Biomedical subjects

M Linden

Publications and source records attributed to M Linden.

At least 73 records · Page 4Linked to original sources

PubMed1999

A low-cost, portable system for the assessment of the postural response of wheelchair users to perturbations.

Maintaining seated postural stability presents a serious challenge to wheelchair users in vehicles, even during normal driving conditions. The purpose of this research was to develop a system for the study of seated postural control in response to perturbations similar to those that might be experienced during vehicle turning and braking. A servo-controlled tilt platform was constructed to provide a low-cost, small, and easily transportable device for generating precise and repeatable perturbations. Tilt platform operation was examined for accuracy and reproducibility of a desired perturbation. Repeatability was high with a mean signal-to-noise ratio (SNR) of 45.4 for a given perturbation measured across 11 subjects. An initial comparison of stability results obtained on the tilt platform and in a vehicle showed a correspondence, although differences were apparent. The tilt platform has been used successfully to assess balance in spinal cord-injured subjects and to test wheelchair securement systems.

Acceleration↗

PubMed1999

Demonstration of bronchial eosinophil activity in seasonal allergic rhinitis by induced plasma exudation combined with induced sputum.

BACKGROUND: Patients with seasonal allergic rhinitis may develop bronchial hyperresponsiveness during the active disease period. Eosinophil activation may occur in the bronchial mucosa and may be reflected by increased sputum levels of eosinophil cationic protein (ECP), especially when ECP binding proteins such as alpha 2-macroglobulin pass through the lamina propria and across the epithelium into the airway lumen. A study was therefore undertaken to determine histamine airway responsiveness (FEV1) and bronchovascular responsiveness (exudation of alpha 2-macroglobulin) to histamine in subjects with seasonal allergic rhinitis, and to explore whether sputum ECP levels are increased by the use of induced exudation followed by induced sputum. METHODS: Eleven patients with seasonal allergic rhinitis were examined before and during a birch pollen season. Sputum was induced by inhalation of 4.5% saline twice before and twice during the pollen season. Histamine inhalations were given before the second of each pair of sputum inductions at increasing concentrations until FEV1 was reduced by 20%. Sputum levels of alpha 2-macroglobulin and ECP were determined as indices of bronchial exudation of plasma and activation of bronchial eosinophils, respectively. RESULTS: Bronchomotor responsiveness increased during the pollen season (median difference in the reduction of FEV1 9% (95% confidence interval (CI) -3 to 26)) but histamine induced exudation of plasma was not increased. Baseline sputum levels of alpha 2-macroglobulin and ECP did not increase. Histamine induced exudation of alpha 2-macroglobulin was associated with increased sputum levels of ECP exclusively during the pollen season (median difference 8.2 ng/ml (95% CI 0.4 to 562.0)). CONCLUSION: Bronchial hyperresponsiveness in seasonal allergic rhinitis may not be associated with bronchovascular exudative hyperresponsiveness. Sputum levels of ECP were increased only during the season, and only after induced exudation (potentially moving ECP to the mucosal surface). It is suggested that the combined method of induced exudation and induced sputum may significantly improve the yield of some markers of inflammation in sputum samples.

Adult↗

PubMed1999

Allergen-induced eosinophil cytolysis is a primary mechanism for granule protein release in human upper airways.

Cytotoxic eosinophil granule proteins are considered important in the pathogenesis of allergic airway diseases such as rhinitis and asthma. To explore the cellular mechanisms behind eosinophil granule release in human allergic airways, 16 symptom-free patients with seasonal allergic rhinitis were challenged daily with allergen during 1 wk. Nasal lavage samples and biopsies, obtained before and 24 h after the last allergen exposure, were processed for immunohistochemical and electron microscopic analysis. The allergen challenges produced nasal symptoms, marked tissue eosinophilia, and an increase in lavage fluid levels of eosinophil cationic protein (ECP). The nasal mucosa areas with intense extracellular immunoreactivity for ECP were associated with abundant free eosinophil granules. Electron microscopy confirmed the free granules and revealed that all mucosal eosinophils were involved in granule release, either by cytolysis (33%) or piecemeal degranulation (PMD) (67%). Resting or apoptotic eosinophils were not observed. Cytolytic eosinophils had less signs of intracellular granule release (p < 0. 001) and a higher content of intact granules (p < 0.001) compared with viable eosinophils in the same tissue. This study demonstrates eosinophil cytolysis (ECL) as a distinct mechanism for granule mediator release in human allergic airway mucosa. The nature and extent of the ECL and its product (i.e., protein-laden extracellular granules) indicate that allergen-induced cytolysis is a primary and major mechanism for the release of eosinophil proteins in human allergic airway inflammation in vivo.

Adolescent↗

PubMed1999

Allergen challenge-induced acute exudation of IL-8, ECP and alpha2-macroglobulin in human rhinovirus-induced common colds.

Rhinovirus infections cause exacerbations of eosinophilic airway disease. The acute effects of allergen-challenge on nasal interleukin-8 (IL-8), eosinophil cationic protein (ECP), and alpha2-macroglobulin were examined in atopic subjects with common cold symptoms. Twenty-three patients with seasonal allergic rhinitis were inoculated with human rhinovirus 16 outside the pollen season. Diluent and allergen challenges, followed by nasal lavages, were carried out about 3 months before and 4 days after virus inoculation. Seventeen patients developed significant common cold symptoms with increased nasal lavage fluid levels of alpha2-macroglobulin, IL-8, and ECP at baseline (p<0.001-0.05 versus before inoculation), and were further increased by allergen challenge (p< 0.001-0.05); IL-8 and ECP levels were correlated (r = 0.63, p<0.001). Before inoculation, the six patients who later did not develop common cold symptoms had high levels of IL-8 and myeloperoxidase (MPO), and exhibited strong allergen-induced plasma exudation responses (alpha2-macroglobulin). After inoculation, IL-8 and ECP did not increase in these symptomless subjects. In conclusion, high nasal interleukin-8 and myeloperoxidase levels and exudative hyperresponsiveness may protect against infection. The association between nasal interleukin-8 and eosinophil cationic protein in common cold, particularly that observed in nasal lavage fluids after allergen-induced acute exudation of plasma, suggests the involvement of interleukin-8 in exacerbation of airway mucosal eosinophil activity.

Adolescent↗

PubMed1999

Alpha2-macroglobulin and eosinophil cationic protein in the allergic airway mucosa in seasonal allergic rhinitis.

As previously demonstrated in seasonal allergic rhinitis, increased microvascular permeability and eosinophil activation are key features of allergic airway inflammation. In the present study, the hypothesis that exudation of alpha2-macroglobulin may cause the appearance of eosinophil cationic protein (ECP) in the airway lumen was explored. Nasal lavages were carried out using the nasal pool device before and during the pollen season both at baseline and after histamine challenge in 10 children with allergic rhinitis. Nasal lavage fluid levels of alpha2-macroglobulin and ECP were determined. All patients experienced nasal symptoms of allergic rhinitis during the pollen season (p<0.01-0.05). Baseline nasal lavage fluid levels of alpha2-macroglobulin and ECP were increased during the season (p<0.01-0.05) and were found to be well correlated (p<0.0001). Histamine produced concentration-dependent plasma exudation before and during the pollen season, but it was only during the pollen season that this caused an increase in the lavage fluid levels of ECP (p<0.05). These data suggest that exudation of plasma and increased tissue levels and output of eosinophil cationic protein characterize nasal mucosal inflammation in children with seasonal allergic rhinitis. The plasma exudation process in part may account for lumenal entry of eosinophil cationic protein molecules that have been released in mucosal tissue compartments. A combination of induced exudation and nasal lavage may improve the yield of important markers of inflammation in studies of nasal diseases.

Biomarkers↗

PubMed1999

Cross-cultural comparison of depressive symptoms in Europe does not support stereotypes of ageing.

BACKGROUND: Stereotypes of older people suggest that they are depressed. AIMS: To examine depression symptoms among people aged > or = 65 in the general population and to ask the following questions. Are there high proportions of depressive symptoms among otherwise well people? Do these levels reflect the prevalence of depression? Do key symptoms vary with age and do they confirm stereotypes? METHOD: Nine centres contributed data from community-based random samples, using standardised methods (GMS-AGECAT package). RESULTS: Proportions of depressive symptoms varied between centres. Some often associated with ageing were rare. Many were more common in women. Low-prevalence centres tended to have fewer symptoms among 'well' people, but there were inconsistencies. Low levels of symptoms among the well population of a centre did not necessarily predict lower levels in the depressed. CONCLUSIONS: Variations in the prevalence of depressive symptoms occurred between centres, not always related to levels of illness. There was no consistent relationship between proportions of symptoms in well persons and cases for all centres. Few symptoms were present in > 60% of the older population--stereotypes of old age were not upheld.

Age Factors↗

PubMed1999

Postural stability of wheelchair users exposed to sustained, external perturbations.

The postural stability of wheelchair users experiencing external perturbations was examined. Rotation of a tilt platform generated moments in the trunks of subjects seated in a manual wheelchair on the platform. The magnitude and duration of the moments were on the order of those that might be encountered in the sagittal plane during controlled braking maneuvers in a vehicle. Four subjects with tetraplegia, four with paraplegia, and five controls participated in experimental trials on the platform. As input, four different Disturbance profiles with either a 0.2 g (gravitational acceleration) or 0.4 g maximal level were imposed. The majority of the subjects with spinal cord injury lost balance at Disturbance levels below 0.2 g. The results suggest that the rate of change of the applied perturbation may also affect stability. The use of a stability index based on normalized motion of the center of pressure with respect to the seat showed efficacy in characterizing the response.

Adult↗

PubMed1998

Antioxidative properties of organotellurium compounds in cell systems.

The protective/antioxidative properties of diaryl tellurides were demonstrated in cellular systems of increasing complexity. In the presence of glutathione, bis(4-hydroxyphenyl) telluride (1a), bis(4-aminophenyl) telluride (1d) and bis(2-carboxyphenyl) telluride (1h) reduced by more than 50% t-butyl hydroperoxide-induced cell death in lung fibroblast cultures at concentrations below 2 microM. Bis(2,6-dimethyl-4-hydroxyphenyl) telluride (2b) reduced by more than 50% leukocyte-mediated and phorbol-12-myristate-13-acetate-stimulated damage to Caco-2 cells at 0.1 microM concentration. As judged by their abilities to reduce formation of thiobarbituric acid reactive substances at concentrations close to 1 microM, diaryl tellurides 1a, 1d and 2b protected rat kidney tissue against oxidative damage caused by anoxia and reoxygenation. The organotellurium compounds also offered protection after systemic administration. In the presence of diaryl telluride 2b (0.1-1 microM), the ischemia/reperfusion-induced vascular permeability increase in the hamster cheek pouch was significantly reduced as compared with the control. Some of the most active organotellurium cell protectants were evaluated for their ability to inhibit formation of the inflammatory mediators leukotriene B4 and interleukin-1beta. An inhibitory effect on the secretion of these species was seen for compounds 1a and 2b at or above 10 microM concentrations. The protective effects of diaryl tellurides against t-butyl hydroperoxide-induced cell injury can be ascribed mainly to the peroxide-decomposing, glutathione peroxidase-like capacity of the compounds. The chain-breaking, electron- or hydrogen atom-donating ability of diaryl tellurides seems to be the main reason for their protection against leukocyte-mediated cell damage in Caco-2 cells and in the oxidatively challenged rat kidney and hamster cheek pouch.

Aniline Compounds↗

PubMed1998

Fluoxetine treatment and single psychotropic comedication: is there an increase in adverse event rates?

After the market launch of fluoxetine (Flx) in Germany in 1990 several series of drug utilization observation studies were carried out under naturalistic conditions (approximately 19,000 patients). This paper focuses on 3158 patients from neuropsychiatric practices comparing adverse event rates plus additional variables in patient groups treated with Flx monotherapy (n=1571) versus those receiving comedication with a single psychotropic (n=737), or those subgroups receiving a single antidepressant (n=222) or antipsychotic drug (n=128). Compared to the monotherapy group, both the comedicated group as a whole and the antidepressant subgroup did not show significant changes in adverse event rates. The subgroup with antipsychotic comedication revealed somewhat higher adverse event rates; the pattern of adverse events, however, was largely comparable, and extrapyramidal symptoms were reported for only a few isolated cases. Thus, these findings suggest that--under naturalistic conditions--comedication of Flx with psychotropic drugs (a commonly used treatment strategy for various reasons) is feasible and does not generally increase patient risk.

Journal Article↗

PubMed1998

Effects of a corticosteroid, budesonide, on production of bioactive IL-12 by human monocytes.

Interleukin 12 (IL-12) has a key role during the initial phase of the immune response, favouring development of T helper class 1 (Th1) cells. IL-12 is composed of two subunits, p35 and p40, which are both needed for bioactivity. The level of p35 expression determines the level of bioactive IL-12 (p70), while the p40 subunit is produced in excess. In the present study we examined the sensitivity of bioactive IL-12 production by human monocytes to a corticosteroid, budesonide. We also compared the corticosteroid sensitivity of IL-12 and two other cytokines, interleukin 1beta and granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocytes obtained from peripheral blood of healthy donors (n=12) were stimulated with lipopolysaccharide (LPS; 10 microg/ml; 20 h) in the presence or absence of budesonide (10(-11)-10(-7) M). The supernatants were assayed for IL-12 (p70), IL-1beta and GM-CSF concentrations using specific immunoassays. Budesonide potently inhibited the production of bioactive IL-12. A significant suppression was obtained by treatment with even very low budesonide concentrations; even 10(-11) M budesonide significantly inhibited IL-12 to 81.6+/-7.6% of the control level (P<0.05). The maximal inhibitory effect of budesonide was seen at 10(-8) M. The inhibition of IL-12 production was significantly higher than the inhibition of GM-CSF (P<0.01) or IL-1beta (P<0.001). Whereas IL-12 production was totally inhibited, GM-CSF production was inhibited to 16.4+/-3.7 and IL-1beta production to 43.1+/-7.3% of control, respectively. The dramatic capacity of corticosteroids to modulate production of IL-12 as well as other cytokines may be a major mechanism underlying the effectiveness of these drugs in a broad spectrum of inflammatory diseases.

Administration, Topical↗

PubMed1998

[Depression in the very elderly].

In the Berlin Aging Study (BASE) an age and gender stratified sample of 516 persons aged 70 to over 100 was assessed by means of the semi-structured GMS-A interview, the CES-D-self-rating scale and the Hamiltion-Depression-observer-rating scale. Prevalence rates were 4.8% for Major Depression, 9.1% for all DSM III-R specified depressive disorders and 26.9% of subthreshold depression was included. There was no increase in prevalence rates with age but an increase in scores on the self rating CES-D. The prevalence rates for DSM III-R specified depression in females was 10.3% and almost double that of men (5.6%). Depressed persons do not show significant cognitive impairment as measured with the MMSE in comparison to controls. As compared to the total sample higher prevalence rates of overall depression were seen in persons with multimorbidity (36.8%) and lower rates in married persons. 13.2% of the elderly talked about feeling tired with life, 7.9% had thoughts about death and 1.2% reported suicidal ideation, which was closely linked to depressive disorders. In 44% of depressed cases undertreatment was observed. Only 6% got Antidepressants but 40% benzodiazepines.

Aged↗

PubMed1998

[Brief scale for assessment of need for care and provision of care].

In accordance with the German law on care for helpless persons, an observer rating scale has been developed to allow a staging of need of care. Construction of the scale, item descriptions, definitions, algorithms for sum score and inter-rater reliability data are reported. The scale can reliably measure the need of care, quality of care, and who is the care provider.

Activities of Daily Living↗

PubMed1998

Patient treatment insistence and medication craving in long-term low-dosage benzodiazepine prescriptions.

BACKGROUND: Long-term low-dosage dependence on benzodiazepines in traditionally explained by withdrawal symptoms. Previous research has not given much attention to reports that suggest that many patients oppose stopping benzodiazepines long before withdrawal symptoms have developed. This study investigates the scope of and factors associated with this pre-withdrawal treatment insistence. METHODS: Patients receiving long-term low-dosage benzodiazepines in primary care were asked to take a drug-holiday of at least 3 weeks. Sociodemographic, medication, morbidity and attitudinal variables were assessed in addition to the GPs' perceptions of their patients. RESULTS: Two-thirds of the patients rejected the drug-holiday proposal. Patients who refused a drug-holiday were less educated and were using a higher percentage of long-acting benzodiazepines than patients who accepted the drug-holiday proposal. Those who refused were seen by their GPs as being more complaining, harder to satisfy and less co-operative. CONCLUSIONS: These results provide evidence for drug-seeking or craving behaviour of patients who receive low-dosage benzodiazepine prescriptions. A major problem in benzodiazepine withdrawal occurs before the withdrawal programme has even begun. These data show that benzodiazepine low-dosage dependence should be considered a real form of dependence.

Aged↗

PubMed1998

Contribution of plasma-derived molecules to mucosal immune defence, disease and repair in the airways.

This review discusses recent observations, in health and disease, on the release and distribution of plasma-derived molecules in the airway mucosa. Briefly, the new data on airway mucosal exudation mechanisms suggest that the protein systems of plasma contribute significantly to the mucosal biology, not only in injured airways but also in such mildly inflamed airways that lack oedema and exhibit no sign of epithelial derangement. Plasma as a source of pluripotent growth factor, adhesive, leucocyte-activating, etc., molecules may deserve a prominent position in schemes that claim to illustrate immunological and inflammatory mechanisms of the airway mucosa in vivo.

Absorption↗

PubMed1998

Specialty training and the personal use of benzodiazepines by physicians affect their proneness to prescribe tranquilizers.

The decision on how to treat a patient does not depend on clinical matters or illness characteristics alone, but also on patient, physician and setting variables such as personality, training, or reimbursement. No research has yet been carried out to answer the question whether personal experience with medications also influences prescribing behavior. In this study, 124 physicians stratified according to specialty (neuropsychiatrists vs. general practitioners), type of institution (private practice vs. hospital), years of professional experience (young vs. old), and region (rural vs. urban) participated in a structured interview to evaluate their proneness to prescribe benzodiazepines for sleep disorders as well as their personal experience in taking benzodiazepines for their own sleep problems. Both specialty and personal experience were significantly related to proneness to prescribe. Other variables tested (region, institution, age, gender) did not help to explain the variance in benzodiazepine prescribing practice. Thus physician variables and, importantly, their own personal experience in taking the medication significantly influence treatment choice. Rational medical decision making and treatment guidelines must therefore take into account medical knowledge as well as knowledge of personal treatment preferences and professional biases.

Adult↗

PubMed1998

Classification of observational data with artificial neural networks versus discriminant analysis in pharmacoepidemiological studies--can outcome of fluoxetine treatment be predicted?

For several years, there has been an ongoing discussion about appropriate methodological tools to be applied to observational data in pharmacoepidemiological studies. It is now suggested by our research group that artificial neural networks (ANN) might be advantageous in some cases for classification purposes when compared with discriminant analysis. This is due to their inherent capability to detect complex linear and nonlinear functions in multivariate data sets, the possibility of including data on different scales in the same model, as well as their relative resistance to "noisy" input. In this paper, a short introduction is given to the basics of neural networks and possible applications. For demonstration, a comparison between artificial neural networks and discriminant analysis was performed on a multivariate data set, consisting of observational data of 19738 patients treated with fluoxetine. It was tested, which of the two statistical tools outperforms the two other in regard to the therapeutic response prediction from the clinical input data. Essentially, it was found that neither discriminant analysis nor ANN are able to predict the clinical outcome on the basis of the employed clinical variables. Applying ANN, we were able to rule out the possibility of undetected suppressor effects to a greater extent than would have been possible by the exclusive application of discriminant analysis.

Antidepressive Agents, Second-Generation↗

PubMed1998

Predictors of relapse and rehospitalization in schizophrenia and schizoaffective disorder.

In a German multicenter treatment study, 354 patients with schizophrenia and schizoaffective disorder were followed for 2 years. The data collected were taken as a basis for the present predictor study. For the first time, the technique of classification and regression tree (CART) analysis has been employed for this purpose. CART yielded informative data and appeared to be a useful instrument in predictor research. On the outcome variables "relapse" and "rehospitalization," significant predictor variables were found in several areas: neuroleptic treatment, onset and previous course (precipitating factors, first manifestation, hospitalization in the preceding year, suicide attempts), psychopathology (residual type, schizoaffective disorder), social adjustment (marital status, employment, intensity of life, Phillips score), previous life experiences (traumatic experiences and psychiatric or developmental disturbances in childhood), and biology (gender, age). Our investigation confirmed the generally prevalent views regarding the value of neuroleptic treatment, the multifactorial etiology, and the vulnerability stress model of schizophrenia.

Adult↗

PubMed1998

Plasma-derived proteins in airway defence, disease and repair of epithelial injury.

One significant characteristic of the airway mucosa in vivo, that cannot easily be mimicked in vitro, is its microcirculation, which generates a highly dynamic, biologically active milieu of plasma-derived molecules that may pass to the airway lumen in vivo. New data on the mechanisms of airway mucosal exudation indicate that the protein systems of circulating plasma may contribute significantly to the biology and immunology of the lamina propria, its surface epithelium and the luminal surface, not only in injured airways, but also in airways that are activated but display no sign of oedema, epithelial disruption, or increased absorption capacity. We suggest that present knowledge of the mechanisms of plasma exudation, together with rapidly emerging information (not detailed herein) on receptors, target cells and cellular responses to the plasma-derived molecules, must be considered in any realistic model that investigates "immuno-inflammatory" mechanisms of the airway mucosa.

Animals↗