New alleles in the B44 family including B*44022, B*44032, B*4411, B*4420, B*4421, B*4424, and B*8301.

Seven new HLA-B locus alleles have been described. B*44022 and B*44032 are silent substitutions altering known alleles. B*4411 carries a unique Bw4-like epitope. B*4420, B*4421, and B*4424 carry new combinations of motifs previously observed in other alleles. B*8301 appears to be the result of the replacement of exon 2 from B*4402 with exon 2 from B*5603.

Mixed lymphocyte culture reactivity of fetal baboons: application for in utero bone marrow transplantation.

Bone marrow transplantation offers a potential cure for patients suffering from genetic diseases such as inborn errors of metabolism. The optimal time to transplant many of these affected individuals would be early in gestation. To date, little information is available on the cellular immune reactivity of fetal primate lymphocytes. Therefore, we tested peripheral blood lymphocytes obtained in utero from baboon fetuses (Papio sp.) for their ability to respond in mixed lymphocyte culture (MLC) against their mothers, against a pool of unrelated animals, and in the case of fetuses given unrelated bone marrow transplants in utero, against their specific bone marrow donors. The majority of fetuses as young as 80 gestational days (182-day normal gestation period) were capable of responding strongly to maternal and unrelated lymphocytes in MLC. Of six fetuses that were transplanted, three did not engraft as indicated by undetectable levels of the donor-specific type B allele of glucose phosphate isomerase in fetal blood samples 1 month post-transplant. The three fetuses that did engraft all lost their grafts before birth. These data demonstrate that fetal lymphocytes obtained in utero can be tested for MLC reactivity and suggest that MLC testing can be used to select appropriate donor-recipient combinations for in utero bone marrow transplantation.

Tolerance of fat emulsions in very low birthweight neonates: effect of birthweight on plasma lipid concentrations.

Plasma concentrations of various lipid fractions (total lipids, free glycerol, true triglycerides, free fatty acids, and cholesterol) were studied in 20 normally grown neonates ranging in birthweight from 820 to 1500 gm and in gestational age from 28 to 34 weeks. They were subdivided into three weight categories: 750 to 999, 1000 to 1249, and 1250 to 1500 gm. A lipid emulsion was infused at a constant rate over 24 hours, beginning with an hourly infusion rate of 0.04 gm/kg and increasing each day by 0.04 gm/kg up to a maximum of 0.16 gm/kg. Neonates who weighed less than 1000 gm had higher mean plasma concentrations of total lipids and free glycerol at hourly infusion rates of 0.08 and 0.16 and of triglycerides and free fatty acids at hourly infusion rate of 0.16 gm/kg than their heavier peers. These data suggest that extreme caution be used when administering parenteral fat emulsions to neonates who weigh less than 1000 gm and that we need to monitor plasma closely for signs of hyperlipemia.

Effect of uncomplicated pregnancy on body water content and distribution in baboons.

Body water content and distribution were estimated before, during, or after 32 pregnancies in baboons. Water content of the various compartments (in liters) correlated with body weight in both nonpregnant and pregnant baboons, and with length of gestation in pregnant baboons. In proportion to body weight (in ml/kg), most water compartments did not change significantly with length of gestation. Mean plasma volume and blood volume were higher during pregnancy than before or after.

Tolerance of fat emulsions in very-low-birth-weight neonates.

Fluid and energy intakes and plasma concentrations of various lipid fractions were studied in 45 newborn infants, weighing between 820 and 1550 g, randomly assigned to one of three regimens for infusion of a fat emulsion: group 1, stepwise increase in daily dosage (1 to 4 g/kg) at a steady rate over 24 hours; group 2, stepwise increase in daily dosage (1 to 4 g/kg) at a steady rate over 16 hours, followed by a rest period of eight hours; and group 3, full dosage (4 g/kg) at a steady rate over 24 hours. At a given daily rate of infusion, mean plasma concentrations of the various lipid fractions tended to be higher in group 2 than in either group 1 or group 3. Plasma lipid concentrations correlated best with the hourly rate of lipid infusion, regardless of whether the infusion was continuous over 24 hours or intermittent.

Tolerance of fat emulsions in very-low-birthweight neonates. Monitoring of plasma lipid concentrations.

Tolerance to parenterally administered fat emulsions was studied in 45 normally grown neonates ranging from 820 to 1550 gm in birthweight, from 27 to 34 weeks in gestational age, and from 2 to 10 days postnatal age. Concentrations of total lipids, free glycerol, true triglycerides, free fatty acids, and cholesterol in plasma were studied over an 8-day period. The aim was to determine whether the concentrations of any one lipid fraction could be used to predict those of other fractions. With 650 pairs of data being correlated, the best correlation coefficients were obtained between total lipids and triglycerides (r = 0.67), total lipids and cholesterol (r = 0.63), free glycerol and free fatty acids (r = 0.55), total lipids and free fatty acids (r = 0.54), and triglycerides and free fatty acids (r = 0.50). Although all correlation coefficients were highly significant statistically (P less than 0.001), the very large standard errors precluded using any of these relationships to make clinical predictions. Problems and limitations of currently available techniques are discussed in order to provide a lead for further research.

Lipids in plasma of enterally-fed very low-birthweight neonates.

Plasma lipid patterns (total lipids, free glycerol, triglycerides, free fatty acids, and cholesterol) were studied in 10 very low-birthweight neonates assigned alternately to continuous drip versus every 2-hr bolus feedings with a formula containing 50% of its fat as medium-chain triglycerides. In the group of neonates fed continuously, plasma lipids did not vary significantly during the 4-day study. In the bolus-fed group, free fatty acid concentrations peaked 30 min after feeding; the other fractions did not vary significantly during 2 hr after feeding. Mean plasma concentrations of total lipids and triglycerides were higher in the continuous than in the bolus-fed neonates; concentrations of the other fractions were similar. Compared to plasma concentrations measured in a group of 4-day-old very low-birthweight neonates before any exposure to exogenous fat, continuously fed neonates had higher total lipid, triglyceride, free fatty acid, and cholesterol concentrations; bolus-fed neonates only had significantly higher triglyceride levels. These data emphasize the need to obtain information on plasma lipid patterns that is specific for gestational maturity, postnatal age, and method and type of feeding.

Fat emulsion tolerance in very low birth weight neonates: effect on diffusion of oxygen in the lungs and on blood pH.

Forty-one very low birth weight neonates (820 to 1,510 g and 27 to 34 weeks of gestation) requiring total parenteral nutrition were randomly assigned to one of three regimens of administration of fat emulsion for a period of eight days. Groups I and II received the emulsion at a constant rate for, respectively, 24 and 16 hours, beginning with a daily dosage of 1 g/kg and increasing daily by 1 g/kg to a maximum of 4 g/kg. Group III received the emulsion at a constant rate or 4 g/kg for 24 hours. Blood pH and alveolar-arteriolar gradient of oxygen diffusion in the lungs were measured at regular intervals. The various regimens and rates of fat infusion appeared to have no deleterious effect on blood pH and alveolar-arteriolar oxygen diffusion gradient. Infusion rates as used in the study for appropriate for gestational age very low birth weight neonates appear to be safe, although caution is always warranted when dealing with tiny neonates whose pulmonary reserve is minimal. In view of data from other studies, it is suggested to infuse fat at a constant rate for 24 hours to avoid overloading the clearance mechanisms of fat particles from plasma.

Effect of extracorporeal membrane oxygenation on body water content and distribution of baboon neonates.

Water contents of the various body compartments were estimated before and after a 7- to 10-h period of extracorporeal membrane oxygenation in five healthy baboon neonates. Total body water, extracellular water, and plasma volume were estimated simultaneously by antipyrine, bromide, and T-1824 dilution. Volumes of intracellular water, interstitial water, and blood and red cells were calculated from the experimental estimates. Mean preextracorporeal membrane oxygenation estimates of body water volume were in agreement with those previously reported in baboon neonates. During extracorporeal membrane oxygenation, no statistically significant changes occurred in the water content of the various body compartments. This absence of changes was contrasted to the changes demonstrated in human infants and adults undergoing intracardiac surgery with extracorporeal oxygenation and hypothermia and various hypotheses were put forward to explain the different changes observed.

Estimates of body water content in normally grown baboons during the first postnatal month.

Water contents of various body compartments were estimated within 9 h of birth in eight baboon neonates and at a mean of 29 days (27-32 days) in seven baboons. All animals were normally grown and delivered spontaneously at term. There was no difference in mean antipyrine space, corrected bromide space, intracellular water, interstitial water, and plasma and blood volumes observed on day 1 and day 29. Mean estimate of red cell volume was lower on day 29 than on day 1.

Body water content and distribution in nonpregnant adult female baboons.

Water contents of the various body water compartments were estimated in 16 nonpregnant adult female baboons and compared to human data. Total body water, extracellular water, and plasma volumes were determined by dilution studies. Intracellular water, interstitial water, blood volume, and red cell volume were calculated. The data were compatible with the finding that baboon females probably have less body fat than their human counterparts. Our data establish a basis for longitudinal studies of the changes in body water content and distribution during normal and pathological pregnancies.