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Biomedical subjects

C Bührer

Publications and source records attributed to C Bührer.

At least 37 records · Page 2Linked to original sources
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Lack of hypoxic stimulation of VEGF secretion from neutrophils and platelets.

Low oxygen (O(2)) is the key stimulus for expression of vascular endothelial growth factor (VEGF) in several adherent cells. Whether hypoxia also directs the release of VEGF protein from neutrophils (polymorphonuclear neutrophils; PMN) and platelets has not been investigated. We therefore compared VEGF release of platelets, PMN, and human vascular smooth muscle cells (HSMC) in response to hypoxia with that to activators of cellular degranulation. In contrast to HSMC, VEGF release from PMN and platelets or VEGF mRNA expression in PMN was not stimulated under hypoxic conditions (1% O(2)). Hypo- or hyperthermia and acidosis, other conditions potentially associated with ischemic and inflammatory tissue injury, also did not stimulate VEGF secretion from PMN. However, stimulation of platelets with thrombin and of PMN with phorbol 12-myristate 13-acetate induced a time-dependent release of VEGF, peaking after 30 and 60 min, respectively. This was blocked by the degranulation inhibitor pentoxifylline but not by the protein-synthesis inhibitor cycloheximide. We conclude that rapid release of VEGF from platelets and PMN may occur independently of oxygenation during inflammation and hemostasis.

Adult↗
PubMed2000

Leukocyte and endothelial activation in a laboratory model of extracorporeal membrane oxygenation (ECMO).

An inflammatory response and a capillary leak syndrome frequently develop during the treatment of neonatal respiratory failure by extracorporeal membrane oxygenation (ECMO). The present study was performed to investigate leukocyte activation and endothelial cell dysfunction that are associated with prolonged contact of blood components with synthetic surfaces. Laboratory ECMO was performed with fresh human blood at 37 degrees C for 8 h (n = 6). Leukocyte activation was measured by L-selectin (CD62L) and CD18 integrin surface expression and by neutrophil-derived elastase release. To monitor endothelial activation, endothelial cell ICAM-1 (CD54) expression was measured in cultured endothelial cells from human umbilical veins (HUVEC) after incubation with plasma from the ECMO experiments. CD18 integrin expression was found significantly up-regulated on polymorphonuclear neutrophils and monocytes after 2-4 h of laboratory ECMO. L-selectin was reduced on both cell types during the total duration of the experiments. Soluble L-selectin (sCD62L) and total and differential leukocyte counts remained unchanged during the experiment. Neutrophil-derived elastase content was maximal after 8 h of ECMO. Plasma from the ECMO experiments did not induce ICAM-1 expression of cultured HUVEC. We conclude that prolonged contact with synthetic surfaces during ECMO activates phagocytes, which may contribute to the inflammatory response seen in ECMO-treated patients. Activated phagocytes do not accumulate in the extracorporeal system nor release humoral factors inducing ICAM-1 expression on endothelial cells.

CD18 Antigens↗
PubMed2000

Circulating L-selectin concentrations in children with recent-onset IDDM.

To clarify conflicting claims of altered serum concentrations of soluble L-selectin (sCD62L) in recent-onset IDDM, sCD62L was measured in 89 children and adolescents with IDDM (35 recent-onset, 12 during the first year of insulin treatment, and 42 with long-standing (> 1 yr) treatment) alongside 124 controls. Children < 14 yr of age both with and without IDDM (n = 160) had grossly elevated sCD62L concentrations (20.2 +/- 4.9 nmol/l), as compared with adolescents (14-18 yr, n = 23; 15.9 +/- 3.9 nmol/l) and adults (> 18 yr, n = 30; 11.2 +/- 2.3 nmol/l) (p < 0.0001). Multivariate analysis confirmed the strong inverse association between age and sCD62L (p < 0.001) while revealing that sCD62L concentrations were slightly elevated in recent-onset IDDM, as compared with insulin-treated IDDM patients or nondiabetic controls (p = 0.028). Actual sCD62L concentrations in the 35 recent-onset IDDM patients were 22.2 +/- 4.9 nmol/L vs 19.6 +/- 3.6 nmol/l in 35 non-diabetic controls matched for age (p = 0.022). While this significant but small rise of systemic sCD62L reflects leukocyte activation, it is obscured by the inverse association between sCD62L and chronological age in children and adolescents. Therefore, determining sCD62L serum concentrations appears to be of limited value for clinical investigators caring for children and adolescents with IDDM.

Adolescent↗
PubMed2000

Inhaled nitric oxide in premature infants--a meta-analysis.

The role of inhaled nitric oxide (iNO) in the treatment of severe hypoxemic respiratory failure of term neonates has been firmly established in several randomized trials. In contrast, the use of iNO in premature newborns has remained controversial. As of 1999, there are data of three randomized controlled trials involving a total of 210 infants below 33 weeks of gestation. None of the trials was able to demonstrate a benefit of iNO with respect to mortality or chronic lung disease. We performed a meta-analysis of the three published trials. Of 111 infants receiving iNO, 44 deaths were observed, compared to 40 of 99 control infants (p = 0.91). The odds ratio in favor of iNO was 0.97 (95% confidence interval 0.54-1.75). There was also no significant difference for treatment failure, defined as death or chronic lung disease (iNO: 32 of 111 infants versus control: 34 of 99, p = 0.39, odds ratio 0.77, 95% confidence interval 0.41-1.45). The rates of intracranial hemorrhage were similar in both groups (35 of 111 infants receiving iNO vs 25 of 99 controls, p = 0.33, odds ratio 1.37, 95% confidence interval 0.69-2.74). We conclude that the use of inhaled nitric oxide may improve oxygenation but not survival in preterm infants with severe hypoxemic respiratory failure.

Administration, Inhalation↗
PubMed1999

Hearing in newborn infants of opiate-addicted mothers.

UNLABELLED: To investigate effects of maternal drug abuse on neonatal hearing, auditory brain-stem evoked potentials were recorded in 132 consecutive newborn infants of mothers who had taken heroin or methadone during pregnancy, alongside 1016 neonates with and 483 hospitalized neonates without risk factors, as defined by the Joint Committee on Infant Hearing. In infants antenatally exposed to opiates, the rate of severe bilateral hearing impairment (> or =50 dB) did not differ from that of hospitalized neonates without risk factors (1.5% vs. 2.5%). In contrast, intra-uterine toxoplasmosis, syphilis, or cytomegalovirus infection, bilirubin serum concentrations >25 mg/dl, craniofacial anomalies, and mechanical ventilation for 5 days or more were independently associated with increased rates of severe hearing impairment by analysis of all 1631 infants studied. CONCLUSION: Newborns of opiate-addicted mothers are not at increased risk for early onset hearing loss.

Evoked Potentials, Auditory, Brain Stem↗
PubMed1999

L-selectin in trauma patients: a marker for organ dysfunction and outcome?

BACKGROUND: Systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) are important factors affecting morbidity and mortality after trauma. Adhesion molecules, e.g. L-selectin (CD62 L), play crucial roles in both conditions. PATIENTS AND METHODS: In 51 multiple trauma patients, CD62 L surface expression on granulocytes, monocytes, lymphocytes, as well as sCD62 L plasma concentrations were determined during the first 6 days after trauma, starting at the site of accident. Clinical parameters were severity of injury scores (ISS, APACHE II), requirement of red blood cell transfusion, acute lung or liver failure, development of MODS or SIRS, early (< or = 6 d) or late (> 6 d), and outcome. RESULTS: CD62 L expression was reversibly elevated on granulocytes, T cells and monocytes in comparison with initial values. sCD62 L plasma concentrations did not show temporal variations but were depressed throughout observation period, in comparison with healthy controls. Lung failure within the first 6 days was associated with increased CD62 L expression on monocytes and B cells on admission and increased sCD62 L concentrations after 12 and 24 h. Patients with more severe injuries (APACHE II > 20 points) had higher sCD62 L concentrations after 24 h. Non-survivors had decreased sCD62 L (on admission) and T-cell CD62 L expression (after 4 h). Patients with early MODS or SIRS showed increased monocyte CD62 L expression after 6 days. CONCLUSIONS: In multiple trauma patients, severe organ dysfunction is associated with altered CD62 L expression on leukocytes and circulating sCD62 L plasma concentrations. However, the obvious complexity of the pattern currently restricts use of CD62 L quantitation for clinical purposes.

Adolescent↗
PubMed1999

Late neurological sequelae of non-hemolytic hyperbilirubinemia of healthy term neonates.

Records of the only children's hospital equipped to perform exchange transfusions in West Berlin were used to identify all 29 non-hemolytic healthy term newborns with total serum bilirubin between 20 and 30 mg/dL, 16 of whom were available for follow-up neurological examination according to Touwen. Compared to 18 case controls with bilirubin <12 mg/dL, jaundiced children scored significantly worse only on the choreiform dyskinesia scale.

Anemia, Hemolytic↗
PubMed1999

HFE gene mutation and transferrin saturation in very low birthweight infants.

AIM: To determine if there is an association between high transferrin saturation and the C282Y HFE gene mutation in very low birthweight (VLBW) infants. METHODS: One hundred and forty three VLBW infants receiving recombinant erythropoietin and 3 to 9 mg/kg/day of enteral iron were studied. Genomic DNA was extracted from filter paper cards. The C282Y mutation was determined by restriction fragment length polymorphism analysis. RESULTS: Six infants were heterozygous for the mutation; none was homozygous. Ten infants had a transferrin saturation above 80% at least once. No infant was positive for both transferrin saturation above 80% and the mutation. CONCLUSIONS: The data strongly suggest that there is no association between high transferrin saturation and the HFE gene mutation in VLBW infants during the first weeks of life.

Female↗
PubMed1998

Soluble L-selectin plasma concentrations in infants undergoing heart surgery: no association with capillary leak syndrome or need for respiratory support.

OBJECTIVE: In critical care patients at risk of developing the acute respiratory distress syndrome (ARDS), low soluble L-selectin (sCD62L) plasma concentrations have been shown to be associated with progression to ARDS and prolonged subsequent mechanical ventilation. This study aimed to determine the usefulness of sCD62L plasma concentrations to identify infants undergoing cardiovascular surgery who are at risk for postoperative pulmonary dysfunction and capillary leaks. DESIGN: Serial measurements of sCD62L plasma concentrations in a cohort of infants with congenital heart disease before, during, and after surgery for 4 consecutive days. SETTING AND PATIENTS: Infants aged 3-337 days undergoing cardiovascular surgery with (N = 27) or without (N = 12) cardiopulmonary bypass in a tertiary care center. RESULTS: sCD62L concentrations before surgery showed a strong correlation with the infant's age (r = 0.77, p < 0.001). During surgery, sCD62L levels dropped from 9.0 +/- 0.7 to 5.6 +/- 0.4 nmol/l (mean +/- SEM; p < 0.001). The minimum sCD62L concentration during and after surgery did not differ between infants operated upon with or without cardiopulmonary bypass (p > 0.1) or in infants who did (N = 10) or did not (N = 29) develop capillary leak syndrome. Whereas capillary leak syndrome was associated with prolonged mechanical ventilation (p < 0.01), there was no relationship between sCD62L concentrations at baseline or at any time thereafter and number of hours on the ventilator(p > 0.1). CONCLUSION: sCD62L concentrations before or after surgery are not apt to identify infants at increased risk of prolonged mechanical ventilation.

Age Factors↗
PubMed1998

Renal impairment in patients with long-standing cyanotic congenital heart disease.

Nephropathy is known to occur in patients with long-standing cyanotic congenital heart disease (CCHD). In order to assess the incidence, nature and degree of the problem among such patients, discriminating urine analyses were performed in 26 patients with CCHD, with a mean age of 22 (10-42) y. Ten patients showed reduced glomerular function, six of whom also had advanced glomerulopathy. Glomerular filtration rates were below normal in half of the patients and occurred with glomerular-type proteinuria in five, with tubular-type proteinuria in one and without pathological proteinuria in four. An elevated haematocrit and duration of cyanosis were identified as the main risks factors for the development of glomerulopathy. The risk of developing glomerular lesions rose sharply during the second decade of life. Nephropathy in CCHD is common and the dominant feature is glomerular damage, which is related to the duration of cyanosis and the extent to which the haematocrit is elevated.

Adolescent↗
PubMed1998

Decreased soluble adhesion molecule L-selectin plasma concentrations after major trauma.

BACKGROUND: Binding of the leukocyte glycoprotein L-selectin to ligands expressed by activated endothelium directs leukocyte recruitment to areas of acute inflammation. Sequestration by activated microvascular endothelium has been proposed to explain the low plasma concentrations of soluble L-selectin (sCD62L) observed early in patients with acute respiratory distress syndrome. We hypothesized that inflammatory endothelial activation may occur in trauma patients, leading to decreased sCD62L plasma concentrations. METHODS: This study was a prospective analysis of sCD62L plasma concentrations in patients with isolated head injuries and multiple trauma patients without head injuries admitted to two tertiary-level intensive care units. sCD62L plasma concentrations were determined in 18 consecutive adult patients with isolated moderate and severe head injuries and in 13 multiple trauma patients without head injuries immediately upon admission to the intensive care unit and then daily for up to 10 days after trauma. RESULTS: Compared with healthy adult controls (n=22), patient sCD62L plasma concentrations were significantly decreased upon admission (5.7+/-1.6 vs. 11.0+/-1.7 pmol/mL; p < 0.001). In all patients, sCD62L concentrations remained depressed throughout the study period. sCD62L concentrations did not differ significantly between patients with isolated head injuries and multiple trauma patients without head injuries, although repeated-measures analysis of variance showed significantly more depressed sCD62L concentrations associated with severe (n=14) compared with moderate head injuries (n=4) during the study period (p < 0.05). CONCLUSION: Patients with major trauma present with a significant reduction of sCD62L plasma concentrations within the first 12 hours after trauma and during subsequent intensive care. This finding suggests widespread microvascular endothelial activation after trauma, which may be associated with increased neutrophil extravasation.

Adolescent↗
PubMed1997

Acute toxicity and effectiveness of idarubicin in childhood acute lymphoblastic leukemia.

Anthracyclines have become important components of multi-agent remission induction and continuation therapy of acute lymphoblastic leukemia (ALL). New anthracycline derivatives are being investigated in an attempt to shift the balance of side effects and antileukemic potency. To evaluate the toxicity and efficacy of idarubicin (IDA) in childhood ALL, a prospective multicenter phase-II study was performed. A total of 51 children with prognostically poor recurrences of ALL were enrolled, all of whom had been exposed to anthracyclines during front-line treatment. A single 48-h continuous infusion of IDA at 24 mg/m2 was started on the first day of salvage treatment without concomitant systemic cytostatic agents. The response was assessed by reduction of leukemic blasts in the bone marrow and other compartments 2 wk later. IDA monotherapy caused complete and partial remissions in 5 and 20 patients, respectively (49%). Delays of treatment with subsequent polychemotherapy courses were frequent and mainly caused by prolonged intervals of myelosuppression and high rates of systemic infection. Non-hematological toxicities including acute cardiac reactions were transient and moderate. Our findings suggest that IDA is an effective drug for remission induction in children with ALL, with acute hematological toxicity being dose-limiting.

Adolescent↗
PubMed1997

Human megakaryoblastic proliferation and differentiation events observed by phase-contrast cinematography.

Microcinematographic documentation of mitoses, amitoses, endomitoses, or cytoplasmic fusion shortly after completion of mitoses was done in bone marrow specimens of patients with quantitative platelet disorders and controls. In patients with platelet disorders, most mitoses with cell duplication occurred in large promegakaryocytes after 4-fold nuclear and cytoplasmic enhancement. Normal specimens showed polyploidization happening in small megakaryoblasts, while mitoses with cell duplication were seen only after cultivation in freeze-thawed sera of patients with platelet disorders. Frequently, lymphocytes were observed to contact megakaryoblastic cells undergoing mitoses, amitoses and endomitoses and to enter the cytoplasm of megakaryocytes (emperipolesis), leaving it again after several hours.

Bone Marrow Cells↗