Artemis P. Simopoulos

Growth Characteristics in Patients with Bartter’s Syndrome

Studies on the growth and development of patients with Bartters syndrome indicate that severe growth retardation occurs during infancy and early childhood. Delayed adolescent growth spurt has occurred in all patients studied thus far who had manifested the syndrome during infancy. Normal stature is eventually attained. Mental development ranges from normal to brain damage and dysfunction; however, the majority of patients show some degree of mental retardation. The coexistence of Leighs encephalopathy with Bartters syndrome in one patient and the finding of severe motor and congnitive retardation with communicating hydrocephalus in another indicate that the prognosis of mental development in some cases of Bartters syndrome is guarded. Particular attention should be given to maintaining normal nutritional status in all patients, particularly during infancy and early childhood.

Neurodegenerative disorders and hyperaldosteronism.

Elevated plasma renin (3 patients) and aldosterone secretion rates (4 patients) have been found in patients with the syndrome of “ophthalmoplegia plus.” Autopsy in one of the patients revealed subacute necrotizing encephalopathy, hyperplasia of the juxtaglomerular apparatus, and nodular hyperplasia of the zona glomerulosa of the adrenal gland. Three of the patients had hypokalemia during the present admission and the fourth patient had hypokalemia in the past. Two of the patients also had hypomagnesemia. Spironolactone given to one patient corrected the hypokalemia but had no effect on the hypomagnesemia. It is suggested that hyperaldosteronism should be looked for in patients with the syndrome of “ophthalmoplegia plus”.

Omega-6/omega-3 fatty acid ratio and trans fatty acids in non-insulin-dependent diabetes mellitus.

Over the last 20 years, many studies and clinical investigations have been carried out on the metabolism of polyunsaturated fatty acids (PUFA) in general and omega-3 fatty acids in particular. Today, we know that omega-3 fatty acids are essential for normal growth and development and may play an important role in the prevention and treatment of coronary artery disease, hypertension, diabetes, arthritis, other inflammatory and autoimmune disorders, and cancer. Research has been carried out in animal models, tissue cultures, and human beings. The original observational studies have given way to controlled clinical trials. Great progress has taken place in our knowledge on the physiological and molecular mechanisms of the various fatty acids in health and disease. This paper discusses the evolutionary aspects of diet in terms of the balance of the omega-6 and omega-3 fatty acid intake; the increase in trans fatty acids as a result of industrialization, agribusiness, and food processing; and their effects on non-insulin-dependent diabetes mellitus (NIDDM).

Characteristics of Obesity: An Overview

Obesity is considered to be a major nutritional disorder in the U.S. and in many parts of the industrialized world. The physiology of the obese and their propensity for chronic disease has been of growing interest over the past few years, and an extensive literature has begun to accumulate. Obesity is a heterogeneous disorder. When viewed in the broadest sense, it has been considered a disorder of energy balance. The development of obesity in humans is of complex etiology, involving genetic and environmental components that affect regulatory and metabolic events. The prevalence of overweight and obesity in a population depends on the particular reference or standard of desirable weight selected for use. A trend toward increasing height and weight has been evident among adults for several centuries, and among children as early as the 7th year of life in developed countries. Overweight persons are at increased risk for coronary artery disease, high blood pressure, diabetes mellitus, and cancer. The degree of overweight that carries additional risk without affecting mortality needs to be defined. Overweight most likely contributes in varying degrees to morbidity in different societies, because the risk for most common chronic diseases is multifactorial. In defining overweight and obesity, morbidity, in addition to mortality, ought to be taken into consideration. The multidisciplinary approach to the study of obesity--borrowing concepts and techniques from endocrinology, neurobiology, genetics, and nutrition--should yield new insights into how environmental factors such as diet and physical expenditure interact to influence energy metabolism and body composition.

Energy imbalance and cancer of the breast, colon and prostate

In Western societies, energy imbalance is characterized by obesity and sedentary life styles and is associated with increased morbidity and mortality from all causes of cancer, including cancer of the breast, colon and prostate. The interrelationships of energy intake and energy retention, to energy expenditure and physical fitness need further investigation from the physiologic, metabolic, endocrine and genetic aspects of cancer development, since obesity, energy expenditure and cancer have a familial predisposition. The effects of exercise on estrogen and prostaglandin metabolism and their relationship to cancer development require further investigation. Although the exact amount and intensity of exercise that confers benefit is not known, physical activity and physical fitness are inversely associated with all-cause mortality, including cancer. These findings have important public health implications, because about one-third of persons in industrialized societies are quite sedentary, and the prevalence of low physical fitness is quite high. The balance between total energy intake and expenditure may be more important in cancer development than the intake of any given dietary component or energy source. Exercise increases prostacyclin and decreases the aggregation of platelets and possibly decreases the platelet derived growth factors (PDGF). One could speculate that exercise may in turn decrease the probability of developing colon cancer in those who are predisposed to it, since the SIS oncogene is in fact a variant of PDGF.

Subacute necrotizing encephalomyelopathy with vacuolated cells in the bone marrow

m Subacute necrotizing encephalomyelopathy (SNE) in children has many neuropathologic similarities to Wernicke’s encephalopathy in adults.’ The latter has been described in adults who have been deprived of an adequate diet by alcoholism or by gastrointestinal, febrile or debilitating diseases.’ -’ The occurrence of a similar disease process in children has been reported from Japan as “breast milk intoxication,”6 since it occurred in infants who were breast fed without supplementary feeding. It has also been found in children with lactic acidosis,’ in those with an inborn error of gluconeogenesis,* and in perfectly healthy infants and children who expired within two weeks to a few months of a mild upper respiratory i n f e ~ t i o n . ~ The fact that the same pathologic picture is found in all these patients does not necessarily point to a single etiology. Leighg has described the findings in an eight month old infant, who appeared entirely normal until six weeks before death, and noted the striking similarity between the histologic changes in brain tissue in his case and those found in Wernicke’s syndrome. Wernicke’s encephalopathy is generally thought to result from deficiency of a vitamin, presumably thiamine, while SNE has been thought to result from a familial, presumably genetic, metabolic defect. Because of the similarity in the pathologic processes in SNE and Wernicke’s encephalopathy, it is probable that both result from a common metabolic abnormality, although the ultimate cause is probably genetic in the former and nutritional in the latter. It is this relationship to Wernicke’s encephalopathy that has led to studies in thiamine metabolism in children with SNE. Cooper and associates’ i1 found thiamine triphosphate absent from the brains of patients who died with SNE; it was present in the brains from four control subjects. They found also a factor in the blood and urine of patients with SNE that inhibits the synthesis of thiamine triphosphate by brain tissue. The inhibitor appears t o be a glycoprotein. This paper describes metabolic, endocrinologic and hematologic abnormalities in a girl with SNE whose urine contained Cooper’s factor. Furthermore, anemia and vacuolation of bone marrow cells were found, as have been observed in alcoholics, thus adding two more pathologic processes common to Wernicke’s encephalopathy and SNE. At autopsy, vacuolation and demyelination of the white matter and

Overnutrition facilitates the development of experimental tumors

SummaryThe summarising panel concluded that, inad lib.-fed and other rats with genetically-determined or carcinogen-induced tumors with numerous localisations, overnutrition does induce tumors or permit then to grow. Epidemiological studies suggest similar mechanisms in man, but with much fewer tumor localisations, and with much less certainty. The role played by saturated and unsaturated fat, the effect of fatty tissues on hormone metabolism, and the effect of soluble and insoluble dietary fiber can not yet be defined. Among areas for further study, epidemiology of genetic diseases becoming manifest during later life was mentioned, as was the need for improved dietary recall (‘bean-counting’) methods, the need to study interaction of nutrients, the need to study the metabolic effects of energy expenditure and physical exercise, and the need for risk assessment in the field of diet and cancer as compared to other fields. It was also agreed that observations disagreeing with the hypotheses advanced should be examined, for instance, the low cancer frequency both in beef-consuming Mormons and in vegetarian Seventh Day Adventists, or the high cancer frequency in Maoris consuming little fat.