Biomedical subjects

D Bader

Publications and source records attributed to D Bader.

At least 19 recordsLinked to original sources

PubMed2002

Sidestream end-tidal capnometry as related to infant's position and maturation.

UNLABELLED: The objective of this study was to investigate the effect of body position on sidestream, end-tidal carbon dioxide (EtCO2) wave measurements in maturing infants. Sidestream EtCO2 wave patterns were analysed longitudinally in 20 preterm infants (born at > or = 32 wk) at 32-37 wk gestation, and in 39 full-term controls. Capnography measurements included maximal EtCO2, inspired CO2 and frequency of apnoea events (>3 s) in the supine, supine with inclination, side and prone positions. Apnoea frequency decreased during maturation, and was less prevalent in the prone than in the supine and side positions in preterm as well as in term infants (p < 0.05). No clinically significant apnoea episodes were found in our cohort. EtCO2 in term infants was lower than that in preterm infants (p < 0.05) and was not affected by sleep position in the most premature (<33 wk) and in term infants (>36 wk). EtCO2 was higher in the prone position than in supine or side positions in infants between 33 and 35 wk gestation (p < 0.01). CONCLUSION: Short apnoeic episodes decrease during maturation, and are less prevalent in the prone position in maturing infants (32-37 wk). Only modest changes in EtCO2 were recorded in the different positions during maturation.

Birth Weight↗

PubMed2001

Functional tests for the characterization of surfactant protein B (SP-B) and a fluorescent SP-B analog.

Surfactant protein B (SP-B) enhances lipid insertion into the alveolar air/liquid interface upon inhalation. The aim of this study was (i) to apply a palette of tests for a detailed biochemical and biophysical characterization of SP-B and (ii) to use these tests to compare native SP-B with a fluorescent (Bodipy) SP-B analog. The method of labeling was fast and resulted in a covalent fluorophore-protein bond. The ability of both proteins to spread a surfactant film on top of a buffer surface was determined in a spreading tray using the Wilhelmy plate technique to allow detection of alterations in surface tension and calculation of spreading velocities. In a captive bubble surfactometer surface tensions of spread films were measured. Similar biophysical properties were found for both native and Bodipy-labeled SP-B. It is concluded that the combination of tests used allows detection of small differences in structure and activity between the two proteins.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2001

Surfactant protein B labelled with [(99m)Tc(CO)3(H20)3](+) retains biological activity in vitro..

UNLABELLED: Labelling of the hydrophobic surfactant protein B (SP-B) under non-reducing conditions was achieved with [(99m)Tc(CO)(3)(H2O)(3)](+) prepared according to Alberto et al. (JACS, 1998). The binding of radioactivity was protein-specific, with an overall radiochemical yield of 50%. Gel electrophoresis and Westernblot analyses showed no structural changes of SP-B. Spreading properties and surface activity of (99m)Tc-labelled SP-B in an air/water interface coincided with those of unlabelled SP-B. (99m)Tc-SP-B seems to be a promising agent to observe surfactant spreading under clinical conditions. BACKGROUND: Therapeutic results for surfactant instillation in clinical trials are conflicting. The (99m)Tc-labelling of surfactant would allow to observe its spreading in the lung under clinical conditions. METHODS: [(99m)Tc(CO)(3)(H2O)(3)](+) was prepared as described by Alberto et al. (JACS, 1998). This carbonyl complex was used for the direct labelling of surfactant protein B (SP-B) under non-reductive conditions by direct incubation with SP-B at elevated temperature followed by extraction into CHCl(3)/MeOH. RESULTS: The hydrophobic protein SP-B was labelled with [(99m)Tc(CO)(3)(H2O)(3)](+). An overall radiochemical yield of about 50% was achieved. HPLC-analysis revealed a single radiolabelled species according to UV elution profile of SP-B, supported by paper and size exclusion chromatography. Gel electrophoresis confirmed that the dimer structure of SP-B was preserved. Spreading properties of (99m)Tc-labelled SP-B in an air/water interface coincided with those of unlabelled SP-B. Spreading of radioactivity observed in a glass trough of 26 cm x 27 cm with a gamma camera was completed during the first 7-9 sec after application of (99m)Tc-labelled SP-B. The corresponding decrease of surface tension to 45 mN/m at the peripheral surface tension sensors took 7 sec +/- 2 sec (MEAN +/- STD; n = 3). CONCLUSIONS: Direct and specific (99m)Tc-labelling of the hydrophobic surfactant protein B was achieved using the [(99m)Tc(CO)(3)(H2O)(3)](+) precursor. This procedure can easily be used to prepare specifically labelled surfactant mixtures with spreading properties that coincide with those of unlabelled surfactant.

Animals↗

PubMed2001

The role of high-dose oral iron supplementation during erythropoietin therapy for anemia of prematurity.

OBJECTIVE: To assess whether a high intake of oral iron would increase the effect of recombinant human erythropoietin (rHuEPO) on hemoglobin synthesis. METHODS: We studied 30 preterm infants (gestational age 29+/-1.8 weeks, birth weight 1161+/-200 g, at age of 28+/-10 days) who were randomly assigned to receive either 8 mg/kg per day (n=15) or 16 mg/kg per day of oral iron during a course of rHuEPO therapy (900 microg/kg per week) for a duration of 4 weeks. Both groups were comparable in regard to clinical and laboratory data at the time of enrollment. RESULTS: rHuEPO caused a significant increase in reticulocyte count in the low- and high-dose iron groups, 17.1+/-5.3 to 34.7+/-9.2 and 16.3+/-3.3 to 42.5+/-5.6 (10(9)/l), respectively (p<0.05). However, in both groups, hematocrit values remained stable at the end of the study as compared to baseline (0.35+/-0.03% vs. 0.30+/-0.03%, 0.35+/-0.05% vs. 0.30+/-0.03%, NS) and in both groups there was a comparable and significant decrease in ferritin level (259+/-109 to 101+/-40 and 168+/-54 to 69+/-38 microg/l, respectively; p<0.01). The rates of bloody stools without any evidence of necrotizing enterocolitis were not significantly different between the two treatment groups (1/15 vs. 4/15, NS). CONCLUSION: We conclude that a higher dose (16 mg/kg per day) of oral iron is not more beneficial when compared to a lower dose (8 mg/kg per day) during rHuEPO therapy for anemia of prematurity. Further studies will define the optimal dosage and route of administration of iron supplementation during rHuEPO therapy.

Administration, Oral↗

PubMed2001

Capnography in spontaneously breathing preterm and term infants.

OBJECTIVE: To investigate sidestream EtCO2 wave patterns as related to prematurity. DESIGN: The EtCO2 wave pattern was analyzed longitudinally in 20 sequential preterm, 32-37 weeks of gestation and 39 fullterm controls. Infants with a cardiorespiratory disease, neurological deficit or a metabolic disorder were not included in the study. Sidestream EtCO2 was employed. Wave patterns were identified and baseline expiratory/inspiratory length and wave amplitude were measured. RESULTS: Two predominant (about 75%) wave patterns were identified: (i) (with plateau) significantly more prevalent among infants born at term as compared with preterm infants across their postconceptional ages (PCA) (P=0.005-0.04), (ii) (plateau free) significantly more prevalent among the youngest preterm infants as compared with the fullterm controls. Expiratory length was significantly correlated with respiratory rate (RR) across ages (P=0.01-0.001) whereas inspiratory length was correlated with RR among the two youngest groups of infants only (P=0.002 and 0.004). Wave patterns were not found to be affected by environmental temperatures, blood pressure, body weight, haemoglobin level, aminophylline or O2 supplementation. CONCLUSION: These findings suggest that EtCO2 wave pattern distribution among preterm infants is distinctly different from that of term controls, regardless of PCA, while inspiration is related to the degree of maturity. Alveolar pathology could probably be missed by sidestream capnography.

Blood Pressure↗

PubMed2001

Validation of a specific activity questionnaire to estimate exercise tolerance in patients referred for exercise testing.

BACKGROUND: Physical activity and symptom questionnaires have been used as surrogates for exercise testing to estimate a patient's functional capacity and to individualize an exercise testing protocol in accordance with exercise testing guidelines. To validate these approaches, they must be compared with measured oxygen uptake (peak VO (2)). METHODS: Before exercise testing was performed, a brief, self-administered questionnaire (Veterans Specific Activity Questionnaire [VSAQ]) was given to 337 patients referred for exercise testing for clinical reasons. The VSAQ was used to estimate exercise tolerance on the basis of symptoms during daily activities to individualize ramp rates on the treadmill so that the test duration would be approximately 10 minutes. Clinical and demographic variables were added to the VSAQ responses in a stepwise regression model to determine their ability to predict both directly measured peak VO (2) and peak metabolic equivalents (METs) predicted from the treadmill workload. RESULTS: The mean exercise time was 9.6 +/- 3 minutes. Responses to the VSAQ and age were the strongest predictors of both measured and predicted exercise capacity. Small but significant contributions to the explanation of variance in both measured and estimated METs were made by resting heart rate, forced expiratory volume in 1 second expressed as a percentage of normal, exercise capacity predicted for age, and body mass index. The multiple R values from the regression equations for measured and estimated METs were 0.58 and 0.72, respectively. CONCLUSIONS: Estimating a patient's symptoms associated with daily activities along with age are the strongest predictors of a patient's exercise tolerance. The VSAQ, combined with pretest clinical data, predicts the estimated MET value from treadmill speed and grade better than directly measured METs do. When used for estimating a patient's symptom limits to individualize ramp rates on a treadmill, this approach yields an appropriate test duration in accordance with recent exercise testing guidelines.

Activities of Daily Living↗

PubMed2000

Analysis of CMF1 reveals a bone morphogenetic protein-independent component of the cardiomyogenic pathway.

Disruption of the CMF1 function in anterior mesoderm inhibits cardiac myogenesis in avian embryos. In the present study, we show that CMF1 is a member of an emerging family of proteins that includes centromeric protein-F, mitosin, and LEK1. These proteins are characterized by their large size (350 kDa), dynamic subcellular distribution, and potential functions in cell division and differentiation. The current data suggest that CMF1 is a unique member of this family by virtue of its restricted protein expression and variant subcellular distribution. Immunochemical analysis demonstrates that CMF1 protein is expressed in cardiogenic cells prior to the activation of cardiac structural gene products. In addition, we show that expression of CMF1 is not dependent on the bone morphogenetic protein (BMP) signaling pathway during development. Still, CMF1 cannot direct cardiomyogenesis in the absence of such factors as NKX-2.5. Taken with our previous data, this study suggests that CMF1 is a BMP-independent component of the cardiomyogenic pathway.

Amino Acid Sequence↗

PubMed2000

Identification and genomic cloning of CMHC1. A unique myosin heavy chain expressed exclusively in the developing chicken heart.

We report the identification and cloning of a unique chick myosin heavy chain (CMHC1) that is expressed exclusively in the heart during embryogenesis. Using primers specific to myosin heavy chains, we used reverse transcriptase-polymerase chain reaction to clone and isolate CMHC1 from embryonic day 10 chicken heart RNA. Sequence analysis indicated that CMHC1 was a novel member of the myosin heavy chain family. Expression of the CMHC1 transcripts was detected in Hamburger Hamilton stage 10 chick embryos in the fusing myocardium. Expression of CMHC1 was maintained at high levels throughout the tubular heart of later stage embryos. Reverse transcriptase-polymerase chain reaction and in situ hybridizations failed to detect CMHC1 transcripts in the developing somites, limb buds, or skeletal musculature at any stage of chick development. Genomic CMHC1 clones have been isolated that contain sequences approximately 5.2 kilobase upstream of the presumptive CMHC1 transcription start site. Portions of the upstream regulatory region induced a 21-fold increase in reporter gene expression in primary cardiomyocytes. Because of its unique cardiac-restricted expression, CMHC1 will provide an excellent model system to study the molecular mechanisms required for the early developmental regulation of heart-specific genes.

3T3 Cells↗

PubMed2000

Potential role of high-frequency ventilation in the treatment of severe congenital pleural effusion.

Newborns with severe congenital pleural effusions often present with respiratory failure at birth. We describe two premature infants born at 31 and 33 weeks of gestation with bilateral pleural effusions. Both were drained prior to delivery under ultrasound guidance. The first infant had severe bilateral congenital chylothorax with pulmonary hypertension; the second infant had severe nonimmune hydrops fetalis. Both could be adequately oxygenated but failed to respond to conventional mechanical ventilation (CMV) and chest tube drainage, so that CO(2) elimination could not be accomplished. Both infants were successfully treated with high-frequency ventilation (HFV). We suggest that HFV may be of significant value in establishing adequate ventilation in cases of severe congenital pleural effusions.

Adult↗

PubMed2000

Characterization of CMF1 in avian skeletal muscle.

This study reports the identification of the CMF1 protein in somites and embryonic limb muscle. We have previously described CMF1 in developing cardiac muscle. CMF1 is a member of the LEK family of proteins, which are involved in regulating mitosis. Our current data suggest that CMF1 expressed in skeletal and cardiac myocytes is the product of a single gene and that the two proteins are homologous or very highly conserved. Immunohistochemistry shows a dynamic subcellular localization of CMF1 in differentiating skeletal myoblasts: Early myoblasts stain positively for CMF1 antigen in the nucleus, while differentiating myoblasts stain positively in the cytoplasm. CMF1 expression precedes myosin. Later, CMF1 and myosin are detected in the cytoplasm of the same cells. Transfection analysis identifies a functional nuclear localization signal (NLS) in CMF1, whose nuclear transport capability is modified by external sequences. To characterize the function of CMF1 in skeletal muscle, we used antisense oligonucleotides to disrupt CMF1 in myoblast cultures. Expression of CMF1 in early myotubes is reduced by an average of 40% on a cell by cell basis, with a 56% reduction in anti-myosin staining. These data suggest that CMF1 is involved in induction and/or accumulation of myosin in differentiating myocytes.

Amino Acid Sequence↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

Selected abstracts

Explore the source record for details and available documents.

Journal Article↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1998

[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↗