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Biomedical subjects

D Bader

Publications and source records attributed to D Bader.

At least 37 records · Page 2Linked to original sources

Effects of a policy of elective cesarean delivery in cases of suspected fetal macrosomia on the incidence of brachial plexus injury and the rate of cesarean delivery.

OBJECTIVE: The aim of this study was to examine the effects of a policy of elective cesarean delivery for suspected fetal macrosomia on the incidence of brachial palsy and on the cesarean delivery rate. STUDY DESIGN: We performed a retrospective assessment of a policy that recommends cesarean delivery for macrosomia (fetal weight > or =4500 g). Fetal weight was estimated by palpation, and ultrasonographic weight estimation was carried out whenever macrosomia was suspected. RESULTS: During the 4 years of the study 16,416 deliveries resulted in 133 infants with macrosomia (0.8%). Macrosomia was suspected in 47 cases and confirmed by birth weight in 21 (45%). Antenatal estimation of fetal weight was carried out for 115 of the fetuses with macrosomia (86%). Macrosomia was correctly predicted in 21 of 115 cases (18.3%). Thirteen infants with undiagnosed macrosomia were delivered by emergency cesarean procedures, and 99 were delivered vaginally. Three infants with macrosomia (3%) and 14 infants without macrosomia (0.1%) sustained brachial plexus injury. Our policy prevented at most a single case of brachial palsy, and it contributed 0.16% to our cesarean delivery rate. CONCLUSIONS: A policy of elective cesarean delivery in cases of suspected fetal macrosomia had an insignificant effect on the incidence of brachial plexus injury. Its contribution to the rate of cesarean delivery was also small.

Birth Injuries↗

Early postnatal dexamethasone treatment and increased incidence of cerebral palsy.

OBJECTIVE: To study the long term neurodevelopmental outcome of children who participated in a randomised, double blind, placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease. METHODS: The original study compared a three day course of dexamethasone (n = 132) with a saline placebo (n = 116) administered from before 12 hours of age in preterm infants, who were ventilated for respiratory distress syndrome and had received surfactant treatment. Dexamethasone treatment was associated with an increased incidence of hypertension, hyperglycaemia, and gastrointestinal haemorrhage and no reduction in either the incidence or severity of chronic lung disease or mortality. A total of 195 infants survived to discharge and five died later. Follow up data were obtained on 159 of 190 survivors at a mean (SD) age of 53 (18) months. RESULTS: No differences were found between the groups in terms of perinatal or neonatal course, antenatal steroid administration, severity of initial disease, or major neonatal morbidity. Dexamethasone treated children had a significantly higher incidence of cerebral palsy than those receiving placebo (39/80 (49%) v. 12/79 (15%) respectively; odds ratio (OR) 4.62, 95% confidence interval (95% CI) 2.38 to 8.98). The most common form of cerebral palsy was spastic diplegia (incidence 22/80 (28%) v. 5/79 (6%) in dexamethasone and placebo treated infants respectively; OR 4.45, 95% CI 1.95 to 10.15). Developmental delay was significantly more common in the dexamethasone treated group (44/80 (55%)) than in the placebo treated group (23/79 (29%); OR 2. 87, 95% CI 1.53 to 5.38). Dexamethasone treated infants had more periventricular leucomalacia and less intraventricular haemorrhage in the neonatal period than those in the placebo group, although these differences were not statistically significant. Eleven children with cerebral palsy had normal ultrasound scans in the neonatal period; all 11 had received dexamethasone. Logistic regression analysis showed both periventricular leucomalacia and drug assignment to dexamethasone to be highly significant predictors of abnormal neurological outcome. CONCLUSIONS: A three day course of dexamethasone administered shortly after birth in preterm infants with respiratory distress syndrome is associated with a significantly increased incidence of cerebral palsy and developmental delay.

Anti-Inflammatory Agents↗

Selected abstracts

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Journal Article↗

Loss of Daxx, a promiscuously interacting protein, results in extensive apoptosis in early mouse development.

The mammalian Daxx gene has been identified in a diverse set of yeast interaction trap experiments. Although a facilitating role for Daxx in Fas-induced apoptosis has been suggested, Daxx's physiologic function remains unknown. To elucidate the in vivo role of Daxx, we have generated Daxx-deficient mice. Surprisingly, rather than a hyperproliferative disorder expected from the loss of a pro-apoptotic gene, mutation of Daxx results in extensive apoptosis and embryonic lethality. These findings argue against a role for Daxx in promoting Fas-induced cell death and suggest that Daxx either directly or indirectly suppresses apoptosis in the early embryo.

Adaptor Proteins, Signal Transducing↗

The cloning and analysis of LEK1 identifies variations in the LEK/centromere protein F/mitosin gene family.

We report the cloning of a novel murine cDNA, LEK1, that is related to human CENP-F and mitosin and more distantly to chicken CMF1. The proteins from these three organisms have significant homology, yet differ in their temporal, spatial, and subcellular localizations. The human proteins bind the kinetochore in mitotic cells, whereas the chicken protein is found only in skeletal and cardiac muscle and is developmentally regulated. Mouse LEK1 is a single copy gene that codes for two developmentally regulated transcripts. The LEK1 protein is expressed early and ubiquitously in mouse development and is generally down-regulated as development proceeds in a manner that correlates to a cessation of mitosis. In adult tissues, the LEK1 protein is detected exclusively in the pronucleus of the oocyte and was not observed in other actively dividing tissues. Subcellular localization revealed that the LEK1 protein in mitotic cells does not bind the kinetochore. From these data, we hypothesize that chicken CMF1, human CENP-F, mitosin, and mouse LEK1 are members of an emerging family of genes that have important and functionally distinct roles in development and cell division.

Amino Acid Sequence↗

bves: A novel gene expressed during coronary blood vessel development.

We have used a subtractive method to clone novel messages enriched in the heart. Here we show that one such message, bves (blood vessel/epicardial substance) is a novel protein that is highly conserved between chicken and mouse. The bves message is detected at high levels in early chick hearts. Using anti-Bves antibodies, we show expression in cells of the proepicardial organ, migrating epicardium, epicardial-derived mesenchyme, and smooth muscle of the developing intracardiac arterial system, including the coronary arteries. Our data suggest that Bves is an early marker of developing vascular smooth muscle cells. In addition, the expression pattern of Bves protein reveals the patterning of intracardiac vascular smooth muscle and possible insights into the cellular regulation of smooth muscle differentiation during vasculogenesis.

Actins↗

Intrapartum drainage of fetal pleural effusion.

Our objective was to describe our experience with intrapartum thoracocentesis in fetuses with severe bilateral pleural effusion. We describe the outcome of four consecutive cases of fetal pleural effusion due to chylothorax that were managed by intrapartum thoracocentesis. These fetuses were not candidates for pleuro-amniotic shunting either because of the need for prompt delivery (three fetuses) or because of advanced gestational age (one fetus). Thoracocentesis was performed in the operating theatre under ultrasound guidance prior to Caesarean delivery. Gestational age at the time of diagnosis and thoracocentesis ranged between 26-34 weeks and 31-34 weeks respectively. Bilateral thoracocentesis was performed in two fetuses and unilateral in the remaining two fetuses. All four infants were born in a relatively good condition; however, all eventually required intubation, ventilation and chest tubes. Chest tubes were introduced between 2 h and 5 days after delivery in three infants, and immediately after birth in one infant who was hydropic. Two infants survived and are developing normally. One infant died from sepsis following successful pleurodesis and one from aspiration on day 51. Our conclusions are that intrapartum thoracocentesis seems to be a relatively simple procedure, that allows newborns with pleural effusion, to breathe spontaneously or be more easily ventilated. This in turn, reduces the need to introduce chest tubes in an emergency situation.

Drainage↗

[Fungus-ball in a preterm infant successfully treated with fluconazole].

Very-low-birth-weight premature infants are at high risk for invasive candidiasis. The most commonly involved organ is the kidney. Renal candidiasis may present as fungus-ball obstructive uropathy. We describe unilateral renal obstruction secondary to fungus-ball in a premature infant. Noninvasive, systemic antibiotic treatment, including amphotericin B and fluconazole, resulted in disappearance of the finding.

Amphotericin B↗

Apnoea-associated heart rate changes among preterm and full-term infants exposed to hyperthermia.

Heart rate (HR) changes associated with apnoea (> 3 s) were analysed in 10 preterm infants (30.6 +/- 1.5 weeks) at post-conceptional age of 40 +/- 1.5 weeks and 10 full-term (FT) infants (39 +/- 1 weeks) before, during and after exposure to increased environmental temperature (5 degrees C above normothermia). A significantly increased HR was found in the study group during the baseline (normothermia), heating, cooling and final normothermic phase compared with the control infants. No significant difference was found between the groups during the hyperthermic stage. A significant relative increase in HR was found among the preterm infants but not among FT infants during central apnoea at the hyperthermia phase. Our results indicate that HR control during apnoea in preterm infants is more labile then among FT infants while being exposed to increased environmental temperature.

Apnea↗

Immunogenicity of hepatitis B vaccine in preterm infants.

AIM: To assess the immunogenicity of hepatitis B vaccine in preterm and term infants, given in a sequence of three doses beginning soon after birth. METHOD: The immunogenicity of hepatitis B vaccine was assessed in 176 preterm infants (< 35 weeks of gestation), immunised soon after birth, and compared with that in 46 term infants. Titres of hepatitis B antibodies were determined one to two months after the third vaccine. The significance of the differences between the term and preterm groups was determined using Student's t test. RESULTS: A similar proportion of infants in both preterm and term groups attained protective titres of hepatitis B antibodies (88.7% vs 93.4%, respectively; p = NS). However, the term infants had a higher geometric mean titre of antibodies after the third vaccine than did the preterm infants (701.2 (745.0) vs 469.1 (486.2) mU/ml, respectively; p < 0.03). CONCLUSION: Hepatitis B vaccine is effective in most preterm infants when given soon after birth. It may be advisable to determine the immune response at 12-24 months of age to booster the non-responders.

Antibody Formation↗

Effect of vitamin K1 on glucose-6-phosphate dehydrogenase deficient neonatal erythrocytes in vitro.

AIM: To determine whether vitamin K1, which is routinely administered to neonates, could act as an exogenous oxidising agent and be partly responsible for haemolysis in glucose-6-phosphat-dehydrogenase (G-6-PD). METHODS: G-6-PD deficient (n = 7) and control (n = 10) umbilical cord blood red blood cells were incubated in vitro with a vitamin K1 preparation (Konakion). Two concentrations of Vitamin K1 were used, both higher than that of expected serum concentrations, following routine injection of 1 mg vitamin K1. Concentrations of reduced glutathione (GSH) and methaemoglobin, indicators of oxidative red blood cell damage, were determined before and after incubation, and the mean percentage change from baseline calculated. RESULTS: Values (mean (SD)) for GSH, at baseline, and after incubation with vitamin K1 at concentrations of 44 and 444 microM, respectively, and percentage change from baseline (mean (SD)) were 1.97 + 0.31 mumol/g haemoglobin, 1.89 +/- 0.44 mumol/g (-4.3 +/- 13.1%), and 1.69 +/- 0.41 mumol/g (-14.5 +/- 9.3%) for the G-6-PD deficient red blood cells, and 2.27 +/- 0.31 mumol/g haemoglobin, 2.09 +/- 0.56 mumol/g (-7.2 +/- 23.2%), and 2.12 +/- 0.38 mumol/g (-6.0 + 14.1%) for the control cells. For methaemoglobin (percentage of total haemoglobin), the corresponding values were 2.01 +/- 0.53%, 1.93 +/- 0.37% (-0.6 +/- 17.4%) and 2.06 +/- 0.43% (5.7 +/- 14.2%) for the G-6-PD deficient red blood cells, and 1.56 +/- 0.74%, 1.70 +/- 0.78% (12.7 +/- 21.9%), and 1.78 +/- 0.71% (20.6 +/- 26.8%) for the control red blood cells. None of the corresponding percentage changes from baseline was significantly different when G-6-PD deficient and control red blood cells were compared. CONCLUSIONS: These findings suggest that G-6-PD deficient red blood cells are not at increased risk of oxidative damage from vitamin K1.

Biomarkers↗

Preauricular tags and pits in the newborn: the role of hearing tests.

The aim of this study was to determine the role of audiometry in a group of newborn infants with preauricular tags or pits. During the 2 years of prospective study, 26 infants were born with preauricular tags or pits (5.7 per 1,000 livebirths) and were assessed for hearing impairment by performing behavioural audiometry on day 3 of life and brainstem-evoked response audiometry at 4 months of age. Five infants had associated congenital anomalies (19%). The behavioural audiometry was abnormal in seven infants (27%). The evoked response audiometry was abnormal in 4/23 (17%) newborn infants with isolated tags or pits, and revealed both conductive and/or sensorineural hearing impairment. The incidence of hearing impairment with isolated preauricular tag/pit was significantly higher (p < 0.001) than the incidence reported in preschool children. We conclude that hearing assessment is recommended in the routine evaluation of the newborn with isolated preauricular tags or pits. This policy may facilitate early diagnosis and treatment of hearing impairment in this population.

Audiometry↗

Sweat analysis following pressure ischaemia in a group of debilitated subjects.

This article examines the application of a simple technique for the collection of sweat to the investigation of tissue metabolites in 11 debilitated subjects attending a rehabilitation unit. It is applicable to subjects with a range of clinical conditions. Sweat was collected at the sacrum with the subjects either seated in a wheelchair or lying in bed, which was representative of their usual daily routine. The tissues could be loaded during sweat collection by sacral support in either of these positions. Collections were made for about 10 hours and interface pressures were recorded on at least two occasions. After the prescribed period, the sweat pads were removed and a quantitative analysis of a range of metabolites was performed. Metabolite concentrations may reflect local tissue viability and responses to loading. In unloaded tissues the metabolite concentrations were similar to those observed in nondisabled subjects in an earlier study. During prolonged loading at relatively low levels of pressure, there was elevation in the levels of some metabolites; for example 39 and 28% increases for lactate and urea respectively. Successive measurements on an individual over a period of months showed variations, which were small compared to those observed in either groups of nondisabled or debilitated subjects. These observations suggest that the technique may be best applied in clinical practice to monitor sequential changes in individual subjects.

Adult↗

Molecular cloning and expression of two novel avian cytochrome P450 1A enzymes induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Transcriptional regulation by the aryl hydrocarbon receptor, for which the environmental toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent ligand, leads in mammalian liver to the induction of genes for two distinct cytochrome P450 (CYP)1A enzymes, CYP1A1 and -1A2. Fish seem to have only one CYP1A enzyme. CYP1A enzymes have been regarded as injurious largely because of their ability to activate chemical carcinogens. We report here the cloning and sequencing of cDNAs for two catalytically distinct TCDD-induced CYP enzymes in chick embryo liver. One mediates classic CYP1A1 activities. The other has some -1A2-like activities and is also responsible for TCDD-induced arachidonic acid epoxygenation, a much more conspicuous effect in liver of chicks than of mammalian species. Amino acid sequence analysis shows that although each chick enzyme can be classified in the CYP1A family, both are more like CYP1A1 than -1A2, and neither can be said to be directly orthologous to CYP1A1 or -1A2. Phylogenetic analysis shows that the two chick enzymes form a separate branch in the CYP1A family tree distinct from mammalian CYP1A1 and -1A2 and from fish CYP1A enzymes. The findings suggest that CYP1A progenitors split into two CYP enzymes with some parallel functions independently in two evolutionary lines, evidence for convergent evolution in the CYP1A family. Northern analysis shows that the chick enzymes have a different tissue distribution from CYP1A1 and -1A2. Polymerase chain reaction and in situ hybridization data show that both chick enzymes are expressed in response to TCDD even before organ morphogenesis. The findings further suggest that beyond their role in activating carcinogens, CYP1A enzymes have conferred evolutionary and developmental advantages, perhaps as defenses in maintaining homeostatic responses to toxic chemicals.

Amino Acid Sequence↗

Sleep architecture as related to temperature changes in neonates at term.

Sleep architecture was assessed under different environmental temperatures in 10 full-term and 10 preterm infants who reached term. Five 30-min periods of baseline, normothermia heating, peak temperature, cooling and normothermia were analysed. A significant decrease in the proportion of active sleep (AS) and an increase in quiet sleep (QS) was noted among the full-term infants during the heating and peak temperature conditions, whereas, among the preterm infants, a similarly significant difference was noted during the heating and cooling stages of the study, but not during the stage of peak temperature. This differential response to environmental hyperthermia is possibly related to maturational factors. This phenomenon may be related to the increased vulnerability of low birth weight infants to apnoea and sudden infant death syndrome.

Body Temperature↗