Biomedical subjects

M Linden

Publications and source records attributed to M Linden.

At least 55 records · Page 3Linked to original sources

PubMed2001

[Generalized anxiety disorders (GAD)--a neglected illness? Background und aims of the GAD-P study].

In the past Generalized anxiety disorder (GAD)--previously classified as anxiety neurosis--was regarded as not being a separate diagnostic entity. On the basis of new explicit criteria for GAD in the 90ies, GAD-specific pharmacological (i.e. SNRI) and psychological treatments with improved efficacy have become available. The Generalized Anxiety and Depression in Primary care study (GAD-P) investigates the prevalence of GAD in primary care settings and evaluates the patterns of care provided. Aims, methods and findings of the GAD-P study are described in this supplement.

Anti-Anxiety Agents↗

PubMed2000

Induced kappa receptor editing shows no allelic preference in a mouse pre-B cell line.

B cell Ag receptor editing is a process that can change kappa antigen recognition specificity of a B cell receptor through secondary gene rearrangements on the same allele. In this study we used a model mouse pre-B cell line (38B9) to examine factors that might affect allelic targeting of secondary rearrangements of the kappa locus. We isolated clones that showed both productive and nonproductive rearrangements of one kappa allele, while retaining the other kappa allele in the germline configuration (kappa(+)/kappa degrees or kappa(-)/kappa degrees ). In the absence of any selective pressures, subsequent rearrangement of the germline alleles occurred at the same frequency as secondary rearrangement of the productive or nonproductive rearranged alleles. Because 38B9 cells lack Ig heavy chains, we stably expressed mu heavy chain protein in 38B9 cells to determine whether heavy-light pairing might affect allelic targeting of secondary kappa rearrangements. Although the expression of heavy chain was found to both pair with and stabilize kappa protein in these cells, it had no effect on preferential targeting Vkappa-Jkappa receptor editing compared with rearrangement of a germline allele. These studies suggest that in the absence of selection to eliminate autoreactive Vkappa-Jkappa genes, there is no allelic preference for secondary rearrangement events in 38B9 cells.

Alleles↗

PubMed2000

Corticosteroids and interferons inhibit cytokine-induced production of IL-8 by human endothelial cells.

IL-8, secreted by endothelial cells at the site of inflammation, participates in recruitment and transmigration of leukocytes. IL-8 may also have pathophysiological consequences in inflammatory and immunological disorders. We have investigated the effect of interferons (IFNs) and glucocorticosteroids (GCs) on cytokine induced secretion and production of IL-8 by human umbilical endothelial cells (HUVEC). There was a low spontaneous secretion of IL-8 by unstimulated HUVEC which increased after 6 or 24 h of stimulation with the pro-inflammatory cytokines TNF-alpha or IL-1beta. IFN-gamma as well as the GCs, Dexamethasone and Budesonide, inhibited TNF-alpha induced IL-8 secretion in a dose-dependent manner. IFNs may have a general modulating effect, since IFN-alpha also inhibited the TNF-alpha-induced IL-8 secretion. There was a slight, but significant, increase in the content of intracellular IL-8 in stimulated HUVEC. However, there was no difference between stimulation with IL-1beta or TNF-alpha alone or in combination with IFNs or GCs, whereas inhibition of IL-8 secretion with monensin increased IL-8 content suggesting that IFNs and GCs inhibit synthesis rather than secretion of IL-8. In conclusion, IFNs or GCs may be useful for inhibiting IL-8 production by endothelial cells and could thus be used for therapeutic modulation of the inflammatory response.

Budesonide↗

PubMed2000

Ranges of psychiatric morbidity in the old and the very old--results from the Berlin Aging Study (BASE).

The purpose of this study was to determine prevalence rates of psychiatric morbidity in the elderly, distinguishing different levels of psychiatric caseness as compared to the diagnoses of the DSM-III-R. In a cross-sectional population-based study in Berlin (West), Germany, 516 people aged 70 to 95+ were randomly selected from the obligatory city registry (1990-1993) and stratified by age and gender (N = 43 men and N = 43 women in each of six 5-year age groups). Psychiatric and physical examinations were carried out in an extensive standardized assessment. Distinct psychopathological syndromes occurred in 72.7% of the elderly (54.6% of the men, 79.1% of the women). A clinically defined psychiatric disorder was found in 49.4% of the elderly (95% confidence interval 43.9%- 54.9%; 36.4% of the men, 54.0% of the women). Excluding insomnia, the overall psychiatric morbidity was 40.4% (30.9% m, 43.8% w). Excluding clinical diagnoses that were not otherwise specified in the DSM-III-R, the overall prevalence of specified DSM-III-R diagnoses was 23.5% (16.3% m, 26.0% w). Excluding dementia, which is known to be age-related, the prevalence was 11.3% (8.5% m, 12.2% w) and no significant effect between the age groups was seen. A considerable proportion of clinically relevant psychiatric morbidity in the elderly does not meet the criteria of specified DSM-III-R diagnoses, although these cases are in need of care. The data show that the threshold and severity of caseness accounts for important differences when overall psychiatric morbidity is assessed.

Aged↗

PubMed2000

Why are patients prescribed psychotropic drugs by general practitioners? Results of an international study.

BACKGROUND: There has been growing interest in factors that might influence the prescription of psychotropic drugs in general practice. METHOD: This was a multi-centre study using a two-phase stratified sampling strategy in primary care facilities from 14 different countries to determine factors associated with the prescription of psychotropic drugs. RESULTS: A total of 1763 consecutive GP attenders aged between 16 and 65 years of age were recruited. Although antidepressants were used more for depressive disorders and anxiolytics for patients with anxiety, the differential diagnosis was otherwise not an important factor in prescribing behaviour. Antidepressants and anxiolytics were prescribed twice as frequently in client centred clinics following a 'personal physician model' as opposed to non-client centred settings, where care was less personalized. The reverse was true of hypnotics (adjusted odds ratio of 0.5). General practitioners with a positive view of their undergraduate psychiatric training and who had had further postgraduate experience in the speciality were significantly less likely to prescribe medication, and if they did they were more likely to use antidepressants. Older patients were significantly more likely to be prescribed psychotropic medication. Several other patient factors emerged when individual classes of medication were considered; these included the loss of a spouse and the absence of physical ill health in the case of antidepressants, and female sex, fewer years of schooling and unemployment in the case of anxiolytics. CONCLUSIONS: Social, health care and GP factors are at least as important as clinical features in the prescription and choice of psychotropic medication.

Adult↗

PubMed2000

Epidemiology and psychiatric morbidity of suicidal ideation among the elderly.

This study investigates the epidemiology and psychiatric morbidity of the wish to be dead, suicidal ideation, and suicidal intent in a group of elderly persons (> 70 years). A representative community sample of 516 persons aged 70 to 105 was extensively investigated by psychiatrists using the structured interview GMS-A and various other self-rating and observer-rating scales. Diagnoses were made according to DSM-III-R and clinical judgment. In a cross-section of this population, we found the following prevalence rates: At the time of the study, 14.7% of the elderly community had symptoms of tiredness of life, 5.4% wished to die, and 1% showed suicidal ideation or gestures. Depending on the intensity of suicidality, 80% to 100% were clinically diagnosed as suffering from psychiatric disorders and 50-75% showed symptoms fulfilling the criteria of at least one specific psychiatric diagnosis. Further, logistic regression analysis showed a significant influence of major depression and specific DSM-III-R diagnosis on suicidality in old age. Our conclusion is that suicidal ideation in the elderly is usually a sign of a mental illness warranting diagnosis and treatment rather than assisted suicide.

Age Factors↗

PubMed2000

Selective localization of Bcl-2 to the inner mitochondrial and smooth endoplasmic reticulum membranes in mammalian cells.

Bcl-2, an anti-apoptotic protein, is believed to be localized in the outer mitochondrial membrane, endoplasmic reticulum, and nuclear envelope. However, Bcl-2 has also been suggested as playing a role in the maintenance of mitochondrial membrane potential, indicating its possible association with the inner mitochondrial membrane. We therefore further examined the exact localization of Bcl-2 in mitochondria purified from wild-type and bcl-2-transfected PC12 cells and pre- and postnatal rat brains. Double immunostaining demonstrated that Bcl-2 was co-localized with subunit beta of F1F0ATPase in the inner mitochondrial membrane. Biochemical analysis of isolated mitochondria using digitonin and trypsin suggests an association of Bcl-2 with the inner mitochondrial membrane. More interestingly, the majority of Bcl-2 disappeared from the inner membrane of mitochondria when cultured under serum deprivation. These results suggest that Bcl-2 acts as an anti-apoptotic regulator by localizing mainly to the inner mitochondrial and smooth ER membranes.

Animals↗

PubMed2000

Efficacy and safety findings from naturalistic fluoxetine drug treatment in adolescent and young adult patients.

This article reports on the efficacy and safety of the selective serotonin reuptake inhibitor, fluoxetine, in 213 patients (ages 11-23 years) treated by psychiatrists/neurologists (PN) or general practitioners/internists (GPI). Data were derived from naturalistic drug utilization observation (DUO) studies with fluoxetine (n = 18,759 patients). Data collection--at the start and the end of the observation period (< or =6 weeks)--included patient characteristics, diagnoses, medication, co-medication, efficacy, and adverse events (AEs). Nonparametric statistics and descriptive p values (two-tailed) were used. Analyses revealed various differences between PN (n = 56) and GPI (n = 157) samples as to patient and treatment characteristics (p < 0.001-0.08). Based on both Clinical Global Impression (CGI; all p < 0.001) and self-assessment (total n = 47; Zung SDS, all p < or = 0.003), both PN and GPI patients showed improvements in their symptomatology over time, including suicidality (all p < 0.001; there were no group differences). Overall AE rates were higher in PN patients (p < 0.01; 17.9% vs. 4.5%); the frequency and type of AEs in both subgroups were typical for fluoxetine and the total DUO samples. In fact, AE rates were lower compared to controlled trials. Findings suggest that PN patients were more severely ill at observation start and suffered a more complicated treatment course. However, clinical efficacy showed highly significant improvements in both subgroups; AE rates were low in both--although higher in PN patients. Thus, results support a positive benefit/risk ratio of fluoxetine use for this young patient population.

Adolescent↗

PubMed2000

Early termination of antidepressant drug treatment.

Guidelines for antidepressant drug therapy recommend continuing treatment for several months, even after recovery. Premature termination of medication is viewed as a significant reason for chronicity in depressive disorders. To study the scope and type of this problem, routine treatment cases must be observed in sufficient numbers. In four subsequent drug utilization observation studies, the time course and reasons for early termination (i.e., during the first weeks of fluoxetine treatment for depression) were investigated in (1) 15,601 patients of 4,696 general practitioners; (2) 2,401 patients of all ages treated by 479 neuropsychiatrists from 1990 to 1991; (3) 757 patients of all ages treated by 213 neuropsychiatrists from 1992 to 1993; and (4) in 977 geriatric subjects treated by 216 neuropsychiatrists. In study 1, treatment was terminated during the first 10 weeks in 32.9% of cases; in study 2, in 48.0%; in study C, in 31.2%; and in study D, in 31.0%. When treatment was discontinued because of adverse events, the median of treatment duration was approximately 15 days; in cases of clinical deterioration, 20 days; in cases of poor response, 40 days; and when the reason was good response, the median of treatment duration was approximately 43 days. This is the largest field study on early termination of antidepressant treatment available to date. The consistency of results, which were collected from a large number of patients of different ages and from specialists as well as general practitioners, speaks for the validity and stability of the observed phenomena. The different forms of early treatment termination are discussed and addressed separately because they each have special risks and are differently associated with treatment failure.

Adult↗

PubMed2000

Immediate effect of topical budesonide on allergen challenge-induced nasal mucosal fluid levels of granulocyte-macrophage colony-stimulating factor and interleukin-5.

The nasal antiinflammatory effects produced by maintenance treatment with topical steroids include reduced production of cytokines. The present study explored nasal mucosal effects induced during the first 9 h after a single dose of topical budesonide. Nine subjects with allergic rhinitis due to birch or timothy pollen were given budesonide (256 microg; Rhinocort Aqua) or placebo in a double-blind, randomized, crossover (4 wk washout) manner. Nasal allergen challenges were performed 30 min after the steroid/placebo pretreatment. Before and 30 min, 1, 3, 5, 7, and 9 h after challenge, filter paper strips were placed on the nasal septum and inferior turbinates for 10 min to sample undiluted mucosal fluids. Strips were then extracted in 1 ml buffer for cytokine analysis (ELISA). Allergen challenge produced acute nasal symptoms that peaked at 30 min and then tapered off. Conversely, both GM-CSF and IL-5 were increased only at 3, 5, 7 and 9 h (p < 0.05 compared with baseline). Budesonide did not affect the nasal symptoms but inhibited (p < 0. 05; compared with placebo treatment) the allergen challenge-induced mucosal output of GM-CSF and IL-5. These data demonstrate that GM-CSF and IL-5 are induced in a nonsymptomatic, late phase response to nasal allergen challenge, and that this cytokine response is prevented by single dose budesonide pretreatment.

Administration, Intranasal↗

PubMed2000

[Comparison of the responsibility spectrum of a community psychiatric emergency service and outpatient emergency care in a psychiatric clinic].

PURPOSE: The need for psychiatric crisis services is generally accepted. Additional to traditional crisis clinics which are located in general or psychiatric hospitals in recent years also special community crisis services were implemented. The question is whether there are differences in patients and type of care between traditional and new services. METHODS: In this study empirical data are reported on reasons for contact, on patients and on interventions for a hospital based crisis clinic and a community crisis service. 132 service and 364 clinic contacts were recorded. RESULTS: There were more neurotic patients in the community service and more psychotic patients in the clinic. In both services inpatient care had to be arranged in one third of the cases. In the hospital based crisis service fewer legal commitments were necessary. A speciality of the community crisis service is the possibility to look after patients in their homes. CONCLUSION: Both services have similar features, but there are also differences which show that the new service offers new possibilities of care.

Ambulatory Care↗

PubMed1999

[Information the family physician gives his patients to take home. Utilization, contents and origin of printed information].

Providing the patient with information is one of the most important tasks of the family doctor, both for legal and medical reasons. Apart from verbal information, a wealth of printed material is also available. In a survey of 62 randomly selected general practices, the volume and nature of such information material was investigated, and its importance in practice established by means of an interview. 88.7% of the doctors interviewed stated that they handed out printed matter every day, and 96.8% considered the availability of such information to be an important aid in their daily work. Most of the printed information dealt with metabolic and cardiovascular disorders, and 93.5% of the material was supplied by the pharmaceutical industry. This means that other institutions which have a task to inform patients are virtually not represented in the doctor's office. Printed material providing health-promoting information, for example, on such topics as smoking, AIDS, exercise, healthy eating and suchlike, were lacking. The data point to an urgent need for additional information material in the doctor's office.

Family Practice↗

PubMed1999

Psychological distress and psychiatric disorders in primary health care patients in East and West Germany 1 year after the fall of the Berlin Wall.

BACKGROUND: The reunification of Germany confronted citizens in East and West Germany with many changes in their lives. These changes may be considered as critical life events. Especially for those in East Germany, life circumstances drastically changed, and individuals were increasingly required to adopt and develop coping capabilities. In addition to new opportunities and freedom, there was threatening uncertainty about the future. Theories of life events and stress postulate that threat events have an impact on human well-being. It was expected that there would be an increased rate of psychiatric morbidity after unification, especially in the eastern part of Germany. METHOD: An international study by the WHO on psychiatric disorders in general health care was carried out in 1990, 1 year after the opening of the Berlin Wall, in both parts of Berlin and in Mainz, West Germany. This allowed for a comparison of the prevalence rates of psychiatric disorders among general health care patients in the East and West, after the euphoria immediately following unification had subsided. RESULTS: The prevalence rates of current ICD-10 diagnoses and of subthreshold disorders in East Berlin were similar to the rates in West Berlin and Mainz. The recognition rate of psychiatric disorders by physicians did not differ in East Berlin as compared to West Berlin and Mainz. CONCLUSION: Contrary to the prediction expected from the literature on individual negative life events, major changes in life circumstances and stressful life events on a societal level within 1 year did not have a major impact on psychological function.

Adult↗

PubMed1999

Experimental common cold increases mucosal output of eotaxin in atopic individuals.

BACKGROUND: In view of recent observations demonstrating that rhinovirus infections are associated with increased local activity of eosinophils, we hypothesized that eotaxin, a selective eosinophil chemoattractant, may be involved in eosinophil recruitment/activation in common cold infections. METHODS: Twenty-three patients with seasonal allergic rhinitis were inoculated with human rhinovirus 16 (HRV 16) outside the pollen season. Sequential diluent and allergen (10(3) SQ-U) challenges, each followed by nasal lavage, were carried out about 3 months before and 4 days after virus inoculation. RESULTS: Seventeen patients developed common cold and were further analyzed. Lavage fluid levels of eotaxin were increased at the height of active common cold (day 4 after inoculation) both at baseline (after diluent challenge) (P<0.01) and acutely after allergen challenge (P<0.05). CONCLUSIONS: Common cold symptoms after nasal HRV 16 inoculation are associated with increased nasal mucosal output of eotaxin, suggesting that this chemokine is partly responsible for recruitment/activation of airway mucosal eosinophils in common cold infections.

Blood Proteins↗

PubMed1999

Circulating eosinophil/basophil progenitors and nasal mucosal cytokines in seasonal allergic rhinitis.

Accumulation of eosinophils in the airways is characteristic of allergic rhinitis and asthma. The tissue eosinophilia may involve both recruitment of mature eosinophils and proliferation of their progenitors. This study examines mature eosinophils (nasal and circulating), their circulating progenitors, and a potential role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in stimulating these progenitors. Twelve subjects with a history of seasonal allergic rhinitis and positive skin prick test for birch pollen were studied during four periods: shortly before, in the early and intense phase, at the end, and well after the Swedish birch-pollen season. Nasal mucosal and circulating eosinophils were examined in both nasal brushings and peripheral blood samples. Eosinophil/basophil progenitors were determined by counting colony-forming units in nonadherent mononuclear blood-cell cultures in methylcellulose at 14 days. The nasal mucosal cytokines GM-CSF, interleukin (IL)-1beta, IL-3, IL-5, IL-6, IL-8, and RANTES were analyzed (ELISA) in nasal lavage (NAL) fluids. All patients developed severe symptoms of rhinitis at the height of the season, with increased numbers of eosinophils in the nasal mucosa (P<0.05) and in the circulation (P<0.05). At this time point, the number of circulating progenitors (P<0.05) and the NAL fluid level of GM-CSF (P<0.05) were also increased. In contrast, there was no change in the NAL fluid levels of IL-1beta, IL-3, IL-6, or IL-8. Neither IL-5 nor RANTES could be detected in any of the NAL fluids. At the end of or after the season, there was no increase in nasal eosinophils or circulating eosinophils or progenitors (P>0.05). Ex vivo addition of GM-CSF (10-100 U) increased the number of blood progenitors grown before (P<0.01) and after (P<0.05) the season, compared with during the season. The in vitro GM-CSF responsiveness of progenitors may be related to whether or not these already have been stimulated endogenously by GM-CSF. Taken together, our data thus suggest that GM-CSF may play a role in vivo to increase production of eosinophilic progenitors in allergic airway disease.

Adult↗

PubMed1999

IL-2 and IL-4 counteract budesonide inhibition of GM-CSF and IL-10, but not of IL-8, IL-12 or TNF-alpha production by human mononuclear blood cells.

1. The combination of interleukin-2 (IL-2) and IL-4 reduces the inhibitory effects of glucocorticoids on granulocyte-macrophage colony-stimulating factor (GM-CSF) production, in agreement with the hypothesis that this combination causes glucocorticoid resistance. Whether a general cytokine resistance to glucocorticoids is induced by IL-2 and IL-4 has not been reported. 2. Mononuclear blood cells from healthy individuals were pre-treated with IL-2, IL-4, or IL-2+ IL-4 (31.3-500 U ml(-1)) for 48 h, prior to lipopolysaccharide (LPS; 10 ng ml(-1); 20 h) and budesonide addition. Cytokine levels in the supernatants were analysed using specific immunoassays. DNA content was analysed to estimate cell numbers. 3. GM-CSF production was totally inhibited by budesonide at 10(-8) M in vehicle treated cultures, while IL-10 was inhibited to 33.4+/-4.3% of control. IL-2, IL-4, or IL-2 + IL-4 reduced the inhibitory effects of budesonide on GM-CSF to similar levels (23.7 6.7, 31.6+/-8.5 and 35.1+/-4.3% of control, respectively). IL-2, IL-4, or IL-2 + IL-4 also reduced the inhibitory effects of budesonide on IL-10 production (46.5+/-6.6, 55.9+/-7.3%, and 68.3+/-9.9% of control, respectively). In contrast, IL-8, IL-12 and TNF-alpha production did not become resistant to budesonide. 4. Thus, glucocorticoid resistance induced by IL-2 and IL-4 is not general at the cytokine production level. While the glucocorticoid sensitivity of GM-CSF and IL-10 production decreased, the sensitivity of IL-8, IL-12 or TNF-alpha production was unchanged. Also, the mixture of IL-2 and IL-4 is not crucial for induction of glucocorticoid resistance of GM-CSF production.

Budesonide↗

PubMed1999

The prescribing of psychotropic drugs by primary care physicians: an international collaborative study.

Psychotropic drugs play a major role in primary care management of mental disorders. This study expands the existing data on prescribing practices using data from a 15-center, primary care epidemiologic survey. Questions to be addressed include the following: Which clinical and nonclinical factors are related to the prescribing of psychotropic drugs by primary care physicians? How do prescribing patterns vary across primary care centers? At each center, primary care patients were screened using the General Health Questionnaire, and a stratified random sample completed a standardized diagnostic assessment. For each patient completing the diagnostic assessment, the treating primary care physician provided data on clinical diagnosis and medications prescribed. Study results indicated that 11.5% of all practice attenders, 51.7% of cases who received a diagnosis of mental disorders by a physician, and 27.6% of cases who received a diagnosis using the Composite International Diagnostic Interview were treated with psychotropic medication because of their psychologic problems. Anxiolytics, hypnotics, and antidepressants each accounted for approximately 20% of all prescriptions. Prescription rates increased with the prominence of psychologic complaints, severity of mental disorder, severity of social disability, female gender, age older than 40 years, lower education, unemployment, and marital separation. Rates and type of drugs also varied among specific mental disorders; 19.3% of patients with brief recurrent depression but 55.0% with agoraphobia got any psychotropic drug. Antidepressant drugs were prescribed in 7.7% of anxiety disorders compared with 31.9% of depressive disorders. There were large differences between international centers. When comparing client-type centers with clinic-type centers, overall prescription rates were similar (51.2 vs. 52.9%), but significant differences were observed with respect to psychotropic polypharmacy (12.6% client, 6.3% clinic), tranquilizer medication (24.2 client, 32.9% clinic), and antidepressant medication (17.3 client, 8.9% clinic). Psychotropic drugs have an important role in the treatment of mental disorders by general practitioners. Prescription is associated with a number of clinical but also nonclinical factors that must be recognized when guidelines for international use are to be published. Recognition of mental disorders and selection of specific drug classes are important areas in which medical practice needs improvement.

Adult↗

PubMed1999

Theory and practice in the management of depressive disorders.

Scientific, professional, and governmental bodies have in recent years intensified efforts to formulate guidelines for the treatment of depression with the goal that medical practice should comply with these standards and thus improve patient care. 'Evidence-based medicine' demands that medical practice should explicitly refer to the best available scientific knowledge. Empirical data on the epidemiology of care suggest that there are major differences between guidelines and routine practice. Failure to detect mental disorders range from 45 to 90%. Only 1 in 10 of those suffering from depression receive adequate treatment. Treatment is insufficient as prescribed dosages are routinely too low, as up to 50% of treatments are ended prematurely and because patient non-compliance interferes with proper treatment application. Psychological treatment is provided only in 60% of cases in need and is mostly unspecific, i.e. listening or giving advice. Furthermore, there are large regional variations in prescribing patterns which show that treatment is influenced by many non-medical factors. Empirical studies show that giving information to physicians or even measures to improve recognition alone are not sufficient to make changes in treatment behaviour. Only if measures are taken to improve treatment interventions directly then, at least for more severe cases, could better illness outcome be shown. If one wants to understand therapist non-compliance with treatment guidelines then one first has to understand the process of medical decision making. Action theory provides a model which brings together theoretical and experimental knowledge, goal setting, medical and emotional assessment, and operational procedures. On the basis of this theory, future guidelines should specify the setting for which they claim to be valid, they should be empirically tested for their feasibility and effects on patient outcome, and they should give proper attention to non-medical factors which have major impact on medical practice.

Depressive Disorder↗