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Biomedical subjects

J W Lammers

Publications and source records attributed to J W Lammers.

At least 109 records · Page 6Linked to original sources

[Bronchiectases; clinical aspects, diagnosis and treatment].

Localised bronchiectasis was diagnosed in three immigrants, a male aged 16 and two females aged 45 and 20 years old. The symptoms were productive coughing (purulent discharge) and (or) haemoptysis. All recovered after surgical resection of the diseased lung parts. With the growing population of immigrants in the Netherlands it is of great importance to consider the presence of localised bronchiectasis in patients from this population who present with a persistent or recurrent bronchopneumonia.

Adolescent↗

The protective effects of ipratropium bromide and terbutaline on distilled water-induced bronchoconstriction.

In a randomized, double-blind, placebo-controlled study, we investigated the protective effects of ipratropium bromide 160 micrograms and 320 micrograms and terbutaline 500 micrograms on ultrasonically nebulized distilled water (UNDW)-induced bronchoconstriction in nine stable asthmatic patients. Both drugs caused a significant increase (P < 0.001) in baseline FEV1 with no significant differences between the drugs or both doses of ipratropium bromide. Pre-inhalation of ipratropium bromide 320 micrograms and terbutaline 500 micrograms inhibited UNDW-induced bronchoconstriction (P < 0.01), whereas ipratropium bromide 160 micrograms had no protective effect. The protective effects of ipratropium bromide showed a large interindividual variation. There was no correlation between the increase in baseline FEV1 and PD20 UNDW, indicating that the protective effect on UNDW-induced bronchoconstriction is not dependent on the bronchodilation induced by terbutaline and ipratropium bromide. It also appears that the UNDW-induced bronchoconstriction is at least partly vagally mediated.

Administration, Inhalation↗

Immunophenotyping of eosinophils recovered from blood and BAL of allergic asthmatics.

Studies of bronchoalveolar lavage (BAL) fluid from patients with allergic asthma have demonstrated active migration of eosinophils into the bronchial lumen after allergen challenge. The mechanisms mediating this eosinophil infiltration and cell activation are largely unexplained. The expression of several cell-surface molecules was measured on eosinophils derived from blood and BAL fluid 4 h after an allergen-induced early asthmatic reaction in order to find indications for a role of these molecules during extravasation to and activation in the bronchial compartment. Nine patients with allergic asthma participated in the study. An eosinophil-specific, high-depolarization signal enabled us to measure expression on eosinophils in a fluorescence activated cell sorter (FACS) analysis without isolation of these cells. Eosinophils recovered from BAL showed a different phenotype than blood eosinophils; upregulation of CR-3, p150/95, CD67, and CD63, and downregulation of L-selectin indicate that the cells are activated in terms of degranulation. Up-regulation of intercellular adhesion molecule-1 (ICAM-1), LFA-3, and human leukocyte antigen II (HLA-II) might enable cell-cell contact between T-lymphocytes and eosinophils, probably leading to immunomodulation and cell activation. The finding that eosinophils in BAL are activated and can interact with T cells is further evidence for the proinflammatory role of these cells in allergic asthma.

Adult↗

Lung function, CT-scan and X-ray in upper airway obstruction due to thyroid goitre.

The purpose of this study was to assess the clinical reliability and to compare routine lung function tests (maximal flows and resistance) and radiological images (computed tomography (CT)-scan and X-ray) in upper airway obstruction. We, therefore, performed these examinations prospectively in 28 female patients (aged 68 +/- 13 yrs) with a goitre and without pulmonary disorders. Lung function measurements consisted of maximum expiratory and inspiratory flow-volume curves and of airway resistance. CT-scans and X-rays were performed during apnoea at functional residual capacity (FRC). Peak expiratory flow was 3.6 +/- 1.3 l.s-1 (i.e. 62 +/- 21% predicted); airway resistance was 0.38 +/- 0.14 kPa (i.e. 149 +/- 58% pred); and specific conductance was 1.0 +/- 0.3 kPa (i.e. 70 +/- 24% pred). Almost all lung function tests were significantly correlated with each other. On CT-scan the tracheal cross-sectional area at the zone of tracheal narrowing could be evaluated in 26 patients and was 58 +/- 17% (CT1/2) of the control area 2 cm above the carina (CT2). On X-ray the sagittal and coronal tracheal diameters at the zone of narrowing could only be measured in 16 subjects and were 60 +/- 17% (X-dia1/2) of the diameter at the control level. CT1/2 and X-dia1/2 were significantly correlated to each other. No correlation was found between the lung function tests and the radiological indices except airway resistance and CT2. Routine lung function and CT-scan do not provide comparable information on the degree of airway obstruction due to a goitre.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Long-term oxygen therapy.

This review discusses the different aspects of long-term oxygen therapy (LTOT). In selected patients with chronic hypoxaemia, LTOT may increase the life-span and quality of life. Since identification of these patients is both important and difficult, the indications for LTOT are discussed. Next, the appropriate time at which LTOT should be initiated is discussed in the section on the physiological criteria. Even in patients who qualify for LTOT, the effectiveness of this therapy may vary. Because they are important in this context, the prescription guidelines are considered. Finally, possible ways of increasing the efficiency of LTOT are reviewed in the sections on home oxygen systems, oxygen-conserving methods and the organization of LTOT in the Netherlands.

Humans↗

Cytokine priming of the respiratory burst in human eosinophils is Ca2+ independent and accompanied by induction of tyrosine kinase activity.

We report that pretreatment of human eosinophils with GM-CSF, IL-3, or IL-5 enhanced the respiratory burst induced by opsonized particles. In order to gain more insight into the intracellular mechanism(s) involved in cytokine priming, the role of [Ca2+]i and tyrosine kinases was studied. Optimal priming concentrations of GM-CSF, IL-3, and IL-5 did not induce a rise in [Ca2+]i, and Ca(2+)-depleted eosinophils ([Ca2+]i < 20 nM) were still primed after preincubation with these cytokines. GM-CSF, IL-3, and IL-5 induced phosphorylation of two proteins (102 and 122 kd) on tyrosine residues, as deduced from Western blot analysis with an antiphosphotyrosine monoclonal antibody (4G10). This cytokine-stimulated tyrosine phosphorylation was not inhibited under Ca(2+)-depleted conditions. In conclusion, this study demonstrates that GM-CSF, IL-3, and IL-5 priming of the opsonized particle-induced respiratory burst in human eosinophils is completely Ca2+ independent. Moreover the tyrosine phosphorylation of a 102-kd and a 122-kd protein is Ca2+ independent, suggesting that this event might be involved in cytokine priming.

Calcium↗

Transient exposure of human eosinophils to the protein kinase C inhibitors CGP39-360, CGP41-251, and CGP44-800 leads to priming of the respiratory burst induced by opsonized particles.

We report that a transient incubation of human eosinophils with the protein kinase C (PKC) inhibitor CGP39-360 (staurosporine) or the more PKC-specific inhibitors CGP41-251 and CGP44-800 prior to activation of the respiratory burst with opsonized particles results in priming of this response. This priming effect was concentration dependent and occurred in the range in which the phorbol myristate acetate-induced respiratory burst was inhibited. CGP39-360 priming was minimally affected in Ca(2+)-depleted cells, indicating that an increase in [Ca2+]i is not important. Also, the binding of serum-treated zymosan (STZ) particles was strongly enhanced by the inhibitors. On the other hand, the release of platelet-activating factor (PAF) induced by opsonized particles was enhanced only by CGP39-360 and not by CGP41-251 and CGP44-800. Therefore, priming of the respiratory burst is not due to an aspecific enhancing effect of the inhibitors. These data indicate that different signal transduction routes are involved in priming of the STZ-induced respiratory burst and PAF release in human eosinophils.

Alkaloids↗

Down modulation of L-Selectin expression on eosinophils recovered from bronchoalveolar lavage fluid after allergen provocation.

In allergic asthma eosinophils infiltrate into the lung after allergen challenge. The mechanism of this cellular infiltration is not fully understood. L-Selectin is involved in leucocyte-endothelial cell recognition and participates in homing of leucocytes into sites of inflammation. To find indications for a role of L-Selectin in the migration of eosinophils to the bronchoalveolar space we measured L-Selectin expression on eosinophils in peripheral blood and bronchoalveolar lavage fluid (BAL) 4 hr after the early allergic reaction after allergen challenge. Nine patients with allergic asthma participated in the study. An eosinophil specific high depolarization signal enabled us to measure L-Selectin expression on eosinophils in a FACS analysis without isolation of these cells. Eosinophils recovered from BAL showed a strong decrease of L-Selectin expression compared to blood eosinophils. This decrease in L-Selectin expression can be induced in vitro by activation of eosinophils with PMA or FMLP whereas priming of eosinophils during several hours with GM-CSF did not influence L-Selectin expression. Our results are a first indication that L-Selectin may play a role during homing of eosinophils in the lung in asthma after allergen challenge. Moreover, the low expression of L-Selectin on eosinophils in the lung is a further indication that these cells exhibit an activated phenotype.

Adult↗

Extracellular and intracellular magnesium concentrations in asthmatic patients.

Magnesium deficiency is associated with increased contractility of smooth muscle cells. Since contractility of bronchial smooth muscle is important in patients with asthma, magnesium deficiency could negatively influence the clinical condition. We wanted to assess whether magnesium deficiency exists in patients with asthma. Extracellular (plasma) and intracellular (erythrocytes and mononuclear leucocytes) concentrations of magnesium were determined in 20 mildly symptomatic patients with asthma and compared to 20 healthy controls. In asthmatic patients, the mean +/- SD magnesium level in plasma was 0.81 +/- 0.05 mmol.l-1, in erythrocytes 0.20 +/- 0.02 fmol.cell-1, and in mononuclear leucocytes 5.10 +/- 2.55 fmol.cell-1; these values did not differ significantly from those of the healthy controls: 0.79 +/- 0.06 mmol.l-1, 0.19 +/- 0.02 fmol.cell-1, and 4.61 +/- 1.75 fmol.cell-1, respectively. No evidence for the existence of a magnesium deficit needing chronic magnesium supplementation was, thus, found in these patients.

Asthma↗

Bronchodilator properties of an inhaled leukotriene D4 antagonist (verlukast--MK-0679) in asthmatic patients.

The safety, tolerability and bronchodilator properties of inhaled verlukast (MK-0679), a new potent and selective LTD4-receptor antagonist, were studied in 12 asthmatic subjects with more than 15% increase in FEV1 after salbutamol inhalation. On three separate study days the patients inhaled placebo, verlukast 2 mg and verlukast 8 mg from a metered dose inhaler according to a randomized, double-blind, cross-over allocation schedule. Pulmonary function and tolerability were assessed regularly and after 8 h a second dose of test drug was inhaled. Thirty minutes later a beta 2-agonist dose-response curve was performed by inhaling salbutamol in cumulative doses of 200, 400 and 800 micrograms. Verlukast (8 mg) caused significant improvement in mean FEV1 from 1.5 through 8 h after inhalation as compared to placebo (P less than 0.05). The maximum change in FEV1 occurred at 2 h after inhalation with mean percent increases above baseline of 3.5, 7.7, and 9.2% after placebo, verlukast 2 mg and 8 mg, respectively. The bronchodilator response to inhaled salbutamol was significantly larger after verlukast 8 mg than after placebo pretreatment (P less than 0.05), whereas verlukast 2 mg afforded no additive bronchodilator effect. We conclude that inhalation of the LTD4-antagonist verlukast induces modest but significant bronchodilatation and may be beneficial in the treatment of asthma.

Administration, Inhalation↗

Ceftazidime monotherapy for pulmonary melioidosis in a traveler returning from Thailand.

A patient with deteriorating pulmonary melioidosis rapidly recovered after treatment with ceftazidime. To prevent possible relapses, an oral maintenance regimen of amoxicillin and clavulanic acid was prescribed for a period of three months. Melioidosis is caused by Pseudomonas pseudomallei. It is an insidious disease because of its variable clinical presentation, possible long-term asymptomatic carriage, broad-spectrum resistance to first-line antibiotics, and high mortality rate. As in our patient, the diagnosis should be particularly considered when there is reduced immunologic resistance and previous exposure in endemic areas, such as Southeast Asia.

Ceftazidime↗

Effect of inhaled beclomethasone and nedocromil sodium on bronchial hyperresponsiveness to histamine and distilled water.

In a randomized, cross-over study we compared the effects of inhaled nedocromil sodium, 4 mg q.i.d., with inhaled beclomethasone dipropionate, 200 micrograms q.i.d. in 23 atopic asthmatic patients. After a 3 week single-blind placebo period, regarded as the baseline, and after 4 and 8 weeks of active treatment, drug effects were assessed with regard to bronchial hyperresponsiveness to histamine and distilled water, lung function and beta 2-agonist use. After 4 and 8 weeks of treatment, nedocromil sodium reduced the histamine responsiveness (p < 0.005 and p < 0.0005), but not the distilled water responsiveness, and did not improve lung function and peakflow measurements compared to baseline. After 4 and 8 weeks of treatment, beclomethasone caused a significant increase in lung function (p < 0.005) and decrease in bronchial hyperresponsiveness to histamine (p < 0.0005) and distilled water (p < 0.0005) as compared to baseline. beta 2-agonist use was significantly diminished after an 8 week treatment with beclomethasone, whereas nedocromil sodium had no effect. Treatment with beclomethasone was superior to treatment with nedocromil sodium with regard to bronchial hyperresponsiveness to histamine and distilled water (p < 0.0005 and p < 0.005), lung function (p = 0.003), peakflow measurements (p < 0.05) and beta 2-agonist use (p < 0.005).

Administration, Inhalation↗

Nonadrenergic, noncholinergic airway inhibitory nerves.

Nonadrenergic, noncholinergic (NANC) nerves, which cause relaxation of airway smooth muscle, have been described in several species including man. Stimulation of efferent vagus nerves during cholinergic and adrenergic blockade induces a pronounced bronchodilation in the cat. In more recent studies in man, capsaicin inhalation or mechanical irritation of the larynx, under conditions of cholinergic and adrenergic blockade, have been shown to cause a transient bronchodilator response. There is some evidence that neuropeptides such as vasointestinal peptide (VIP) or peptide histidine methionine (PHM) may be the neurotransmitter of NANC nerves, but this is not conclusive. Nitric oxide may be another neurotransmitter. In mild asthma, the NANC bronchodilator response is similar to that observed in normal subjects; on the other hand, a reduction in VIP immunoreactivity has been reported in more severe patients. The contribution of NANC dilator nerves in pathophysiological situations is not known, but their effect may be modulated during allergic responses. Use of antagonists or inhibitors of putative neurotransmitters, and molecular biological techniques will be useful in defining both the physiological and pathophysiological roles of NANC inhibitory nerves in the airways.

Animals↗

Bronchial vagal tone and responsiveness to histamine, exercise and bronchodilators in adult patients with cystic fibrosis.

Atopy and bronchial responsiveness to histamine, exercise and bronchodilators were investigated in 18 adult patients with cystic fibrosis (CF). Reversibility of airflow limitation was measured after ipratropium bromide and terbutaline, and histamine and exercise provocation tests were performed. Histamine hyperresponsiveness was observed in 10 out of 18 patients and was not confined to those with severe airway obstruction. The positive histamine responders showed significantly better bronchodilatation after terbutaline, when compared to negative histamine responders. Histamine responsiveness was not related to atopy or exercise responsiveness. Exercise challenge caused bronchodilatation without bronchoconstriction in all patients. The exercise-induced bronchodilatation correlated with bronchodilatation after ipratropium bromide. It is proposed that an increased vagal tone may lead to an increased resting bronchomotor tone which can be reduced by ipratropium bromide and by exercise in adult patients with cystic fibrosis.

Adolescent↗

Chronic extrinsic allergic alveolitis in a family with idiopathic pulmonary fibrosis: the importance of histological diagnosis.

We report a patient who presented with progressive exertional dyspnoea, chronic cough and radiographic signs of interstitial lung disease. Since several of his family members were known to have familial idiopathic pulmonary fibrosis he was also suspected to suffer from this disease. After thorough investigation, including histological examination of lung biopsies obtained by thoracoscopy, a diagnosis of chronic extrinsic allergic alveolitis was made. Current knowledge of familial idiopathic pulmonary fibrosis is discussed. This case report underlines the importance of a histological diagnosis in interstitial lung disease.

Alveolitis, Extrinsic Allergic↗