PCO2 and room air saturation values in premature infants at risk for bronchopulmonary dysplasia.

OBJECTIVE: To determine the capillary partial pressure of carbon dioxide (PCO(2)) and room air transcutaneous hemoglobin saturation (RA SAT) at 36 weeks' postmenstrual age (PMA) in infants born with weight between 501 and 1250 g. STUDY DESIGN: Multicenter, prospective investigation with primary data collection within 72 h of 36 weeks PMA or discharge, whichever first. PCO(2) and RA SAT determinations were done at rest on infants not requiring mechanical ventilation or nasal continuous positive airway pressure (NCPAP). RESULT: A total of 220 infants were enrolled (mean gestational age 27.7 weeks, mean birthweight 951 g). In infants with traditionally defined chronic lung disease (CLD) compared to those without CLD, the mean PCO(2) was significantly higher (54 versus 45 mm Hg) and the median RA SAT significantly lower (<80 versus 97%). In infants with the new classification of bronchopulmonary dysplasia (BPD), there was a significant linear trend toward increasing PCO(2) with increasing severity of BPD (45, 47, 54 and 62 mm Hg in No, Mild, Moderate and Severe BPD). There was a significant linear trend toward decreasing RA SAT with increasing severity of BPD (97, 95 <80, <80% in No, Mild, Moderate and Severe BPD). CONCLUSION: Defining CLD as BPD based upon a RA SAT test is a more discriminate, objective method to categorize lung injury. PCO(2) is an objective measure of lung function that inversely correlates with RA SAT. These determinations done together at 36 weeks PMA may provide more precise and accurate estimates of lung injury that might allow for better understanding of pulmonary therapies and clearer comparison of BPD rates and severities among NICUs.

Calcium chloride in neonatal parenteral nutrition: A 15 year experience.

OBJECTIVE: The objective of this study was to determine if outcomes at our neonatal intensive care units (NICUs) since we began using calcium chloride (CaCl2) as our preferred calcium additive in order to reduce aluminum (Al) exposure are within expected outcome ranges for NICUs in the U.S. where calcium gluconate in glass vials (CaGlu-Gl) has been the preferred additive. STUDY DESIGN: A retrospective study of very low birth weight infants born between January 1, 2000 and December 31, 2014. Outcomes in two intensive care units (NICUs) using CaCl2 were compared to all U.S. NICUs in the Vermont Oxford Network. Primary outcomes were chronic lung disease (CLD), percent requiring supplemental oxygen at 28 days, and mortality excluding early deaths (MEED). The incidence of IV infiltrates of all admissions to the study NICUs in 2013-2014 was compared to the literature. RESULTS: The incidence of CLD and those requiring oxygen at 28 days were 24.0% vs 28.6% and 46.2% vs 51.8% for the study NICUs compared to all U.S. NICUs, respectively (both p < 0.0001). The MEED was 8.7% vs 10.3% (p < 0.002). All major morbidities were lower at the study NICUs. The incidence of infiltrates was lower than that in the literature. CONCLUSION: The use of CaCl2 was not associated with any detectable adverse effects. Calcium chloride appears to be a safe alternative to the use of CaGlu-Gl based upon studies of clinical outcomes.

The quest for sustained multiple morbidity reduction in very low-birth-weight infants: the Antifragility project.

OBJECTIVE: Can a comprehensive, explicitly directive evidence-based guideline for all therapies that might affect the major morbidities of very low-birth-weight (VLBW) infants help a neonatal intensive care unit (NICU) further improve generally favorable morbidity rates? Can Antifragility principles of provider adaptive growth from stressors, enhanced infant risk assessment and adherence to effective therapies minimize unproven treatments and reduce all morbidities? STUDY DESIGN: Prospectively planned observational trial in VLBW infants: control group born October 2011 to September 2013 and study group October 2013 to September 2015. Multi-disciplinary evidence-based review assigned all NICU treatments into one of four distinct categories: (1) always employ this therapy for VLBW infants, (2) never use this therapy, (3) employ this questionable therapy thoughtfully, only in certain circumstances and (4) this therapy has insufficient evidence of efficacy and safety. Extensive staff education emphasized evidence-based potentially better practice (PBP) selection with compliance checks, appreciation of intertwined co-morbidities and prioritizing infant risk reduction strategies. RESULTS: Control included 221 infants, mean (s.d.) age 29 (2.6) weeks, birth weight 1129 (257) g and Study included 197 infants, 29 (2.7) weeks, 1093 (292) g. One hundred and four distinct therapies were placed into categories 1 to 4, with 32 specific compliance checks. Overall mean compliance with the process checks during the second era was 70%, high: 100% (exclusive breast milk use), low: 24% (correct pulse oximetry alarm settings). Morbidity and mortality rates did not significantly change during the second era. CONCLUSIONS: In our NICU with favorable morbidity rates, an expanded effort using a comprehensive therapy guideline for VLBW infants did not further improve outcomes. We need deeper understanding of continuous quality improvement (CQI) fundamentals, therapy compliance, co-morbidity relationships and enhanced sensitivity of risk assessment. Our innovative Antifragility PBP guideline could be useful to other NICUs seeking improvement in VLBW infant morbidities, as we offer a reasoned and concise template of a broad array of therapies categorized efficiently for transparency and review, designed to enhance responsible CQI decision-making.

Extremely premature birth and the choice of neonatal intensive care versus palliative comfort care: an 18-year single-center experience.

OBJECTIVE: Review all live births 22 0/7 through 26 6/7 weeks gestation born 1996 through 2013 at our institution to describe the decision process and immediate outcomes of palliative comfort care (PCC) versus neonatal intensive care (NICU) and whether any significant family complaints or quality assurance concerns arose. STUDY DESIGN: Retrospective chart review, physician and ethicist interview process and database review focused upon our established periviability counseling guidelines that are directive of PCC at 22 weeks gestation and NICU at 26 weeks but supportive of informed family choice of either option at 23, 24 and 25 weeks. RESULT: At 22 weeks--all 54 infants had PCC; at 23 weeks--29/78 (37%) chose NICU care, 6/29 (21%) infants survived; at 24 weeks--79/108 (73%) chose NICU care, 47/79 (59%) survived; at 25 weeks--147/153 (96%) chose NICU care, 115/147 (78%) survived; and at 26 weeks--all infants had NICU care, 176/203 (87%) survived. Over 18 years and 606 births, we identified only three significant concerns from families and/or physicians that required formal review. CONCLUSION: Most pregnant women and families choose NICU care for their extremely premature infant, but if given the option via shared decision making, a significant proportion will choose PCC at gestational ages that some NICUs mandate resuscitation. We support a reasoned dialogue and bioethical framework that recognizes human values to be irreducibly diverse, sometimes conflicting, and ultimately incommensurable--value pluralism. Respectful shared decision making requires thoughtful and compassionate flexibility, nuanced and individualized suggestions for PCC or NICU and the reduction of hierarchical directives from physicians to families. We continue to advocate and rely upon informed family preference between 23 and 25 weeks gestation in our updated 2015 periviability guidelines.

Progressive recruitment of follicular cells with graded secretory responsiveness during stimulation of the thyroid gland by thyrotropin.

One of the earliest responses of the thyroid cells to TSH is macropinocytosis with formation of intracellular colloid droplets. We demonstrate here that increasing stimulation with TSH not only elicits a highly individual macropinocytotic response among different follicular cells but that the fraction of TSH-responsive cells is also a function of the TSH dose. After pretreatment with T4, mice and rats were injected ip with bovine TSH and killed 2 h later. The macropinocytotic response to TSH was evaluated on periodic acid-Schiff-stained 3-microns sections of the thyroids in terms of droplet number per 25 follicles and, in addition, by assessing recruitment, i.e. percentage of droplet-containing cells. Both variables increased with increasing TSH stimulation until they reached a plateau at about 9 mU TSH in mice and at about 300 mU TSH in rats: the percentage of droplet-containing cells gradually increased in mice from 2% (no TSH) to 67% (9 mU TSH) and in rats from 11% (no TSH) to 54% (300 mU TSH). Overall pinocytotic response as well as thyrocyte recruitment could be modified by extra- and intrathyroidal factors: for example, pretreatment of the mice with an iodine-deficient diet increased the maximal percentage of droplet containing cells to nearly 90%. Obviously, two separate components of the macropinocytotic response of the thyroid gland to TSH can be distinguished: the first is the gradually increasing fraction of droplet-containing cells, the second is the well known increase of the number of colloid droplets in each TSH-responsive cell with progressive TSH stimulation. Recruitment of thyrocytes with a gradually increasing natural threshold to a hormonal stimulus appears to be a fundamental mechanism in the thyroid gland and possibly in other organs.

Generation of intercellular heterogeneity of growth and function in cloned rat thyroid cells (FRTL-5).

The most characteristic hallmarks of human nodular goiters are nodular growth and heterogeneity of structure and function between different areas of the same goiter. In search of the earliest detectable stage of thyroid heterogeneity we have observed doubling times, TSH dependency, and thyroglobulin production in colonies formed from individual FRTL-5 cells growing as monolayers in slide flasks. Single cells and the colonies derived thereof were followed on photographs taken daily until confluence. We observed that each cell had its individual stable multiplication rate throughout the observation period. This was true for all TSH doses tested (0.625-10 mU/ml). A wide range of doubling times (20 h to almost infinite) in the individual cells was observed. The mean growth velocity of subcloned cell lines was highly reproducible in consecutive passages, although a minority of cells escaped this rule. Cells with either high or low thyroglobulin content occurred in clusters, indicating again that specific traits tend to remain stable in the offspring. We conclude that a highly individual growth program, unrelated to mutation, appears to be switched on at the very moment a cell is generated and that this program is passed on to the majority of the offspring, with a minority of cells acquiring qualities differing from those of their sister cell. Therefore, goiter heterogeneity may be the in vivo amplification of a natural phenomenon occurring in all growing cells. Monoclonal adenomas in vivo and nontransformed immortal cell lines in vitro may represent the far end of the large spectrum of individual growth potency among normal thyrocytes.

Colloidal aggregates of insoluble inclusions in human goiters.

To shed some light on the physicochemical properties of the thyroid follicular colloid, we have screened retrospectively the autoradiographs of 60 human nodular goiters labeled 17 h preoperatively with 100 microCi 125I for evidence of colloid compartmentalization. In 87% (52/60) of all goiters examined, sporadic or multiple colloidal inclusions ('colloid stones') not mixing with newly labeled Tg were detected. The detailed analysis of 17 goiters revealed a mean incidence of 0.09+/-0.11 'colloid stones' of variable size per follicle ranging from 0.02+/-0.01 (10) to 0.43+/-0.09 (5) (mean values +/- S.D., number of sections examined in brackets). In this study we did not find a clear-cut association of incidence of 'colloid stones' with sex, age or nosologic group (hyperthyroid, preclinically hyperthyroid, euthyroid). The existence of different colloidal compartments as demonstrated in this and other studies is of considerable importance for thyroid function, interpretation of iodine kinetics, and studies on the role of iodine on growth and function of the thyrocytes. Different thyroidal iodine compartments could well be of functional relevance, for example in the adaptation of thyroid hormone secretion to antithyroid drugs or in severe and prolonged iodine deficiency, when very slow compartments become an important source of minimal quantities of iodine and thyroid hormone. 'Colloid stones', for example, may well explain the repeatedly observed, surprisingly large total iodine store in human endemic goiters, even in the presence of severe iodine deficiency. It is evident that the existence of multiple iodine compartments and, in particular, of particulate slow-turnover pools complicates the interpretation of total glandular iodine measurements with modern techniques such as X-ray fluorescence and positron emission tomography.

Epidermal growth factor stimulates cell proliferation and inhibits iodide uptake of FRTL-5 cells in vitro.

In accordance with the available data most authors conclude that epidermal growth factor (EGF) has very little or no effect on FRTL-5 cells. This has been viewed as a serious handicap of this cell line. In the present study we cultivated three strains of FRTL-5 cells from different sources and assessed their response to EGF with regard to proliferation, function and differentiation. Cell proliferation was assessed by counting in a Coulter cell counter after culturing cells at suboptimal conditions in well plates. Cell function was studied by measuring iodide uptake. Cell differentiation was examined immunocytochemically by staining monolayer cultures for thyroglobulin (Tg) and EGF receptor (EGFr) as well as morphologically by microscopical evaluation of monolayer cultures. All three FRTL-5 cell lines investigated express EGFr. In two wild type FRTL-5 cell lines EGF stimulates growth, an effect that is enhanced by the presence of TSH, and partially inhibits iodide uptake. A third mutated strain of FRTL-5 cells does not respond to EGF. Tg expression can be demonstrated immunocytochemically in EGF-treated cells as well as in controls. Morphologically, in monolayer culture EGF-treated cells cannot be distinguished from controls. Contrary to previous reports, these studies demonstrate EGF effects on FRTL-5 cells that are consistent with EGF effects established in other thyroid follicular cells.

Acquired and naturally occurring resistance of thyroid follicular cells to the growth inhibitory action of transforming growth factor-beta 1 (TGF-beta 1).

While the multifunctional proteins of the transforming growth factor-beta (TGF-beta) family have a potent antiproliferative effect on thyroid follicular cell growth, increased expression of TGF-beta in proliferating thyroid cells and in thyroid tumours has recently been described, suggesting a secondary counter-regulatory role of these proteins. We have studied further this apparent paradox in vitro using FRTL-5 cells, 5 continuous cell strains from feline multinodular goitres (MNG) and 29 primary cultures prepared from human MNG. While dose dependent inhibition of FRTL-5 cell growth was confirmed, a variable fraction of these cells was naturally resistant towards TGF-beta 1, thus explaining the large interassay variability of growth inhibition (36 to 98% within 2 days, n = 19). After 40 days of continuous exposure, FRTL-5 cells became fully refractory towards TGF-beta 1 inhibition, due to the selective growth of naturally resistant subclones, as demonstrated for example by microscopic observation of three-dimensionally growing collagen-embedded cell clusters. The refractoriness could still be demonstrated even after several cell passages. In addition, 2 out of 5 feline thyroid cell strains obtained from feline MNG and 18 out of 29 primary cultures from human MNG showed a high degree of refractoriness towards TGF-beta. We conclude that constitutively TGF-beta resistant cells may occur in thyroid glands and that persistent TGF-beta refractoriness may secondarily be acquired. Resistant cells may escape regular growth control mechanisms and hence may contribute to the notorious heterogeneity of thyroid growth and to nodular transformation.

Low intrathyroidal iodine concentration in non-endemic human goitres: a consequence rather than a cause of autonomous goitre growth.

Iodine may have an inhibitory and, in some circumstances, a stimulatory effect on thyroid follicular cell growth. Exogenous iodine deficiency causes the growth of endemic goitres and it has been claimed that low intrathyroidal iodine stores stimulate growth. On the other hand, the role of iodine, if any, in regulating the growth of human nodular goitres exposed to an ample supply of iodine has not been studied systematically. Very few data on intrathyroidal iodine concentration in this type of goitre are available. In the present work we have investigated total iodine content in 24 samples from 11 clinically and histomorphologically well-defined fast and autonomously growing human nodular goitres from a non-endemic area. Iodine was fractionated into thyroglobulin-iodine and non-thyroglobulin-iodine. The regional distribution of intrathyroidal iodo-compounds was also assessed in three goitres. Total iodine concentration, as well as its sub-fractions, i.e. thyroglobulin-iodine and non-thyroglobulin-iodine, were significantly lower than in normal thyroids. Furthermore, there was large inter- and intraindividual heterogeneity of all iodo-compounds as well as of thyroglobulin. Total iodine concentration varied by a factor of almost 40 between different goitre samples and by a factor of 20 between samples taken from the same goitre. Total non-thyroglobulin-iodine, the only fraction comprising possible cell growth-regulating iodo-compounds, varied by a factor of > 60 between different goitres and by a factor of > 6 between different samples of the same goitre. The low iodine concentration in all our goitre samples did not differ from values reported in the literature for endemic iodine-deficient goitres. Since all goitres studied here were actively growing while exposed to an ample supply of iodine, iodine shortage cannot be a primary and causal factor for the growth of this type of sporadic goitre. Rather, the low concentration and the large inter- and intraindividual heterogeneity of all iodo-compounds appear to be secondary incidental events well explained by the recently developed concept of autonomous thyroid growth.

Galactose clearance and carbohydrate metabolism across the gastrointestinal tract in the newborn lamb.

We prepared 16 newborn lambs with chronically indwelling catheters in the portal vein, mesenteric vein, femoral vein, and femoral artery to study galactose clearance, portal venous blood flow, and carbohydrate metabolism across the gastrointestinal (GI) tract. Galactose clearance was measured by infusing galactose into the femoral vein to achieve a steady-state galactose concentration in the femoral artery. We observed a curvilinear relationship between galactose clearance and the steady-state galactose concentration. The relationship could be modeled as an apparent Michaelis-Menten system: Clearance = Vmax/(Km + [Gal]ssa), where Vmax = 17.0 +/- 2.5 mg/min/kg body weight and Km = 11.0 +/- 0.4 mg/dL. Substrate/oxygen quotients across the viscera drained by the portal vein were measured in the fasted state and during systemic galactose infusion. A net uptake of glucose and galactose by the GI tract was found with quotients of 0.19 +/- 0.07 and 0.05 +/- 0.02, respectively. There was a relatively large net efflux of lactate across the portal circulation, with a quotient of -0.13 +/- 0.03. The indicator-dilution technique was used to estimate portal venous blood flow (PVBF) in the neonatal period with a resting, fasted state value of 92.8 +/- 4.4 mL/min/kg body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression patterns of extracellular matrix components in native and cultured normal human thyroid tissue and in human toxic adenoma tissue.

The extracellular matrix (ECM) and basement membranes (BM, a specialized form of ECM) greatly influence proliferation, differentiation, and function of cells and the structure of tissues. While a considerable amount of information is available on thyroid cellular proliferation, differentiation and function, much less is known about thyroid ECM and BM. In this study the presence of the ECM/BM components fibronectin, collagen IV, alpha1, beta1, gamma1 laminin, several laminin variants, osteonectin, and perlecan was demonstrated in cryosections of nonadenomatous and toxic adenoma human thyroid tissue. Also, positive immunohistochemical staining for collagen IV, laminin, perlecan, and fibronectin was obtained in sections of human thyroid tissue cultured in a three-dimensional (alginate) culture system. The present study provides methods and data that will facilitate the investigation of the interaction between cells and ECM in thyroid tissue.

Alginate gel culture allows the retention of extracellular matrix and follicular structure of rat thyroid tissue but does not lead to the formation of follicles by FRTL-5 cells.

Extracellular matrix (ECM) and basement membrane (BM) components were studied by immunohistological methods in native rat thyroid tissue, and in rat thyroid tissue and FRTL-5 cells cultured in a three-dimensional alginate bead system. In all three situations, the presence of collagen IV, laminin, perlecan, and fibronectin was demonstrated. There were marked differences between rat thyroid tissue and FRTL-5 cells in culture. Rat thyroid tissue maintained a follicular structure, whereas FRTL-5 cells did not form follicles. Rat thyroid cells multiplied more slowly than FRTL-5 cells and thyroglobulin (Tg) was visible in the follicular lumen, while in FRTL-5 cells Tg was only seen intracellularly. Tg iodination was much lower in FRTL-5 cells than in rat cells. In rat thyroid cells, positive staining for collagen IV, laminin, and perlecan was seen in thin membranes around individual follicles, and for fibronectin around groups of follicles. In FRTL-5 cells, these ECM/BM components could be identified, but were not organized into equally regular networks around groups of cells. These results demonstrate that of the two types of cells examined, primary cultures of rat thyroid cells in alginate beads maintain structural and functional similarities to native thyroid tissue and would therefore be suitable for future in vitro studies of thyroidal ECM/BM and their interrelationship with growth and function of this organ. FRTL-5 cells cultured in alginate beads show some functional, but not structural similarities to native thyroid tissue and so would be less valuable for use in such studies.

Developing a frenotomy policy at one medical center: a case study approach.

The objective of this study was to change procedures in our medical center regarding frenotomy for ankyloglossia (tongue-tie). The medical and breastfeeding outcomes of 36 fullterm infants who received frenotomies were studied. The information was used to develop frenotomy eligibility standards that would guide other physicians and insure timely treatment to avoid breastfeeding cessation.

What happens when the patent ductus arteriosus is treated less aggressively in very low birth weight infants?

OBJECTIVE: It remains unclear whether indomethacin (INDO) and/or surgical ligation (LIGATE) are necessary to improve outcomes in premature infants with a patent ductus arteriosus (PDA). We have adopted a conservative approach to PDA management that emphasizes waiting for spontaneous closure unless certain cardiorespiratory distress criteria are met. STUDY DESIGN: This was a before-after observational study in infants born 501 to 1,500 g in two distinct epochs. Era 1 (January 2005 to December 2007) featured traditional management with INDO and LIGATE used early to close all moderate and large PDAs in infants receiving any respiratory support. Era 2 (January 2008 to June 2009) emphasized modest fluid restriction, watchful waiting and limited INDO and LIGATE to only those infants with large PDAs who met certain cardiorespiratory distress criteria. RESULT: Era 1 included 139 infants with a PDA, mean (s.d.) gestational age 27.5 (2) weeks; Era 2 72 infants, mean (s.d.) gestational age 27.5 (2) weeks. In Era 2, INDO use significantly decreased (79% of infants to 26%, P<0.001), and 28 day total fluids decreased (140 vs. 130 ml kg(-1) day(-1), P<0.001). LIGATE rate was 45% in Era 1, 33% in Era 2 (P=0.11). There were no significant differences in supplemental oxygen, nasal continuous positive airway pressure, or mechanical ventilation days. There were no significant differences in mortality or individual morbidities. The combined outcome of chronic lung disease (CLD) or mortality after Day 7 significantly increased (Era 1, 40%, Era 2, 54%, P=0.04). More infants were discharged home with a PDA in Era 2, but most resolved spontaneously and the need for closure therapy after discharge from the neonatal intensive care unit (NICU) did not increase. Multiple regression analysis demonstrated Era 2 management did not predict an increased risk of one or more interlinked morbidities. CONCLUSION: Tolerance of the PDA with watchful waiting for spontaneous closure, modest fluid reduction, and less INDO use is a reasonable treatment strategy that is not associated with significant changes in NICU mortality or individual morbidities. We did note an increase in the combined outcome of CLD or mortality after Day 7, thus our investigation supports the urgency of a randomized controlled trial comparing traditional PDA management with a true control group similar to our Era 2 management to answer important questions of short and long-term outcomes.

Hyperglycemia, insulin and slower growth velocity may increase the risk of retinopathy of prematurity.

OBJECTIVE: Strategies to reduce Retinopathy of Prematurity (ROP) have focused primarily on respiratory management. Hyperglycemia (HG) and insulin use, risk factors for adult diabetic retinopathy, as well as growth rates may be modifiable variables useful to reduce ROP. STUDY DESIGN: This was a retrospective chart review of all infants born at <30 weeks gestation from 2003 to 2007 who survived to discharge in our neonatal intensive care unit (NICU). All whole-blood glucose values (BG in mg dl(-1)) done in the first 29 days of life were collected for analysis. RESULT: BGs were done at least every 3 to 6 h for the first 48 to 96 h of life, then every 6 to 24 h thereafter, as long as infants remained on hyperalimentation. Hyperglycemia was defined as mild (BG 151 to 180), moderate (181 to 210) or severe (>210). Insulin use (given if BG>180 to 210) was also noted for each simultaneous BG. ROP was classified as none, mild (stage 1 to 2) or severe (stage 3 to 4). Growth velocity (g kg(-1) per day), length and head circumference were also analyzed. In all, 372 infants mean (s.d.) gestational age 27.6 (1.4) weeks, mean (s.d.) birth weight 994 (242)g had 18,649 BGs analyzed. 103 (28%) of the infants had mild ROP and 29 (8%) had severe ROP. 137 (37%) of the infants received at least 1 day of exogenous insulin (median days 9, range 1 to 26). Higher cumulative mean BG, more episodes of HG, and more insulin exposure were associated with an increased incidence and severity of ROP. Ordinal logistic regression identified lower gestational age, male gender, fetal growth restriction, slower NICU growth velocity, and higher BG as predictors for severity of ROP. However, insulin use was a stronger predictor than BG, and replaced it in the risk model. CONCLUSION: After adjusting for important risk factors, HG and especially insulin use in premature infants may increase the risk of ROP. In addition, slower NICU growth velocity, but not rates of head or length growth, was predictive of ROP.

Galactose, glucose, and lactate concentrations in the portal venous and arterial circulations of newborn lambs after nursing.

We have used the newborn lamb prepared with chronic indwelling catheters to study carbohydrate metabolism in the unstressed, postprandial state. Lambs were fasted 5 h and then allowed to nurse ad libitum from their mothers for 20 min. Serial determinations of whole blood galactose, glucose, and lactate concentration were then made from the portal venous and arterial circulations. Portal venous galactose concentration increased significantly after milk ingestion, but arterial galactose concentration did not increase from baseline unless the portal venous galactose concentration exceeded 10-12 mg/dl suggesting a threshold effect for hepatic galactose clearance. Glucose concentration increased significantly in both circulations with portal venous galactose concentration greater than arterial galactose concentration in all cases. Galactose and glucose were absorbed from the intestine at approximately equal rates. Lactate was not absorbed into the portal venous circulation to any great extent after lactose ingestion.