Biomedical subjects

S Petersen

Publications and source records attributed to S Petersen.

At least 19 recordsLinked to original sources

PubMed2003

Potentiation of prelimbic field potentials during and seconds after trains of excitations in the rat hippocampo-prefrontal pathway.

Field potentials were recorded in the prelimbic cortex of anaesthetized rats after excitations of the hippocampo-prefrontal pathway. Stimuli were delivered to the hippocampal CA1 region and short-term changes of field potential amplitudes were observed in two situations. (1) Amplitudes were monitored during trains of stimulations given at frequencies between 1 and 20 Hz. Within trains, potentiation was followed by depression. Both types of changes were frequency dependent. (2) The time course of recovery from within-train plasticity was obtained from field potentials evoked at varying intervals after trains. This revealed a post-train potentiation having a maximum after 2-4 s and lasting for approximately 10 s. The maximal post-train potentiation was nearly independent of the frequency of the preceding train.

Animals↗

PubMed2003

Increasing prevalence of overweight in young schoolchildren in Umeå, Sweden, from 1986 to 2001.

AIM: To investigate the current prevalence and trend of overweight in young schoolchildren in Umeå, Sweden. METHODS: Two cross-sectional samples of children were studied: 1115 randomly selected children from preschool class to grade 6 (aged 6-13 y) attending school in 2001 and a matched sample of 507 schoolchildren from grades 0, 1 and 4 (aged 6-11 y) attending school in 1986. Overweight was defined according to age- and gender-specific body mass index (BMI) cut-off values, corresponding to BMI values of 25 kg/m2 (level 1) and 30 kg/m2 (level 2) at late adolescence. RESULTS: In the population from 2001, the prevalence of overweight was 23% (18% at level 1, 5% at level 2). The prevalence differed with age, with a higher prevalence at the ages of 6 and 13 y. Comparing children from grades 0, 1 and 4, attending school in 1986 and 2001, respectively, the total prevalence of overweight was twice as high in 2001 as in 1986. Regarding severe overweight (level 2), the difference was even larger (five times). In the 1986 sample, the prevalence of overweight did not differ between girls and boys, while significantly more girls than boys were overweight in 2001. CONCLUSION: In this sample of young children from Sweden, the prevalence of overweight doubled over the past 15 y and severe overweight increased even more, suggesting a need for intensified preventive efforts in young schoolchildren.

Adolescent↗

PubMed2002

Assessment of infant physiology and neuronal development using magnetic resonance imaging.

Previous work has demonstrated both that there are substantial individual differences in the rate of physiological development,and that infants with risk factors for Sudden Infant Death Syndrome (SIDS) develop more slowly, suggesting that their increased vulnerability may be due to delayed neuronal development associated with compromised development in fetal or early neonatal life. This project aims to test the hypothesis that individual differences in the rate of physiological development of infants correlate with measurable differences in the rate of brain development as assessed by magnetic resonance imaging (MRI). Sixty infants were recruited to this study in three different groups that are known to have differing rates of physiological development. MRI was performed successfully in 49 cases at 6 weeks of age without sedation. Forty-one of these cases had full follow-up (15 normal; 19 IUGR; 11 'high risk'). Postnatal physiological development was assessed by measuring age-related deep body temperature patterns during sleep. Neuronal development was assessed by subjective analysis of MRI images and objective measurements relating to myelination using T1 and diffusion weighted (23 cases) MRI images. As expected the normal group acquired the adult temperature pattern earlier, but this was not statistically significant. All MRI scan appearances were within normal limits. Ranking cases subjectively in order of maturity revealed no significant pattern. The normal group had a significantly higher myelination score than the IUGR and 'high risk' groups (P = 0.001). This trend was also shown by the diffusion weighted myelination score but did not reach statistical significance. No significant differences were seen in both the subjective and objective MRI measurements and development of nocturnal temperature patterns. The results suggest there may be differences in neurodevelopment between the different groups at 6 weeks of age but these are not linked to late development of temperature patterns. It is therefore unlikely that this related to a global delay in maturation.

Brain↗

PubMed2002

[Surgical management of severe peritonitis].

Despite all the efforts made in the areas of intensive care and surgery, severe peritonitis remains a feared condition that is associated with a high mortality rate. Severe abdominal infections are accompanied with a high level of endotoxin production, resulting in the so called systemic inflammatory response syndrome (SIRS), which is often complicated by multiple organ failure. The surgical eradication of the infectious focus is the most important prerequisite for a successful treatment. According to the severity of the local inflammation, different forms of abdominal lavage can be applied. We analysed patient characteristics and the clinical outcome of 180 patients with diffuse peritonitis, including 36 patients with more than 29 MPI-Points. The mean severity of peritonitis (n = 36) was 33 using the Mannheim Peritonitis Index (MPI). The hospital mortality rate was 58 % in this group.

Adult↗

PubMed2002

Bone mineralisation in premature infants cannot be predicted from serum alkaline phosphatase or serum phosphate.

BACKGROUND: The bone mineral content of premature infants at term is lower than in mature infants at the same postconceptional age. Serum alkaline phosphatase and serum phosphate are often used as indicators of bone mineralisation. OBJECTIVE: To analyse the association between bone mineral content and serum alkaline phosphatase and serum phosphate. METHODS: Serum alkaline phosphatase and phosphate were measured at weekly intervals during admission in 108 premature infants of gestational age below 32 weeks (mean (SD) gestational age 29 (2) weeks; mean (SD) birth weight 1129 (279) g). Bone mineral content was measured at term (mean gestational age 41 weeks) by dual energy x ray absorptiometry and corrected for body size. RESULTS: Serum alkaline phosphatase was significantly negatively associated with serum phosphate (p < 0.001). Bone mineral content was not associated with mean serum alkaline phosphatase (p = 0.8), peak serum alkaline phosphatase (p = 0.5), or mean serum phosphate (p = 0.2) at term. CONCLUSION: Routine measurements of serum alkaline phosphatase and serum phosphate are of no use in predicting bone mineralisation outcome in premature infants.

Absorptiometry, Photon↗

PubMed2002

Extreme prematurity in the UK and Denmark: population differences in viability.

BACKGROUND: Previous studies comparing different models of neonatal intensive care have generally not been population based. The objective of this study was to compare the perinatal services of two total populations. METHODS: Observational study based on two geographically defined populations: the whole of Demark (some centralisation of neonatal intensive care but most delivered locally by small perinatal centres-48 in total) and the Trent Health Region of the UK (no formal centralisation however deliveries almost all focussed on 16 major hospitals with > 90% of the intensive care provided by 13 hospitals). Information was recorded about the course of every liveborn infant < 28 weeks gestation and or < 1000g birth weight and > or = 21 weeks gestation in 1994 and 1995. RESULTS: Despite having a smaller population the number of liveborn children meeting the study criteria was significantly higher in Trent (Demark 461 (3.3 per 1000 births, 95% confidence interval (CI) 3.0 to 3.6); Trent 572 (4.9 per 1000 births, 95% CI 4.5 to 5.3)). In Denmark 91.1% of these infants were admitted for intensive care and 85.5% in Trent. Despite significantly more Trent infants being exposed to antenatal steroids their outcome was worse (median Clinical Risk Index for Babies (CRIB) score 7 v 4; proportion receiving ventilation 87.6% v 40.0%; survival to discharge (uncorrected for disease severity) 42.3% v 35.0%). CONCLUSION: The population characteristics of Trent seemed to produce a higher prematurity rate compared to Denmark. These infants as a group appeared sicker and, despite more intensive care delivered by a more specialised service, outcomes were worse.

Birth Weight↗

PubMed2001

Application of C1-esterase inhibitor during reperfusion of ischemic myocardium: dose-related beneficial versus detrimental effects.

BACKGROUND: Complement activation during reperfusion of ischemic myocardium augments myocardial injury, and complement inhibition with C1-esterase inhibitor (C1-INH) at the time of reperfusion exerts marked cardioprotective effects in experimental studies. Application of C1-INH in newborns, however, was recently reported to have dangerous and even lethal side effects. This study addresses the essential role of dosage in studies using C1-INH. METHODS AND RESULTS: Cardioprotection by C1-INH was examined in a pig model with 60 minutes of coronary occlusion followed by 120 minutes of reperfusion. C1-INH was administered intravenously 5 to 10 minutes before coronary reperfusion without heparin at a dose of 40, 100, and 200 IU/kg body wt. Compared with the NaCl controls, C1-INH 40 IU/kg reduced myocardial injury (44.1+/-13.8% versus 76.7+/-4.6% necrosis of area at risk, P</=0.05) and significantly suppressed local C3a and C5a generation. Myocardial protection was accompanied by reduced plasma concentrations of creatine kinase and troponin T. In contrast, no beneficial effects were observed when 100 IU/kg C1-INH was used. Furthermore, application of 200 IU/kg C1-INH provoked severe side effects and coagulation disorders. CONCLUSIONS: When applied at the correct dose, C1-INH significantly protects ischemic tissue from reperfusion damage. However, overly high doses (>/=100 IU/kg) of C1-INH will provoke detrimental side effects, probably via its procoagulatory action.

Anaphylatoxins↗

PubMed2001

Diversity of gene expression in adenocarcinoma of the lung.

The global gene expression profiles for 67 human lung tumors representing 56 patients were examined by using 24,000-element cDNA microarrays. Subdivision of the tumors based on gene expression patterns faithfully recapitulated morphological classification of the tumors into squamous, large cell, small cell, and adenocarcinoma. The gene expression patterns made possible the subclassification of adenocarcinoma into subgroups that correlated with the degree of tumor differentiation as well as patient survival. Gene expression analysis thus promises to extend and refine standard pathologic analysis.

Adenocarcinoma↗

PubMed2001

Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization.

Renal cell carcinoma (RCC) are frequently chemo- and radiation resistant. Thus, there is a need for identifying biological features of these cells that could serve as alternative therapeutic targets. We performed suppression subtractive hybridization (SSH) on patient-matched normal renal and RCC tissue to identify variably regulated genes. 11 genes were strongly up-regulated or selectively expressed in more than one RCC tissue or cell line. Screening of filters containing cancer-related cDNAs confirmed overexpression of 3 of these genes and 3 additional genes were identified. These 14 differentially expressed genes, only 6 of which have previously been associated with RCC, are related to tumour growth/survival (EGFR, cyclin D1, insulin-like growth factor-binding protein-1 and a MLRQ sub-unit homologue of the NADH:ubiquinone oxidoreductase complex), angiogenesis (vascular endothelial growth factor, endothelial PAS domain protein-1, ceruloplasmin, angiopoietin-related protein 2) and cell adhesion/motility (protocadherin 2, cadherin 6, autotaxin, vimentin, lysyl oxidase and semaphorin G). Since some of these genes were overexpressed in 80-90% of RCC tissues, it is important to evaluate their suitability as therapeutic targets.

Biomarkers, Tumor↗

PubMed2001

Increased plasma homocysteine in liver cirrhosis.

Background: Homocysteine (Hcy), is an atherogenic and thrombogenic risk factor which has also been proposed to be involved in hepatic fibrinogenesis. Hcy metabolism, depends on the cofactors folate, vit. B12, and the vit. B6 vitamer pyridoxalphosphate (PLP). Metabolism of these vitamins is frequently disturbed in cirrhotics, but little is known about plasma Hcy levels in these patients. Methods: Plasma levels of Hcy, methionine, serine, cysteine, PLP, vit. B12 and folate, and standard clinical/biochemical parameters of liver disease were measured in 43 postabsorptive patients with biopsy proven cirrhosis of different origin. Results: 74% of the patients had elevated plasma Hcy levels defined as >13.4 µmol/l (mean+2SD of healthy age matched controls). Increased plasma Hcy concentrations were seen in alcoholic as well as in non-alcoholic cirrhosis. Excluding patients with impaired renal function (n=7), Hcy concentrations remained elevated in 69% of the patients. We found a high prevalence of pathological plasma vitamin concentrations of 33% for increased vit. B12 levels and 5% and 80% for decreased folate and vit. B6 levels, respectively. Mean plasma vitamin B12 concentrations increased, folate remained unchanged and PLP concentrations decreased with deteriorating liver function. Hcy concentrations were correlated with levels of creatinine (r=0.44, P<0.01), serine (r=-0.46, P<0.01), and cysteine (r=0.38, P<0.05), but showed no association with parameters of liver function and with plasma levels of folate, vit. B12 und vit. B6. This was contrary to data obtained in healthy individuals. In a stepwise multiple regression serine and cysteine best explained the variance in Hcy levels. Conclusions: Elevated basal Hcy-plasma levels are frequently seen cirrhotic patients. Variations of Hcy concentration in liver cirrhosis are not explained by plasma levels of cofactors of Hcy metabolism.

Journal Article↗

PubMed2001

Targeted disruption of the Nijmegen breakage syndrome gene NBS1 leads to early embryonic lethality in mice.

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive human disease whose clinical features include growth retardation, immunodeficiency, and increased susceptibility to lymphoid malignancies. Cells from NBS patients exhibit gamma-irradiation sensitivity, S-phase checkpoint defects, and genomic instability. Recently, it was demonstrated that this chromosomal breakage syndrome is caused by mutations in the NBS1 gene that result in a total loss of full-length NBS1 expression. Here we report that in contrast to the viability of NBS patients, targeted inactivation of NBS1 in mice leads to early embryonic lethality in utero and is associated with poorly developed embryonic and extraembryonic tissues. Mutant blastocysts showed greatly diminished expansion of the inner cell mass in culture, and this finding suggests that NBS1 mediates essential functions during proliferation in the absence of externally induced damage. Together, our results indicate that the complex phenotypes observed in NBS patients and cell lines may not result from a complete inactivation of NBS1 but may instead result from hypomorphic truncation mutations compatible with cell viability.

Animals↗

PubMed2001

A universal framework for 13C metabolic flux analysis.

A general methodology is presented for the modeling, simulation, design, evaluation, and statistical analysis of (13)C-labeling experiments for metabolic flux analysis. The universal software framework 13C-FLUX was implemented to support all steps of this process. Guided by the example of anaplerotic flux determination in Corynebacterium glutamicum, the technical details of the model setup, experimental design, and data evaluation are discussed. It is shown how the network structure, the input substrate composition, the assumptions about fluxes, and the measurement configuration are specified within 13C-FLUX. Based on the network model, different experimental designs are computed depending on the goal of the investigations. Finally, a specific experiment is evaluated and the various statistical methods used to analyze the results are briefly explained. The appendix gives some details about the software implementation and availability.

Biomedical Engineering↗

PubMed2001

Metabolic consequences of altered phosphoenolpyruvate carboxykinase activity in Corynebacterium glutamicum reveal anaplerotic regulation mechanisms in vivo.

Corynebacterium glutamicum possesses high in vivo activity of the gluconeogenic phosphoenolpyruvate carboxykinase (PEPCk) during growth on glucose, resulting together with anaplerotic carboxylation reactions in a PEP/pyruvate/oxaloacetate substrate cycle. The present study investigated the changes in intracellular fluxes and metabolite concentrations that are caused by altered PEPCk activity in L-lysine-producing C. glutamicum MH20-22B, applying a recently developed (13)C labeling-based strategy for anaplerotic flux resolution and quantification. Abolition of PEPCk activity by deletion of the respective pck gene resulted in increased intracellular concentrations of oxaloacetate L-aspartate, alpha-ketoglutarate, pyruvate, and L-lysine and in a 60% enhanced flux toward L-lysine biosynthesis, whereas increasing the PEPCk activity by pck overexpression had opposite effects. The results of the combined measurements of enzyme activities, in vivo fluxes, and metabolite concentrations were exploited to elucidate the in vivo regulation of anaplerotic reactions in C. glutamicum, and implications for the metabolic engineering of amino-acid-producing strains are discussed.

Corynebacterium↗

PubMed2001

Macronutrients in milk from mothers delivering preterm.

UNLABELLED: Premature infants require large amounts of protein and energy to achieve normal growth. Feeding with human milk alone is therefore only regarded acceptable if the protein and energy content is adequate. METHODS: 476 milk samples from 101 mothers delivering before the 32nd gestational week (mean gestational age, 28 weeks) were obtained on a weekly basis until 36 weeks of gestational age and analyzed for true protein, total carbohydrate, and fat content by infrared analysis. Fat measurements were validated with the Folch method. Milk was collected by complete expression with an electric pump into 24-hour pools. RESULTS: The protein concentration decreased significantly with time (P = 0.00001). The carbohydrate, fat, and energy concentration was significantly lower in the first 2 weeks after delivery, after which they increased to a constant level. The macronutrient level in milk was not associated with gestational age (P = 0.3). The energy content of these milk samples was high, and feeding 200 mL/kg would provide sufficient energy until 36 weeks of gestational age for all infants, and 65% of the infants would receive > or =3g total protein/kg/day.

Dietary Carbohydrates↗

PubMed2001

Diet, growth, and bone mineralization in premature infants.

Energy, protein, and mineral requirements in premature infants are high, hence increasing the risk of poor growth and development of metabolic bone disease. This double-blind study included 127 consecutive premature infants with gestational age below 32 weeks. Both sick and healthy infants participated. Average duration of ventilator treatment: 2 days, CPAP treatment: 10 days (range, 0-50d). Infants were randomized to 3 groups from 1 week old to 37 weeks of gestational age and fed the following: a) human milk (their own mother's milk or banked milk) supplemented with phosphate, b) human milk fortified with protein, calcium, and phosphate, or c) unsupplemented mother's milk or preterm formula. Infants randomized to preterm formula were fed formula only if their own mother's milk was not available, hence there were 2 subgroups of infants fed either unsupplemented human milk or preterm formula. Volume of intake was 191+/-14mL/kg/d (mean +/- SD); linear growth was measured weekly by knemometry; head circumference was measured weekly; and growth rate was calculated by linear regression for each infant. Bone mineralization and body composition were measured by DEXA-scan (Hologic 1000/W) at term. There was a tendency toward slower growth and less bone mineral content in infants fed unsupplemented human milk but, surprisingly, the difference was small and not significant.

Absorptiometry, Photon↗

PubMed2001

The results of colorectal cancer treatment by p53 status: treatment-specific overview.

PURPOSE: Both negative and positive influences of mutant p53 on treatment outcome have been reported, and we present here a meta-analysis of published studies where outcome was reported for defined treatment groups. METHODS: We identified articles on the effect of p53 status by treatment modality, excluding those not stratified by method of treatment. A common hazard ratio was estimated from studies that reported a multivariate analysis. We also estimated the numbers of patients expressing the endpoint at the mean or median follow-up time and calculated a pooled odds ratio. RESULTS: Twenty-eight articles were evaluable (23 using immunohistochemistry to detect overexpression of p53 and 8 using DNA sequencing), for a total of 4,416 patients. For patients treated with surgery only, the immunohistochemistry studies showed a significant influence of p53 status on disease-free survival and a marginally significant influence on overall survival. In the studies using DNA sequencing, by contrast, there was a significant influence of p53 mutations on overall survival, but not disease-free survival. For patients treated with surgery and radiotherapy, the influence of p53 status on disease-free survival was either insignificant or marginally significant, depending on test used; there was no influence on overall survival. CONCLUSIONS: Although this pooled analysis of published studies where treatment was accounted for shows that there is a borderline significant hazard associated with p53 overexpression or mutation vs. p53 wild-type, it is unlikely that p53 can be applied in a routine clinical setting alongside factors such as T stage, nodal status, and residual tumor, whose prognostic value is much stronger.

Adenocarcinoma↗

PubMed2001

The challenge of p53 as prognostic and predictive factor in Hodgkin's or non-Hodgkin's lymphoma.

The results of individual studies examining the role of p53 as a predictive and prognostic factor in lymphoid malignancies have varied considerably. In order to summarize the available data on the overexpression or mutation of p53 in Hodgkin's and non-Hodgkin's lymphoma, a systematic literature review was performed. Twenty-four studies met the eligibility criteria. With respect to non-Hodgkin's lymphoma, most studies seem to support the hypothesis that patients whose tumors contain wild-type p53 respond better to treatment and have increased survival rates. If true, the implication may be that patients with p53 mutated tumors could be selected for non-standard treatment. With respect to Hodgkin's lymphoma, comparable associations were rarely reported. However, techniques for assessing the inactivation of p53 varied widely. Furthermore, in most instances, the study design and/or statistical methods did not allow sufficient analyses of the influence of confounding factors such as histologic type, stage, first-line and salvage treatment, etc. Therefore, it remains unclear whether the apparent influence of p53 status on outcome in non-Hodgkin's lymphoma is independent of established parameters such as stage, performance status, etc. Further studies involving large numbers of specimens derived from patients treated in clinical trials with identical regimens, follow-up and salvage strategies are needed. These studies should also be stratified according to histologic subtypes.

Disease-Free Survival↗

PubMed2001

[MR angiography and flow measurement in coronary arteries and coronary bypass grafts].

Better MR image quality of coronary arteries and coronary grafts is the product of increased spatial and temporal resolution. Breathing artifacts could be reduced by implementing breath-holding and navigator techniques. With these developments normal coronary arteries can often be imaged reliably. Several trials have been performed in order to test the reliability of MR angiography to detect coronary artery stenosis. But up to now, sensitivity and specificity have proven to be too low to introduce these techniques in clinical routine. The patency of coronary grafts can be detected reliably using different MR techniques. Coronary flow reserve can be measured using the MR phase contrast technique. This noninvasive approach was tested in diseased coronary arteries and in graft stenoses. A reduced MR coronary flow reserve corresponded to reduced flow reserve measured invasively. Measurement of MR flow reserve in normal and diseased coronary grafts revealed significant differences (3.3 +/- 0.4 vs. 1.3 +/- 0.2).

Blood Flow Velocity↗