Skin exposure during conventional phototherapy in preterm infants: A randomized controlled trial.

OBJECTIVE: To assess the effect of reduced skin exposure in preterm infants receiving overhead phototherapy treatment on total serum bilirubin (TSB). METHODS: Randomized controlled trial. Preterm infants (>1500 g birthweight and < or = 36 weeks gestation) were randomized to being nursed either partially clothed with only disposable nappies and in posturally supported positions (n = 30) or naked without postural support (n = 29). Primary outcome was mean TSB percentage change at 24 h of completed conventional overhead phototherapy treatment (irradiance of 6 microW cm(-2)/nm at a wavelength of 425-475 nm). The incidence of rebound jaundice, number of infants continuing to receive phototherapy treatment at 24 h periods, parental stress, mother-infant interaction and mean TSB percentage change at 24 h of completed conventional overhead phototherapy treatment were examined. RESULTS: Mean TSB percentage change at 24 h of completed treatment for the partially clothed group was 15.4% (+/-18) and for the naked group 19% (+/-15) (mean difference 3.6% 95% CI -5.1, 12.3). No other outcomes were significantly affected by reduced skin exposure to overhead phototherapy treatment. CONCLUSION: Our results show no statistically significant difference in TSB level change using either nursing practice.

Adamts-1 is essential for the development and function of the urogenital system.

Successful ovulation and implantation processes play a crucial role in female fertility. Adamts-1, a matrix metalloproteinase with disintegrin and thrombospondin motifs, has been suggested to be regulated by the progesterone receptor in the hormonal pathway leading to ovulation. With the primary aim of investigating the role of Adamts-1 in female fertility, we generated Adamts-1 null mice. Forty-five percent of the newborn Adamts-1 null mice die, with death most likely caused by a kidney malformation that becomes apparent at birth. Surviving female null mice were subfertile, whereas males reproduced normally. Ovulation in null females was impaired because of mature oocytes remaining trapped in ovarian follicles. No uterine phenotype was apparent in Adamts-1 null animals. Embryo implantation occurred normally, the uteri were capable of undergoing decidualization, and no morphological changes were observed. These results demonstrate that a functional Adamts-1 is required for normal ovulation to occur, and hence the Adamts-1 gene plays an important role in female fertility, primarily during the tissue remodeling process of ovulation.

Gowning by attendants and visitors in newborn nurseries for prevention of neonatal morbidity and mortality.

BACKGROUND: Overgowns are widely used in newborn nurseries and neonatal intensive care units. It was thought that they may help to prevent the spread of nosocomial infection and serve as a reminder to staff and visitors to wash their hands before contacts with the infant. OBJECTIVES: The objective of this review was to assess the effects of the wearing of an overgown by attendants and visitors for the prevention of infection and death in infants in newborn nurseries. SEARCH STRATEGY: The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2002), MEDLINE (1966-January 2003) and CINAHL (1982-January 2003). SELECTION CRITERIA: All published trials using random or quasi-random patient allocation, in which overgowns worn by attendants or visitors were compared with no overgowns worn by attendants or visitors. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. Data extraction and study quality were independently assessed by the two authors. Missing information was sought from three authors but only one responded. Results are expressed as relative risk or mean difference with 95% confidence intervals. MAIN RESULTS: Eight trials were included, reporting outcomes for 3,811 infants. Trial quality varied; two were of good quality. Not wearing overgowns was associated with a trend to reduction in the death rate, typical RR 0.84 (95% CI 0.70, 1.02) compared to wearing overgowns, but these results did not reach statistical significance. There was no statistically significant effect of gowning policy on incidence of systemic nosocomial infection, typical RR 1.24 (CI 0.90,1.71). The overall analysis showed no significant effects of gowning policy on the incidence of colonisation, length of stay or handwashing frequency. No trials of visitor gowning were found. REVIEWER'S CONCLUSIONS: The evidence from this systematic review and meta analysis does not demonstrate that overgowns are effective in limiting death, infection or bacterial colonisation in infants admitted to newborn nurseries.

Systematic review of the role of pre-oxygenation for tracheal suctioning in ventilated newborn infants.

Pre-oxygenation for endotracheal suctioning for mechanically ventilated infants is routine practice in many neonatal intensive care units. In the present systematic review the evidence to support its use is discussed and the authors conclude that no confident recommendations can be made from the results of this review.

Dscr1, a novel endogenous inhibitor of calcineurin signaling, is expressed in the primitive ventricle of the heart and during neurogenesis.

We have demonstrated that DSCR1 acts as a negative regulator of calcineurin-mediated signaling and that its transcript is overexpressed in the Down syndrome (DS) fetal brain. To evaluate the possible involvement of DSCR1 in DS, we have cloned the mouse gene and analyzed its expression pattern in the central nervous system (CNS). Early expression of Dscr1 is detected mainly in the heart tube and in the CNS in rhombomere 4 and the pretectum. From embryonic day 14.5 onwards, Dscr1 is widely distributed in the CNS but becomes more restricted as the brain matures. We confirmed its neuronal expression pattern in the adult, preferentially in Purkinje and pyramidal cells, by double labeling with glial fibrillary acidic protein. We also show that although Dscr1 is present in trisomy in the Ts65Dn mouse, the adult brain expression pattern is not significantly altered. This expression pattern indicated that Dscr1 is a developmentally regulated gene involved in neurogenesis and cardiogenesis and suggests that it may contribute to the alterations observed in these organ systems in DS patients.

Postnatal depression: use of health services and satisfaction with health-care providers.

The objective of this study was to compare health-care use and satisfaction with health-care providers between depressed and non-depressed women in the first 4 months after childbirth. Sixteen weeks after delivery a questionnaire, which included the Edinburgh Postnatal Depression Scale (EPDS) and items about health-care use and satisfaction, was mailed to women who attended the antenatal clinic, Royal Women's Hospital, Brisbane. Completed questionnaires were returned by 574 (86.4%) of the 664 women surveyed. During the study period most women (91%) visited a general practitioner at least once and 117 (12%) saw their doctor on five or more occasions. A total of 118 (20.7%) scored above 12 on the EPDS. Depressed women were more likely to visit a psychiatrist (OR, 9.2; 95% CI, 4.3-19.6), social worker (OR, 6.1; 95% CI, 3.3-11.1), postnatal depression group (OR, 4.0; 95% CI, 1.3-12.6), paediatrician (OR, 2.5; 95% CI, 1.6-3.9), or a general practitioner (OR, 2.1; 95% CI, 1.4-3.2) than non-depressed women. Twenty-two (18.5%) of the depressed women had contact with a psychiatrist. Compared with non-depressed women, those scoring above 12 on the EPDS were less satisfied with the services of general practitioners (P=< 0.000), paediatricians (P=0.002), Nursing Mothers' Associations of Australia (P=0.043) and obstetricians (P=0.045). Postpartum depression leads to an increase use of health-care services and has a negative effect on satisfaction with some services.

Neonatal pneumonia: comparison of 4 vs 7 days of antibiotic therapy in term and near-term infants.

OBJECTIVE: To compare a 4-day course of antibiotic therapy to a 7-day course in selected term and near-term neonates with pneumonia. METHODS: The diagnosis of pneumonia was made in neonates admitted to the normal Newborn Nursery (NBN) who later had signs of respiratory distress and whose chest radiographs were consistent with pneumonia. Infants were excluded if any of the following was present: moderate or thick meconium-stained amniotic fluid, prior antibiotic therapy > 24 hours, or need for supplemental oxygen > 8 hours. Infants who were asymptomatic after 48 hours of antibiotic therapy were prospectively randomized to a 4-day group (n = 35) or a 7-day group (n = 38). Infants in the 4-day group were observed in the hospital for 24 hours following cessation of antibiotics and were seen in follow up within several days of discharge. RESULTS: The groups were comparable with regard to demographic factors, duration of rupture of membranes, and incidence of maternal chorioamnionitis. Median postnatal age at the time of identification of respiratory distress symptomatology was 19 hours (range 0.5 to 55 hours) in the 4-day group and 12 hours (range 1 to 72 hours) in the 7-day group. No study infants had a positive blood culture. Mean reduction in length of hospitalization was 2.1 days, with estimated savings of greater than US$700 per shortened hospitalization. Two infants in the 4-day group developed tachypnea during the 24-hour observation period. However, no infants were rehospitalized for sepsis or pneumonia following discharge. With 95% confidence, the true rate of success for the 4-day group was at least 92%. CONCLUSION: Four days of antibiotic therapy plus a 24-hour period of observation for selected cases of neonatal pneumonia appears to be comparable to 7 days of therapy. It is important to note that newborns in our institution receive a single dose of penicillin soon after birth as part of our group B streptococcal sepsis prophylaxis program, and all infants in this study received prophylaxis prior to the onset of respiratory symptoms. Furthermore, only infants who were asymptomatic after 48 hours of antibiotic therapy were included in this study, and a 24-hour observation period at the end of the 4-day course was required. These qualifications should be taken into account before use of this approach is considered, and additional studies are necessary to further establish its safety and benefits.

Development of evidence-based guidelines in midwifery and gynaecology nursing.

OBJECTIVE: To develop an effective and efficient method for basing nursing practice on research evidence. SETTING: The Royal Women's Hospital, Brisbane, Australia. METHOD: Nurses and midwives from various clinical areas were invited to participate in an evidence-based practice project. Standard procedures for retrieving relevant articles and evaluating their quality were observed. Where possible, raw data from studies with similar methods were summarised using appropriate statistical tests. FINDINGS: Several guidelines have been developed, staff involved with the project have become 'research literate' and the project is contributing to the hospital-wide quality improvement activities. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: It is possible to translate research findings into practice when small groups use systematic reviews to develop practice guidelines.

The "gene dosage effect" hypothesis versus the "amplified developmental instability" hypothesis in Down syndrome.

Two hypotheses exist to explain the Down syndrome (DS) phenotype. The "gene dosage effect" hypothesis states that the phenotype is a direct result of the cumulative effect of the imbalance of the individual genes located on the triplicated chromosome or chromosome region. In a nut shell, the phenotype results directly from the overexpression of specific chromosome 21 genes. The "amplified developmental instability" hypothesis contends that most manifestations of DS may be interpreted as the results of a non-specific disturbance of chromosome balance, resulting in a disruption of homeostasis. This hypothesis was proposed in an attempt to explain the similarities between the phenotypes of different aneuploid states and the observation that all of the phenotypic traits in DS are also seen in the general population but at lower frequency, with less severity and usually only present as a single trait. Herein, we review recent data and present evidence to support the theory that the phenotypic traits of aneuploid syndromes, and DS in particular, result from the increased dosage of genes encoded on the triplicated chromosome.

A patient with autistic disorder and a 20/22 chromosomal translocation.

The case history of a 3-year-old boy without speech and who met 10 criteria of an autistic condition (DSM-IV) (American Psychiatric Association 1994) is reported. Psychometric evaluation, excluding the verbal scale, resulted in an IQ score of 56. The cytogenetic study showed a 20/22 translocation and an interstitial deletion within the region 22q11: 45,XY, -22, +der(20), t(20;22) (q13.3;q11.2), which was confirmed by fluorescence in situ hybridisation (FISH). Although deletions at 22q11 are responsible for the DiGeorge syndrome; clinical, metabolic, and neurological image studies of the patient were inconsistent with this syndrome. In the clinical examination the patient presented with a mildly dysmorphic facies, pectus excavatum, and a short thumb. A 99mTc HMPAO brain perfusion SPECT showed a hypoperfusion of the left temporoparietal cortex. As there have been no previous reports of autistic patients with abnormalities involving both chromosomes 20 and 22, these findings merit some discussion either as a possible cause of autism or as accompanying factors.

Genomic organization, alternative splicing, and expression patterns of the DSCR1 (Down syndrome candidate region 1) gene.

Down syndrome is a major cause of mental retardation and congenital heart defects and is due to the presence of three copies of human chromosome 21 in the affected individual. We have identified a gene, DSCR1 (HGMW-approved symbol), from the region 21q22.1-q22.2, which is highly expressed in human fetal brain and adult heart. Structural features of the conceptual protein encourage us to propose involvement of DSCR1 in the regulation of transcription and/or signal transduction. Higher expression of RNA in the brains of young rats compared to adults suggests a possible role for the gene in the development of the central nervous system. We have determined the genomic organization of DSCR1 and identified three additional alternative first exons by RACE and cDNA library screening. DSCR1 spans nearly 45 kb of genomic DNA and comprises seven exons, four of which (exons 1-4) are alternative first exons. All the exons are flanked by splice junctions that conform to the consensus AG-GT motif. We have studied the expression patterns of the alternative first exons. Exon 2 was detected in fetal brain and liver by RT-PCR. Both exons 1 and 4 were differentially expressed in fetal brain, lung, liver, and kidney and in all adult tissues tested by Northern analysis with two notable exceptions: exon 1 was not detected in adult kidney and exon 4 was not found in adult brain. The high level of expression of exon 1 in fetal brain suggests that this alternative form of DSCR1 has an important role in brain development. This information should help us to understand the possible relationship of DSCR1 with Down syndrome and aid in the development of animal models.

A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region.

The minibrain (mnb) gene of Drosophila melanogaster encodes a serine-threonine protein kinase with an essential role in postembryonic neurogenesis. A corresponding human gene with similar function to mnb could provide important insights into both normal brain development and the abnormal brain development and mental retardation observed in many congenital disorders. Trisomy 21 or Down syndrome (DS) is the most frequent human birth defect. It is associated with mental retardation and a broad spectrum of physical abnormalities. A region on human chromosome 21 has been designated the Down syndrome critical region (DSCR) and when present in three copies, this is responsible for many of the characteristic features of DS, including mental retardation. We have isolated a human homologue of mnb from the DSCR. MNB encodes a 6.1 kb transcript which is expressed in foetal brain, lung, kidney and liver. Using a human probe, two major transcripts (6.1 and 3.1 kb) were identified in mouse and expression was detected in situ in several regions of the mouse brain, including the olfactory bulb, the cerebellum, the cerebral cortex, the pyramidal cell layer of the hippocampus and several hypothalamic nuclei. This expression pattern corresponds to the regions of the brain that are abnormal in individuals with DS and suggests that overexpression of MNB could have detrimental consequences in DS patients.

A new human gene from the Down syndrome critical region encodes a proline-rich protein highly expressed in fetal brain and heart.

Down syndrome is a major cause of mental retardation and congenital heart defects. While most of the affected individuals have three copies of chromosome 21, patients with partial trisomy 21 have also been described. These rare cases define a minimal region for the Down syndrome phenotype encompassing about 3 Mb around D21S55. By using a new method for the identification of coding sequences (Alu-splice PCR) we have identified a new gene, DSCR1, from region 21q22.1-q22.2. DSCR1 encodes a novel protein which has an acidic domain, a serine-proline motif, a putative DNA binding domain and a proline-rich region with the characteristics of a SH3 domain ligand. These features suggest that DSCR1 could be involved in transcriptional regulation and/or signal transduction. DSCR1 is highly expressed in human brain and heart, and increased expression in the brains of young rats compared with adults suggests a role for DSCR1 during central nervous system development. Structural characteristics, together with its particular expression in brain and heart, encourage us to suggest that the overexpression of DSCR1 may be involved in the pathogenesis of Down syndrome, in particular mental retardation and/or cardiac defects.

Molecular cloning and chromosomal localisation of the human homologue of a receptor related to tyrosine kinases (RYK).

A cDNA encoding the human homologue of mouse RYK (related to receptor tyrosine kinases) has been cloned from an interleukin 1 (IL-1)-stimulated human hepatoma cDNA library by cross-species hybridization using the mouse RYK cDNA as a probe. The sequence of the 3067-bp cDNA clone encoding human RYK predicts a transmembrane protein with a cytoplasmic domain that contains the consensus sequences (subdomains I-XI) of the protein tyrosine kinase (PTK) family. The highly conserved motif -D-F-G- (subdomain VII) of the catalytic domain of other receptor-type tyrosine kinases is altered to -D-N-A- in human RYK. In addition, a number of other changes were found in the ATP binding site (subdomains I and II) and the motif [-I-H-R-D-L-A-A-R-N-] found in subdomain VI. Comparison of the human and mouse RYK sequences shows a 92% conservation at the nucleotide level and 97% at the amino acid level. There was no significant homology between the extracellular domain of RYK and the other families of receptor tyrosine kinases described to date. RYK therefore appears to define a new subclass of receptor-type tyrosine kinases whose structure has remained highly conserved across species.

Two members of the JAK family of protein tyrosine kinases map to chromosomes 1p31.3 and 9p24.

A member of a new class of protein tyrosine kinases, JAK1, has been mapped to 1p31.3 by in situ hybridization and Southern blot analysis of a panel of mouse-human hybrid cell lines. A murine protein tyrosine kinase, related to, but distinct, from JAK1, was mapped by in situ hybridization to human Chromosome (Chr) 9p24 and 1p31.3.

The interleukin-4 receptor gene (IL4R) maps to 16p11.2-16p12.1 in human and to the distal region of mouse chromosome 7.

The chromosomal location of both the human and the mouse interleukin-4 receptor (IL4R) genes have been determined. The human gene was localized to 16p11.2-16p12.1 by in situ hybridization and confirmed by Southern blot analysis of DNA from a panel of mouse-human hybrid somatic cell lines. The mouse homolog was positioned in the distal region of chromosome 7 by interspecific backcross analysis. The results suggest that the IL4R locus is unlinked to other members of the hematopoietin receptor family. Interestingly, the position on human chromosome 16 suggests that the IL4R may be a candidate for rearrangements, as 12;16 translocations are often associated with myxoid liposarcomas.

A cloned I-factor is fully functional in Drosophila melanogaster.

I-R hybrid dysgenesis in Drosophila melanogaster occurs in female progeny of crosses between reactive strain females and inducer strain males, and is controlled by transposable elements called I-factors. These are 5.4 kb elements that are structurally similar to mammalian LINE elements and other retroposons. We have tested the activity of an I-factor directly, by introducing it into the genome of a reactive strain, using P-element mediated transformation. It confers the complete inducer phenotype on the reactive strain, and can stimulate dysgenesis when transformed males are mated with reactive females. It has transposed in the transformed lines, and we have cloned one of the transposed copies. This is the first time that it has been possible to demonstrate that a particular retroposon is transposition proficient, and to compare donor and transposed elements. We propose a mechanism for I-factor transposition based on these results, and the coding capacity of these elements. We have been unable to detect either autonomous transposition of a complete I-factor from a plasmid injected into reactive strain embryos, or transposition of a marked I-factor when co-injected with a complete element.

Effects of methotrexate on intraperiplasmic and axenic growth of Bdellovibrio bacteriovorus.

The intraperiplasmic growth rate and cell yield of wild-type Bdellovibrio bacteriovorus 109J, growing on Escherichia coli of normal composition as the substrate, were not markedly inhibited by 10-3 M methotrexate (4-amino-N10-methylpteroylglutamic acid). In contrast, the growth rate and cell yield of the mutant 109Ja, growing axenically in 0.5% yeast extract +0.15% peptone, were strongly inhibited by 10-4 and 10-3 M methotrexate. Thymine, thymidine, and thymidine-5'-monophosphate, in increasing order of effectiveness, partially or completely reversed the inhibition. E. coli depleted of tetrahydrofolate and having an abnormally high protein/deoxyribonucleic acid (DNA) ratio was obtained by growing it in the presence of methotrexate. B. bacteriovourus grew at a normal rate on these depleted E. coli cells but with somewhat reduced cell yield. Mexthotrexate (10-3 M) inhibited intraperiplasmic growth of bdellovibrio on the depleted E. coli somewhat more than it inhibited growth on normal E. coli, but the effects were small compared with inhibition of axenic growth of the mutant. Total bdellovibrio DNA after growth on the depleted E. coli in the presence or absence of methotrexate exceeded the initial quanity of E. coli DNA present. Thymidine-5'-monophosphate (10-3 M) largely reversed the inhibition and increased the amount of net synthesis of DNA. The data are consistent with the prediction that intraperiplasmic growth of B. bacteriovorus should be insensitive to all metabolic inhibitors that act by specifically preventing synthesis of essential monomers. The data also indicate that B. bacteriovorus possesses thymidylate synthetase, thymidine phosphorylase, and thymidine kinase, and has the potential to carry out de novo DNA synthesis from non-DNA precursors during intraperiplasmic growth. The results also suggest that methionyl tRNAfMet is not required for initiation of protein synthesis by B. bacteriovorus.