April 1995 Growth, Development, and Nutrition A739

O SHOULD PATIENTS WITH ACUTE PANCREATITIS RECEIVE EARLY TOTAL ENTERALNUTRITION? SA McClave, LMGreene, HL Snider, LJK Makk, WG Cheadle, NA Owens, LG Dukes. Depta of Med and Surg, Univ of Louisville School of Med & VA Medical Center, Louisville, KY. INTRO: Because of potential pancreatic stimulation, total enteral nutrition (TEN} has been believed to be contra- indicated in acute pancreatitie. Benefits of TEN in other disease states and recent evidence that nasojejunal feeds cause no pancreatic stimulation prompted us to study the safety, efficacy, and cost of TEN versus total parenteral nutrition (TPN) in this clinical setting. METHODS: Patients with acute pancreatitis were randomized within 48 hours of admission to reneive isocaloric/iaonitrogenous feedings (goal: 25 cal/kg/d) either by TPN (central or peripheral) or TEN (PEPTAMENe, Clintec) through a naaojejunal (NJ) tube. Safety was assessed by serial monitoring of pancreatic enzymes, subjective pain score, Ranaon Criteria (RC), APACHE III (A III), multiple organ failure (MOP) score, and incidence of nosocomial infection. Efficacy parameters included % goal calories received and days until advancement to PO diet. Cost of nutritional euppert was calculated. Student's t, Mann- Whitney U and Fisher's Exact tests were used for statistical analysis. RESULTS: Twenty-six patients were studied during 28 admissions for acute pancreatitis. TPN was given on 14 admissions and TEN on 14. Results are shown on table below:

TEN(n=14) TPN(n=14) SIGNIF

Age(yrs) 48.0 46.4 (% male) (71%) (86%} Initial RC 1.21 1.54 Initial AIII 17.5 21.8 Initial MOF 1.21 1.31 %~oal feeds(3d) 70.1% 89.7%

Days to nl amyl 5.1 days 7.1 days Days to Po diet 5.0 days 7.2 days Length hosp adm 8.8 days 12.7 days % Nosocomial infect 7.7% 14.0% Cost per patient $708 $3292

Fhere were no deaths and no differences between

NS NS NS NS NS p=0.10

NS NS MS NS p~0.001

groups in serial RC, A III, MOF, or subjective pain scores. An exacerbation of pancreatitis occurring in 1 TEN patient when the NJ tube was dislodged into the stomach, resolved after placement back into the jejunum. Two patients who became asymptomatic and normalized amylase on TEN, flared upon advancement to PO diet. CONCLUSIONS: TEN is as safe and effective, has a comparable impact on patient outcome, but is significantly less costly than TPN in patients with acute pancreatitis. TEN via jejunal feeding should be used preferentially in this disease setting.

• MECHANISM OF L-CARNITINE UPTAKE BY CACO-2 HUMAN INTESTINAL EPITHELIAL CELL. E McCIoud. TY Ma, KE Grant, RK Mathis, HM Said. Departments of Pediatrics, Medicine and Physiology/Biophysics. University of California, Irvine, Memorial Miller Children's Hospital and VA Medical Center, Long Beach, CA.

L-Carnitine, an essential co-factor for the metabolism of long chain fatty acids, is synthesized endogenously and obtained from dietary sources. The major site of L-carnitine absorption is the small intestine. The mechanism of enterocyte L-carnitine uptake is not clear. The aim of this study was to examine some of the mechanisms of enterocyte L-carnitine uptake and investigate the possible role of intraeellular signalling mechanisms in regulating its uptake process using the Caco-2 human derived intestinal epithelial cells. Confluent Caco-2 monolayers have been shown to be useful intestinal epithelial model for studying transport of a number of nutrients. METHOD: Apical membrane uptake of L-carnitine was determined by measuring transport of tritium labeled L-carnitine across the apical membrane of 7 days post-confluent Caco-2 cells. RESULTS: L-Carnitine uptake was a) linear and appreciable up to 7 min, at high and low concentration, b) dependent on Na ÷, c) independent of pH, d) temperature-dependent, e) saturable as a function of increasing concentration, with an apparent Km of 45 ± 6.4 uM and Vmax of 83,539 ± 5597.7 pmol/mg prot/5 min, f) inhibited by structural analogues and metabolic inhibitors, and g) not inhibited by stmctrually unrelated compounds and membrane transport inhibitors. L-Carnitine intestinal uptake was significantly reduced by inhibitors of Ca+Vcalmodulin - dependent phosphodiesterases, but not effected by second messenger inhibitors or stimulators involving protein kinase A and protein kinase C intracellular signalling pathways. CONCLUSION: These results demonstrate the existence of an apical membrane carrier for L-carnitine in the confluent Caco-2 cells, that is Na ÷, temperature- and energy-dependent Furthermore, Caco-2 uptake of L-carnitine appeared to be regulated by the Ca++/calmodulin dependent protein kinases, but not protein kinase A or C. Based on the present study confluent Caco-2 cell appear to be useful intestinal epithelial model to further study the molecular regulation of L- camitine uptake.

BONE TURNOVER AND BONE LOSS IN ADULT COELIAC DISEASE ~ , AK Bhatla, DAF Robetrson. Royal United Hospital, Combe Park, Bath BA1 3NO England.

Change in bone mass in adult life is due to the net difference between osteoclastie resorption and osteoblastic formation. Osteecalcin is the main noncollagen protein synthesised by osteoblasts during formation, and the type I collagen crosslinks (Pyridinoline; Pyr, and Deoxypyridinoline; DPyr) are products of resorption. We have investigated the relationship between bone turnover and bone loss in patients with coelia¢ disease. METHODS: 55 patients, (22 post- and 23 pre- menopausal female, 10 male; average age 50 years) with treated adult coeliac disease had bone mineral density (BMD) measured with dual energy X-ray absorptiometry at lumbar spine and hip on entry to the study and after 12 months. Serum osteocalcin (~g/L), and urinary Pyr and DPyr (~mol/nunol creatinine) were measured using ELISA and HPLC respectively. RESULTS: Bone turnover markers and ammual % change in BMD are expressed as mean (range) in the table.

normal pro- post- male Irange menopausal menopausal

osteocalcin [4-10 15.2 (3.0-9.8) I 6.3 (3.2-12) 6.6 (3.9-19.0) Pyr [4-22 115:9(7.3-48.5)116.7(1.4-42.0) 15.2(6.7-28.4) DPyr 12-6 15.6 (1.1-n.9) 15.6 (0.3-13.8) 4.8 (3.2-6.4) % spine J- ]+ 1.1 (-3 to +7)[-0.7 (-7 to +4) +2.6 (-2 to 15) % h i p - J+ 1.4 (-5 to 10) [-1.2 (-11 to 8) +2.3 (-1 to 12)

In postmenopausal females Pyr and DPyr were correlated with % change in spine BMD (r=-0.75, Speerman's rank correlation, p<0.001); those with Pyr and DPyr above normal lost bone. In males there was a positive correlation between % change at hip and DPyr (r=0.7, p<0.05), males with values above normal gained bone. There was no such association in premenopausal females. Bone biopsy demonstrated osteeporosis with trabecular thinning and evidence of high turnover. COMMENT: Serum osteecalcin and urinary pyridinolines have been used in coeliae disease to assess the rate of skeletal remodelling. Active remodelling may be associated with either loss or gain in BMD, and this information is useful in directing effective therapy for osteoporosis in coeliae disease.

• INTESTINAL CALCIUM ABSORPTION AND BONE MINERAL DENSITY IN TREATED ADULT COELIAC DISEASE XA McFarlane. AK Bhalla, DAF Robetrson. Royal United Hospital, Combe Park, Bath, BAI 3NG England.

Low bone mineral density (BMD) is found at diagnosis of adult coeliac disease and there is evidence that calcium malabsorption persists despite compliance with a gluten flee diet (GFD). Our aim was to determine whether BMD, or rate of loss of BMD in treated coeliac disease, were related to intestinal strontium absorption (iSA) which correlates closely with Calcium absorption (r=0.95, p<0.05, BMJ 1987: 295; p231- 234). METHODS 33 patients (26 females) average age 52 years, with adult ¢oeliac disease (on GFD for median 4.8 years) had lumbar spine and hip BMD measured by dual energy X-ray absorptiometry and expressed as a Z score (number of standard deviations by which patient BMD differs from BMD of age and sex matched normals). Serum calcium, phosphate, alkaline phosphatase, 25- hydroxyvitamin D and parathyroid hormone were measured. Dietary calcium intake and compliance with GFD were assessed. Strontium absorption test comprised a standard breakfast and ingestion of 2.5mmol of stable strontium isotope as a 200 ml solution, after an overnight fast. iSA (% of ingested strontium distributed in extraeellular fluid) was calculated from the 4 hours postprandial plasma strontium concentration determined by atomic absorption spectroscopy.

RESULTS Average iSA was 7% (interquartile range 4 to 9%) in females and 7% (range 3% to 10%) in males, wheras in normal adults iSA was 11% (range 9-12%). In males there was a correlation between iSA and Z score at hip (r=0.86, p<0.05 Spearmans rank correlation), and spine (r=0.78, p=0.05). There was no correlation in females, and no association between iSA and %/year change of BMD, serum biochemistry, dietary calcium intake or compliance with GFD in males or females.

COMMENT The positive association between iSA and Z score in males suggests that continued calcium malabsorption is a dominant risk factor for low bone mass in this group. The lack of association in females who have lower BMD implies that the effect of calcium malabsorption is overiddan by other factors such as oestrogen deficiency.