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Biomedical subjects

Frank Stüber

Publications and source records attributed to Frank Stüber.

14 recordsLinked to original sources
PubMed2006

Integrated catalytic wet air oxidation and aerobic biological treatment in a municipal WWTP of a high-strength o-cresol wastewater.

This study examines the feasibility of coupling a Catalytic Wet Air Oxidation (CWAO), with activated carbon (AC) as catalyst, and an aerobic biological treatment to treat a high-strength o-cresol wastewater. Two goals are pursued: (a) To determine the effect of the main AC/CWAO intermediates on the activated sludge of a municipal WasteWater Treatment Plant (WWTP) and (b) To demonstrate the feasibility of coupling the AC/CWAO effluent as a part of the influent of a municipal WWTP. In a previous study, a high-strength o-cresol wastewater was treated by AC/CWAO aiming to establish the distribution of intermediates and the biodegradability enhancement. In this work, the biodegradability, toxicity and inhibition of the most relevant intermediates detected in the AC/CWAO effluent were determined by respirometry. Also, the results of a pilot scale municipal WWTP study for an integrated AC/CWAO-aerobic biological treatment of this effluent are presented. The biodegradation parameters (i.e. maximum oxygen uptake rate and oxygen consumption) of main AC/CWAO intermediates allowed the classification of the intermediates into readily biodegradable, inert or toxic/inhibitory compounds. This detailed study, allowed to understand the biodegradability enhancement exhibited by an AC/CWAO effluent and to achieve a successful strategy for coupling the AC/CWAO step with an aerobic biological treatment for a high-strength o-cresol wastewater. Using 30%, as COD, of AC/CWAO effluent in the inlet to the pilot scale WWTP, the integrated AC/CWAO-biological treatment achieved a 98% of total COD removal and, particularly, a 91% of AC/CWAO effluent COD removal without any undesirable effect on the biomass.

Bacteria, Aerobic↗
PubMed2006

Genomic variations and transcriptional regulation of the human mu-opioid receptor gene.

The mu-opioid receptor (MOR1) is a target of endogenous and exogenous opioids and plays a pivotal role for anesthesia and analgesia. Variations in the 5' flanking sequence of the mu-opioid receptor gene may influence transcriptional regulation and ultimately alter protein expression of MOR1. In the present study we investigated the influence of eight single nucleotide polymorphisms (SNP) within the mu-opioid receptor promoter on promoter activity and evaluated the frequencies of the relevant SNPs in 700 patients under opioid medication. Reporter-gene-constructs were created by means of PCR and site directed mutagenesis, testing eight SNPs previously described. The neuroblastoma cell line SHSY5Y was used for transfection and promoter activity was estimated by luciferase activity. Of the eight reporter gene constructs employed to test genomic variations, two produced a significant change in luciferase activity when compared to wild-type constructs. The G-554A variation located within a known NFkB binding element resulted in a decreased activity whereas the A/G base exchange at position -1320 showed an increased luciferase activity. This particular variant generated a myeloid zinc finger (MZF1) cis-acting element known to impact transcription. The allele frequency of the -1320G variant was 0.21% in 700 Caucasian patients under opioid medication in contrast to 9.1% reported previously in drug addicted African Americans. Because of this unexpected low frequency an association analysis to opioid requirements and effects of mu-opioid receptor agonists was not feasible. In conclusion, transcriptional regulation of MOR1 is modified by two genetic variations at positions -554 and -1320 of the mu-opioid receptor promoter. Individuals presenting these variations may have an altered level of MOR expression. A possible association of these genomic variants on efficacy and side effects of opioid treatment in different ethnic groups has to be elucidated.

5' Flanking Region↗
PubMed2006

A single nucleotide polymorphism of macrophage migration inhibitory factor is related to inflammatory response in coronary bypass surgery using cardiopulmonary bypass.

OBJECTIVE: Cardiac surgery causes induction and release of inflammatory mediators that may be regulated by genetic background. Macrophage migration inhibitory factor (MIF) is a proinflammatory mediator that is known to be up-regulated in patients undergoing cardiac operations. Here we analyzed genotype distribution and allele frequency of the MIF-173*G/C single nucleotide polymorphism (SNP) and MIF plasma levels in patients undergoing surgical revascularization with (on-pump, n=45) and without (off-pump, n=34) cardiopulmonary bypass (CPB). METHODS: Genotyping was performed using a real-time PCR-based system with a hybridization probe system specific for the MIF-173*G/C SNP. In on-pump patients, blood samples were drawn before start of CPB, after termination of CPB and 12h postoperatively. In off-pump patients, blood samples were collected before stabilizer placement, after removal of the stabilizer and 12h postoperatively. MIF levels were measured using ELISA technique. RESULTS: Genotype distribution and allele frequencies were comparable between on-pump and off-pump patients. When comparing patients according to MIF genotype, a significant increase of MIF plasma levels after completed coronary bypass grafting using CPB was found in patients heterozygous for the MIF-173*G/C SNP (p<0.05). Moreover, on-pump patients showed significantly decreased MIF plasma levels after 12h postoperatively (p<0.05). In off-pump patients, MIF plasma levels were not significantly different over the time-course and were independent of the genotype. CONCLUSIONS: Patients carrying the C-allele showed significantly increased levels of the proinflammatory cytokine MIF compared to G/G homozygous when revascularization was carried out using CPB. The G/C genotype may be associated with a severe inflammatory reaction and therefore preoperative screening could be beneficial for patients undergoing cardiac surgery using CPB.

Adult↗
PubMed2005

Intracellular detection of macrophage migration inhibitory factor in peripheral blood leukocytes.

The oxidoreductase MIF is currently discussed as a new promising target of immunomodulatory therapy in patients with severe sepsis. An increasing body of evidence attributes an important role especially to intracellular MIF for regulation of endotoxin responsiveness as well as regulation of nuclear transcription factors. Up to now, measurement of MIF relied on ELISA techniques, lacking the ability to directly measure intracellular MIF and distinguish between different leukocyte subpopulations. Therefore, we developed a sensitive and robust flow cytometry-based method to reliably detect intracellular levels of MIF. This method can readily be applied in cultured cells as well as in subsets of human leukocytes in whole blood. Intracellular MIF content of whole-blood leukocyte subsets is detected simultaneously, and is individually determined for T-lymphocytes, B-lymphocytes, macrophages, and granulocytes, respectively. When tested in an ex vivo whole-blood stimulation system using PMA/Ionomycin the intracellular MIF content doubled in CD3+ T-lymphocytes and increased threefold in CD14+ macrophages. Baseline intracellular MIF levels of different leukocyte subpopulations were quantified in 22 healthy blood donors. Baseline intracellular MIF levels in T-lymphocytes are twice as high compared to those in B-lymphocytes and macrophages.

Enzyme-Linked Immunosorbent Assay↗
PubMed2005

Genetics and variability in opioid response.

The human genome project has revealed data on genomic variation which may influence the pharmacological responses. In pain therapy, the genetic background influencing the efficacy of opioid therapy is of special interest. Screening for variations in expression of drug metabolizing enzymes has been suggested as a potential tool for improving patient therapy. CYP2D6 genetic variability is supposed to be a major factor of adverse drug reaction, possibly influencing hospital stay and total costs. Further candidate genes involved in pain perception, pain processing and pain management like opioid receptors, transporters and other targets of pharmacotherapy are under investigation. Aspects of genetic differences influencing efficacy, side effects and adverse outcome of pharmacotherapy will be of importance for future pain management.

Analgesics, Opioid↗
PubMed2003

A tumor necrosis factor gene polymorphism influences the inflammatory response after cardiac operation.

BACKGROUND: The genetic background may influence cytokine release evoked by cardiac operation. Thus we determined the allele frequency and genotype distribution of a bi-allelic tumor necrosis factor (TNF) gene polymorphism and TNF-alpha concentrations in patients undergoing cardiac operations with and without cardiopulmonary bypass (CPB). METHODS: The TNF NcoI gene polymorphism was identified by polymerase chain reaction followed by restriction analysis of the polymerase chain reaction product. Reading the size of the resulting DNA bands from the agarose gel defined the genotype as homozygous or heterozygous for the two alleles TNFB1 and TNFB2. Blood samples to determine TNF-alpha plasma levels were drawn from the patients before induction of general anesthesia after termination of CPB or after finishing coronary revascularization on the beating heart in non-CPB patients and 12 hours postoperatively. RESULTS: The genotype distribution and allele frequencies in 47 patients undergoing cardiac operation with CPB were comparable with those found in 36 patients undergoing cardiac operation without CPB. The TNF-alpha plasma levels over time were comparable in patients with and without CPB. However, patients homozygous for the TNF-B2 allele had significantly higher TNF-alpha plasma levels after termination of the CPB (40.2 +/- 3.5 pg/mL; mean +/- standard error of the mean; n = 28) compared with non-CPB patients (29.8 +/- 2.5 pg/mL; mean +/- standard error of the mean; n = 15) (p < 0.05). CONCLUSIONS: Patients homozygous for the TNF-B2 allele showed significantly higher TNF-alpha plasma levels after termination of CPB compared with non-CPB patients. Therefore preoperative TNF genotyping may be useful as patients with genetically determined increased proinflammatory cytokine expression with multiple comorbidities may in particular benefit from avoiding the use of CPB.

Adult↗
PubMed2002

The influence of genomics on outcome after cardiovascular surgery.

Recent findings in molecular research suggest that the outcome of cardiovascular surgery is at least partly determined by the individual patient's genetic predisposition to react to surgical trauma and extracorporal circulation. The activation of cellular as well as humoral cascades occurs in the perioperative period, and influences the extent of pro- and anticoagulation and pro- and anti-inflammation. These events contribute to the incidence and severity of perioperative ischaemia or organ dysfunction, and thus determine adverse outcomes in patients undergoing cardiac surgery. Candidate genes that are possibly involved in the development of adverse outcomes not only consist of genes relevant to the field of coagulation and inflammation, but also genes functioning in lipid metabolism, ion channels, membrane integrity and others. Genomic variations may prove to serve as future diagnostic tools for the risk stratification of patients undergoing cardiovascular surgery.

Journal Article↗
PubMed2002

Anaesthesia for non-scheduled caesarean delivery.

In many countries there has been an increase in the number of women who deliver by caesarean section. This article reviews anaesthetic management of non-scheduled caesarean section. The choice of anaesthetic technique (regional anaesthesia versus general anaesthesia) is discussed and highlighted particularly from the viewpoint of urgency of operative delivery. A multidisciplinary approach is mandatory especially in emergency cases to prevent morbidity and mortality in mothers and neonates.

Journal Article↗
PubMed2002

Rapid and reliable method for cytochrome P450 2D6 genotyping.

BACKGROUND: Single-nucleotide polymorphisms and single-base deletions within the cytochrome P450 2D6 (CYP2D6) gene have been associated with a poor metabolizer (PM) phenotype and display a frequency of 7-10% in the Caucasian population. METHODS: We developed a reliable and rapid procedure to identify five major PM-associated mutations (CYP2D6*4, *7, and *8) and deletions (CYP2D6*3 and *6) by real-time PCR with subsequent fluorometric melting point analysis of the PCR product. These polymorphisms within the CYP2D6 gene were detected by use of two primer pairs and five different pairs of hybridization probes. DNA extracted from whole blood of 323 individuals was analyzed, and results were compared with genotypes obtained by allele-specific multiplex PCR. In case of uncertain results, additional sequence analysis was performed. RESULTS: Genotyping results by real-time PCR were 100% reliable, whereas conventional allele-specific multiplex PCR produced uncertain results for 12.1% of samples, as confirmed by sequence analysis. Costs for reagents and consumables were considerably higher for the real-time PCR technology, but labor time was reduced by 2 h compared with allele-specific PCR. The allele frequencies in the population investigated were 0.186 for allele *4, 0.026 for allele *5, 0.009 for allele *3, 0.031 for allele *6, and 0.002 for allele *8. The defective CYP2D6*7 allele was not found. In addition, three additional mutations were detected, one of them displaying a PM genotype. CONCLUSION: Genotyping of CYP2D6 by real-time PCR with fluorometric melting point analysis is a rapid and reliable method.

Cytochrome P-450 CYP2D6↗
PubMedDate not supplied

TNF-alpha promoter polymorphism in relation to TNF-alpha production and clinical status in cystic fibrosis.

The severity of lung disease in cystic fibrosis may be related to the genetic propensity of the host to produce tumor necrosis fector alpha (TNF-alpha). A polymorphism in the promoter region of the TNF-alpha gene at nucleotide 308 relative to the transcription start site may be important in determing the host's TNF-alpha response. The aim of this study was to assess the correlation between a TNF-308 promoter polymorphism, ex vivo TNF-alpha production (before and after lipopolysaccharide (LPS) stimulation), and clinical status [FEV1, weight (z-score), BMI, Shwachman score, incidence of diabetes mellitus, and Pseudomonas aeruginosa infection). Genotyping for the biallelic TNF-308 polymorphism was performed by using a real-time PCR cycler. Patients (homozygous for Delta F 508) were grouped according to genotype (TNF2 carriers, n = 16, median age = 15 yr, female/male = 5/11; TNF1 homozygotes, n = 37, median age = 21 yr, female/male = 18/19). TNF-alpha was measured using a chemiluminescent immunometric assay. There was a trend toward higher TNF-alpha values [median TNF2 carriers vs. TNF1 homozygotes: x = 56 vs. 43.5 pg/ml, n.s. (Mann-Whitney U-test] in those carrying the polymorphism and better lung function results [FEV(1) (%) 81 vs. 65, n.s.]. These differences equalized [TNF2 carriers vs. TNF1 56 vs. 51 pg/ml, n.s.; FEV1 (%) 84 vs. 79, n.s.] after age adjustment (+/- 2 yr, n = 15, median age TNF2 vs. TNF1-17/18 yr). There were no significant differences for TNF values after LPS stimulation and the incidence of diabetes mellitus. The TNF-308 promoter polymorphism does not seem to influence TNF-alpha release in whole blood cells and clinical status.

Adolescent↗
PubMedDate not supplied

A survey of acute pain services in Germany and a discussion of international survey data.

BACKGROUND AND OBJECTIVES: Acute pain services (APS) have been introduced worldwide to improve postoperative pain management. However, data are lacking on organization and quality of these services in Germany. METHODS: A questionnaire on postoperative pain management was mailed to 773 departments of anesthesiology. Practice was compared between hospitals with and without APS and between services that did or did not meet basic quality criteria (QC): personnel assigned for APS, policies during nights and weekends, written protocols of pain management, and regular assessment and documentation of pain scores at least once a day. RESULTS: With 446 responding hospitals, 161 operated an APS. Large hospitals organized an APS more frequently than smaller hospitals (P <.001). Staff being assigned for the APS comprised anesthesiologists in 68.3% and nurses in 23.6% of the departments. In total, only half of the APS complied with basic QC. Regular assessment and documentation of pain scores were the QC most often missing (46.6%). Patient-controlled analgesia (PCA) was performed in 93.8%, 74.1%, and 69.8% of the departments providing APS with QC, APS without QC, and no APS. Epidural analgesia (EA) was available in nearly all departments (96.9%). A total of 75.6% of the departments performed EA on general wards (with QC: 93.8%, without QC: 82.7%, and no APS: 68.4%, P <.001). Frequency of PCA and EA use was highest in hospitals providing an APS with QC. CONCLUSIONS: As 50% of German APS do not comply with QC, we believe structured policies, as well as quality assurance measures, should be emphasized in the future. A comparison to international survey data showed that APS, in general, often do not consider QC.

Analgesia, Epidural↗