Search PubMed⌕ Search

Biomedical subjects

S Petersen

Publications and source records attributed to S Petersen.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

[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↗

Overexpression of c-erbB2 protein correlates with disease-stage and chromosomal gain at the c-erbB2 locus in non-small cell lung cancer.

Overexpression of the c-erbB2 protein is observed in a variety of malignancies including non-small cell lung cancer (NSCLC). We aimed to determine the rate of c-erbB2-overexpression in our tumour collection and to clarify its correlation with the chromosomal status at the c-erbB2 locus 17q21 in NSCLC. Eighty-nine NSCLC were analysed immunohistochemically using a polyclonal c-erbB2 antibody (DAKO). The staining was scored according to the guidelines of the Clinical Trial Assay recommendations (0-3+). Of these, 44 cases were also analysed by comparative genomic hybridisation (CGH). Overexpression was observed in 37% of the cases (score>1) which was associated with higher disease stages and a positive nodal status in adenocarcinomas. Chromosomal gains at 17q21 were clearly correlated with overexpression of the gene (P=0.009). In addition, there was a highly significant correlation between the c-erbB2 expression comparing the whole section immunostaining analysis and a 127 lung tumour tissue array which included 74 of the 89 cases that were analysed by the classical procedure. We conclude that c-erbB2 is a marker of tumour progression in NSCLC which can be observed on protein level and reflects chromosomal alterations at 17q21.

Adult↗

Predictors of homicidal ideation and intent in schizophrenia: an empirical study.

Correlations of age, gender, and psychosocial variables with ratings of current homicidal ideation and intent were investigated among psychiatric facility clients with schizophrenia. Multiple regression analyses revealed, irrespective of age or gender, significantly positive correlations of three psychosocial variables--manic symptoms, psychotic symptoms, and impaired global functioning--with homicidal ideation and intent. Implications for research are discussed.

Adolescent↗

[Perfusion MR imaging of the heart with TrueFISP].

OBJECTIVE: Development and test of a saturation-recovery TrueFISP (SR-Trufi) pulse sequence for myocardial perfusion MR imaging (MRI) using improved gradient hardware. MATERIAL AND METHODS: Measurements were performed on a 1.5 T scanner with prototype gradients (50 mT/m, minimum rise time 300 microseconds). T1-weighted first-pass MRI of Gd-DTPA (0.025 mumol/kg) kinetics in the myocardium was performed using an SR-Trufi pulse sequence (TR/TE/alpha = 2.6 ms/1.4 ms/55 degrees) with a saturation preparation of TD = 30 ms before the TrueFISP readout. Measurements were performed in volunteers (n = 4) and in a pig model of chronic ischemia (n = 1). RESULTS: In phantoms, the signal intensity was linear with contrast concentration up to 0.9 mmol/kg Gd-DTPA. MR images obtained with SR-Trufi had a good image quality and high spatial resolution of 2.1 mm x 2.1 mm. Differences of the contrast agent's kinetics between a subendocardial perfusion deficit and neighboring myocardium were well visible on both MR images and signal-time curves derived from the region-of-interest analysis. CONCLUSION: SR-Trufi appears to be an interesting new technique for the assessment of myocardial microcirculation using dedicated cardiovascular MR systems.

Adult↗

[Management of hemorrhage and perforation following endoscopic sphincterotomy].

Bleeding and perforation are rare but dangerous complications of diagnostic and therapeutic ERCP and endoscopic sphincterotomy (EST). To evaluate the clinical outcome of patients treated for complicated EST in our surgical department, data were collected prospectively between 1/1995 and 3/2000. A total of 9 patients were admitted to our department, 7 women and 2 men, average age 60 (range 41-72) years. 5 patients were treated for severe hemorrhage, all of them underwent laparotomy following duodenotomy and oversewing of the sphincterotomy site. In average 10 hours (range 4-20) after endoscopy. One of these patients died due to multiple organ failure. In 4 additional patients a retroperitoneal perforation was discovered, 2 of these patients underwent laparotomy and drainage of the retroperitoneal cavity. The other two patients were sufficiently treated by percutaneous drainage. One of the patients, who underwent surgical drainage for retroperitoneal perforation died. In conclusion for severe hemorrhage duodenotomy and oversewing of the bleeding site is recommended in combination with common bile duct T-drain or other draining procedures. The treatment for perforation should depend on the clinical finding. A laparotomy seems not always to be necessary.

Adult↗

Deep prosthesis infection in incisional hernia repair: predictive factors and clinical outcome.

OBJECTIVE: To evaluate the incidence of prosthetic infection in incisional hernia repairs, to determine whether there are any factors associated with prosthetic infection and to describe the clinical outcome. DESIGN: Retrospective clinical study. SETTING: Teaching hospital, Germany. SUBJECTS: 121 consecutive patients who underwent incisional hernia repair in our department from December 1994 to December 1999. INTERVENTION: Hernia repair by implantation of an alloplastic prosthesis by the Stoppa-Rives technique. MAIN OUTCOME MEASURES: Postoperative deep prosthetic infection and associated factors. RESULTS: All 121 patients had the mesh implanted in the subfascial plane, 77 had a polypropylene mesh (Prolene) (64%), 7 had a polyester mesh (Mersilene) (6%), and 37 patients had a expanded polytetrafluoroethylene patch (ePTFE, Gore-Tex) (31%). Postoperatively the mesh became infected in 8 patients (7%), a mean of 4.5 months (range 0.5-16) after hernia repair. All three infected ePTFE patches had to be removed whereas drainage was sufficient treatment for the infected polypropylene and polyester meshes. CONCLUSION: Once a mesh infection is verified adequate drainage seems to be sufficient for polypropylene and polyester meshes but ePTFE patches should be removed.

Aged↗

Self-regulation predictors of medication adherence among ethnically different pediatric patients with renal transplants.

OBJECTIVE: To predict medication adherence among ethnically different pediatric patients with renal transplants between the ages of 6 and 20 years old, using self-regulation variables including motivation, perceived control and responsibility, and perceived support. METHODS: Twenty-six African American children and 42 Caucasian children were verbally administered the Self-Regulation of Medication Adherence Battery to assess their (1) motivation to be medication adherent, (2) perceived control of and responsibility for medication adherence, and (3) perceived support of medication adherence from their primary caregiver. Four measures were used to assess medication adherence: self-ratings, nephrologists' ratings, cyclosporine levels, and pill count/refill histories. RESULTS: For the African American patients, regression analyses revealed that responses to motivation and perceived control questions that focused on self-efficacy were unique predictors of medication adherence as rated by their primary nephrologist. For the Caucasian patients, one motivation question regarding how often they forget to take their medication predicted their self-reported adherence. CONCLUSIONS: Facilitating their beliefs that they can regularly take their medications may help promote medication adherence among African American children with renal transplants, whereas for Caucasian children, providing cues and reminders to take their medications may help. We discuss implications of the results for multimodal assessment of medication adherence and for ethnic group-specific medication adherence research and interventions.

Adolescent↗

Towards a genetic-based classification of human lung cancer.

Lung cancer is a highly aggressive neoplasm which is reflected by a multitude of genetic aberrations being detectable on the chromosomal and molecular level. In order to understand this seemingly genetic chaos, we performed Comparative Genomic Hybridisation (CGH) in a large collective of human lung carcinomas investigating different tumor entities as well as multiple individual tumour specimens of single patients. Despite the considerable genetic instability being reflected by the well known morphological heterogeneity of lung cancer the comparison of different tumour groups using custom made computer software revealed recurrent aberration patterns and highlighted chromosomal imbalances that were significantly associated with morphological histotypes and biological phenotypes. Specifically we identified imbalances in NSCLC being associated with metastasis formation which are typically present in SCLC thus explaining why the latter is such an aggressive neoplasm characterized by widespread tumor dissemination. Based on the genetic data a new model for the development of SCLC is presented. It suggests that SCLC evolving from the same stem cell as NSCLC should be differentiated into primary and secondary tumors. Primary SCLC corresponding to the classical type evolved directly from an epithelial precursor cell. In contrast, secondary SCLC correlating with the combined SCLC develops via an NSCLC intermediate. In addition, we established libraries of differentially expressed genes from different human lung cancer types to identify new candidate genes for several of the chromosomal subregions identified by CGH. In this review, we summarise the status of our results aiming at a refined classification of lung cancer based on the pattern of genetic aberrations.

Carcinoma, Non-Small-Cell Lung↗

Physical illness: social construction or biological imperative?

All cultures have metaphors for mental illness that define how it is diagnosed, treated, and experienced by the patient. Cultural metaphors that define mental illness have been traced predominantly to biomedical and systems models. However, the research on factors such as progression of illness, survival rates, adherence to medical regimens, level of disability, and experience of pain in chronic and acute life-threatening illnesses suggests another metaphor. This article not only explores how a constructivist metaphor makes sense of this research, but also suggests an approach to consider in helping patients and their families deal with the difficult life circumstances that illness imposes. Implications for nurses are outlined.

Culture↗