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Biomedical subjects

J S Millar

Publications and source records attributed to J S Millar.

At least 37 records · Page 2Linked to original sources
PubMed1997

MRI in the localization of CSF fistulae: is it of any value?

Coronal T2-weighted magnetic resonance imaging (MRI) has been reported to be a useful technique for the localization of both spontaneous and traumatic CSF (cerebro spinal fluid) fistulae. We reviewed the magnetic resonance imaging (MRI) scans of 50 patients with temporal lobe epilepsy in whom such sequences were routinely acquired to determine if this asymptomatic population fulfilled any of the criteria for the diagnosis of a CSF fistula. We found that a large proportion did and conclude that using MRI as the initial radiological investigation in the localization of CSF fistulae is of such low specificity that it is of little or no value.

Adolescent↗
PubMed1997

Lovastatin decreases de novo cholesterol synthesis and LDL Apo B-100 production rates in combined-hyperlipidemic males.

The effect of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, on the kinetics of de novo cholesterol synthesis and apolipoprotein (apo) B in very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) was investigated in five male patients with combined hyperlipidemia. Subjects were counseled to follow a Step 2 diet and were treated with lovastatin and placebo in randomly assigned order for 6-week periods. At the end of each experimental period, subjects were given deuterium oxide orally and de novo cholesterol synthesis was assessed from deuterium incorporation into cholesterol and expressed as fractional synthesis rate (C-FSR) and production rate (C-PR). Simultaneously, the kinetics of VLDL, IDL, and LDL apo B-100 were studied in the fed state using a primed-constant infusion of deuterated leucine to measure fractional catabolic rates (FCR) and production rates (PR). Drug treatment resulted in significant decreases in total cholesterol (-29%), VLDL cholesterol (-40%), LDL cholesterol (-27%), and apo B (-16%) levels and increases in HDL cholesterol (+13%) and apolipoprotein (apo) A-I (+11%) levels. Associated with these plasma lipoprotein responses was a significant reduction in both de novo C-FSR (-40%; P = .04) and C-PR (-42%; P = .03). Treatment with lovastain in these patients had no significant effect on the FCR of apoB-100 in VLDL, IDL, or LDL, but resulted in a significant decrease in the PR of apoB-100 in IDL and LDL. Comparing the kinetic data of these patients with those of 10 normolipidemic control subjects indicates that lovastatin treatment normalized apoB-100 IDL and LDL PR. The results of these studies suggest that the declines in plasma lipid levels observed after treatment of combined hyperlipidemic patients with lovastatin are attributable to reductions in the C-FSR and C-PR of de novo cholesterol synthesis and the PR of apoB-100 containing lipoproteins. The decline in de novo cholesterol synthesis, rather than an increase in direct uptake of VLDL and IDL, may have contributed to the decline in the PR observed.

Adult↗
PubMed1997

Interaction of very-low-density, intermediate-density, and low-density lipoproteins with human arterial wall proteoglycans.

The specific interaction of lipoproteins with arterial wall constituents, particularly proteoglycans (APG), is believed to play an important role in the development of atherosclerosis. The objective of this study was to examine the interaction of apolipoprotein B (apoB) containing lipoprotein subfractions (VLDL1, Sf 60 to 400; VLDL2, Sf 20 to 60; IDL1, Sf 16 to 20; IDL2, Sf 12 to 16; LDLA, Sf 8 to 12; and LDLB, Sf 0 to 8) prepared by cumulative density gradient centrifugation with chondroitin sulfate-rich APG. Eighteen subjects were studied, and a similar pattern of interaction between the lipoprotein species and APG was found in all. The order of reactivity (as measured by increased turbidity due to insoluble complex formation) was IDL Sf 12 to 16 > or = LDL Sf 8 to 12 > LDL Sf 0 to 8 > IDL Sf 16 to 20 >> VLDL Sf 20 to 60 > VLDL Sf 60 to 400. When the subjects were divided on the basis of their LDL subfraction profile, the extent of insoluble complex formation was highest in the group in which small, dense LDLIII was predominant; intermediate in the group whose LDL was mainly LDLII; and lowest in the group with a high proportion of LDLI (the mean reactivity, AU at 600 nm. of APG with IDL Sf 12 to 16 and LDL Sf 8 to 12 was 0.66; 0.62 and 0.46, 0.43 and 0.20, and 0.21 for the three groups, respectively). Fibrate lipid-lowering treatment decreased the percentage of LDLIII and increased the percentage of LDLI within total LDL and reduced the reactivity of all apoB-containing lipoprotein fractions toward APG. Sialic acid content varied in different lipoprotein subfractions, being the highest in VLDL and lowest in LDL. However, across lipoprotein species, it did not significantly correlate with APG-binding reactivity, suggesting that other factors are important in determining the interaction of lipoproteins with APG. Modification of LDL arginine and lysine residues abolished the ability of the lipoprotein to interact with APG, a finding that supports the hypothesis that the interaction is dependent on key positively charged amino acids on apoB. These findings demonstrate that (1) the overall reactivity of apoB-containing lipoproteins is greatest in individuals with small, dense LDL and (2) within an individual, IDL of Sf 12 to 16 is the most reactive species, and this may in part explain the positive correlation between IDL and risk of coronary heart disease.

Adult↗
PubMed1995

Optimization of radiographic technique for chest radiography.

Over 1500 patients undergoing chest radiography in the West Midlands have been monitored for entrance surface doses using lithium borate thermoluminescent dosemeters. In total 63 X-ray tubes were monitored from 30 hospital departments. The mean patient entrance surface dose is 0.15 mGy, and the 75th percentile entrance surface dose is 0.18 mGy. A reference level of 0.18 mGy has been recommended for PA chest radiography in the West Midlands. Image quality has been assessed on patient radiographs. Departmental radiologists were responsible for assessing radiographs taken within their hospital. Independent analysis was performed by a control radiologist. Film-screen processor sensitivity has been assessed on 48 film-screen processor combinations. Significant differences were observed between the nominally quoted sensitivities and the measured sensitivities. Only 26% of systems produced measured sensitivities within 10% of the nominal values. A four variable regression model, explaining 78% of the variance, provided the best description for the variation in patient dose. These variables were actual sensitivity, applied potential, generator waveform and radiographic quality. Four recommendations have been made to lower patient doses; these are: (1) an increase in applied potential to a minimum of 90 kVp; (2) a film-screen sensitivity of 400; (3) optimization of processor performance and (4) regular radiological audits to reduce repeat rates to a level of 5%. If all of these recommendations are followed, an estimated overall entrance surface dose saving of 53% would result. Changing the applied potential alone will see the variation in the mean entrance surface dose from non-gridded systems reduce from a factor of 4 to a factor of 2.

Humans↗
PubMed1995

Impact of age on the metabolism of VLDL, IDL, and LDL apolipoprotein B-100 in men.

Levels of plasma very low density lipoprotein (VLDL) and low density lipoprotein (LDL) constituents increase with age. In an attempt to further define the mechanisms responsible for these changes, kinetic studies of VLDL and LDL apolipoprotein (apo) B-100 were carried out in 19 normolipidemic male subjects with plasma total cholesterol and triglyceride levels below the 90th percentile whose ages ranged from 24 to 73 years. Subjects were maintained on standardized diets consisting of 47-49% of calories as carbohydrate, 15% protein, and 36-40% fat (15-17% saturated, 15-17% monounsaturated, 6% polyunsaturated) with 150 mg cholesterol/1000 kcal. At the end of the diet period, the metabolism of apoB-100 within VLDL, intermediate density lipoprotein (IDL), and LDL was studied in the fed state using a primed-constant infusion of [2H3]leucine. Data were fit to a multicompartmental model to determine residence times and production rates of apoB-100 in each fraction. There were significant positive correlations between age and VLDL, IDL, and LDL apoB-100 concentrations (r = 0.50, 0.62, and 0.69; P = 0.03, 0.004, and 0.001, respectively). There was a positive correlation between age and the production rate of VLDL apoB-100 (r = 0.50, P = 0.03), but there was no significant relationship between age and either IDL or LDL apoB-100 production rates. Age was also positively correlated with the residence time of LDL apoB-100 (r = 0.68 P = 0.001). Our data suggest that the age-associated increase in VLDL apoB-100 is due to an increased production rate of this constituent, whereas the age-associated increase in LDL apoB-100 is due to an increased residence time of these particles in plasma.

Adult↗
PubMed1993

Detection of significant abnormalities on lumbar spine radiographs.

The purpose of this study was to determine the proportion of significant abnormalities detected on anteroposterior (AP) and lateral radiographs of the lumbar spine when viewed separately, in a series of cases where the prevalence of abnormalities had been artificially increased. Five radiologists of varying experience were required to report separately on the AP and lateral films of 300 cases in which randomly included were 30 cases with metastatic disease, a disc infection or an inflammatory spondylitis. At a later date, unaware of their initial observations, the radiologists repeated the exercise reviewing all the films together. As might be expected the false positive rate was relatively high, particularly in the least experienced radiologists' responses. Nevertheless the overall results indicate that the majority of early inflammatory spondylitis cases will be missed on a solitary lateral film as will many of the metastases. Conversely, fractionally more of the disc infections were observed on the lateral film than on the AP. Further analyses in terms of sensitivity, specificity, positive and negative predictive values are presented. The authors conclude that it is preferable to reduce the overall number of lumbar spine examinations performed, by adherence to accepted guidelines, than to prejudice the detection of significant, albeit rare, abnormalities by restricting the routine series of radiographs.

Discitis↗
PubMed1993

Contribution of apoB-48 and apoB-100 triglyceride-rich lipoproteins (TRL) to postprandial increases in the plasma concentration of TRL triglycerides and retinyl esters.

After the ingestion of a fat-rich meal, there is a postprandial increase in the plasma concentration of both apolipoprotein B-48- and apoB-100-containing triglyceride-rich lipoproteins (apoB-48 and apoB-100 TRL). In order to determine the contribution of these lipoproteins to postprandial lipemia, the concentration of triglycerides (TG) and retinyl esters (RE) was measured in apoB-48 and apoB-100 TRL after an oral fat load. Six normolipidemic male subjects were fed heavy cream (1 g fat per kg body weight) containing vitamin A (3000 retinol equivalents). TRL were isolated by ultracentrifugation from plasma samples obtained at regular intervals after the meal, and apoB-100 TRL were separated from apoB-48 TRL by affinity chromatography using monoclonal antibodies. Postprandial increase in plasma TG concentration was due to an increase in TG in the TRL fraction, which in turn was predominantly (82 +/- 4%) due to an increase in TG in apoB-48 TRL. Contribution of apoB-100 TRL to postprandial increase in TRL TG was 3-27% in individual subjects. ApoB-100 TRL remained a significant carrier of total plasma triglyceride in the fed state, as reflected by similar apoB-100 and apoB-48 TRL TG concentrations at 2, 4, and 6 h after the fat meal. Retinyl esters were regularly detected in apoB-100 TRL. Seventy-five (+/- 9) percent of the increase in TRL-RE was due to RE in apoB-48 TRL and 25 +/- 9% was due to RE in apoB-100. These data suggest that RE in plasma are not always associated with apoB-48-containing lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Measurement of human apolipoprotein B-48 and B-100 kinetics in triglyceride-rich lipoproteins using [5,5,5-2H3]leucine.

A primed-constant infusion of deuterated leucine was used in humans to determine the maximal level of enrichment at plateau of apolipoprotein (apo)B-48 and apoB-100 which are synthesized in the intestine and liver, respectively, and to compare the kinetics of these two proteins under identical conditions. Eight normal subjects (four post-menopausal females and four males) over the age of 40 were studied in the constantly fed state over a 20-h period by providing small hourly feedings of identical composition. [5,5,5-2H3]Leucine (10 mumol/kg body weight followed by 10 mumol/kg body weight per hour) was infused over 15 h intravenously. The enrichment of deuterated leucine in apoB-48 and apoB-100 triglyceride-rich lipoproteins isolated by ultracentrifugation (d less than 1.006 g/ml) was determined during the entire infusion period. The plateau level of enrichment in triglyceride-rich lipoprotein apoB-48 was 3.96 +/- 1.41 tracer/tracee ratio (%) which was 39.7% of the plasma leucine enrichment level. The plateau level of enrichment in triglyceride-rich lipoprotein apoB-100 was 7.23 +/- 1.17 tracer/tracee ratio (%) which was 72.5% of the plasma leucine enrichment level. Mean fractional secretion rates of triglyceride-rich lipoprotein apoB-48 and apoB-100 were 4.39 +/- 2.00 and 5.39 +/- 1.98 pools per day, respectively, with estimated residence times of 5.47 and 4.45 hours, respectively. The data indicate that in the fed state there is about a twofold difference in the plateau enrichment of an intestinally derived protein, as compared to one of hepatic origin, most likely attributable to differences in the enrichment of the intracellular leucine in the two organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

The effects of intermittent dietary restriction on weight gain and body fat in white-footed mice, Peromyscus leucopus.

The effects of repeated food restriction-refeeding cycles were investigated in second generation captive Peromyscus leucopus. Mice were maintained on 50% of their individual predetermined ad lib diet for 5 days followed by 10 days of refeeding ad lib. Cycles were repeated 3 times. When compared with controls maintained ad lib for the same time period, no significant differences in final weight or fat content were observed. Restricted-refed mice were, however, observed to both lose and regain weight at increasing rates with each subsequent cycle.

Adipose Tissue↗
PubMed1990

Measurement of very low density and low density lipoprotein apolipoprotein (Apo) B-100 and high density lipoprotein Apo A-I production in human subjects using deuterated leucine. Effect of fasting and feeding.

Six normolipidemic male subjects, after an 8-h overnight fast, were given a bolus injection and then a 15-h constant intravenous infusion of [D3]L-leucine. Subjects were studied in the fasted state and on a second occasion in the fed state (small, physiological meals were given every hour for 15 h). Apolipoproteins were isolated by preparative gradient gel electrophoresis from plasma lipoproteins separated by sequential ultracentrifugation. Incorporation of [D3]L-leucine into apolipoproteins was monitored by negative ionization, gas chromatography-mass spectrometry. Production rates were determined by multiplying plasma apolipoprotein pool sizes by fractional production rates (calculated as the rate of isotopic enrichment [IE] of each protein as a fraction of IE achieved by VLDL (d less than 1.006 g/ml) apo B-100 at plateau. VLDL apo B-100 production was greater, and LDL (1.019 less than d less than 1.063 g/ml) apo B-100 production was less in the fed compared with the fasted state (9.9 +/- 1.7 vs. 6.4 +/- 1.7 mg/kg per d, P less than 0.01, and 8.9 +/- 1.2 vs. 13.1 +/- 1.2 mg/kg per d, P less than 0.05, respectively). No mean change was observed in high density lipoprotein apo A-I production. We conclude that: (a) this stable isotope, endogenous-labeling technique, for the first time allows for the in vivo measurement of apolipoprotein production in the fasted and fed state; and (b) since LDL apo B-100 production was greater than VLDL apo B-100 production in the fasted state, this study provides in vivo evidence that LDL apo B-100 can be produced independently of VLDL apo B-100 in normolipidemic subjects.

Adult↗
PubMed1990

Comparison of deuterated leucine, valine, and lysine in the measurement of human apolipoprotein A-I and B-100 kinetics.

The production rates of apolipoprotein (apo)B-100 in very low density lipoprotein and in low density lipoprotein and apolipoprotein A-I in high density lipoprotein were determined using a primed-constant infusion of [5,5,5,-2H3]leucine, [4,4,4,-2H3]valine, and [6,6-2H2,1,2-13C2]lysine. The three stable isotope-labeled amino acids were administered simultaneously to determine whether absolute production rates calculated using a stochastic model were independent of the tracer species utilized. Three normolipidemic adult males were studied in the constantly fed state over a 15-h period. The absolute production rates of very low density lipoprotein apoB-100 were 11.4 +/- 5.8 (leucine), 11.2 +/- 6.8 (valine), and 11.1 +/- 5.4 (lysine) mg per kg per day (mean +/- SDM). The absolute production rates for low density lipoprotein apoB-100 were 8.0 +/- 4.7 (leucine), 7.5 +/- 3.8 (valine), and 7.5 +/- 4.2 (lysine) mg per kg per day. The absolute production rates for high density lipoprotein apoA-I were 9.7 +/- 0.2 (leucine), 9.4 +/- 1.7 (valine, and 9.1 +/- 1.3 (lysine) mg per kg per day. There were no statistically significant differences in absolute synthetic rates of the three apolipoproteins when the plateau isotopic enrichment values of very low density lipoprotein apoB-100 were used to define the isotopic enrichment of the intracellular precursor pool. Our data indicate that deuterated leucine, valine, or lysine provided similar results when used for the determination of apoA-I and apoB-100 absolute production rates within plasma lipoproteins as part of a primed-constant infusion protocol.

Adult↗
PubMed1989

Effect of exercise and menstrual cycle status on plasma lipids, low density lipoprotein particle size, and apolipoproteins.

Habitual physical exercise has been reported to have beneficial effects on plasma lipoproteins. To examine this question in women, plasma cholesterol, triglyceride, and apolipoprotein (apo) A-I and B levels, and low density lipoprotein (LDL) particle size were determined in 25 women runners (9 of whom had exercise-related secondary amenorrhea) and 36 age-matched nonexercising women (controls). The eumenorrheic runners had significantly lower apo B levels and significantly greater mean apo A-I/apo B ratios and LDL particle sizes than did the control women (P less than 0.05). Lower apo B levels were correlated with decreased body mass index, a known exercise effect (P less than 0.0001). In addition, normally menstruating runners had cholesterol and triglyceride levels that were 7.6% and 25.4% lower, respectively, and apo A-I levels that were 6.4% higher than control women (P = NS). In amenorrheic runners all parameters were similar to values in control women, except that apo B levels were 20% lower (P less than 0.05). Amenorrheic runners had lower plasma apo A-I levels (13%) and significantly lower apo A-I/apo B ratios and estradiol levels than eumenorrheic runners, and serum estradiol values in the runners were correlated with apo A-I levels (P less than 0.01). These data indicate that the beneficial effects of strenuous exercise on plasma apo A-I levels and apo A-I/apo B ratios in women runners can be reversed by exercise-induced amenorrhea and decreased serum estradiol levels, and that women runners have lower apo B levels than nonexercising women, regardless of menstrual status.

Adult↗
PubMed1988

Epidemic jejunitis.

Explore the source record for details and available documents.

Disease Outbreaks↗
PubMed1985

Meat consumption as a risk factor in enteritis necroticans.

The association between the consumption of animal protein and enteritis necroticans (EN) was investigated in a case-control study of 60 proven cases of acute surgical EN. A very high risk of EN was found in association with the recent ingestion of pork and other meats with the exception of tinned fish. The control group was characterized by the more frequent and regular ingestion of animal protein (predominantly in the form of tinned fish) suggesting a protective effect. No conclusions about the causality of the observed associations could be drawn but the implications for preventive intervention are discussed.

Adult↗
PubMed1985

Analyses of vegetables from the highlands of Papua New Guinea.

Ten vegetable foods of the highlands were analysed for crude protein, amino acids and trypsin inhibitor. Pandanus nut, lima bean, fern, greens, pitpit and choko had good to acceptable crude protein contents and the proteins of fern, pitpit, Rungia klossii and Indian mustard were of good quality. Lima beans had a very high content of trypsin inhibitor and all others had small or zero amounts, including fern, which is used at pig feasts and hence does not contribute to pig bel.

Amino Acids↗