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Biomedical subjects

Christoph Bührer

Publications and source records attributed to Christoph Bührer.

At least 37 records · Page 2Linked to original sources
PubMed2005

Birth weight and parental BMI predict overweight in children from mothers with gestational diabetes.

OBJECTIVE: To investigate the growth of children from pregnancies with gestational diabetes mellitus (GDM) and its association with antenatal maternal, fetal, and recent anthropometric parameters of mother and father. RESEARCH DESIGN AND METHODS: In 324 pregnancies of Caucasian women with GDM, BMI before pregnancy, maternal glycemic values, and measurements of the fetal abdominal circumference were recorded. The weight and height of infants were measured at birth and at follow-up at 5.4 years (range 2.5-8.5). In addition, somatic data from routine examinations at 6, 12, and 24 months and the BMI of parents at follow-up were obtained. BMI standard deviation scores (SDSs) were calculated based on age-correspondent data. RESULTS: At all time points, BMI was significantly above average (+0.82 SDS at birth; +0.56 at 6, +0.35 at 12, and +0.32 at 24 months; and +0.66 at follow-up; P < 0.001). BMI at birth was related to BMI at follow-up (r = 0.27, P < 0.001). The rate of overweight at follow-up was 37% in children with birth BMI > or =90th percentile and 25% in those with normal BMI at birth (P < 0.05). Abdominal circumference of third trimester and postprandial glucose values were related to BMI at follow-up (r = 0.22 and r = 0.18, P < 0.01). Recent maternal, paternal, and birth BMI were independent predictors of BMI at follow-up (r = 0.42, P < 0.001). Sixty-nine percent of children of parents with BMI > or =30 kg/m(2) were overweight at follow-up compared with 20% of those with parental BMI <30 kg/m(2) (P < 0.001). CONCLUSIONS: Children of mothers with GDM have a high rate of overweight that is associated both with intrauterine growth and parental obesity.

Anthropometry↗
PubMed2004

Oxygen-regulated expression of the RNA-binding proteins RBM3 and CIRP by a HIF-1-independent mechanism.

The transcriptional regulation of several dozen genes in response to low oxygen tension is mediated by hypoxia-inducible factor 1 (HIF-1), a heterodimeric protein composed of two subunits, HIF-1alpha and HIF-1beta. In the HIF-1alpha-deficient human leukemic cell line, Z-33, exposed to mild (8% O(2)) or severe (1% O(2)) hypoxia, we found significant upregulation of two related heterogenous nuclear ribonucleoproteins, RNA-binding motif protein 3 (RBM3) and cold inducible RNA-binding protein (CIRP), which are highly conserved cold stress proteins with RNA-binding properties. Hypoxia also induced upregulation of RBM3 and CIRP in the murine HIF-1beta-deficient cell line, Hepa-1 c4. In various HIF-1 competent cells, RBM3 and CIRP were induced by moderate hypothermia (32 degrees C) but hypothermia was ineffective in increasing HIF-1alpha or vascular endothelial growth factor (VEGF), a known HIF-1 target. In contrast, iron chelators induced VEGF but not RBM3 or CIRP. The RBM3 and CIRP mRNA increase after hypoxia was inhibited by actinomycin-D, and in vitro nuclear run-on assays demonstrated specific increases in RBM3 and CIRP mRNA after hypoxia, which suggests that regulation takes place at the level of gene transcription. Hypoxia-induced RBM3 or CIRP transcription was inhibited by the respiratory chain inhibitors NaN(3) and cyanide in a dose-dependent fashion. However, cells depleted of mitochondria were still able to upregulate RBM3 and CIRP in response to hypoxia. Thus, RBM3 and CIRP are adaptatively expressed in response to hypoxia by a mechanism that involves neither HIF-1 nor mitochondria.

Animals↗
PubMed2004

Extrahepatic biliary atresia and caudal regression syndrome in an infant of a diabetic mother.

Although most cases of extrahepatic biliary atresia are thought to result from perinatal obliterating inflammation, some are associated with a faulty morphogenesis. The authors report on a baby girl of a mother with ill-managed insulin-dependent diabetes mellitus. The baby presented with sacro-coccygeal agenesis, clubfoot, and ano-urinary incontinence. In addition, there was polysplenia, no inferior vena cava, and the portal vein was grossly distorted. Progressive conjugated hyperbilirubinemia prompted liver biopsy at 4 weeks of age, showing intracanalicular cholestasis without fibrosis. The diagnosis of extrahepatic biliary atresia was confirmed during laparotomy performed for hepatoportojejunostomy. Some cases of extrahepatic biliary atresia might be part of a spectrum of malformations associated with maternal diabetes mellitus.

Abnormalities, Multiple↗
PubMed2004

Erythropoietin protects the developing brain against N-methyl-D-aspartate receptor antagonist neurotoxicity.

Pharmacological blockade of NMDA receptor function induces apoptotic neurodegeneration in the developing rat brain. However, the use of NMDA receptor antagonists as anesthetics and sedatives represents a difficult-to-avoid clinical practice in pediatrics. This warrants the search for adjunctive neuroprotective measures that will prevent or ameliorate neurotoxicity of NMDA receptor antagonists. The NMDA receptor antagonist MK801 triggered apoptosis in the neonatal rat forebrain, most notably in cortex and thalamus. MK801 exposure reduced mRNA levels of erythropoietin (EPO) and the EPO receptor, suggesting that loss of endogenous EPO activity may contribute to MK801-induced apoptosis. Coadministration of recombinant EPO (rEPO) conferred 50% neuroprotection, partially restored MK801-induced reduction of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) mRNA, and prevented decreased phosphorylation levels of extracellular signal-regulated protein kinase-1/2 (ERK1/2) and Akt. These observations indicate that rEPO partly rescues newborn rats from MK801-mediated brain damage by enhancing neurotrophin-associated signaling pathways.

Animals↗
PubMed2004

Oxygen causes cell death in the developing brain.

Substantial neurologic morbidity occurs in survivors of premature birth. Premature infants are exposed to partial oxygen pressures that are fourfold higher compared to intrauterine conditions, even if no supplemental oxygen is administered. Here we report that short exposures to nonphysiologic oxygen levels can trigger apoptotic neurodegeneration in the brains of infant rodents. Vulnerability to oxygen neurotoxicity is confined to the first 2 weeks of life, a period characterized by rapid growth, which in humans expands from the sixth month of pregnancy to the third year of life. Oxygen caused oxidative stress, decreased expression of neurotrophins, and inactivation of survival signaling proteins Ras, extracellular signal-regulated kinase (ERK 1/2), and protein kinase B (Akt). The synRas-transgenic mice overexpressing constitutively activated Ras and phosphorylated kinases ERK1/2 in the brain were protected against oxygen neurotoxicity. Our findings reveal a mechanism that could potentially damage the developing brain of human premature neonates.

Aging↗
PubMed2004

A randomized trial evaluating a predominantly fetal growth-based strategy to guide management of gestational diabetes in Caucasian women.

OBJECTIVE: To compare the management of Caucasian women with gestational diabetes (GDM) based predominantly on monthly fetal growth ultrasound examinations with an approach based solely on maternal glycemia. RESEARCH DESIGN AND METHODS: Women with GDM who attained fasting capillary glucose (FCG) <120 mg/dl and 2-h postprandial capillary glucose (2h-CG) <200 mg/dl after 1 week of diet were randomized to management based on maternal glycemia alone (standard) or glycemia plus ultrasound. In the standard group, insulin was initiated if FCG was repeatedly >90 mg/dl or 2h-CG was >120 mg/dl. In the ultrasound group, thresholds were 120 and 200 mg/dl, respectively, or a fetal abdominal circumference >75th percentile (AC>p75). Outcome criteria were rates of C-section, small-for-gestational-age (SGA) or large-for-gestational-age (LGA) infants, neonatal hypoglycemia (<40 mg/dl), and neonatal care admission. RESULTS: Maternal characteristics and fetal AC>p75 (36.0 vs. 38.4%) at entry did not differ between the standard (n = 100) and ultrasound groups (n = 99). Assignment to (30.0 vs. 40.4%) and mean duration of insulin treatment (8.3 vs. 8.1 weeks) did not differ between groups. In the ultrasound group, AC>p75 was the sole indication for insulin. The ultrasound-based strategy, as compared with the maternal glycemia-only strategy, resulted in a different treatment assignment in 34% of women. Rates of C-section (19.0 vs. 18.2%), LGA (10.0 vs. 12.1%), SGA (13.0 vs. 12.1%), hypoglycemia (16.0 vs. 17.0%), and admission (15.0 vs. 14.1%) did not differ significantly. CONCLUSIONS: GDM management based on fetal growth combined with high glycemic criteria provides outcomes equivalent to management based on strict glycemic criteria alone. Inclusion of fetal growth might provide the opportunity to reduce glucose testing in low-risk pregnancies.

Adult↗
PubMed2003

Endothelial nitric oxide synthase (NOS) is upregulated in rapid progressive pulmonary hypertension of the newborn.

OBJECTIVE: To provide evidence for the upregulation of endothelial nitric oxide synthase (eNOS) or inducible nitric oxide synthase (iNOS) in the assumed imbalance in the pathophysiology of rapid progressive pulmonary hypertension of the newborn (RPPHN), which is characterized by abnormal hypertrophy of the pulmonary arterioles and arteries leading to increased pulmonary vascular resistance. Furthermore, to determine the cellular source and topographic distribution of eNOS and iNOS. MATERIAL AND METHODS: Lung biopsies were taken from two term neonates with clinical and echocardiographic evidence of RPPH and of three controls. Biopsies were obtained at an early stage of the disease as well as at post mortem and examined immunohistochemically for the presence of eNOS, iNOS and nitrotyrosine. RESULTS: The endothelial cells of pulmonary arterioles stained significantly for eNOS protein in RPPHN patients. This was not the case in the control infants. There were no differences for nitrotyrosine or iNOS between RPPHN patients and controls. CONCLUSION: Rapid progressive pulmonary hypertension of the newborn leads to compensatory induction of eNOS synthesis specifically in endothelial cells of the pulmonary arterioles. This mechanism of compensation can lead to delayed presentation of RPPHN during the late neonatal period. Exogenous inhaled nitric oxide therapy does not lead to suppression of the endogenous synthesis of nitric oxide.

Endothelium↗
PubMed2003

Hyperoxia causes inducible nitric oxide synthase-mediated cellular damage to the immature rat brain.

Relative hyperoxia is a condition frequently encountered in premature infants, either spontaneously or during treatment in the Neonatal Intensive Care Unit. The effects of high inspiratory oxygen concentrations on immature brain cells and their signaling cascades are largely unknown. The aim of the study was to investigate the effect of hyperoxia on the amount and topographic distribution of iNOS-expression (inducible nitric oxide synthase) in the immature rat brain, and to localize hyperoxia-induced formation of peroxynitrite as a potential marker of cellular damage to immature cerebral structures. Seven-day-old Wistar rat pups were exposed to >80% oxygen for 24 h and were then transcardially perfused. Following paraformaldehyde fixation, brains were paraffin-embedded and immunohistochemically stained for iNOS and nitrotyrosine. iNOS protein was quantified by Western blot; iNOS mRNA expression was studied by RT-PCR. Total brain iNOS mRNA was up-regulated, demonstrating a peak at 6 h following the onset of hyperoxia. Immunohistochemical staining was predominantly observed in microglial cells of hippocampus and frontal cortex with some iNOS reactivity in endothelial and perivascular cells. Nitrotyrosine staining was positive in apical dendrites of neurons in the frontal cortex. There was no positive staining for iNOS or nitrotyrosine in control animals. Hyperoxia causes iNOS mRNA and protein up-regulation in microglial cells of the immature rat brain. Positive neuronal nitrotyrosine staining indicates formation of peroxynitrite with potential deleterious effects for immature cellular structures in the neonatal brain.

Animals↗
PubMed2003

Isolated cardiomegaly in the second trimester as an early sign of fetal hydrops due to intracranial arteriovenous malformation.

We report the case of a 27-year-old pregnant woman in whom isolated mild fetal cardiomegaly, diagnosed prenatally on sonographic examination at 22 weeks' menstrual age, was the first sign of development of an arteriovenous malformation of the vein of Galen. The arteriovenous malformation was visualized on sonographic examination at 29 weeks' menstrual age; prenatal MRI at 32 weeks confirmed the diagnosis. At 34 weeks' menstrual age, repeat sonographic examination demonstrated polyhydramnios, cardiomegaly, and generalized hydrops with ascites and pleural effusion. After vaginal delivery, the male neonate died of respiratory distress. We present the findings of prenatal gray-scale, color Doppler, and power Doppler sonography; MRI; and postmortem examination.

Cardiomegaly↗
PubMed2002

Preconceptional factors associated with very low birthweight delivery in East and West Berlin: a case control study.

BACKGROUND: Very low birthweight, i.e. a birthweight < 1500 g, is among the strongest determinants of infant mortality and childhood morbidity. To develop primary prevention approaches to VLBW birth and its sequelae, information is needed on the causes of preterm birth, their personal and social antecedents, and on conditions associated with very low birthweight. Despite the growing body of evidence linking sociodemographic variables with preterm delivery, little is known as to how this may be extrapolated to the risk of very low birthweight. METHODS: In 1992, two years after the German unification, we started to recruit two cohorts of very low birthweight infants and controls in East and West Berlin for a long-term neurodevelopmental study. The present analysis was undertaken to compare potential preconceptional risk factors for very low birthweight delivery in a case-control design including 166 mothers (82 East vs. 84 West Berlin) with very low birthweight delivery and 341 control mothers (166 East vs. 175 West). RESULTS: Multivariate logistic regression analysis was used to assess the effects of various dichotomous parental covariates and their interaction with living in East or West Berlin. After backward variable selection, short maternal school education, maternal unemployment, single-room apartment, smoking, previous preterm delivery, and fetal loss emerged as significant main effect variables, together with living in West Berlin as positive effect modificator for single-mother status. CONCLUSION: Very low birthweight has been differentially associated with obstetrical history and indicators of maternal socioeconomic status in East and West Berlin. The ranking of these risk factors is under the influence of the political framework.

Berlin↗
PubMed2002

Vascular endothelial growth factor and erythropoietin concentrations in cerebrospinal fluid of children with hydrocephalus.

INTRODUCTION: Hypoxia induces transcription of vascular endothelial growth factor (VEGF) and erythropoietin (EPO) genes. We set up the hypothesis that elevated intracranial pressure in patients with hydrocephalus triggers release of VEGF and EPO into cerebrospinal fluid (CSF). METHODS AND RESULTS: VEGF and EPO concentrations, measured in 57 CSF aliquots obtained from infants and children with hydrocephalus undergoing surgery or therapeutic taps, were significantly elevated compared with those in 41 CSF aliquots of sex- and age-matched children undergoing routine diagnostic lumbar puncture for unrelated reasons ( P<0.001 and P=0.015, respectively). In hydrocephalus samples, median (interquartile range) VEGF concentrations were 135 (35-410) pg/ml, and 4 of 57 hydrocephalus samples had a VEGF concentration below the detection limit (1 pg/ml), compared with 38 of 41 control samples. Erythropoietin was undetectable (<0.1 pg/ml) in 34 of 57 hydrocephalus samples and in 34 of 41 controls. CONCLUSION: We conclude that conditions necessitating surgical intervention in hydrocephalus patients result in increased CSF concentrations of VEGF and EPO.

Brain Neoplasms↗
PubMed2002

Soluble l-selectin (sCD62L) in relapsed childhood acute lymphoblastic leukaemia.

Soluble l-selectin (sCD62L) plasma concentrations at diagnosis and outcome were investigated in 193 children at first relapse of acute lymphoblastic leukaemia (ALL) after treatment according to the Berlin-Frankfurt-Münster relapsed ALL multicentre trials, ALL-REZ BFM 95 and 96. sCD62L was low (< fifth paediatric reference percentile) in 63 (33%) and high (> 95th percentile) in 36 (19%) children, and was independent of remission duration, sex, BCR-ABL fusion or extramedullary disease. High sCD62L was associated with circulating blasts and T-cell phenotype. More initial adverse events occurred in children with high and low levels of sCD62L (23 out of 99) than in those with normal levels (9 out of 94, P = 0.018). Among 75 worst-prognosis patients (risk groups S3/S4, isolated bone marrow relapse occurring less than 6 months after elective cessation of front-line therapy, or T-cell phenotype with bone marrow involvement), 27 had low sCD62L and decreased event-free survival (EFS) probability (PEFS5 = 0.09 at 5 years) and duration (219 d) compared with normal sCD62L (29 out of 75, PEFS5 = 0.24, 640 d, P = 0.01). Low (44 out of 118), normal (72 out of 118), and high (19 out of 118) sCD62L non-S3/S4 patients fared similarly (average PEFS5 = 0.45, 1369 d; P = 0.5). Low sCD62L may be a marker of malignant blasts replacing normal sCD62L-producing haematopoietic cells. In children with first relapse of ALL and worst prognosis, plasma sCD62L may be useful for risk-adapted stratification.

Adolescent↗
PubMed2002

Intravascular granulocyte aggregates caused by the selectin-binding carbohydrate fucoidin in pig kidneys.

1. Renal postischaemic reperfusion injury constitutes a significant problem after kidney transplantation. The polysaccharide fucoidin improves postischaemic function in lamb hearts, presumably by blocking selectin-mediated leucocyte adhesion. 2. In the present study, eight pairs of ischaemic pig kidneys were reperfused in an ex vivo model with autologous blood with or without fucoidin (100 mg/L). 3. Fucoidin resulted in a significant decrease in renal blood flow (45 +/- 5 vs 178 +/- 22 mL/min per 100 g; P < 0.001) and increased vascular resistance (3.80 +/- 0.07 vs 0.60 +/- 0.12 mmHg/mL per min per 100 g; P < 0.001). 4. Histological examination revealed granulocyte emboli in afferent glomerular arteries in five of six fucoidin-treated kidneys and in one of six controls (Fisher's exact test; P < 0.001). 5. In vitro experiments with human granulocytes showed that large granulocyte aggregates were induced by fucoidin at concentrations similar to those used in reperfused kidneys, whereas slightly lower doses of fucoidin prevented l-selectin-dependent homotypic granulocyte adhesion. 6. The formation of embolizing granulocyte aggregates defines a narrow therapeutic range for fucoidin and calls into question its experimental use as an inhibitor of selectin-mediated leucocyte adhesion.

Animals↗
PubMed2002

Myoid differentiation in mesoblastic nephroma: clinicopathologic and cytogenetic findings of a rare case.

The authors report the case of a benign renal mesenchymal tumor in a baby boy detected by ultrasound scanning during prenatal diagnosis. Histologically, the tumor was diagnosed as a congenital mesoblastic nephroma (CMN) with myoid differentiation. The tumor normally is characterized by a fascicular proliferation of bland, spindle-shaped cells. CMN is the most common renal tumor in the neonatal period and presumedly results from a neoplastic transformation affecting the pluripotent mesodermal nephric blastema. In embryonic life, tumorigenic influences acting on the nephric blastema might result in selective overgrowth of its mesoblastic derivates. CMN must be differentiated from other spindle-shaped tumors, like Wilms' tumor, rhabdoid tumor of the kidney, clear cell sarcoma, nephrogenic adenofibroma, fibroma and fibrosarcoma, leiomyoma, metanephric stromal tumor, and, in this case especially, from tumors with myoid differentiation like infantile myofibromatosis. Numerical molecular abnormalities are observed frequently in renal mesenchymal tumors, especially in chromosome 11. Cytogenetic findings in our tumor after comparative genomic hybridization (CGH) showed full trisomies of chromosomes 20 and 22q, partial trisomies for the distal part of 11q and 1p, and an approximately full monosomy of chromosome 4 (4qter-4p15). The chromosomal imbalances of the tumor can be described as: rev ish enh(1p31pter,11q23qter,20,22), dim(4)(p15qter).

DNA, Neoplasm↗