[COPD and psychopathology: a review].
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Biomedical subjects
Publications and source records attributed to A Gillissen.
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BACKGROUND AND OBJECTIVES: Topical glucocorticoids (GCs) are potent inhibitors of cellular inflammatory mediator production. Differences in receptor binding activities are believed to correlate with inhibition of mediator release and anti-inflammatory efficacy in vivo. To further assess this hypothesis we compared in cultured human monocytes the inhibitory activity of classic synthetic GCs on leukotriene B4 (LTB4), prostaglandin E2 (PGE2), interleukin 1 beta (IL-1beta) and c-phospholipase A 2 activity (cPLA2). METHODS: Normal human monocytes (10(5) /ml) were tested for 20 hrs with increasing concentrations (range 10(-12) -10(-5) M) of triamcinolone acetonide (TAA) compared to beclomethasone dipropionate (BDP), budesonide (BUD), dexamethasone (DEX), or the ethanol diluent together with 10 microg/ml of lipopolysaccharide (LPS). Mediator production and spontaneous cPLA subset 2-activity was determined by direct enzyme immunoassay methods. RESULTS: TAA at therapeutically relevant concentration (10(-8) M) inhibited significantly (p<0.01, n = 9) mediator production of TNF-alpha > IL-1beta > TxB2 > LTB subset 4 in a dose dependent manner by 75%, 65%, 41%, and 33%. IL-1beta inhibition at 10(-8) M by TAA (65%)> BDP (52%)> BUD (47%) was not different (ANOVA, p>0.2). Also spontaneous cPLA2-activity at 10(-8) M was inhibited to a similar degree (ANOVA, p> 0.6) by BUD (17.3%) > TAA (11.4%) > BDP (8.6%). In the same culture conditions spontaneous PGE2-secretion was inhibited by BDP (28.8%) > BUD (24.2%) > TAA (11.4%) with no significant effect for TAA. CONCLUSION: Clinically well established GCs have a similar inhibitory capacity on monocyte cytokine production and surprisingly only weak effects on AA-metabolism. Small receptor binding activity may account for the lack of cytokine inhibition by subtherapeutic (<10(-8) M) airway concentrations of TAA and BDP. Partial mediator inhibition by GCs at therapeutically known airway concentrations may be relevant to control bursts of airway inflammation during acute exacerbation but unfavourable to effectively delay progression of chronic airway inflammation.
BACKGROUND: Beta2-adrenergic receptor agonists have several effects on airway function, most of which are mediated in a variety of cell types resulting in increased c-AMP-production and inhibition of inflammatory mediator production. However, their stimulating effects on cAMP-production became known to be inversed by increasing phosphodiesterase (PDE) activity and degradation of cAMP. Therefore, in this study we have evaluated the efficacy of reproterol, a dual acting beta2-adrenoceptor agonist and PDE-inhibitor, as compared to salbutamol and fenoterol with respect to production of cAMP and LTB4 in cultured monocytes. METHODS: Isolated human monocytes (10(5)/ml) were incubated (n = 9) in suspension with beta2-adrenoceptor agonists (10(-10) -10(-4) M) for 30 minutes with and without IBMX. Then, cAMP production was determined following treatment with Triton-X100. Production of LTB4 was measured following incubation of beta2-adrenoceptor agonists for 4 hrs in the presence of LPS (10 mg/ml). cAMP and LTB subset 4 were measured in culture supernatants by enzyme immunoassay. RESULTS: At 10(-5) M, production of cAMP was significantly stimulated by reproterol > fenoterol > salbutamol in a dose-dependent manner to an extent of *128%, *65%, 13% (*p<0.04) respectively. In contrast, LTB4-production was inhibited significantly to a similar degree by salbutamol and reproterol in a dose-dependent manner by 59% and 49% (10(-5) M, p<0.03), respectively, with decreasing inhibition (15%) after fenoterol. Following co-incubation with IBMX, cAMP production only increased significantly (p<0.002) after fenoterol (+110%) compared to salbutamol (+29%) and reproterol (+50%) (ANOVA, p<0.001). CONCLUSION: These data suggest effects of the theophylline constituent of reproterol to inhibit adenylyl cyclase induced phosphodiesterase activity. The advantageous synergistic effects of reproterol on cAMP-production need to be further explored in trials.
OBJECTIVES: The aim of this enquiry was to compare the doctor's attitude with the patient's opinion on asthma treatment, in order to reveal gaps in each other's relationship, which could be the basis of designing a better information strategy and improve disease management. METHODS: General practitioners (n = 202) and Internists (n = 103) in private practice, as well as asthma patients (n = 244) were asked to take part in telephone interviews regarding their treatment beliefs. To accomplish this, a structured questionnaire was used by an experienced interviewer. 50 % of the patients were treated with steroids. RESULTS: Over 90 % of the patients were treated with short- and long acting beta (2)-agonists (alone or in combination). Up to 20% more patients reported suffering from cough, bronchitis, hay fever, and sinusitis than the physician's estimated. Although treated patients reported frequent cough episodes and wheezing. 42 % of all patients (in contrast to 52 % according to their physician had estimated) "side effects" and 21 % (46 % estimated by physicians) named "frequency of application" as their major concern. Patients preferred the oral application form (tablet, capsule) to the same extent as metered dose inhalers (40 % positive answers). Physicians overestimated the preference of the oral application form (62 % positive answers). CONCLUSION: Our inquiry revealed high incidence of typical asthma symptoms despite therapeutic interventions, and a disparity of the physician's assessment of their patient's aversions and preferences of asthma medication and the mode of application. This investigation may help to improve the patient-physician relationship by contributing to a better understanding of patients' individual attitudes, and eventually leading to better asthma control.
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A patient was admitted to the hospital to clarifying a left-sided pleural effusion. Typical cytological findings in pleural effusion did not leave a doubt about being present a pancreatitis in conformity with clearly increased levels of lipase and amylase in the effusion fluid. The CT of the upper abdomen showed signs of a exsudative pancreatitis. In the chest CT as well as in transesophageal ultrasound evaluation large structures of soft-tissue-density together with areas of encapsulated fluid were seen in the dorsal mediastinum reaching down to the diaphragm and abdomen. Just with subsequent diet and strict termination of any alcohol consumption the pathological findings recovered completely. Due to the expansive involvement of the pleural, mediastinal and abdominal compartments this is an extraordinary case of acute pancreatitis.
Asthma treatment is suboptimal in many patients, with impacts on morbidity and mortality, healthcare resource utilisation and patients' quality of life. The reasons for this include the inherent variability of asthma and the unpredictability of exacerbations, which can range from mild to fatal. In addition, asthma can be difficult to diagnose, particularly in the very young and old. Although treatment guidelines are widely available and well publicised, surveys have identified a significant gap between treatment aims and current levels of asthma control. Patient adherence to inhaled corticosteroids is poor, and many patients rely on short-acting beta2-agonists. The reasons for this are complex but are believed to include poor perception by patients of their asthma severity, concerns about the safety and efficacy of medication and low treatment expectations. Patients appear to be unaware of the extent to which airway inflammation can be controlled and are therefore satisfied with poor asthma control, accepting a high level of symptoms. Increasing patient understanding of asthma and its treatment, allowing patients greater involvement in treatment decisions, increasing the role of asthma nurses and improved communication between physicians and patients may improve outcomes in patients with asthma.
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Among the major allergic pulmonary disorders are bronchial asthma, extrinsic allergic alveolitis, allergic aspergillosis and berylliosis. Asthma is diagnosed on the basis of clinical symptoms (wheezing, respiratory distress, tight chest, coughing) and lung function tests possibly supplemented by allergic and provocative testing. Asthma treatment is differentiated into long-term medication and as-required medication. Specific immunotherapy is considered the sole causal therapy. Extrinsic allergic alveolitis is work- or hobby-related (farmer's/cheese worker's/bird-fancier's lung) and manifests as diffuse pneumonitis with dyspnea, coughing and fever. For the diagnosis, the antigen provocative test in particular plays a major role. In the main, treatment comprises strict avoidance of allergens. The diagnosis of allergic pulmonary aspergillosis is based on the history, clinical findings, skin tests, serology and radiography. Treatment is stage-related by means of immunosuppressive agents. In terms of radiographic and pulmonary function findings, berylliosis is similar to sarcoidosis. Here, too, immunosuppressive agents are to the fore.
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An increase in Haemophilus influenzae resistance has been documented around the world during the last 30 years. Resistance is due to the production of beta-lactamases, and/or changes to penicillin-binding protein (PBP) targets. The resistance problem has led to the need for new therapeutic strategies aimed at maintaining effective management of both upper respiratory tract infections (URTIs) and lower respiratory tract infections (LRTIs). Among antimicrobial agents tested, third-generation cephalosporins have been shown to possess excellent in vitro activity against beta-lactamase-positive and -negative isolates, corresponding with proven clinical efficacy in a wide range of RTIs. The role of H. influenzae in RTIs is outlined, changing trends in epidemiological surveillance studies monitored and implications for therapy, based upon results of clinical trials discussed.
Airway hypersecretion is mediated by increased release of inflammatory mediators and can be improved by inhibition of mediator production. We have recently reported that 1.8-cineol (eucalyptol) which is known as the major monoterpene of eucalyptus oil suppressed arachidonic acid metabolism and cytokine production in human monocytes. Therefore, the aim of this study was to evaluate the anti-inflammatory efficacy of 1.8-cineol by determining its prednisolone equivalent potency in patients with severe asthma. Thirty-two patients with steroid-dependent bronchial asthma were enrolled in a double-blind, placebo-controlled trial. After determining the effective oral steroid dosage during a 2 month run-in phase, subjects were randomly allocated to receive either 200 mg 1.8-cineol t. i.d. or placebo in small gut soluble capsules for 12 weeks. Oral glucocorticosteroids were reduced by 2.5 mg increments every 3 weeks. The primary end point of this investigation was to establish the oral glucocorticosteroid-sparing capacity of 1.8-cineol in severe asthma. Reductions in daily prednisolone dosage of 36% with active treatment (range 2.5-10 mg, mean: 3.75 mg) vs. a decrease of only 7% (2.5-5 mg, mean: 0.91 mg) in the placebo group (P = 0.006) were tolerated. Twelve of 16 cineol vs. four out of 16 placebo patients achieved a reduction of oral steroids (P = 0.012). Long-term systemic therapy with 1.8-cineol has asignificant steroid-saving effect in steroid-depending asthma. This is the first evidence suggesting an anti-inflammatory activity of the monoterpene 1.8-cineol in asthma and a new rational for its use as mucolytic agent in upper and lower airway diseases.
Enlarged lymph nodes are a common diagnosis in clinical practice. The causes are varied and both benign or malignant processes might be responsible. Clearly it is important to quickly discern whether the origin is malignant or benign. The aim of this study was to evaluate the reliability and efficacy of aspiration cytology of enlarged lymph nodes. 398 patients with peripheral enlarged lymph nodes, who, in the course of a five-year period, were subjected to at least one immediate cytologic analysis (bed-side-analysis), were included in the study. For comparison the gold standard was defined as either the histological result of a corresponding biopsy or the clinical outcome within an observation period of one year. Cytology analysis reached a sensitivity of 97.6% and a specificity of 96.0% of all lymph nodes analysed. For metastatic lymph nodes of solid neoplasmas (mainly bronchial carcinoma) sensitivity was even 98.7% (90.6% for malignant lymphomas). In conclusion, fine needle lymph node aspiration cytology is a quick, reliable, technically simple method for further assessment of enlarged lymph nodes in order to distinguish between benign and malignant causes. Further differentiation of the underlying type of malignant origin can be achieved with high efficacy. Thus, in the hands of a qualified investigator, fine needle lymph node aspiration cytology is a suitable method for use on a bed-side basis.
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BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are a common cause of hospital admission. Many exacerbations are believed to be due to upper and/or lower respiratory tract viral infections, but the incidence of these infections in patients with COPD is still undetermined. METHODS: Respiratory syncytial virus (RSV), influenza A and B, parainfluenza 3, and picornaviruses were detected by nested reverse transcription polymerase chain reaction (RT-PCR) in upper (nasal lavage) and lower respiratory tract specimens (induced sputum). In a 2:1 case-control set up, 85 hospitalised patients with AE-COPD and 42 patients with stable COPD admitted for other medical reasons were studied. RESULTS: Respiratory viruses were found more often in sputum and nasal lavage of patients with AE-COPD (48/85, 56%) than in patients with stable COPD (8/42, 19%, p<0.01). The most common viruses were picornaviruses (21/59, 36%), influenza A (15/59, 25%), and RSV (13/59, 22%). When specimens were analysed separately, this difference was seen in induced sputum (exacerbation 40/85 (47%) v stable 4/42 (10%), p<0.01) but was not significant in nasal lavage (exacerbation 26/85 (31%) v stable 7/42 (17%), p=0.14). In patients with AE-COPD, fever was more frequent in those in whom viruses were detected (12/48, 25%) than in those in whom viruses were not detected (2/37, 5%, p=0.03). CONCLUSION: Viral respiratory pathogens are found more often in respiratory specimens of hospitalised patients with AE-COPD than in control patients. Induced sputum detects respiratory viruses more frequently than nasal lavage in these patients. These data indicate that nasal lavage probably has no additional diagnostic value to induced sputum in cross-sectional studies on hospitalised patients with AE-COPD and that the role of viral infection in these patients is still underestimated.
Sarcoidosis is a systemic disease of unknown etiology and highly variable clinical presentation that manifests most frequently in the hilus lymph nodes, skin and eyes. The present case is a 63-year-old woman who was admitted for investigation of progressive apnea. Numerous typical, but also rare, organic symptoms were assignable to a chronic form of sarcoidosis: epileptiform attacks and depression, as also cutaneous changes affecting the scalp, and long wrongly diagnosed granulomatous "tumour" in the left orbit. The correct diagnosis was established on the basis of bronchoscopy and a chest CT that revealed inflammatory fibrotic changes in the lungs, and the histological work-up of tissue biopsies obtained from the various cutaneous lesions.