Neonatologists' perspectives of palliative and end-of-life care in neonatal intensive care units.

OBJECTIVE: Determine palliative and end-of-life care practices, barriers and beliefs among US neonatologists, and relationships between practice characteristics and palliative care delivery. STUDY DESIGN: A descriptive cross-sectional survey with ordinal measurements. The survey was sent to 1885 neonatologists. RESULTS: There were 725 responses (38.5%) with 653 (34.6%) completing the survey. Of those, 58.0% (n=379) have palliative care teams and 72.0% (n=470) have staff support groups or bereavement services. Palliative care education was deemed important (n=623) and needed. Barriers include emotional difficulties, staff disagreements and difficulty forming palliative care teams. Palliative care teams or staff bereavement groups were significantly predictive of willingness to initiate palliative care and more positive views or experiences. CONCLUSION: Neonatologists believe that palliative care is important. Education and palliative care teams help provide quality care. Exploration of differing views of palliative care among team members is needed.

The Raf-1 protein mediates insulin-like growth factor-induced proliferation of erythroid progenitor cells.

Previous studies from this and other laboratories have shown that insulin-like growth factor-1 (IGF-I) and insulin-like growth factor-2 (IGF-II) support erythroid colony formation in cultures supplemented with serum substitute and recombinant erythropoietin. Subpopulations of IGF-I- and IGF-II-dependent, erythropoietin-independent colony-forming unit-erythroid (CFU-E)-derived colonies and BFU-E-derived colonies were identified under serum-substituted conditions for adult bone-marrow-derived erythroid progenitors which proliferate in the absence and presence of exogenous anti-erythropoietin receptor monoclonal antibody and in serum-substituted medium that was preadsorbed with anti-erythropoietin IgG. To assess whether Raf-1 is required for the formation of IGF-dependent, erythropoietin-independent human erythroid colonies, 5-15 microM sense or antisense oligomer to raf-1 were added to serum-substituted cultures containing either 2 U/ml recombinant human erythropoietin (rHuEpo) alone or 0-1,000 ng/ml IGF-I or IGF-II with/without 2 U/ml rHuEpo. Both erythropoietin-induced and IGF-induced erythroid colony formation were completely blocked by antisense (but not sense) oligomers to raf-1. Purified human CFU-Es were examined for Raf-1 message and protein. Total RNA was extracted, and raf-1 mRNA was detected on Northern blots. Furthermore, a 74 kD protein, corresponding to Raf-1, was also detected in CFU-Es purified from human adult sources. Together, these studies support the hypothesis that the Raf-1 protein mediates both erythropoietin-induced and IGF-induced signal transduction in human erythroid progenitor cells.

Impact of gastroesophageal reflux on growth and hospital stay in premature infants.

BACKGROUND: Gastroesophageal reflux (GER) is associated with failure to thrive in term infants with severe GER; however, this association has not been shown in premature infants. A retrospective case-control study of growth velocities, caloric intake, and length of hospital stay in premature infants with GER was conducted to determine the impact of GER on their growth. METHODS: Twenty-three patients with clinically significant GER were identified from a database containing records for all infants admitted to the University of Connecticut Health Center Neonatal Intensive Care Unit. Patients and control subjects (n = 23) were matched for gestational age, birth weight, gender, and severity of bronchopulmonary dysplasia. Each infant's average weekly weight gain and average weekly caloric intake were calculated, using daily bedside nursing flow sheets. Comparisons were also made of the number of days it took each infant to achieve full oral feedings, number of days from full oral feedings to discharge, and length of hospital stay. RESULTS: There were no significant differences between patients and control subjects for each week in average weekly weight gain, caloric intake, grams gained per calorie given, or weekly increments gained in length and head circumference. There were, however, significant differences in time required to achieve full oral feedings (32 +/- 13 days versus 19 +/- 12 days; p < 0.0008) and length of hospital stay (99 +/- 27 days versus 70 +/- 31 days; p < 0.002) as well as postmenstrual age (PMA) at discharge (43 +/- 3 weeks versus 39 +/- 3 weeks, p < 0.001). CONCLUSIONS: GER did not have a significant impact on caloric intake, effective use of calories, or growth velocities in the study population. It is more likely that the constant monitoring of weight gain and caloric intake while in the intensive care environment protects against the failure to thrive often seen in older infants with GER. Premature infants with GER had a significantly increased length of hospital stay. More aggressive medical management and consideration of alternative feeding strategies may help facilitate discharge for premature infants diagnosed with GER.

Level of nutrition modulates the dynamics of oestradiol feedback on plasma FSH in ovariectomized ewes.

The frequency of multiple ovulations in mature, cyclic ewes is strongly influenced by the level of nutrition, but it is difficult to demonstrate concurrent changes in plasma concentrations of gonadotropins. The failure to do so might be a consequence of rapid compensation by the homeostatic feedback mechanism linking secretion by the hypothalamus/pituitary gland and ovarian hormones. Most experimental models have examined the components of the homeostatic feedback system after steady state relationships had been established. We hypothesised that the effects of nutrition might be observed more readily if the system were disrupted and then examined while equilibrium was being re-established. This hypothesis was tested in three experiments in Merino ewes by allowing gonadotropin secretion to escape feedback for 5 days after ovariectomy and then replacing ovarian hormones and examining effects of feeding regimen on the return of plasma concentrations of FSH to baseline values. In all three experiments, oestrogen replacement caused plasma concentrations of FSH to decline more rapidly (P < 0.05) in ewes fed at 0.5x maintenance, than in ewes fed at 1.4x maintenance, with groups fed at maintenance being intermediate. No effect of diet was observed on plasma FSH concentrations in the absence of oestradiol, and neither progesterone nor charcoal-treated bovine follicular fluid influenced the effect of nutrition. Plasma concentrations of oestradiol were 9.8% lower on average (NS) in ewes fed above maintenance than in the sheep fed below maintenance over the three experiments, suggesting that there may have been a reduced clearance of oestradiol which contributed to the result. We conclude that feeding regimen affects the secretion or clearance of gonadotropins in mature ewes, as in the mature ram, and that this is one mechanism by which ovulation rate may be affected.

Mealtime behavior and parent-child interaction: a comparison of children with cystic fibrosis, children with feeding problems, and nonclinic controls.

Examined the role of family interaction factors in dietary compliance problems reported by parents of children with cystic fibrosis (CF). The family mealtime interactions of children with CF, children with feeding problems and nonclinic controls were observed, and parents monitored children's eating behavior at home. Parents of children with CF reported more concern about feeding problems and recorded more disruptive mealtime behavior than parents of nonclinic children. Observational data showed children with CF to display overall rates of disruptive mealtime behavior not significantly different from either comparison group. Mothers of children with CF were observed to engage in higher rates of aversive interaction with their child than did mothers of nonclinic controls. Fathers of children with CF reported lower marital satisfaction than fathers of controls. Both mothers and fathers of children with CF reported lower parenting self-efficacy than non-CF families. Clinical implications are discussed.

Effect of diet on the clearance of estradiol-17 beta in the ewe.

The twinning rate of ewes is poorly related to plasma concentrations of gonadotropins. In this study, we tested an alternative hypothesis for the control of twinning rate, by testing whether nutritional treatment sufficient to affect twinning could alter estrogen metabolism, with a particular focus on the enterohepatic recirculation. Groups of 5 ovariectomized ewes were fed either above maintenance (supplemented) or below maintenance (restricted). The metabolism of estradiol-17 beta was examined by following the fate of a single i.v. injection of 1.45 micrograms [3H]estradiol-17 beta. In both groups, 74% of the radioactivity was recovered from the feces within 10 days, predominantly as free estradiol-17 alpha, but excretion was slower in the nutritionally restricted ewes. A further 6% of injected radioactivity was excreted in the urine, mostly within 24 h, with no effect of dietary group. Radioactivity in plasma was characterized by ion-exchange chromatography and HPLC. Within 30 min of injection, the main circulating radioactive compound was estradiol-17 alpha sulfate. This remained at a greater concentration than free steroid for the next 48 h, and was greater after 16 h (p < 0.05) in plasma of nutritionally restricted ewes than in the supplemented group. At 0.5 and 2 h, the free steroid was almost entirely estradiol-17 beta, but a polar compound, which appeared by 4 h and probably arose by recirculation from the intestine, remained the major unconjugated metabolite in plasma for the next 24 h. Plasma concentrations of this compound were higher (p < 0.05) in the restricted ewes than in the supplemented ewes during this period.(ABSTRACT TRUNCATED AT 250 WORDS)

Morning glory syndrome in children. Association with endocrine and central nervous system anomalies.

OBJECTIVE: To identify morning glory syndrome, an uncommon optic disc anomaly. Generally, it is an isolated ocular abnormality; however, some cranial facial and neurologic associations have been reported. PATIENTS: We herein report two patients with morning glory syndrome and associated pituitary dwarfism. In one patient, the pituitary insufficiency was secondary to compression of the pituitary gland by a basal encephalocele; in the second patient, causative factors were not identified. CONCLUSIONS: Patients with morning glory syndrome should have a complete general physical examination and growth evaluation so that early recognition and treatment of the patient with pituitary dwarfism can occur.

Development of uterus-like redifferentiation in the cervix of the ewe after exposure to estradiol-17 beta.

Prolonged treatment with estrogen causes the cervix of the ewe to redifferentiate to become more like uterus, and results in permanent infertility. Such permanent infertility has been observed only in ewes that have received two successive exposures to estrogen, raising the possibility that the initial exposure has a priming effect for subsequent treatment. In the study presented here, we examined whether any priming effects could be detected in the development of uterus-like histological changes in cervix of ewes given a single or two successive treatments with estradiol. Exposure to estradiol for 180 days resulted in stratified squamous hypertrophy of the cervical epithelium and also produced glandular hyperplasia, an increased proportion of lamina propria tissue in the endocervix, and fewer cervical folds. During the 30 days after treatment ceased, the epithelium returned to normal, while changes in cervical structure, as measured by reduced number of folds, became more marked. A second treatment with estradiol 180 days later produced a response similar to that after the first exposure, so it was not possible to identify any specific priming effect of the initial treatment with estrogen. However, treatment with estrogen established a process of cervical redifferentiation, and some aspects of this change appeared to be dependent on the withdrawal of estrogen.

The relationship between children's treatment-related behaviour problems, age and clinical status in cystic fibrosis.

This study examined the relationship between parents' and physicians' reports of treatment-related behaviour and adjustment problems of children with cystic fibrosis (CF), and children's clinical status as assessed by measures of pulmonary functioning and global ratings of clinical status. Parents completed a Cystic Fibrosis Problem Checklist which measures the extent to which children experience behaviour and adjustment difficulties with different aspects of treatment, including chest physiotherapy, medication taking and diet. A high proportion of parents in each age group reported at least some treatment-related behaviour difficulties, with significantly more problems being reported with younger children. There was no significant relationship, however, between the child's age, sex and clinicians' ratings of compliance. A stepwise multiple regression showed that the only variables which significantly predicted clinicians' ratings of the severity of the child's disease were forced expired volume and height. Clinicians' ratings of compliance explained a small amount of extra variance (2.4%). It was found that parental reports of treatment-related behaviour problems were not related to clinical status. The implications of the findings for clinical practice are discussed.

Immunization of ovariectomized ewes against progesterone, oestrogen or cortisol to detect effects of adrenal steroids on reproduction.

Ovariectomized ewes were immunized against cortisol, oestrogen or progesterone to determine whether steroids of non-ovarian origin occur in sufficient amounts to influence the reproductive system. Ewes immunized against oestrogen (oestrone + oestradiol) had smaller uteri (P less than 0.05) and a lower concentration of oestradiol in uterine tissue (P less than 0.05), while the adrenal gland was heavier (P less than 0.05). In the peripheral plasma of immunized ewes, the concentration of FSH, but not LH, was increased (P less than 0.05). Ewes immunized against cortisol also had smaller uteri (P less than 0.05) and heavier adrenal glands (P less than 0.05), but gonadotrophins and the concentration of oestradiol in the uterus were unaffected. Immunization against progesterone, or injection with synthetic glucocorticoids, did not affect any of the characteristics measured. We conclude that the adrenal gland of the ewes produced sufficient oestrogen or aromatizable androgen to have significant effects on the reproductive system. In contrast, adrenal production of progesterone did not produce detectable biological effects. Immunization against cortisol did affect the reproductive system, but the mechanism of this action could not be determined.

Effects of oestradiol implants on the ovulation rate of the ewe.

In a series of 5 experiments, ewes were treated with implants releasing oestradiol-17 beta and the effects on ovulation rate were observed. Large doses of oestradiol-17 beta (greater than 20 micrograms/day) produced anovulation while smaller amounts only reduced the proportion of twin ovulations. Amounts of exogenous oestradiol comparable to ovarian production rate in the luteal phase (less than 1 microgram/day) produced a significant (P less than 0.01) suppression in ovulation rate. Treatment during the follicular phase of the oestrous cycle was most effective, but treatment during the luteal phase alone also appeared to suppress ovulation rate. Furthermore, in 2 of 3 experiments ewes treated with low amounts of oestradiol during the first half of the luteal phase were less likely to have multiple ovulations at the subsequent oestrous period. The results support the hypothesis that oestrogen is involved in the physiological control of ovulation rate in the ewe, but this action is probably not restricted to the assertion of dominance by a maturing follicle during the follicular phase.

Persistent infertility in ewes after prolonged exposure to oestradiol-17 beta.

Merino ewes were treated with implants which released 300 micrograms oestradiol-17 beta per day or 5 mg progesterone per day, or both, for 9 months (Months 1-9), and after an 11-month intermission were treated again for 6 months (Months 20-26). Ewes were run with rams at Months 16, 28 and 40. Fertility was not affected by the first exposure period, but the second exposure to oestradiol reduced the fertility of ewes at both subsequent mating periods. Affected ewes returned to service more frequently (P less than 0.01) and were less likely to conceive (P less than 0.05). After mating, a normal population of spermatozoa was established in the caudal cervix, but transport through the cervix was impaired in affected ewes and there were fewer spermatozoa (P less than 0.01) in the cranial cervix. In affected ewes, the spinnbarkeit of cervical mucus was reduced (P less than 0.05), and the histological appearance of the cervix changed, looking like that of the uterus. Treatment with progesterone did not affect fertility, cervical mucus or sperm transport, but diminished the histological abnormalities produced by oestradiol (P less than 0.05). These results show that oestradiol-17 beta given after puberty can cause the same kind of permanent sexual transdifferentiation that is produced by the oestrogenic isoflavones in ewes with clover disease. The results suggest that this change may require more than a single exposure to oestrogen.