Search PubMed⌕ Search

Biomedical subjects

S Schaefer

Publications and source records attributed to S Schaefer.

At least 19 recordsLinked to original sources
PubMed2006

Kidney transplantation using elderly non-heart-beating donors: a single-center experience.

Although acceptable outcomes have been reported in both non-heart-beating (NHB) and elderly donors individually, the large pool of elderly NHB donors has not yet been fully utilized. In 1994, we expanded our transplant protocol to include NHB donors aged over 65 years and this study compares the clinical outcomes with regular NHB transplantations. Up to June 2005, 24 patients were transplanted at our center with kidneys from NHB donors aged 65 years or more, whereas 176 patients received grafts from conventional NHB donors during the same period. Grafts from older donors were associated with inferior glomerular filtration rates (29 vs. 44 mL/min after 1 year, p=0.01) and graft survival (52% vs. 68% after 5 years, p=0.19) compared to younger NHB donor grafts, although the difference in graft survival was not statistically significant. Exclusion of older NHB donor kidneys with severe vascular pathology resulted in similar graft survival of older and younger NHB donor kidneys. We conclude that the use of elderly NHB donors in order to expand the donor pool was associated with unacceptable clinical outcomes and cannot be justified without further refinement in their selection, for example, by histological assessment of pretransplant biopsies.

Adolescent↗
PubMed2006

Valdecoxib does not interfere with the CYP2D6 substrate metoprolol.

OBJECTIVE: We reported recently that celecoxib inhibits the metabolism of the cytochrome P450 (CYP)2D6 substrate metoprolol in volunteers. Valdecoxib, the active metabolite of parecoxib, has also been claimed to interfere with the metabolism of CYP2D6 substrates. However, little support for this contention is available despite the intensive use of parecoxib in the perioperative setting. Therefore, the objective of this study was to examine the effect of valdecoxib on the pharmacokinetics of the clinically relevant CYP2D6 substrate metoprolol. METHODS: An open, randomized, 3-period crossover study was performed in 15 healthy male volunteers. Metoprolol (50 mg) was given in all 3 periods without, or following a 7-day pre-treatment with valdecoxib (20 mg, o.d.) or rofecoxib (25 mg, o.d.), to achieve steady state conditions of COX-2 inhibitors in Periods 2 and 3. In a small group of extensive metabolizers (EM/EM), short-term application of twice the dose was investigated. RESULTS: No effect of valdecoxib (20 mg/d) or rofecoxib (25 mg/d) were detected on the area under the plasma concentration-time curve of metoprolol (323 +/- 333 to 324 +/- 296 or 309 +/- 256 microg x h/l) or at a higher dose. No significant changes of pharmacokinetic or pharmacodynamic parameters of metoprolol were apparent. CONCLUSION: We conclude that, at therapeutic doses, valdecoxib and rofecoxib do not influence the CYP2D6 substrate metoprolol.

Adult↗
PubMed2005

Is granulocyte colony-stimulating factor level predictive for human IVF outcome?

BACKGROUND: We investigated granulocyte colony-stimulating factor (G-CSF) in human reproduction. METHODS: From a total sample of 93 patients, we analysed in group 1 (n = 82) the level of G-CSF and estradiol (E(2)) in serum and follicular fluid (FF) on day of follicular puncture (FP). Furthermore, in response to ovarian stimulation, G-CSF levels in serum were compared between low (n = 11), moderate (n = 53) and high (n = 18) response patients. In group 2 (n = 23) serum for G-CSF assessment was collected throughout menstrual cycle until gestation. Group 3 (n = 11) patients with endometriosis were assessed for G-CSF in serum and FF on day of FP without further differentiation. RESULTS: G-CSF in FF was higher than in serum (P < 0.01). G-CSF in serum increased from low through moderate to high response (P < 0.001); pregnancy rates were 0, 24.5 and 33.5% respectively. G-CSF in serum increased throughout stimulation, reached a peak with ovulation induction (P = 0.01) and decreased until embryo transfer (P=0.001). G-CSF level only in pregnant patients (n = 11) increased from embryo transfer to implantation to gestation (P = 0.005). In endometriosis patients G-CSF in serum and FF was lower than in non-endometriosis patients (P < or = 0.03) and corresponded with low response patients. CONCLUSIONS: G-CSF is involved in follicle development and may be a predictor of IVF outcome.

Adult↗
PubMed2005

Hepatitis B virus: significance of genotypes.

Hepatitis B Virus (HBV) genotypes have come of age. The concept that HBV genotypes may influence the course of disease and relevant biological differences has now been recognised. However, there are still major gaps in our knowledge. Most clinical data come from Asia and describe findings in patients infected with genotypes B and C. Large scale studies with genotypes A and D as found in Europe or A, D and E from Africa are urgently needed to broaden our understanding. Experimental data which explain in vivo findings in terms of differences in molecular biology in vitro are still in the beginning. The succeeding years will see many interesting studies which will aid our understanding of how variants and genotypes of HBV influence the spectrum of disease in people infected with HBV.

Base Sequence↗
PubMed2003

Automation in sludge dewatering by novel on-line characterisation of flocculation.

A novel on-line method and system for characterisation of sludge flocs in view of improving sludge dewatering has been developed. The characterisation of sludge flocs was carried out after the conditioning or the flocculation process. The system uses a conventional CCD-line scan camera providing an on-line monitoring of the relative floc size distribution by image processing procedures. The image processing procedure has been re-evaluated and adapted to the practical dewatering results, obtained from a chamber filter press of 250 x 250 mm size. A good correlation between the calculated sensor signal and the sludge dewaterability of digested sludge in terms of the up-concentration factor was found. Although different sludge compositions and flocculation systems have been tested within the whole experimental period of six months, a good reproducibility of this correlation was also found. A well balanced floc size distribution is necessary showing that not too many but still some fine flocs and also not too large but compact flocs lead to improved dewaterability. This has been illustrated by an extended range of floc size measurements ranging between 50 microm and 29 mm. The conditioning monitoring system would be suitable for the control of production of good size-balanced flocs to compensate fluctuations in sludge characteristics of the sludge to be conditioned.

Automation↗
PubMed2002

[Preclinical care of trauma patients in air rescue. Results of the medical quality management for patients with severe head injury and polytrauma in the years 2000 and 2001].

In a retrospective study of mission data of ADAC Air Rescue of the years 2000 and 2001 the quality of preclinical care of 1,946 patients with severe head injuries and 1,878 polytraumatized patients was examined. The actual preclinical care of these patients was compared with a catalogue of eleven thesis-like recommendations. These recommendations were previously derived from corresponding publications of national and international specialist companies and were introduced in a binding manner by the senior doctors of the participating air rescue centres. The results of the study show that 73.3% of the severe head injuries were preclinically intubated and 94.4% were supplied with oxygen, 82.2% were analgosedated. 94.8% could be delivered to the hospital of destination. 65.9% had a systolic blood pressure of >120 mmHg upon admission to the hospital. 71.4% of severe head injury victims were equipped with a cervical support, 23.3% had the blood pressure documented. 47.3% reached the hospital of destination in less than 60 minutes. Among polytraumatic patients the intubation was performed in 75.7%, the supply with oxygen in 90.7%, 88.6% of the patients were analgosedated. 78.7% of patients suffering from concomitant head injuries were provided with a cervical support and only 22.8% had a blood sugar measurement documented. A concomitant severe thorax trauma was treated by a thorax drainage in 59.2%. 35.6% of the polytraumata reached the hospital of destination in less than 60 minutes. The work describes the preclinical patient care of severe head injuries and polytraumata, pointing out deficits and presenting optimization possibilities, particularly in the area of training. Furthermore, the work shows the concept of the medical quality management in an air rescue enterprise. The total evaluation of all air rescue centres participating in data collection forms the basis of an external quality comparison. The data evaluation of a single station makes regional strengths and weaknesses visible, deficits can be proven and proposals for optimization be developed. The presentation of the time history of data yields continuous standard information on the state of the patient care at the relevant air rescue location and enables the analysis of improvement concepts based on the updated data.

Air Ambulances↗
PubMed2002

Molecular approaches to validate disinfectants against human hepatitis B virus.

Disinfection is an important measure to prevent hepatitis B virus (HBV) transmission by instruments. However, virucidal testing of disinfectants against HBV is difficult, because no simple quantitative infectivity assay exists. Since molecular changes of viral epitopes and the genome may indicate virus inactivation, we measured the alteration of these constituents with 0.065% peracetic acid (PAA) for exposure times up to 1 h. Plasma of a chronic HBV carrier with 10(9) HBV genomes/ml served as viral source in the form of a 10% dilution or of a purified HB-antigen preparation. Alterations of HBV epitopes were analyzed with four monoclonal antibodies in an enzyme-linked immunosorbent assay. Changes of the HBV genomes were determined by the inability to amplify the target sequence with a quantitative real-time polymerase chain reaction, either of a short fragment (189 bp) or of the full-length (3,200 bp). The determination of the epitope and genome alteration was quantified as log10 reduction factor (RF) with the parallel line bioassay. Under a high protein load of 10% human plasma, PAA induced a HBV genome alteration of RF = 1.5 after an exposure time of 60 min. Similar RFs were seen with the four HB epitopes. Without protein load, the alteration of these epitopes amounted to a RF of more than 3.5 within 30 min. Such inhibition of PAA activity by protein load was also seen in the virucidal tests with parvovirus. Although the RF were higher in the virucidal tests, the time-dependent dose-response curves for the epitope and genome alteration and for the infectivity inactivation followed the same inactivation kinetics. The molecular alteration and disintegration epitope and genome test may therefore be suitable to measure antiviral activity of disinfectants against HBV.

Animals↗
PubMed2001

Fasting limits the increase in intracellular calcium during ischemia in isolated rat hearts.

INTRODUCTION: Fasting has been shown to limit ischemic injury and improve functional activity after global ischemia. Because calcium overload is considered a mechanism of ischemic injury, we hypothesized that fasting would limit the accumulation of intracellular calcium [Ca]i during ischemia, potentially due to reduced accumulation of intracellular sodium [Na]i. METHODS: To address this hypothesis, hearts isolated from rats fed either a normal diet or fasted for 24 hours underwent 20 min of global ischemia at 37 degrees. In addition to functional parameters, [Na]i and [Ca]i were measured using 21Na and 19F spectroscopy using thulium-DOTP-5 and 5F-BAPTA, respectively. In vitro measurement of sarcoplasmic reticulum calcium uptake and release, as well as activity of the sarcolemmal Na-Ca exchanger, was performed in hearts from fed and fasted animals under baseline and ischemic conditions. RESULTS: Hearts from fasted animals showed greater recovery of developed pressure (37+/-9 vs. 11+/-6 cm H2O, p < 0.05) and less contracture (end-diastolic pressure 25+/-2 vs. 47+/-2 cm H2O, p < 0.05) by the end of the reperfusion period. [Na]i was similar in the 2 groups during the first half of the ischemic period, albeit with a higher concentration of [Na]i in hearts from fed compared to fasted animals at reperfusion. Fasting markedly limited calcium accumulation during ischemia, with end-ischemic calcium being 419+/-46 nM in the hearts from fasted animals and 858+/-140 nM in the hearts from fed animals (p < 0.01). There was no significant effect of fasting on calcium uptake or release by the SR, nor on sarcolemmal Na-Ca exchange activity. CONCLUSIONS: Fasting for 24 hours improves functional recovery and markedly limits [Ca]i accumulation during ischemia and early reperfusion. The mechanism for this phenomenon remains to be elucidated.

Animals↗
PubMed2001

Blockade of adenosine receptors with aminophylline limits ischemic preconditioning in human beings.

BACKGROUND: Ischemic preconditioning is characterized by the limitation of infarct size or ischemic signs after one or more brief episodes of ischemia, a process that probably involves stimulation of adenosine receptors. One human model of ischemic preconditioning is repetitive occlusion of a coronary artery during angioplasty. By using this method of inducing ischemia, we tested the hypothesis that blockade of adenosine receptors with aminophylline would abolish ischemic preconditioning in human beings. METHODS: Twenty-six patients undergoing angioplasty were randomly assigned to receive either aminophylline (6 mg/kg IV) or placebo before repetitive coronary occlusion (two 2-minute occlusions separated by 5 minutes). ST-segment changes on the surface electrocardiogram were used as a measure of myocardial ischemia. Serum theophylline levels and the conduction response to an intravenous bolus of adenosine were used to assess the efficacy of adenosine receptor blockade. RESULTS: Repetitive coronary occlusion resulted in a reduction in ST-segment shift in 9 of 13 patients given placebo. In contrast, 9 of 13 patients receiving aminophylline had an increase in ST-segment shift on the second occlusion (P =.002). Patients receiving aminophylline (mean serum theophylline level of 8.38 +/- 0.45 mg/dL) did not have significant conduction block with intravenous adenosine. CONCLUSIONS: Repetitive coronary occlusion reduces the signs of ischemia in human beings, a process limited by blockade of adenosine receptors.

Aminophylline↗
PubMed2001

Duck hepatitis B virus expresses a regulatory HBx-like protein from a hidden open reading frame.

Duck hepatitis B viruses (DHBV), unlike mammalian hepadnaviruses, are thought to lack X genes, which encode transcription-regulatory proteins believed to contribute to the development of hepatocellular carcinoma. A lack of association of chronic DHBV infection with hepatocellular carcinoma development supports this belief. Here, we demonstrate that DHBV genomes have a hidden open reading frame from which a transcription-regulatory protein, designated DHBx, is expressed both in vitro and in vivo. We show that DHBx enhances neither viral protein expression, intracellular DNA synthesis, nor virion production when assayed in the full-length genome context in LMH cells. However, similar to mammalian hepadnavirus X proteins, DHBx activates cellular and viral promoters via the Raf-mitogen-activated protein kinase signaling pathway and localizes primarily in the cytoplasm. The functional similarities as well as the weak sequence homologies of DHBx and the X proteins of mammalian hepadnaviruses strongly suggest a common ancestry of ortho- and avihepadnavirus X genes. In addition, our data disclose similar intracellular localization and transcription regulatory functions of the corresponding proteins, raise new questions as to their presumed role in hepatocarcinogenesis, and imply unique opportunities for deciphering of their still-enigmatic in vivo functions.

Amino Acid Sequence↗
PubMed2001

Preconditioning limits mitochondrial Ca(2+) during ischemia in rat hearts: role of K(ATP) channels.

Prolonged myocardial ischemia results in an increase in intracellular calcium concentration ([Ca(2+)]i), which is thought to play a critical role in ischemia-reperfusion injury. Ischemic preconditioning (PC) improves myocardial function during ischemia-reperfusion, a process that may involve opening mitochondrial ATP-sensitive potassium (K(ATP)) channels. Because pharmacological limitation of mitochondrial calcium concentration ([Ca(2+)]m) overload during ischemia-reperfusion has been shown to improve myocardial function, we hypothesized that PC would reduce [Ca(2+)]m during ischemia-reperfusion and that this effect was mediated by opening mitochondrial K(ATP) channels. Isolated rat hearts were subjected to 25 min of global ischemia and 30 min of reperfusion with or without PC in the presence of mitochondrial K(ATP) channel opening (diazoxide, 100 microM) and blockade [5-hydroxydecanoic acid (5-HD), 100 microM]. Contracture during ischemia (end-diastolic pressure) and functional recovery on reperfusion (developed pressure) were assessed. Total [Ca(2+)]i and [Ca(2+)]m were measured using indo 1 fluorescence. Both PC and diazoxide limited the increase in end-diastolic pressure and resulted in greater functional recovery after 30 min of reperfusion, functional effects that were partially or completely abolished by 5-HD. PC and diazoxide also significantly limited the increase in [Ca(2+)]m during ischemia-reperfusion. In addition, PC lowered [Ca(2+)]i during reperfusion, whereas diazoxide paradoxically resulted in increased [Ca(2+)]i during reperfusion. There was an inverse linear relationship between [Ca(2+)]m and developed pressure during reperfusion. PC limits the ischemia-induced increase in mitochondrial, but not total, [Ca(2+)]i, an effect mediated by opening mitochondrial K(ATP) channels. These data suggest that the lowering of mitochondrial calcium overload is a mechanism of cardioprotection in PC.

Animals↗
PubMed2001

Protection of ischemic myocardium in diabetics by inhibition of electroneutral Na+-K+-2Cl- cotransporter.

Diabetes increases both the incidence of cardiovascular disease and complications of myocardial infarction and heart failure. Studies using diabetic animals have shown that changes in myocardial sodium transporters result in alterations in intracellular sodium (Na(i)) homeostasis. Because the changes in sodium homeostasis can be due to increased entry of Na+ via the electroneutral Na+-K+-2Cl- cotransporter (NKCC), we conducted experiments in acute diabetic hearts to determine if 1) net inward cation flux via NKCC is increased, 2) this cotransporter contributes to a greater increase in Na(i) during ischemia, and 3) inhibition of NKCC limits injury and improves function after ischemia-reperfusion. These issues were investigated in perfused type I diabetic and nondiabetic rat hearts subjected to ischemia and 60 min of reperfusion. A group of diabetic and nondiabetic hearts was perfused with 5 microM of bumetanide, an inhibitor of NKCC. Flux via NKCC, Na(i), and ATP was measured in each group with the use of radiotracer 86Rb, 23Na, and 31P nuclear magnetic resonance spectroscopy, respectively, whereas ischemic injury was assessed by measuring creatine kinase release on reperfusion. Cation flux via NKCC, as measured by 86Rb uptake, was significantly increased in diabetic hearts. Inhibition of NKCC significantly reduced ischemic injury in diabetic hearts, improved functional recovery on reperfusion, attenuated the ischemic rise in Na(i), and conserved ATP during ischemia-reperfusion. Parallel studies in nondiabetic hearts showed that NKCC inhibition was not cardioprotective. These findings demonstrate that flux via NKCC is increased in type I diabetic hearts and that inhibition with bumetanide attenuates changes in Na(i) and ATP during ischemia and protects against ischemic injury. The data suggest a therapeutic role for pharmacological agents that inhibit flux via NKCC in diabetic patients with myocardial ischemia.

Animals↗
PubMed2001

Na(+)/H(+) exchange subtype 1 inhibition reduces endothelial dysfunction in vessels from stunned myocardium.

Myocardial ischemia and reperfusion cause myocyte and vascular dysfunction, frequently termed "stunning." We hypothesized that inhibiting the Na(+)/H(+) exchanger subtype 1 isoform (NHE(1)) during ischemia and reperfusion limits myocardial and coronary microvascular stunning. Anesthetized rats completed 2 x 10-min coronary artery occlusions separated by 5-min of reperfusion, followed by 15 or 60 min of reperfusion. Vehicle (saline) or the NHE(1) inhibitor cariporide (HOE-642) was administered 15 min before ischemia and was continued throughout each protocol. After reperfusion, hearts were excised, and the reactivity of resistance arteries (internal diameter, approximately 120 microm) was assessed. The first derivative of left ventricular (LV) pressure, LV developed pressure, and LV systolic wall thickening were depressed (P < 0.05) similarly in vehicle- and cariporide-treated rats during ischemia and after 15 or 60 min of reperfusion compared with sham-operated animals that were not exposed to ischemia (i.e., controls). In vessels obtained after 15 min of reperfusion, the maximal response to acetylcholine-induced relaxation (10(-8)-10(-4) M) was blunted (P < 0.05) in vessels from vehicle- (approximately 35%) and cariporide-treated rats (approximately 55%) compared with controls (approximately 85%). However, the percent relaxation to acetylcholine was greater (P < 0.05) in cariporide-treated rats compared with vehicle-treated rats. Maximal contractile responses to endothelin-1 (10(-11)-10(-7) M) were increased (P < 0.05) similarly in vehicle- and cariporide-treated rats compared with controls. Relaxation to sodium nitroprusside (10(-4) M) was not different among groups. Results were similar in vessels obtained from animals after 60 min of reperfusion. These findings suggest that NHE(1) inhibition before coronary occlusion lessens ischemia-induced microvascular dysfunction for 15-60 min after reperfusion but does not alter myocardial contractile function in the area at risk.

Acetylcholine↗
PubMed2001

Optimised conditions for the production of hepatitis B virus from cell culture.

In chronically infected patients, hepatitis B virus (HBV) particles reach numbers as large as >10(9) genome equivalents (GE)/ml of serum. However, expression of infectious HBV particles in cell culture only yields 10(5)-10(6) GE/ml, which is insufficient for many studies. HBV transcription and possibly replication is dependent on hepatocyte-specific differentiation. Thus, we tested several cell culture parameters that have been reported to enhance the expression of hepatocyte-specific markers, such as growth on different extracellular matrices, different cell culture media, low concentrations of fetal calf serum (FCS) and the addition of dimethyl sulfoxide (DMSO) to the medium. Lower concentrations of FCS, growth on collagen and inclusion of DMSO in the medium only moderately enhanced HBV production in vitro when applied individually. However, combinations of these parameters optimised cell culture conditions and reproducibly increased the release of HBV particles about 100-fold to titres >10(8) GE/ml of culture medium.

Cell Culture Techniques↗
PubMed2000

Induction of apoptosis by the transactivating domains of the hepatitis B virus X gene leads to suppression of oncogenic transformation of primary rat embryo fibroblasts.

Epidemiology shows a clear correlation between chronic infection with the hepatitis B virus (HBV) and development of hepatocellular carcinoma (HCC). The potential role of the transactivating hepatitis B virus X protein (HBx) in transformation by HBV is controversial. Here we report that HBx suppresses transformation of primary rat embryo fibroblasts (REFs). Cooperating oncogenes like c-Ha-ras and c-myc transform REF very efficiently but cotransfection with HBx suppressed transformation of REFs down to 5%. Similarly, transfection of HBx together with the cooperating oncogenes Ha-ras and SV40 LTAg or c-Ha-ras and mutant p53 reduced the number of foci to 13%. Comparable results were obtained with HBx in the context of the whole HBV. Suppression of focus formation in REF could be partly relieved by cotransfection of apoptosis inhibitors Bcl-2 or E1B. However, cotransfection of apoptosis inhibitors crmA and p35 did not influence the proapoptotic functions of HBx. Thus, HBx may specifically activate the Bcl-2 sensitive pathway leading to apoptosis. Experiments with 13 HBx linker scanning mutants revealed that the domains necessary for HBx dependent transactivation overlap with the domains needed for the apoptotic/growth arrest functions of HBx.

Animals↗
PubMed2000

Dietary monotony and food cravings in young and elderly adults.

Many hypothesized mechanisms for food cravings focus on nutritional deprivation. However, outside of the laboratory, nutritional inadequacy is often confounded with dietary monotony. Therefore, one aim was to examine the effects of a nutritionally adequate, liquid, sweet, monotonous diet on food cravings in young and elderly adults. In addition, previous retrospective questionnaire work has indicated that elderly individuals report fewer food cravings than do young adults. Because there are possible age differences in cognitive capacity, another goal of this work was to develop a prospective method (i.e.. a method that depends less on memory) of studying cravings that permits comparison of adults of different ages. Young adults reported significantly more cravings per day during the monotony manipulation than during the baseline period. Therefore, nutritional deprivation is not a necessary condition for food cravings. There were no gender differences. The increase was due primarily to a greater number of cravings for entrees (i.e., foods that differed in sensory quality from the monotonous diet). Cravings for sweets did not change. In contrast to predictions that liking for the monotonous diet would decline as a result of "repetition revulsion," there was no significant change in liking for the diet over the study period. In contrast to the young adults, elderly subjects were not responsive to the monotony manipulation. Elderly men reported almost no cravings at any time during the study. Elderly women reported as many cravings as did young adults during the baseline period, but did not show an increase in cravings during the monotony period. This lack of response to dietary monotony by the elderly could result in nutritionally inadequate diets.

Adult↗