Fairfield Goodale

Chemico-anatomic studies in the geographic pathology of arteriosclerosis: Comparison of adipose tissue fatty acids and plasma lipids in diabetics from east africa and the united states with different frequencies of myocardial infarction

Abstract Three groups of patients with diabetes mellitus examined at autopsy, a North American white group, a North American Negro group and an East African group, were found to have a high, intermediate and low frequency (approximately 50, 25 and 0 per cent, respectively) of myocardial infarcts. It appears that while diabetes mellitus predisposed to the occurrence of myocardial infarction in the North American white diabetics, factors other than diabetes per se were contributory. Because of the suggested relationship of lipids to myocardial infarcts, the fatty acids of adipose tissue and plasma lipids were measured in age- and sex-matched groups of diabetic patients from the same hospitals from which the autopsy data were drawn. This was done to learn if lipid values were different in these three diabetic groups with a disparate occurrence of myocardial infarcts. Despite the wide difference in the frequency of myocardial infarcts in North American whites and Negroes, only small differences were found in the adipose tissue fatty acids of the two groups, and no significant difference was present in the plasma cholesterol levels. If plasma cholesterol serves as even a rough indication of the possible occurrence of myocardial infarction in a group, one would expect the frequency of myocardial infarcts confirmed at autopsy to increase in Negro diabetics in the years ahead. The East African diabetic group showed, in addition to minor adipose tissue fatty acid differences, a considerably lower adipose tissue oleic acid level than the North American white or Negro diabetic groups. A similar low adipose tissue oleic acid level has been noted in Guatemalan nondiabetics, who also have a low incidence of myocardial infarcts as compared to North American nondiabetics. Whether or not this finding of a low adipose tissue oleic acid level in groups with a low incidence of myocardial infarction is biologically significant must await further work. The plasma cholesterol of the East African group was significantly lower than that of either North American group, possibly because of their lower quantitative dietary fat intake. It is possible that the low adipose tissue oleic acid value of the East African group is the result of a different qualitative fatty acid intake, but dietary studies so far carried out in Uganda are not adequate enough to warrant this conclusion. This study shows that three groups of diabetics with differing frequencies of myocardial infarcts by autopsy evidence have, as well as differences in adipose tissue fatty acids and plasma lipids, many similarities, at least in the case of two groups, North American Negro and white diabetics. It will be of great interest in the case of East African diabetics, with their socioeconomic and dietary patterns possibly becoming more similar to the American groups, to see whether or not their lipid patterns and their occurrence rates of myocardial infarction will also change.

Chemico-anatomic studies in the geographic pathology of arteriosclerosis: A comparison of fatty acids of adipose tissue and of plasma lipids in nondiabetics and diabetics from Guatemala and the United States☆

Abstract Poor urban and rural Guatemalan nondiabetics have been reported previously to have less arteriosclerosis than comparable North Americans. In this study fatty acids of adipose tissue and plasma lipids were compared in age- and sex-matched subjects from these groups; adipose tissue fatty acids were measured because, in part, they reflect the dietary fatty intake. Because of the high occurrence of myocardial infarcts in diabetics, at least in North America, Guatemalan and North American diabetics were compared as separate groups. Of the six fatty acids measured and equated to 100%, the relative percentage of oleic acid was significantly lower and palmitoleic acid significantly higher in Guatemalan than in North American nondiabetics; of four plasma lipids measured, cholesterol and TEFA were significantly lower in the Guatemalan nondiabetic group. Comparison of Guatemalan and North American diabetics showed no significant difference in either plasma lipids or adipose tissue fatty acids, while Guatemalan diabetics showed higher plasma cholesterol and adipose tissue oleic acid values, and lower linoleic and palmitoleic adipose tissue values than Guatemalan nondiabetics. Such small differences in adipose tissue fatty acids occurring in groups in this study must be interpreted with caution but they suggest that the type of fatty acid consumed by nondiabetic poor urban and ural Guatemalans may be slightly different than that of comparable North Americans. The wide difference in arteriosclerosis between the two groups, however, is more likely explained by the reported great difference in the quantitative fat intake between Guatemalan and North American nondiabetics. The absence of differences in either plasma lipids or adipose tissue fatty acids between Guatemalan and North American diabetics suggests that the Guatemalan diabetic either has a different dietary fat intake than the nondiabetic Guatemalan or that he reacts differently to the same diet. Information regarding arteriosclerosis in Guatemalan diabetics is not as yet sufficient to warrant conclusions, but in view of the findings reported herein it will be of considerable interest to find out the degree of arteriosclerosis in this group.

Geographic pathology of arteriosclerosis: A study of the age of onset of significant coronary arteriosclerosis in adult Africans and New Yorkers☆

Abstract The purpose of this study was to compare the amount of coronary arteriosclerosis in West Africans, 20 years of age and over, with that of corresponding East Africans and New Yorkers; and to find the period in young adult life when significant differences in the amount of coronary arteriosclerosis actually began to appear between Africans and New Yorkers. We found that the amount of coronary arteriosclerosis and incidence of myocardial infarcts in West Africans was similar to that in East Africans and far less than that in New Yorkers. We also found that differences in amount of coronary arteriosclerosis between Africans (West and East) and New Yorkers were already apparent in the youngest age group that was studied (20–29). This suggests that the factors accounting for the differences are operative even before adulthood is reached and that studies of childhood and adolescent groups are warranted.

Geographic Pathology of Myocardial Infarction

Abstract Myocardial infarction is common in the United States and rare in certain parts of the Orient and Africa. Such geographic variations in occurrence rates of myocardial infarction could be due either to genetic factors or to environmental factors such as diet, climate and socioeconomic factors. If the genetic factor is the main factor responsible for the apparent geographic differences in the occurrence rates of myocardial infarction, the Orientals and Negroes who immigrated to the United States should maintain their low occurrence rates at least to some extent. On the other hand, if environmental factors are mainly responsible for variations, the occurrence rates of myocardial infarcts in those people should have changed considerably when they moved into an entirely different environment. To investigate the importance of genetic compared to environmental factors, we have analyzed all death certificates, autopsy data from 17 general hospitals and from coroners in San Francisco, and from 3 general hospitals in Los Angeles for the period 1956 to 1960. Detailed information was obtained on all Orientals, including Chinese, Japanese and Filipinos. All the autopsied Oriental cases were compared with age-sex matched cases from the white populations. Similar information was obtained from Japan, Korea, Uganda and Nigeria, and from Negro and white groups in New Orleans and Albany. The average length of residence of the Orientals in San Francisco and Los Angeles was approximately 30 years, and the occurrence rates of myocardial infarction in those Orientals were much higher in all age groups than in the Orientals in their home lands, and approached those of the whites. In the male 50 to 59 age group which included substantial numbers of cases for meaningful comparisons, the occurrence rates of myocardial infarction were similar in both racial groups. This suggests that environmental factors seem to play a major role among the Orientals in the etiology of myocardial infarction and coronary thrombosis, and the genetic factor plays a relatively minor role, if any. In the Uganda and Nigeria autopsy series, myocardial infarction was almost nonexistent. Negroes in the United States have lived in this country for many generations and the occurrence rates of myocardial infarction among them are significantly greater than among Negroes in Africa and approach the occurrence rates of whites. As with the Orientals, this suggests that environmental factors are more important in the etiology of myocardial infarction than genetic factors in Negroes in the United States. However, definitive conclusions cannot be drawn for many reasons including the fact that whites, Orientals and Negroes do not represent pure genetic strains since all three groups have immigrated to the United States only a few generations ago from diverse regions and have not remained as sharply defined races.

Geographic pathology of arteriosclerosis: A study of the “critical level” of dietary fat as related to myocardial infarction in Koreans☆

Abstract It is well established that people whose diet contains little fat (10% or less by calories) have low serum lipid levels and a very low incidence of myocardial infarction. By contrast, people whose diet contains much fat (40% or more), such as most Americans, have higher serum lipid levels and a relatively high occurrence rate of myocardial infarction. Whether or not the relationships between dietary fat and myocardial infarction is one of cause and effect, it seems probable that at some as yet-to-be determined critical level of dietary fat above 10%, infarcts begin to appear, possibly to increase in frequency in proportion to an increase in fat, or possibly to reach a point beyond which no further increase in frequency of infarcts occurs, regardless of diet. Although it is not difficult to find peoples at the dietary extremes, with diets containing less than 10% or more than 40% fat, it is difficult to establish clear-cut dietary groups that lie in between and from whom information as to a possible critical level of dietary fat might be obtained. Our studies in three socio-economic groups of Koreans have shown that dietary fat intake is 7% of calories in farmers, 13% in middle class and 17% in upper class people. Myocardial infarcts are practically nonexistent in lower economic classes but do occur in small numbers in higher economic classes suggesting the possibility that a “critical level” of dietary fat at or near 17% may exist beyond which myocardial infarcts become increasingly common. All the individuals studied were well nourished and in apparent good health. Although this study allows for tentative opinions or hypotheses regarding critical levels of fat, it is apparent that more information is needed before definitive conclusions are made. Among other things, we would like to have true cross sections of the population groups in which we are interested with selection based on census rolls; dietary histories checked for accuracy by sample “weigh-backs”; information regarding chemical content of foods based on actual analyses instead of on standard tables; autopsy data on status of coronary arteries on at least some of the subjects of this study. The implications of the information already obtained would appear to warrant further investigation along these lines.

Lack of Correlation Between Fatty Acid Patterns in Adipose Tissue and Amount of Coronary Arteriosclerosis

T HIS study is one of a seniesm -7 designed to explore the possible relationships between the anatomic manifestations of coronary arterial disease and lipid patterns of blood and tissue. This report deals specifically with a comparison between the amount of coronary arteriosclerosis (with or without myocardial infancts) and fatty acid patterns of adipose tissue (as determimied by vapor phase chromatography) in fifty-seven New Yorkers who were examined at autopsy. In subsequent reports similar comparisons will be made using persons from other geographic areas,

Chemico-anatomic studies of arteriosclerosis and thrombosis in diabetics: I. Coronary arterial wall thickness, thrombosis, and myocardial infarcts in autopsied North Americans

Abstract It is well established that myocardial infarcts are more common in diabetic than in nondiabetic North Americans. Since myocardial infarcts are usually the result of thromboses developing in arteriosclerotic coronary arteries, differences in number of infarcts between two groups are most likely the results of differences in blood clotting characteristics (hematologic factor) or in amount or quality of coronary arteriosclerosis (local factor) or both. Surprisingly little objective information is available as to the role of either factor in diabetics. To study the hematologic factor we first compared the number of thromboemboli in the venous and pulmonary circulation of autopsied diabetics and nondiabetic controls. Second, using a thrombelastograph, we compared the clot-lysis and recalcification times of 26 living diabetics with 26 nondiabetic controls. No significant differences were noted between the diabetic and nondiabetic patients in either the number of pulmonary or venous thromboemboli or in clot-lysis and recalcification times. To study the local factor of arteriosclerosis we made caliper measurements of coronary wall thickness as a basis for judging the amount of coronary arteriosclerosis and gross observations were made of multiple cross sections of coronary arteries in an attempt to evaluate qualitative features. The amount of coronary arteriosclerosis as judged in this way is greater in diabetics than in age-sex matched nondiabetics. Qualitative differences were not demonstrated. However, data obtained by matching not only by age and sex but also wall thickness suggest that differences in wall thicknesses do not account entirely for differences between diabetics and nondiabetics in occurrence rates of coronary occlusions and myocardial infarcts. It seems probable that some differences in either a qualitative factor of arteriosclerosis or in an unmeasured hematologic factor must also be present.

Geographic pathology of arteriosclerosis: A study of disease patterns in autopsied individuals from Kampala, Uganda; Ibadan, Nigeria; and Albany, New York☆

Abstract A study of disease patterns of autopsied individuals over 20 years of age from Kampala, Uganda; Ibadan, Nigeria; and Albany, New York has been carried out. One marked difference between the African and the New York autopsy series is the difference in age distribution. Any comparisons of prevalence of any disease must therefore be based on comparisons of specific age groups. Cirrhosis was more common among Africans in the age groups under 40 than in New Yorkers, but in those over 40 there were no important differences. Infectious diseases were common in all age groups, but in the New Yorkers they usually occurred as a complication whereas in the Africans they were more often the only important disease found at autopsy. Overt parasitic diseases (in contrast to simple infestation by parasites) were not as frequent among the Africans as is often supposed, accounting for less than 12% of all the diseases seen at autopsy. Parasitic infestation in Africans, however, is common, and we still do not know the long-term effects on the hosts response to other disease processes. Neoplasms were common in all groups. Thromboembolic diseases were much less common among the Africans in all age-groups than among the New Yorkers. The most striking difference was in the occurrence rate of myocardial infarction, which was almost nonexistent among Africans even in the older age groups and relatively common in New Yorkers. It seems unlikely from this study that differences between Africans and New Yorkers in underlying disease patterns of autopsied patients are sufficient to explain differences in amounts of coronary arteriosclerosis and its complications.

Diffuse coronary arteriosclerosis versus isolated plaques in the etiology of myocardial infarction

Abstract This study was designed to determine the relation of quantitatively measured coronary arteriosclerosis to the occurrence of occlusions and myocardial infarcts. By using mean thickness of the coronary wall measured by calipers as an indicator of coronary arteriosclerosis, a direct relation between mean thickness and the occurrence rate of myocardial infarct was demonstrated. This relation was largely independent of age and sex. Myocardial infarction in this study was principally the result of occlusive thrombosis forming in a coronary artery showing extensive arteriosclerosis. Myocardial infarction as a result of thrombosis occurring in isolated arteriosclerotic plaques was virtually nonexistent.

Chemical properties of leucocytic pyrogen. I. Partial purification of rabbit leucocytic pyrogen.

Abstract Rabbit leucocytes, if properly stimulated, will yield an endogenous or leucocytic pyrogen that is chemically and biologically distinct from exogenous pyrogens such as bacterial endotoxins. Just how the leucocytic pyrogen is produced is not yet known but the present study was undertaken in an effort to learn more of its chemical properties. Crude leucocytic pyrogen, obtained from sterile peritoneal exudates, was dialyzed against distilled water, freeze-dried, and applied first to a DEAE column to remove much of the protein, then to a phosphorylated cellulose column which adsorbed leucocytic pyrogen while allowing virtually all of the remaining protein to be eluted. The leucocytic pyrogen in turn was eluted by a stepwise increase in pH with a resulting thirty-fold increase in pyrogenic activity per gram of protein as compared with the crude pyrogen. This pyrogenic protein material is inactivated by 60°C for 5 minutes and by trypsin digestion. It is electrophoretically homogenous at pH 5.0 and 8.0 and yields at least nine amino acids on hydrolysis. The methods outlined above enable rabbit leucocytic pyrogen to be obtained in a relatively pure form so that further chemical characterization is now possible.