The neonatal intensive parenting unit: an introduction.

This paper describes a paradigm shift occurring in neonatal intensive care. Care teams are moving from a focus limited to healing the baby's medical problems towards a focus that also requires effective partnerships with families. These partnerships encourage extensive participation of mothers and fathers in their baby's care and ongoing bi-directional communication with the care team. The term Newborn Intensive Parenting Unit (NIPU) was derived to capture this concept. One component of the NIPU is family-integrated care, where parents are intimately involved in a baby's care for as many hours a day as possible. We describe six areas of potentially better practices (PBPs) for the NIPU along with descriptions of NIPU physical characteristics, operations, and a relationship-based culture. Research indicates the PBPs should lead to improved outcomes for NIPU babies, better mental health outcomes for their parents, and enhanced well-being of staff.

NICU discharge planning and beyond: recommendations for parent psychosocial support.

Parents will interact with a multitude of teams from various disciplines during their child's admission to the neonatal intensive care unit. Recognition of the emotional stressors experienced by these parents is a first step in working to provide the crucial support and parenting skills needed for bonding and caring for their infant from admission through discharge and beyond. Family-centered care involves time-sensitive two-way communication between parents and the multidisciplinary team members who coordinate care transition by providing emotional, educational, medical and home visitor support for these families. To do this well, a thoughtful exchange of information between team members and parents is essential to identify psychosocial stress and ameliorate family concerns. Parents will need emotional and educational support and follow-up resources. Establishing individualized, flexible but realistic, pre- and post-discharge plans with parents is needed to start their healthy transition to home and community.

Recommendations for involving the family in developmental care of the NICU baby.

Family involvement is a key to realize the potential for long-lasting positive effects on physical, cognitive and psychosocial development of all babies, including those in the neonatal intensive care unit (NICU). Family-centered developmental care (FCDC) recognizes the family as vital members of the NICU health-care team. As such, families are integrated into decision-making processes and are collaborators in their baby's care. Through standardized use of FCDC principles in the NICU, a foundation is constructed to enhance the family's lifelong relationship with their child and optimize development of the baby. Recommendations are made for supporting parental roles as caregivers of their babies in the NICU, supporting NICU staff participation in FCDC and creating NICU policies that support this type of care. These recommendations are designed to meet the basic human needs of all babies, the special needs of hospitalized babies and the needs of families who are coping with the crisis of having a baby in the NICU.

Mechanisms of insulin resistance in cultured fibroblasts from a patient with leprechaunism: resistance to proteolytic activation of glycogen synthase by trypsin.

Post-receptor or post-binding events in the action of insulin have been investigated in cultured skin fibroblasts from an infant with leprechaunism. Both diminished binding of insulin and multiplication-stimulating activity (MSA) to these cells as well as deficits distal to binding were described in a previous publication. Exposure of control fibroblasts to low concentrations (0.001 to 0.01%) of trypsin for one min without glucose in the medium activated the enzyme glycogen synthase; activation was less than that observed with a maximally effective concentration (10(-6) M) of insulin alone. In cells from the patient with leprechaunism, the effect of trypsin was much smaller than in the control fibroblasts. Exposing the control cells to soybean trypsin inhibitor before addition of trypsin prevented activation of glycogen synthase and demonstrated the specificity of the proteolytic action of trypsin. The rates of activation and inactivation of glycogen synthase in vitro were similar in extracts of the control subject's and the patient's fibroblasts and indicated that the enzymes regulating the phosphorylation/dephosphorylation of glycogen synthase were intact in the patient's cells. Total glycogen synthase activity and glycogen content were also indistinguishable in control and leprechaun fibroblasts. These results are compatible with the presence of an abnormality in the structure or availability of the protease substrate from which chemical mediators of insulin action are formed in the patient's cells. Two possible models for a receptor-coupling complex are proposed. Either a mutation in a regulator-substrate unit of the receptor-coupling complexes for insulin and certain insulin-like growth factors or an alteration in the environment of the unit are postulated to explain the findings.

Mechanisms of insulin resistance in cultured fibroblasts from a patient with leprechaunism: impaired post-binding actions of insulin and multiplication-stimulating activity.

The binding and action of insulin and of the insulin-like growth factor, multiplication-stimulating activity (MSA), were studied in cultured skin fibroblasts from an infant with leprechaunism and associated insulin resistance. Three actions of insulin were reduced in the leprechaun cells: activation of glycogen synthase was 30% as great as in control fibroblasts, the increase in 2-deoxyglucose transport was 33% of the control value, and the uptake of alpha-aminoisobutyric acid was sevenfold less sensitive to enhancement. On a molar basis, MSA was at least as effective as insulin in activating glycogen synthase in control fibroblasts; in the patient's cells there was a reduction in activation that paralleled the changes observed with insulin. To localize the site of insulin resistance, the binding of both [125I]-insulin and [125I]-MSA to fibroblasts was measured and found to be reduced in the leprechaun cells. However, the impairment of the actions of insulin and MSA in the patient's cells was not explained solely by the diminished binding of the two polypeptides. Since the hexose transport system and the terminal enzymes studied thus far are intact, the defect is postulated to involve the post-binding coupling mechanism and mediator formation.

Effect of pH and 3-hydroxybutyrate on insulin binding and action in cultured human fibroblasts.

The influence of pH and 3-hydroxybutyrate on insulin binding and action has been studied in cultured human fibroblasts. When the pH of the incubation medium was decreased from 7.6 to 6.8, insulin stimulation of glycogen synthase and total glucose uptake was decreased. The decreased pH induced both an increase in the insulin concentration for half-maximal response, and a decrease in maximal responsiveness. When insulin binding was measured at lower pH, receptor affinity was decreased. The effect of 3-hydroxybutyrate on insulin binding and action was assessed at pH 7.4 and 6.9. In the presence of 3-hydroxybutyrate, insulin binding increased, but insulin action on glycogen synthase and total glucose uptake was unaffected. The data show that insulin action is impaired at lower pH. The decreased sensitivity is probably related to the decrease in insulin binding affinity at lower pH, but decreased maximal responsiveness implies that postreceptor components are also affected by lower pH. The results also suggest that 3-hydroxybutyrate induced a dissociation between binding and response, since an increase of insulin binding was not accompanied by changes in the regulation of glycogen synthase and total glucose uptake.

Glucose kinetics in leprechaunism: accelerated fasting due to insulin resistance.

Postprandial and postabsorptive glucose metabolism was studied in a 3-yr-old girl with leprechaunism by substrate and hormonal measurements and by quantifying hepatic glucose output during continuous infusion of D-[6-6-2H2]-glucose. Hepatic glucogen content and the activity of glycogen synthase and phosphorylase were also measured in the post-prandial state on a separate occasion. During the 4-h postprandial state, plasma glucose, alanine, lactate, beta-hydroxybutyrate, and glycerol were normal, as were hepatic glycogen, glycogen synthase, phosphorylase, and hepatic glucose output of 7.5 mg kg-1 min-1. Intravenous injection of glucagon (30 micrograms kg-1) caused an immediate almost 3-fold rise in glucose production consistent with brisk glycogenolysis. During the 8- to 12-h postabsorptive state, however, the patient had elevated levels of glycerol (330-508 microM) and beta-hydroxybutyrate (3291-3801 microM) and decreased levels of glucose 24-29 mg/dl) and alanine (121-135 microM) consistent with a much longer period of fasting in the normal child. Furthermore, hepatic glucose output was reduced to 3.9 mg kg-1 min-1, and iv glucagon injection failed to increase this rate; both of these observations are consistent with a hepatic state generally found only later in fasting in the normal child. From these observations we conclude that the hypoglycemia reported in the leprechaunism syndrome is due to an accelerated fasting state secondary to insulin resistance. As with long-fasted, glycogen-depleted normal children, gluconeogenesis alone is often not capable of adequately meeting the child's large noninsulin-dependent cerebral glucose requirements.

Insulin stimulation of glycogen synthase in cultured human diploid fibroblasts.

The effect of insulin on glycogen synthase activity in human diploid fibroblasts has been studied. As little as 2 X 10(-10) M insulin increased the glycogen synthase / activity without changing the total activity. Stimulation occurred within 5 min and became maximal in 30 min. A half-maximal increase of / activity was achieved at 3 X 10(-9) M insulin. Glucose starvation increased the magnitude of response of glycogen synthase to insulin but did not change the insulin concentration necessary to give a half-maximal stimulation. Glucose increased the basal level of / activity in human diploid fibroblasts; the effect of insulin was additive. During in vitro senescence the total glycogen synthase activity declined, but the concentration of insulin that produced a half-maximal stimulation remained unchanged. These data indicate that regulation of glycogen synthase activity in human diploid fibroblasts is responsive to physiologic insulin levels and that the system provides a useful model for the in vitro study of insulin sensitivity.

Further studies in man of Hsw1N1 influenza viruses.

Two subpopulations of antigenically different Hsw1N1 influenza viruses, cloned from 'swine' New Jersey virus 1976, were individually inoculated into antibody-free volunteers. One clone contained a haemagglutinin so far seen only in swine viruses prevalent in 1971 and after, the other a haemagglutinin of earlier strains dating back to a least 1957. Each of the viruses was infectious for man and intermediate in human virulence between a wild human virus and swine pathogens of 1966 and 1967, which had earlier been tested in man. Antigenically comparable clones segregated from viruses recovered in Wisconsin from a pig and a human contact, respectively, were also infectious for man; however, they were less virulent than their New Jersey counterparts. Differences between the Wisconsin clones themselves were small, but there was an indication of a relationship between human passage. and human virulence. There was no evidence of inherently greater human virulence in the newer Hsw1N1 serotype as compared with the earlier serotype. Hence, recent detection of swine influenza-like viruses in man is unlikely to be the consequence of a host-range mutation concurrent with an antigenic mutation. We believe that the Hsw1N1 viruses recovered from the human influenza outbreak at Fort Dix, New Jersey, and from recent single human infections were wholly derived from enzootic swine viruses that underwent limited human adaptation through man-to-man passage.

Astrovirus infection in volunteers.

An extract and a filtrate prepared from feces of a child with mild gastroenteritis were shown by electron microscopy to contain numerous astrovirus particles and were given to eight volunteers by mouth. One subject developed diarrheal illness and concurrently shed large amounts of astrovirus in feces, and one other had mild constitutional symptoms with a lower level of virus shedding. Nine other volunteers were given fecal filtrate from the volunteer with diarrhea, and astrovirus shedding subsequently occurred in two of them. The syndrome accompanying virus shedding appeared distinct from that associated with the "W" agent in previous experiments. Thirteen of 16 astrovirus-inoculated subjects subsequently developed a rise in titer of the homologous antibody in serum. It was concluded that astrovirus causes a transmissible infection that is of low pathogenicity for adults. Immunofluorescence of human embryo kidney cells inoculated with astrovirus and shown by electron microscopy to contain 28 nm virus-like particles was used both to detect virus in feces and to assay astrovirus antibody.

Effect of a polynucleotide interferon inducer of fungal origin on experimental rhinovirus infection in humans.

A double-stranded RNA of fungal origin (BRL 5907) was given intranasally to volunteers. Apart from mild local irritancy of the higher dosage, the compound was well tolerated. A double-blind placebo-controlled trial of a three-day course (5 mg per day) of BRL 5907 against challenge with rhinovirus type 4 showed that treatment was associated with a delay in onset of symptoms and a reduction in shedding of virus, but the differences were not statistically significant. Low titers of interferon were found in nasal washings.

A trial of ascorbic acid in the treatment of the common cold.

A randomised controlled trial was carried out to study the effect of 10 g of ascorbic acid taken during the first 2 1/2 days on the symptoms of the common cold. Altogether 1524 volunteers were recruited from a number of working groups in different parts of the country; 482 developed colds. There was no evidence that upper respiratory or general constitutional symptoms were alleviated by ascorbic acid. Among the men who had any colds at all, significantly fewer on active than on placebo treatment had two or more colds; however, this effect was not seen in women. Ascorbic acid is of no value in the treatment of the common cold; its preventive effect, if any, is not such as to justify advising its general use as a prophylactic measure.

Experiments in the preparation of live influenza B vaccines.

A study is described of the selection of influenza B virus recombinants. Three virulent viruses isolated in 1970, 1970 and 1973, were crossed with host-range mutants of low virulence for man, which had originally been isolated in 1940, 1959 and 1956, respectively. Nine presumptive recombinants were inoculated into volunteers with low initial HI antibody titres. Although a number proved attenuated and there was evidence of high frequency of recombination, antigenic characterization of neuraminidases proved difficult. There was always some crossing between parental surface antigens, and appropriate antigenic hybrids for preparation of reference antisera were not available. Comparative virus titres at 33 degrees C and 38 degrees C were of limited value as a genetic marker. It is suggested that biological methods are unsatisfactory for the study of influenza B virus recombinants, and should be replaced by biochemical techniques designed to trace the parental origins of individual RNA segments.