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Biomedical subjects

N E Miller

Publications and source records attributed to N E Miller.

At least 55 records · Page 3Linked to original sources

Behavioral treatment of scoliosis and kyphosis.

A behavioral treatment of scoliosis and kyphosis was tested with 27 adolescent patients (19 scoliosis, eight kyphosis patients) to determine in which cases the conspicuous and restraining brace treatment could be replaced. In 22 compliant patients, posture biofeedback (PB) was highly effective compared to five non-compliant patients. Biologically more mature scoliosis patients (menarche at the beginning of treatment) seemed to profit more from PB. With kyphosis patients the PB treatment resulted in rapid straightening of the spine and removal of structural deformities of Scheuermann's disease. PB may serve as an unobtrusive yet effective treatment alternative for both juvenile scoliosis and kyphosis.

Adolescent↗

Implementation of a collaborative quality assessment program.

The authors describe a collaborative quality assessment program between the department of anesthesia and critical care and the department of nursing. Data were collected on patient outcomes and were presented, through case reviews, at monthly quality assessment rounds. The program has been successful in stimulating important discussions between physicians and nurses about patient care.

Aged↗

Associations of the HDL2 and HDL3 cholesterol subfractions with the development of ischemic heart disease in British men. The Caerphilly and Speedwell Collaborative Heart Disease Studies.

BACKGROUND: The relative importance of HDL2 and HDL3 cholesterol as risk factors for ischemic heart disease (IHD) is still uncertain. Their associations with the incidence of IHD in the Caerphilly and Speedwell prospective studies are described. METHODS AND RESULTS: The two studies have a common core protocol and are based on a total of 4860 middle-aged men from the general population. The first follow-up was at a nearly constant interval of 5.1 years in Caerphilly and 3.2 years in Speedwell: 251 major IHD events had occurred. Lipid levels were measured on fasting samples. Different laboratories were used by the two studies. Each laboratory used ultracentrifugation to separate HDL2 and HDL3. Both subfractions were inversely associated with risk of IHD. Standardized relative odds of developing major IHD were 0.95 (95% confidence interval [CI], 0.80 to 1.14) for HDL2 cholesterol and 0.83 (95% CI, 0.68 to 1.00) for HDL3 cholesterol in Caerphilly and 0.76 (95% CI, 0.57 to 1.01) for HDL2 and 0.64 (95% CI, 0.49 to 0.83) for HDL3 in Speedwell. The association with incident IHD appeared to be stronger for HDL3 in both areas. No linear combination of the two subfractions was a better predictor of IHD than total HDL cholesterol alone. CONCLUSIONS: In British men, both HDL2 and HDL3 cholesterol are inversely associated with the incidence of IHD. However, the prediction of the risk of IHD from total HDL cholesterol alone could not be improved upon by measurement of the two HDL subfractions. The relative value of the two HDL subfractions as predictors of risk is still unresolved. The uncertainty may be due, at least in part, to problems associated with their measurement.

Cholesterol, HDL↗

An operant approach to rehabilitation medicine: overcoming learned nonuse by shaping.

A new approach to the rehabilitation of movement, based primarily on the principles of operant conditioning, was derived from research with deafferented monkeys. The analysis suggests that a certain proportion of excess motor disability after certain types of injury involves a learned suppression of movement and may be termed learned nonuse. Learned nonuse can be overcome by changing the contingencies of reinforcement so that they strongly favor use of an affected upper extremity in the chronic postinjury situation. The techniques employed here involved 2 weeks of restricting movement of the opposite (unaffected) extremity and training of the affected limb. Initial work with humans has been with chronic stroke patients for whom the approach has yielded large improvements in motor ability and functional independence. We report here preliminary data suggesting that shaping with verbal feedback further enhances the motor recovery.

Animals↗

Gemfibrozil increases apolipoprotein A-I and cholesterol concentrations in human peripheral lymph.

Peripheral lymph lipoproteins were studied in four hyperlipidaemic men before and after 6 weeks of treatment with gemfibrozil, a drug which is known to increase the fractional catabolic rate of very low density lipoproteins (VLDL) by raising lipoprotein lipase activity in peripheral tissues. Decreases in plasma triglycerides of 18-60% (mean, 45%) were accompanied by increases in lymph apolipoprotein (apo) A-I concentration of 30-108% (mean, 66%; P < 0.01), and in lymph cholesterol concentration of 35-100% (mean, 59%; P < 0.05). The additional lymph cholesterol was distributed over a broad range of lipoprotein particle sizes. Effects on plasma apo A-I concentration (mean, +7%) and plasma total cholesterol concentration (-7%) were not statistically significant. No changes were observed in four untreated control subjects. These findings are compatible with the hypothesis that lipolysis of VLDL at the blood-endothelium interface increases the transfer of apo A-I from plasma to interstitial fluids, and thereby promotes cholesterol efflux from cells.

Adult↗

Technique to improve chronic motor deficit after stroke.

The unaffected upper extremity of chronic stroke patients was restrained in a sling during waking hours for 14 days; on ten of those days, these patients were given six hours of practice in using the impaired upper extremity. An attention-comparison group received several procedures designed to focus attention on use of the impaired upper extremity. The restraint subjects improved on each of the laboratory measures of motor function used--in most cases markedly. Extensive improvement, from a multi-year plateau of greatly impaired motor function, was also noted for the restraint group in the life situation and these gains were maintained during a two-year period of follow-up. For the comparison group only one measure showed small to moderate improvement, and this was lost during the follow-up period; there was essentially no overlap between the individuals of the two groups. Thus, prolonged restraint of an unaffected upper extremity and practice of functional movements with the impaired limb proved to be an effective means of restoring substantial motor function in stroke patients with chronic motor impairment identified by the inclusion criteria of this project.

Activities of Daily Living↗

Some examples of psychophysiology and the unconscious.

Different sources of the unconscious are discussed and illustrated, namely, failure to have learned an appropriate perception, repression motivated by an aversive emotion and reinforced by the reduction produced in it when the person stops the thoughts or other cue-producing responses eliciting that emotion, an interference with thoughts or perceptions by a distraction or stimulus overload, and failure to perceive a correct cause-and-effect relationship. The ways in which each of these forms of unconsciousness can reduce the adaptiveness of behavior are described and illustrated as well as how psychophysiological recording can facilitate therapy to improve consciousness and thus voluntary control and behavior that is more intelligent and adaptive.

Amnesia↗

Plasma triglyceride and high density lipoprotein cholesterol as predictors of ischaemic heart disease in British men. The Caerphilly and Speedwell Collaborative Heart Disease Studies.

OBJECTIVE: To assess the roles of plasma triglyceride and high density lipoprotein (HDL) cholesterol concentrations in predicting ischaemic heart disease. DESIGN: Two prospective cohort studies with common core protocols. SETTING AND PARTICIPANTS: Both cohorts are 100% samples of middle aged men. In Caerphilly the 2512 men were living within a defined area. In Speedwell the 2348 men were registered with local general practitioners. MAIN OUTCOME MEASURES: Fasting blood samples were taken at initial examination and plasma lipid concentrations were measured. Major ischaemic heart disease events were assessed from hospital notes, death certificates, and electrocardiograms. RESULTS: At first follow up, after an average of 5.1 years in Caerphilly and 3.2 years in Speedwell, 251 major ischaemic heart disease events had occurred. Men with triglyceride concentrations in the top 20% of the distribution had a relative odds value for ischaemic heart disease of 2.3 (95% confidence interval (95% CI) 1.3 to 4.1) compared with men in the bottom 20%, after adjusting for both plasma total and HDL cholesterol, and non-lipid risk factors. Men in the lowest 20% of the distribution of HDL cholesterol concentration had a relative odds value of 1.7 (95% CI 1.0 to 2.8) compared with the top 20%, after adjustment was made for total cholesterol and triglyceride concentrations, and non-lipid risk factors. These relations were not caused by beta blockers, which were being taken by 5% of the men. CONCLUSIONS: Plasma triglyceride concentration predicts major ischaemic events after allowance is made for total and HDL cholesterol concentrations and other risk factors. In these populations, triglyceride is a more important predictor than total cholesterol concentration.

Adrenergic beta-Antagonists↗

The very-high-density lipoprotein fraction of rabbit plasma is rich in tissue-derived cholesterol.

When plasma from rabbits, which several weeks earlier had been infused with [3H]cholesterol, was subjected to equilibrium density gradient ultracentrifugation, the specific radioactivity of cholesterol in the very-high-density lipoprotein (VHDL) fraction (d 1.22-1.32 g/ml) was three to 8-fold greater (mean, 5.5-fold; P less than 0.001) than that in high-density lipoproteins (HDL; d 1.06-1.21 g/ml). On size exclusion chromatography of plasma, no increase in specific radioactivity was seen in particles smaller than HDL. These findings suggest that those apolipoprotein-lipid complexes that dissociate from HDL during ultracentrifugation to form the VHDL fraction contain proportionately more tissue-derived cholesterol than do those that are more tightly bound to HDL.

Animals↗

Evidence that reverse cholesterol transport is stimulated by lipolysis of triglyceride-rich lipoproteins.

The hypothesis that reverse cholesterol transport by high density lipoprotein (HDL) is augmented by lipolysis of triglyceride-rich lipoproteins received support from experiments in rabbits whose tissue cholesterol had been pre-labeled with [3H]cholesterol several weeks earlier. When lipolysis was stimulated by intravenous heparin (which releases lipoprotein lipase from vascular endothelium), reciprocal changes in plasma triglyceride and HDL cholesterol concentrations were accompanied by a rise in the specific radioactivity of HDL cholesterol, indicative of increased transfer of cholesterol into HDL from slowly exchanging cholesterol pools in extra-hepatic tissues.

Animals↗

Lipoproteins of human peripheral lymph. Apolipoprotein AI-containing lipoprotein with alpha-2 electrophoretic mobility.

Evidence from diverse sources has implicated a central role of apolipoprotein AI (apo AI), the most abundant protein of plasma high-density lipoproteins, in the transport of cholesterol from peripheral tissues to the liver (reverse cholesterol transport). Particles containing only apo AI appear to be more effective as cholesterol acceptors in tissue culture than do particles which also contain apo AII. The apo AI-containing lipoproteins of plasma have been extensively studied, but there is less information on those in tissue fluids, to which most peripheral cells are exposed. In the present study the heterogeneity of apo AI-containing particles in human peripheral lymph, collected from the dorsum of the foot, has been examined by starch block electrophoresis, exclusion chromatography and immunoelectrophoresis. The apo AI-containing particles of lymph were found to be more variable in both electrophoretic mobility and size than those of plasma from the same subjects. Of particular interest was a subpopulation which migrated on electrophoresis with the same mobility as alpha-2-macroglobulin. This fraction accounted for approximately 7% (range: 4-12%; n = 5) of lymph apo AI, contained no immunodetectable apo AII, and by exclusion chromatography was composed of particles the size of, or smaller than, albumin. Such physicochemical properties suggest that these alpha-2 migrating particles may function as the principal primary acceptors of cell cholesterol in the extracellular matrix of human peripheral tissues. By isoelectric focusing, lymph apo AI was found to contain a higher proportion of more negatively charged isoforms than the apo AI of plasma.

Adult↗

Enzymatic fluorometric procedure for phospholipid quantification with an automated microtiter plate fluorometer.

We describe a new enzymatic assay for phospholipids that is rapid, sensitive, convenient, and inexpensive. The method is based on the fluorometric detection of H2O2, generated by the choline oxidase-catalyzed oxidation of choline, after liberation of choline from phospholipids by phospholipase D. Significant advantages over existing methods are that the entire reaction sequence can take place in a single vessel, a 12 x 8 well microtiter plate, and that the fluorescence intensity can be measured automatically with a Fluoroskan II (Labsystems Oy) detector. Extracting samples with organic solvents is unnecessary, although the method can be applied to extracts in isopropanol. The assay is approximately 60-fold more sensitive and has a limit of detection eightfold lower than currently available enzymatic colorimetric methods. Including solvent blanks, eight standards, and three quality-control pools, 34 samples can be pipetted and assayed in duplicate in 60 min. Results obtained by this procedure for total phospholipid choline in lipoproteins in primate plasma agreed well with those obtained for inorganic phosphorus by the Bartlett acid-digestion procedure.

Animals↗

Hormonal determinants of apolipoprotein B,E receptor expression in human liver. Positive association of receptor expression with plasma estrone concentration in middle-aged/elderly women.

The relationships of the expression of hepatic low-density lipoprotein (LDL) receptors (apo B,E receptors) to several plasma hormone concentrations were examined in 15 fasted women aged 37-75 years (mean, 57 years), who were undergoing laparotomy for non-neoplastic disease. No subject had clinical or biochemical evidence of familial hypercholesterolemia, renal disease, hepatic disease, or endocrine disease. Hepatic apo B,E receptor expression was quantified in vitro as the EDTA-suppressible binding of 125I-labeled human LDL (15 micrograms protein/ml) by liver homogenate at 37 degrees C; values were 23-75 ng LDL protein/mg cell protein (mean, 47 ng/mg). Receptor expression was strongly correlated with plasma estrone concentration (rs = +0.70, P = 0.035), but was unrelated to the concentrations of testosterone, thyroxine, free triiodothyronine, cortisol, sex hormone-binding globulin (SHBG) or cortisol-binding globulin. Insulin and estradiol concentrations were mostly very low. The correlation of receptor expression with plasma total estrone concentration reflected associations with both the albumin-bound (rs = +0.78, P = 0.014) and unbound (rs = +0.80, P = 0.009) fractions, but not with the SHBG-bound fraction (rs = -0.22, P = 0.574), of this hormone. As the non-SHBG-bound fractions of gonadal steroids are considered to be the biologically active components, these results are consistent with experimental evidence that the synthesis of apo B,E receptors in hepatocytes is stimulated by estrogens, and suggest that circulating estrone may be the major hormonal determinant of receptor expression in fasted middle-aged/elderly women.

Adult↗

Pharmacotherapy of disorders of plasma lipoprotein metabolism.

Pharmacologic intervention for altering plasma lipoproteins is aimed principally at reducing atherogenesis and thereby preventing coronary artery disease. These drugs should be prescribed only after nonpharmacologic interventions (reduction of saturated fat and cholesterol consumption, weight reduction, aerobic exercise, cessation of cigarette smoking) have failed to achieve an adequate effect. The plasma concentration of the atherogenic low-density lipoprotein (LDL) may be reduced in hypercholesterolemic patients by increasing hepatic LDL receptor synthesis (bile acid sequestering resins, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors) or by reducing hepatic very low density lipoprotein synthesis (gemfibrozil, nicotinic acid). LDL concentration may also be reduced by treatment with one of the fibrates (e.g., fenofibrate). Several classes of lipid-lowering drugs also increase the plasma high-density lipoprotein (HDL) cholesterol concentration. In the case of the fibrates, this appears to be principally mediated through an increase in lipoprotein lipase activity. Gemfibrozil additionally stimulates apolipoprotein AI synthesis. The increase in HDL cholesterol produced by nicotinic acid is due primarily to decreased clearance of HDL particles from the circulation. The increase in HDL concentration produced by gemfibrozil was shown in the Helsinki Heart Study to make a major contribution to a reduced incidence of coronary artery disease, independently of that made by the decrease in LDL. The Cholesterol-Lowering Atherosclerosis Study demonstrated that combined therapy with a resin (colestipol) and nicotinic acid can reduce the progression of coronary atherosclerosis and the development of graft lesions in patients who have undergone coronary artery bypass graft surgery.

Apolipoproteins B↗