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Biomedical subjects

M Obladen

Publications and source records attributed to M Obladen.

At least 73 records · Page 4Linked to original sources

Neuron-specific enolase: reference values in cord blood.

With foetal sonography prenatal detection of tumours has become more frequent. To evaluate and treat these infants it is necessary to identify the tumour postnatally. Elevated neuron-specific enolase is a biochemical marker of neuroblastoma. Since conditions during birth may influence neuron-specific enolase concentration in foetal serum, specific reference values in cord blood are required. Cord blood samples were taken from 192 healthy term newborns and concentration of neuron-specific enolase was measured by enzyme immunoassay (EIA). Median neuron-specific enolase concentration in the reference group was 8.0 micrograms/l and the 5th-95th percentiles were 4.8-19.4 micrograms/l. No differences between male and female newborns were detected (p = 0.13). Measurement of neuron-specific enolase in cord blood, in comparison with our reference values, offers an early postnatal possibility of confirming the diagnosis of neuroblastoma.

Biomarkers, Tumor↗

Low degree of regionalization and high transfusion rates in very low birthweight infants: a survey in Germany.

Although anemia is common in very low birthweight (VLBW) infants, widely accepted guidelines for red blood cell transfusions are lacking. Questionnaires regarding transfusion policy in VLBW infants in 1994 were sent to 391 German pediatric departments. 208 questionnaires were returned. 51 departments reported not to admit VLBW infants. Thus, results are based on 157 completed questionnaires. 54% of the respondents admitted less than 30 VLBW infants per year and 52% of the VLBW infants were admitted to departments with less than 50 VLBW infants per year. Overall transfusion rate ranged from 0 to 100% (median 65%). This range narrowed with the departments' size indicating stricter guidelines with less variation. Indication for transfusion varied considerably depending on the infants' postnatal age and need for ventilatory support. 34% of the respondents applied directed transfusions, most frequently from the infant's father. 70% used satellite packs. 51% stored the packs up to 7 days, 10% longer than 14 days. Red cells were irradiated in 35%, and washed in 23% of the departments. Median single transfusion volume was 12 ml/kg. We conclude that regionalization of VLBW infants in Germany is far from completeness and that hospital policies for transfusion show large variety especially in small departments.

Blood Transfusion↗

Predicting chronic lung disease in very low birthweight infants: comparison of 3 scores.

AIM: To evaluate 3 scores in their ability to predict Chronic Lung Disease (CLD) in very low birthweight (VLBW) infants. METHODS: The records of 188 VLBWs admitted to neonatal intensive care within two years were retrospectively reviewed. Two mortality scores -the CRIB (clinical risk index for babies) score and the Berlin admission score- and one morbidity score developed to predict CLD (Sinkin score) were assigned to each infant. Areas (AUC) under receiver operating characteristic (ROC) curves were used for comparison. RESULTS: The Sinkin score and the Berlin admission score had AUCs of 89.0 and 85.8% to predict CLD ("alive in oxygen at 28 days of life"). The AUCs were 87.7 and 81.2%, respectively, using the CLD definition "alive in oxygen at 36 weeks gestational age", the CRIB had an AUC of 77.0%. CONCLUSION: To enroll patients in trials aimed at early interference with the course of CLD, the Berlin admission score or the Sinkin score could be used.

Aging↗

Neonatology in Europe. Training, accreditation, and research.

OBJECTIVE AND DESIGN: In order to assess training, accreditation, and scientific status of neonatology in the European countries, a structured questionnaire on availability, duration, and accreditation of neonatology training programs was mailed to the pediatric and neonatal societies. A medline search was performed on the item 'infant, newborn' and the data were related to the population number, total fertility, and infant mortality. RESULTS: In most European countries, two year training programs in neonatology exist in addition to 4 or 5 years pediatric training. Numbers of certified neonatologists ranged from 2 to 10 per million inhabitants. An inverse correlation of infant mortality and medline entry rate was found (R(s) -0.91, P < 0.001). CONCLUSIONS: Conforming training and accreditation in Europe may help to compensate delays in infant mortality and scientific productivity and would facilitate subspecialist mobility.

Accreditation↗

Comparison of mortality risk: a score for very low birthweight infants.

AIM: To develop and evaluate a score which quantifies mortality risk in very low birthweight (VLBW) infants (birthweight below 1500 g) at admission to the neonatal intensive care unit. METHODS: Five hundred and seventy two VLBW infants admitted from 1978 to 1987 were randomly assigned to a cohort (n = 396) for score development and a cohort (n = 176) for score validation. Two hundred and ninety four VLBW infants admitted from 1988 to 1991 were used to compare risk adjusted mortality between the two eras. RESULTS: Using multiple regression analysis, birthweight, Apgar score at 5 minutes, base excess at admission, severity of respiratory distress syndrome, and artificial ventilation were predictive of death in the development cohort. According to regression coefficients, a score ranging from 3 to 40 was developed. At a cutoff of 21, it predicted death in the validation cohort with a sensitivity of 0.85, a specificity of 0.73, and a correct classification rate of 0.76. The area under the receiver operating characteristic curve was 0.86. There was no significant difference in risk severity and in risk adjusted mortality between the eras 1978-87 and 1988-91. CONCLUSION: The present score is robust, easily obtainable at admission, and permits early randomisation based on mortality risk.

Apgar Score↗

Partial trisomy/monosomy 6q in fetal cells and CVS long-term culture not present in CVS short-term culture.

A cytogenetic discrepancy in chorionic villi with implications for prenatal diagnosis is described. Chromosome analysis revealed a normal karyotype in banded metaphases from short-term culture and a chromosome count of 46 in cells of the long-term culture. After the birth of a malformed infant, a structurally aberrant chromosome 6 was found in lymphocytes and skin fibroblasts. Re-analysis of chorionic villi confirmed the result from short-term culture but disclosed the presence of the structural aberration in cells of the long-term culture. This type of inconsistency is reported for the first time and stresses the importance of a numerical and structural analysis of both short-term and long-term culture. The application of three techniques, chromosome banding, comparative genomic hybridization (CGH), and fluorescence in situ hybridization (FISH) analysis, was essential to prove that the derivative chromosome carried a combined partial trisomy/monosomy for 6q. The findings are discussed with respect to the origin of the structural aberration and to the consequences for prenatal diagnosis on chorionic villi and genetic counselling.

Adult↗

CD45 engagement induces L-selectin down-regulation.

The CD45 glycoprotein isoforms exhibit a receptor-like composition and display intracellular protein tyrosine phosphatase (PTPase) activity. The present study links CD45 to the regulation of L-selectin (CD62L), a leucocyte glycoprotein important for extravasation and homotypic aggregation. Monoclonal antibodies (MoAbs) IOL1b and AICD45.2, but not GAP8.3, all of which are directed against common CD45 epitopes, were found to elicit lymphocyte L-selectin down-regulation. Lymphocyte L-selectin down-regulation in response to anti-CD45 MoAbs was enhanced by high cell density and partially antagonized by the protein tyrosine kinase (PTK) inhibitor, herbimycin A. The MoAbs IOL1b, AICD45.2 and GAP8.3 recognized granulocyte-expressed CD45 but did not induce loss of L-selectin expression of granulocytes. In contrast, the CD45 PTPase inhibitor, vanadate, induced L-selectin down-regulation both in lymphocytes and granulocytes. The PTPase activation by nitric oxide (NO) or the NO-generating compound, sodium nitroprusside, did not affect L-selectin surface expression. Increased concentrations of soluble L-selectin were detected after anti-CD45 or vanadate-induced down-regulation of L-selectin surface expression. While activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) induces rapid L-selectin down-regulation of L-selectin surface expression in both lymphocytes and granulocytes, the PKC inhibitor, H 7, was also found to down-regulate lymphocyte and granulocyte L-selectin surface expression. The inhibitor H 7 synergized with vanadate in down-regulating lymphocyte L-selectin surface expression, but partially inhibited vanadate-induced granulocyte L-selectin down-regulation. The results suggest that in a cell type-specific fashion the PKC system and tyrosine phosphorylation and dephosphorylation cascades are involved in the regulation of L-selectin surface expression.

Adult↗

Cerebrospinal fluid soluble L-selectin (sCD62L) in meningoencephalitis.

The leucocyte adhesion molecule L-selectin (CD62L) is rapidly cleaved off proteolytically after cell activation, generating soluble L-selectin (sCD62L) molecules. sCD62L concentrations were determined in 185 cerebrospinal fluid (CSF) samples obtained from children aged 1 month to 17 years. In 36 CSF samples of children with meningoencephalitis, sCD62L was significantly higher (median 209 fmol/ml) than in samples of children with other febrile diseases (n = 67, median 50 fmol/ml) or non-febrile disorders (n = 82, median 44 fmol/ml). There was a positive correlation between CSF protein and CSF sCD62L (rS = 0.68), suggesting that a disturbed blood-brain barrier contributes to raised sCD62L concentrations in the CSF. However, the CSF sCD62L/protein ratio of children with meningoencephalitis was significantly higher than in children with other febrile diseases or non-febrile disorders, indicating that sCD62L concentrations in children with meningoencephalitis were higher than expected from plasma leakage alone. It is concluded that both an impaired blood-brain barrier and the generation of sCD62L by infiltrating leucocytes contribute to raised CSF sCD62L concentrations in children with meningoencephalitis.

Acute Disease↗

Factors related to transfusion in very low birthweight infants treated with erythropoietin.

The need for red cell transfusions is reduced but not eliminated by recombinant human erythropoietin (rhEPO) in very low birthweight (VLBW) infants. To detect factors associated with the decision to transfuse VLBW infants during rhEPO treatment and to explain rhEPO 'non-responders', the subgroup of those 120 VLBW infants who were treated with rhEPO 750 IU/kg per week in the second European Multicentre rhEPO Trial was evaluated. Sixty (50%) infants received at least one transfusion during erythropoietin treatment. Transfusion was frequent in infants with extremely low birthweight (79% for 750-999 g), low gestational age (70% for < or = 28 weeks), low initial haematocrit or low initial reticulocyte count (61% for haematocrit < or = 0.48 and reticulocytes < or = 9%, respectively). Considerable differences among centres were found for sampling blood loss, iron supply, and transfusion rate, which ranged from 13% to 73% and was related to the volume of diagnostic blood loss (19% vs 80% for blood loss < 1 vs > or = 1 ml/kg per day). The prognostic variables birthweight, initial haematocrit, and gestational age were found to be most predictive for transfusion. To improve rhEPO response in VLBW infants, there is a need to minimise diagnostic blood loss, to prevent iron deficiency, and to develop rational criteria for transfusion in preterm infants.

Birth Weight↗

Rapid tracheal infusion of surfactant versus bolus instillation in rabbits: effects on oxygenation, blood pressure and surfactant distribution.

UNLABELLED: Surfactant bolus instillation may be associated with a drop in blood pressure. Platelet-activating factor (PAF) has been found in surfactant preparations. The aim of this study was to evaluate rapid tracheal infusion of surfactant during 5 min as an alternative to bolus instillation and to examine whether a PAF receptor antagonist is able to prevent the decrease in blood pressure. METHODS: Surfactant deficiency was induced in 16 adult rabbits by lung lavages with saline. Six animals received a bolus of a porcine surfactant preparation (Curosurf (CS); 200 mg/kg), labeled with red microspheres to assess pulmonary distribution. In another 5 rabbits, the same amount of labelled CS was instilled by tracheal infusion within 5 min. A third group of 5 animals received 3 mg/kg body weight of the PAF antagonist WEB 2170 before CS bolus instillation. RESULTS: After CS bolus administration, mean PaO2 increased by 44.7 +/- 8.3 kPa (mean +/- SD) within 2 min and remained at this level. Mean arterial blood pressure dropped transiently by 2.3 +/- 2 kPa within 5 min. Pulmonary distribution of surfactant was even. After infusion, mean PaO2 rose by 22.4 +/- 16.3 kPa within 15 min. Blood pressure dropped by 1.8 +/- 1.1 kPa within 15 min. The distribution was extremely uneven. Blood pressure decreases also occurred after pretreatment with PAF receptor antagonist. CONCLUSION: Rapid tracheal infusion of surfactant results in poorer oxygenation, an inhomogeneous distribution and a similar decrease in blood pressure compared to the bolus instillation method. Blood pressure changes could not be prevented by a PAF receptor-specific antagonist.

Animals↗

Parents' estimation of psychomotor development in very low birthweight (VLBW) infants.

BACKGROUND: Within a longitudinal developmental surveillance project we tested the accuracy of the Revised Prescreening Developmental Questionnaire (R-PDQ) to detect developmental retardation in very low birthweight (VLBW) infants. METHODS: Seventy surviving VLBW-infants born between July 1992 and December 1993 were re-examined at 6 months corrected age. The parent-completed questionnaires (n = 67) were compared with developmental assessment using the Griffiths Developmental Scale. RESULTS: At 6 months corrected age, normal results of the Griffiths Developmental Scale (developmental quotient > or = 81) were found in 61/67 (91%) VLBW-infants and in 45/67 (67%) questionnaires (no or one 'delay'). The parents identified all six infants with psychomotor retardation on the Griffiths Developmental Scale (co-positivity 100%). However, only 45/61 infants with normal development were so identified with the R-PDQ (co-negativity 74%, positive predictive value 27%). CONCLUSIONS: The R-PDQ discovered all infants whose developmental quotient was two standard deviations below the mean on the Griffiths Developmental Scale. The relatively high proportion of false positive R-PDQ results corresponded to lower developmental quotients within the normal range. Therefore, the R-PDQ provides a useful screening instrument for VLBW-infants.

Adolescent↗

Autosomal-recessive neural crest syndrome with albinism, black lock, cell migration disorder of the neurocytes of the gut, and deafness: ABCD syndrome.

We report on a macrosomic newborn girl with albinism, a black lock at the right temporo-occipital region, and retinal depigmentation. Bilateral deafness was confirmed by brainstem auditory-evoked potentials. In addition, the infant had a severe defect of intestinal innervation. Biopsy showed aganglionosis of the large intestine, and total absence of neurocytes and nerve fibers in the small intestine, indicating a total lack of sympathetic and parasympathetic innervation. The infant died of intestinal dysfunction at 5 weeks. She was the 14th child of consanguineous Kurdish parents. Four sibs of our patient had the same syndrome and died a few days after birth. The other 9 sibs are well, with an unremarkable phenotype. A syndrome of albinism, black lock, deafness, and a total lack of intestinal neural innervation has not yet been reported. It represents a new neural crest syndrome with autosomal-recessive inheritance.

Albinism↗

Influence of clinical and ventilatory parameters on morphology of bronchopulmonary dysplasia.

Our aim was to assess multiple factors which contribute to bronchopulmonary dysplasia (BPD) in prematurely born neonates. Specific morphologic features might relate to cumulative oxygen dose, barotrauma, prematurity, infection, and persistent ductus arteriosus (PDA). Seventy-two patients dying from BPD as defined by the histopathologic criteria of Stocker were analyzed retrospectively. Median (range) gestational age was 28 (25-35) weeks, and median survival was 16 (5-386) days. The infants were ventilated for 15 (15-149) days with a mean inspired oxygen fraction (FiO2) of 0.78. The cumulative oxygen dose and mean airway pressures were determined. The presence of neonatal infection, PDA, and interstitial lung emphysema (ILE) was assessed. Baseline lung disease was estimated as proposed by Palta. At autopsy, the degree of hyaline membranes, epithelial cell necrosis, emphysema, atelectasis, interstitial cell proliferation, and lung fibrosis was scored semiquantitatively (0 to 3+). The influence of neonatal infection, PDA, gestational age, survival, oxygen dose, or barotrauma on morphological findings was examined by multivariate analysis. We found "acute" BPD in 22, "reparative" in 34 and long-standing-"healed" in 16 cases. ILE within the first week was associated with interstitial cell proliferation and lung fibrosis in infants surviving more than 28 days. Initial barotrauma contributes to lung fibrosis in infants with BPD.

Autopsy↗

Dose-response to inhaled nitric oxide in acute hypoxemic respiratory failure of newborn infants: a preliminary report.

In acute hypoxemic respiratory failure of term and near-term neonates, extra- and intrapulmonary right-to-left shunting contribute to refractory hypoxemia. Inhaled nitric oxide (NO) decreases pulmonary arterial pressure and improves ventilation-perfusion mismatch in a variety of animal models and selected human patients. We report on 10 consecutive term and near-term newborns with severe acute hypoxemic respiratory failure due to diaphragmatic hernia, meconium aspiration syndrome, group B streptococcus sepsis, pneumonia or acute respiratory distress syndrome, who received increasing doses of inhaled NO (up to 80 ppm) to improve the arterial partial pressure of oxygen (PaO2). The response to NO and the optimum NO concentration which improved PaO2 varied considerably between patients. Improvement of PaO2 was absent or poor (less than 10 mm Hg) in the 4 newborns with meconium aspiration syndrome and in 1 patient with congenital diaphragmatic hernia, while in the other 5 patients inhaled NO increased the mean (+/- SE) PaO2 from 41 +/- 6 to 57 +/- 9 mm Hg (P < 0.05). Optimum NO concentrations determined by dose-response measurements performed during the first 8 hr of NO inhalation were 8-16 ppm except for 2 newborns with congenital diaphragmatic hernia who required 32 ppm to effectively increase PaO2. Four of the 5 patients in whom the PaO2 rose by more than 10 mm Hg received inhaled NO for extended periods of time (5 to 23 days) with no signs of tachyphylaxis. The optimum NO concentration dropped to less than 3 ppm after prolonged mechanical ventilation or when intravenous prostacyclin was given concomitantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Acute and chronic fetal hypoxia in monochorionic and dichorionic twins.

OBJECTIVE: To assess the risk for acute and chronic fetal hypoxia in twin pregnancies. METHODS: We investigated 50 sets of twins (24-38 weeks' gestation, 660-3200 g birth weight) admitted consecutively to our neonatal intensive care unit. Seventy-six infants were appropriate for gestational age (AGA; tenth to 90th percentile), 20 were small for gestational age (SGA; below the tenth percentile), and four were large for gestational age (above the 90th percentile). Twenty-six singleton AGA term newborns served as controls. Umbilical arterial pH was used as a marker for acute and umbilical venous erythropoietin concentration for chronic fetal hypoxia. The results are given as median followed by quartiles. RESULTS: We identified 40 sets of diamniotic-dichorionic twins and ten sets of diamniotic-monochorionic twins with transplacental vascular shunts. In the second-born twin, umbilical arterial pH was lower (7.29, 7.23-7.33) than in the firstborn (7.31, 7.25-7.34) (P = .03), and the incidence of a low pH (less than 7.20) was higher (19 versus 11%). Two second-born twins and none of the firstborn twins had an umbilical arterial pH less than 7.05. In SGA twins, the erythropoietin concentration was elevated (34.8, 22.8-325 mU/mL) compared with that in AGA twins (16.2, 8.2-26.6 mU/mL) (P < .01). In AGA twins, erythropoietin concentration did not differ from that in AGA singleton newborns (19.6, 14.7-31.6 mU/mL). In 12 of 17 twin sets with weight discordancy greater than 15% and in all five twin sets with weight difference greater than 25%, erythropoietin concentration was higher in the smaller twin. The proportion of infants and of complete sets with elevated erythropoietin levels was higher (P < .01) in monochorionic than in dichorionic pregnancies. CONCLUSION: The second-born twin is at increased risk for acute birth asphyxia. Fetal growth restriction in twin pregnancies is associated with chronic fetal hypoxia. Monochorionic twins are at higher risk for chronic fetal hypoxia than are dichorionic twins.

Acute Disease↗

Soluble L-selectin (sCD62L) umbilical cord plasma levels increase with gestational age.

L-Selectin (CD62L) is a leukocyte surface membrane glycoprotein involved in extravasation and homotypic aggregation which is rapidly cleaved off after cellular activation. From culture supernatants and body fluids, soluble L-selectin (sCD62L) has been recovered with its functional activity retained. We devised a sensitive enzyme-linked immunoassay for quantitation of sCD62L which was used to measure sCD62L in umbilical cord plasma of 255 human newborns with a gestational age (GA) of 23-43 wk (median 38 wk). sCD62L levels ranged from 1.14-13.8 pmol/mL (median 7.2 pmol/mL) and showed strong correlations with GA (r = 0.71, p < 0.001), birth weight (r = 0.66, p < 0.001), and absolute neutrophil cell counts (ANC) (r = 0.62, p < 0.001) obtained from a peripheral vein within the first 6 h of life (n = 153), whereas there was a weak inverse correlation with absolute normoblast counts (r = -0.27, p < 0.001). In multiple regression analysis, only GA and ANC retained a significant association with sCD62L levels (p < 0.001). Decreased sCD62L levels were found to be associated with multiple gestation (4.8 +/- 2.4 pmol/mL versus 7.7 +/- 2.3 pmol/mL, p < 0.05) also when considering GA and ANC as covariates. In contrast, increased sCD62L levels in infants born from meconium-stained amniotic fluid, and decreased levels in newborns with acute bacterial infection could be fully attributed to differences in GA and ANC.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗

Recombinant erythropoietin for prevention of anemia in preterm infants.

In order to prevent or to treat anemia of prematurity, more than 800 preterm infants were enrolled into controlled studies with recombinant erythropoietin (rhEPO) during the past five years. The effective dosage seems to be within the range of 300 to 1200 IU/kg per week, markedly higher than in adults or children with anemia due to renal failure. No adverse events nor impairment of granulopoiesis or platelet formation could be attributed to erythropoietin. Statistical metaanalysis of eight controlled trials revealed an 18% reduction of transfused infants. The preventive effect was scarce in very small and very sick preterm infants, and during the first two weeks of life, when hemorrhagic anemia due to diagnostic blood loss is predominant. rhEPO treatment is one step in the concept to prevent anemia of prematurity. This concept should also include placental transfusion, minimizing of diagnostic sampling, miniaturized laboratory tests, adequate iron supplementation, and optimal nutritive protein administration.

Anemia, Neonatal↗