Building a sustainable, risk-bearing IPA.

HMOs are increasingly relying on risk-bearing IPAs to expand their networks. Physicians see IPAs as a way to access HMO patients without relinquishing their autonomy. To build a sustainable IPA to bear global risk for HMO enrollees, the IPA's organizers should select a provider panel that is committed to centralized medical management and dominated by primary care physicians, invest in talented managers, empower a strong governing board, and access a management information system that can perform the functions necessary to manage care. Additionally, the interests of any potential outside capital sources should be weighed carefully, and the financial incentives of all of the IPA's providers aligned with the IPA's goal of providing appropriate, cost-effective care.

Lipases in human milk: effect of gestational age and length of lactation on enzyme activity.

Human milk contains two lipases, bile salt-stimulated lipase (BSSL) and lipoprotein lipase (LPL). In the mammary gland, LPL provides long-chain fatty acid for milk fat synthesis. LPL has no known function in milk, but has been implicated in milk fat hydrolysis during cold storage. BSSL may have an important role in infant fat digestion. The aims of the present studies were to assess (1) the methodological validity of using whole milk to analyze BSSL activity, (2) the longitudinal variation of BSSL and LPL activity in the milk of mothers delivering premature and full-term infants, and (3) the stability of BSSL and LPL activity during cold storage. Diluted whole milk and purified BSSL were shown to have similar characteristics. LPL activity was equally stable at -20 and -70 degrees C, whereas BSSL activity was higher in milks stored at -70 than at -20 degrees C (38.8 +/- 0.88 vs 33.3 +/- 0.87 U/ml milk, respectively; 1U = 1 mumol free fatty acid release/min). Levels of BSSL activity in preterm and term milk were similar. LPL activity tended to be higher in term milk. Overall, BSSL activity showed significant longitudinal variation, being highest at 1 and 3 weeks of lactation (43.2 +/- 0.04 and 42.6 +/- 1.03 U/ml milk, respectively). For LPL, the longitudinal pattern of activity depended upon the length of pregnancy. Implications for infant nutrition and mammary gland biology are discussed.

Total parenteral nutrition with intralipid in premature infants receiving TPN with heparin: effect on plasma lipolytic enzymes, lipids, and glucose.

Plasma lipolytic activity (lipoprotein lipase and hepatic lipase), free fatty acids (FFA), triglycerides, cholesterol, and glucose levels were measured in 21 premature infants [gestational age 26-37 weeks (mean +/- SEM 30.4 +/- 0.63 weeks), aged 1-8 days (mean +/- SEM 3.00 +/- 0.35 days)]. All infants were maintained on total parenteral nutrition with heparin (1 U/ml) and were given Intralipid, 1, 2, and 3 g/kg/day, over 15 h on days 1, 2, and 3, respectively. Blood samples were drawn before and at the end of Intralipid administration. Baseline plasma lipolytic activity, before the start of lipid infusion, was 1.54 +/- 0.24 U/ml (1 U = 1 mumol [3H]oleic acid released from tri[3H]olein/h). Lipolytic activity increased after lipid infusion to 4.04 +/- 0.96, 4.32 +/- 0.63, and 6.09 +/- 1.00 U/ml on days 1, 2, and 3 of the study. Hepatic lipase amounted to 38-47% of total lipolytic activity. During the 3 days of lipid infusion, there were dose-dependent increases in plasma FFA, triglyceride, and cholesterol. Whereas FFA and triglyceride concentrations returned to prelipid infusion levels 9 h after stopping the infusion of Intralipid, 1, 2, or 3 g/kg, there was a cumulative increase in plasma cholesterol and glucose concentrations. The close correlation between FFA concentrations and plasma lipolytic activity (r = 0.655, p less than 0.001) suggests considerable intravascular lipolysis. The positive correlation between plasma FFA and triglycerides (r = 0.632, p less than 0.001) and FFA and cholesterol (r = 0.582, p less than 0.001) indicate, however, that intravascular lipolysis does not prevent the lipemia associated with Intralipid infusion to low birth weight infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipases and lipids in human milk: effect of freeze-thawing and storage.

Frozen storage is often used by milk banks to preserve expressed human milk for later use. Optimal storage and handling conditions which ensure minimum alteration of lipid composition have not been well defined. Therefore we investigated the effect of rapid freeze-thawing and storage conditions (-20 and -70 degrees C) on the free fatty acid (FFA) levels and on the activities of lipoprotein lipase (LPL) and bile salt-stimulated lipase (BSSL) in human milk. Since during mechanical expression leakage of serum components into milk may occur, we also investigated the effect of the presence of serum on human milk LPL during storage. Lipase activity levels were unaffected by rapid freeze-thawing (x3) followed by storage for 1 month at -20 or -70 degrees C. LPL activity (nmol FFA released/ml milk/min) was 414 +/- 128, 451 +/- 37, and 351 +/- 20 and BSSL activity (mumol FFA/ml milk/min) was 5.7 +/- 0.7, 5.5 +/- 0.8, and 5.7 +/- 0.2 in fresh, freeze-thawed, and stored milk, respectively. FFA levels (% of total lipid) were 3.01 +/- 1.05 and 10.3 +/- 1.6 in fresh-frozen milk stored at -70 and -20 degrees C for 5 months, and 3.78 +/- 1.08 and 13.60 +/- 1.25 in specimens of freeze-thawed (x3) before storage at -70 or -20 degrees C. Addition of serum had no effect on milk LPL at either temperature. We conclude that LPL and BSSL remain fully active during frozen storage of human milk and that milk fat is hydrolyzed at -20 degrees C but not at -70 degrees C. We suggest that banked human milk be stored routinely at -70 degrees C.

Effect of heparin on serum and tissue lipases in the developing rat.

The frequent inclusion of heparin in fluids used for total parenteral nutrition in infants, prompted an investigation of the ability of heparin to release lipoprotein lipase (LPL) and hepatic lipase (HL) from the endothelial surface into the circulation, and of the effect of heparin on tissue stores of lipase in the postnatal period. In rat pups, plasma postheparin lipolytic activity (PHLA) released by IP administration of heparin (0.5 unit/g body wt) was 15% of adult values at birth and increased rapidly to reach 60% on day 10. Repeated doses of heparin (in adult rats, given 0.1 unit/g IV) at 1 and 4 h after the initial dose did not affect the maximal response to heparin. In all age groups 80% of PHLA was inhibited by 0.5 M NaCl, suggesting a mostly nonhepatic origin for the released enzyme. Heart, lung, and liver lipase activities of rat pups were not significantly different from controls not given heparin. The pattern of change in tissue enzyme content was similar for heart and lung, but different from hepatic lipase. LPL activity in the former increased from 10 and 30% to 60 and 100% of adult values between birth and 10 days while in the latter enzyme activity exceeded adult levels at birth and decreased to 50% of adult values during the latter half of the suckling period (days 10-21). Our results demonstrate that heparin does not cause depletion of tissue lipases in the postnatal period. The parallel increases in LPL content of peripheral tissues and PHLA suggest that in all age groups heparin-induced release of LPL into the circulation is proportional to tissue lipolytic activity.

Essential fatty acid deficiency: effects of cross-fostering mice at birth on myelin levels and composition.

Female mice were assigned an essential fatty acid (EFA)-deficient diet or a control diet at mating, and litters were cross-fostered at birth to produce three groups of animals: pups fed a control diet prenatally and deficient diet postnatally (C leads to D); a deficient diet prenatally and a control diet postnatally (D leads to C); and a control diet throughout life (C leads to C). The yield of myelin, the developmental pattern of the major proteins, and the proportion of major lipids were examined in the purified myelin of the three groups at 3, 6, and 9 weeks. Myelin yield was lower at 9 weeks in both the (C leads to D) and (D leads to C) groups compared to controls. There was an alteration in the ratios of the proteins and major lipid classes in myelin from the (C leads to D) animals at 9 weeks, whereas the ratios of these components were normal in the (D leads to C) animals at this age. However, at three weeks the lipid composition of the myelin isolated from (D leads to C) animals was abnormal. The results suggest that postnatal EFA deficiency results in hypomyelination in mice and that the myelin formed is of abnormal composition during early postnatal brain development. Prenatal EFA deficiency results in less severe hypomyelination with only the earliest myelin formed being of abnormal lipid composition.