What is bad news in fertility care? A qualitative analysis of staff and patients' accounts of bad and challenging news in fertility care.

STUDY QUESTION: What do fertility staff and patients think is bad news in fertility care? SUMMARY ANSWER: Staff and patients agree bad news is any news that makes patients less likely to achieve parenthood spontaneously or access and do successful treatment, but their appraisals of how bad the news is are differently influenced by specific news features and the context of its delivery. WHAT IS KNOWN ALREADY: Bad news is common in fertility care, but staff feel unprepared to share it and four in 10 patients react to it with unanticipated emotional or physical reactions. Research has paid much attention to how bad news should be shared, but considerably less to what news is perceived as bad, despite the fact this may dictate elements of its delivery. STUDY DESIGN, SIZE, DURATION: Two cross-sectional, online, mixed-method surveys (active 7 January-16 July 2022) were distributed to fertility staff and patients across the UK and Europe. PARTICIPANTS/MATERIALS, SETTING, METHODS: Staff inclusion criteria were being a healthcare professional working in fertility care and having experience of sharing bad news at least once a month. Patients' inclusion criteria were being adults and having had a conversation in which staff shared or explained bad news concerning their fertility care within the last 2 months. Surveys were created in English using Qualtrics, reviewed by patients and healthcare professionals, and distributed via social media, Prolific, fertility organizations, and scientific societies. Patients were asked, regarding the last time bad news were shared with them, 'What was the bad news?' and 'What other news would you consider bad news in fertility care?'. Staff were asked to 'List the three most challenging topics of bad news you share with your patients'. Staff and patient data were separately thematically analysed to produce basic codes, organized into sub-themes and themes. Themes emerging from patients' and staff data were compared and synthesized into meta themes. MAIN RESULTS AND THE ROLE OF CHANCE: Three hundred thirty-four staff accessed the survey, 286 consented, and 217 completed (65% completion rate). Three hundred forty-four patients accessed the survey, 304 consented, and 222 completed (64% completion rate). Eighty-five percent of participants were women, 62% resided in Europe, and 59% were in private care. Average staff age was 45.2 (SD = 12.0), 44% were embryologists or lab technicians, 40% were clinicians (doctors, consultants, or physicians), and 8% nurses or midwifes. Average patient age was 32.2 (SD = 6.4) and 54% had children. Staff answers originated 100 codes, 19 sub-themes and six themes. Patients' answers produced 196 codes, 34 sub-themes, and 7 themes. Staff and patient themes were integrated into three meta-themes reflecting main topics of bad news. These were Diagnosis and negative treatment events and outcomes, Inability to do (more) treatment, and Care and patient factors disrupting communication. Staff and patients agreed that some news features (uncertain, disruptive, definitive) made news more challenging but disagreed in relation to other features (e.g. unexpected/expected). Patient factors made bad news more challenging to staff (e.g. difficult emotions) and care factors made bad news more challenging to patients (e.g. disorganized care). LIMITATIONS, REASONS FOR CAUTION: Participants were self-selected, and most were women from private European clinics. Questions differed for staff and patients, focused on subjective perceptions of news, and did not measure news impact. WIDER IMPLICATIONS OF THE FINDINGS: The badness of fertility news is not only a product of the extent to which the news compromises parenthood goals but also of its features (timing, nature, number) and the context in which the news is delivered. Guidance on sharing bad news in fertility care needs to go beyond easing the process for patients to also consider staff experiences. Guidance may need to be tailored to news features and context. STUDY FUNDING/COMPETING INTEREST(S): Cardiff University funded the research. S.G., J.B., O'.H., and A.D. report funding from the Higher Education Funding Council for Wales and the European Society for Human Reproduction and Embryology (ESHRE) to develop fertiShare: a sharing bad news eLearning course for fertility care. fertiShare will be distributed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Licence (CC BY-NC-SA 4.0). No other conflicts are reported in relation to this work. TRIAL REGISTRATION NUMBER: N/A.

Plasma and urine riboflavin during riboflavin-free nutrition in very-low-birth-weight infants.

BACKGROUND: Very-low-birth-weight (VLBW; birth weight <1500 g) infants receive enteral and parenteral nutriture that provides greater daily riboflavin (vitamin B2) than does term infant nutriture, and elevated plasma riboflavin develops in these infants after birth. The purpose of this study was to measure plasma and urine riboflavin concentrations in VLBW infants during riboflavin-free nutrition. Our hypothesis was that elevated plasma riboflavin develops in VLBW infants because of high daily intake and immature renal riboflavin elimination. METHODS: Eighteen clinically healthy VLBW infants received parenteral nutrition and preterm infant formula during the first postnatal month. On postnatal days 10 and 28, the infants received specially prepared riboflavin-free enteral and parenteral nutrition for the 24-hour study period. Serial collections of plasma were made at time 0 and at 12 and 24 hours. Urine was collected continuously for the 24-hour period in 4-hour aliquots. Samples were analyzed for riboflavin concentration. RESULTS: During the 24-hour riboflavin-free study period on postnatal day 10, plasma riboflavin decreased 56% from 185 +/- 37 ng/mL (mean +/- SEM), and urine riboflavin decreased 75% from 3112 +/- 960 mg/mL. Similarly, on postnatal day 28, plasma riboflavin decreased 79% from 184 +/- 32 ng/mL, and urine riboflavin concentration decreased 91% from 5092 +/- 743 ng/mL during the 24-hour riboflavin-free study period. Riboflavin half-life (t(1/2)) was 18.5 hours on postnatal day 10 and decreased 48% by postnatal day 28. Riboflavin elimination was 145.1 +/- 20.6 mg/kg per day on postnatal day 10 and increased 40% by postnatal day 28. CONCLUSION: The VLBW infants who received parenteral nutrition and preterm infant formula had elevated plasma riboflavin on postnatal days 10 and 28. Plasma riboflavin t(1,2) was shorter and renal riboflavin elimination was greater on postnatal day 28 than on postnatal day 10. Plasma riboflavin was normal after 24 hours of riboflavin-free nutrition. The pattern of plasma and urine riboflavin in VLBW infants suggests a lower daily intake would maintain plasma riboflavin close to normal.

Plasma and urine riboflavin and pyridoxine concentrations in enterally fed very-low-birth-weight neonates.

Preterm infant formulas (PIFs) for very-low-birth-weight (VLBW) infants (birth weight, < 1,500 g) are augmented to provide daily riboflavin and pyridoxine at levels up to five-fold greater than in term infant formula and 18-fold greater than in human milk. We evaluated plasma riboflavin and pyridoxine concentrations in VLBW infants who received PIF during their first postnatal month. Eighty-eight plasma and 124 urine samples were collected for riboflavin- and pyridoxine-concentration measurements from 57 clinically healthy VLBW infants weekly during their first postnatal month. Concentrations were measured using high-performance liquid chromatography. At the time of the sample, patients were receiving > or = 80% of their total calories via enteral feedings. Plasma riboflavin concentrations rose from 45.3 +/- 7.3 ng/ml at baseline (mean +/- SEM) to 173.5 +/- 20.3 ng/ml by 1 week of age and remained at 177.3-199.7 ng/ml during the following three weekly measurements; values were up to 14-fold above baseline concentration. Urine riboflavin concentration increased from 534 +/- 137 ng/ml at baseline to 3,521 +/- 423 ng/ml by 1 week of age and remained at 4,451-5,216 ng/ml during the next 3 weeks. In a similar pattern, baseline plasma (69.4 +/- 10.4 ng/ml) and urine (145 +/- 30 ng/ml) pyridoxine concentrations were significantly increased by 1 week postnatal age; they remained at 163-248 ng/ml (plasma) and 1,573-2,394 ng/ml (urine) through the first postnatal month. Plasma and urine riboflavin and pyridoxine concentrations in enterally fed VLBW infants increased from baseline concentrations by 1 week of postnatal age and remained elevated for the first postnatal month. High daily intake and immature renal development are probable contributing causes of the elevated plasma riboflavin and pyridoxine concentrations. We suggest that lower daily enteral administration of riboflavin and pyridoxine should maintain adequate blood concentrations and minimize potential toxicity.

Retinol (vitamin A) and riboflavin (vitamin B2) administration and metabolism in very low birth weight infants.

The combination of marginal hepatic retinol stores at delivery and the reduction of daily retinol dose due to complications with the delivery system places the VLBW infant receiving parenteral nutrition at high risk for retinol deficiency during the first month of life. This has serious health implications because retinol is essential during this period for normal growth and repair of the pulmonary tissue in VLBW infants. Enterally fed VLBW infants, on the other hand, receive relatively higher doses of retinol from vitamin-supplemented premature infant formula and fortified breast milk. Equally serious is the problem of monitoring vitamin A status in infants receiving supplemental doses of vitamin A. It seems clear that while plasma vitamin A levels are the most easily available method of monitoring vitamin A status, further studies are necessary to determine if these levels correlate with hepatic content. This is of particular concern since liver disease is common in VLBW infants and vitamin A hepatotoxicity has been described in a cohort of 41 patients receiving therapeutic doses of the vitamin. While further research of daily enteral and parenteral retinol requirements of VLBW infants should continue, formulation of a specific VLBW parenteral vitamin supplement should also be developed.

Prospective observations of 100 high-risk neonates by high-field (1.5 Tesla) magnetic resonance imaging of the central nervous system: I. Intraventricular and extracerebral lesions.

The results of observations of the first 100 neonates at the University of Texas Health Science Center (Houston) who received magnetic resonance imaging of the central nervous system by means of a high-field image (1.5 T) are reported. All were assessed prospectively to be at risk neurodevelopmental delay. This first report specifically addresses the appearance of primarily hemorrhagic intracranial lesions, including intraventricular hemorrhage (n = 28), and extracerebral lesions, which include 3 cases of venous sinus thrombosis (n = 20). The signal intensities of hemorrhage underwent a characteristic evolution with time with only minor variations in the study group. Magnetic resonance imaging detected direct evidence of hemorrhage for up to 2 months, but hemosiderin was detected as a late indicator of hemorrhage for up to 9 months. Magnetic resonance imaging was equal in benefit to head ultrasonography and computed tomography for the diagnosis of intraventricular hemorrhage, but magnetic resonance imaging was also able to approximate the time of onset of hemorrhage. Magnetic resonance imaging was superior for the evaluation of extracerebral hemorrhage; ultrasonography failed to detect any of these lesions and computed tomography detected only 3 of 7. Short-term neurological abnormality was assessed, but the ability of magnetic resonance imaging to predict long-term neurodevelopmental delay is unknown and is the subject of an ongoing project.

Prospective observations of 100 high-risk neonates by high-field (1.5 Tesla) magnetic resonance imaging of the central nervous system. II. Lesions associated with hypoxic-ischemic encephalopathy.

One hundred neonates determined prospectively to be at risk for neurologic handicap underwent magnetic resonance imaging with a high-field (1.5 T) imager. Thirty-three demonstrated a total of 37 lesions consistent with hypoxic-ischemic encephalopathy, including periventricular leukomalacia (n = 12), basal ganglia hemorrhage (n = 5), multicystic encephalomalacia (n = 5), and focal parenchymal hemorrhage (n = 15). Diagnoses by ultrasonography and computed tomography were compared with those by magnetic resonance imaging in 29 and 17 infants, respectively. Ultrasonography agreed more frequently with magnetic resonance imaging than did computed tomography. Ultrasonography detected 79% of lesions demonstrated by magnetic resonance imaging whereas computed tomography detected only 41%. Periventricular leukomalacia was seen most often in preterm infants, basal ganglia hemorrhage and multicystic encephalomalacia primarily occurred in term infants, and focal parenchymal hemorrhage occurred at all gestational ages. Basal ganglia hemorrhage and multicystic encephalomalacia were strongly associated with histories of perinatal asphyxia, seizures, and early abnormal neurological status. All infants with basal ganglia hemorrhage (5/5) and multicystic encephalomalacia (5/5) and the majority with periventricular leukomalacia (9/12) and focal parenchymal hemorrhages (9/15) had developmental abnormalities at discharge.

Twenty-four hour in-house coverage for neonatal intensive care units in academic centers: who, how, and why?

Twenty-four-hour in-house coverage by attending physicians is becoming more common in academic centers in certain subspecialties in pediatrics. The actual percentage of programs providing this coverage in most subspecialties is not documented. We report the results of a survey of in-house coverage by attending physicians in neonatal intensive care units at academic centers in the United States. Of the 238 surveys distributed, 204 (86%) were returned and completed. At the time of the survey, 47 of 204 programs (23%) provided 24-hour in-house coverage for their neonatal intensive care units. These programs had more manpower than those programs not providing this coverage. If this trend continues, it will significantly alter projections for neonatal manpower needs in the United States.

Vitamin concentrations in very low birth weight infants given vitamins intravenously in a lipid emulsion: measurement of vitamins A, D, and E and riboflavin.

Because total parenteral nutrition with vitamins added to the glucose-amino acid mixture is often associated with a reduction in blood levels of vitamin A (retinol) during the routine treatment of many very low birth weight (VLBW) infants (less than 1500 gm), and because retinol losses in the plastic delivery system can be prevented by adding the vitamins to an intravenous lipid emulsion, seven VLBW infants with a mean birth weight of 900 gm (range 450 to 1360 gm) were given 40% of a unit dose vial, per kilogram of body weight, of a multivitamin preparation (M.V.I. Pediatric) (280 micrograms retinol; 160 IU vitamin D; 2.8 mg tocopherol; 0.68 mg riboflavin) in a lipid emulsion, Intralipid. After treatment with the intralipid-vitamin mixture for 19 to 28 days, plasma vitamin A (retinol) concentrations increased significantly from 11.0 +/- 0.76 (mean +/- SEM) before intralipid to 19.2 +/- 0.97 micrograms/dl after the intralipid-vitamin mixture (p less than 0.01); 25-hydroxyvitamin D concentrations increased from an initial value of 12.6 +/- 2.6 to 20.2 +/- 1.9 mg/dl (p less than 0.01); alpha-tocopherol concentrations increased from an initial value of 0.31 +/- 0.06 to 2.44 +/- 0.13 mg/dl (p less than 0.01); and riboflavin levels increased from 64.1 +/- 7.8 ng/ml to concentrations between 20 and 100 times the initial level. Erythrocyte riboflavin levels increased from 71.8 +/- 14 initially to 166 +/- 41 ng/gm hemoglobin, and erythrocyte flavin-adenine dinucleotide levels increased similarly from 972 +/- 112 initially to 2005 +/- 294 ng/gm hemoglobin. These results show that the addition of M.V.I. Pediatric to Intralipid decreases the extensive in vivo loss of retinol and is associated with an increase in plasma retinol concentrations in VLBW infants. The daily doses of vitamins D (160 IU/kg) and E (2.8 mg/kg) appear sufficient, but the dose of vitamin A (280 micrograms/kg) is insufficient to raise blood levels of all infants into the normal range. The current dose of riboflavin is excessive and may be harmful.

Intestinal absorption of bile acid glucuronides in rats.

While the intestinal absorption of taurine, glycine, and sulfate conjugates of bile acids has been studied extensively, nothing is known about the absorption of bile acid glucuronides. In the present study, the intestinal phase of the enterohepatic circulation of two bile acid glucuronides was examined. [3 beta-3H]cholic acid 3-O-beta-D-glucuronide or [3 beta-3H]lithocholic acid 3-O-beta-D-glucuronide was perfused through isolated segments of ileum or jejunum with intact blood supply in rats prepared with a biliary fistula. [14C]Taurocholic acid was perfused simultaneously with each glucuronide to compare glucuronide absorption with that of an actively transported bile acid. Intestinal absorption was determined by measuring the rate of secretion of labeled bile acid in bile. The absorption of [3H]cholic acid glucuronide by the ileum and jejunum was one fortieth and one eighth, respectively, that of [14C]taurocholic acid. Comparison of the two glucuronides show that [3H]lithocholic acid glucuronide absorption was 18 and 10 times greater than [3H]cholic acid glucuronide absorption from the jejunum and ileum, respectively. Collectively, the above observations suggest that glucuronidation of bile acids markedly reduces absorption from the small intestine.

The relationship of lactic dehydrogenase to epithelial cells in the urine of normal neonates.

Urinary lactic dehydrogenase (LDH) isoenzyme assays in 20 female and 15 male normal newborn infants during the first 3 days of life revealed higher levels than in older populations and a tendency toward a "slow zone pattern" (predominance of isoenzymes 4 and 5). Total LDH and LDH-5 activities were higher in the female (33.2 +/- 5.2 and 12.4 +/- 2.8 mU/mL, respectively), than in the male population (9.7 +/- 2.2 and 1.0 +/- 0.3 mU/mL, respectively). The amount of LDH correlated with the presence of epithelial cells in the urine that also were prominent in female patients and were apparently derived from the vagina. Separation of epithelial cells by centrifugation and filtration decreased total LDH and isoenzyme activities in the remaining sample, while sonification of the resuspended cells increased TLDH and LDH-5 activities by 6- and 12-fold respectively. Saline washings of the perineum and vagina revealed large numbers of epithelial cells and similar LDH isoenzyme patterns suggesting that contamination of the urine with these cells is a frequent occurrence during collection of voided and/or bag urine samples, and that these cells are responsible for much of the LDH activity found in the urine. We conclude that epithelial cells can increase both total LDH and isoenzyme activity in voided urine samples from otherwise normal female neonates. In this age group, urine collected by other methods (catheterization or suprapubic aspiration) must be studied to minimize the possibility of contamination of the sample with epithelial cells from the vagina or the perineum or both.

Intracranial hemorrhage in term or near-term newborns with persistent pulmonary hypertension.

To substantiate the clinical impression of an increased incidence of intracranial hemorrhage (ICH) in term and near-term infants with persistent pulmonary hypertension (PPH), a retrospective chart review of 35 affected patients was performed. ICH was diagnosed in 40 percent of the patients. Multiple regions of the brain were affected; in many patients, at more than one location. In addition, 43 percent of ICH victims had hemorrhages of the type associated with periventricular bleeding in preterm newborns. Of multiple obstetric and neonatal factors analyzed, many of which are identified risk factors for periventricular hemorrhage, only thrombocytopenia (p = 0.02) was significantly associated with ICH. We conclude that the risk of ICH in newborns with PPH is significant and warrants consideration by clinicians caring for this population. Risk factors (except thrombocytopenia) previously implicated in other types of neonatal ICH, particularly periventricular hemorrhage, do not significantly correlate with ICH in infants with PPH.

Bile salt-induced calcium fluxes in artificial phospholipid vesicles.

The ionic permeability of selected biological membranes is increased by bile salts. To examine changes in calcium permeability during the exposure of artificial membranes to bile salts, we investigated calcium uptake by unilamellar and multilamellar phospholipid vesicles. In the presence of 750 microM taurodeoxycholate, uptake of radiolabelled calcium by unilamellar vesicles increased 2.5-fold over control values. Calcium uptake by multilamellar vesicles as measured with a free calcium indicator, arsenazo III, increased 2.2- or 21-fold in the presence of 60 microM lithocholate or 3 beta-hydroxy-5-cholenoate, respectively. Results were directly influenced by experimental variables such as bile salt hydrophobicity, external calcium concentration, and the bile salt/lipid molar ratio. Observed membrane solubilization was minimal despite increased calcium permeability. Comparison of radiolabelled calcium uptake with radiolabelled sodium or radiolabelled rubidium uptake indicated that bile salt-dependent calcium uptake was 60-140-times greater than bile salt-dependent uptake of either monovalent cation. In an effort to delineate forces affecting calcium translocation, vesicles were exposed either to valinomycin, which induced an electrochemical gradient across the membrane, or to nigericin, which induced a proton gradient. Exposure to valinomycin minimally influenced bile salt-induced calcium uptake while exposure to nigericin significantly promoted uptake by 40-70%. The results suggest that bile salts promote calcium uptake by a mechanism which may be similar to those of other carboxylic ionophores.

Bile salts induce calcium uptake in vitro by human erythrocytes.

At high concentrations, bile salts induce hemolysis by comicellization of lipid components of the cell membrane. However, bile salts are also associated with hemolysis at lower concentrations by mechanisms which have not been characterized. To investigate the possibility that bile salts promote calcium uptake by red blood cells and that bile salt-associated hemolysis is, in part, calcium-mediated, calcium uptake by red blood cells was measured in the presence of individual bile salts, and hemolysis dependence upon calcium availability was examined. Washed human red blood cells with or without ATP depletion were incubated with 1 mM CaCl2 and tracer amounts of 45CaCl2 in the presence of selected bile salts at concentrations (0.01 to 0.3 mM) reported to be below critical micellar concentrations. Calcium uptake (defined for the purposes of this study as 45Ca retained in red blood cells) was monitored over 5 hr, after which hemolysis and membrane phospholipid content were determined. The presence of bile salts stimulated calcium uptake 4- to 25-fold--the magnitude of which was partly related to the lipid solubility of the bile salts. ATP depletion or exposure to trifluoperazine, procedures which inhibit calcium pump activity in red blood cells, enhanced bile salt-induced calcium uptake relative to controls. The percentage of associated hemolysis (2 to 14%) at the end of 5 hr correlated directly with the observed calcium uptake. Removal of calcium from the extracellular space reduced hemolysis in the presence of bile salts to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolism of 24-norlithocholic acid in the rat: formation of hydroxyl- and carboxyl-linked glucuronides and effect on bile flow.

24-Norlithocholic (3 alpha-hydroxy-24-nor-5 beta-cholan-23-oic) acid is the lower homologue of lithocholic acid, a potent cholestatic agent. In order to characterize its cholestatic potential and metabolic fate, 3 beta-tritiated 24-norlithocholate was infused intravenously into adult male Sprague-Dawley rats prepared with an external biliary fistula. The results demonstrate that 24-norlithocholate does not induce cholestasis in rats when administered in doses in excess of those necessary for lithocholate to produce cholestasis. Hydroxyl- and carboxyl-linked glucuronides were identified as major metabolites secreted in the bile. Especially noteworthy is the identification of carboxyl-linked glucuronides of mono-, di- and trihydroxylated C23 bile acids. Their total amount (25% of recovered radioactive products) is comparable to that of the hydroxyl-linked glucuronide of 24-norlithocholic acid (41%). In this study, for the first time, a bile acid diglucuronide, substituted both at 3-hydroxyl and carboxyl groups, was detected (11%).

Calcium binding by lithocholic acid derivatives.

Lithocholic acid (LCA) and its sulfate (LCS) and glucuronide (LCG) derivatives are potent cholestatic agents. During the course of LCG-induced cholestasis in rats, calcium (Ca) salts of LCG precipitate in bile. To characterize the affinity of bile salts for Ca, solutions of selected bile salts were titrated with Ca. Apparent equilibrium constants (KcaBS) were determined from the unbound Ca ion concentrations that were measured spectrophotometrically with metallochromic indicators antipyrylazo III or murexide or with a Ca-selective electrode. KCaBS values were 1.12 +/- 0.04 X 10(-4) M for LCS, 2.88 +/- 0.26 X 10(-4) M for LCG, 3.09 +/- 0.21 X 10(-4) M for LCA, 1.93 +/- 0.07 X 10(-3) M for taurocholic acid (TC), 2.69 +/- 0.08 X 10(-3) M for glycocholic acid (GC), and 6.07 +/- 0.27 X 10(-3) M for taurolithocholic acid sulfate (TLCS). The KCaBS for LCG measured by a Ca-selective electrode under identical conditions was 5.53 +/- 2.75 X 10(-4) M. Comparing relative cholestatic potential with affinity for Ca, cholestatic bile salts LCS, LCG, and LCA bind Ca 10-60 times more avidly than TC, GC, and TLCS. At the unbound Ca ion concentrations of serum or bile (approx 1 mM), only LCS, LCG, and LCA would be expected to bind significant amounts of Ca.

Lithocholate glucuronide is a cholestatic agent.

Lithocholic acid and its taurine, glycine, and sulfate derivatives are potent cholestatic agents. Lithocholate glucuronide is present in the plasma and urine of patients with cholestatic syndromes, but little is known of its metabolism, excretion, and cholestatic potential. [3 beta-3H]lithocholate 3-O-beta-D-glucuronide was synthesized, and chemical and radiochemical purity were established. The aqueous solubility of lithocholate glucuronide was determined and found to be greater than that of lithocholic acid or several of its derivatives. In the range of concentrations examined, calcium ions precipitated lithocholate glucuronide stoichiometrically. The material was administered to rats prepared with an external biliary fistula. When 17-25 micrograms quantities were administered, 89.1 +/- 4.5% (mean +/- SEM) of the radiolabel was secreted in bile within the first 20 h after administration, the major fraction being secreted in less than 20 min. Four-fifths of the radiolabeled material in bile was the administered unaltered parent compound, while a minor fraction consisted of a more polar derivative(s). We showed that increasing biliary concentrations of more polar derivatives were observed with milligram doses of [3H]lithocholate glucuronide, and with time after the administration of these loading doses. Milligram doses of [3H]lithocholate glucuronide resulted in partial or complete cholestasis. When induced cholestasis was partial, secretion in bile remained the primary excretory route (82.5-105.6% recovery in bile), while, when complete cholestasis was induced, wide tissue distribution of radiolabel was observed. Cholestasis developed rapidly during infusion of [3H]lithocholate glucuronide. Bile flow was diminished within 10-20 min of the start of an infusion of 0.05 mumol, 100 g-1 body weight, minute-1, administered concomitantly with an equimolar infusion of taurocholate. The results establish that lithocholate glucuronide exerts cholestatic effects comparable to those exerted by unconjugated lithocholic acid.

The care by parent unit. A tool for decreasing anxiety in mothers of high risk infants.

The delivery of a premature infant, especially one of very low birth weight, represents a crisis for a family. Bidder et al. have determined through a series of interviews that mothers of preterm infants are anxious at two particular points in their infant's neonatal course: the time of birth and the time of discharge. The Care By Parent Unit (CBPU) was developed at Hermann Hospital in Houston, Texas, to provide a transition from the specialized care of the Neonatal Intensive Care Unit (NICU) to home and to aid the parents in viewing their infant as a normal, "safe" child to take home. To evaluate the impact of a CBPU on maternal anxiety, the mothers' responses before and after the CBPU experience were evaluated.

Diversity of bile acids in the fetus and newborn infant.

The bile acids found in the fetus and newborn are more numerous and diverse than has generally been appreciated. The four conventional bile acids, cholic, chenodeoxycholic, deoxycholic, and lithocholic acids, are found. In addition, however, stereoisomers of the conventional bile acids, bile acids with functional groups at different positions or in greater number than found in conventional bile acids, and "short-chain" and "long-chain" bile acids are found. The site of origin, pathways of synthesis, metabolism, and excretory routes of these unconventional bile acids are largely unknown. Their effects on the function of the liver and other tissues have not yet been established. It is uncertain which of these compounds is peculiar to the fetus and newborn, and which will be found in normal or abnormal adults. This review is an early look at a field bound to advance rapidly in the next several years.

Constituents of human meconium--I. Identification of 3-hydroxy-etianic acids.

The monohydroxylated fraction of bile acids of human meconium was analyzed by capillary GC-MS. In the sulfate-glucuronide fraction three saturated, and one unsaturated C20 steroidal acids were found. These acids were identified as 3 alpha-hydroxy-5 alpha-, 3 alpha-hydroxy-5 beta-,3 beta-hydroxy-5 alpha-androstane-17 beta-carboxylic, and 3 beta-hydroxyandrost-5-ene-17 beta-carboxylic based on the unequivocal GC-MS comparison with standards of all possible epimers at C-3, 5 and 17. The amount of the major C20 acid, 3 alpha-hydroxy-5 alpha-androstane-17 beta-carboxylic, in meconium was 0.2 nmol/g, i.e. 5 to 10 times the amount of lithocholic acid. To prevent the oxidation of 21-hydroxy-20-oxopregnanes to C20 acids meconium was extracted in the presence of sodium borohydride. In the absence of this reducing agent the amount of 3 beta-hydroxyandrost-5-ene-17 beta-carboxylic acid was increased and its 17 alpha-epimer could be detected. This indicates partial artifactual formation of this C20 acid from 21-hydroxypregnenolone, which is known to be present in human meconium. The amount of the saturated C20 acids was unaffected by the presence of sodium borohydride in the extraction medium, and their native occurence in human meconium was further confirmed by the absence of their 17 alpha-epimers in extracts obtained both with and without borohydride. The probable metabolic origin of C20 acids in the fetal-placental-maternal unit is discussed.