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Biomedical subjects

K Richter

Publications and source records attributed to K Richter.

At least 37 records · Page 2Linked to original sources
PubMed2003

Reproducibility of forced inspiratory and expiratory volumes after bronchodilation in patients with COPD or asthma.

The aim of the present study was to assess the reproducibility of changes in forced inspiratory volumes after bronchodilator inhalation. Thirteen patients with chronic obstructive pulmonary disease (COPD) (FEV1, 32-75%pred) and 10 patients with asthma (FEV1, 43-75%pred) inhaled either 200 microg fenoterol or 200 microg oxitropium bromide or placebo, each of them on three occasions, on nine different days in a randomised, cross-over, double-blind fashion. Forced expiratory (FEV1) and inspiratory (FIV1) volumes were measured before and 30 min after inhalation. In patients with COPD, the increase in FEV1 (coefficient of variation) was 221 ml (43%) after fenoterol and 235 ml (33%) after oxitropium; changes in FIV1 were 301 ml (45%) and 360 ml (29%). In patients with asthma, FEV1 improved by 618 ml (26%) and 482 ml (25%), FIV1 by 553 ml (41%) and 475 ml (23%). In less severe COPD or asthma, the reduction in dyspnoea was associated with the improvements in both FIV1 and FEV1, but in severe COPD with the improvement in FIV1 only. The data demonstrate that, at least in terms of relative changes, the reproducibility of bronchodilator responses in terms of FIV1 is similar to that of FEV1 and they underline the assertion of FIV1 being a sensible parameter particularly in severe COPD.

Adrenergic beta-Agonists↗
PubMed2003

Data assimilation in the decision support system rodos.

Model predictions for a rapid assessment and prognosis of possible radiological consequences after an accidental release of radionuclides play an important role in nuclear emergency management. Radiological observations, e.g. dose rate measurements, can be used to improve such model predictions. The process of combining model predictions and observations, usually referred to as data assimilation, is described in this article within the framework of the real time on-line decision support system (RODOS) for off-site nuclear emergency management in Europe. Data assimilation capabilities, based on Kalman filters, are under development for several modules of the RODOS system, including the atmospheric dispersion, deposition, food chain and hydrological models. The use of such a generic data assimilation methodology enables the propagation of uncertainties throughout the various modules of the system. This would in turn provide decision makers with uncertainty estimates taking into account both model and observation errors. This paper describes the methodology employed as well as results of some preliminary studies based on simulated data.

Algorithms↗
PubMed2003

Repeated measurements of allergens and endotoxin in settled house dust over a time period of 6 years.

BACKGROUND: Studies investigating the effect of exposure to indoor allergens and endotoxin on human respiratory health usually take dust samples only at one single point of time and consider them to be representative for the indoor biocontaminant burden during a time period of several years. This singly measured biocontaminant concentration is related to adverse respiratory outcomes such as asthma, wheeze or others. OBJECTIVE: We analysed two repeated measurements of mite and cat allergens in mattress and living room floor dust as well as endotoxin concentrations in living room floor dust. The repeated samples were taken over a time period of about 6 years. We investigated the repeatability over time of their concentrations by determining correlation coefficients and computing within- and between-home variance components. METHODS: Our analysis was based on the population of a study on Indoor Factors and Genetics in Asthma (INGA) being carried out in 1995/96 and followed up in 2000/01. Complete data were available from 152 participants. RESULTS: The measured allergen concentrations were low and a considerable percentage of the values was below the limit of detection. The crude Spearman's rank correlation coefficients between the two measurements taken in 1995/96 and 2000/01 ranged from 0.32 to 0.61 for the dust mites allergens, from 0.21 to 0.44 for cat allergen and from 0.35 to 0.51 for endotoxin. Correlations were higher if measurements were performed on the same floor or the same mattress at both sampling time-points. The within-home variance for all measured biocontaminant concentrations was of about the same order as the between-home variance. CONCLUSION: For studies like ours with low allergen and endotoxin concentrations, the repeatability of these concentrations over a time period as long as 6 years is low and a single measurement does not accurately reflect the true long-term exposure in the homes.

Allergens↗
PubMed2003

The salt paradox of the early diabetic kidney is independent of renal innervation.

Glomerular filtration rate (GFR) is inversely and thus paradoxically related to dietary NaCl intake in rats and patients with early type 1 diabetes mellitus (DM). Enhanced sensitivity of proximal reabsorption to NaCl diet inducing secondary adaptations in GFR through actions of tubuloglomerular feedback causes this salt paradox. We studied the role of renal nerves for the salt paradox in rats with streptozotocin (STZ)-induced DM since a regulatory influence of renal nerves on proximal reabsorption is well established. The left kidney (LK) was denervated before induction of STZ-DM. Subsequently, the normal diet was continued or a low NaCl diet was initiated and 1 week later animals were prepared for clearance experiments under anesthesia including ureter catheterization to measure GFR for each kidney. In diabetic rats, the right innervated as well as the left denervated kidney showed higher values for GFR and kidney weight in animals on a low versus a normal NaCl diet indicating that the salt paradox occurs independent of renal innervation. In addition, evidence is provided that the renal nerves of non-diabetic rats do not contribute to renal Na(+) retention during dietary NaCl restriction but modulate renal hemodynamics and kidney weight under these conditions.

Animals↗
PubMed2003

Montelukast attenuates the airway response to hypertonic saline in moderate-to-severe COPD.

This study assessed the effect of the leukotriene receptor antagonist montelukast on hypertonic saline-induced airway obstruction. A total of 29 patients with chronic obstructive pulmonary disease (forced expiratory volume in one second (FEV1), 42+/-4% predicted) received either 10 mg montelukast and 3 h later placebo via metered-dose inhaler (MDI) (M), or placebo and 3 h later 200 microg salbutamol (S), or two doses of placebo (P), in a randomised order. Patients inhaled salbutamol 1 h after MDI and the challenge was performed 15 min later (3% saline, 5 min). Data are given as per cent changes versus baseline. Compared to P, S caused significant bronchodilation in FEV1 (7.3%) and forced inspiratory volume in one second (FIV1) (4.5%), and M in FIV1 (1.5%). The saline-induced fall in FEV1 was lower after M (-5.8%), compared with S (-10.3%) and P (-13.1%). FEV1 (11.3%) and FIV1 (7.6%) was improved over baseline after recovery by M but not P and S. Recovery times regarding FEV1 (8.5 min) and FIV1 (15.2 min) were shortest after M, respective values for S being 16.8 and 20.4 min, and for P 15.9 and 21.2 min. Effects were strongest in patients with low baseline FEV1 and/or inhaled corticosteroids. Data from this study indicate beneficial effects of montelukast on hypertonic saline-induced airway responses in patients with chronic obstructive pulmonary disease, particularly those with severe disease. The major effect was an accelerated recovery leading to values above baseline.

Acetates↗
PubMed2002

Increasing sample throughput in pharmacological studies by using dual-column liquid chromatography with tandem mass spectrometry.

A robust novel technology of parallel chromatography combined with tandem mass spectrometry was successfully applied to a biological matrix extract for analyte detection. The presented study shows how only by using an additional isocratic pump, a second column and a 10-port valve the throughput is twice of that of a conventional single column system with the same sensitivity. Analytes and matrix were separated and eluting peaks of the first column were detected while the second column was equilibrated. The system was tested and used for the determination of several drugs, metabolites and endogenous compounds (i.e., propiverine, talinolol, scopolamine and leukotrienes).

Adrenergic beta-Antagonists↗
PubMed2002

The neuron-specific Ca2+-binding protein caldendrin: gene structure, splice isoforms, and expression in the rat central nervous system.

Caldendrin is the founder member of a recently discovered family of calmodulin-like proteins, which are highly abundant in brain. In this study we examined the organization of the murine and human caldendrin gene as well as the expression pattern of transcripts for caldendrin and two novel splice variants. In addition the distribution of caldendrin in rat brain has been assessed by immunohistochemistry. Caldendrin is localized to the somatodendritic compartment of a subpopulation of mainly principal neurons in brain regions with a laminar organization and is present only at a subset of mature excitatory synapses. Caldendrin immunoreactivity (IR) is tightly associated with the cortical cytoskeleton, enriched in the postsynaptic density (PSD) fraction, and associates late during development with the synaptic cytomatrix. The expression is highly heterogenous within cortex, with highest levels of caldendrin IR in layer III of the piriform and layer II/III of the somatosensory cortex. The segregated cortical distribution to areas, which represent the most important primary sensory systems of the rodent brain, may reflect different requirements for dendritic Ca2+-signaling in these neurons. The presence of caldendrin in the PSD of distinct synapses may have important implications for Ca2+-modulated processes of synaptic plasticity.

Alternative Splicing↗
PubMed2002

Repeated ozone exposures enhance bronchial allergen responses in subjects with rhinitis or asthma.

BACKGROUND: Single exposures to > 200 p.p.b. of ozone are capable of enhancing the early-phase lung function response to allergen. OBJECTIVE: The aim of the present study was to compare the effect of single vs. repeated exposures to ozone on early and late-phase allergen responses. METHODS: Eleven subjects with allergic asthma and 22 subjects with allergic rhinitis underwent single exposures to filtered air, 125 p.p.b. and 250 p.p.b. ozone, as well as repeated exposures to 125 p.p.b. ozone on four consecutive days. Twenty hours after the (final) exposure, subjects inhaled a single dose of allergen and a sputum induction was performed 6-7 h later. RESULTS: In the subjects with rhinitis, the mean early-phase response of FEV1 and the number of > or = 20% reductions were significantly greater after exposure to 250 or 4 x 125 p.p.b. ozone compared with filtered air. In addition, most of the > or = 15% late-phase responses in FEV1 occurred after exposure to 4 x 125 p.p.b., as well as the strongest effects on sputum parameters. The rise in the number of eosinophils was statistically significant in both groups. Regarding the number of lymphocytes and the concentrations of mast cell tryptase, histamine or LDH, significance was, however, only reached in the asthma group. CONCLUSION: Our data suggest that repeated exposure to ozone, at a peak ambient air level, can enhance both functional and inflammatory responses to inhaled allergen in subjects with pre-existing allergic airway diseases, and that these effects might reach a clinically relevant magnitude.

Adult↗
PubMed2002

[European Community Respiratory Health Survey in Adults (ECRHS)].

The European Community Respiratory Health Survey (ECRHS) was the first study to assess the geographical variation in asthma, allergy, and allergic sensitization in adults using the same instruments and definitions. The database of the ECRHS includes information from approximately 140 000 individuals aged 20 - 44 years from 22 countries. The aim of this review is to summarize the results of the ECRHS and to present the specific contribution of the German centers in Hamburg and Erfurt. The prevalence ranged from 2.0 - 11.9 % for asthma, 9.5 - 40.9 % for allergic rhinitis, 4.0 - 32.0 % for wheeze, 3.4 - 27.9 % for bronchial hyperreactivity, and 16.2 - 44.5 % for allergic sensitisation against common aeroallergens. Although the prevalence of these atopic disorders were found to be consistently higher for the Hamburg center compared to the Erfurt center, strong regional differences in the prevalences were also found within several other European countries. Overall Europe, the lowest prevalences were seen in the Eastern and Middle European countries with the center Erfurt, followed by the Mediterranean region. The highest prevalences were reported for all English speaking centers. Strong geographic variation was reported for medication for asthma. Asthma seems to be undertreated in several countries. Environmental exposures and in particular indoor factors, and exposures at the workplace are playing a major role for asthma in adulthood. Furthermore, protective effects on atopy were found for exposures to pets (dogs) and a large number of siblings in early childhood. In conclusion, the ECRHS has shown that the prevalence of asthma varies widely. The fact that the geographical pattern is consistent with the distribution of atopy and bronchial responsiveness supports the conclusion that the geographical variations in the prevalence of asthma are true and likely due to environmental factors.

Adult↗
PubMed2002

Acute protection against exercise-induced bronchoconstriction by formoterol, salmeterol and terbutaline.

The onset of bronchoprotection as obtained by various beta2-agonists has not been examined in a comparitive study. In this study, the onset of bronchodilation and protection against exercise-induced bronchoconstriction in asthmatics after inhalation of the long-acting beta2-agonists formoterol and salmeterol and the short-acting beta2-agonist terbutaline were measured. Twenty-five subjects with asthma and a history of exercise-induced bronchoconstriction (mean baseline forced expiratory volume in one second (FEV1): 90% predicted; mean fall in FEV1 after exercise: 31% from baseline) were enrolled in this double-blind, double-dummy, placebo-controlled, randomized, four-period crossover study. Exercise challenges were performed on 12 days at either 5, 30, or 60 min after inhalation of a single dose of formoterol (12 microg Turbuhaler), salmeterol (50 microg Diskus), terbutaline (500 microg Turbuhaler) or placebo. Exercise-induced bronchoconstriction (maximum fall in FEV1 or area under the curve) did not differ significantly between terbutaline, formorerol and salmeterol either 5, 30, or 60 min after inhalation of the study medication. In contrast, the onset of bronchodilation was slower after salmeterol compared to terbutaline and formoterol (p<0.05, each), which both showed a similar time course. At all time points between 5 and 60 min, formoterol provided significantly greater bronchodilation than salmeterol (p<0.05). These data indicate that equipotent doses of the bronchodilators salmeterol, formoterol and terbutaline were similarly effective with respect to their short-term protective potency against exercise-induced bronchoconstriction, despite the fact that the time course of bronchodilation was significantly different between the three beta2-agonists.

Administration, Inhalation↗
PubMed2002

Montelukast versus fluticasone: effects on lung function, airway responsiveness and inflammation in moderate asthma.

Whether leukotriene receptor antagonists exhibit adequate anti-inflammatory effects in the treatment of asthma is still a controversial issue. The aim of the present study was to perform a direct comparison of the effects of a 4-week treatment with either montelukast (10 mg, once a day) or low-dose inhaled fluticasone (100 microg b.i.d.) on functional and inflammatory parameters in steroid-naïve patients with moderate asthma. Forty patients (forced expiratory volume in one second (FEV1), 60-80% predicted) were studied in a double-blind, randomised, crossover design. Treatment periods were separated by 3-8 weeks of washout. At the beginning and end of each period, FEV1, airway responsiveness to inhaled methacholine (provocative concentration causing a 20% fall in FEV1 (PC20)), the level of exhaled nitric oxide (NO) and sputum differential cell counts were determined. Only short-acting beta2-agonists were allowed for relief of symptoms. FEV1 increased by 0.50+/-0.07 L (mean+/-SEM) after fluticasone and by 0.37+/-0.07 L after montelukast (p<0.001, each), and PC20 by 1.33+/-0.13 (p<0.001) and 0.15+/-0.17 (NS) doubling doses, respectively. Correspondingly, percentages of sputum eosinophils were reduced by factor 2.7 (p<0.01) and 1.4 (nonsignificant (NS)), and the levels of exhaled NO (at 50 mL x s(-1)) by factor 2.1 (p<0.01) and 1.1 (NS). These data indicate a comparable bronchodilator action of montelukast and fluticasone in patients with moderate asthma, but additional attenuation of airway inflammation by fluticasone as detectable through noninvasive methods.

Acetates↗
PubMed2002

Dose reduction of inhaled corticosteroids under concomitant medication with montelukast in patients with asthma.

The present study aimed at comparing the effects of a dose reduction of inhaled corticosteroids on lung function, indirect measures of airway inflammation and clinical scores during treatment with a leucotriene receptor antagonist. In 50 patients (mean forced expiratory volume in one second (FEV1) 94% predicted), steroid doses (800 microg beclomethasone dipropionate) were first reduced to 50% and then to 25%, for 6 weeks each. One group received a placebo and the other group received montelukast (10 mg). The first reduction did not cause significant effects. During the second, FEV1 and peak expiratory flow decreased in both groups (p<0.001). Daytime symptoms were not altered with placebo but were reduced by montelukast (p<0.05). Night-time symptoms were slightly elevated with placebo (p<0.05) but not montelukast, as well as the use of supplemental salbutamol. Changes in provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), sputum eosinophils and exhaled nitric oxide were mostly nonsignificant for both placebo and montelukast. These data demonstrate that a 75% reduction in the dose of steroid given to patients with asthma led to a deterioration in lung function not prevented by montelukast, whereas changes in clinical state seemed to favour montelukast treatment. It therefore appears that potential effects of montelukast, in the presence of low-dose steroids, could not be attributed to single indices of lung function or airway inflammation.

Acetates↗
PubMed2002

Predictors of cat allergen (Fel d 1) in house dust of German homes with/without cats.

BACKGROUND: Exposure to cat allergen is a major risk factor for sensitization and the development of asthma in many parts of the world. The study was designed to examine the levels of cat allergen (Fel d 1) in homes of two German cities and to detennine predictors of Fel d 1 exposure. METHODS: We collected dust samples from 405 randomly selected homes in Hamburg (n = 201) and Erfurt (n = 204). In each apartment dust samples were taken from living room floor (LR), bedroom floor (BR), and mattress surface (MA) using vacuum sampling and analyzed by two-site monoclonal antibody ELISA. Environmental variables were assessed by questionnaire to obtain information on factors supposed to have an impact on the Fel d 1 levels in house dust. The effects of possible predictors of Fel d 1 were assessed by multiple linear regression models. RESULTS: Fel d 1 was present in 98% of the homes (395/405), ranging from 0.015 to 7.278 microg/g dust (GM 0.486 microg/g). The levels were similar in floors (GM for LR 0.575 microg/g and BR 0.469 microg/g) and in MA (GM 0.424 microg/g). Higher allergen concentrations (> 2 microg/g) were detected in 99% of the homes keeping cats, in 55% of homes that had had a cat during the last year, and in 28% of the homes without a cat. Fel d 1 levels were significantly higher in homes with a cat (628-682-fold, MA, floor) and in homes in which a cat had previously lived (11-12-fold, floor, MA) than in homes that never had a cat. Furthermore, after controlling for possible other confounders, Fel d 1 levels were significantly higher in summer and in homes with low frequency of cleaning and low ventilation rate. CONCLUSION: It could be confirmed that keeping a cat has the highest impact on Fel d 1 concentration. Besides, a continuous influx of Fel d 1 in homes without cat, as a result of direct or indirect cat contact outside the home, is likely. High frequencies of dusting and ventilation might reduce cat allergens in homes with and without cats.

Allergens↗
PubMed2001

Donor-derived soluble MHC antigens plus low-dose cyclosporine induce transplantation unresponsiveness independent of the thymus by down-regulating T cell-mediated alloresponses in a rat transplantation model.

BACKGROUND: In vitro, soluble MHC (sMHC) antigens modulate and induce apoptosis in alloreactive and antigen-specific T cells, demonstrating their potency to regulate T cell-mediated immune responses. However, their efficacy to regulate immunological responses in vivo remains unclear. Here, we report that repetitive intraperitoneal injection of recombinant Lewis rat-derived MHC class I antigens in Dark Agouti (DA) rats modulates alloreactivity. METHODS: RT1.A1 (Lewis derived) genes were cloned into mammalian expression vectors, and RT1.Aa (DA derived) genes were used to transfect a rat myeloma cell line. RT1.A1 molecules were injected intraperitoneally in DA recipients that subsequently underwent transplantation with Lewis-derived cardiac allografts. RESULTS: Soluble class I antigens were secreted by the transfected cells and were shown to be heterodimeric, peptide-loaded, and conformationally folded. Injection of donor-derived soluble MHC significantly reduced the ability of recipient animals to mount a cytotoxic T-cell response to donor-derived tissue. More interestingly, this treatment significantly prolonged donor-graft survival and allowed 60% of treated animals to develop graft tolerance (>120 days), when donor sMHC were combined with a single subtherapeutic dosage of cyclosporine. Thymectomy of recipient animals before transplantation did not interfere with induction of peripheral tolerance. CONCLUSIONS: Donor-derived sMHC are potential tolerogens for down-regulating the cytotoxic T-cell response of animals that undergo transplantation. Thus, these data provide for the first time a rationale for the application of directly injected sMHC in vivo to down-regulate immunological responses and aid the induction of graft tolerance.

Animals↗
PubMed2001

Quantum transport in nonuniform magnetic fields: Aharonov-Bohm ring as a spin switch.

We study spin-dependent magnetoconductance in mesoscopic rings subject to an inhomogeneous in-plane magnetic field. We show that the polarization direction of transmitted spin-polarized electrons can be controlled via an additional magnetic flux such that spin flips are induced at half a flux quantum. This quantum interference effect is independent of the strength of the nonuniform field applied. We give an analytical explanation for one-dimensional rings and numerical results for corresponding ballistic microstructures.

Journal Article↗
PubMed2001

Classical and quantum periodically driven scattering in one dimension.

Irregular scattering at harmonically driven one-dimensional potential wells is studied both on the classical and the quantum level. We show that an ac-driven single square well, and a smooth well with oscillating bottom, are sufficient to generate chaotic scattering. For a square well with oscillating bottom, we introduce the concept of pseudointegrable scattering. The quantum dynamics of these models is treated using Floquet scattering theory, which is exact for arbitrary amplitude and frequency of the driving. In the deep quantum regime, scattering is dominated by multiphoton exchanges with the driving field, leading to complex resonance structures in transmission and reflection. For strong and fast driving, the ac-driven square well develops an effective double-well potential that introduces coherent tunneling in the scattering. We identify signatures of classical chaotic scattering in a phase-space representation of the quantum dynamics.

Journal Article↗
PubMed2001

Coordinated ATP hydrolysis by the Hsp90 dimer.

The Hsp90 dimer is a molecular chaperone with an unusual N-terminal ATP binding site. The structure of the ATP binding site makes it a member of a new class of ATP-hydrolyzing enzymes, known as the GHKL family. While for some of the family members structural data on conformational changes occurring after ATP binding are available, these are still lacking for Hsp90. Here we set out to investigate the correlation between dimerization and ATP hydrolysis by Hsp90. The dimerization constant of wild type (WT) Hsp90 was determined to be 60 nm. Heterodimers of WT Hsp90 with fragments lacking the ATP binding domain form readily and exhibit dimerization constants similar to full-length Hsp90. However, the ATPase activity of these heterodimers was significantly lower than that of the wild type protein, indicating cooperative interactions in the N-terminal part of the protein that lead to the activation of the ATPase activity. To further address the contribution of the N-terminal domains to the ATPase activity, we used an Hsp90 point mutant that is unable to bind ATP. Since heterodimers between the WT protein and this mutant showed WT ATPase activity, this mutant, although unable to bind ATP, still has the ability to stimulate the activity in its WT partner domain. Thus, contact formation between the N-terminal domains might not depend on ATP bound to both domains. Together, these results suggest a mechanism for coupling the hydrolysis of ATP to the opening-closing movement of the Hsp90 molecular chaperone.

Adenosine Triphosphatases↗