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Biomedical subjects

G T Malcom

Publications and source records attributed to G T Malcom.

At least 55 records · Page 3Linked to original sources
PubMed1995

Apolipoprotein E and atherosclerosis in Alaska Natives.

Arterial, liver, and serum specimens were collected from 130 Alaska Natives who underwent forensic necropsy (mean age, 36.9 years; age range, 9-85 years; 38 females and 92 males). Based upon the observed frequencies of the six common apo E genotypes, the estimates of the relative frequencies of the corresponding alleles in the population are 0.020 +/- 0.009 for E2, 0.787 +/- 0.026 for E3 and 0.193 +/- 0.025 for E4. Analysis showed significant differences, by apo E genotype, in the extent of total surface lesion involvement in both the right and left coronary arteries. In all but the abdominal aorta, the pattern of lesion involvement by genotype is consistent with a decrease in lesions for genotypes with the E2 allele and an increase in lesions for the genotypes with the E4 allele, relative to the E3 homozygotes. After adjustment for low + very low density lipoprotein cholesterol (LDL + VLDL-C), the differences fell below statistically significant levels. Analysis by genotype of total serum cholesterol, high density lipoprotein cholesterol (HDL-C) and LDL + VLDL-C showed no statistically significant differences in analyte levels among genotypes. However, evidence is seen of a pattern in which total cholesterol and VLDL + LDL-C is less in genotypes with the E2 allele and greater in those with the E4 allele. We conclude that there does appear to be an effect by apo E genotype upon extent of atherosclerosis in the coronary arteries of Alaska Natives and this effect is likely due to the previously reported effect of apo E polymorphisms on serum cholesterol, particularly LDL + VLDL-C.

Adolescent↗
PubMed1995

Environmental and genetic risk factors in early human atherogenesis: lessons from the PDAY study. Pathobiological Determinants of Atherosclerosis in Youth.

A multi-institutional study 'Pathobiological Determinants of Atherosclerosis in Youth' (PDAY) was initiated to document the natural history of atherosclerosis, its relationship to risk factors, and pathobiology of lesion development in young subjects. Pathology laboratories in nine centers collected arteries and tissues from over 2000 persons from 15 through 34 years of age whose deaths were attributed to homicides, accidents, or suicides. Arteries were evaluated for lesions, and risk factors were analyzed in a central laboratory. Post-mortem risk factors included serum lipoproteins, serum thiocyanate (smoking), glycohemoglobin (diabetes), thickness of panniculus adiposus (obesity), small renal artery changes (hypertension) and apoprotein isoforms. This study documents the development of atherosclerosis at an early age. It also shows that the recognized risk factors for coronary heart disease are associated with lesion development in the arteries of these young subjects. The PDAY study has a counterpart in Japan where the development of atherosclerosis has been studied in young subjects. This Japanese study, in a population in which coronary heart disease has not yet become a major epidemic, has findings quite similar to the findings from the PDAY study. Studies of atherosclerosis in both Japan and the USA provide strong justification for reducing risk factors in young persons.

Arteriosclerosis↗
PubMed1995

Relation of glycohemoglobin and adiposity to atherosclerosis in youth. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group.

In a cooperative multicenter study (Pathobiological Determinants of Atherosclerosis in Youth, PDAY) of 1532 young persons 15 through 34 years of age who died of external causes and were autopsied in medical examiners' laboratories, we quantified atherosclerosis of the aorta and the right coronary artery. We analyzed postmortem blood cells for glycohemoglobin and postmortem serum for lipoprotein cholesterol and thiocyanate (as an indicator for smoking). We measured the thickness of the panniculus adiposus and the body mass index (weight per height squared) as indicators of adiposity. Glycohemoglobin levels exceeding 8% were associated with substantially more extensive fatty streaks and raised lesions in the right coronary artery in persons more than 25 years of age and with more extensive raised lesions in the aorta in persons more than 30 years of age. Both thickness of the panniculus adiposus and body mass index were associated with more extensive fatty streaks and raised lesions in the right coronary artery. The associations of atherosclerotic lesions with glycohemoglobin and adiposity were not explained by a less favorable lipoprotein profile or smoking. The results show that atherosclerosis in young adults is associated with the prediabetic or early diabetic state, as indicated by elevated glycohemoglobin levels, and with obesity.

Adipose Tissue↗
PubMed1995

Prominence of coronary arterial wall lipids in human heart allografts. Implications for pathogenesis of allograft arteriopathy.

Transplant arteriopathy is a major late complication in human heart allograft recipients and the pathogenesis of such arteriopathy remains uncertain. The degree to which lipids and atheromata are involved in the arteriopathic lesions remains unsettled, and there is uncertainty regarding the significance of insudation or retention of lipids within the coronary artery walls of transplanted hearts. On current immunosuppressive regimens, most patients experience an increased serum total cholesterol and low-density lipoprotein cholesterol after transplant. Elevation of these blood lipids has an undetermined relationship to arteriopathy. We carried out morphological, morphometric, immunohistochemical, ultrastructural, and biochemical studies of particular coronary artery segments from 23 unselected explant or autopsy allografts and donor age-matched native coronary controls. Patients died of cardiac and non-cardiac reasons over a period of 4 to 1610 days after transplant. Atheromata were frequent, and diffuse intra- and extra-cellular accumulation of lipids in both intimal and medial walls was documented by oil red O positivity, immunohistochemical staining (muscle-specific alpha-actin), transmission and scanning electron microscopy, and biochemical analysis. Mean total cholesterol, esterified cholesterol, free cholesterol, and phospholipid content (microgram/cm2 intimal surface area) and concentration (microgram/mg dry defatted weight) in arteriopathic coronaries were > 10-fold higher than in comparable native coronary segments. Extent of lipids in the arterial walls was highly correlated with digitized percent luminal narrowing, mean daily and cumulative cyclosporin dose, and mean cumulative prednisone dose. Our data suggests strongly that lipid accumulation is an important early and persistent phenomenon in the development of transplant arteriopathy.

Adolescent↗
PubMed1994

Ascorbic acid, Helicobacter pylori and Lewis phenotype among blacks and whites in New Orleans.

Gastric juice ascorbic acid concentrations were examined in black and white patients. Significantly lower concentrations were found in blacks, in the absence of a significant difference in the plasma concentration of vitamin C between races. Blacks had higher prevalence of Helicobacter pylori infection, higher gastric pH, more severe acute and chronic inflammation of the gastric mucosa and higher frequency of Lewis (a-b-) phenotype. Although most of these factors have been related to low ascorbic acid levels in gastric juice, none of them could account entirely for the difference between races either individually or after joint consideration. These observations may help to explain the high incidence of gastric carcinoma among the black population in southern Louisiana.

Ascorbic Acid↗
PubMed1994

Helicobacter pylori-associated gastritis and the ascorbic acid concentration in gastric juice.

Patients infected with Helicobacter pylori have abnormally low ascorbic acid concentration in gastric juice. Low vitamin C intake and Helicobacter pylori infection have been related to an increased risk of gastric carcinoma. This report examines the association between ascorbic acid and Helicobacter pylori in patients referred for upper gastrointestinal endoscopy. Elevated gastric pH and the damage to the gastric surface epithelium were inversely associated with the ascorbic acid concentration in gastric juice. We postulate that these two factors mediate the ascorbic acid-decreasing effect of Helicobacter pylori. Patients with nonpremalignant conditions (normal gastric histology, diffuse antral gastritis, or duodenal ulcer) had lower gastric pH, less damage to the gastric epithelium, and higher levels of ascorbic acid in gastric juice than patients with atrophic gastritis, intestinal metaplasia, or dysplasia.

Adolescent↗
PubMed1994

Long-term induction and regression of diet-induced atherosclerotic lesions in rhesus monkeys. II. Morphometric evaluation of lesions by light microscopy in coronary and carotid arteries.

Atherosclerotic lesions were induced in rhesus monkeys (Macaca mulatta) by feeding them a high-saturated fatty acid and high-cholesterol diet. After 5.4 years the extent of lesions in three major coronary arteries and the right carotid artery was evaluated morphometrically by light microscopy in one group of animals (group P). The remaining animals were switched to a low-cholesterol diet that remained high in saturated fatty acids and provided the same percentage of total calories as did the atherogenic diet. Lesion regression was then evaluated in one group of monkeys 1.9 years (group R4) and in another group of monkeys 3.7 years (group R5) after withdrawal of cholesterol alone from the diet. In group P, the mean intimal thickness varied between 26 and 47 microns, maximum intimal thickness between 70 and 92 microns, and luminal reduction between 9% and 12% in the three major coronary arteries. Luminal reduction varied between 1% and 11% in right carotid artery segments. After 1.9 years of consuming the basal diet, group R4 animals were no different from group P animals with respect to morphometric measures. Total intimal and medial areas of the left anterior descending (LAD) coronary artery in groups P and R4 were also similar. In contrast, after 3.7 years of consuming the basal diet, group R5 animals showed consistently although not statistically significantly lower values than those in group P for the morphometric measures in coronary arteries and total intimal area in the LAD. Similar results were obtained for the common carotid and external carotid arteries. Thus, our study shows that long-term diet-induced lesions in coronary arteries and in common and external segments of the right carotid artery regressed only when the animals were fed the basal diet for 3.7 years. We conclude that atherosclerotic lesions induced in coronary and carotid arteries can regress toward normal to a certain extent, but they require a longer time for regression than do other arterial segments. These findings support the results of clinical trials in human subjects.

Animals↗
PubMed1994

Long-term induction and regression of diet-induced atherosclerotic lesions in rhesus monkeys. I. Morphological and chemical evidence for regression of lesions in the aorta and carotid and peripheral arteries.

Atherosclerotic lesions were induced in rhesus monkeys by feeding a high-saturated fatty acid and high-cholesterol diet. After 5.4 years the extent of fatty streaks and raised lesions was evaluated in one group of animals (group P) by visual estimation in 10 arterial segments and chemically in four arterial segments. The remaining animals were switched to a basal regression diet low in cholesterol but high in saturated fatty acids for up to 3.7 years. Regression of lesions was evaluated in one group for 1.9 years (group R4) and in another for 3.7 years (group R5) after deleting cholesterol from the diet. The atherogenic diet increased serum cholesterol levels in all animals from a mean of 150 mg/dL to a mean of about 430 mg/dL. The atherogenic diet produced lesions in group P in all arterial segments (involving up to 50% of the arterial intimal surface) and increased cholesterol content in four arterial segments (varying between 443 and 506 micrograms/cm2). Switching to the basal regression diet decreased serum cholesterol levels to normal after 12 to 18 weeks. The switch to the basal diet significantly decreased the extent of fatty streaks in most arterial segments in both groups. Although differences in the mean extent of raised lesions among groups were not statistically significant, 7 of 10 arterial segments in group R4 and 9 of 10 segments in group R5 showed a lesser extent of raised lesions than in group P. Cholesterol content was lower (P < .05) in all four arterial segments in group R5 than in group P.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Nephrosclerosis, glycohemoglobin, cholesterol, and smoking in subjects dying of coronary heart disease.

Subjects dying of coronary heart disease (CHD) were compared with subjects in a control (basal) group in two series of forensic autopsies. Serum cholesterol assessed in postmortem heart blood was significantly greater in the CHD than in the basal group. CHD subjects were smokers more often than basal subjects, as determined from postmortem serum thiocyanate levels, but the statistical significance is ambiguous (P < 0.06). After exclusion of overt diabetics, a stepwise increase in the percentage of subjects with CHD was observed throughout the normal range for glycohemoglobin. Fibroplasia of small renal arteries, the most reliable postmortem proxy for hypertension, did not differ between CHD and basal groups. These results suggest that young (mean age 49.2 yr) black and white men and women classified from autopsy findings as having CHD as cause of death are often not hypertensive, but instead tend to be hyperlipidemic and glucose intolerant. A surprising result was that arteriolar hyalinization and arterial fibroplasia of the renal cortex often failed to parallel each other between groups of subjects. This was true in comparisons between black and white, male and female, blood cholesterol and glycohemoglobin groupings, and between CHD and basal subjects. This outcome suggests that hyalinization of renal arterioles is an especially reliable marker for CHD and that this association may not be mediated entirely through high blood pressure.

Adult↗
PubMed1994

Vitamin C concentration in gastric juice before and after anti-Helicobacter pylori treatment.

OBJECTIVES: To investigate the change of vitamin C concentration (ascorbic and dehydroascorbic acid) in gastric juice after anti-Helicobacter pylori treatment, and to relate any observed change to gastric pH, inflammatory compromise of the gastric mucosa, plasma vitamin C concentration, and smoking habits. METHODS: Plasma and gastric juice vitamin C, fasting gastric juice pH, gastric histology, and smoking status were studied in 70 patients with H. pylori-associated gastritis before and after therapy. RESULTS: Gastric juice ascorbic acid increased significantly after H. pylori clearance. For the most part, this change was confined to patients who experienced reduction of gastric pH. It was also related to improvement of the compromise of the gastric epithelium, reduction of the proportion of vitamin C composed by dehydroascorbic acid, and increase of the gastric juice/plasma vitamin C concentration gradient. Smokers had lower vitamin C concentrations in plasma and gastric juice before and after H. pylori clearance than nonsmokers. CONCLUSIONS: The findings are consistent with a causal association between H. pylori infection and low ascorbic acid levels in gastric juice, and support two mechanisms for this association: increased oxidation and a decreased secretion of ascorbic acid.

Amoxicillin↗
PubMed1993

Atherosclerosis in young white males: arterial collagen and cholesterol.

As part of a multicenter study on atherosclerosis, we examined defined segments of thoracic and abdominal aortas from 118 white males, age 15-34 years, who died from external causes. One half of each aorta specimen was graded for lesions. Intima-media preparations were assayed for collagen and cholesterol in two standardized regions (dorsal and ventral) derived from the alternate half of each segment. Even though the mean extent of intimal surface involvement with raised lesions remained minimal (0-6%), the data revealed a remarkable transition in vessel wall chemistry over this time span. For example, the amount of collagen per unit surface area increases with age in all vessel segments except the ventral domain of the thoracic aorta. The amount of collagen as a percent of total vessel protein rises with age only in the ventral and dorsal regions of the abdominal aorta. Free and esterified cholesterol levels per unit surface area increase with age in all vessel segments. There is a significant correlation between collagen and esterified cholesterol per unit surface area in all vessel regions with the exception of the abdominal ventral segment. In the latter segment increases in collagen per unit surface area occur without a corresponding increase in cholesterol level suggesting that connective tissue proliferation may actually precede lipid deposition in the genesis of atherosclerosis. Esterified cholesterol is present at higher levels in the dorsal domains of the thoracic and abdominal aortas than in the ventral domains. These findings provide chemical data confirming that the dorsal domains is the most lesion-prone region of these vessel segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Cocaine: an independent risk factor for aortic sudanophilia. A preliminary report.

Several recent autopsy reports indicate an increased prevalence of coronary atherosclerosis in ischemic heart disease temporally associated with cocaine abuse. The objective of this study was to conduct a retrospective analysis of sudanophilic lesions in young asymptomatic individuals who abused cocaine. Twenty-six cases (15-34-year-old black males) were examined from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. Sixteen subjects (mean age 25 +/- 1 years) had a positive toxicologic screen for cocaine and/or its major metabolites at autopsy and were confirmed habitual cocaine abusers. The remaining 10 cases (mean age 24 +/- 2 years) were subjects with a negative toxicologic screen at autopsy and no history of illicit drug abuse. Post-mortem blood was collected for lipoprotein analysis and determination of smoking status. The aorta and right coronary arteries were stained with Sudan IV and the degree and extent of sudanophilia was quantitated by image analysis. Multiple linear regression analysis of cocaine, age, smoking status, VLDL+LDL-C/HDL-C ratio and HDL-C as predictor variables of percentage intimal surface involvement, revealed an association between cocaine abuse and the extent of sudanophilia in both the thoracic and abdominal aorta (P = 0.002 and 0.049, respectively). Analysis of risk factors or of cocaine abuse as predictors of sudanophilia did not achieve statistical significance in the right coronary artery. These preliminary results suggest that habitual use of cocaine, through unknown mechanism(s), increases aortic sudanophilia independent of traditional risk factors.

Adolescent↗
PubMed1992

Early lesions of atherosclerosis in childhood and youth: natural history and risk factors.

This paper traces the development of knowledge concerning early lesions of atherosclerosis and the relationship to risk factors in children, youth, and young adults. Autopsy studies have shown that atherosclerosis begins in childhood with the appearance of aortic fatty streaks. Aortic fatty streaks of some degree are present in practically all individuals from every human population. Coronary fatty streaks begin to form in adolescence. Most persons 20-29 years of age have coronary fatty streaks of some degree, regardless of sex, race, or national origin. While fatty streaking is clinically harmless and potentially reversible, progression to fibrous plaques and more advanced lesions often leads to a critical stage of atherosclerosis in which clinical disease develops. Development of fibrous plaques begins in the 20s. The most recent studies of atherosclerosis in youth and young adults provide additional details to establish the relationship of these lesions to serum lipids and lipoproteins and other identified risk factors for atherosclerosis and coronary heart disease in adults. One report shows that microscopic counterparts of fatty streaks occur in the left anterior descending coronary artery in the majority of children 10-14 years of age. Over 5% have more advanced microscopic lesions at this age. Autopsy studies of youth have shown that serum total cholesterol and low-density lipoprotein cholesterol levels are strongly related to aortic fatty streaks and the very-low-density lipoprotein cholesterol levels are positively correlated to coronary artery fatty streaks. Finally, a definitive report indicates that serum lipoprotein cholesterol concentrations and smoking are important determinants of the early stages of atherosclerosis in adolescents and young adults.

Aging↗
PubMed1992

Renal microvascular features of hypertension in Japan, Guatemala, and the United States.

The finding of benign arteriolar nephrosclerosis at autopsy usually implies the prior existence of essential hypertension. It was found in this study that minor degrees of incipient nephrosclerosis in young people can be shown to correlate with seemingly trivial blood pressure elevations. In this study, autopsy tissues were used to assess the magnitude of early nephrosclerosis in five population groupings. A comparison of males in Tokyo, Japan, Guatemala, and New Orleans, La (blacks and whites); and females in Tokyo revealed significant differences among these populations. Blacks exceeded whites in New Orleans in the magnitude of incipient nephrosclerosis in all 10-year age groups from 15 through 24 years to 45 through 54 years. Guatemalan males were, on average, less affected than New Orleans whites in all age groups. The data for all males (age range, 15 through 54 years) in Tokyo revealed little difference in nephrosclerosis from those in New Orleans whites. Blood pressure data were obtained from reports of cross-sectional surveys in these five populations. Blood pressure in males varied across age x race subgroups in close parallel with nephrosclerosis (r = .90), implying that variation in blood pressure among groups of subjects is strongly nephrosclerosis linked, even at very young ages; findings for Tokyo females were aberrant in this correlation. The results suggest that the lifelong progression toward the hypertensive state begins in childhood, and that these beginnings are measurably in the population averages of both nephrosclerosis and blood pressure elevations. Moreover, population differences in these two commensurate measures of the early precursors of hypertension were found to be well established by the ages of 15 through 24 years and were sustained at least into the ages of 45 through 54 years. The years of adolescence are here brought under suspicion of special importance in setting the lifelong course toward the hypertensive state.

Adolescent↗
PubMed1990

Variations with age and serum cholesterol level in the topographic distribution of macroscopic aortic atherosclerotic lesions as assessed by image analysis methods.

The topographic distribution of macroscopic atherosclerotic lesions in the aorta was studied by image analysis of aortas taken at autopsy from 155 males aged 10 to 54 yr. In both the thoracic and abdominal aorta, fatty streaks (FS) appear before raised lesions (RL) affecting preferential areas located longitudinally along the intercostal ostia, at the aorta bifurcation, and surrounding the points of origin of branches of the abdominal aorta. Later RL appear in the same areas of the aortic intima affected by FS at younger ages. As for the effect of serum total cholesterol (TC) in the progression of atherosclerosis, the prevalent involvement areas by FS and RL were similarly distributed as indicated by our analyses. However, areas showing frequent occurrence of FS and RL in each aortic segment were distributed more extensively at identical areas in the higher serum TC groups than in the lower TC level group. Thus, it can be concluded that FS are the precursor lesions of RL in the aorta and that the serum TC promotes the progression of atherosclerosis.

Adolescent↗
PubMed1989

Fatty acid composition of adipose tissue in humans: differences between subcutaneous sites.

We compared the fatty acid composition of adipose tissue from three different sites, one deep-seated site (perirenal) and two subcutaneous sites (abdominal and buttock), in 143 autopsied adult humans aged 24-61 y. The proportion of saturated fatty acids was highest in the perirenal adipose tissue and lowest in buttock adipose tissue. The proportions of monounsaturated fatty acids in the three sites were in the reverse order. Linoleic and linolenic acids were similar in the three adipose-tissue sites, an important finding for those concerned about the essential fatty acids, which are solely derived from the diet. The results clearly show that the fatty acid composition of the two subcutaneous fat depots differ significantly. We conclude that abdominal fat is more saturated than buttock fat.

Abdomen↗
PubMed1988

Lipoproteins and apolipoproteins in postmortem serum.

In order to correlate lipoprotein and apolipoprotein profiles with atherosclerotic lesions at autopsy, the feasibility of using postmortem serum in these determinations was evaluated. Lipoprotein and apolipoprotein profiles in dogs and monkeys were compared in pre- and postmortem serum samples, and it was found that, up to 24 h postmortem, no appreciable differences were observed in apolipoprotein A-I, B, E, and A-IV serum concentration when compared to premortem values. Electrophoretic mobilities and apolipoprotein gradient gel immunoblotting also revealed no differences in apolipoprotein size distribution. We conclude that postmortem sampling up to 24 h can be used effectively to approximate premortem lipoprotein and apolipoprotein profiles provided that careful sampling techniques are observed.

Animals↗