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Biomedical subjects

M Linden

Publications and source records attributed to M Linden.

At least 19 recordsLinked to original sources
PubMed1995

Filling the bone defect with osteogenic material. An experimental study.

In this experimental study with bone defects, we focussed on the one hand on external and internal osteogenic callus formation after filling the defect and on the other on the osteochondrogenic differentiation capacity of 4-day-old fibrous-like callus grafts and 12-day-old woven bone grafts in an osteogenic environment. A standard cortical bone defect of the femur was created in 95 young rats. The defect was filled with a cortical bone graft and 4- and 12-day-old callus grafts. The grafts were transplanted as such or in Nucleopore chambers. Follow-up was done at 1, 2, 3 and 6 weeks. The osteochondrogenic tissue formed was studied histologically and histomorphometrically. The results suggest that the filling of the bone defect had no influence on the primary external and internal osteogenic callus formation at 1 and 2 weeks. At 3 and 6 weeks in the chamber groups the persisting internal bridging woven bone was converted into more compact lamellar bone whereas periosteal callus remained at the edges of the defect. In the other groups at 3 and 6 weeks the normal shape of the cortex was reconstituting. Four-day-old fibrous-like callus formed bone in the Nucleopore chamber, indicating that fibrous-like callus tissue at 4 days contains osteogenic cells. Twelve-day-old callus consisting of woven bone was partially differentiated to cartilage, showing that woven bone contains cells capable of chondrogenic differentiation.

Animals↗
PubMed1995

Nasal cytokines in common cold and allergic rhinitis.

Coronavirus-induced common cold and allergen-induced rhinitis are characterized by nasal mucosal exudation of bulk blood plasma. The mucosal exudation process involves 'flooding' of the lamina propria with plasma-derived binding proteins and it is possible that subepithelial inflammatory cytokines and mediators may be moved by the exudate to the mucosal surface. In this study, we have analysed cytokine levels in nasal lavage (NAL) fluids from non-allergic subjects inoculated with coronavirus (n = 20) and from subjects with allergic (birch pollen) rhinitis subjected to additional allergen challenge (samples were obtained 35 min post challenge) in the laboratory (n = 10). Ten of the 20 inoculated subjects developed common cold and 10 remained healthy. Interferon-gamma (IFN gamma), interleukin-1 beta (IL-1 beta), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, and IL-6 were analysed in unprocessed NAL fluids using immunoassays. The subjects who developed common cold had increased NAL fluid levels of IFN gamma (P < 0.05) that correlated well with the symptoms (P < 0.001). IFN gamma did not increase in subjects with allergic rhinitis. IL-1 beta levels were similar in NAL fluids obtained from all inoculated subjects. In the subjects with allergic rhinitis NAL fluid levels of both IL-1 beta and GM-CSF were increased (P < 0.05). GM-CSF was not detected in common cold. IL-4 and IL-6 were not detectable in any of the NAL fluids. The present cytokines may not only emanate from superficial mucosal cells. By aiding plasma exudation subepithelial cytokines may potentially also be retrieved on the mucosal surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Effect of allergen provocation on inflammatory cell profile and endothelin-like immunoreactivity in guinea-pig airways.

The effect of allergen challenge on the number of leucocytes and the concentration of endothelin 1-like immunoreactivity (ET-LI) in bronchoalveolar lavage fluid (BALF) was investigated in guinea-pigs sensitized to Ascaris suum. The animals were twice exposed to allergen aerosol. All animals responded to the second challenge with bronchoconstriction. Twelve hours later, a significant increase in the number of eosinophilic granulocytes in BALF, compared to unsensitized and unprovoked control animals, was noted. Twenty-four hours after provocation, there was also an elevation of ET-LI concentration and content of neutrophils. During the first day post-challenge, the ET-LI values were moderately correlated to the eosinophil levels. One week after challenge, the ET-LI level and the neutrophil count did not differ from corresponding values in control animals whereas the number of eosinophils remained elevated. Pretreatment with dexamethasone before the second allergen challenge did not consistently affect the parameters studied during the first 24 h. Bronchoconstriction induced by carbachol aerosol affected significantly neither the ET-LI concentration nor the number of inflammatory cells in BALF. It is concluded that the allergen-induced inflammation in the guinea-pig airways causes an elevation in the ET-LI concentration in BALF and that this is moderately correlated to the influx of eosinophils during the first 24 h.

Allergens↗
PubMed1995

The impact of somatic morbidity on the Hamilton Depression Rating Scale in the very old.

The Hamilton Depression Rating Scale (HDRS) is world-wide the most important observer rating scale for depression. Many items of this scale refer to somatic symptoms of depression which cast doubt on the validity of HDRS scores in the presence of somatic comorbidity as, for example, in elderly patients. The present study, therefore, was planned to investigate the validity of the HDRS in cases in which the patient is suffering from a depressive illness together with somatic illnesses. The study population (n = 516) is a representative sample of citizens aged 70 years and older in West Berlin. They were assessed independently by internists and psychiatrists. Each positive item of the HDRS scale was then rated by the internists as to what degree it reflects somatic morbidity. Results show that multimorbidity interferes with the validity of the HDRS. There were 8 items for which more than half of all positive scores as rated by psychiatrists were seen by the internists as being possibly related to somatic disorders. Patients with corrections in the HDRS score showed a somewhat increased rate of medicines and cardiovascular diagnoses. There was less ambiguity for items with greater severity.

Aged↗
PubMed1995

Anaesthesia for urological endoscopic procedures in adult outpatients.

The aim of this study was to establish whether propofol in combination with fentanyl or ketamine provides a good quality of anaesthesia and recovery time in urological endoscopic outpatient surgery. Sixty patients (ASA I-II) were assigned randomly to receive either 2.5 micrograms kg-1 fentanyl or 1 mg kg-1 ketamine. In both groups anaesthesia was induced with propofol 1.5 mg kg-1 and maintained with 7 mg kg-1 h-1. Patients breathed nitrous oxide and oxygen 3:2 spontaneously. Cardiovascular parameters were more stable after ketamine. The most important side effect was the presence of apnoea lasting longer than 60 s in 14 patients receiving fentanyl. The time to establish alertness was shorter in the ketamine group, who also had a better (P < 0.05) as well as post-anaesthetic recovery room score.

Aged↗
PubMed1994

Interactions between brain mitochondria and cytoskeleton: evidence for specialized outer membrane domains involved in the association of cytoskeleton-associated proteins to mitochondria in situ and in vitro.

The surface distribution of several proteins (porin, hexokinase, and two proteins associated with microtubules or actin filaments) on the outer membrane of brain mitochondria was analyzed by immunogold labelling of purified mitochondria in vitro. The results suggest the existence of specialized domains for the distribution of porin in the outer mitochondrial membrane. Similarities between the distribution of porin and the distribution of microtubule-associated proteins bound in vitro to mitochondria suggested that mitochondria and microtubules interact by binding microtubule-associated proteins to porin-containing domains of the outer membrane. This hypothesis was supported by biochemical studies on outer mitochondrial proteins involved in in vitro binding of cytoskeleton elements. In vitro interactions between mitochondria and microtubules or neurofilaments were analyzed by electron microscopy. These studies revealed cross-bridging between the outer membrane of mitochondria and the two cytoskeleton elements. Cross-bridging was influenced by ATP hydrolysis and by several proteins associated with the surface of mitochondria or with microtubules. In addition, unidentified proteins which were recognized by antibodies to all intermediate filaments subunits were associated either with the mitochondrial surface or with microtubules. This data suggest the participation of additional cytoplasmic proteins in the interactions between cytoskeleton elements and mitochondria.

Animals↗
PubMed1994

Effects of a corticosteroid, budesonide, on alveolar macrophage and blood monocyte secretion of cytokines: differential sensitivity of GM-CSF, IL-1 beta, and IL-6.

Down-regulation of cytokine production in activated human blood monocytes (BMs) and alveolar macrophages (AMs) can be achieved in vitro by treatment with corticosteroids. The inhibition of cytokine secretion by corticosteroids may have important therapeutic consequences in e.g. asthma. However, relatively little is known about possible differences in the sensitivity of different cytokines to corticosteroid treatment. Homologous BMs and AMs were obtained from six healthy volunteers. Secretion of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the cultures of lipopolysaccharide (LPS) stimulated adherent BMs and AMs was analysed using specific immunoassays. Sensitivity of the IL-1 beta, IL-6, and GM-CSF secretion to the in vitro treatment with a synthetic corticosteroid, budesonide, was compared. BMs and AMs displayed significant differences in both cytokine secretion and susceptibility to regulation by budesonide. When added to the BM cultures concomitantly with LPS, budesonide suppressed IL-1 beta and IL-6 only partially (to 30% of the control level). In contrast, GM-CSF release in these cultures was almost totally inhibited by budesonide (> or = 10(-8) M). The IC50 for inhibition of the GM-CSF secretion was as low as 2 x 10(-10) M. In the AM cultures, budesonide had very little effect on IL-1 beta and IL-6 secretion (inhibition to 80% and 60% of control levels, respectively), while GM-CSF secretion was suppressed to 20% of control by budesonide concentrations > or = 10(-7) M.(ABSTRACT TRUNCATED AT 250 WORDS)

Budesonide↗
PubMed1994

Antioxidant activity of some diarylselenides in biological systems.

The selenoorganic compounds di(4-aminophenyl)selenide (10) and 4-nitro-4'-amino-diphenylselenide (36) were shown to inhibit lipid peroxidation in ADP/Fe2+/ascorbate-treated microsomes and tert-butylhydroperoxide-treated hepatocytes with IC50s of 3 and 10 microM, and 14 and 10 microM, respectively. In the former system, these inhibition constants compare favourably with those of Ebselen and classical antioxidants such as butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA). In the cell system, these selenium compounds were equipotent with BHA but more potent than Ebselen and its analogues. The diamino compound (10) was also an effective inhibitor of lipid peroxidation initiated by diquat redox cycling in hepatocytes, again being equipotent with BHA but more potent than Ebselen and its analogues, which actually stimulated lipid peroxidation in this test system. Manipulation of the amino functions of (10) and (36) by alkylation or acylation altered the antioxidant capacity. Optimal activity in this series was achieved by N-ethylation or N-isobutylation of (10). This produced antioxidants having IC50s below 1 microM in the microsome system, 3-13 microM in the tert-butylhydroperoxide system, and being 100% effective in the diquat model at 50 microM. On the other hand, acylation or alkylation of the amino groups with long chain acyl or alkyl groups reduced the efficacy of the structures below that of the parent diamine. As with other antioxidant compounds, several of the chalcogenides were relatively selective inhibitors of monocyte 5'-lipoxygenase-dependent secretion of LTB4 as compared to their effect on cyclooxygenase-dependent secretion of PGE2 (for example compound 42 had IC50s of 0.6 microM and 10 microM, respectively). No correlation was observed between the redox-properties of the chalcogenides and their respective abilities to inhibit these enzymes.

Adenosine Diphosphate↗
PubMed1994

Therapeutic standards in psychopharmacology and medical decision-making.

Treatment surveys regularly show deviations of routine treatment from treatment guidelines. An analysis of the scientific basis of classical treatment standards, as derived from controlled treatment trials, shows that they do not take into account many variables with major impact on routine treatment. A better theoretical framework for understanding medical decision-making under complex stimulus conditions is provided by action theory. Studies that test treatment strategies instead of treatments and field observational studies, for both of which examples are given, are necessary adjuncts to controlled clinical trials in the quest for more scientifically based treatment guidelines.

Decision Making↗
PubMed1994

Structure and feasibility of a standardized stepwise drug treatment regimen (SSTR) for depressed inpatients.

"Standardized stepwise treatment regimes" (SSTR) are one way to rationally guide treatment in cases where the first treatment intervention did not yield satisfactory results. At the Department of Psychiatry of the Free University of Berlin a SSTR has been implemented into routine drug treatment for depressive disorders. The SSTR consists of eight consecutive treatment steps. If there is no sufficient change in the Bech-Rafaelsen Melancholy Scale (< 25% score reduction) in the course of two weeks, treatment has to progress to the next step. This paper describes the overall feasibility and efficacy of the strategy and the progress of the patients within the SSTR. Of those who enter the "antidepressant monotherapy phase" 52% finish treatment successfully at this stage or during the following "lithium augmentation phase". The results of this treatment-monitoring study also show that during consecutive phases of the SSTR a considerable proportion of patients in a university inpatient setting had their treatment modified according to special attitudes and clinical experiences of physicians and patients. The reasons for deviating from the SSTR obviously were more convincing than the rationale for progressing to the next step. SSTR, therefore are an important tool to give complex treatment courses a rational basis, even in patients where clinical case management requires deviations from the outlined sequence of treatment steps.

Antidepressive Agents↗
PubMed1994

Clinical recognition and drug treatment of depression in cases found by standardized assessment.

The determination of need of care is an important problem for public health. In an epidemiological perspective the question is whether the right people get the right treatment. The answer depends on a variety of methodological issues such as case-definition, case-identification, sampling, and treatment assessment. Case-definition is done by patients themselves and by experts such as physicians or scientists. This study compares the clinical approach of family physicians with the standardized approach of epidemiologists. In two epidemiological studies, the Berlin Aging Study (BASE) and the WHO Study on Psychological Problems in General Health Care (WHO/PPGHC), diagnosis and treatment of major depression in the field were analyzed. In spite of different methods, both studies showed a high rate of unrecognized major depressions as defined by DSM-III-R criteria. This lack of case-recognition by the primary care physicians corresponds to the fact that less than then percent of these patients were treated with antidepressants and none of them had been seen by a psychiatrist. The question to be discussed is whether these results speak for an underrecognition of cases that are in need of care under clinical conditions or an inflation of the respective numbers by standardized methods.

Aged↗
PubMed1994

Seasonal variation in the function of blood monocytes obtained from healthy nonsmokers, asymptomatic smokers, and smokers with chronic bronchitis.

The present study focused on two questions: What effects do cigarette smoking and chronic bronchitis have on the function of the precursors of alveolar macrophages, the blood monocytes? Can seasonal variations affect the function of these cells? Phagocytic activity (the proportion of yeast-ingesting cells and the mean number of yeast particles per ingesting cell) and metabolism of arachidonic acid [secretion of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in zymosan-stimulated cultures] were studied as markers of monocyte function during three seasons: spring (May-June), autumn (November-December), and winter (February). Smokers with chronic bronchitis (SCBs) and asymptomatic smokers (ASs) had a lower proportion (p < 0.05) of ingesting monocytes than healthy nonsmokers (HNSs) during spring, but not during the other two seasons. The secretion of PGE2 was highest during autumn and lowest during spring in the monocytes of all three groups. In autumn, LTB4 secretion was increased in the monocytes of HNSs (p < 0.05) but not in those of ASs and SCBs. LTB4 secretion was similar in all groups during the other two seasons. Cigarette smoking and chronic bronchitis seem to impair the function of monocytes and may thereby affect the systemic host defense activity. Cells collected during autumn were generally more active than those sampled in spring, indicating marked seasonal variation in the function of monocytes from all three groups.

Arachidonic Acid↗
PubMed1993

Aspirin effect on early and late changes in acute lung injury in sheep.

OBJECTIVE: There have been several studies that have already explored the potential beneficial role of cyclo-oxygenase (CO) inhibitors on oleic acid (OA)-induced lung injury in different species. These studies report no significant effect of CO inhibition, though thromboxane B2 (TxB2) was effectively blocked. However, recent studies indicate that pre-treatment with aspirin (ASA) preserve gas exchange in OA lung injury in dogs. Aim of our study has been to evaluate the potential beneficial effects of the pre-treatment with low doses of ASA on gas exchange, hemodynamics, respiratory mechanics, prostanoids and lung histology in OA-induced lung injury in sheep. DESIGN: 0.09 ml/kg of OA was administered into the right atrium of 14 anaesthetized sheep. Six received a bolus of ASA (10 mg/kg i.v.) 30 min before OA, the others saline as placebo. MEASUREMENTS AND RESULTS: Pulmonary and tissue gas exchange, pulmonary and systematic hemodynamics, respiratory system mechanics, TxB2 and 6-keto-PGF1 alpha, leukocytes and platelets concentrations were measured throughout the subsequent 3 h and lung histology was effected at end-experiment. The principal findings of our study are: 1) ASA reduces OA-induced early pulmonary vasoconstriction and bronchoconstriction, parallelled by a suppression of TxB2 generation; 2) the late increase in pulmonary artery pressure and airway resistance due to OA is not inhibited by ASA; 3) the early disturbance in pulmonary gas exchange is reduced by ASA, whereas the late severe deterioration is exaggerated by ASA; 4) the stability of tissue exchange ratio (R) at approximately 1 in ASA-group compared to its fall to approximately 0.7 in controls. CONCLUSION: Our findings suggest that ASA: 1) is only effective to treat the very transient TxB2-induced pulmonary vasoconstriction resulting in hydrostatic edema, and it is ineffective, even accentuates, the subsequent major pulmonary endothelial cell injury leading to alveolar flooding that is unrelated to TxB2; 2) has a transient protective effect on the TxB2-induced early bronchospasm; 3) has a biphasic behaviour on gas exchange, with a benefit which lasts only one hour and then results in a worse gas exchange; 4) has an immediate, stabilizing, persisting effect on R, contrasting with its transient effect on pulmonary hemodynamics and PaO2.

6-Ketoprostaglandin F1 alpha↗