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Biomedical subjects

M E Stewart

Publications and source records attributed to M E Stewart.

At least 55 records · Page 3Linked to original sources

Dilutional effect of increased sebaceous gland activity on the proportion of linoleic acid in sebaceous wax esters and in epidermal acylceramides.

Sebaceous wax esters and epidermal acylceramides were isolated from skin surface lipid obtained from children and from young adults. Fatty acid methyl esters (FAME) were prepared from the esterified fatty acids of these lipid classes and analyzed to ascertain the proportions of methyl linoleate (18:2 delta 9,12), methyl sebaleate (18:2 delta 5,8), and methyl sapienate (16:1 delta 6). On the same subjects, 2 measures of sebum secretion rate were obtained, namely the sustainable wax ester secretion rate (WESR) on the forehead and the ratio of wax esters/(cholesterol + cholesterol esters) [WE/(CH + CE)] in the surface lipid. The proportions of methyl linoleate in FAME from the wax esters decreased, and the proportions of methyl sebaleate increased, with increased rates of sebum secretion. For both methyl linoleate and methyl sebaleate, a better correlation was obtained when the ratio of WE/(CH + CE) was used as a measure of sebum secretion rather than the WESR. The proportions of methyl linoleate in the FAME from the acylceramides were also inversely related to ratios of WE/(CH + CE). In acylceramides, linoleate was replaced by sapienate, a major fatty acid of human sebum. It appears, therefore, that sebum fatty acid composition may change with changes in sebaceous gland activity, and that sebum fatty acids can enter the epidermis and be incorporated into epidermal lipids.

Acne Vulgaris↗

Effects of dietary selenium and vitamin E on plasma lipoprotein cholesterol levels in male rats.

Male Fischer-344 rats fed a diet deficient in both vitamin E and selenium (Se) for 20 weeks had higher levels of low-density lipoprotein cholesterol than age-matched rats fed an identical diet but supplemented with these micronutrients. The rats supplemented with both vitamin E and Se were switched to a diet deficient in both these micronutrients at week 20. These rats eventually developed elevated levels of low-density lipoprotein cholesterol compared to age-matched rats either continuously maintained on the diet supplemented with vitamin E and Se or rats switched (at week 20) from the vitamin E-and Se-deficient diet to a diet supplemented with both these micronutrients. In a second experiment, we found that Se deficiency alone was sufficient to significantly elevate low-density lipoprotein cholesterol. The basal diet used in these experiments had a very low cholesterol content and the observed alterations in lipoprotein cholesterol levels are likely to reflect alterations in the metabolism of endogenously synthesized cholesterol.

Animals↗

Changes in sebum secretion and the sebaceous gland.

New data have shown that sebum secretion is highest in young adults and then declines steadily throughout life in both men and women. This parallels the decline in androgen levels, but this cannot be the sole factor because there is so much overlap in sebaceous gland activity between men and women. The increased occurrence of dry skin in the elderly has been shown to be unrelated to the sebum secretion rate. This is not unexpected, as children, with even less sebum, rarely have this problem. Seborrheic dermatitis, which is also much more common in the elderly, is also unrelated to sebum secretion rate.

Adolescent↗

The time course of sebum secretion in the guinea-pig.

The time course of sebum secretion in the guinea-pig (Cavia porcellus) was determined by intradermal injection of [1-14C]acetate followed by daily collection of the skin surface lipids at the injection site. The skin surface lipids reached a peak of radioactivity at 5-6 days, indicating that this is the time which elapses between the synthesis of sebum and the surface excretion of the sebaceous lipids. Of the three major skin surface lipid components, the sterol esters (25%) and the wax diesters (25%) showed similar peaks of radioactivity after labelling, but the glycerol ether diesters (30%) showed no radioactivity at any time, suggesting that this lipid is not produced in the skin.

Acetates↗

Fascicular conduction disturbances and ischemic heart disease: adverse prognosis despite coronary revascularization.

In patients with ischemic heart disease, fascicular conduction disturbances are associated with increased mortality. This study reveals that increased mortality also exists for certain types of fascicular conduction disturbances after myocardial revascularization. In 227 consecutive patients undergoing bypass surgery, 24 had preoperative and an additional 52 developed at surgery a fascicular conduction disturbance. At 66 +/- 14 months of follow-up, 6 (4%) of 148 control patients without pre- or postoperative fascicular conduction disturbances had died from cardiac causes. Although right bundle branch block and left hemifascicular block were the most common form of fascicular conduction disturbance, only 1 of 55 of these patients died (p = NS). Mortality rates were much higher for patients with left bundle branch block or an intraventricular conduction defect; 8 (38%) of 21 died from cardiac causes (p less than 0.05). A high risk subgroup was identified by comparing 14 consecutive patients with left bundle branch block or an intraventricular conduction defect who survived more than 1 year postoperatively with 21 consecutive patients with these same conduction defects who died within 1 year of surgery. The following variables were significantly (p less than 0.05) different (survivors versus nonsurvivors): age (58 +/- 7 versus 65 +/- 9 years); class IV angina (2 of 14 versus 16 of 21), prior myocardial infarction (9 of 14 versus 21 of 21), left ventricular ejection fraction (53 +/- 18 versus 41 +/- 15%), three vessel disease (9 of 14 versus 20 of 21) and left ventricular aneurysm (2 of 14 versus 13 of 21).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Proportions of various straight and branched fatty acid chain types in the sebaceous wax esters of young children.

The fatty acid composition of sebaceous wax esters was examined in 20 children, ages 6-8, using quartz capillary gas chromatography. The results were compared with a previously reported study of wax ester composition in 10 adults, in which the same analytical techniques were used. The children's wax esters showed more variability in the proportions of all fatty acid chain types than was found in adults. The most striking difference between the 2 age groups was in the proportions of iso-branched fatty acids with odd numbers of carbon atoms. These ranged from 1-26% of fatty acids in the children's wax esters but were not more than 3% of fatty acids in the adults' wax esters. Some of the variability in wax ester fatty acid composition in children seemed to be related to variation in rates of sebum production. The highest percentages of terminally branched (iso-even, iso-odd, and anteiso) and the lowest percentages of internally branched fatty acids were found in the children with the lowest rates of sebum secretion. However, even in children with similar rates of sebum secretion there were considerable differences in wax ester fatty acid composition, especially with respect to iso-even fatty acids. The results suggest that sebum fatty acid composition is influenced both by genetic factors and by limitations on the supply of precursors for terminally branched, but not internally branched, fatty acids.

Adult↗

Measurement of sebum secretion rates in young children.

Sustainable rates of lipid secretion were measured on the foreheads of 24 children, ages 6-8. The method of measurement involved absorption of skin surface lipid into bentonite clay and subsequent separation and measurement of the various lipid classes by quantitative thin-layer chromatography. In 9 of the children, sebum secretion appeared to be virtually nonexistent, judging by the low amounts of lipid recovered and the low percentages of wax esters and squalene, which are purely sebaceous lipid classes. An effect of age on sebum secretion rates was observed with median rates of wax ester secretion, being 7, 28, and 48 micrograms/10 cm2/3 h for 6-, 7-, and 8-year-olds, respectively. These values are well below those of most young adults. The relation between wax ester secretion rate and skin surface lipid composition on the forehead was investigated and found to conform to the formula: microgram wax esters/10 cm2/3 h = 28 X wax esters/(cholesterol + cholesterol esters), with a correlation coefficient (r) of 0.94.

Aging↗

Age-related changes in sebaceous wax ester secretion rates in men and women.

Sustainable rates of sebaceous wax ester secretion were measured on the foreheads of 109 men and 167 women, aged 15-97. Each measurement was made after first depleting the cutaneous sebum reservoir by overnight absorption of lipid into a layer of bentonite clay. Lipid was then absorbed for 3 h into fresh clay in which two 2-cm cloth disks were embedded. The absorbed lipid was extracted from the disks with ether and analyzed for wax esters by thin-layer chromatography. For both men and women there was a wide range of wax ester secretion rates at all ages. Rates were highest in the 15- to 35-year-olds and appeared to decline continuously throughout the adult age range. Values of log(wax esters) were better correlated with age than the untransformed values of wax ester secretion. The equations of best fit of log(wax esters) vs age suggested that sebum secretion declines about 23% per decade in men and 32% per decade in women.

Adolescent↗

Diffuse slow washout of myocardial thallium-201: a new scintigraphic indicator of extensive coronary artery disease.

When coronary artery disease is extensive and of relatively uniform severity, regional myocardial hypoperfusion may be balanced during stress, precluding development of spatially relative perfusion defects. Assessment of the washout of thallium-201 from myocardial regions may provide diagnostic assistance in these cases because washout analysis is spatially nonrelative and hypoperfused myocardial regions manifest a slow thallium-201 washout rate. In 1,265 consecutive patients having quantitatively analyzed stress-redistribution scintigraphy, 46 had a diffuse slow washout pattern with no or a maximum of one regional perfusion defect. Thirty-two underwent clinically indicated coronary angiography, and 23 (72%) of these were found to have three vessel or left main disease. Of 30 similar patients without a diffuse slow washout pattern and with no or a maximum of one perfusion defect, only 5 (17%) had extensive coronary disease. An independent relation between diffuse slow washout and extensive coronary disease was demonstrated by a Mantel- Haentzel chi-square analysis of a wide variety of other indexes of extensive disease. A diffuse washout abnormality, even in the absence of other scintigraphic, clinical or electrocardiographic indicators, carries a high predictive value for three vessel or left main coronary artery disease. The predictive value is maintained when the exercise level achieved is submaximal. Although an infrequent occurrence (3.6% of tested patients), a diffuse slow washout pattern without other scintigraphic indications of extensive coronary disease should lead to further diagnostic testing.

Coronary Angiography↗

Suppression of sebum secretion with 13-cis-retinoic acid: effect on individual skin surface lipids and implications for their anatomic origin.

The contribution of the keratinizing epidermis to the human skin surface lipid film has been difficult to ascertain because, after its release from the epidermal cells, epidermally derived lipid inevitably becomes mixed with sebum. In the present study, the sustainable rates of production of the 5 neutral lipid classes found on the skin surface (triglycerides + free fatty acids, wax esters, cholesterol, cholesterol esters, and squalene) were measured on the foreheads of acne patients before, during, and following treatment with 13-cis-retinoic acid, a drug which suppresses sebum production profoundly. Since sebum production was high in the patients before treatment and was suppressed to a few percent of the pretreatment level in some of the patients during treatment, data covering a wide range of sebum production rates were obtained. By using squalene as a measure of sebum production and plotting the rates of production of the other lipid classes vs the rate of production of squalene, it was possible through extrapolation to estimate the residual (i.e., epidermal) rate of production of each lipid class at zero sebum production. The results indicated that epidermis releases triglycerides + free fatty acids and cholesterol to the skin surface. The cholesterol esters in freshly secreted skin surface lipids appeared to be almost entirely sebaceous in origin. Measurements were also made of the percentages of cholesterol esters in lipid collected from the scalp after several days' accumulation and were compared to corresponding values for the forehead lipid. The percentages of cholesterol esters in scalp lipid tended to rise when sebum production was suppressed by the drug, rather than remaining relatively constant as occurred in the freshly secreted forehead lipid. This result indicated that epidermis may contribute to skin surface cholesterol esters, probably through skin surface esterification of epidermal cholesterol.

Acne Vulgaris↗

Variation in sebum fatty acid composition among adult humans.

Quartz capillary gas chromatography was used to analyze the wax ester fatty acids of 4 sebum samples collected at 2-week intervals from each of 10 adult human subjects. Marked differences in wax ester fatty acid composition between subjects were apparent. The greatest variation was present in the even-carbon-numbered iso-branched acids, which ranged from 1-22% of the monounsaturated acids and from 1-13% of the saturated acids. The anteiso chain structures formed 3-7.5% of the unsaturated acids and 3-13.5% of the saturated acids. Fatty acids bearing one or more methyl branches at other positions in the chain made up 12-22% of the saturated acids, but were not present in the unsaturated fatty acid fraction. This and other features of the composition of the unsaturated fatty acids indicate that the delta 6-desaturase that produces the monounsaturated fatty acids of human sebum requires a substrate having a straight chain of at least 12 carbon atoms extending from the carboxyl group. The differences in fatty acid composition between subjects and the constancy of composition for each of the subjects over the 2-month period indicate that the synthesis of each of the types of chain structure is under genetic control.

Adult↗

Severe neutropenia associated with sustained-release procainamide.

Neutropenia is a rare complication of procainamide therapy. However, over a period of 20 months, 8 patients developed severe neutropenia while taking a sustained-release preparation of the drug. Seven patients presented with fever and constitutional symptoms and one patient was asymptomatic. Bone marrow examinations showed myeloid aplasia or maturation arrest in 5 patients and myeloid hyperplasia in 1. Neutropenia resolved within 30 days of drug withdrawal, and all patients survived. A case-control study showed a significant association between sustained-release procainamide therapy and severe neutropenia in 5 of 114 patients (4.4%) recovering from open-heart surgery (Mantel-Haenszel chi square = 13.84; p less than 0.001). Thus, life-threatening neutropenia may be common with sustained-release procainamide preparations.

Aged↗

The St. Jude Medical bileaflet valve prosthesis. A 5 year experience.

A 5 year experience with the bileaflet St. Jude Medical valve is reported. Between March, 1978, and June, 1982, 198 patients received 233 such valves (90 mitral, 73 aortic, and 35 double mitral-aortic valve replacements). Total follow-up was 4,896 patient-months; survivors were followed up for 1 to 5 years (mean 35 months). Early (30 day) mortality was 6.6% overall and 11.1% after mitral, 2.7% after aortic, and 2.9% after double valve replacement. Total late mortality was 15.2%; the actuarial survival rate at 4 years was 67% after mitral, 79% after aortic, and 79% after double valve replacement. Ischemic mitral valve disease was associated with an early mortality of 26.7% and a 4 year survival rate of 34%; without this high-risk subset, early mortality was 3.3% and the 4 year survival rate was 77% after mitral valve replacement. A multivariate logistic regression model identified three preoperative patient characteristics associated with increased postoperative mortality: ischemic mitral valve disease (p less than 0.001), a depressed left ventricular ejection fraction (less than 55%; p less than 0.05), and advanced New York Heart Association class (IV; p less than 0.05). Valve-related complications occurred in 14 patients (3.4% per patient-year). There were no instances of primary structural failure or hemolysis. Thromboembolism (nine patients, 2.2% per patient-year) occurred more frequently after double (3.7% per patient-year) or mitral valve replacement (2.3% per patient-year) than after aortic valve replacement (1.3% per patient-year) and more frequently in 12 patients receiving aspirin and dipyridamole (6.5% per patient-year) than in 173 patients receiving warfarin (1.9% per patient-year). No thromboembolic event was fatal. Reoperation was necessary because of one valve thrombosis, one valve erosion, and two perivalvular leaks due to endocarditis; three of the four patients survived reoperation (one valve-related death, 0.5%). Of 154 patients alive at latest follow-up, 85% were in New York Heart Association Class I or II, and 90% had improved by at least one class. This intermediate experience with the St. Jude Medical valve indicates that, in addition to its previously demonstrated excellent hemodynamic performance, there have been no instances of primary structural failure or hemolysis. Warfarin anticoagulation is recommended in all patients.

Adolescent↗

Mitral valve replacement: impact of coronary artery disease and determinants of prognosis after revascularization.

From 1969 to 1982, 419 patients underwent single mitral valve replacement; of these, 48% had associated coronary artery disease (9% single vessel, 8% double vessel, 28% triple vessel, 3% left main). In 216 patients with no associated coronary disease, in 179 patients with coronary disease that was revascularized, and in 24 patients with coronary disease that was not revascularized, the 30 day mortalities were 4.2%, 13.9%, and 29.2% (p less than .05) after valve replacement. Actuarial survivals at 8 years were 68%, 44%, and 15%, respectively (p less than .01), with 1 to 165 months of follow-up (mean 52). After matching the three cohorts of patients in age, sex, left ventricular ejection fraction, and valve lesion, the presence of associated coronary artery disease decreased long-term survival and revascularization improved survival (p less than .05 for both). Incidental coronary disease in patients with rheumatic mitral valve disease had a significant negative influence on survival if left unbypassed (p less than .05); after revascularization and valve replacement, the 30 day mortality was 7.3% and the 8 year survival was 52%. Coronary disease etiologically related to ischemic mitral regurgitation identified a high-risk group of patients, with a 30 day mortality of 19.6% and an 8 year survival of 37% after the combined procedure. A multivariate logistic regression model was used to determine which preoperative and intraoperative variables predicted early and late outcome after combined mitral valve replacement and coronary revascularization. Predictors of early death were advanced age (greater than 60 years), New York Heart Association functional class (IV), an ischemic etiology of the mitral valve disease, and a depressed left ventricular ejection fraction (less than 55%). Predictors of late death were triple-vessel or left main coronary disease, increased left ventricular end-diastolic volume (greater than 120 ml/m2), and depressed left ventricular ejection fraction (less than 55%). These findings highlight the important etiologic and prognostic role of coronary artery disease in patients requiring mitral valve replacement.

Adolescent↗

Prognostic value of beta-thromboglobulin in patients with transient cerebral ischaemia.

Plasma levels of beta-thromboglobulin (BTG) and fibrinopeptide A (FPA), markers of platelet alpha-granule release and thrombin generation respectively, were measured in 27 subjects with transient cerebral ischaemic attacks (TIA), 43 age-matched controls, and 32 young controls. BTG and FPA were both higher in elderly controls than in young controls. BTG was higher in TIA subjects than in age-matched controls and higher in the 12 TIA subjects who had further vascular events in the next year than in those who had no further events. FPA was not significantly associated with TIA or with further events. These results support a relationship between platelet activation and TIA and suggest that BTG levels indicate a group at higher risk of further vascular events.

Adult↗

Regional distribution of pulmonary blood volume: an index of pulmonary capillary wedge pressure determined from blood pool scintigraphy.

Progressive redistribution of pulmonary blood flow to the lung apices occurs with increasing degrees of left ventricular failure, and correlates with increasing pulmonary capillary wedge pressure (PCWP). If similar changes in pulmonary blood volume (PBV) occur, then technetium-99m equilibrium blood pool scintigraphy, by assessing relative distribution of PBV, may allow prediction of PCWP. Therefore 30 patients being monitored with pulmonary artery balloon flotation catheters underwent imaging. PCWP was compared with the average radioactive count density arising from apical (A) and basal (B) regions of interest within the right lung, expressed as an A/B ratio. Correlation was strong for patients imaged erect, either posteriorly (r = 0.864, p = 0.001) or in the 45 degrees left anterior oblique position (r = 0.842, p = 0.001), and only slightly less impressive for patients imaged supine (r = 0.678, p = 0.001). Especially when imaging was performed with patients erect, an A/B ratio greater than unity identified with high sensitivity (100%) and specificity (83 to 88%) an abnormally elevated PCWP (greater than 12 mm Hg). Moreover, directional changes in the A/B ratio reflected concomitant changes in PCWP after intervention. Thus, analysis of lung A/B radioactive count ratios obtained by equilibrium blood pool scintigraphy may be used to evaluate PCWP.

Adult↗

Alcohol-mediated effects on the level of cytochrome P-450 and heme biosynthesis in cultured rat hepatocytes.

Interaction of alcohol and drugs in the liver appears to involve common microsomal oxidative enzymes which utilize cytochrome P-450. Since alcohol augments the toxicity of a variety of drugs, the regulation of the P-450 hemoprotein, a primary component in hepatic drug metabolizing systems, may play a vital role in this phenomenon. We utilize an adult rat liver culture system as a model to explore the action of levels of alcohol below that which is necessary to produce intoxication in humans. The addition of 16 mM ethanol (70 mg/dl) to these hepatocytes results in a 49.5% decrease in cytochrome P-450 activity after 24 h, and a 3-fold increase in the activity of delta-aminolevulinate synthase, the rate-limiting enzyme in hepatic heme biosynthesis. Furthermore, ethanol treatment also causes a transient decrease in the level of intracellular heme. However, the diminished level of total heme does not appear to act as a repressor for delta-aminolevulinate synthase, since it occurs after the initial stimulation of the enzyme by ethanol.

5-Aminolevulinate Synthetase↗

Skin lipids.

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Aging↗