or clofibrate as appropriate for the lipoprotein disorder. Mean cholesterol and triglyceride levels were 19% and 37% lower in the treatment group. Arteriography was repeated after a mean period of 19 months. With attention to blinding of observers, changes in arteriograms were quantitated using computerised image analysis and visual methods, and expressed both by patient and by arterial segment. All end-points were in conformity and showed a lower rate of progression of arterial disease in the treatment group, and a higher frequency of segmental regression in treated patients. In this small trial of patients with functionally-significant atherosclerosis, effective treatment of hyperlipidaemia favourably affected the course of the arterial disease.

Angiography↗
PubMed1985

Plasma apolipoprotein B metabolism in familial type III dysbetalipoproteinaemia.

Lipoprotein metabolism was studied in eleven patients with Type III hyperlipoproteinaemia, one with normolipidaemic dysbetalipoproteinaemia and eight controls. Apolipoprotein B kinetics in very low density, intermediate density and low density lipoproteins (VLDL, IDL and LDL) was investigated. Fractional catabolic rates (FCRs) of VLDL-apo B and IDL-apo B were lower (P less than 0.005 and P less than 0.001) in the patients: 0.064 +/- 0.018 and 0.059 +/- 0.006 h-1 respectively, (mean +/- SEM), compared with 0.219 +/- 0.035 and 0.243 +/- 0.028 h-1. Synthetic rates (SRs) of IDL-apo B varied widely from 1.5 mg kg-1 day-1 in the subject with normolipidaemic dysbetalipoproteinaemia to 2.8-25.2 mg kg-1 day-1 in Type III. The mean time for conversion of IDL-apo B to LDL-apo B was prolonged, 18.7 h compared with 3.8 h in the controls (P less than 0.001). LDL-apo B pool size and SR were lower in the patients (P less than 0.05 for both). Two patients treated with gemfibrozil showed reduced hyperlipidaemia and decreased SR of VLDL-apo B and IDL-apo B. Dysbetalipoproteinaemia is associated with pronounced impairment of IDL and VLDL-remnant catabolism, lipoprotein levels reflecting an interaction between this defect and SR of these lipoproteins.

Adult↗
PubMed1985

Biliary sclerosis in patients receiving hepatic arterial infusions of floxuridine.

High response rates have been reported with hepatic intra-arterial infusions of floxuridine in patients having colorectal carcinoma metastatic to the liver. The major toxicity of this therapy has been described as "chemical hepatitis." In a randomized trial of intravenous v intra-arterial floxuridine, we observed that all 35 patients receiving intra-arterial therapy developed significant increases in alkaline phosphatase and, in some cases, serum glutamic oxaloacetic transminase and/or bilirubin. Seven patients receiving intra-arterial therapy were studied with cholangiography which, in all cases, demonstrated sclerosis of the intrahepatic and/or extrahepatic bile ducts. In addition, liver biopsies showed cholestasis and pericholangitis with minimal hepatocyte damage. These findings suggest that "biliary sclerosis" rather than "chemical hepatitis" is the predominant toxicity associated with hepatic intra-arterial infusions of floxuridine.

Aged↗
PubMed1985

Sequential infusions of methotrexate and 5-fluorouracil in advanced cancer: pharmacology, toxicity, and response.

Preclinical studies have suggested that synergistic antitumor toxicity occurs when methotrexate (MTX) is administered prior to 5-fluorouracil (FUra). A protocol of sequenced, overlapping infusions of MTX and FUra was designed to achieve 5 microM MTX serum levels lasting 36 h and 1 to 5 microM FUra levels lasting 24 h, with leucovorin started at the end of the MTX infusion. Thirty-nine patients with metastatic neoplasms received a total of 127 treatment courses; two-thirds of the patients had received prior treatment with radiation therapy or chemotherapy; most of the latter treatment regimens included MTX or FUra. In three patients, the duration of FUra infusion was prolonged up to 72 h to determine the toxic limits of therapy. Blood samples were collected during treatment courses to estimate the half-lives and total-body clearances of MTX and FUra. The initial serum half-lives and total-body clearances of both MTX and FUra appeared within the range of reported normal values. The terminal half-life of MTX appeared less than previously reported values, and there appeared to be a substantial delay in achieving a FUra steady-state concentration; these two differences may have resulted from either the prolonged intervals of drug infusion or from metabolic interaction between the two drugs. During the 127 courses of treatment, nearly one-half of the patients experienced mild toxicity occurring after at least one treatment, but this toxicity was predominantly Grade I mucositis and/or diarrhea. Of the three patients who received extended intervals of FUra infusion, none was able to tolerate more than 48 h of FUra without developing mucositis. Thirty-four patients were evaluable for response; no one experienced a complete response, but 11 (32%) patients had either a partial or minimal response. Adenocarcinomas as a group, arising from the lung, gut, breast, and unknown site, appeared to respond best. Sequenced MTX-FUra infusion by this schedule is a generally well-tolerated regimen that deserves further clinical assessment.

Adult↗
PubMed1984

Metabolic study of variation in plasma cholesterol level in normal men.

Variation in plasma cholesterol in normal populations underlies a 2-5 fold range of risk of coronary heart disease. The metabolic basis of this variation was studied in a healthy population recruited from a general-practice list. Compared with men in the modal decile of plasma cholesterol, those in the top decile maintained their high levels by overproduction of low-density lipoprotein (LDL). Men in the bottom decile of plasma cholesterol had low levels of LDL, resulting chiefly from a greater rate of fractional catabolism of this lipoprotein; and blood mononuclear cells from men in the bottom decile catabolised LDL more rapidly in vitro than did cells from other men. Intake of dietary lipids by men in the top, modal, and bottom deciles did not differ significantly. Different mechanisms appear to underlie high and low levels of plasma cholesterol in a normal population.

Adult↗
PubMed1984

Inhibition of cholesterol synthesis reduces low-density-lipoprotein apoprotein B production without decreasing very-low-density-lipoprotein apoprotein B synthesis in rabbits.

The kinetics of the apoprotein B (apo B) of very-low-density (VLDL; d less than 1.006) and low-density (LDL; d 1.019-1.063) lipoproteins were studied in six rabbits by using radioiodinated homologous lipoproteins, before and during oral administration of mevinolin (5 mg/kg per day), a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 1.1.1.34), to explore the mechanism by which the drug reduces LDL synthesis. Before treatment LDL-apo B production greatly exceeded VLDL-apo B production in all animals, indicating that a large proportion of plasma LDL was derived from a VLDL-independent pathway. Five animals responded to mevinolin with a fall in plasma cholesterol (mean change - 53%; P less than 0.01). This was associated with a 66% decrease in LDL-apo B synthesis (P less than 0.05). In contrast, VLDL-apo B synthesis was unaffected by mevinolin. Furthermore, in all but one animal the decrement in LDL-apo B synthesis was greater than the rate of VLDL-apo B synthesis before treatment, demonstrating that mevinolin had reduced the VLDL-independent production of LDL.

Animals↗
PubMed1984

A multifactorial diet in the management of hyperlipidaemia.

To augment the effectiveness of conventional lipid-lowering treatment, a diet has been evolved combining modified fat content with an increase in vegetable-derived fibre and protein. This was evaluated in 37 hyperlipidaemic and normal ambulant subjects in whom plasma lipid and lipoprotein responses were measured for 4.7-11 months. Mean reductions in plasma cholesterol, triglyceride and low density lipoprotein cholesterol levels were 22, 24 and 25% respectively; there was no significant change in the cholesterol concentrations in high density lipoprotein or in its HDL2 subclass. The effectiveness of the diet in reducing hyperlipidaemia, its influence in optimizing the distribution of cholesterol between plasma lipoprotein classes, and its nutrient composition suggest that it is an advance on existing lipid-lowering dietary patterns.

Adult↗
PubMed1984

Thromboembolism and bleeding after mitral valve replacement with porcine valves: influence of thromboembolic risk factors.

The risk of postoperative thromboembolism (PTE), anticoagulant related hemorrhage (ARH), and the influence of thromboembolic risk factors ( TERF ) were assessed retrospectively in 206 unselected patients undergoing mitral valve replacement (MVR) with porcine xenobioprotheses ( PXBP ). Other aims were to identify the "high-risk" group with respect to PTE and to assess the effectiveness of long-term anticoagulant therapy (AT) in this subset, as well as to elucidate the most adequate method of AT and ascertain if AT is strictly necessary in patients undergoing MVR with PXBP . Patients were divided in two groups: Group I (N = 115) received long-term AT; there were 22 PTE. Group II (N = 91) with only 8 weeks of AT had 2 PTE (P less than 0.01). ARH was the same in both groups. Actuarially , 71.7% of the patients in group I and 96.3% of the patients in group II were free of PTE at 6 years. Long-term AT proved ineffective in preventing PTE and carried a significant incidence of ARH. ARH surpassed PTE (3.5:1) in patients on short-term AT. Patients without TERF have a low incidence of PTE, and AT is not indicated. The "high-risk" group were patients in postoperative atrial fibrillation and left atrial enlargement. One week heparin therapy and 3 months oral AT is suggested for patients with TERF . PXBP for MVR in patients with TERF is significantly thrombogenic. Early operation is advocated to avoid development of TERF that will affect patient outlook after MVR with PXBP due to the significantly increased risks of PTE and (if placed on AT) ARH.

Adult↗
PubMed1984

Disfluencies at the onset of stuttering.

This study describes disfluencies in rare speech samples obtained from young children in temporal proximity to their stuttering onsets. Ten 2 and 3 year olds diagnosed by parents to have begun stuttering for periods of 2 months or less and 10 matched normally speaking children served as subjects. Analyses of spontaneous speech indicated that stutterers were three times more disfluent than nonstutterers. Part-word repetitions and sound prolongations were found to distinguish the two groups significantly. Stutterers were also found to have significantly more repetition units per instance of disfluency than control subjects. Theoretical and practical conclusions are discussed.

Child, Preschool↗
PubMed1984

Risk factors for coronary heart disease--assessment in airline pilots.

Biochemical risk factors have a potent impact on the overall risk in the development of coronary heart disease (CHD). This impact is greater in men and in women after the menopause. The prevalence of familial hypercholesterolaemia (Familial Type IIa) in the U.K. is approximately 2.5/1000, and 50% of affected males develop overt CHD by the age of 50. The prevalence of Type III hyperlipoproteinaemia is lower. More minor elevations of the plasma cholesterol in association with smoking and/or hypertension, however, may confer a similar overall risk of CHD. Usually minor adverse biochemical effects may be produced by treatment with antihypertensive agents. It is suggested that measurement of fasting cholesterol, including the HDL fraction, together with triglyceride and glucose in new applicants for medical certificates to fly, will identify a small subset at high risk for the development of CHD. Repeat studies at intervals would then be needed. The presence of abnormalities in the plasma lipids associated with excessive smoking and/or minor hypertension make a reasonable case for denying a single-crew certification.

Adult↗
PubMed1984

Cytogenetic analysis of a segment of the Y chromosome of Drosophila melanogaster.

Males carrying a large deficiency in the long arm of the Y chromosome known to delete the fertility gene kl-2 are sterile and exhibit a complex phenotype: (1) First metaphase chromosomes are irregular in outline and appear sticky; (2) spermatids contain micronuclei; (3) the nebenkerns of the spermatids are nonuniform in size; (4) a high molecular weight protein ordinarily present in sperm is absent; and (5) crystals appear in the nucleus and cytoplasm of spermatocytes and spermatids. In such males that carry Ste+ on their X chromosome the crystals appear long and needle shaped; in Ste males the needles are much shorter and assemble into star-shaped aggregates. The large deficiency may be subdivided into two shorter component deficiencies. The more distal is male sterile and lacks the high molecular weight polypeptide; the more proximal is responsible for the remainder of the phenotype. Ste males carrying the more proximal component deficiency are sterile, but Ste+ males are fertile. Genetic studies of chromosome segregation in such males reveal that (1) both the sex chromosomes and the large autosomes undergo nondisjunction, (2) the fourth chromosomes disjoin regularly, (3) sex chromosome nondisjunction is more frequent in cells in which the second or third chromosomes nondisjoin than in cells in which autosomal disjunction is regular, (4) in doubly exceptional cells, the sex chromosomes tend to segregate to the opposite pole from the autosomes and (5) there is meiotic drive; i.e., reciprocal meiotic products are not recovered with equal frequencies, complements with fewer chromosomes being recovered more frequently than those with more chromosomes. The proximal component deficiency can itself be further subdivided into two smaller component deficiencies, both of which have nearly normal spermatogenic phenotypes as observed in the light microscope. Meiosis in Ste+ males carrying either of these small Y deficiencies is normal; Ste males, however, exhibit low levels of sex chromosome nondisjunction with either deficient Y. The meiotic phenotype is apparently sensitive to the amount of Y chromosome missing and to the Ste constitution of the X chromosome.

Animals↗