[Persistent pulmonary hypertension of the newborn--new modes of therapy].
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Biomedical subjects
Publications and source records attributed to D Bader.
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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.
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.
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.
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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.
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.
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.
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.
Erythropoietin (rHuEPO) therapy has been shown to be beneficial in preventing and treating anaemia of prematurity and to decrease the need for blood transfusions. There is, however, only scanty data on the effect of rHuEPO therapy on iron metabolism. We studied 29 preterm infants (age 34 +/- 14 days) who were randomly assigned to receive either rHuEPO 900 U kg-1 week-1 with 6 mg kg-1 day-1 of iron for 4 weeks (n = 15) or no therapy. The following parameters were evaluated and compared between and within groups at the beginning, during and at the end of the study: Haematocrit (SI), reticulocytes (10(9) micrograms l-1), serum ferritin (microgram 1-1) and iron (mumol l-1). The results were as follows. At the baseline, erythropoietin levels were similar in both groups: 7.2 +/- 5.6 versus 6.2 +/- 3.2 mU ml-1 (NS). In the treated infants the haematocrit remained stable during the study and was significantly higher than in the control group by the end of the study: 0.34 +/- 0.03 versus 0.28 +/- 0.05 (p = 0.001). rHuEPO therapy increased the reticulocyte count from 130 +/- 70 to 430 +/- 200 (p = 0.0002). However, rHuEPO therapy depleted both serum ferritin and iron levels from 321 +/- 191 to 76 +/- 58 micrograms l-1 (p = 0.04) and from 18 +/- 5 to 13 +/- 4 mumol l-1 (p = 0.03), respectively. We conclude that rHuEPO therapy prevented anaemia and its sequelae; however, serum ferritin and iron levels were depleted. We suggest that the effect of rHuEPO may be further increased by higher iron supplementation.
OBJECTIVE: To study the effect of early postnatal dexamethasone (days 1-3) on the incidence and severity of chronic lung disease in preterm infants with respiratory distress syndrome. METHODS: A multicentre, randomised, placebo controlled, blinded study was carried out in 18 neonatal intensive care units in Israel. The primary outcome measure was survival to discharge without requirement for supplemental oxygen therapy beyond 28 days of life. The secondary outcome measures were requirement for mechanical ventilation at 3 and 7 days, duration of ventilation or oxygen therapy, need for subsequent steroids for established chronic lung disease and incidence of major morbidities. RESULTS: The study consisted of 248 infants (dexamethasone n = 132; placebo n = 116). No differences were found in the outcome variables except for a reduction in requirement for mechanical ventilation at age 3 days in treated infants (dexamethasone 44%, placebo 67%; P = 0.001). Gastrointestinal haemorrhage, hypertension, and hyperglycaemia were more common in treated infants, but no life threatening complications, such as gastrointestinal perforation, were encountered. CONCLUSIONS: These data do no support the routine use of early postnatal steroids, but may justify further study in a selected, high risk group of infants.
A novel cDNA, pCMF1, which is expressed exclusively and transiently in the myogenic cells of the differentiating chicken heart was isolated and characterized. The full-length cDNA of pCMF1 has one open reading frame encoding 1538 predicted amino acids. While computer analysis predicts the presence of specific structural motifs, the overall sequence of pCMF1 is unique. The pattern of pCMF1 gene expression during heart formation was determined by whole-mount in situ hybridization. pCMF1 is transiently expressed within the myogenic cells of the primitive heart tube from stages 9 to 18 and is not detected in the heart or any other tissue thereafter. A replication-deficient retrovirus was used to mediate pCMF1 antisense expression in cardiogenic mesoderm. These analyses determined that the presence of pCMF1 antisense sequences disrupted myosin heavy chain expression during cardiac mesoderm differentiation. pCMF1 antisense had no effect on myosin heavy chain expression in differentiated cardiac myocytes. These data suggest a potential function for pCMF1 during cardiac myogenesis.
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A clonal cell line (QCE-6) sharing many properties with splanchnic mesodermal cells has been derived from 20-methylcholanthrene-treated cardiogenic mesoderm of the Japanese quail. QCE-6 cells which have been stably maintained for over 4 years in vitro display positive staining with antibodies to cytokeratin, vimentin, cingulin, and N-cadherin but were negative for markers of endothelial, fibroblastic, smooth, and skeletal muscle cell lineages. In the present study, we show that addition of retinoic acid and growth factors initiated cardiomyogenic differentiation in approximately 50% of QCE-6 cells as indicated by the expression of muscle- and cardiac-specific proteins. The distribution of these proteins in induced cells was similar to precontractile cardiac myocytes. In addition to these myogenic cells, cultures of induced QCE-6 cells contained endothelial cells as visualized by the presence of QH1 antigen and extracellular matrix molecules associated with endothelial cells. These data demonstrate that the QCE-6 cell is a progenitor of both cardiac myogenic and endothelial cell lineages and along with other recent studies (Linask and Lash, 1993; Garcia-Martinez and Schoenwolf, 1993) suggest that these two cell lineages may have a common embryonic origin.
The ability of undifferentiated cardiogenic mesoderm to generate diversified myogenic phenotypes was assayed in a minimal culture system. During cardiogenesis in vivo, the anterior and posterior segments of the avian heart have distinct patterns of contractile protein gene expression when they first differentiate. To assess the potential of undifferentiated cardiogenic tissue to diversify into distinct anterior and posterior lineages prior to heart formation, cardiogenic mesoderm and endoderm were removed together from the embryo at Hamburger and Hamilton stages 4-8. Explants from each of these stages differentiated in defined medium as indicated by the expression of muscle-specific genes. However, the ability to express the atrial-specific myosin heavy chain (AMHC) mRNA was confined to posterior cardiac progenitors. Diversification was not dependent on anterior endoderm, suggesting that inductive interactions between the mesoderm and endoderm are not necessary to maintain diversified cardiac lineages after stage 4. The diversified potential of explanted cardiogenic tissue was altered with retinoic acid treatment, resulting in the activation of AMHC1 gene expression in the anterior progenitors. Anterior cardiogenic cells removed from the embryo at stage 8, when the heart begins to differentiate in vivo, are not susceptible to the alteration of diversified phenotype by retinoic acid treatment. Therefore, the potential to form distinct cardiomyogenic cell lineages is present in the anterior lateral plate mesoderm soon after gastrulation and the maturation of these lineages in a positionally dependent manner is maintained in a simple defined culture system in vitro.
UNLABELLED: The diagnosis and evaluation of perinatal asphyxia can be problematic and objective means of assessing its severity are lacking. To study the validity of urinary uric acid as a marker of the degree of perinatal asphyxia, the ratio of urinary uric acid to creatinine (UA/Cr) in urine specimens obtained after birth was measured in two groups of infants. Eighteen term infants with Apgar scores < or = 5 at 5 min and/or an umbilical cord blood pH < or = 7.2, and a base deficit > or = 12 meq/l were compared to 50 healthy controls. The severity of the perinatal asphyxia was determined by using an ASPHYXIA SCORE. The UA/Cr was higher in the asphyxiated group when compared to controls. (2.06 +/- 1.12, vs. 0.64 +/- 0.48; P < 0.001). Within the perinatal asphyxia group, a significant correlation was found between the UA/Cr ratio and the asphyxia score. (r = 0.86, P < 0.01). CONCLUSION: Infants with perinatal asphyxia have a significantly higher urinary UA/Cr ratio. This may be used as an indicator of the severity of perinatal asphyxia.
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