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Biomedical subjects

M Obladen

Publications and source records attributed to M Obladen.

At least 19 recordsLinked to original sources

Mild postischemic hypothermia is neuroprotective in the immature rat neocortex slice.

Mild hypothermia as an intervention after perinatal asphyxia may prevent neurological damage in the newborn. We used stimulus-induced field potentials to monitor recovery from oxygen and glucose deprivation (OGD) in neocortex slices of 6-8-day-old wistar rats. OGD after a latency of 10.7+/-2.1 min (mean+/-S.E.) resulted in an anoxic depolarisation with an amplitude of 5.4+/-2.4 mV. Mild hypothermia of 31 degrees C (vs. 35 degrees C in the control group) was applied for 60 min after end of OGD. The 20, 40, 60 and 80% recovery of the field potential amplitude was significantly faster in the hypothermia group in comparison to the control group. These data indicate that mild postischemic hypothermia may have neuroprotective effects after perinatal asphyxia.

Animals↗

Early cessation of breast milk feeding in very low birthweight infants.

This investigation was carried out to comparatively assess the duration of breast milk feeding and to analyze risk factors for early cessation of breast milk feeding in term and very preterm infants. A cohort study was performed in 89 consecutive very low birthweight (VLBW) infants (<1500 g) who survived for at least for one week, and 177 term infants with birthweights >2500 g born in the same hospital matched for gender and multiplicity. Median duration of breast milk feeding, as determined from charts and questionnaires mailed to the mothers at 6 and 12 months corrected age, was 36 days in VLBW infants, compared to 112 days in control infants (P<0.0001). In both VLBW and control infants, smoking during pregnancy, low maternal and low paternal school education were each significantly associated with short duration of breast milk feeding. In VLBW infants, multiple pregnancy and gestational age <29 weeks were each associated with prolonged breast milk feeding, as were maternal age >35 years and spontaneous pregnancy (as opposed to pregnancy following infertility treatment) in term infants. Multivariate analysis revealed that VLBW, smoking and low parental school education were independent negative predictors of breast milk feeding. While these results emphasize the need for special support of VLBW infant mothers promoting lactation, the relationships between smoking, school education and breast milk feeding in both strata show that efforts to increase breast milk feeding require a public health perspective.

Breast Feeding↗

Familial recurrence of spontaneous fetal intracranial hemorrhage: ultrasonographic diagnosis and postnatal magnetic resonance imaging (MRI).

We report fetal intracranial hemorrhage in term siblings from consanguineous parents, spontaneously occurring in the third trimester of pregnancy. Prenatal ultrasound in one case and postnatal MRI in both demonstrated massive parenchymal bleeding involving large areas of the cerebral cortex, white and gray matter. Vasculopathies, vascular malformations, coagulopathies, thrombocytopenia and relevant metabolic disorders could be excluded.

Brain↗

In-vitro activation of complement system by lactic acidosis in newborn and adults.

INTRODUCTION: Complement activation occurs secondary to a variety of external stimuli. Lactic acidosis has been previously shown to activate the complement factors C3a and C5a. In the present investigation we examined the differential effect of lactic acidosis on anaphylatoxin levels in cord and adult blood. Furthermore we aimed to determine if the entire complement cascade could be activated by lactic acidosis. METHODS: Cord and adult blood samples (n = 20 each) were collected and incubated for one hour in either untreated condition or with the addition of lactate in two concentrations (5.5 mmol/l vs. 22 mmol/l). Following incubation, levels of C3a, C5a and sC5b-9, and blood gas parameters were determined. RESULTS: Anaphylatoxin (C3a and C5a) and sC5b-9 levels increased with the addition of lactate in a dose-dependent manner in cord and adult blood (C3a: 1 h, 5.5 mmo/l, 22 mmol/l: 418/498/622 microg/l in cord blood; 1010/1056/1381 microg/l in adult blood, p<0,05; similar results were found for C5a and sC5b-9). CONCLUSION: Lactic acidosis leads to an activation of the entire complement system in neonates and in adults. This activation is dose-dependent and more pronounced in adults as compared to neonates.

Acidosis, Lactic↗

Increased cerebrospinal fluid concentrations of soluble Fas (CD95/Apo-1) in hydrocephalus.

BACKGROUND AND AIMS: The ventricular enlargement observed in children with chronically raised intracranial pressure (ICP) causes a secondary loss of brain tissue. In animal studies of hydrocephalus, programmed cell death (apoptosis) has been found as a major mechanism of neuronal injury. One of the regulators of the apoptotic cell death programme is the receptor mediated Fas/Fas ligand interaction. METHODS: The apoptosis regulating cytokines soluble Fas (sFas) and soluble Fas ligand (sFasL) were studied in the cerebrospinal fluid (CSF) of 31 hydrocephalic children undergoing shunt surgery for symptomatic hydrocephalus and 18 controls. RESULTS: High concentrations of sFas were observed in children with hydrocephalus (median 252 ng/ml); in controls sFas was below the detection limit (0.5 ng/ml). sFasL was undetectable in all but one sample. CONCLUSION: High concentrations of sFas in the CSF of children with hydrocephalus suggest intrinsic sFas production, potentially antagonising pressure mediated Fas activation.

Adolescent↗

Early biochemical indicators of hypoxic-ischemic encephalopathy after birth asphyxia.

Hypoxic-ischemic encephalopathy (HIE) after perinatal asphyxia is a condition in which serum concentrations of brain-specific biochemical markers may be elevated. Neuroprotective interventions in asphyxiated newborns require early indicators of brain damage to initiate therapy. We examined brain-specific creatine kinase (CK-BB), protein S-100, and neuron-specific enolase in cord blood and 2, 6, 12, and 24 h after birth in 29 asphyxiated and 20 control infants. At 2 h after birth, median (quartiles) serum CK-BB concentration was 10.0 U/L (6.0-13.0 U/L) in control infants, 16.0 U/L (13.0-23.5 U/L) in infants with no or mild HIE, and 46.5 U/L (21.4-83.0 U/L) in infants with moderate or severe HIE. Serum protein S-100 was 1.6 microg/L (1.4-2.5 microg/L) in control infants, 2.9 microg/L (1.8-4.7 microg/L) in asphyxiated infants with no or mild HIE, and 17.0 microg/L (3.2-34.1 microg/L) in infants with moderate or severe HIE 2 h after birth. No significant difference was detectable in serum neuron-specific enolase between infants with no or mild and moderate or severe HIE 2 and 6 h after birth. A combination of serum protein S-100 (cutoff value, 8.5 microg/L) and CK-BB (cutoff value, 18.8 U/L) 2 h after birth had the highest predictive value (83%) and specificity (95%) of predicting moderate and severe HIE. Cord blood pH (cutoff value, <6.9) and cord blood base deficit (cutoff value, >17 mM) increase the predictive values of protein S-100 and CK-BB. We conclude that elevated serum concentrations of protein S-100 and CK-BB reliably indicate moderate and severe HIE as early as 2 h after birth.

Asphyxia↗

An effective and safe protocol involving zidovudine and caesarean section to reduce vertical transmission of HIV-1 infection.

OBJECTIVE: To investigate zidovudine prophylaxis with caesarean section to reduce mother-to-infant HIV transmission. INTERVENTIONS: Elective caesarean section before labour, usually at 36-38 weeks of gestation, plus a short oral course of zidovudine, normally starting at week 32, intravenous zidovudine before caesarean section and for 10 days for the neonate (the reduced Berlin regimen). RESULTS: Of 179 mother-infant pairs 104 received no antiretroviral prophylaxis or therapy (control group), 48 received the reduced Berlin prophylaxis regimen, 18 received combination therapy and nine received only part of the prophylaxis regimen. Of the antiretroviral group, 68 were delivered by elective caesarean section. The HIV transmission rate was zero in the antiretroviral group [95% confidence interval (CI) 0-4.7] and 12.6% (6.4-19.0) in the control group. The reduction in vertical transmission was 90% for the Berlin regimen, with an 80 and 70% reduction in risk associated with antiretroviral treatment and caesarean section, respectively. Maternal CD4 cell count but not viral load had some confounding effect on the reduction in risk attributed to caesarean section and the prophylactic regimen. Neonatal haematological abnormalities associated with antiretroviral intervention lasted for up to 7 weeks. Weight and length, although significantly lower at birth, were normal by 6-8 weeks. CONCLUSION: A much reduced three-arm regimen of zidovudine prophylaxis in combination with caesarean section before labour is highly effective in reducing the risk of vertical HIV transmission and is safe for the infant.

Adult↗

Ultrasonic surfactant nebulization with different exciting frequencies.

Intratracheal bolus instillation of natural lung surfactant is the treatment of choice in neonatal respiratory distress syndrome and an increasing part in adults' therapy. For reasons of hemodynamics, surfactant distribution and efficiency the application mode should be improved. Nebulization seems to have some advantages but its technical realization is difficult. The aim of the present study was to investigate if ultrasonic nebulization with exciting frequencies higher than 2.8 MHz can improve the efficiency of surfactant nebulization without changing the surface-active properties of the material. Exciting frequencies of 1.7, 3.3 and 4.0 MHz were used to produce a surfactant aerosol. The phospholipid content in the liquefied aerosol and particle size distinctly dropped with higher frequencies. The surface activity was not altered in the produced aerosol and neither in the surfactant remaining in the nebulizer. Although possible, ultrasonic nebulization of surfactant suspensions is ineffective because of a striking decrease in phospholipid content.

Aerosols↗

[Attitude of medical students to psychiatry. A study with the German translated, expanded version of the ATP-30].

Medical students' attitudes toward psychiatry are very important for the future care of psychiatric patients and the recruitment of qualified graduates. We examined the attitudes of 105 German medical students toward psychiatry using a German translation of the ATP-30, a reliable, self-administered questionnaire. In spite of a marked interest in psychiatry, most students thought it improbable that they would become psychiatrists. Attitudes toward psychiatry were generally positive (ATP-30 score: 104.6 +/- 13.4, where 90 represents middle, or neither positive nor negative) but showed clear differences in some aspects. Attitudes toward psychotherapy were markedly positive, while those toward psychiatric therapy in general or the scientific basis of psychiatry were less positive. We could find no influence of sex on the ATP score, whereas students having previous experience with psychiatry showed more positive attitudes towards it.

Adult↗

The CRIB (Clinical Risk Index for Babies) score and neurodevelopmental impairment at one year corrected age in very low birth weight infants.

OBJECTIVE: To assess the ability of the Clinical Risk Index for Babies (CRIB) to predict long-term neurodevelopmental impairment in very low birth weight (VLBW) infants. DESIGN: Single-center cohort study. SETTING: Tertiary neonatal care hospital and follow-up clinic. PATIENTS: Four hundred fifty-five VLBW infants consecutively admitted from 1992 to 1997 inclusive. MEASUREMENTS AND RESULTS: Calculations of CRIB scores from birth weight, gestational age, the presence of congenital malformations, worst base excess, maximum and minimum appropriate fraction of inspired oxygen (FIO2) during the first 12 h of life was possible in 430 infants. Three hundred eighty-six infants survived until discharge (89%) and 352 (91%) were examined at 1 year corrected age using the Griffiths scales of mental development. Major neurodevelopmental impairment (general quotient < 2 standard deviations below average) was observed in 76 infants (22%). CRIB scores and the individual CRIB components differed significantly between infants with and those without neurodevelopmental impairment. By logistic regression analysis, CRIB scores and minimum FIO2 were independent predictors of death, while CRIB and maximum FIO2 were independently associated with neurodevelopmental impairment. For combined poor outcome (death or impairment), CRIB, minimum and maximum FIO2 were independent predictors. In predicting major neurodevelopmental impairment, the area under the receiver operating characteristic curve for CRIB (0.703 +/- 0.035) did not differ significantly from that of birth weight (0.697 +/- 0.035) or any other CRIB component. CONCLUSION: While high CRIB scores are associated with major neurodevelopmental impairment, the CRIB score is of limited value for stratification in randomized trials or for adjustments in comparing performance between hospitals with neurodevelopmental impairment as the main outcome measure.

Cohort Studies↗

Changing practices of red blood cell transfusions in infants with birth weights less than 1000 g.

OBJECTIVE: Extremely low birth weight (ELBW) infants frequently undergo transfusion because they are critically ill, often need artificial ventilation, and have the highest blood sampling loss in relation to their weight. During the last decade our transfusion guidelines were changed 3 times to become more restrictive. We hypothesized that these modifications substantially decreased the number of transfusions in our ELBW infants. METHODS: We performed a single-center analysis of 256 infants with birth weights from 500 to 999 g who were admitted from 1989 to 1997 and included 3 study periods, each starting with newly modified transfusion guidelines in April 1989, September 1991, and January 1995. We evaluated prospectively recorded clinical data and retrospective chart analysis for transfusion-related information. RESULTS: The median number of transfusions per infant decreased from 7 in the first period to 2 in the third period, whereas donor exposure decreased from 5 to 1 and blood volume transfused decreased from 131 to 37 mL/kg birth weight (P <.01). The median venous hematocrit measured before transfusion decreased from 43% to 35% in infants who underwent ventilation and from 41% to 31% in spontaneously breathing infants. The median birth weight decreased from 870 to 740 g and the median gestational age from 27 to 25 completed weeks (P <.01). The overall survival rate was 75% and did not change. The incidences of retinopathy, intraventricular hemorrhage, and patent ductus arteriosus remained unchanged. CONCLUSION: Over this 9-year period with increasingly restrictive transfusion guidelines, the transfusion number decreased by 71% and the donor exposure by 80% in ELBW infants without adverse clinical effects.

Blood Donors↗

Hypoxic-ischemic encephalopathy with cystic brain stem necroses and thalamic calcifications in a preterm twin.

A severe and rare ischemic brain lesion in a preterm twin boy is reported. The boy was born after two weeks of anhydramnios and amnionic infection at 24 weeks of gestation. Following a difficult Caesarean section and prolonged umbilical cord compression he developed prenatal acidosis with an umbilical cord pH of 6.96. At the age of 7 h, heart rate variability narrowed due to severely disturbed brain stem function and the patient developed clinical signs of hypoxic-ischemic encephalopathy. Sonography demonstrated extensive symmetrical brain stem and basal ganglia lesions. After a prolonged comatose and apneic state, death occurred at the age of 25 days. Autopsy confirmed columnar bilateral cavitation of basal ganglia, diencephalon, brain stem and spinal gray matter, as well as focal calcifications in the palladium, thalamus, and brain stem. The findings highly resemble those observed after experimental or clinical cardiac arrest.

Brain Stem↗

Parental and professional agreement in developmental assessment of very-low-birthweight and term infants.

The aim of this prospective follow-up study was to evaluate the accuracy of a parent-completed questionnaire compared with professionally detected developmental delay. Parents of 108 very-low-birthweight (VLBW) infants and parents of 279 term control infants completed the German version of the Revised Prescreening Developmental Questionnaire (R-PDQ) at the corrected age of 12 months. Simultaneously, infants underwent developmental examination using the Griffiths Developmental Scale. Sixty-nine VLBW infants were classified as not delayed, 16 as delayed by both methods (conegativity 76% and copositivity 94%), as compared to 240 and six term control infants (conegativity 88%, copositivity 94%). The questionnaire suggested delay in 22 VLBW infants and 32 control infants, which was not substantiated by professional examination (P=0.006). In contrast, examination-diagnosed delay was missed by the questionnaire in one infant in each group. The R-PDQ is a reliable monitoring instrument for both VLBW and term infants at the age of 12 months. Parents of VLBW infants tend to underestimate their infants' development.

Child Development↗

Fetal-onset severe skeletal muscle glycogenosis associated with phosphorylase-b kinase deficiency.

We report on a premature newborn girl delivered after 32 weeks of gestation by cesarean section after sparse limb movements, fetal tachycardia and late heart rate decelerations had suggested fetal distress. Following 1 day of mechanical ventilation, adequate pulmonary gas exchange was achieved by spontaneous breathing. Main symptoms were virtually complete absence of spontaneous movements, increased flexor tonus of the extremities, and hypotonia of the trunk. Inability to suck or swallow required nasogastric gavage feeding. There were no hypoglycemic episodes. Echocardiography revealed normal myocardial function. Creatine kinase was 237 U/I at 2 days of life, declining to normal values thereafter. Muscle biopsy revealed increased glycogen storage with subsarcolemmal glycogen deposits and low phosphorylase-a activity while total phosphorylase was normal after in vitro activation, suggestive of phosphorylase-b kinase deficiency. No mutation was detected in exon 1 of the myophosphorylase gene. No psychomotor development was observed, and the infant died of central apnea at 3 months of age.

Adult↗

Growth and neurodevelopmental outcome of very low birthweight infants with necrotizing enterocolitis.

UNLABELLED: The aim of the study was to assess the effect of necrotizing enterocolitis (NEC) on neurodevelopmental outcome and growth. Neurodevelopmental outcome of 20 out of 22 suriviving very low birthweight infants (VLBW) diagnosed with NEC between 1992 and 1996 was compared with 40 control infants matched for gestational age and year of admission. Follow-up studies were performed at 12 and 20 mo of corrected age. The German revision of the Griffiths' scales was used for development assessment. Neurodevelopment was significantly delayed in infants with NEC at 12 mo (median general developmental quotient: 90.0 vs 97.8; p = 0.04) and 20 mo (86.4 vs 97.7; p = 0.004) of age. Somatic growth did not differ between infants with and without NEC. Fifty-five percent of infants suffering from NEC but only 22.5% of the infants without NEC were severely retarded (developmental quotient < -2 SD of a control group of healthy newborns) at 20 mo of corrected age. CONCLUSION: Preterm infants developing NEC are at risk for neurodevelopmental impairment and need close neurodevelopmental follow-up for the first years of life.

Developmental Disabilities↗

Endotracheal surfactant atomization: an alternative to bolus instillation?

OBJECTIVE: To investigate the effect of an intratracheal surfactant fog on oxygenation, blood pressure, distribution, and recovery rate as a pilot study to intratracheal surfactant aerosol. DESIGN: Prospective, randomized study. SETTING: University laboratory. SUBJECTS: A total of 15 New Zealand White rabbits. INTERVENTIONS: The anesthetized ventilated rabbits were surfactant-deprived by repeated lung lavages and then received 200 mg/kg of a 99mTc-labeled porcine surfactant (Curosurf) either as bolus or as intratracheal surfactant fog. MEASUREMENTS AND MAIN RESULTS: Blood gases and pressure were measured and distribution as well as recovery rate of the surfactant determined by means of the radio label (gamma camera images and lung processing with subsequent gamma counter measurements). Respiratory function normalized immediately, no difference could be found between the two groups with regard to PaO2, PaCO2, and blood pressure. Even distribution of the radiolabel was found with both methods, the bolus group showing a higher percentage of lung pieces with label concentrations of double average or more. Recovery rates were 82.5%+/-13.1% (mean +/- SD) in the bolus group and 86.5%+/-7.7% in the fog group. CONCLUSION: Endotracheal surfactant fog application is as effective as bolus instillation and may have a role in the treatment of adult respiratory distress syndrome. It has to be considered as a first step in producing an effective aerosol.

Aerosols↗

Il-1 beta, Il-6, Il-8 and G-CSF in the diagnosis of early-onset neonatal infections.

OBJECTIVE: To determine whether inflammatory cytokine concentrations (Il-1 beta, Il-6, Il-8 and G-CSF) in umbilical cord blood are useful predictors of an early-onset neonatal infection. MATERIAL AND METHODS: 240 women and their newborns were enrolled in our study and umbilical cord blood samples collected from neonates (n = 240) were subjected to ELISA for Il-1 beta, Il-6, Il-8 and G-CSF. Clinical outcome of the neonates was followed and documented. Placenta histology was also available in majority of the cases (n = 195). RESULTS: Early-onset neonatal infection was diagnosed in 5.4% of neonates (13/240) and placental examination showed histologic chorioamnionitis in 17.9% (35/195). Both Il-1 beta and Il-6 cord blood concentrations were elevated in association with histologic chorioamnionitis (Il-1 beta-2.7 vs. 2.1 pg/ml, p < 0.05 and Il-6 15.6 vs. 12.8 pg/ml, p < 0.005). Only Il-6 was elevated (16.0 vs. 13.2 pg/ml, p < 0.05) in neonates with early-onset bacterial infections. ROC analysis showed acceptable diagnostic performance of Il-6 in the identification of acute histologic chorioamnionitis and clinical neonatal infection. CONCLUSION: Il-6 in umbilical cord blood seems to be a promising predictor for early-onset neonatal infections.

Chorioamnionitis↗

Venous and arterial hematologic profiles of very low birth weight infants. European Multicenter rhEPO Study Group.

OBJECTIVE: In very low birth weight (VLBW) infants, diagnostic and therapeutic decisions depend on hematologic values. As few data are available, we studied the course during the first 6 weeks of life. DESIGN: Four prospective longitudinal cohort studies were retrospectively combined assessing hematologic profiles of 562 VLBW infants. For characterization of red blood cells and iron, infants receiving erythropoietin were excluded. For characterization of white blood cells and platelets, infants receiving antibiotics were excluded. RESULTS: The third (3rd)/median/97th percentiles on day 3 were as follows: hemoglobin: 11.0/15.6/19.8 g/dL; hematocrit: 35/47/60%; red blood cells: 3.2/4.2/5.3 x 10(12)/L; reticulocytes:. 6/7.1/27.8%; platelets: 58/203/430 x 10(9)/L; white blood cells: 3. 6/9.5/38.3 x 10(9)/L; neutrophils:.7/4.7/25.3 x 10(9)/L; ferritin: 27/140/504 ng/mL; iron:.8/7.5/26.7 micromol/L; transferrin saturation: 2.6/22.7/79.8%. Transferrin saturation was <24% in 51%, ferritin concentration <100 ng/mL in 32%, and platelets <150 x 10(9)/L in 29% of this population. The steady decrease of red cell parameters was mitigated by transfusions. Neutrophils decreased steadily, and were <1.75 x 10(9)/L in 35% at 6 weeks. CONCLUSIONS: Iron indices and platelet counts on day 3 and neutrophil counts at 2 to 6 weeks of age are lower than previously assumed in VLBW infants and lower than in larger prematures.

Blood Cell Count↗