NUTRITION RESEARCH, Vol. 1, pp.303-309, 1981 0271-5317/81/030303-07502.00/0 Printed in the USA. Copyright (c) 1981 Pergamon Press Ltd. All r ights reserved.

SUMMARIES OF CONFERENCES

Society for Pediatr ic Research

The annual meeting of the Society was held in San Francisco Apri l 27-April 30, 1981. In the summaries of selected presentations that fo l low, the abstract number (published in Pediatr ic Research 15: 440-734, 1981) is given in parenthesis fol lowing the name of the chief author.

Studies of the interact ion of in fant feeding and growth has continued to be a productive area of study for pediatr ic ians. In fact , as J. BERNBAUM and co-workers reported (1247) non-nut r i t ive sucking alone in small premature effects a s ign i f i can t reduction in the time of feeding, a shorter t rans i t ion to total post-operative feeding, a reduced in tes t ina l t r ans i t time, and a greater percent weight gain per week, despite an ident ical calor ic intake compared to other gavage-fed infants. Once the chi ld is on oral intake, S.J. Gross reported (559) that breast milk obtained from donors fol lowing pre-term del ivery induced a better weight gain than milk obtained from donors three months post-partum. Infants fed pre-term breast milk demonstrated s imi lar growth and metabolic responses to infants fed cow's milk formula.

PENCHARZ and co-workers (620) fur ther showed that rates of protein f l ux , whole body protein synthesis, and catabolism were a l l s i gn i f i can t l y higher among 30 pre-term infants fed breast-milk. These results are consistent with increased recycl ing of endogenous protein and amino acids, and suggest that the level of protein in term breast milk may be only marginally adequate for the growth of the premature in fant . A second paper by the same group (1392) report- ed that smal l- for-gestat ional age (SC~A) infants had rates of protein turnover, synthesis and catabolism that were 20-30% greater than those in normal premature infants. Similar nitrogen balance, and increased 3-methyl-hist id ine excretion in the SGA in fants , suggested higher rates of muscle degradation, perhaps re f lec t ing more rapid maturation and remodelling of muscle t issue. Another study from Toronto, by Chessex et a l . (233), used ind i rec t calorimetry to calculate the cost of growth of very low bir thweight (VLBW) infants. There was a high, pos i t ive, correlat ion ( r = 0.86) between metabolic rate and weight gain. Approximately 53% of energy intake was used for growth; 45% of intake was e i ther the actual protein or energy stored, and 8% was for t issue synthesis. However, fat accretion was three times greater than that in the fetus. The authors commented fur ther that although energy intake is lower among breast fed infants, rates of protein deposition are s imi lar but fat deposition is in the range of in t rauter ine fat accretion. In a subsequent poster session (531), th is same group demonstrated a s ign i f i can t in ter re la t ionsh ip between age, energy in- take, metabolic rate and weight gain.

With regard to supplemental feeding of low b i r th weight infants two relevant papers were presented. VlLEISlS and others (1457) compared the effects of t r ig lycer ide infusions ( I n t r a l i p i d ) on glucose levels in two groups of pre-

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mature infants. Group A was given 0.25 gm/kg/d, and group B O.5um/kg/d. Although glucose levels were comparable in the two groups, group B had a s igni f icant ly greater increase in glucose above baseline levels. One potential mechanism is that In t ra l ip id may drive gluconeogenesis by increasing the available supply of glycerol. In t ra l ip id may also reduce the k i l l i ng potential of polymorphonuclear leukocytes by acting as a particulate stimulus to phagocytosis and superoxide production thereby exhausting substrate available for these reactions (Cleary, et al , 533). The in v i t ro correlate of this phenomenon is not clear.

Two papers considered the possib i l i ty that the fetal alcohol syndrome (FAS) was a consequence of intrauterine undernutrition. Fisher et al. (549) recognized that the microcephaly, LBW, and reduced length of FAS infants was consistent with fetal undernutrition, and showed that high doses of alcohol (2, 5, I0 and 20 ~M) progressively inhibited amino acid uptake. Since these doses were 103 times those found in humans after alcohol ingestion, the physiologic consequence of their observations is not clear. Ghishan et al. (554) suggested that zinc deficiency might be implicated in the FAS. Studies of pregnant rats given alcohol reduced placental zinc uptake by 40%; chronic alcohol ingestion resulted in decreased fetal weights, reduced total body zinc and diminished zinc uptake as well.

Both SaudUbray et al. (1181) and Wolfsdorf et al. (1191) studied the metabolic response of normal children to a 24-hour fast. In both studies, ketone levels were inversely related to age, and levels at the end of 24 hours were higher than those observed in adults fasted for one week. No differences were seen in the ketotic response of children with ketotic hypoglycemia. Both papers emphasized the need to consider age in the assessment of the ketotic response.

Several papers on obesity indicated the increased attention th~shighly prevalent disorder has begun to receive. EPSTEIN and co-workers (47) studied the effect of targeting the obese child and obese parent (Sroup I) only the obese child (Group I I ) , or specifying neither (Group I I I ) for therapy. Children in two parent families in which at least one parent was obese were treated. Although no signi f icant differences in weight loss occurred, s igni f icant ly more children from group I maintained their losses. As compli: ance increases, more attention should logical ly focus on diet. As Dietz et al. (540) foun~the inclusion of igm/ kg IBW/d of glucose with 1.5gm/kg IBW/d of protein appeared more optimal for protein metabolism than an isocaloric, isonitrogenous diet containing fat. Glucose metabolism, measured direct ly us- ing a primed constant infusion of 1-13C-glucose, was direct ly related to protein catabolism but only in the absence of carbohydrate; these data suggested that the interrelationship of glucose and protein metabolism was strongly dependent on the diet considered. Although the fai lure to achieve a plateau in nitrogen losses occurred in three of nine adolescents studied on carbohydrate free diets, Archibald et al. (2), using 2.5 gm protein/kg IBW/d, did not observe this phenomenen in a study of 17 obese adolescents. Of concern in this la t ter study was that the loss of body potassium appeared bipnasic, despite adequate supplements of potassium. One of the long-term complications of obesity, the effect of diabetes on the outcome of pregnancy, may be s igni f icant ly improved by the use of an inBulin pump during pregnancy according to RUDOLF and co-workers (1408). Improved control of blood glucose, reduced fluctuations of glucose and normal levels of glycosylated hemoglobin were shown in seven class C to FR pregnant diabeticstreated by insulin pump therapy. Their infants had no macrosomid, normal skinfolds, no hypoglycemia, respiratory distress syndrome, jaundice or polycythemia. Such therapy promises improved outcomes for infants of diabetic mothers.

Summaries of Conferences 305

More fuel for the controversy regarding iron and infection was presented by Pearson et al. (849). Although they found the addition of iron to normal heat-treated serum abolished the bacteriostatic properties of that serum, they observed no differences in the ab i l i t y of three iron deficient, 17 normal, or 13 iron overloaded sera to support the growth of two pathogenic E. coli strains in v i t ro. Therefore the effect of adding iron to sera cannot be replicated by normal physiologic sera, perhaps because added iron is more available for bacterial growth. These data do not support the role of iron in enhancing suscept ibi l i ty to infection.

When does iron deficiency have pathologic consequences? Before the hemoglobin fa l l s , according to OSKI and co-workers (846). In this study a larger group of 9-13 month old infants were tested with the Bayley test for mental development, al l of whom had hemoglobins above I I .0 gm/dl. Infants were divided into four categories based on f e r r i t i n , free erythrocyte proto- porphyrin, and mean corpuscular volume. After i n i t i a l testing, each infant was treated with intramuscular iron and retested one week later. Scores rose signi f icant ly higher among the two groups with a high FEP, with or without a low MCV, suggesting strongly that iron deficiency without anemia was accompan~d by behavioral change.

According to Greer et al. (557), bone mineral content measured by photon absorptiometry, and serum levels of 25-0H vitamin D were decreased in six month-old breast fed infants whose mothers did not receive supplemental vitamin D. After the study was unblinded at six months, al l breast fed infants received 400 IU/d of vitamin D supplements and by 12 months of age, no differences were observed. The relationship of serum D levels to hypocalcemia in infants of diabetic mothers was investigated by STEICHEN and co-workers (144Q). The observation of comparable levels of 25-0H vitamin D and 1,25 OH- vitamin D in hypocalcemic and normocalcemic infants, and the s igni f icant ly increased prevalence of hypocalcemia in infants whose mothers were in poor diabetic control during pregnancy suggested that diabetic control rather than vitamin D metabolism was the major factor contributing to hypocalcemia.

Continued controversy on the antioxidant role of vitamin E in oxygen- induced lung damage was provided by HANSEN and BLAND (1319). Vitamin E provided no protective effect on either lung f lu id f i l t r a t i on or micro- vascular permeability to protein in lambs, despite a ten-fold increase in plasma tocopheral levels.

A report of carnitine deficiency in a pair of twins was presented by KERR and co-workers (1142). Both presented with fat ty l i ver , transient erythroblastopenia, hypoglycemia and cardiomyopathy. After finding low levels of carnitine in the tissue of one of the pair who died at age 7 months, low levels of carnitine were also found in the plasma, muscle, and l i ver of the surviving twin. An RQ prior to carnitine therapy was 0.94, and after carnitine administration was 0.78 suggesting that increased glucose ut i l izat ion induced hypoglycemia. Carnitine administration improved muscle, hepatic, and cardiac function.

Finally, two papers considered specific nutr i t ional problems in cystic f ibrosis. Studies by ISENBERG and POWELL (566) showed that despite normal fat digestion, absorption of free fat ty acids was s t i l l impaired. Micellar in- corporation of free fatty acids appeared reduced although bi le acid concentra- tions and intraluminal pH were normal. According to Harper et al . (1663) essential fat ty acid deficiency in rabbits impaired macrophage lysozyme production and intracel l ul ar ki 11 ing of Staphylococcus aureus and Pseuodomonas aeruginosa. These results suggested that essential fat ty acid deficiency could

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contribute to impaired lung defense mechanisms in cystic fibrosis.

W. H. DIETZ, JR.

AmeriCan Federation for Clinical Research

The clinical meetings were held in San Francisco April 24-28, 1981. This brought together members of the American Society for Clinical Nutrition, the American Federation for Clinical Research, the American Society for Clinical Investigation, the American Association of Physicians and the Society for Investigative Dermatology in individual and joint plenary and subspecialty sessions. Selected short scientific papers in nutrition were presented in the ASCN meeting, and the combined ASCN/AFCR/AAP sessions had a number of papers of nutritional interest as well.

The winner of the 1981ASCN Medical Student Research Award was CHARLES L. BAUM of the Pritzker School of Medicine, University of Chicago. Working in I.H. ROSENBERG'S laboratory, BAUM studied the Hydrolysis of Nicotinamide Adenine Dinucleotide by Intestinal Brush Border Membranes. The research concluded that the food form of niaCin, NAD, was hydrolyzed prior to intest- inal uptake by phosphorylase enzymes in the brush border.

Two papers presented exciting innovative news of value to all clinical nutritionists as they represented emerging topics. N.N. ABUMARD reported on a case of Amino Acid Intolerance During Prolonged Total Parenteral Nutrition Reversed by Molybdenum. The patient showed low urinary and serum levels of uric acid and elevation of circulating methionine responsive to supplementation with ammonium molybdate. The clinical and biochemical pattern was ascribed to decreased activity of xanthin oxidase and sulfite oxidase, the two molybdeno- metalloenzymes in mammals. This is the f i r s t time a report of putative human molybdenum deficiency had been presented to a forum of nutritionists. These findings may explain some additional features of TPN-induced abnormalities in man. That some of the reliance on TPN may be shifted to an enteral route even in patients with severely compromised intestinal function was indicated by H.L. GREEN of Vanderbilt in his paper on Nasogastric Tube Feeding at Home: A Method for Adjunctive Nutritional Support of Malnourished Patients. His patients were maintained at home, and most gained or maintained body weight. The treatment was even successful in patients with imflammatory bowel disease in which "bowel rest" has been considered to be a necessary concomitant of intensive nutritional repletion. The experience with tube feeding in IBD patients at the University of Chicago has also been encouraging, I.H. ROSENBERG reported in the discussion. The enteral route certainly provides more safety, versati l i ty and economy than the parenteral alternative. More will certainly be heard from the home enteral nutrition experience.

Elsewhere among the program of scientific papers, a number of presenta~ons focused on TPN. M.E. BURT from the NIH reported data on the Effect of Total Parenteral Nutrition on Protein Metabolism in Man. In this instance, patients with localized, obstructive esophageal cancer - receiving only radiation therapy appeared to maintain weight and body composition. Endogenous insulin appeared to facil itate maintenance of nitrogen metabolism. M. SHIKE of Toronto reported another experience of TPN in patients with malignancy in the paper Nutritional Status of Patients with Lung Carcinoma: The Effect of Chemotherapy and Parenteral Nutrition. Patients on TPN during a four week period of chemo- therapy gained more weight, exclusively fat, than orally-fed patients. This

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suggested to the authors that small cell carcinoma of the lung produces a hypermetabolic (but not protein wasting) state which cannot be met by spontaneous caloric intake. The unusual tr ial of short-bowel syndrome, antibiotic therapy and a decade of home parenteral nutrition provides a setting in which R.C. BOZIAN of Cincinnati described Biotin Deficiency During Prolonged, Home Total Parenteral Nutrition. A biotin-responsive exanthem and buccal lesion developed in their patient. The valididy of endogenous biotin production in the colon is supported by this demonstration. The authors suggest the inclusion of biotin in vitamin formulations for long-term TPN. Finally, from Atlanta, D. RUDMAN in a paper on Requirements for Cystine and Tyrosine in Cirrhosis, provided insight into the capacity of conventional amino acid mixtures used in TPN to support N retention in severely decompensated cirrhosis. Commercial TPN solutions omit the highly insoluble tyrosine and cystine on the assumption that they will be produced as needed by hepatic metabolism of phenylalanine and methionine. Abnormal plasma aminograms and negative N balance despite TPN were observed in a group of cirrhotic patients with severe hepatic dysfunction. These were normalized by the provision and doses of cystine and tyrosine.

A concern with obesity and its treatment was an original tenet of clinical nutrition as a medical subspecialty. Active interest in issues of energy regulation and adipose accumulation continues. Two papers from the laboratory of F.X. PI-SUNYER bear on these issues. In the presentation on the Effect of Excise on Spontaneous Calorie Intake in Obesity, R. WOO was unable to demon- strate a compensatory increase in food intake of obese women (mean of 167% ideal~weight) when mild and moderate increases in energy expenditure were induced with treadmill exercises. A negative energy balance of over 400 kcal/ day was maintained throughout a 19-day period of moderately augmented energy output. F.X. PI-SUNYER presented a paper on Cholecystokin Octapeptide (CCK-8) Decreases Food Intake in Obese Men in which an infusion of saline or CCK-8 was given to obese men (means 138% ideal weight) in a double b l ind fashion during a standard l i qu id breakfast. The octapeptide decreased intake by an average of 112 kcal, pr imar i ly due to an ea r l i e r cessation of food consumption. WILLIAM H. DIETZ, JR. of M.~.T. presented a paper on Hypocaloric Diets in Obese Adolescents: Effects of Dietary Glucose or Fat on ~he In ter re la t ionsh ip of Protein and Glucose Metabolism in which data on hepatic glucose production and nitrogen balance in nine obese adolescents consuming a protein plus fat or protein plus glucose diet ( isoca lor ic ) were reported. Cumulative nitrogen balance was better on the protein plus carbohydrate diet . Innovative metho- dology including the use of stable isotope-label led substrates ( ~ 8 0 to determine body composition; 13C-glucose to measure glucose oxidat ion) was an exci tory feature of th is work. N. BABA of Columbia Universi ty presented Enhanced Thermogenesis and Diminished Deposition of Fat in Response to Over- feeding with Diet Containing Medium Chain Tr ig lycer ide. In a gastrostemized rat model, overfeeding MCT produced smaller weight increases, small adipocytes, and increased oxygen consumption and BMR as compared to long chain t r ig lycer ides . Increased thermogenesis on the MCT diet explained the decreased fat composition.

Vitamin D commanded attention at the San Francisco meetings in both clinical nutrition and metabolism sessions. The intestinal metabolism of the vitamin was covered in two papers from I.H. ROSENBERG'S laboratory in Chicago. K.L. POLLACK, an undergraduate student, presented a paper entitled Chylomicron- Dependent Absorption and Transport of Vitamin D and 25-Hydroxy-Vitamin D in the Rat, while his co-worker, M.D. SITRIN presented an extension of this work Influence of Bile Salts and Fat on Intestinal Absorption of Vitamin D and 25- Hydroxy-vitamin D in the Rat. Both studies employed cannulation of the bile and thoracic ducts and intestinal inst i l lat ion of radio-labelled vitamins; both demonstrated a less efficient absorption of vitamin D than 25-OH-vitamin D and

308 Summaries of Conferences

a predominant uptake into the portal blood as compared to the lymphatic drain- age. This observation might explain the relatively lesser expression of osteo- malacia as compared to other manifestations of fat-soluble vitamin deficiencies in abetalipoproteinemic patients.

Important new findings related to vitamin D in human nutrition were presented. Two presentations from the Massachusetts General Hospital addressed the issue of vitamin D nutrition in the aged. M. HOLICK discussed Aging Significantly Decreases the Capacity of Human Epidermis to Produce Vitamin D, while D. SLOVICK presented Deficient 1,~25-(OH)2-vitamin D Production in Osteoporotic Patients. The pool of F-dehydrocholesterol the pro- vitamin D, in human skin was reduced in skin biopsies from older subjects as compared to younger volunteers, and equivalent ultraviolet treatment produced less vitamin D in the aged sample. Renal production of 1~,25 dihydroxy- vitamin D during a 24-h infusion of the 1-34 synthetic peptide fragment of parathyroid hormone was reduced in aged subjects with osteoporosis (mean age, 59 years) as compared with a group of younger subjects (mean age, 29 years). The lack of age-matched controls in the latter study makes any conclusion about the dominance of age versus bone disease tendency in the renal hypo- responsiveness less valid. A group of Army researchers, which includcd ~he late ROBERT HERMAN, also provided new insights into hormonal ~'esponses and bone metabolism. The paper, presented by D.D. BIKLE and entitled Cyclic Nucleotide and Bone Mineral Responses to Dietary Calcium by S~bjects with Osteoporosis and Hyperparathyroidism, suggested a hyperresponsiveness to endogenous regulators of the cyclic nucleotides (cAMP, cGMP) of the kidney in four post-menopausal osteoporotic subjects. The study manipulated daily caldum intake (100 mg vs. 1000 mg). Unfortunately, control and hyperparathyroid subjects were not matched for age or sex.

Trace mineral nutrition was strongly represented in the scientific programs. J. COOK of the University of Kansas developed a Rapid Qualitative Assessment of Iron Status for field use which requires no laboratory equipment, but, by visual inspection, permits differences in serum ferr i t in concentrations representing iron deficiency, iron adequacy, and @ron overload to be distinguished. Clinical evaluation of zinc nutrition may be facilitated by the data presented by A.S. PRASAD of Detroit on Nucleoside Phosphorylase in Zinc Deficiency. The activity of this enzyme was reduced in the red cells of zinc deficient rats as compared to their pair-fed controls and in a patient followed prospectively through zinc depletion and repletion. Two additional studies from Detroit looked at zinc status in urBmic patients on hemodialysis. In a paper presented by W.A. BRIGGS, Mononuclear and Polymorphonuclear Cell Function in Zinc Deficient Hemodialysis Patients, an effect of zinc deficiency on the chemotatic function was reported. In a paper Zinc Deficiency in Uremia: Response to Oral Zinc Supplementation S.K. MAHAJAN showed that a daily dose of supplemental zinc administered to patients with uremia could improve indices of zinc nutrition including plasma zinc, leukocyte zinc and serum RNA- ase. This suggested that zinc depletion is, indeed, common in uremic patients undergoing hemodialysis.

The symposium on The Biological Availability of Mineral and Trace Mineral from Food co-chaired by I.H. ROSENBERG and N.W. SOLOMONS, included discussion of calcium (L.H. ALLEN), selenium (V.R. YOUNG), zinc (N.W. SOLOMONS# and copper (H.H. SANDSTEAD). A pre-meeting workshop on the complementary theme Mineral and Trace Mineral Absorption in Man was organized by the ASCN Committee on Research. The ASCN Presidential Address was delivered by VICTOR HERBERT was entitled Will Questionable Nutrition Overwhelm Nutritional Science? I t was an impassioned call for those who represent the community of nutritional scientists and scholars - adherents of premises of the experimental methods,

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peer review, c l i n i ca l t r i a l - to confront and address the misinformation and open in t imidat ion from those who promote questionable and unsc ien t i f i c nu t r i t i ona l be l ie fs and pract ices.

N.W. SOLOMONS