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Biomedical subjects

W J Stevens

Publications and source records attributed to W J Stevens.

At least 19 recordsLinked to original sources

Detection of hypodense eosinophils by Percoll multilayer density gradient centrifugation in subjects with normal or slightly elevated eosinophilia. Poor reproducibility and eosinophils of density < 1.077 g/ml.

In patients with marked hypereosinophilia 'hypodense' and 'normodense' eosinophils have been found after density gradient centrifugation. Subsequently this terminology has also been used in studies of patients with milder eosinophilia. However, in these cases the differentiation between normo- and hypodense eosinophils was less clear. This might be due to the high imprecision of the test of density gradient centrifugation, as demonstrated in the first part of this study: the mean within-assay variance of the number of eosinophils in the different density layers was 35%. It was calculated that the test must be performed eight times to obtain an estimate of the true mean for the individual patient. In the second part of the study, the absolute number of 'hypodense eosinophils' in groups of patients with asthma (adults and children) and rheumatoid arthritis (adults) were compared to normal controls. Although a difference in the absolute number of hypodense eosinophils between groups of patients and controls could be demonstrated, the high imprecision of the test of density gradient centrifugation suggested that the technique used was not useful in an individual with normal or slightly elevated eosinophils in the peripheral blood.

Adult

Leukocytosis, monocytosis and neutrophilia: hallmarks of severe depression.

To date, there has been a small number of reports that severe depression is accompanied by disturbances in total white blood cell (i.e. leukocytosis) and leukocyte subset (i.e. neutrophilia, monocytosis, lymphopenia) counts. These results, however, have not yet been validated in a large-scale, well-controlled study. To this end, we have counted the number of leukocytes, monocytes, lymphocytes and granulocytes (neutrophils, eosinophils, basophils) in 22 healthy controls and in 109 depressed inpatients. We noted leukocytosis in major depressed patients compared with normal subjects, whilst minor depressives manifested intermediate findings. Leukocytosis was significantly more pronounced in major depressed males compared with major depressed females. Major depression related leukocytosis appears to be characterized by neutrophilia and monocytosis. There was a significant positive relationship between the overall severity of illness on one hand, and the degrees of leukocytosis, neutrophilia and monocytosis on the other. The total number of both phagocytic cell populations (i.e. monocytes and neutrophils) was significantly and positively related. Our results might point to the existence of an inflammatory process in major depressed subjects, particularly in males.

Adult

A significantly increased number and percentage of B cells in depressed subjects: results of flow cytometric measurements.

Recently, there have been some reports that depression may be accompanied by indices of polyclonal B cell proliferation. In order to examine whether depression is characterized by an altered B cell subset profile we determined the number and percentage of the following B cells: HLADR+, CD19+, CD20+, and CD21+. We found a significantly increased number of HLADR+ and CD19+ B cells in depressed subjects compared with normal controls. Depressed patients exhibited a significantly higher percentage of HLADR+ and CD21+ B cells than normal controls. The number of CD21+ cells and the percentage of CD19+ cells were higher in melancholics than in normal controls. The increase in the number of the various B cells was highly sensitive (63%) and specific (94%) for melancholia. Our results may indicate B cell proliferation in depression, and particularly in melancholia.

Adult

Experimental arthritis in rats induced by intra-articular injection of IgE aggregates: evidence for arthritogenic role of complexed IgE.

An experimental arthritis model in the rat was used to study the arthritogenic potential of complexed IgE. IgE aggregates were produced in vitro by cross linking monoclonal rat IgE by dimethyl suberimidate and were injected into the knee joints. Animals which had not been injected and animals injected with phosphate buffered saline served as controls. The concentration of histamine in tissues, diffusion into the joint of bovine serum albumin labelled with iodine-125 injected intravenously, and the histology of the joints were studied. There was a significant decrease in the concentration of histamine in synovial tissue 8 and 24 hours after the injection of the IgE aggregates. A decreased number of stainable mast cells were found 8, 24, and 48 hours after exposure. A moderate hyperplasia of the synovial lining layer was also noted. These results provide further evidence for the arthritogenic potential of complexed IgE, especially in the initiation of arthritis through activation of mast cells.

Animals

Pharmacotherapy of childhood asthma. An inflammatory disease.

The recognition that asthma constitutes 2 kinds of physiopathological reactions, namely bronchospasms (immediate reactions) and inflammatory responses (late reactions), suggests that the treatment should be focused against these events. Furthermore, the allergen provocation model, showing the existence of immediate and late asthmatic reactions, can be used to study the effects of different antiasthmatic drugs. Recently, the importance of inflammation in the pathogenesis of asthma in adults has led to the development of therapeutic regimens in which anti-inflammatory treatments are used frequently as a first-line step in the management of asthma. Although at the moment the hard data showing inflammation in childhood asthma are scarce, it is assumed that childhood asthma constitutes the same kind of chronic inflammatory processes as in adult asthma and that its treatment should also include anti-inflammatory drugs.

Adrenal Cortex Hormones

Effect of hyposensitization upon the immediate and late asthmatic reaction and upon histamine reactivity in patients allergic to house dust mite (Dermatophagoides pteronyssinus).

The effect of hyposensitization (HS) upon the allergen evoked immediate asthmatic reaction (IAR), late asthmatic reaction (LAR) and upon bronchial reactivity towards histamine was examined. Eighteen young asthmatic patients were studied using a double-blind, placebo-controlled design. All were allergic to house dust mite (HDM) and demonstrated an IAR and a LAR after bronchial provocation with HDM. Furthermore, all, except one child, demonstrated bronchial hyperreactivity towards histamine (median provocative dose producing a 20% fall in forced expiratory volume in one second (PD20) histamine = 0.19 mg.ml-1, range: 0.02-8 mg.ml-1). The subjects were randomly divided into two groups to receive HDM or placebo injections during one year. After the one year period, the IAR was less severe in the subjects who received HDM injections (p = 0.02), while this reduction was not observed in the subjects who received placebo injections. Also, in the HDM group a small but significant increase of the median PD20 HDM was observed (p = 0.04). Furthermore, the LAR was less severe in the subjects who received HDM injections (p = 0.02), while the subjects who received placebo injections showed the same severity of LAR after one year (p = 0.44). Histamine reactivity did not change after HDM injections or after placebo injections. Thus, HS reduces the severity of the IAR and LAR without any change in histamine reactivity.

Administration, Inhalation

Activation of inflammatory cells by immune complexes containing IgE in serum and synovial fluid of patients with rheumatoid arthritis: a study using flow cytometric analysis.

Neutrophil and monocyte activation by immune complexes containing IgE from serum and synovial fluid of patients with rheumatoid arthritis is reported. Activation of the inflammatory cells was measured by stimulation of the respiratory burst with production of intracellular hydrogen peroxide. Generation of hydrogen peroxide was analysed by a flow cytometric method, using the fluorochrome dichlorofluorescein. The technique was modified to allow measurement of cell activation of both neutrophils and monocytes by immune complexes in suspension. Ten of 14 polyethylene glycol precipitates from serum of patients with rheumatoid arthritis and 10/16 synovial fluids of these patients could activate neutrophils. A positive relation was found between the activation of neutrophils and the total concentration of immune complexes, the presence of IgG, and the presence of IgE in the immune complexes. Activation of monocytes was also shown, but to a lesser extent (8/14 rheumatoid serum samples and 8/16 rheumatoid synovial fluids activated monocytes). There was a weak correlation between the concentration of IgE immune complexes and the intensity of fluorescence measured in the monocytes.

Antigen-Antibody Complex

Portal and pulmonary vessel thrombosis associated with systemic lupus erythematosus and anticardiolipin antibodies.

We describe a 26-year-old patient with systemic lupus erythematosus and pulmonary and portal hypertension associated with the presence of anticardiolipin antibodies. Postmortem histological examination revealed the presence of recent thromboses of pulmonary and portal vessels. Our findings further support the concept of pulmonary hypertension being part of the antiphospholipid syndrome and suggest that portal hypertension due to intrahepatic portal vein thrombosis might be another manifestation of this syndrome.

Adult

Ultrasonography of the salivary glands in the evaluation of Sjögren's syndrome. Comparison with sialography.

Ultrasonography (US) was evaluated as noninvasive method to determine salivary gland involvement and compared with sialography in patients with Sjögren's syndrome (SS) and patients with only objective xerostomia and/or xerophthalmia. Patients with complaints of dry eyes and dry mouth but with no objective abnormalities served as control group. Ultrasound revealed a decreased parotid gland reflectivity in most of the patients with SS, compared with only 2 patients in the other group (p = 0.002). Our study suggests that US can be a useful, noninvasive method in the diagnostic work-up of patients with sicca complaints.

Humans

Aerosolized budesonide in asthmatic infants: a double blind study.

The efficacy of nebulized budesonide (0.5 mg b.i.d.) against placebo was evaluated in the management of asthma in 23 infants, aged 3 to 17 months, using a double blind crossover design. After an initial treatment period of 2 weeks placebo and budesonide were randomly administered during two consecutive treatment periods of 1 month. The progress of the patients was monitored using diary score cards, the number of salbutamol doses needed during the treatment periods, clinical examinations using standardized scoring cards, and registration of parents' preference period. Although there was a tendency toward fewer wheezing periods during budesonide, the results of the diary score cards were not significantly different between the budesonide period and the placebo period. The number of salbutamol doses used was also the same during both periods. Clinical examination after budesonide revealed less rhinitis and a less pathological lung auscultation, but the difference between the two periods was also not significant. Furthermore, the parents' preference could not distinguish between budesonide and placebo. We conclude that the trends in favor of nebulized budesonide are not significant and do not suggest that the suspension is effective in severe infantile asthma.

Administration, Intranasal

Osmolality and pH of anti-asthmatic drug solutions.

Mixtures of different drugs are frequently used in aerosol solution for treatment of asthma. These drugs have different pH and osmolality values as stock solutions. It has been suggested that acidity and osmolality interact in provoking bronchoconstriction and cough. Therefore, pH and osmolality of anti-asthmatic drug solutions and mixtures were measured in the nebulizer at 0, 1, 2, 5, 10 and 15 minutes of nebulisation, pH of fenoterol, ipratropium bromide, salbutamol and disodium cromoglycate ranged between 2.0 and 5.7 and did not change during nebulisation. Nearly all drug solutions were hypoosmolar and the osmolality increased during nebulisation with 11 to 62%. Therefore, it is suggested to dilute these drugs with saline 0.9% and to restrict nebulisation time to 10 minutes, since the most striking increase of osmolality was noted after 10 minutes.

Aerosols

IgE-containing immune complexes in synovial fluid of patients with rheumatoid arthritis.

The prevalence and composition of IgE-containing immune complexes in paired synovial fluid and serum of 42 patients with classical or definite rheumatoid arthritis were studied. IgE-containing immune complexes were found in 15/42 synovial fluids; 15 sera were also positive. The correlation between serum and synovial fluid complexed IgE levels was high (r = 0.77). The mean ratio of synovial fluid/serum levels was 1.96, i.e. significantly higher than 0.33, the synovial fluid/serum ratio for alpha-2-macroglobulin (molecular weight 820 kD), which was taken as high molecular weight control protein (p less than 0.0001). Apart from IgE in immune complex form, monomeric IgE was also significantly higher in synovial fluid compared to serum (ratio = 2.94). Other constituents which could be found in the immune complexes, i.e. anti-IgE antibodies, rheumatoid factors and anticollagen antibodies, were also higher in synovial fluid than predicted. Our results suggest intra-articular production of IgE-containing complexes in the synovial fluid, in addition to possible exudation of the complexes from the serum. These findings provide further evidence for the role of IgE-containing immune complexes in rheumatoid synovitis.

Antigen-Antibody Complex

The effect of inhaled fenoterol, administered during the late asthmatic reaction to house dust mite (Dermatophagoides pteronyssinus).

A double-blind, placebo-controlled crossover study was set up to investigate the effect of fenoterol (400 micrograms) during the late asthmatic reaction (LAR). Twenty young subjects with asthma (mean age, 11.8 years; range, 8.3 to 20.6 years) were selected on the basis that they developed an LAR after bronchial challenge with Dermatophagoides pteronyssinus. After the LAR occurred, a placebo and fenoterol were administered blindly by a metered-dose inhaler, with an interval of 15 minutes and in alternating, random sequence. At the start of the study, that is, a documented LAR, the two groups of subjects had the same severity of LAR, as expressed by the fall of the FEV1 (mean, -34.5% versus -33.5%). The mean FEV1 of the 10 patients who received placebo first changed only -1.1% (+/- 5.0), whereas after fenoterol, The FEV1 increased by 20.7% (+/- 10.8). In the 10 patients receiving fenoterol first, the mean FEV1 rose by 18.8% (+/- 8.0), whereas the placebo inhalation resulted in a supplementary increase of 3.1% (+/- 7.0). The paired Student's t test between these differences (placebo versus fenoterol) was highly significant (p less than 0.001). Although it was demonstrated in some studies that beta-agonists did not prevent the LAR, the present study demonstrates that the administration of fenoterol can reverse the FEV1 significantly, although it was not reversed completely, during an allergen-induced LAR.

Administration, Inhalation

Evolution of the late asthmatic reaction during immunotherapy and after stopping immunotherapy.

In previous studies it was demonstrated that the frequency and the severity of the late asthmatic reaction (LAR) can be attenuated by immunotherapy (IT). The present study was set up to observe the evolution of the LAR under IT and after having stopped IT. Nineteen children with bronchial asthma and an LAR to house dust mite (Dermatophagoides pteronyssinus) (HDM) were selected for this study. All subjects received IT with HDM extract during 1 year. Thereafter, the children were divided randomly into two groups to receive, double-blind, during a second year, IT with HDM (N = 9) or placebo injections (N = 10). Bronchial challenges were performed after the first and second year. After the first year, a significant decrease in the severity of the LAR was noted in all but one subject (mean decrease of FEV1 before, 40.53% versus after 1 year, 22.95%; p less than 0.0001). After the second year, the severity of the LAR remained the same in the group that received HDM injections during the second year (20.78% versus 23.00%), but in the group that received placebo injections during 1 year, a significant worsening of the LAR was observed after the second year (24.90% versus 31.20%; p = 0.038). From this study it can be concluded that the severity of the LAR decreases after the first year of IT but that the severity of the LAR remains the same after the second year of IT. In children who stop receiving IT after 1 year, we observed a recurrence of the LAR after 1 year to the same level as before IT was started.

Adolescent