Robert E. Hodges

Pantothenic Acid Deficiency in Man

For the past seven years we have been studying the role of pantothenic acid in human nutrition and metabolism. This is part of a larger study aimed at defining more clearly the principles of clinical assessment of an essential nutrient in human subjects. It has been assumed that pantothenic acid is necessary for the maintenance of health in man but its abundance in natural foods was such that spontaneous deficiency either did not occur or had not been recognized. Presumably even in very poor diets, other vitamin deficiencies were limiting factors before pantothenic acid deficiency caused definite trouble. At least two avenues of investigation lay before us: to prepare and feed a diet devoid of pantothenic acid, or to give analogs of the vitamin and test possible antivitamin effects. Experiences in devising a deficient diet and testing several antagonists have been described (1-5). Clinical and laboratory abnormalities appeared in healthy young men given an artificial diet, partly synthetic and partly of purified ingredients, the whole virtually devoid of pantothenic acid. The mixture had to be given by stomach tube. The most extensive abnormalities occurred when in addition to the deficient diet large amounts of omega-methyl pantothenic acid were given. By the time we began the work and subsequently, other investigators described in detail the nature of pantothenic acid deficiency in several laboratory animals (6-10). In growing animals, the earliest evidence of pantothenic acid deficiency is a decline in the rate of growth (11, 12). Strange variations occur in the color of the fur. Exudative lesions appear around the eyes and nose. They are pigmented and contain porphyrin (13). In swine a peculiar neuropathy causes

Sjögren's Syndrome in Scurvy

Abstract Five men were deprived of ascorbic acid until they became scorbutic. During deficiency of ascorbic acid, Sjogrens syndrome became apparent in two subjects. In these two and one other keratoconjunctivitis sicca developed. All five had one or more manifestations of the sicca syndrome, including keratoconjunctivitis sicca, enlargement of the salivary glands, xerostomia, dry skin, excessive hair loss, dental decay and recurrent breakdown of dental restorations. Sjogrens syndrome or component features of the syndrome developed when the men had obvious clinical signs of scurvy. Evidence of deficiency other than of ascorbic acid was absent. During repletion with ascorbic acid, as plasma levels of ascorbic acid rose and the size of the body pool of the vitamin increased, the signs of scurvy and of Sjogrens syndrome disappeared. An association between scurvy and Sjogrens syndrome therefore seems apparent.

Pantothenic acid deficiency induced in human subjects.

Summary 1. An abnormal metabolic state has been induced in 4 human volunteers through combined use of a diet deficient in pantothenic acid and a metabolic antagonist, (omega-methyl pantothenic acid). 2. This abnormal state was accompanied by clinical and biochemical abnormalities suggesting adrenal cortical insufficiency, and by a peripheral neuropathy. 3. Administration of pantothenic acid alone did not immediately reverse the abnormal state. A good diet of natural foods and multiple vitamins resulted in rapid complete recovery.

Autonomic reflexes and vascular reactivity in experimental scurvy in man

Ascorbic acid is a required cofactor in the conversion of dopamine to norepinephrine in vitro, and the deficiency of this vitamin in guinea pigs is associated with degeneration of autonomic ganglion cells and with cardiac supersensitivity to norepinephrine. Because of these findings, we tested the hypothesis that ascorbic acid deficiency in man alters autonomic cardiovascular reflexes and vasomotor responses to adrenergic stimuli. We studied five normal volunteers who had been deprived of ascorbic acid for a period of 3 months; they had developed symptoms and signs of scurvy and their plasma levels of ascorbic acid averaged 0.178 +/-SE 0.07 mg/100 ml. We repeated the studies after giving the subjects vitamin C for a period of 4 months; they had become asymptomatic and their plasma ascorbic acid had increased to an average of 1.68 +/-0.151 mg/100 ml. Blood flow to the left forearm (plethysmograph), arterial and central venous pressures, and heart rate were measured before and after exposure of the lower half of the body to subatmospheric levels of pressure and before and after intravenous and intra-arterial (left brachial artery) infusions of norepinephrine and tyramine. Average values of blood flow (7.9 +/-1.4 ml/min per 100 ml), arterial pressure (91.2 +/-4.6 mm Hg), heart rate (68 +/-4.4 beats/min), central venous pressure (6.1 +/-1.1 mm Hg), and plasma catecholamines (0.68 +/-0.20 mug/liter) obtained during ascorbic acid deficiency were not altered significantly after correction of the deficiency. Vasoconstrictor responses to intra-arterial norepinephrine and tyramine were augmented after vitamin repletion. During ascorbic acid deficiency, four subjects had reduced responsiveness of resistance vessels of the forearm to lower body negative pressure as compared to the responsiveness observed after vitamin repletion. Reflex tachycardia during lower body negative pressure and reflex bradycardia during the pressor responses to intravenous tyramine and norepinephrine were similar during the two studies. The results suggest that the decreased vascular responsiveness to intra-arterial norepinephrine and tyramine and to lower body negative pressure during ascorbic acid deficiency is caused by a defect in the ability of resistance vessels to constrict in response to adrenergic stimuli. Ascorbic acid deficiency in man does not interrupt autonomic reflexes and does not appear to cause significant depletion of endogenous norepinephrine.

Effect of anti-rheumatic drugs on synovial membrane permeability.

Summary and Conclusions (1) Permeability studies were performed in rabbits and in patients with rheumatoid arthritis using the method of Seifter which employs injection of PSP into the joint, and recovery of the dye from the urine. (2) Cortisone and ACTH were given to rabbits and patients to determine any effect upon synovial membrane permeability and to detect any anti-hyaluronidase effect in rabbits. (3) Our results fail to demonstrate significant alterations of synovial permeability in rabbits or humans following parenteral therapy with ACTH or Cortisone. There was no evidence of hyaluronidase inhibition in rabbits. (4) Cortisone injected into the joints of rabbits impaired the absorption of PSP. A mechanical blocking effect was not excluded. (5) The injection of PSP into joints is not necessarily a valid measurement of permeability of synovial membranes to physiologic substances.

Atrophic beriberi: A complication of jejunoileal bypass surgery for morbid obesity

Abstract Four months after jejunoileal bypass surgery for morbid obesity, a 37 year black woman who ate a grossly inadequate diet was hospitalized complaining of diffuse abdominal pain, complete loss of appetite, burning feet, generalized weakness and inability to walk without assistance; she had had a weight loss of 100 pounds. Physical findings were limited to the neurologic examination and revealed bilateral glove hypesthesia to midforearms, bilateral stocking hypesthesia to the ankles and partial loss of all sensory modalities. She also had distal muscle weakness with inability to make a firm fist or to stand without assistance. Routine laboratory studies were not diagnostic. She was admitted to the surgical service with a diagnosis of electrolyte imbalance secondary to gastrointestinal losses; she was fed a high-protein diet as tolerated and given intravenous electrolyte therapy, but her neurologic condition deteriorated severely over a two week period. She had a complete loss of deep tendon reflexes in all extremities; the extent of sensory loss increased slightly and motor function disappeared completely below the knees with minimal function in the thighs. Hip motion remained normal. Finger and wrist extension were absent and flexion was very poor, although shoulder and central nervous system functions were all intact. Several serum vitamin studies made at that time showed only a severe depletion of thiamine. Atrophic beriberi secondary to jejunoileal bypass surgery and poor diet was appreciated for the first time. Replacement therapy with thiamine followed by an elemental diet containing all essential nutrients administered through a jejunostomy tube resulted in gradual improvement. Atrophic beriberi should be suspected whenever peripheral neuropathy develops after jejunoileal bypass for morbid obesity.

Modern Nutrition in Health and Disease.

Some of the most exciting developments in medicine today are occurring in the field of clinical nutrition. Its application has become vividly apparent in relation to coronary heart disease, diabetes mellitus, inborn errors of metabolism, obesity, and many other clinical disorders. Furthermore, nutrition representing the clinical outgrowth of the brilliant work of enzymatic chemists, is beginning to assume a prominent role in investigations ranging all the way from the antimetabolites in the field of neoplastic disease to the relationships between micronutrient deficiencies in infancy and the development of chronic diseases in adult life. Thus, the concept of nutrition as a clinical subject has reached maturity and is well presented in an excellent book edited by two prominent nutritionists, Drs. Wohl and Goodhart. This book has chapters or sections contributed by an impressive array of scientists, both clinicians and biochemists. The book is well organized into three sections: the first dealing

Therapeutic Nutrition with Tube Feeding.

A fact often forgotten by clinicians is that nutrition may constitute the most important therapeutic measure in management of a patient. Most serious disorders are accompanied by loss of appetite, and when this becomes prolonged, malnutrition develops to the point of jeopardizing survival. This problem has been ignored or met ineffectively by most physicians. The use of tube feeding, while not new, has been employed with some restraint. This is the topic of Pareiras book. He has reviewed the historical development of the technique and described modern facilities. Moreover, he has compared diets, methods of feeding, and results obtained under a variety of conditions. The fact that tube feeding is successful in a wide variety of illnesses comes as no surprise. The puzzling aspect is; why have we been so reluctant to employ this method before our patients became malnourished? In this concise volume, the author has detailed this technique