Search PubMed⌕ Search

Biomedical subjects

M Linden

Publications and source records attributed to M Linden.

At least 145 records · Page 8Linked to original sources

Prevention of anaphylactic-anaphylactoid reactions to anesthetics in high-risk allergic patients.

To confirm the role of preventive procedures in high-risk allergic patients, immunological tests in vivo for anesthetics were carried out in 251 atopic patients. The 6-month follow-up showed a complete absence of adverse reactions during the clinical use of hypnotic and muscle relaxant drugs. In the case of local anesthetics, five adverse reactions were observed after dental treatment--four were related to a psychogenic mechanism, and one could not be clearly linked to the local anesthetic. It is possible to confirm that the use of a tested drug that yields negative results has a lower probability of inducing anaphylactic-anaphylactoid reactions during anesthesia.

Adolescent↗

Differences in adverse drug reactions in phase III and phase IV of the drug evaluation process.

The study of medications in routine use is called "Phase IV" of the drug evaluation process. Information gathered about drugs in Phases I through III does not provide a sufficient basis for final conclusions about the clinical value of medications after marketing. Changes in preferred indications, patient characteristics (e.g., multimorbidity), treatment mode, or treatment setting in routine as compared to controlled scientific studies lead to changes in causes, incidence, prevalence, predictability, meaning, consequences, and cost-benefit ratios of adverse drug reactions (ADRs). Rare but serious ADRs are only one aspect of postmarketing surveillance; other questions are at least as important. In contrast to Phase III, which has a single study design--the controlled, randomized, double-blind study--Phase IV requires different designs for each of the many different questions. Established methodologies include spontaneous reports, stimulated spontaneous reports, comprehensive observation studies, Phase IV intervention studies, case control studies, prescription event record linkage, and data bank comparisons.

Clinical Trials, Phase III as Topic↗

Depressive syndromes in schizophrenic patients under neuroleptic therapy. ANI Study Group Berlin, Düsseldorf, Göttingen, Munich, Federal Republic of Germany.

Schizophrenic outpatients (= 364) were assigned at random to three different treatment strategies: (1) continuous medication with neuroleptic drugs, (2) intermittent medication with crisis intervention and (3) intermittent medication with early intervention. Depressive syndromes were rated according to three different scales for depressive syndromes (Brief Psychiatric Rating Scale anxious depression factor, Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie/depression, and the self-rating Paranoid Depression Scale) after 1 and 2 years of treatment. No differences in depression scores were found between the three treatment strategies. Comparisons between patients treated with neuroleptic drugs at the time and patients without neuroleptics revealed significantly higher depression scores in the neuroleptics group in most comparisons. No differences were found between patients treated with low versus high potency neuroleptics and between oral versus depot neuroleptics. However, depression correlated with extrapyramidal symptoms.

Administration, Oral↗

Effects of endothelin and relaxin on rat uterine segment contractility.

In order to determine the effects of endothelin (ET) and relaxin on uterine contractility, immature female rats were treated with estrogen (E, 1 microgram s.c., Days 1-3) or estrogen and progesterone (2 mg s.c. [E + P], Days 2 and 3), and killed; the uterine horns were removed and suspended in muscle baths. Initially, we determined the contractile response to varying doses of ET and how this response was altered by pretreatment with progesterone. Uterine strips from animals treated with E + P (n = 10) were less sensitive to the stimulatory effects of ET than were strips from E-treated animals (n = 10). This difference was significant at ET doses above 2.5 nM. After completion of the dose-response studies, contractile patterns in response to ET and relaxin were then studied in animals treated with E (n = 10) or E + P (n = 9). ET (5 nM) significantly increased uterine contractility, mostly through an effect on the frequency of contractions (p less than 0.01). Relaxin (25 ng/ml) decreased contractility, affecting all contractile parameters measured (p less than 0.01). ET stimulated contractility in uterine horn segments previously inhibited by relaxin (p less than 0.01), and relaxin reduced the increased contractility produced by earlier exposure to ET (p less than 0.01). These data indicate that ET and relaxin can interact reversibly to control contractility in uterine horn segments in vitro, and that progesterone pretreatment can diminish the contractile response to the stimulatory effects of ET.

Animals↗

The effects of beta 2-adrenoceptor agonists and a corticosteroid, budesonide, on the secretion of inflammatory mediators from monocytes.

1. The in vitro effects of the beta 2-adrenoceptor agonists (1 x 10(-9)-10(-5) M), terbutaline, salmeterol, and formoterol, on the release of inflammatory mediators, i.e. the eicosanoids leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) and the cytokine interleukin-1 beta (IL-1 beta), were assessed in cultures of human blood monocytes. For comparison, the effects of a 5-lipoxygenase inhibitor, BW A4C (1 x 10(-9)-10(-5) M), and a corticosteroid, budesonide (1 x 10(-10)-10(-5) M) were also examined. Sotalol was used to investigate whether the actions of beta 2-agonists were mediated through beta-adrenoceptors. 2. Terbutaline, like budesonide, had no significant effect on LTB4 release, whereas BW A4C (IC50 = 2 x 10(-8) M) was a potent inhibitor. All concentrations of formoterol approximately halved the LTB4 secretion, whereas high concentrations (1 x 10(-7)-10(-5) M) only, of salmeterol, inhibited release. Only salmeterol, at high concentrations (greater than 1 x 10(-6) M), lowered the secretion of PGE2 in monocyte cultures. Formoterol and salmeterol reduced the secretion of IL-1 beta only at the highest dose (1 x 10(-5) M). In contrast, budesonide (greater than or equal to 1 x 10(-9) M) was a potent suppressant of this secretion. 3. Treatment of monocyte cultures with sotalol (1 x 10(-5) M) did not significantly antagonize the inhibitory effects of salmeterol and formoterol. These results suggest that the inhibitory action of these beta 2-agonists on the release of eicosanoids or IL-1 beta, is not mediated via beta 2-adrenoceptors.4. This study does not support a therapeutic importance of the anti-release effects of beta2-agonists since high concentrations were generally required. Furthermore, the anti-secretory action of beta2-agonists was distinct from that of corticosteroids.

Adrenergic beta-Agonists↗

Histology and histomorphometry of bone regeneration after experimental injuries.

Reparative callus formation upon tubular bone was studied after surgical injuries of different degrees. Thirty-seven young rats were divided into three groups. In the periosteum group the bone was scraped, in the fissure group we made a slit reaching the medulla, and in the defect group a standard defect was sawn. Rats were killed at 6, 12 and 18 days. The formed callus was studied histologically and histomorphometrically. The results suggest than even the primary osteochondrogenic callus formation is dependent on the mode of injury. At six days the three groups differed both qualitatively and quantitatively in regard to callus formation. At 12 and 18 days the total area of woven bone was proportional to the degree of trauma according to the linear regression line Y = 0.883 x X + 0.226 (r = 0.876, P less than 0.001). In the fissure and defect groups reparative bone filled the hole proportionally to the same extent. Periosteal and endosteal woven bone formed round the bone. Medullary bone formation was limited mainly to the area immediately adjacent to the trauma, the result being a cylinder-shaped callus. Cartilage formation was most abundant at six days and was related to the amount of woven bone in the external callus (r = 0.854, P less than 0.001) and to the trauma area (r = 0.707, P less than 0.05).

Animals↗

Prescription and intake patterns in long-term and ultra-long-term benzodiazepine treatment in primary care practice.

Pharmacoepidemiological data show that long-term treatment accounts for a considerable part of benzodiazepine prescriptions in primary care practice. Prescription and intake patterns were, therefore, investigated in a study of 196 patients who had been treated with benzodiazepines for longer than six months by internists or general physicians in private practice. Patients were 64 years of age on average, half of them being 65 years or older. Females were in the majority (73.5%). The average duration of tranquilizer or hypnotic intake was 11.0 years, or 5.3 years for the current benzodiazepine medication. The mean daily dose was 9 mg diazepam equivalent. All benzodiazepine hypnotics and 61% of benzodiazepine tranquilizers had been prescribed solely for night-time use. Only 6% of the patients were taking benzodiazepines as single medication: on average they were taking 3.1 additional types of medication for other conditions, these being predominantly cardiac and antirheumatic/analgesic in nature. One in five patients was taking additional psychotropic medication. The compliance coefficient was on average 0.8, showing that patients did not tend to abuse benzodiazepines, with noncompliance generally being similar to noncompliance with other forms of medication.

Adult↗

Recoveries of phosphatidylcholine and alveolar macrophages in lung lavage from healthy light smokers.

Twenty-one healthy volunteers, 11 light smokers and 10 non-smokers, were studied by broncho-alveolar lavage. The levels of the phosphatidylcholine (PC) in broncho-alveolar lavage were measured and used as an index of surfactant. The PC levels in broncho-alveolar lavage obtained from the smokers were significantly lower than in lavage fluid from the non-smokers. There was an inverse correlation between PC levels and cumulated tobacco smoke exposure, as estimated by the number of pack-years, and to current smoking habits as estimated by the number of cigarettes smoked per day. The number of alveolar macrophages was significantly higher in broncho-alveolar lavage obtained from smokers, and there was a significant inverse correlation between PC levels and numbers of alveolar macrophages in the lavage fluids. The potential role of alveolar macrophages in the elimination of surfactant lipids is discussed.

Adult↗

Granulocytes and their secretory products, myeloperoxidase and eosinophil cationic protein, in bronchoalveolar lavage fluids from two lung lobes in normal subjects.

The interlobar variability of lavage neutrophils and eosinophils was studied in twelve healthy subjects. In addition, the interlobar variation of the neutrophil cell marker myeloperoxidase (MPO) and the eosinophil cell marker eosinophil cationic protein (ECP) was assessed. Bronchial washes (BW), as defined by the first aspirated lavage aliquot, and bronchoalveolar lavage (BAL) fluids were compared. One subsegment of the right middle lobe and one subsegment of the right lower lobe were lavaged in the same session. Interlobar consistency of neutrophil and eosinophil cell recoveries was observed but, in contrast, the levels of MPO or ECP did not correlate in lavage fluids aspirated from the two lobes. These results suggest that BAL cell content from a single lobe of the lung in healthy subjects does reflect the cell populations throughout the airways, while the levels of soluble proteins may differ between the lobes. Such a variation questions the correlation between cells and their secretory products or the correlation between levels of solutes in lavage fluid and in the underlying tissue. Further methodological studies appear warranted to elucidate whether cell and solute recoveries accurately reflect the underlying pathology.

Adult↗

[Schizophrenic patients in ambulatory treatment of a psychiatric hospital and in general practice of established psychiatrists].

Two large samples of schizophrenic patients treated in a psychiatric hospital outpatient clinic (n = 108) and by psychiatrists in office practice (n = 265) are compared in regard to socio-demographic and illness characteristics, pharmacological treatment, tardive dyskinesia rate and psychopathological status--also with respect to results on an outcome-scale. For the outpatient clinic patients changes in hospitalization rates and duration of stay, together with predictors of psychosocial outcome dimensions are reported. The strongest differences between the samples are found in a more complicated course of illness for the outpatient clinic patients, which is interpreted as indication for a higher vulnerability. Against expectation, socio-demographic variables showed no significant differences.

Activities of Daily Living↗

The prominent role of thromboxane A2 formation on early pulmonary hypertension induced by oleic acid administration in sheep.

The early increase of pulmonary artery pressure observed in different models of experimentally induced lung injury have been shown to be associated with the release of vasoconstrictive agents by activated platelets. The aim of this study was to evaluate the pattern of these metabolites, in particular TxA2, and the effects of the inhibition of their production by ASA on the modifications of pulmonary hemodynamics induced by oleic acid administration in sheep. Group I (8 sheep) was infused with oleic acid (0.09 ml/kg at 0.02 ml/min) while in group II (6 sheep) ASA (10 mg/kg i.v.) was administered 30 minutes before oleic acid infusion. In group I pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) were significantly higher at the end of the infusion while cardiac output (CO) significantly decreased in comparison to baseline values. A marked increase in plasma TxB2 levels paralleled pulmonary hemodynamic changes. Also plasma 6 keto PGF levels increased after OA infusion. The early increase in PAP and PVR was significantly lower in group II (p less than 0.005) while CO did not undergo any significant change. ASA pretreatment significantly blunted the rise of TxB2 concentrations and prevented the elevation of 6 keto PGFa. These results indicate that early pulmonary hypertension in oleic acid induced injury is mainly related to TxA2 released from platelets and leukocytes and that pulmonary hemodynamic changes are significantly inhibited by ASA pretreatment.

6-Ketoprostaglandin F1 alpha↗

Inflammatory indices for chronic bronchitis and chronic obstructive airway disease. Cell populations in bronchial and bronchoalveolar lavage.

The development of chronic bronchitis (CB) and chronic obstructive airway disease (COAD) seems to be related to inflammatory changes of airway structure. However, the cause and the exact location and type of these changes resulting in altered airway function are not known. Mucosal inflammation is characterized by the recruitment of granulocytes, macrophages and lymphocytes as well as by the shedding of epithelial cells. The present chapter discusses the usefulness of bronchial lavage (BL; 50 ml of lavage volume) directly followed by bronchoalveolar lavage (BAL; 200 ml), for the characterization and quantification of inflammation in proximal and peripheral airways, respectively. On the basis of results from the literature and a pilot study on CB patients with or without coexisting COAD, the following conclusions may be drawn: There is a profound difference in lavage cell composition and numbers between non-smokers and smokers. However, within the group of smokers there are few additional changes in cell numbers and composition when concomitant airway disease is present. The obstruction of the COAD patients is correlated to a reduced recovery of BL and BAL fluid. Furthermore, these patients seem to have a reduced number of most cell types in their BL. This diminitution is not just related to the reduced fluid recovery. The BL cells have a lower viability and BL macrophages have a reduced phagocytic capacity when compared with matching BAL cells. The viability of cells was lowest in BL from the COAD group. These findings may suggest that COAD entails a reduced transport of macrophages to the small airways and/or an enhanced turnover of these cells in the bronchi. Functional studies of lavage cells may supply additional, and perhaps more specific, information on the mechanisms involved in the inflammatory process.

Bronchi↗

Seasonal variation in the phagocytic activity and arachidonic-acid metabolism of human blood monocytes in healthy non-smokers, smokers and chronic bronchitics.

Peripheral blood monocytes are precursor cells to alveolar macrophages (AMs). Many studies have been performed with a view to assessing the differences, in respect of morphology and function, between the AMs of smokers and those of non-smokers. Disturbed host-defence activity of smokers' AMs is reflected by, for instance, decreased phagocytic activity and impaired arachidonic acid metabolism. However, very little attention has been paid to the question what effects cigarette smoking and chronic bronchitis may have on the function of the precursors of these cells--the blood monocytes. The collection of blood monocytes is much less laborious than the sampling of AMs. Therefore, it would be a great advance if the deteriorated host defence in chronic bronchitis could be detected and followed by studies of blood monocytes. However, a seasonal variation in monocyte function, discussed in this paper, may counteract the advantage inherent in repeated sampling. This seasonal variation in cellular host-defence mechanisms should be taken into account when designing longitudinal intervention trials in chronic bronchitis.

Arachidonic Acid↗