Biomedical subjects

J König

Publications and source records attributed to J König.

At least 19 recordsLinked to original sources

PubMed2003

Influence of inhaled iloprost on transpulmonary gradient of big endothelin in patients with pulmonary hypertension.

BACKGROUND: The pulmonary circulation is an important site for the production and clearance of endothelin (ET)-1, a potent vasoactive and mitogenic peptide. In healthy individuals, 40% to 50% of circulating ET-1 is removed on each passage through the lungs resulting in an arteriovenous ratio of <1, whereas many patients with pulmonary arterial hypertension (PAH) have ratios >1, indicating reduced clearance or increased release of endothelin. The influence of inhaled prostanoids on endothelin clearance is unknown. METHODS AND RESULTS: In a prospective investigation, plasma concentrations of big endothelin-1 (big ET-1, Elisa) were measured in 15 patients with pulmonary hypertension undergoing right heart catheterization with iloprost inhalation (4 m, 11 f, aged 35 to 75 years, mean pulmonary arterial pressure (PAPm) 54+/-2.3 mm Hg, pulmonary vascular resistance (PVR) 1061+/-141 dyn x sec x cm(-5)). There was a significant transpulmonary gradient for big ET-1 with 31% +/-11% higher concentrations in the radial artery than in the pulmonary artery (P<0.001). After inhalation of iloprost a significant decrease in the AV-ratio from 1.31+/-0.11 to 0.92+/-0.06 (P<0.007) was observed. The pulmonary net release of 3.10+/-0.65 pmol/min big ET-1 at baseline decreased to -1.24+/-1.32 pmol/min (P=0.013) within 15 minutes indicating a restored balance. Patients under long-term treatment with iloprost (n=7) tended to have a lower net release and AV-ratio for big ET-1 than patients without pretreatment. CONCLUSION: An increase in pulmonary clearance of big-ET could be a mechanism contributing to the beneficial effects of inhaled prostanoids in the treatment of PAH.

Administration, Inhalation↗

PubMed2003

Personality traits in multiple sclerosis (MS) patients with and without fatigue experience.

OBJECTIVES: To determine the impact of personality characteristics on feelings of fatigue in multiple sclerosis (MS) patients and to compare the results with the impact of bodily impairment. PATIENTS AND METHODS: Eighty patients with definite MS (mean age 38.5 +/- 9.0 years, 62 females) were surveyed using questionnaires assessing fatigue experience and personality traits (German Freiburg Personality Inventory-Revised; FPI-R) and by clinical examination assessing the Expanded Disability Status Scale. RESULTS: Increased levels of "neuroticism", and "excitability" and decreased levels of "extraversion" were found to relate independent of fatigue scores (0.21 < beta < 0.52; 0.05 < P < 0.0001). The impact of these personality traits on fatigue (partial R2 ranging up to 0.32; 0.02 < P < 0.0001) was much higher than the impact of physical impairment (partial R2 ranging up to 0.04; not significant). CONCLUSION: Our results support a psychological model of fatigue in MS. FPI-R-items over-weighted somatic sources of the fatigue syndrome in MS and may specifically relate to fatigue experience in chronical disorders.

Adult↗

PubMed2002

Learning root debridement with curettes and power-driven instruments. Part I: a training program to increase effectivity.

BACKGROUND/AIMS: In a dummy-head trial, we assessed how effectively untrained operators were able to learn scaling with curettes and power-driven instruments. METHODS: Two untrained operator groups (n = 11 each) received six 2-h lessons during a 10-week period following a training program. Subgingival scaling was performed with curettes (GRA) and a power-driven system (PP). At 6 test days each subject had to instrument 10 test teeth. The percentage of debrided area was assessed with an image analysis program. Learning success was measured as a percentage of debrided root area and scaling time. Furthermore, the effectivity was related to difficulty in anatomical situations and access to root surfaces. Statistical analysis was carried out with SPSS. RESULTS: At baseline, effectivity was 63.1% (GRA) vs. 52.3% (PP). Between weeks 9 and 11, operators reached a plateau for group GRA at 84.7% and group PP at 81.3%. Scaling time did not differ between the two groups. Debridement of teeth with complex root shapes that were hard to access was less effective with the power-driven system. CONCLUSION: Independent of the instrument used, untrained operators were only able to debride root surfaces at low levels of efficacy. With systematical training, effective scaling with the power- driven system was as easy to learn as with hand instruments. On root surfaces with complicated shape and anatomy or difficult accessibility, the power-driven system works significantly less effectively.

Alveolar Bone Loss↗

PubMed2002

Learning root debridement with curettes and power-driven instruments in vitro: the role of operator motivation and self-assessment.

The influence of systematic dummy-head training with Periopolishe (PP, group A) and Gracey instruments (GRA, group B) on the effectiveness of root debridement was evaluated by Rühling et al., 2002 (9). Their results indicate that independent of the instrument used, untrained operators were only able to debride root surfaces at low levels of effectiveness. It was possible to increase effectiveness to a high level through systematic training in both groups. The aim of the present study was to assess the role of operator motivation and self-assessment on scaling effectiveness. Before baseline, operators were asked to answer a questionnaire rating the expectation of the instrument performance. Four groups of inexperienced operators (n = 11 each) received 10 weeks dummy-head training. In groups A (GRA) and B (PP), training was combined with a motivational programme. Groups C (GRA) and D (PP) received the same training, but no additional motivational programme. In a dummy-head, 10 test teeth were debrided and operators were asked to estimate their effectiveness of debridement at each test day. Effectiveness was calculated as percentage of debrided root area on 10 test teeth at different time points with an image analysis programme (NIH Image) and ANOVA. Two groups were compared using the Mann-Whitney U-test (unpaired) and the Wilcoxon signed ranks test (paired). Motivated groups (A and B) reached about 25% higher debridement results (p < 0.001) and were able to estimate their effectiveness more precisely compared to groups C and D. In the low motivation groups (C and D), overestimation of more than 20% was evident (p < 0.001). The questionnaires revealed underestimation of the GRA instruments and overestimation of PP instruments. Operator motivation and self-assessment greatly influence learning of effective root debridement.

Analysis of Variance↗

PubMed2002

Hohenheim consensus workshop: copper.

Copper (Cu) is an essential trace element with many physiological functions. Homeostatic mechanisms exist to allow Cu to act as a cofactor in enzymatic processes and to prevent accumulation of Cu to toxic levels. The aim of this commentary is to better understand the role of dietary Cu supply in deficiency and under physiological and pathological conditions. The essentiality of Cu can be attributed to its role as a cofactor in a number of enzymes that are involved in the defence against oxidative stress. Cu, however, has a second face, that of a toxic compound as it is observed with accumulating evidence in hepatic, neurodegenerative and cardiovascular diseases. The destructive potential of Cu can be attributed to inherent physico-chemical properties. The main property is its ability to take part in Fenton-like reactions in which the highly reactive and extremely deleterious hydroxyl radical is formed. Diseases caused by dietary Cu overload could be based on a genetic predisposition. Thus, an assessment of risk-groups, such as infants with impaired mechanisms of Cu homeostasis regarding detoxification, is of special interest, as their Cu intake with resuspended formula milk may be very high. This implies the need for reliable diagnostic markers to determine the Cu status. These topics were introduced at the workshop by the participants followed by extensive group discussion. The consensus statements were agreed on by all members. One of the conclusions is that a re-assessment of published data is necessary and future research is required.

Cardiovascular Diseases↗

PubMed2002

Expression of CD44v6 has no prognostic value in patients with colorectal cancer.

BACKGROUND AND AIMS: In colorectal cancer patients' mortality is largely influenced by spreading of tumour cells from the primary tumour site and subsequent metastasis formation. CD44 is an adhesion molecule and represents a highly variable family of isoforms. The isoform CD44v6 has been associated with metastatic spread and poor prognosis in animal models and several human cancers. Results of immunohistological studies in primary colorectal cancer are mostly retrospective and contradictory. The aim of our prospective study was to assess the controversial role of CD44v6 as a prognostic factor in colorectal cancer. METHODS: In 93 patients we analysed tumour CD44v6 expression in prospectively sampled stage I-IV colorectal adenocarcinomas using RT-PCR and Southern blotting. The prognostic value of the CD44v6 expression was assessed using univariate and multivariate analysis. RESULTS: CD44v6 expression was found in 47 % of the cases. CD44v6 expression failed to show any association with the clinical or histological variables examined. CD44v6 expression did not correlate with survival in long-term follow-up. The most important prognostic factor in this cohort was tumour stage. CONCLUSIONS: Changes in CD446 expression level do not predict tumour spread or patient survival in colorectal cancer.

Adenocarcinoma↗

PubMed2002

The function of the chloroplast 2-cysteine peroxiredoxin in peroxide detoxification and its regulation.

The Arabidopsis genome contains nine open reading frames with homology to members of the peroxiredoxin (prx) family: one 1-Cys-prx, two 2-Cys-prx, five type II-prx, and one peroxiredoxin Q. The function of the peroxiredoxins in plant metabolism is only slowly emerging. They are assumed to reduce toxic peroxides to their corresponding alcohols with a rather broad substrate specificity. The 2-Cys peroxiredoxins (2-CP) were recently identified as members of the antioxidant defence system of chloroplasts. Knock-out mutants of Synechocystis and antisense mutants of Arabidopsis have provided insight into the function of 2-CPs in the photosynthetic antioxidant network. This review summarizes present knowledge on the enzymatic mechanism, the physiological context and the genetic regulation of the 2-CPs in plants and cyanobacteria. In addition, an extrapolation on the metabolic role of the chloroplast 2-CP is attempted based on the molecular features of 2-CPs from other organisms.

Antioxidants↗

PubMed2002

Ordinal classification in medical prognosis.

OBJECTIVES: Medical prognosis is commonly expressed in terms of ordered outcome categories. This paper provides simple statistical procedures to judge whether the predictor variables reflect this natural ordering. METHODS: The concept of stochastic ordering in logistic regression and discrimination models is applied to naturally ordered outcome scales in medical prognosis. RESULTS: The ordering stage is assessed by a data-generated choice between ordered, partially ordered, and unordered models. The ordinal structure of the outcome is particularly taken into consideration in the construction of allocation rules and in the assessment of their performance. The specialized models are compared to the unordered model with respect to the classification efficiency in a clinical prognostic study. CONCLUSIONS: It is concluded that our approach offers more flexibility than the widely used cumulative-odds model and more stability than the multinomial logistic model. The procedure described in this paper is strongly recommended for practical applications to support medical decision-making.

Anesthesia↗

PubMed2001

[Daily activities and circadian variation of ventricular tachyarrhythmias in patients with implanted defibrillator].

BACKGROUND AND STUDY AIM: Acute cardiovascular events may be triggered by physical and mental stress. Does also the typical circadian variation of arrhythmia recurrence (morning peak of events) in patients with implanted cardioverter-defibrillator correlate with the individual circadian variation of physical and mental daily activities? PATIENTS AND METHODS: In 29 consecutive patients with a minimum of three documented ventricular tachyarrhythmias after defibrillator implantation the circadian variation of habitual daily activities was determined in a standardized interview and compared to the individual circadian variation of arrhythmic events saved in the defibrillator event memory during long-term follow-up. RESULTS: The habitually highest physical and mental activity was determined during the time period with most arrhythmic events in 55 % and 23 % of patients, respectively. A comparison of the level of activity during the time period with the highest event frequency to the mean activity level during the rest of the day (without sleeping time) revealed significantly higher physical activity during the time of day with the highest arrhythmia recurrence. There was a positive correlation between circadian variation of arrhythmic events and the sum of all activities (r = 0.34, p < 0.05) and physical activities alone (r = 0.25, p = 0.056) while a relationship to mental activities alone could not be shown (r = 0.02, p = 0.84) CONCLUSION: The circadian variation of acute cardiovascular events may be discussed as an essential factor influencing the circadian variation of habitual daily activities in patients with cardiac disease.

Activities of Daily Living↗

PubMed2001

The cystic fibrosis transmembrane conductance regulator (CFTR) inhibits ENaC through an increase in the intracellular Cl- concentration.

Activation of the CFTR Cl- channel inhibits epithelial Na+ channels (ENaC), according to studies on epithelial cells and overexpressing recombinant cells. Here we demonstrate that ENaC is inhibited during stimulation of the cystic fibrosis transmembrance conductance regulator (CFTR) in Xenopus oocytes, independent of the experimental set-up and the magnitude of the whole-cell current. Inhibition of ENaC is augmented at higher CFTR Cl- currents. Similar to CFTR, ClC-0 Cl- currents also inhibit ENaC, as well as high extracellular Na+ and Cl- in partially permeabilized oocytes. Thus, inhibition of ENaC is not specific to CFTR and seems to be mediated by Cl-.

Animals↗

PubMed2001

Kondo correlations and the Fano effect in closed Aharonov-Bohm interferometers.

We study the Fano-Kondo effect in a closed Aharonov-Bohm (AB) interferometer which contains a single-level quantum dot and predict a frequency doubling of the AB oscillations as a signature of Kondo-correlated states. Using the Keldysh formalism, the Friedel sum rule, and the numerical renormalization group, we calculate the exact zero-temperature linear conductance G as a function of the AB phase phi and level position epsilon. In the unitary limit, G(phi) reaches its maximum 2e(2)/h at phi = pi/2. We find a Fano-suppressed Kondo plateau for G(epsilon) similar to recent experiments.

Journal Article↗

PubMed2001

Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension.

BACKGROUND: The application of iloprost, a stable prostacyclin analogue, by inhalation has been shown to improve hemodynamic variables in patients with primary pulmonary hypertension. However, repetitive inhalations are required due to its short-term effects. One potential approach to prolong and increase the vasorelaxant effects of aerosolized iloprost might be to combine use with phosphodiesterase inhibitors. METHODS AND RESULTS: The short-term effects of 8.4 to 10.5 microgram of aerosolized iloprost, the phosphodiesterase type 5 inhibitor sildenafil, and the combination thereof were compared in 5 patients with primary pulmonary hypertension. Aerosolized iloprost resulted in a more pronounced decrease in mean pulmonary arterial pressure (PAP) than sildenafil alone (9.4+/-1.3 versus 6.4+/-1.1 mm Hg; P<0.05). The reduction in mean PAP after sildenafil was maximal after the first dose (25 mg). The combination of sildenafil plus iloprost lowered mean PAP significantly more than iloprost alone (13.8+/-1.4 versus 9.4+/-1.3 mm Hg; P<0.009). No significant changes in heart rate or systemic arterial pressure were observed during any treatment. The treatments were well tolerated, without major adverse effects. CONCLUSIONS: Sildenafil caused a long-lasting reduction in mean PAP and pulmonary vascular resistance, with a further additional improvement after iloprost inhalation. These data suggest that small doses of a phosphodiesterase type 5 inhibitor may be a useful adjunct to inhaled iloprost in the management of pulmonary hypertension.

Administration, Inhalation↗

PubMed2001

PHF3-specific antibody responses in over 60% of patients with glioblastoma multiforme.

Glioblastoma multiforme (GBM), a malignant astrocytic tumour, represents the most frequent tumour of the human brain. Nevertheless, its molecular pathology is not well understood. We utilized the immune system, which contributes to cancer protection, to help identify new GBM-related genes. By screening a human GBM cDNA library with autologous patient serum (SEREX-approach), we isolated a gene termed PHF3 (PHD finger protein 3). The gene product of PHF3 is immunogenic in GBM as tested in an allogenic patient serum screening demonstrating antibodies in 24 of 39 (61.53%) sera, whereas none of the 14 healthy persons had antibodies against PHF3. While previous SEREX studies revealed allogenic antibody responses up to 40%, our results for PHF3 represent the highest reported rate for a specific antibody response. We show that GBM patients with an antibody response against PHF3 show significant better survival than patients without PHF3-specific antibodies. Because the amino acid sequence of PHF3 contains a PHD finger (also termed LAP motif), a TFIIS homology, a proline rich region and nuclear localization signals, it supposedly functions as a transcription factor. A polyclonal antibody generated against PHF3 shows nuclear expression in most investigated formalin-fixed, paraffin embedded tissues. In GBM, PHF3 expression is concentrated in cells surrounding necroses.

Adult↗

PubMed2001

Coherence and partial coherence in interacting electron systems.

We study coherence of electron transport through interacting quantum dots and discuss the relation of the coherent part to the flux-sensitive conductance for three different types of Aharonov-Bohm interferometers. Contributions to transport in first and second order in the intrinsic linewidth of the dot levels are addressed in detail. We predict an asymmetry of the interference signal around resonance peaks as a consequence of incoherence associated with spin-flip processes. Furthermore, we show by strict calculation that first-order contributions can be partially or even fully coherent. This contrasts with the sequential-tunneling picture which describes first-order transport as a sequence of incoherent processes.

Journal Article↗

PubMed2001

Expression of the multidrug resistance proteins MRP2 and MRP3 in human hepatocellular carcinoma.

Treatment of hepatocellular carcinoma (HCC) by chemotherapy is often impeded by the intrinsic multidrug resistance (MDR) of this frequent primary cancer of the liver. The MDR phenotype can be caused by ATP-dependent export of chemotherapeutic drugs across the plasma membrane being mediated by transporters of the MDR P-glycoprotein family or of the multidrug resistance protein (MRP) family. To elucidate the role of MRP family members in HCC, we analyzed the expression and subcellular localization of MRP1 (ABCC1), MRP2 (ABCC2) and MRP3 (ABCC3); all 3 isoforms have been shown to confer resistance to chemotherapeutic drugs. Semiquantitative RT-PCR demonstrated that MRP2 and MRP3 mRNA expression in HCC was at least 10-fold higher than MRP1 mRNA expression. MRP2 immunostaining was observed in 87% (33/38) of HCC samples. MRP2 was localized in the plasma membrane in a polarized fashion, either in trabecular structures resembling the canalicular membrane or in the luminal membrane when cells had a pseudoglandular arrangement. MRP3 was detected in all samples examined (9/9) by RT-PCR and by immunofluorescence microscopy. MRP3 was localized to the basolateral membrane of carcinoma cells. Double-label immunofluorescence microscopy with antibodies specific for MRP2 or MRP3 indicated that carcinoma cells expressed both MRP isoforms simultaneously. When MRP1 was detected by immunofluorescence microscopy, it was localized on the intracellular membranes of carcinoma cells. Thus, plasma membrane expression of MRP2 and MRP3, but not of MRP1, can contribute to the MDR phenotype of HCC.

Adenosine Triphosphate↗

PubMed2001

Subgingival polishing compared to scaling with steel curettes: a clinical pilot study.

BACKGROUND: Recently, we have developed teflon-coated sonic scaler inserts which remove plaque without removing tooth substance; they polish subgingivally. In a preclinical test, we showed that these modified inserts remove plaque nearly as effectively as do conventional sonic scaler inserts. The present investigation was intended as a proof-of-principle of subgingival polishing. The aim was to study the effect of subgingival polishing on the resolution of gingival inflammation in comparison to conventional scaling. MATERIAL AND METHODS: In 10 patients with moderate to advanced periodontal disease, who had at least 2 single-rooted teeth with a probing depth of >6 mm in each quadrant, all single-rooted teeth were subjected to one treatment regimen consisting of 2 instrumentation episodes (1st/2nd treatment): curette/curette, curette/teflon-coated sonic scaler, teflon-coated sonic scaler/teflon-coated sonic scaler, and an untreated control. The second treatment session was performed 3 months after the first instrumentation, and the final registration 3 months after the second instrumentation. Clinical measurements included probing depth, change of clinical attachment level, bleeding upon probing, and plaque scores. RESULTS: Probing depth, attachment level, and bleeding scores were reduced in the 3 instrumentation groups versus the control group in the 1st period; in the 2nd period, no further change occurred. Subgingival polishing with teflon-coated sonic scaler inserts was slightly less effective than conventional scaling. CONCLUSION: Subgingival polishing with teflon-coated sonic scaler inserts seems to be nearly as effective as conventional scaling. Thus, it may be the instrumentation of choice for maintenance treatment of residual pockets.

Adult↗

PubMed2001

Retrospective comparison of clinical variables between compliant and non-compliant patients.

BACKGROUND: The aim of this retrospective study was to evaluate if patients with moderate to advanced periodontitis had comparable periodontal conditions at baseline and during supportive periodontal therapy (SPT) whether they were compliant or not. METHOD: Patient-related variables were compared: age, tooth mobility, furcation involvement, number of teeth, pocket probing depth, plaque index. Compliant patients (n = 142) received complete periodontal treatment and were followed over at least 10 years (group A). Non-compliant patients either discontinued supportive periodontal therapy (n = 42, group B) or dropped out before or during periodontal surgery (n = 44, group C). RESULTS: At baseline, there were no significant differences between the 3 groups except for mobility. During SPT, mean pocket probing depth and plaque index differed significantly. CONCLUSION: These results indicate that non-compliant patients compared to compliant patients had similar periodontal conditions at baseline, but responded less favourably to periodontal surgery and maintenance.

Adult↗

PubMed2001

The multidrug resistance protein MRP1 mediates the release of glutathione disulfide from rat astrocytes during oxidative stress.

The release of glutathione disulfide has been considered an important process for the maintenance of a reduced thiol redox potential in cells during oxidative stress. In cultured rat astrocytes, permanent hydrogen peroxide-induced oxidative stress caused a rapid increase in intracellular glutathione disulfide, which was followed by the appearance of glutathione disulfide in the medium. Under these conditions, the viability of the cells was not compromised. In the presence of cyclosporin A and the quinoline-derivative MK571, inhibitors of multidrug resistance proteins (MRP1 and MRP2), glutathione disulfide accumulated in cells and the release of glutathione disulfide from astrocytes during H2O2 stress was potently inhibited, suggesting a contribution of MRP1 or MRP2 in the release of glutathione disulfide from astrocytes. Using RT-PCR we amplified a cDNA from astroglial RNA with a high degree of homology to MRP1 from humans and mouse. In contrast, no fragment was amplified by using primers specific for rat MRP2. In addition, the presence of MRP1 protein in astrocytes was demonstrated by its immunolocalization in cells expressing the astroglial marker protein glial fibrillary acidic protein. Our data identify rat astrocytes as a MRP1-expressin, brain cell type and demonstrate that this transporter participates in the release of glutathione disulfide from astrocytes during oxidative stress.

ATP Binding Cassette Transporter, Subfamily B, Mem↗