Publications by authors named "Hans Günther Wahl"

12 Publications

  • Page 1 of 1

Determination of red blood cell fatty acid profiles: Rapid and high-confident analysis by chemical ionization-gas chromatography-tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2017 Jan 13;1040:1-7. Epub 2016 Nov 13.

Institute of Laboratory Medicine and Pathobiochemistry, Philipps-University Marburg, Germany. Electronic address:

Cellular fatty acid (FA) profiles have been acknowledged as biomarkers in various human diseases. Nevertheless, common FA analysis by gas chromatography mass spectrometry (GC-MS) requires long analysis time. Hence, there is a need for feasible methods for high throughput analysis in clinical studies. FA was extracted from red blood cells (RBC) and derivatized to fatty acid methyl esters (FAME). A method using gas chromatography tandem mass spectrometry (GC-MS/MS) with ammonia-induced chemical ionization (CI) was developed for the analysis of FA profiles in human RBC. We compared this method with classical single GC-MS using electron impact ionization (EI). The FA profiles of 703 RBC samples were determined by GC-MS/MS. In contrast to EI ammonia-induced CI resulted in adequate amounts of molecular ions for further fragmentation of FAME. Specific fragments for confident quantification and fragmentation were determined for 45 FA. The GC-MS/MS method has a total run time of 9min compared to typical analysis times of up to 60min in conventional GC-MS. Intra and inter assay variations were <10% for all FA analyzed. Analysis of RBC FA composition revealed an age-dependent increase of the omega-3 eicosapentaenoic and docosahexaenoic acid, and a decline of the omega-6 linoleic acid with a corresponding rise of the omega-3 index. The combination of ammonia-induced CI and tandem mass spectrometry after GC separation allows for high-throughput, robust and confident analysis of FA profiles in the clinical laboratory.
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http://dx.doi.org/10.1016/j.jchromb.2016.11.019DOI Listing
January 2017

Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment.

Clin Endocrinol (Oxf) 2014 Dec 7;81(6):907-15. Epub 2014 Jul 7.

Department of Nuclear Medicine, Klinikum Luedenscheid, Luedenscheid, Germany.

Objective: We examined the interrelationships of pituitary thyrotropin (TSH) with circulating thyroid hormones to determine whether they were expressed either invariably or conditionally and distinctively related to influences such as levothyroxine (L-T4) treatment.

Design And Methods: This prospective study employing 1912 consecutive patients analyses the interacting equilibria of TSH and free triiodothyronine (FT3) and free thyroxine (FT4) in the circulation.

Results: The complex interrelations between FT3, FT4 and TSH were modulated by age, body mass, thyroid volume, antibody status and L-T4 treatment. By group comparison and confirmation by more individual TSH-related regression, FT3 levels were significantly lower in L-T4-treated vs untreated nonhypothyroid autoimmune thyroiditis (median 4·6 vs 4·9 pm, P < 0·001), despite lower TSH (1·49 vs 2·93 mU/l, P < 0·001) and higher FT4 levels (16·8 vs 13·8 pm, P < 0·001) in the treated group. Compared with disease-free controls, the FT3-TSH relationship was significantly displaced in treated patients with carcinoma, with median TSH of 0·21 vs 1·63 (P < 0·001) at a comparable FT3 of 5·0 pm in the groups. Disparities were reflected by calculated deiodinase activity and remained significant even after accounting for confounding influences in a multivariable model.

Conclusions: TSH, FT4 and FT3 each have their individual, but also interlocking roles to play in defining the overall patterns of thyroidal expression, regulation and metabolic activity. Equilibria typical of the healthy state are not invariant, but profoundly altered, for example, by L-T4 treatment. Consequently, this suggests the revisitation of strategies for treatment optimization.
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http://dx.doi.org/10.1111/cen.12527DOI Listing
December 2014

How accurately do we measure blood glucose levels in intensive care unit (ICU) patients?

Best Pract Res Clin Anaesthesiol 2009 Dec;23(4):387-400

Medizinisches Labor Wahl, Paulmannshöher Str. 14, 58515 Lüdenscheid, Germany.

Hyperglycaemia is commonly found in critically ill patients as a result of numerous processes such as increased gluconeogenesis and glycogenolysis caused by elevated levels of corresponding hormones and insulin resistance. As the clinical consequence of hyperglycaemia has been shown to increase morbidity and mortality in various clinical settings, many hospitals by now use tight glycaemic control protocols for their patients in intensive care units to maintain normoglycaemia. The success of the intensive insulin therapy depends crucially on frequent and accurate blood glucose measurements with immediate feedback of results. Therefore, in almost all cases, this will be done by point-of-care testing methods, raising the question of how accurately blood glucose levels are actually measured and what devices should be used. This review focusses on glucose assay principles, specimen matrices, influences and interferences of glucose measurements and finally looks at the numerous evaluation reports on point-of-care glucose testing devices.
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http://dx.doi.org/10.1016/j.bpa.2009.09.003DOI Listing
December 2009

Biochemical markers of bone turnover in patients with localized and metastasized prostate cancer.

BJU Int 2007 Feb 1;99(2):330-4. Epub 2006 Dec 1.

Department of Urology, Medical School, Philipps University Marburg, Germany.

Objective: To evaluate and compare the value of several markers of bone turnover in different stages of prostate cancer, as bone metastases are a common feature in this disease, and for assessing bone metastases both bone formation and bone resorption markers are diagnostic.

Patients And Methods: The prospective study included 219 men, i.e. 129 undergoing radical retropubic prostatectomy (RRP) and 25 with bone metastases due to prostate cancer, and 65 with benign urological disorders who served as controls. Before any treatment the concentrations of alkaline phosphatase (ALP), osteocalcin, serum C-terminal telopeptide of type I collagen (S-CTX) and tartrate-resistant acid phosphatase type 5b (TRACP5b) were determined.

Results: Men undergoing RRP were divided into those with lymph node-negative, localized (pT3, 101) and lymph node-positive (28) disease, after histological examination. The controls had the lowest marker levels while patients with bone metastases due to prostate cancer had the highest levels, with significance for ALP, osteocalcin and TRACP5b. Patients with lymph node-positive cancer had significantly high serum levels of TRACP5b and ALP but not for osteocalcin and S-CTX.

Conclusions: Bone turnover markers represent a new diagnostic tool in prostate cancer; the present data show that both bone resorption and bone formation are crucial for detecting bone metastases in prostate cancer. The value of bone turnover markers in high-risk patients should be evaluated in a longitudinal study.
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http://dx.doi.org/10.1111/j.1464-410X.2006.06604.xDOI Listing
February 2007

Immunochemical quantification of free light chains in urine.

Clin Chem 2005 Jun;51(6):1033-5

Department of Clinical Chemistry and Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany.

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http://dx.doi.org/10.1373/clinchem.2004.045435DOI Listing
June 2005

Palmitate-induced interleukin-6 expression in human coronary artery endothelial cells.

Diabetes 2004 Dec;53(12):3209-16

Department of Endocrinology, Metabolism and Pathobiochemistry, Medical Clinic, Eberhard-Karls-University, Tübingen, Germany.

Obesity-linked insulin resistance is associated with chronic inflammation and cardiovascular complications. Free fatty acids (FFAs) are prominent candidates for the molecular link between these disorders. In this study, we determined whether FFAs contribute to vascular inflammation via induction of interleukin (IL)-6 in coronary artery endothelial cells (CAECs) and coronary artery smooth muscle cells (CASMCs) and whether this is reflected in vivo. In contrast to our findings regarding IL-6 and gp130 (the glycoprotein of 130 kDa) expression, IL-6 receptor mRNA expression was very low in these cells. Palmitate, but not linoleate, induced a significant increase in IL-6 mRNA expression in CAECs (P < 0.001) and, to a less relevant extent, in CASMCs (P < 0.01). gp130 remained unaffected. As to potency, palmitate was comparable with the IL-6-inducer IL-1beta. To substantiate our in vitro data, we examined the plasma FFA pattern in 54 healthy human subjects and studied the relation of individual FFAs with plasma IL-6. IL-6 levels correlated with palmitate, but not with other abundant FFAs, even after adjusting for body fat (r = 0.33, P < 0.05) and total FFAs (r = 0.29, P < 0.05). We show here that the common plasma FFA palmitate induces high levels of IL-6 in CAECs. Furthermore, palmitate correlates with IL-6 in vivo. This points to a potential contribution of palmitate to vascular inflammation.
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http://dx.doi.org/10.2337/diabetes.53.12.3209DOI Listing
December 2004

Discrimination of Type 2 diabetic patients from healthy controls by using metabonomics method based on their serum fatty acid profiles.

J Chromatogr B Analyt Technol Biomed Life Sci 2004 Dec;813(1-2):53-8

National Chromatographic R. and A. Center, Dalian Institute of Chemical Physics, Chinese Academy of Science, 116011 Dalian, P.R. China.

Metabonomics, the study of metabolites and their roles in various disease states, is a novel methodology arising from the post-genomics era. This methodology has been applied in many fields, including work in cardiovascular research and drug toxicology. In this study, metabonomics method was employed to the diagnosis of Type 2 diabetes mellitus (DM2) based on serum lipid metabolites. The results suggested that serum fatty acid profiles determined by capillary gas chromatography combined with pattern recognition analysis of the data might provide an effective approach to the discrimination of Type 2 diabetic patients from healthy controls. And the applications of pattern recognition methods have improved the sensitivity and specificity greatly.
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http://dx.doi.org/10.1016/j.jchromb.2004.09.023DOI Listing
December 2004

4-Heptanone is a metabolite of the plasticizer di(2-ethylhexyl) phthalate (DEHP) in haemodialysis patients.

Nephrol Dial Transplant 2004 Oct 27;19(10):2576-83. Epub 2004 Jul 27.

Klinikum der Philipps-Universität Marburg, Department of Clinical Chemistry and Molecular Diagnostics, D-35033 Marburg, Germany.

Background: There is an ongoing discussion about the risks of di(2-ethylhexyl) phthalate (DEHP) exposure for the general population as well as for specific subgroups in various medical settings. Haemodialysis patients certainly belong to the group with the highest exposure taking into account the repeated treatments over a long period of time. Many studies have shown that DEHP metabolites are more active with regard to cellular responses than DEHP itself. Although 4-heptanone has been shown to be a DEHP metabolite in rats, this has never been tested in humans. On the other hand, 4-heptanone was reported to be associated with diabetes mellitus.

Methods: After establishing analytical methods for all postulated metabolites, we analysed (i) plasma samples from 50 patients on haemodialysis and 50 controls; (ii) urine samples from 100 diabetic patients and 100 controls; and (iii) urine samples from 10 controls receiving DEHP intravenously.

Results: 4-Heptanone concentrations in urine did not differ between controls (128.6+/-11.4 micro g/l, mean+/- SEM) and diabetic patients (131.2+/-11.6 micro g/l) but were significantly elevated in plasma from haemodialysis patients (95.9+/-9.6 micro g/l) compared with controls (10.4+/-0.5 micro g/l). Exposure to DEHP led to a significant increase (P<0.001) of the metabolite 4-heptanone and all the proposed intermediates in urine of healthy persons within 24 h.

Conclusions: These studies show that 4-heptanone is not associated with diabetes but is a major DEHP metabolite in humans. Studies concerning the toxicity of DEHP in haemodialysis patients and other highly exposed groups should therefore include 4-heptanone together with DEHP and its primary metabolites mono(2-ethylhexyl) phthalate (MEHP) and 2-ethylhexanol.
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http://dx.doi.org/10.1093/ndt/gfh425DOI Listing
October 2004

Elimination of the cardiac natriuretic peptides B-type natriuretic peptide (BNP) and N-terminal proBNP by hemodialysis.

Clin Chem 2004 Jun;50(6):1071-4

Klinikum der Philipps-Universität Marburg, Department of Clinical Chemistry and Molecular Diagnostics, 35033 Marburg, Germany.

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http://dx.doi.org/10.1373/clinchem.2003.030692DOI Listing
June 2004

Reliability of IFCC method for lactate dehydrogenase measurement in lithium-heparin plasma samples.

Clin Chem 2003 Dec;49(12):2094-6

Klinikum der Philipps-Universität Marburg, Department of Clinical Chemistry, 35033 Marburg, Germany.

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http://dx.doi.org/10.1373/clinchem.2003.026336DOI Listing
December 2003

Retraction.

J Lipid Res 2002 Aug;43(8):1348

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August 2002

Troglitazone downregulates delta-6 desaturase gene expression in human skeletal muscle cell cultures.

Diabetes 2002 Apr;51(4):1060-5

Department of Endocrinology and Metabolism, University of Tübingen, Tübingen, Germany.

Delta-6 Desaturase, one of the rate-limiting enzymes, catalyzes the conversion of linoleic acid (C18:2 omega6) into gamma-linolenic acid (C18:3 omega6), arachidonic acid (C20:4 omega6), and further metabolites. Recently, it has been shown that human Delta-6 desaturase is expressed not only in liver but in a variety of human tissues, including muscle. Skeletal muscle is a major site of insulin action, and insulin sensitivity may be related to the fatty acid composition of muscle lipids. We examined the effects of troglitazone on the regulation of Delta-6 desaturase gene expression in human muscle cell cultures obtained from muscle biopsies (n = 15). Delta-6 Desaturase mRNA and peroxisome proliferator-activated receptor gamma2 (PPARgamma2) mRNA were quantified by two-step RT-PCR, and the activity of the Delta-6 desaturase enzyme was estimated by gas chromatographic analysis of the omega 6-C18:3/C18:2 fatty acids ratio. In cells treated with 11.5 micromol troglitazone for 4 days, PPARgamma2 mRNA levels were significantly increased (301.0 +/- 51.5%, P < 0.05) and Delta-6 desaturase mRNA levels were significantly decreased (41.7 +/- 5.9%, P < 0.0005) compared with the untreated controls. In accordance with the decrease of Delta-6 desaturase mRNA, there was a significant decrease in the omega6-C18:3/C18:2 ratio down to 47.4 +/- 7.5% in cholesterol esters, 54.2 +/- 7.4% in phospholipids, 56.7 +/- 6.5% in nonesterified fatty acids, and 67.7 +/- 5.9% in triglycerides. The troglitazone-induced decrease in Delta-6 desaturase mRNA is associated with a change in the unsaturated fatty acid composition of the muscle cells. These results add new aspects to the known thiazolidinedione effects on lipid metabolism.
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http://dx.doi.org/10.2337/diabetes.51.4.1060DOI Listing
April 2002