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Biomedical subjects

M Linden

Publications and source records attributed to M Linden.

At least 91 records · Page 5Linked to original sources
PubMed1998

Effects of orally inhaled budesonide in seasonal allergic rhinitis.

It has previously been demonstrated that topical nasal treatment with glucocorticosteroids has significant effects on the bronchial airways. Less is known about effects on nasal disease by topical bronchial treatment with these drugs. The present study examined effects on nasal allergic disease of inhaled budesonide (avoiding nasal deposition of the drug). Patients with seasonal allergic rhinitis, but without asthma, were thus given inhalations of budesonide (600 microg b.i.d.) or placebo. The aim of the design was to allow the study of eosinophilic airway disease in a part of the airway other than the directly treated locus. Moderate to high birch pollen levels were recorded during the study season, and nasal symptoms were significantly increased in both treatment groups, although they were milder in patients receiving budesonide than in the placebo group (p<0.05). Nasal brush eosinophils and nasal lavage fluid levels of eosinophil cationic protein as well as blood eosinophils were increased during the season (p<0.05), but these increases were prevented by the inhaled budesonide. Nasal lavage fluid levels of alpha2-macroglobulin were particularly elevated in the placebo group but did not differ between patients receiving placebo and budesonide. Budesonide prevented the seasonal development of increased bronchoconstrictor responses to methacholine challenge (p<0.05). In conclusion, budesonide reduced the seasonal eosinophilia both in the circulation and in the nose along with an attenuation of seasonal nasal symptoms. Hence, at a daily dose of 600 microg b.i.d., known to cause no, or minimal, adverse effects, inhaled budesonide produces clinically significant anti-inflammatory effects in the entire airways, including the nasal mucosa, which is not exposed topically to the drug. We suggest that nasal and systemic anti-eosinophil actions are produced at commonly employed dose levels of orally inhaled budesonide.

Administration, Inhalation↗
PubMed1998

Effects of beta2-agonists and budesonide on interleukin-1beta and leukotriene B4 secretion: studies of human monocytes and alveolar macrophages.

The aims of the present study were to determine whether beta2-agonists (short- and long-acting) and a glucocorticoid (budesonide) influence the secretion of a pro-inflammatory cytokine (interleukin-1, [IL-1]) and a granulocyte attractant (leukotriene B4 [LTB4]) and to compare these effects on blood monocyte and alveolar macrophages. Alveolar macrophages (obtained by bronchoalveolar lavage) and blood monocytes from 26 healthy nonsmokers were stimulated with lipopolysaccharide or human serum opsonized zymosan. The influence of four beta2-agonists (salbutamol, terbutaline, formoterol, and salmeterol) and a corticosteroid (budesonide) on the release of interleukin-1beta (IL-1beta) and LTB4 was studied in a dose-response manner (10(-8)-10(-5) mol/L for beta2-agonists and 10(-10)-10(-6) mol/ L for budesonide). The stimulated IL-1beta secretion was significantly greater in blood monocytes than in alveolar macrophages (p < 0.05), but alveolar macrophages were much more capable of secreting LTB4 than were blood monocytes (p < 0.001). Budesonide significantly inhibited the release of IL-1beta from blood monocytes (p < 0.001), but no such effect was observed in alveolar macrophages. Budesonide did not influence the release of LTB4 in either cell type. The beta2-agonists neither influenced the LTB4 nor the IL-beta secretion in either cell type with the exception of formoterol, which stimulated IL-1beta secretion at the highest concentration (10(-5) mol/L, p < 0.05). In conclusion, beta2-agonists exhibited only minor effects on IL-1beta secretion from blood monocytes and no effect on LTB4-secretion from either cell type, and budesonide effectively inhibited the IL-1beta release in blood monocytes, but not in alveolar macrophages. Thus, induced secretion of LTB4 and IL-1beta , and the sensitivity to corticosteroids with regard to IL-1beta secretion, change during the transformation from blood monocytes to alveolar macrophages.

Administration, Topical↗
PubMed1998

Differences in self-reported sleep complaints in elderly persons living in the community who do or do not take sleep medication.

BACKGROUND: Sleep disorders and the use of sleep medication are major health issues. Since complaints about sleep disturbances are subjective phenomena, the aim of the present study was to investigate which sleep complaints and self-reported disturbances of sleep behavior are connected with the utilization of sleep medication. METHOD: In the Berlin Aging Study, a random sample of 516 persons aged 70 to over 100 underwent extensive psychiatric and medical examinations including several medication assessments and a special interview on sleep complaints and sleep behavior. RESULTS: 19.1% of the elderly were taking some form of sleep medication. Univariate and discriminant analyses showed that neither self-reported duration of sleep time nor difficulties with sleeping through the night but complaints about difficulties initiating sleep and global complaints about disturbed sleep differentiated between those who do or do not take sleep medication. CONCLUSION: Persons taking sleep medication nevertheless have a higher rate of sleep-related complaints than those who take no medication. Waking up in the night per se does not discriminate between drug users and controls. Instead, it is the inability to fall asleep or fall back into sleep after waking and global discontent with subjective sleep quality that make a difference.

Age Distribution↗
PubMed1998

The effects of detection and treatment on the outcome of major depression in primary care: a naturalistic study in 15 cities.

BACKGROUND: This study reports the responses of patients with confirmed depressive illnesses to different treatments in the WHO Mental Disorders in General Health Care study, conducted in 15 cities around the world. AIM: To discover how depressions recognized by the doctor compare with unrecognized depressions, both in terms of the initial illnesses and their outcomes, and to compare the outcomes of those depressions treated with antidepressants with those treated with daytime sedatives. METHOD: The design of the study was naturalistic, in that physicians were free to treat patients however they wished. Patients with confirmed depressive illnesses were assigned to four groups: treatment with an antidepressant; treatment with a daytime sedative (usually a benzodiazepine); patients recognized as having depression by the physician but were not offered drug treatment; and patients unrecognized as having depression by their physician. RESULTS: Both groups receiving drugs had illnesses of equal severity, were demographically similar to one another, and had similar previous histories of depression. Those receiving antidepressants had significantly fewer overall symptoms and fewer suicidal thoughts than those treated with sedatives. By the end of one year, differences between the groups had disappeared: patients not given drugs had milder illnesses but did significantly better than those receiving drugs, both in terms of symptoms lost and their diagnostic status. Unrecognized depressions were less severe than recognized depressions, and had a similar course over the year. CONCLUSIONS: Patients receiving antidepressants were better in terms of overall symptoms and suicidal thoughts than those treated with sedatives at three months, but this advantage does not persist. Depression emerges as a chronic disorder at one-year follow-up--about 60% of those treated with drugs, and 50% of the milder depressions, still meet criteria for caseness. The study does not support the view that failure to recognize depression has serious adverse consequences, but, in view of the poor prognosis of depression, measures to improve compliance with treatment would appear to be indicated.

Adolescent↗
PubMed1998

[The social status of schizophrenic patients].

In the German multicenter ANI study comparing continuous prophylactic treatment with intermittent medication, the social situation of a large sample of 364 schizophrenic patients was investigated and followed up over a 2-year period of outpatient aftercare. Effective therapy and prophylaxis substantially reduced relapses and rehospitalization. On the other hand, the psychosocial situation still showed considerable disadvantages. Of the patients (35 years old on average), 60% were still unmarried. Almost one-half of the patients still lived alone or with their parents, and one-third lived a very solitary life. At the end of the 2-year aftercare period, one-third was able to earn their own living. Almost one-half retired early from their occupations. Predictors and intervening variables are presented in order to stimulate early rehabilitation approaches. Schizophrenics are particularly placed at a disadvantage by tighter competition in the employment market, even though the course of illness can be improve. Social psychiatry must to be involved in helping to improve social contacts, accommodation and employment in order to prevent major distress.

Adult↗
PubMed1997

Interleukin-2 and -4 induce resistance of granulocyte-macrophage colony-stimulating factor to corticosteroids.

In vitro pretreatment of human mononuclear blood cells with a combination of interleukin-2 and interleukin-4 decreases corticosteroid receptor affinity and reduces the anti-proliferative effects of corticosteroids. Similar abnormalities have been observed in mononuclear blood cells of steroid-resistant asthmatics. In vitro steroid resistance was induced by 48 h pretreatment of mononuclear blood cells from healthy individuals (n = 10) with interleukin-2 and interleukin-4 (500 Units (U)/ml). The effects of three structurally different corticosteroids (10(-7)-10(-11) M) on lipopolysaccharide-stimulated (10 ng/ml; 20 h) production of granulocyte-macrophage colony-stimulating factor (GM-CSF) were examined. GM-CSF production was efficiently inhibited by all three corticosteroids in the control cultures. Cortivazol was significantly more potent (IC50 = 3 x 10(-11) M) than budesonide and tipredane (IC50 = 2.5 x 10(-10) M and IC50 = 2 x 10(-10) M, respectively). However. interleukin-2 and interleukin-4 pretreatment counteracted the inhibitory effects of all three corticosteroids to a similar degree. The results highlight the importance of interleukin-2 and interleukin-4 in the induction of steroid resistance, since pretreatment of mononuclear blood cells with these cytokines impaired corticosteroid inhibition of GM-CSF production.

Androstadienes↗
PubMed1997

The impact of psychosocial and clinical variables on duration of inpatient treatment for depression.

The duration of psychiatric hospital stays becomes increasingly important as economic pressures on medicine mount. Psychiatric hospitals, in particular, search for ways to cut costs without sacrificing efficiency. There is no doubt that clinical depression is one of the most important cost factors in psychiatry. Former studies have concentrated mainly on the influence of clinical variables such as the severity or subtype of depression on the length of stay (LOS). However, it can also be assumed that life situations or psychosocial variables in general might influence LOS. Data from 736 admissions between January 1983 and 1991 with a diagnosis of depression were examined to test the hypothesis that psychosocial and clinical variables influence LOS. Results showed a significant influence of age, marital status and gender, as well as severity and type of depression, on duration of inpatient treatment. Age, female gender, being widowed or divorced, the diagnosis of "endogenous depression" and severity were all associated with longer LOS. There was an interaction of gender, marital status and perceived loneliness, as well as an interaction of severity of depression with gender, both of which were associated with LOS.

Adolescent↗
PubMed1997

1997 IPA/Bayer Research Awards in Psychogeriatrics. The wish to die in very old persons near the end of life: a psychiatric problem? Results from the Berlin Aging Study.

The wish to die in elderly persons is currently under debate. Experts are questioning whether it is natural for these individuals to show a wish to die, whether the right to eventually kill oneself should be respected, or whether suicidal intentions in old age are expressions of mental disorders that need intensive, professional care. A representative community sample of 516 persons aged 70 to 105 was extensively investigated by psychiatrists using the structured interview Geriatric Mental State Examination-Version A (GMS-A) and several self-rating and observer-rating scales. Diagnoses were made according to DSM-III-R criteria and by clinical judgment. The goal of the study was to find examples of "pathology-free wishes to kill oneself." A total of 115 out of 516 very old (70 to 105 years) persons, which represents 21.1% of the community population, said at the time of investigation that they wanted to die or felt life was not worth living (Hamilton Depression Rating Scale [HAMD] score 1, 2, or 3). Forty-three very old persons (6% of the community population) had the wish to be dead according to the HAMD or the GMS-A, and 11 persons (2% of the community population) had suicidal intentions. Depending on the intensity of suicidality, 80% to 100% were clinically diagnosed as having psychiatric disorders and half to three quarters showed symptoms fulfilling the criteria of at least one specified psychiatric diagnosis. Acute suicidal intentions were in all cases associated with at least one specified diagnosis according to DSM-III-R. Thirteen persons out of 54 who actually wanted to die (GMS-A category 4, 5, 6 or HAMD category 2, 3) did not fulfill criteria for specified diagnoses. Seven individuals showed scores in self-rating and observer-rating scales that speak for mental disorders apart from pure suicidality. Six remaining persons are described in greater detail in short case vignettes. They showed either mild but chronic psychiatric disorders, fluctuating courses, or an atypical phenomenology of psychiatric disorders. The results of this study strongly suggest that the wish to be dead in the very old is most probable, and suicidal intentions are definitely associated with psychiatric disorders.

Aged↗
PubMed1997

Antidepressant drug use: differences between psychiatrists and general practitioners. Results from a drug utilization observation study with fluoxetine.

Between 1990 and 1993, a series of drug utilization observation studies with fluoxetine (Flx) were conducted in Germany in several waves. 3,158 patients treated by psychiatrists/neurologists (PN) and 15,601 patients treated by general practitioners/internists (GPI) were included; data collection at start and end of treatment focussed on diagnoses, symptoms, prescription, comedication, efficacy (CGI, Zung scale), and adverse events. Differences between PN and GPI patients were of major interest. For more than 90% of both the PN and the GPI cases. Fix was used for the indication of "depression", with a dosis of 20 mg/day. More PN patients (47%) than GPI patients (28%) were diagnosed as "endogenous"; GPI patients more often presented with first episodes (36 vs. 24%). "suicidal ideation" was less prominent compared to PN subjects (17 vs. 28%). Psychotropic comedication was regarded as necessary in 39% (PN) and 10% (GPI) of the cases. Early treatment termination because of "remission/major improvement" was observed in 13% (PN) vs. 21% (GPI) and because of "adverse events" in 11% (PN) vs. 3% (GPI) of the patients. At observation end, 53% (PN) vs. 74% (GPI) were rated as "symptom-free/markedly improved" (CGI); self-ratings reflected comparable results, marked improvements over time, but still PN/GPI differences at the end. "Suicidality" related to depression was more pronounced in the PN group at both points in time. 24% (PN) vs. 6% (GPI) of the cases reported "routine" adverse events, while in 2% (PN) and 1% (GPI) "serious" adverse events were observed. (For all the above comparisons p < 0.001 to < 0.0001.) These findings reveal that-under routine conditions handled by PNs and GPIs-Fix shows an efficacy and safety consistent with clinical trial data. The body of data suggests that PN patients present with more severe depression and more suicidality, require more comedication, and end up with a poorer outcome. Differences in the physicians' perception of psychiatric and somatic symptomatology and their treatment routines may also have something to do with the PN/GPI group differences observed.

Adolescent↗
PubMed1997

What happens to patients after the end of a clinical trial? Systematic follow-up observational study of an open moclobemide trial in major depression.

Controlled clinical drug trials typically last several weeks. At the end of this fixed time period approximately two-thirds of the patients in trials with antidepressant drugs are classified as responders, i.e. the initial severity score is reduced by about fifty percent. In a clinical perspective this means that many patients, even among the responders, are still quite ill and require further treatment. Nevertheless, to date there do not appear to have been any studies on treatment and course of illness after the termination of controlled clinical trials. In a "naturalistic" follow-up surveillance study of 202 patients who had taken part in a controlled trial with the antidepressant moclobemide for six weeks, treatment and clinical status were monitored through questionnaires sent out to their treating physicians (n = 78) at two assessment points four weeks and six months later. Results showed that sixty percent of patients continued to receive the study drug moclobemide after the completion of the clinical trial. Twenty percent were switched to other antidepressants and twelve percent received no further psychotropic drugs. In the course of six months a considerable variation in treatment modes could be observed. Patients under ongoing active treatment made considerable additional progress. A correlation was found between insufficient response and repeated switching of medication. Patients who had been taken off antidepressant medication because of early good response did not experience early relapse after the end of treatment.

Antidepressive Agents↗
PubMed1997

An investigation of the representativity of neuropsychiatrists and their patients in a drug utilization observation study on fluoxetine.

This study presents a methodological approach to an expost facto investigation of sample bias in drug utilization observation (DUO) studies using the example of a DUO with the nontricyclic antidepressant fluoxetine. A total of 479 psychiatrists and neurologists and 2,401 patients were investigated. The purpose of the study was to judge the representativeness of our DUO sample for two populations: first, for all psychiatrics and neurologists prescribing fluoxetine or all patients being treated with fluoxetine in Germany and, second, for all psychiatrists and neurologists prescribing antidepressants or all patients being treated with antidepressants in Germany. Criteria for the representativeness test were physician variables (gender, size of community where practicing, federal state, age, volume of prescriptions) and patient variables (gender, age, prescription-related diagnosis, concurrent illnesses, concomitant medications). The study shows that the DUO sample can rightfully claim representativeness in the majority of parameters for the psychiatrists and neurologists prescribing fluoxetine and for the patients being treated with fluoxetine. There are more noticeable discrepancies with regard to the psychiatrists and neurologists in general and to the patients being treated with antidepressants in general. The methodological problems of pharmacoepidemiological investigation of representativeness are discussed.

Adult↗
PubMed1997

Guidelines for the implementation of drug utilization observation (DUO) studies in psychopharmacological therapy. The "Phase IV Research" Task-Force of the Association for Neuropsychopharmacology and Pharmacopsychiatry (AGNP).

The task-force on Phase-IV-Research of the Association for Neuropharmacology and Pharmacopsychiatry (AGNP) has developed guidelines for the implementation of scientifically sound drug utilisation observation studies (DUO studies). These guidelines have been adopted by the executive committee as the position of the association. DUO studies are prospective pharmacoepidemiological studies, by which prescription, illness, and patient data of individual patients are collected without interference with the routine course of treatment. They can answer questions on the interaction of treatment modalities with positive and negative treatment outcome. Scientific standards require that there is a study protocol which describes the epidemiological, statistical, procedural, and quality assurance methodology and states who is responsible for what. As such studies can violate data protection regulations or can be used for sales instead of scientific purposes, consultation of an ethics committee is recommended.

Clinical Trials, Phase IV as Topic↗
PubMed1997

Tenascin is increased in airway basement membrane of asthmatics and decreased by an inhaled steroid.

Tenascin and fibronectin are extracellular matrix glycoproteins expressed during morphogenesis and tissue repair. In the present study bronchial biopsies were studied by the morphometric method of immunocytochemistry to reveal the distribution of different tenascin and fibronectin isoforms as well as the presence of inflammatory cells in the airway mucosa of patients with chronic asthma (n = 32) and those with seasonal birch-pollen-sensitive asthma out of season (n = 17), both in comparison with healthy control subjects (n = 12). The results showed an increase in tenascin immunoreactivity in the bronchial subepithelial reticular basement membrane layer in patients with chronic asthma (p < 0.0001) and in those with seasonal asthma (p < 0.01) compared with control subjects. The tenascin immunoreactivity, appearing as an intense wide subepithelial band in asthma, was seen only occasionally in the basement membrane of control specimens. Instead, a diffuse immunoreaction against both total fibronectin and locally produced extradomain A fibronectin was similarly visible in the airway mucosa of both patients and control subjects. Despite the significant increase in the airway mucosa of eosinophils and lymphocytes in patients with chronic asthma (p < 0.0001 and p < 0.0001, respectively) and of eosinophils in patients with seasonal asthma (p < 0.001), there was no correlation between the number of these cell types and level of tenascin expression. In patients with birch-pollen-sensitive asthma during the birch-pollen season, inhaled corticosteroid treatment, budesonide 400 micrograms twice daily, decreased tenascin immunoreactivity, in comparison with effects of placebo (p = 0.01). Our results suggest that the higher amount of tenascin reflects disease activity in asthma and may be an indicator of a remodeling process rather than of injury itself.

Adult↗
PubMed1997

Predicting health care utilization in the very old. The role of physical health, mental health, attitudinal and social factors.

The purpose of this paper is to predict health care utilization in the very old from a combination of individual-based factors such as physical and mental health, health attitudes and beliefs, sociodemographic characteristics, and life circumstances. This study was conducted within the context of the Berlin Aging Study (BASE). Higher use of medications was most strongly predicted by more medical diagnoses, better cognitive status, and health attitudes. Physician contact was only weakly predicted by physical health variables, hypochondriasis, and living alone. In contrast, living alone was the greatest predictor of the utilization of increased levels of caregiving services, while having children nearby served as a protective factor against the need for more formal caregiving services. These results show that utilization of health care depends on interaction between physical and mental health, attitudinal, and social factors.

Aged↗