The susceptibility to autoxidation of human red cell lipids in health and disease.
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Biomedical subjects
Publications and source records attributed to J Stocks.
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Lung resistance (RL) and airway resistance (Raw) were measured in 33 healthy and sick infants. Using strict criteria for quality control, calibrated pressure-flow (P-V) curves were produced with the aid of a computer so that resistance could be analyzed at several points over the breathing cycle. In a subgroup of 11 infants from whom simultaneous measurements were obtained, values of RL and Raw were comparable, suggesting that the tissue component may make only a minimal contribution to lung resistance in infants. For both RL and Raw, the P-V relationship remained linear up to 50% maximum inspiratory flow in all infants. At other points of the respiratory cycle, there were marked changes in resistance, values calculated between points of mid-isovolume or peak pressure being significantly higher than those measured over the linear portion of inspiratory flow. While no single value can accurately reflect the changes in respiratory resistance that occur during the breathing cycle, the authors suggest that for purposes of comparison, RL or Raw should be measured as the slope of the inspiratory loop from the origin up to 50% of maximum inspiratory flow. From a calibrated tidal pressure flow curve values of resistance over other portions of the breathing cycle can easily be determined.
Calibrated pressure-flow (P-V) curves were plotted by computer using data from both the plethysmographic method for measuring airway resistance and the esophageal balloon technique for measuring lung resistance. P-V curves from 100 sick, healthy, and convalescent infants (age range 2 days to 19 months, weight range 0.9-10.4 kg) were classified into five distinctive types according to shape and direction of looping. Two of these patterns, one with a virtually closed, the other with a narrow figure-of-eight loop, reflected the normal physiologic changes in airway caliber that may occur during tidal breathing. The remaining three patterns, with far more marked changes in resistance, were associated with particular pathophysiologic mechanisms of airway obstruction. A wide figure-of-eight configuration, in which the expiratory loop rotated clockwise with marked flow limitation toward end expiration, was found for infants with chronic lung disease. By contrast, a rise in initial expiratory resistance due to dynamic glottic narrowing, with an anticlockwise rotated expiratory P-V loop, occurred in infants with reduced or unstable lung volumes. A clockwise inspiratory loop was observed only for infants intubated during the neonatal period, many of whom had clinical evidence of extrathoracic airway obstruction. Inspection and analysis of P-V curves provides more information about the state of the airways than does a single numerical expression of resistance. However, since normal patterns of P-V curves are not restricted to infants with healthy airways, a combined qualitative and quantitative approach to these measurements is recommended.
Assessment of the esophageal pressure technique for measuring dynamic lung compliance (Cdyn) showed that accurate results were obtained in only 5 of 15 studies of sick intubated infants, whereas they were obtained in 6 of 6 studies of convalescent nonintubated infants. In sick infants, inaccuracy was due to large variations in esophageal pressure change (delta Pes) at different esophageal depths and difficulties validating Pes using the occlusion test. Methods of assessing lung stiffness that depend on the measurement of esophageal pressure are unreliable and should not be used in sick intubated infants.
Measurements of total compliance of the respiratory system (CRS) by the weighted spirometer technique and functional residual capacity (FRC) by helium gas dilution were attempted in 63 healthy children (aged 2 to 7 years). Weighted spirometry was well tolerated in all but six children, and FRC measurements were successful in 42. Both measurements were reproducible and not affected by posture. Good correlations were found between CRS and height (r = 0.73) and age (r = 0.83) as well as between FRC and height (r = 0.83) and age (r = 0.74). No differences were found between boys and girls. CRS also correlated significantly with FRC (r = 0.67). In five children with cystic fibrosis, measurements of CRS, FRC and specific compliance correlated with disease severity. Our data suggest these well-tolerated techniques may provide a useful means to distinguish the effects of disease from those of growth.
The occlusion technique to measure total respiratory system compliance (Cocc) was used in 28 sedated infants with a variety of cardiopulmonary diseases and 14 anaesthetised infants during the first 2 years of life. In this report, we describe some of the potential problems in the technique and how to avoid them. Invalidation of the occlusion technique because of consistent failure to relax during brief airway occlusions occurred in only four of 42 infants despite the fact that only four infants were studied during the first month of life and 17 were between 12 and 26 months old. The technique was invalidated in two intubated infants because of persistent leaks around the endotracheal tube. In the remaining 36 infants, data sometimes had to be excluded as a result of instability and end-expiratory volume, intermittent leaks, or failure to relax during occlusions performed at low lung volumes or during inspiration. However, by performing 15-25 occlusions per infant, it was possible to obtain sufficient reliable data for accurate analysis of Cocc in all these infants. Providing that the potential errors and limitations of the occlusion technique are recognized, it appears to be applicable to a wide range of healthy and sick infants.
Respiratory system compliance (Crs) can be used to assess lung stiffness in sick, intubated infants, avoiding the use of an esophageal balloon. Crs was assessed in a group of 15 sick, intubated infants using the occlusion and inflation techniques. The occlusion technique gave satisfactory results in 13 infants. Apneic pauses following occlusion were obtained in infants up to 10 months of age. Satisfactory measurements of Crs were obtained in all 15 infants using the inflation technique, but difficulty was experienced in obtaining data over the tidal volume range in three of them. A close agreement was found between the two methods of measuring Crs in the ten infants in whom a direct comparison was possible.
The polypeptide composition of a variant lipoprotein (d less than 1.006) carrying a relative excess of apolipoprotein C-II has been characterised by polyacrylamide gel electrophoresis and isoelectric focussing. The apo-C peptides of the variant lipoprotein contained 45.2 +/- 1.3 (n = 9) % of apo C-II compared with 21.5 +/- 5.4 (n = 30) % for hypertriglyceridaemic controls. The variant lipoprotein activated purified bovine milk lipoprotein lipase normally, but was an inefficient substrate for this enzyme as assessed by direct release of fatty acids from the lipoprotein or by a substrate competition assay. Electron microscopy revealed the variant lipoprotein as non-spherical flattened particles compared with the more spherical appearance of control triglyceride-rich lipoproteins. We suggest that the relative proportion of apo C peptides associated with the lipoprotein particle may be critical for optimal enzyme-substrate interaction.
We examined the impact of a G-->A mutation at position -75 of the apolipoprotein AI gene promoter in subjects with hypertriglyceridaemia from two racial groups, Caucasians (n = 52) and Japanese (n = 19) compared to their controls (n = 56 and n = 21 respectively). The mutation was genotyped by the polymerase chain reaction and subsequent digestion using HpaII, and BstNI. We found no significant differences in allele frequency in either control-control or case-control comparisons in European and Japanese populations. Linkage disequilibrium was observed between the mutation and the common alleles of two restriction fragment length polymorphisms, MspI and SstI located in the APOA1 and APOC3 genes, respectively, in the Japanese population. On the basis of these results, the G-75-->A mutation is unlikely to be aetiological in predisposing to hypertriglyceridaemia.
Plasma levels of total high density lipoprotein cholesterol (HDL) and its subfractions (HDL2 and HDL3) were measured in 366 healthy Caucasian males; these values were related to a number of coronary risk factors. On univariate statistical analysis, total HDL was negatively correlated with cigarette consumption, body mass index, and serum triglycerides, and positively associated with level of physical activity and alcohol consumption. HDL2 showed an inverse relationship with cigarette consumption, body mass index, triglycerides, and systolic blood pressure and a positive relationship with age. HDL3 was negatively correlated with cigarette smoking, body mass index, and triglycerides and positively associated with exercise level and alcohol consumption. Total HDL and HDL2 were inversely related to coronary risk rating, but HDL3 showed no significant correlation. Many of these relationships became nonsignificant after allowing for the effects of other variables. In particular, none of the HDL measurements correlated significantly with risk score after allowing for the effect of triglycerides. There is insufficient evidence at present to recommend the inclusion of HDL subfractions as routine screening tests for heart disease.