Irvine McQuarrie

Study of Certain Tissue Lipids in Generalized Lipodystrophy (“Lipohistiodiaresis”) .∗

An unusual opportunity to study the lipid composition of various tissues in an extremely rare condition, that of generalized lipodystrophy, was offered when death occurred in a 9-year-old boy in whom an almost complete absence of adipose tissue from the body had been present for the past 6 years (Case 1). In addition to this remarkable apparent lack of body fat, the symptom complex was composed of cirrhosis of the liver, chronic fibrosis of the spleen, pancreas and certain lymph nodes, and diabetes mellitus. Necropsy was begun within one hour following demise, at which time samples of various tissues were obtained. After being weighed, the specimens (usually about 1 g of tissue) were placed in 95% alcohol and allowed to stand for 24 hours. The tissues were then ground with sea sand in a mortar, rinsed several times with alcohol and ether, returned to the original flasks, and sufficient ether added to make approximately a 3:1 alcohol-ether mixture. The flasks were immersed in a boiling water bath for about 5 minutes and allowed to cool; the contents were filtered through fat-free filter paper into volumetric flasks, brought to volume, and stored in a refrigerator until analyses were made. Aliquots were measured and the following procedures employed: The method of Wilson and Hansen 1 was used for the determination of the unsaponifiable and saponi-fiable fractions, while the technic followed by Hansen 2 was used for the determination of the fatty acids in the acetone-insoluble (phospholipid) fraction and the acetone-soluble (cholesterol ester-neutral fat) fraction. The total cholesterol and cholesterol esters were determined by the procedure described by Bloor, 3 4 the photoelectric colorimeter being used in obtaining the final readings. For the control studies, similar tissues from a 14-vear-old boy dying in uremia from subacute nephritis (Case 2), the best available material at the time, were used.

Labeled Methionine as an Indicator of Protein formation in Children with Lipoid Nephrosis.

Summary 1. The rate of serum protein formation as indicated by the incorporation of methionine labeled with S35 was determined in 4 patients with lipoid nephrosis and in two control subjects. 2. The rate of serum protein formation thus determined would appear to be greater in the nephritic patients than in the control subjects.

Effects of Various Salts on Carbohydrate Metabolism and Blood Pressure in Diabetic Children

The excessive loss of minerals from the body in diabetic acidosis has recently been presented quantitatively in detailed balance studies by Peters 1 and Atchley 2 and their co-workers. Kydd 3 has emphasized the depletion of chloride in excess of other electrolytes, as if the base lost with the ketone acids might be derived from NaCl rather than from bicarbonate. He stresses the need for replacement of chloride during recovery from coma. Diabetic children not infrequently manifest an unusual craving for salt, even when not excreting ketone bodies in abnormal amounts. This has been interpreted by Joslin as most likely being due to the high potassium content of their vegetable diets. The present study was suggested by our experience in the case of a 15-year-old boy, who, as he emerged from diabetic coma, begged for salt and voraciously consumed 80 gm. of NaCl in the course of 24 hours. The water intake was proportionately increased. When it was observed that the craving for salt did not abate long after the disappearance of ketosis and that the patient continued to take 60 gm. daily before being satisfied, he was placed in the metabolism ward where complete balance studies could be carried out under standard conditions. He was given a constant diet containing protein 16, fat 33, carbohydrate 42, and water 1200 gm. every 6 hours. This was made up from powdered milk, bread, butter, eggs, cane sugar, lemon juice and a small amount of powdered yeast. The insulin dosage was kept constant for each period, totaling 32 units per day. This dosage of insulin permitted the occurrence of glycosuria in every 6-hour period, thus making comparative measurements possible. Shortly after the study was undertaken, it was discovered (1) that the high NaCl intake was accompanied by an elevation of arterial blood pressure from an average of 110 mm. of mercury systolic and 80 diastolic to 175 systolic and 115 diastolic and (2) that the urinary excretion of glucose fell from a control level of between 60 and 70 gm. to between 10 and 20 gm. daily under the same conditions. Reduction of the NaCl intake to the control value of about 4 gm. daily caused a return of the glucose excretion to the original level and a fall in the blood pressure to normal.

Random notes concerning the etiological mechanisms and treatment of spontaneous hypoglycemia.

It has been estimated by some authorities ( 5 , 7 ) that the total number of persons afflicted with spontaneous hypoglycemia due to all causes is almost as great as the number suffering from diabetes mellitus. However this niay be for the adult population, our personal experience indicates clearly that hypoglycemia, exclusive of the transient form seen in newly born infants, occurs far more frequently than diabetes in infants and children under school age. Since this is the time of life when severe uncontrolled hypoglycemia has its most devastating effects on the brain, the clinical problem must be regarded as one of exceedingly great significance. The clinical states in which abnormally low blood glucose levels2 are encountered may be listed as follows: 1. transiently in newly born normal infants, 3. more severe form in some infants born of diabetic mothers (islet hyperplasia? ), 3 . essential glycogenosis or glycogen storage disease of von Gierke of hepatic type, 4. congenital galactosemia (galactosuric “diabetes”) with hypoglycosemia, 5. adrenocortical insufficiency or Addison’s disease, 6. anterior pituitary insufficiency, 7 . hypothyroidism, 8. extensive cirrhosis or other destructive disease of the liver, 9. post prandial, alimentary or “functional” hyperinsulinism, 10. gastrointestinal disturbances: extreme inanition, severe vomiting, diarrhea, or moribund state, 11. periodic or recurrent hypoglycemia, 13. severe renal glycosuria, 13. islet cell tumor of the pancreas (beta cell), 1.1. hypertrophy or hyperplasia of pancreatic islands (beta cells), 15. intraeranial disease (e.g, hypothalamic or diencephalic syndrome), and 16. infantile idiopathic hypoglyceniosis. The causative mechanisms or functional disturbances, which are responsible for the subnormal blood glucose level in the foregoing clinical conditions, differ widely. The nature of the therapy varies accordingly. Tn many of these

Effects of Pituitary Adrenocorticotropic Hormone (ACTH) in Children with Non-Addisonian Hypoglycemia

Summary The effects of ACTH on the fasting blood sugar level and glucose tolerance test; on the potassium and inorganic phosphorus content of the serum; on the nitrogen, phosphorus, chloride, sodium and potassium balances; on the urinary excretion of uric acid, creatinine and adrenal corticosteroids and on the blood eosinophil counts were determined in 5 young children with non-Addisonian (familial) hypoglycemia. The type of response to ACTH was similar in all respects to that of the normal adult. However, under the conditions of this experiment, instead of producing a transient state of diabetes mel-litus, as it does in the normal subject, the ACTH appeared merely to reverse the hypoglycemic tendency, with return of the fasting blood sugar level and the glucose tolerance curve to normal. While the eosinophil count returned to normal promptly upon withdrawal of ACTH, the blood sugar remained above the threshold for hypoglycemic reactions for at least 10 days without ACTH in the most severe case in the series (Fig. 1). Administration of 18 mg of ACTH in one dose every 48 hours thereafter served to maintain this one-year-old patient in an essentially non-hypoglycemic state for more than three additional weeks. Results of the study suggest that ACTH may prove to be as effective in the control of this non-Addisonian hypoglycemic disorder as insulin is in the control of diabetes mellitus.

Influence of Acute Infection and of Artificial Fever on Plasma Lipoids

During another investigation on the lipoids of the plasma in children, it was observed in several instances that values for lecithin, cholesterol and total fatty acids were all markedly influenced by acute infections. Although the literature revealed the fact that cholesterol has previously been found to be lowered in certain acute infectious diseases 1 , 2 and in tuberculosis, 3 , 4 little is actually known regarding the significance of this change and practically no information is available regarding the effect of infection on the lecithin and total fatty acid levels in the blood. The various lipoid fractions have been determined by the methods of Bloor 5 , 6 , 7 in 15 children with various acute infections, first at the height of the disease and again after recovery. To ascertain the influence of fever per se as against that of the other effects of infection, determinations were made before, during and after the artificial production of fever, in one case of dystonia progressiva deformans by use of phenylethylhydantoin and in one case of chronic arthritis by diathermy. Determinations were also made before, during and after high fever on 2 occasions in each of 3 congenitally syphilitic children, who were inoculated with plasmodia malariae as a therapeutic measure. No particular attention was given to the factor of diet in the first 7 cases with acute infection, but in the other 13 cases studied a standard diet was given several days before and throughout the entire period of observation. The diet contained adequate amounts of vitamins and water and 2 gm. each of protein and fat and 5 gm. of carbohydrate per kilo of body weight. The 15 cases with acute infection were distributed as follows: Uncomplicated pneumonia, 6; pneumonia complicated by mastoiditis, otitis media or empyema, 3; uncomplicated acute tonsillitis and nasopharyngitis, 3, and one each of acute appendicitis, acute otitis media and acute rheumatic fever.

Mechanism of Insulin Convulsions. III. Effects of Varying Partial Pressures of Atmospheric Gases After Adrenalectomy

Conclusions Anoxic anoxia (breathing 5% O2 plus 95% N2) causes hypoglycemia in adrenalectomized dogs without insulin in contrast to the hyperglycemia observed in normal animals. Insulin convulsions are prevented by anoxia of this degree even when the fall in blood sugar is maximal. Breathing 15% CO2 likewise tends to prevent insulin convulsions from occurring.

Effects of Desoxycorticosterone Acetate on Water and Electrolyte Content of Brain and Other Tissues

In a previous study on the antagonistic action between pitressin and desoxycorticosterone acetate in epileptic subjects, the authors 1 found the latter substance to have a striking anti-convulsive effect for both spontaneously occurring and pitressin-induced seizures. The principal experimental subject involved- in that investigation, a young man with extremely severe epilepsy, has remained essentially free from convulsive attacks during the intervening 3 years while continuing to receive this synthetic hormone sublingually or by subcutaneous pellet implantation. The present experimental study was undertaken with the hope of obtaining some information regarding the physiological or pharmacological mechanism responsible for this effect. Our immediate objective was to determine the effects of the hormone on the water and electrolyte content of the brain tissue of normal animals. It has been abundantly demonstrated by Darrow and Miller 2 , 3 , and by Ferrebee and co-workers 4 that the potassium content of skeletal muscle, as well as that of blood plasma, is greatly reduced and the sodium content is somewhat increased by daily injections of comparatively large doses of desoxycorticosterone acetate. Heart muscle and liver showed much less, or (in some animals) no alteration. 3 Data regarding the brain were not reported by these authors. In the present study, changes in skeletal muscle, liver and heart muscle were determined for the purpose of comparison. Eighty young hooded rats (initial weights, 150 to 200 g each) maintained continuously from the time of weaning and throughout the experiments on a standard rat diet containing 0.605 g of K, 0.565 g of Na, and 1.155 g of CI per 100 g, were divided into two equal groups.

Mechanism of Insulin Convulsions. II. Effects of Varying Partial Pressures of Atmospheric O2, N2 and CO2

In connection with a study on the relationship between the levels of potassium, inorganic phosphorus and glucose in the blood and the occurrence of insulin convulsions 1 dogs were subjected to atmospheres varying greatly in their partial pressures of O2, N2 and CO2. The finding by Glickman and Gellhorn 2 that rats subjected to lowered O2 tension (air in low pressure chamber at 460 mm Hg) became more sensitive to insulin and had convulsions sooner than they did in ordinary air, suggested the use of induced anoxic anoxia as an additional means of modifying our experimental conditions. The fact that the convulsions of epilepsy 3 and those of hypoparathyroidism can not infrequently be prevented or aborted by the subjects breathing a gaseous mixture containing 10% CO2 and 90% O2 further suggested the desirability of investigating the influence of such alterations in the air breathed on the various constituents of the blood and on the occurrence of convulsions following the administration of insulin. The method used was that of determining the effects of insulin administration, first, when the experimental animal was allowed to breath room air, and again, one week later when the same animal was kept in an ordinary oxygen tent containing O2, N2 and CO2 at different partial pressures. The insulin was given subcutaneously in large single doses (10 to 25 units per kilo of body weight). In addition to the preliminary control experiments performed on all animals, the following studies were carried out : 17 experiments with low O2 percentages; 4 with high O2; 4 with high O2 plus high CO2; 4 with low O2 plus high CO2, and 10 with high CO2 plus 20% 02. The specific effects of the various gaseous mixtures per se were determined before insulin was administered in some instances.

Calcium enriched meat compared with milk as source of calcium, phosphorus and protein.

Summary The nutritional value of a Ca-enriched meat diet has been investigated from the viewpoint of protein, Ca and P utilization. This has been compared experimentally with a milk diet containing the same quantities of essential food constituents. Balance studies were carried out in 2 young hospital patients. Total carcass and separate femur analyses were also made in rats on the 2 types of diet. The results of these studies indicated clearly that the Ca-supplemented meat diet was equally good as the milk diet as a source of Ca, P, and protein.