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Biomedical subjects

A Nicoll

Publications and source records attributed to A Nicoll.

161 records · Page 9Linked to original sources
PubMed1980

Quantitative studies of very low density lipoprotein: conversion to low density lipoprotein in normal controls and primary hyperlipidaemic states and the role of direct secretion of low density lipoprotein in heterozygous familial hypercholesterolaemia.

Autologous 131I-labelled very low density lipoprotein (VLDL) and 125I-labelled low density lipoprotein (LDL) were injected into seven normal subjects and twenty-eight genetically classified hyperlipidaemic patients to quantitate lipoprotein interconversion. The apoprotein B specific activity--time curves for VLDl and intermediate density lipoprotein (IDL, density = 1 . 006--1 . 019 g/ml) intersected at or before the IDL-B maximum in thirty-one studies (five normal controls and twenty-six hyperlipidaemic subjects) implying that all IDL-B may be derived from VLDL-B. The fractional conversion of VLDL-B to LDL-B (density 1 . 019--1 . 063 g/ml) following a simultaneous spike injection of 131I-VLDL and 125-LDL was obtained by deconvolution of the 125I and 131I-LDL-B activity curves. 21--65% (mean = 44%) of VLDL-B was converted to LDL-B in twenty-three subjects studied. The mean conversion time ranged from 10 to 24 h in ten normotriglyceridaemic subjects and from 19 to 42 h (mean = 33 h) in twelve hypertriglyceridaemic subjects. In one patient with broad-beta disease the mean conversion time was 55 h. LDL-B production from VLDL-B and total LDL-B synthetic rate were essentially equal in normal controls and normocholesterolaemic subjects and in the patient with broad-beta disease. But in all six patients with familial hypercholesterolaemia LDL-B synthetic rate significantly exceeded LDL-B production from VLDL-B, indicating direct secretion of 20--72% of LDL-B at a rate which correlates positively with plasma LDL concentration. Three of five patients with familial combined hyperlipidaemia showed a lesser but nevertheless significant direct secretion of LDL-B.

Humans↗
PubMed1980

Evaluation of the roles of lipoprotein lipase and hepatic lipase in lipoprotein metabolism: in vivo and in vitro studies in man.

The roles of lipoprotein lipase (LPL) and hepatic lipase in very low density lipoprotein (VLDL) and VLDL remnant metabolism were investigated by (1) in vivo studies where the kinetics of VLDL-apo B removal were measured in patients with non-functioning lipoprotein lipase systems, and (2) in vitro studies where the relative capacities of hepatic lipase and LPL to hydrolyse the triglyceride (TG) of different lipoprotein substrates was measured. The results indicated that VLDL-apo B removal was not impaired in patients with non-functional LPL, nor ws there any apparent abnormality in the conversion of VLDL-apo B to intermediate- (IDL) and low (LDL) density lipoprotein-apo B. Post-heparin plasma hepatic lipase activity against VLDL was normal in these subjects. Purified normal hepatic lipase had a similar Km for VLDL-TG hydrolysis (1.57 mmol/l) to that of LPL (1.49 mmol/l). However, at equal lipoprotein TG concentration, hepatic lipase had increasing activity with lipoproteins of decreasing particle size, in the order chylomicrons much less than VLDL of Sf 100-400 less than VLDL of Sf 60-100 less than VLDL of Sf 20-60 less than IDL. The mean contribution of hepatic lipase to VLDL-TG hydrolysis by post-heparin plasma was 35% in normal controls, but the contribution to IDL-TG hydrolysis was significantly higher (mean - 58%). It is concluded that hepatic lipase plays a significant role in VLDL and, especially, IDL metabolism, at least in patients with non-functioning lipoprotein lipase.

Adult↗
PubMed1980

Use of the Streptosec test for grouping beta-haemolytic streptococci.

The Streptosec test, which embodies the coagglutination principle for grouping beta-haemolytic streptococci, was used against 72 streptococci previously grouped by precipitin methods. Only two of the 72 strains failed to react. The test is easy to manipulate, represents a considerable saving in time and effort, and produces results with an acceptable degree of accuracy.

Agglutination Tests↗
PubMed1979

Splanchnic production of discoidal plasma high-density lipoprotein in man.

The morphology of human plasma high-density lipoprotein (H.D.L.) subfractions in arterial and hepatic venous blood from seven human subjects was investigated by electron microscopy. The H.D.L.3 subclass from both sources and the H.D.L.2 subclass from arterial blood were composed of spherical particles, identical with normal human peripheral venous H.D.L. In contrast, H.D.L.2 isolated from hepatic venous blood was composed of a mixture of spherical and discoidal particles. The latter tended to form rouleaux, and had a diameter similar to that of nascent H.D.L. particles obtained from the peripheral venous blood of a patient with lecithin: cholesterol acyltransferase deficiency. This supports the view that nascent H.D.L. is secreted into the splanchnic bed in man.

Adult↗
PubMed1977

Influence of lipid concentrations and age on transfer of plasma lipoprotein into human arterial intima.

Transfer of low-density lipoprotein (L.D.L.2) from plasma to arterial intima was studied in 16 patients undergoing arterial surgery. Autologous labelled lipoprotein was used to demonstrate that L.D.L.2 enters the intima from plasma. Net flux of L.D.L.2 appeared to increase with age. Within each age-group the net flux of L.D.L.2 showed a pronounced positive correlation with plasma-L.D.L.-cholesterol concentrations. This may account in part for the association between hypercholesterolaemia and the development of atherosclerosis.

Adult↗
PubMed1977

Intravenous fat tolerance. Correlation with very low density lipoprotein apoprotein B kinetics in man.

The intravenous fat tolerance test (IVFTT) has been introduced as a measure of the fractional catabolic rate of the endogenous triglyceride of plasma. To assess the validity of this test we have compared this test in 21 normal and hyperlipidaemic subjects with direct measurement of the fractional catabolic rate of autologous radio-iodinated VLDL. There was a strong positive correlation between the rate constant K2 of the IVFTT and the fractional catabolic rate of VLDL-apolipoprotein B (r=+0.87). The two rates were considerably different in magnitude. The IVFTT appears to be a valid index of the fractional catabolic rate of VLDL. Its limitations and uses are discussed.

Adult↗
PubMed1977

Turnover of apolipoprotein-B in two subjects with familial hypobetalipoproteinemia.

The metabolism of the apoprotein of low-density apoliporprotein-B was studied in a father and son with familial hypobetalipoproteinemia. The synthetic rate of apolipoprotein-B was below the normal range in both subjects, while the fractional removal rate was normal. It is concluded that the subnormal concentration of low-density lipoprotein (LDL) inthese two subjects is due to a low synthetic rate. The synthetic rate of apolipoprotein-B of very low-density lipoprotein (BLDL-apoB) measured in the father was subnormal. The fraction of the VLDL-apoB pool which was oncverted into LDL-apoB was within the normal range. It is suggested that a low synthetic rate of VLDL may underlie the disorder.

Adult↗
PubMed1976

The metabolism of low density lipoprotein in endogenous hypertriglyceridaemia.

The metabolism of low density lipoprotein (LDL) was studied in eighteen hypertriglyceridaemic patients by injecting autologous radioiodinated LDL. Over 95% of the label was bound to the protein moiety of LDL and therefore the metabolic data reflect the fate and distribution of LDL apoprotein (apo B). The hypertriglyceridaemic subjects included ten with Type V, five with Type IV, two with Type III and one with Type IIb hyperlipoproteinaemia. For comparison identical studies were carried out in seven normal subjects and five patients with heterozygous familial hyperbetalipoproteinaemia (Type IIa). The groups differed considerably in mean LDL-cholesterol concentration. The patients with Type V lipoprotein pattern had significantly lower LDL-cholesterol concentration (mean 0.754 g/1) than the normal group (mean 1.237 g/1). Raised LDL-cholesterol levels were observed in all patients with heterozygous familial hyperbetalipoproteinaemia. The synthetic rate of LDL-apoprotein was found to be similar in all three groups (hypertriglyceridaemic, normal and hypercholesterolaemic). The highest synthetic rate was observed in the patient with Type IIb pattern. However, the fractional catabolic rate (FCR) of LDL-apoprotein differed significantly. The highest mean FCR was found in the Type V group (0.65 +/- 0.17 day-1) compared with 0.41 +/- 0.09 day-1 in the normal group and 0.185 +/- 0.05 day-1 in the Type IIa group. A strong inverse correlation was found between FCR and LDL apoprotein concentration in the whole series (r = -0.90, p less than 0.001) as well as within the Type V group (r = -0.87, p less than 0.01). These data indicate that the low plasma levels of LDL frequently observed in patients with very high plasma triglyceride levels are due to a high removal rate of LDL in these patients rather than to abnormal LDL synthesis.

Adult↗
PubMed1976

Metabolism of very low density lipoproteins in hyperlipidaemia: studies of apolipoprotein B kinetics in man.

The metabolism of very low density lipoprotein-B (VLDL-B) peptide was studied in nineteen subjects with endogenous hypertriglyceridaemia (Types V, IV and IIb), three patients with heterozygous familial hyperbetalipoproteinaemia (Type IIa) and eight healthy subjects, by reinjecting autologous radioiodinated VLDL. The kinetics of VLDL-B peptide were followed. The mean turnover rate of VLDL-B peptide was significantly higher in the hypertriglyceridaemic group than in the control group but a considerable overlap in turnover rate was found between these groups. The patients with heterozygous familial hyperbetalipoproteinaemia had a normal turnover rate of VLDL-B peptide. A significant positive correlation was found between the turnover rate of VLDL-B peptide and VLDL-triglyceride concentration in the whole series. It is concluded that the underlying defect in endogenous hypertriglyceridaemia is heterogeneous. Overproduction of VLDL is a major determining factor in some patients whereas a reduced clearance is the determining factor in others.

Adult↗
PubMed1975

Conversion of very low density lipoprotein to low density lipoprotein. A metabolic study of apolipoprotein B kinetics in human subjects.

The interrelationship between apolipoprotein B in very low density lipoprotein (VLDL-B) and in low density lipoprotein (LDL-B) was studied in seven normal and hyperlipidemic men and women, with purified radioiodinated VLDL. The time-course of the appearance of radioactivity in LDL was followed. As the specific activity curves intersected at the masimal height of the LDL-B curve, it was inferred that all or most LDL-B peptide is derived from VLDL-B peptide. This transfer was further quantitated in seven normotriglyceridemic subjects by simultaneous i.v. injection of purified 131I-VLDL and 125I-LDL. By a deconvolution method, a quantitative description of the rate of entry of 131Ivldl-b into 131I-LDL-B was derived by analysis of 131I-LDL-B and 125I-ldl-b radioactivity in plasma. The results indicate that approximately 90% of VLDL-B mass is converted into LDL-B in subjects with normal serum triglyceride concentrations. The synthetic rates of VLDL-B and LDL-B peptide were simultaneously measured in six normal subjects, and two patients with heterozygous familial hypercholesterolemia (type IIa). The turnover rates for VLDL-B and LDL-B peptide were similar in these subjects. The findings in the three parts of this study were consistent with the view that most if not all VLDL-B is converted into LDL-B peptide, and most if not all LDL-B is derived from VLDL-B peptide in normotriglyceridemic subjects.

Adult↗
PubMedDate not supplied

Integrated management of childhood illness in resource-poor countries: an initiative from the World Health Organization.

It is estimated that each year around 12 million children aged < 5 years die in resource-poor countries and that 70% of these deaths are due to communicable diseases and/or malnutrition. The same conditions are responsible for an even higher percentage of childhood illness. Since the mid-1990s the World Health Organization has been leading the development of an integrated approach to care for ill children at the primary care level, a programme know as Integrated Management of Childhood Illness (IMCI). The approach essentially combines improved management of childhood illness with aspects of nutrition, immunization and maternal health. IMCI replaces or complements a number of 'vertical' child health programmes aimed at specific groups of conditions including control of diarrhoeal diseases (CDD), acute respiratory infections (ARI) and the Expanded Programme on Immunization (EPI). As of late 1998 the programme, at various stages of development, had been introduced to 51 countries: Introduction (19 countries), Early Implementation (29 countries) or Expansion (9). The approach has many advantages not least that it is well accepted by tropical country paediatricians because it conforms to practice in secondary care. In some countries paediatricians are playing a greater leadership role than they did with previous specific programmes. Many problems remain: programmatic issues, probable over-diagnosis of malaria, relationships with other specific initiatives ('Roll Back Malaria' and new-born care) and how to integrate HIV infection into the diagnosis and care 'package'. However the initiative deserves support by paediatricians and public health specialists in industrialized countries.

Africa↗
PubMedDate not supplied

Surveillance for the impact in the UK of HIV epidemics in South Asia.

OBJECTIVES: To determine whether, because of the extensive recent spread of HIV infection in South Asia, South Asians (those people who classify themselves as Indian, Pakistani, Bangladeshi or Sri Lankan in origin) resident in the UK were at increased risk of HIV infection and to review current surveillance systems for detecting any such increase. DESIGN: Analysis of: ethnic grouping and probable country of infection recorded on voluntary confidential reports of AIDS cases and newly diagnosed HIV infections; blood donation testing data; reports of imported gonorrhoea infections; country of birth data from the unlinked anonymous (UA) survey of Sexually Transmitted Disease (STD) clinic attenders; district of residence data from the UA survey of pregnant women; ethnic grouping of prevalent diagnosed HIV infections. RESULTS: Few reported AIDS cases or HIV infections were found in people of South Asian ethnic origin and few reported HIV or gonorrhoea infections were associated with exposure in South Asia. Data derived from the UA programme suggested as yet no increase in HIV prevalence in either STD clinic attenders born in South Asia or in pregnant women resident in districts containing substantial numbers of ethnic South Asians. CONCLUSIONS: There was no evidence that South Asians resident in the UK are currently at greater risk of HIV infection than people of white ethnicity or, therefore, that south Asian heterosexuals are a group deserving priority in HIV prevention. However, as rapid spread of HIV infection is being recorded in the Indian subcontinent, continuous monitoring is necessary. This will be facilitated by improved collection of ethnic group information in all surveillance activities.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Anthrax the facts.

Explore the source record for details and available documents.

Anthrax↗
PubMedDate not supplied

Simplified antiviral prophylaxis with or and without artificial feeding to reduce mother-to-child transmission of HIV in low and middle income countries: modelling positive and negative impact on child survival.

BACKGROUND: Antiviral prophylaxis is recommended for HIV positive mothers to prevent mother-to-child transmission of HIV. To date UNAIDS and WHO policy has been based on a study in Thailand which showed a reduction in transmission by half with short course AZT (Zidovudine) treatment together with artificial feeding. We modelled the possible positive and negative effects on child deaths in low and middle resource developing country settings of two interventions to reduce mother to child transmission (MTCT) of HIV: antenatal testing, short-course antivirals (zidovudine or nevirapine), firstly with and then without artificial feeding. MATERIAL AND METHODS: Estimates are made of child lives likely to be saved by the programme by age ten years, balanced against increases in deaths due to more uninfected mothers choosing to use artificial feeds where these are part of the intervention. Mid-point values for variables affecting the balance of mortality gains and losses are taken from recent published data for low and middle income developing countries and a sensitivity analysis is undertaken. RESULTS: In low income settings the use of antivirals alone would result in an estimated gain in child survival of around 0.36%, representing 360 deaths avoided from a birth cohort of 100,000 by age 10 years. Adding artificial feeding could reduce the gain to 0.03% (30 deaths avoided). In middle income settings the gain from antivirals alone would be 0.26% but as 'spill-over' of artificial feeding to uninfected women was more likely it could result in a net increase of child deaths of up to 1.08% (1,080 additional deaths). A sensitivity analysis emphasised this potential for regimens using artificial feeding if progamme participation was low, and under most circumstances in middle income settings. CONCLUSIONS: HIV testing and use of antivirals by infected mothers, if well implemented, will be effective at a population level in reducing MTCT. However the addition of artificial feeding is potentially be a high risk strategy, especially in middle income countries.

Anti-HIV Agents↗