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Biomedical subjects

Michael Vogeser

Publications and source records attributed to Michael Vogeser.

33 records · Page 2Linked to original sources
PubMed2004

Brain natriuretic peptide and exercise capacity in lung fibrosis and pulmonary hypertension.

Pulmonary hypertension (PH) can develop in lung fibrosis, and contributes to increased morbidity and mortality. Noninvasive parameters in the evaluation of PH in lung disease could aid in the management of these subjects. In this study, we aimed to characterize the role of brain natriuretic peptide (BNP) and the six-minute walk distance (6-MWD) in the assessment of pulmonary hypertension (PH) in subjects with lung fibrosis. Subjects with lung fibrosis and elevated BNP levels (n = 20) had significantly more severe PH during right heart catheterization than those with lung fibrosis, and normal BNP levels (mean pulmonary arterial pressure (40.85 +/- 3.2 mm Hg vs. 23.42+/-1.44 mm Hg, respectively) (n = 19) (p < 0.001). Significant correlations between lung volumes and BNP concentrations were not observed. A weak correlation existed between capillary pO(2) and 6-MWD (r = 0.42; p < 0.001). The presence of moderate-severe PH was associated with significant reduction of the 6-MWD. BNP concentrations predicted moderate-severe PH with 100% sensitivity and high specificity (89%). We conclude that BNP is an excellent marker for the presence of PH in patients with lung fibrosis. In addition, our data suggest that PH contributes significantly to exercise limitation in patients with severe lung fibrosis, raising the possibility that treatment of PH may be beneficial in these patients.

Biomarkers↗
PubMed2004

Clinical significance of brain natriuretic peptide in primary pulmonary hypertension.

OBJECTIVES: The aim of this study was to investigate the potential role of brain natriuretic peptide (BNP) levels in the assessment of functional status and right heart performance in primary pulmonary hypertension (PPH). BACKGROUND: Primary pulmonary hypertension is a progressive disease leading to right heart failure and death. Right heart catheterization and maximal or submaximal exercise tests are employed to assess the course of the disease and the effect of therapeutic interventions. Additional noninvasive and reproducible parameters would be helpful to assess the status of patients with PPH. The natriuretic peptide system is up-regulated in PPH patients. Brain natriuretic peptide (BNP) is produced from the cardiac ventricles and elevated in PPH. The aim of our study was to evaluate the clinical significance of BNP in PPH patients. METHODS: Correlation analysis was performed for plasma BNP levels of 28 PPH patients and World Health Organization (WHO) functional class (WHO-class), distance walked in 6 min, peak oxygen uptake (peak Vo(2)), and oxygen pulse during spiroergometry and various hemodynamic parameters, including pulmonary vascular resistance (PVR), pulmonary artery pressure (PAP), right atrial pressure (RAP), and cardiac index. RESULTS: The BNP levels were inversely correlated with the 6-min walk (r = -0.70; p < 0.001) and peak Vo(2) (r = -0.61; p < 0.01), and positive correlation was observed with WHO-class (r = 0.79; p < 0.001). Moreover, BNP levels were also correlated to PVR (r = 0.61; p < 0.01), PAP (r = 0.48; p < 0.05), and RAP (r = 0.78; p < 0.01), and were inversely related to cardiac index (r = -0.48; p < 0.05). CONCLUSIONS: Our data suggest that plasma BNP levels are closely related to the functional impairment of PPH patients and parallel the extent of pulmonary hemodynamic changes and right heart failure. Serial measurements of plasma BNP concentrations may help improve the management of PPH patients.

Exercise Test↗
PubMed2004

Mycophenolate mofetil and sirolimus as calcineurin inhibitor-free immunosuppression for late cardiac-transplant recipients with chronic renal failure.

BACKGROUND: Calcineurin-inhibitor (CNI)-related renal failure is a common problem after cardiac transplantation (HTx). The aim of this study was to introduce a CNI-free immunosuppressive regimen to HTx recipients with late posttransplant renal impairment and to evaluate the impact of conversion to this new immunosuppression (mycophenolate mofetil [MMF] and sirolimus [Sir]) treatment on renal function. METHODS AND RESULTS: Thirty-one HTx patients (25 men, 6 women; 0.2-14.2 years after transplantation) with CNI-based immunosuppression and a serum creatinine greater than 1.9 mg/dL were included in the study. Creatinine and cystatin levels were monitored to detect renal function. Mean patient age was 50+/-14 (range 19-74) years. Conversion was started with 6 mg Sir, continued with 2 mg, and the dose was adjusted to achieve target trough levels between 8 and 14 ng/mL. MMF was continued with trough level adjusted (1.5-4 microg/mL). Subsequently, the CNIs were tapered down and stopped. Clinical follow-up (first and every 3 months after conversion) included endomyocardial biopsies, echocardiography, and laboratory studies. Survival was 90% after a mean follow-up of 13+/-95 months. No acute rejection episode was detected during the study period. Renal function improved significantly after conversion: creatinine preconversion vs. postconversion: 3.14+/-0.76 mg/dL vs. 2.14+/-0.83 mg/dL, P =0.001. Cystatin preconversion vs. postconversion: 2.95+/-1.06 mg/L vs. 2.02+/-1.1 mg/L, P =0.01. In three patients, hemodialysis therapy was stopped completely after conversion. Graft function remained stable. Fractional shortening preconversion vs. postconversion: 36.9+/-6% vs. 36.4+/-6%. There were no serious adverse events. One patient had to be excluded because of noncompliance. CONCLUSIONS: Conversion from CNI-based immunosuppression to MMF and Sir in HTx patients with chronic renal failure was safe, preserved graft function, and improved renal function.

Adult↗
PubMed2004

Airway anastomosis complications in de novo lung transplantation with sirolimus-based immunosuppression.

A prospective, pilot trial was started to evaluate the effect of a sirolimus-based immunosuppressive regimen on acute and chronic rejection in de novo lung transplant patients. Primary lung transplant (LTx) recipients received a sirolimus- and tacrolimus-based immunosuppressive therapy immediately after transplantation. Both immunosuppressants were administered with trough level adjusted, while steroid administration was minimized. Four patients were enrolled (2 single-lung transplants, 1 double-lung transplant, 1 heart-lung transplant) in the study. Mean ischemia time was 387 +/- 92 minutes. Acute rejection (at least Grade A1 ISHLT) was detected in 1 patient. Incidence of infection was 0.6 infection per 100 patient-days (3 Aspergillus infections). Until hospital discharge mean sirolimus trough level was 6.2 +/- 1.2 ng/ml. Depending upon mean sirolimus trough levels of each patient, severe wound-healing complications were seen in 3 patients, resulting in bronchial airway dehiscence in 2 patients with lethal outcome in 1 patient. As a result of these complications, we revised the study design after inclusion of only 4 patients: Sirolimus administration is now started after completion of bronchial wound-healing. Sirolimus-based immunosuppressive therapy administered immediately after lung transplantation seems to be associated with severe wound-healing complications of the bronchial anastomosis.

Adrenal Cortex Hormones↗
PubMed2004

Sirolimus impairs gonadal function in heart transplant recipients.

The impact of sirolimus on hormone levels involved in the hypothalamus-pituitary-gonad axis in male heart transplant recipients was investigated. A pair-matched analysis with 132 male heart transplant recipients on either sirolimus based- or calcineurin inhibitor-based immunosuppression was performed. Matching criteria were age, years after transplantation and creatinine levels. Measured parameters were testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), sexual hormone-binding globulin (SHBG) and free androgen index (FAI). Mean testosterone was 3.86 +/- 1.41 ng/mL in the sirolimus group and 4.55 +/- 1.94 ng/mL in the controls (p = 0.025). Serum LH was 12.82 +/- 11.19 mlU/mL in the sirolimus patients and 6.2 +/- 5.25 mlU/mL in the controls (p = 0.015). Follicle stimulating hormone levels were 13.31 +/- 18.4 mlU/mL vs. 7.32 +/- 5.53 mlU/mL, respectively (p = 0.015). The analysis revealed a significant decrease in testosterone and a significant increase in FSH and LH in the sirolimus group. The duration of sirolimus treatment correlated positively with SHBG (p < 0.01), LH (p < 0.05) and FSH (p < 0.05) and negative with the FAI (p < 0.05). Sirolimus trough levels correlated with LH and FSH levels (p < 0.01). Heart transplant recipients treated with sirolimus revealed significantly lower testosterone levels and a significant increase in gonadotropic hormones. These effects were trough-level dependent. All candidates awaiting organ transplantation should be informed about these adverse effects.

Adolescent↗
PubMed2003

Liquid chromatography-tandem mass spectrometry--application in the clinical laboratory.

This review provides a concise survey of liquid chromatography-tandem mass spectrometry (LC-TMS) as an emerging technology in clinical chemistry. The combination of two mass spectrometers with an interposed collision cell characterizes LC-TMS as an analytical technology on its own and not just as a more specific detector for HPLC compared with conventional techniques. In LC-TMS, liquid chromatography is rather used for sample preparation but not for complete resolution of compounds of interest. The instrument technology of LC-TMS is complex and comparatively expensive; however, in routine use, methods are far more rugged compared to conventional chromatographic techniques and enable high-throughput analyses with very limited manual handling steps. Moreover, compared to both gas chromatography-mass spectrometry (GC-MS) and conventional HPLC techniques, LC-TMS is substantially more versatile with respect to the spectrum of analyzable compounds. For these reasons it is likely that LC-TMS will gain far more widespread use in the clinical laboratory than HPLC and GC-MS ever did. In this article, the key features of LC-TMS are described, method development is explained, typical fields of application are discussed, and personal experiences are related.

Chemistry, Clinical↗
PubMed2003

Free serum cortisol during the postoperative acute phase response determined by equilibrium dialysis liquid chromatography-tandem mass spectrometry.

In severely ill patients low concentrations of the corticosteroid binding globulin are typically found; the aim of this study was to quantify directly free bioactive cortisol concentrations in the sera of postoperative cardiosurgical patients. Serum samples of 12 consecutive patients undergoing aortocoronary bypass surgery taken preoperatively and on the postoperative days 1 to 4 were analyzed. Total serum cortisol was quantified using liquid chromatography-tandem mass spectrometry with an on-line sample extraction system and tri-deuterated cortisol as the internal standard, and free serum cortisol was measured after over-night equilibrium dialysis. Whereas on the first postoperative day, the median total serum cortisol concentration was approximately two-fold increased compared to preoperative samples (preoperatively, 245 nmol/l (interquartile range (IQR) 203-293 nmol/l); first postoperative day, 512 nmol/l (IQR 410-611 nmol/l)), median dialyzable free cortisol concentration was almost seven-fold increased (preoperatively, 14.2 nmol/l (IOR 10.9-20.7 nmol/l); first postoperative day, 98.3 nmol/l (IQR 81.3-134 nmol/l)). On the fourth postoperative day, median free cortisol was still significantly increased compared to baseline sampling (p < 0.05), whereas median total cortisol was not. A median of 5.7% (IQR 5.4-7.0%) of total cortisol was found as free cortisol on the preoperative day, 21.2% (IQR 18.9-23.5%) on the first postoperative day and 10.5% (IQR 9.8-14.0%) on the fourth postoperative day. It is concluded that during the postoperative period the free-to-bound ratio of cortisol is highly variable and that during the acute phase response direct quantification of free bioactive cortisol concentrations seems to be biologically more appropriate than the measurement of total cortisol concentrations.

Acute-Phase Reaction↗
PubMed2003

Determination of itraconazole and hydroxyitraconazole in plasma by use of liquid chromatography-tandem mass spectrometry with on-line solid-phase extraction.

In this paper a method for the simultaneous quantification of the anti-fungal drug itraconazole and its co-active metabolite hydroxyitraconazole in plasma employing liquid chromatography tandem-mass spectrometry and automated solid-phase extraction is described. The method proved rugged, enables short turn-around times and is highly specific. Since there is growing evidence for the importance of therapeutic drug monitoring of itraconazole in the prophylaxis and treatment of invasive fungal infections, the method described here is of interest for a large number of tertiary care hospital laboratories.

Antifungal Agents↗
PubMed2002

Dialyzable free cortisol after stimulation with Synacthen.

OBJECTIVES: To compare the changes in free vs. total serum cortisol concentrations after acute stimulation of the adrenal cortex. DESIGN AND METHODS: Paired serum samples of ten individuals taken immediately before and 1 h after stimulation with 250 microg ACTH (1-24) (Synacthen) given i.v. were analyzed. Total cortisol was quantified using liquid chromatography tandem-mass spectrometry with an online sample extraction system and tri-deuterated cortisol as the internal standard. Free cortisol was measured with the same method after equilibrium dialysis. Concentrations of the corticosteroid-binding globulin (CBG) were determined by radioimmuno assay. RESULTS: Total cortisol increased by a mean of 106% (mean basal cortisol 312 nmol/L (SD 140 nmol/L), stimulated 686 nmol/L (SD 163 nmol/L); p < 0.001, paired t-test for differences); no significant change of CBG concentrations was found (874 nmol/L (SD 179 nmol/L) before stimulation, 869 nmol/L (SD 225 nmol/L) after stimulation). The mean increase of free cortisol was 263% (mean basal free cortisol 20.3 nmol/L (SD 13.2 nmol/L), stimulated 73.8 nmol/L (SD 26.7 nmol/L); p < 0.001) and thus substantially more pronounced compared to the increase of total cortisol (p < 0.01). The ratio of free to total serum cortisol was significantly increased after stimulation (6.1% (SD 1.7%) before stimulation, 10.6% (SD 1.9%) after stimulation; p < 0.001). CONCLUSIONS: After acute neuroendocrine stimulation of the adrenal cortex the relative increase of free bioactive cortisol concentrations is substantially more pronounced than the increase of total cortisol concentrations.

Adrenal Cortex↗
PubMed2002

Quantification of sirolimus by liquid chromatography-tandem mass spectrometry using on-line solid-phase extraction.

Quantification of the new immunosuppressant sirolimus (syn. rapamycin; Rapamune) in whole blood by chromatography is essential for its clinical use since no immunoassay is available although monitoring is mandatory. Here we report on a rapid and convenient liquid chromatography (LC-tandem mass spectrometry method and describe our practical experience with its routine use. Whole blood samples were hemolyzed and deproteinized using an equal volume (150 microl) of a mixture of methanol/zinc sulfate solution containing the internal standard desmethoxy-rapamycin. After centrifugation, the clear supernatants were submitted to an on-line solid-phase extraction procedure using the polymeric Waters Oasis HLB material, with elution of the extracts onto the analytical column in the back-flush mode by column switching. For analytical chromatography a RP-C18 column was used with 90/10 methanol/2 mM ammonium acetate as the mobile phase. A 1:10 split was used for the transfer to the mass spectrometer, a Micromass Quattro LC-tandem mass spectrometry system equipped with a Z-spray source and used in the positive electrospray ionization mode. The following transitions were recorded: sirolimus, 931>864 m/z, and desmethoxy-rapamycin (I.S.), 901>834 m/z. The analytical running time was 5 min, including on-line extraction. The method has a linear calibration curve (r>0.99; range 1.6-50 microg/l) and is rugged and precise with monthly CVs <7% at a sirolimus concentration of 13.1 microg/l in routine use; the instrumentation proved to be reliable and required minimal maintenance. Clin Chem

Chromatography, Liquid↗
PubMed2002

Serum erythropoietin concentrations in patients with anemia--preliminary hemoglobin-related reference ranges.

Serum erythropoietin (EPO) determination is useful in the diagnosis of renal anemia. In anemic patients with normal renal function increased EPO concentrations are typically found, however, so far hemoglobin-related reference ranges for serum EPO had not been established. In a cross-sectional manner we determined serum EPO in 280 patients with anemia and normal serum concentrations of creatinine and urea. Each 70 consecutive anemic patients with hemoglobin concentrations within four intervals were included (<8 g/dL; 8.1-9.0 g/dL; 9.1-10.0 g/dL; 10.1-11.0 g/dL). 97 patients were from surgical disciplines, 183 were from internal disciplines. Serum EPO was determined by use of an automated sandwich immunoassay that is standardized according to the WHO 2nd IRP 67/343. The ranges between the 20th and 80th percentile of EPO concentrations for the four specified hemoglobin intervals were as follows: Hb <8 g/dL, EPO 61.8-366 IU/L; Hb 8.1-9.0 g/dL, EPO 43.3-242 IU/L; Hb 9.1-10.0 g/dL, EPO 31.8-113 IU/L; Hb 10.1-11.0 g/dL, EPO 22.3-71.2 IU/L. Since no complete diagnostic evaluation of the patients' renal and respiratory functions was performed in this cross-sectional study we propose the 20th percentile of EPO concentrations as a preliminary hemoglobin-related reference range; serum EPO concentrations below this percentile speak for a contribution of EPO deficiency in the individual etiology of anemia.

Adolescent↗
PubMedDate not supplied

The effect of hyperglycemic hyperinsulinemia on small-intestinal mucosal protein synthesis in patients after surgical stress.

Hyperglycemic hyperinsulinemia cannot stimulate intestinal protein synthesis in healthy individuals but does so in conditions characterized by an altered somatotropic axis such as diabetes. Only in a state of growth hormone resistance (high growth hormone but low insulin like growth factor [IGF-1] concentrations), extra insulin may acutely reverse the impaired, growth-hormone-induced IGF-1 release, thereby exerting anabolic actions at the intestinal tract. Growth hormone resistance can be also found in patients after surgical stress. Therefore, we wanted to test the hypothesis whether hyperglycemic hyperinsulinemia would stimulate ileal protein synthesis in the latter condition. Mass spectrometry techniques (capillary gas chromatography/combustion isotope ratio mass spectrometry) were used to directly determine the incorporation rate of 1-[(13)C]-leucine into ileal mucosal protein. All subjects had an ileostomy, which allowed easy access to the ileal mucosa, and consecutive sampling from the same tissue was performed during continuous isotope infusion (0.16 mumol/kg min). Isotopic enrichments and fractional protein synthesis were determined at baseline (period I) and after a 4-hour glucose infusion (170 mg/kg/h) or after infusion of saline (control group) (period II). In controls, ileal protein synthesis declined significantly during prolonged isotope infusion (period I: 1.11 +/- 0.14%/h, period II: 0.39 +/- 0.13%/h, p < .01). In contrast, ileal protein synthesis remained constant during glucose infusion (period I: 1.32 +/- 0.35%/h, period II: 1.33 +/- 0.21%/h, n.s. vs period I, but p < .005 vs the corresponding value at the end of period II in the control group). Using the continuous tracer infusion technique, ileal protein synthesis seemingly declines over a short time in control subjects. We found evidence that this artificial decline was due to mass effects of a rapidly turning over mucosa protein pool in which an isotopic plateau was reached during the experiment and of which the size amounted to approximately 4% of the total mixed protein pool. Maintenance of ileal protein synthesis during glucose infusion therefore indicates a rise of ileal protein synthesis in a slowly turning over protein pool. This effect in postsurgical patients would be compatible with the concept of intestinal insulin action to depend on the specific clinical state (eg, growth hormone resistance).

Aged↗