Dendritic cells with antigen-presenting capability reside in airway epithelium, lung parenchyma, and visceral pleura.

In this study, we identified a population of dendritic cells (DC) that exists throughout human and mouse pulmonary tissues, including the trachea, bronchi, alveoli, and visceral pleura. In human tissue, these DC were shown to be positive for HLA-DR and T200 antigens. In the mouse, the DC expressed not only Ia and the T200 antigen, but also Fc-IgG and C3bi receptors. Unlike alveolar macrophages, the DC were negative for nonspecific esterase staining and shared ultrastructural similarities with the DC described by Steinman (1), and with Langerhans' cells, even though they did not contain Birbeck granules. We were able to demonstrate that mouse pulmonary DC function in antigen presentation, as observed with the other DC. Thus, the respiratory tract contains DC that are capable of functioning in antigen presentation and that may be important in pulmonary immune responses.

Pharmacodynamic effects of inhaled dry powder formulations of fenoterol and colforsin in asthma.

The airway and tremor response and cardiovascular and hypokalemic effects of single doses of inhalative fenoterol dry powder capsules (0.4 mg) were compared with the fenoterol metered dose inhaler (0.4 mg) and colforsin (forskolin) dry powder capsules (10.0 mg), a direct activator of the adenylate cyclase system, in 16 patients with asthma. Subjects (FEV1 < or = 60% predicted) were investigated in a randomized, double-masked, placebo-controlled, four-period, crossover trial for a 120 minute period. All active drugs caused a significant increase in specific airway conductance (p < 0.05); the order of potency (mean +/- SEM maximum increase from baseline) was fenoterol metered dose inhaler (0.51 +/- 0.06 sec-1 x kPa-1), fenoterol dry powder capsules (0.49 +/- 0.07), and colforsin dry powder capsules (0.30 +/- 0.03). A marked increase in finger tremor amplitude resulted after fenoterol metered dose inhaler only (62.93% +/- 10.21%; p < 0.05) in contrast to fenoterol dry powder capsules (15.84% +/- 4.35%; p < 0.05) and colforsin dry powder capsules (12.87% +/- 10.44%; p > 0.05). A decrease in plasma potassium was found after fenoterol (metered dose inhaler > dry powder capsules; p < 0.05). In conclusion, fenoterol dry powder capsules caused less tremor response and hypokalemic effects than the metered dose inhaler, although the bronchodilator capacity was similar. Colforsin dry powder capsules resulted in a measurable bronchodilatation in patients with asthma.

Vasoactive intestinal peptide receptors in rat spleen and brain: a shared communication network.

The binding sites for [125I]-vasoactive intestinal polypeptide (125I-VIP) in rat spleen and brain were localized using autoradiography. High affinity VIP receptors are present in rat spleen, and competition studies reflect structure-activity relationship typical of VIP receptors elsewhere. In spleen, specific binding of 125I-VIP occurs on red pulp and, most abundantly, on the periarteriolar lymphoid sheath (PALS) of white pulp. Unlabeled VIP competes for binding to both red pulp and white pulp, whereas secretin displaces binding to PALS more potently than to red pulp. This indicates that expression of VIP and/or secretin type receptors is limited to T lymphocytes of white pulp. In red pulp, VIP receptor bearing cells probably are monocytes/macrophages since this is the most abundant red pulp cell type. In the brain, VIP receptors are widely distributed with the highest densities occurring in "sensory" areas. Receptors are abundant in the olfactory bulb, thalamic nuclei, several cranial nuclei and the area postrema. High levels of 125I-VIP binding occurred on inner walls of blood vessels of the brain and spleen. The distribution patterns of receptors for "VIP-ergic signals" in brain and lymphoid tissue indicate interrelatedness of the two organ systems. This may serve as one biochemical rationale for a bio-psycho-social view of health and disease.

Effects of neuropeptide Y and vasoactive intestinal peptide on human venous smooth muscle in vivo.

The direct and noradrenaline-modulating effects of neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) on venous smooth muscle were studied in healthy volunteers employing the dorsal hand vein compliance technique. Local infusions of NPY had no measurable effect on venous tone, but coinfusion of a constant high dose of NPY (242 pmol/min) with noradrenaline caused a 2.9-fold increase in the mean ED50 for noradrenaline. The dilating effect of VIP on preconstricted hand veins was weak, maximal venodilation could not be achieved, because systemic side effects occurred at submaximally venodilating doses. Coinfusion of noradrenaline with a weakly venodilating, constant dose of VIP (93.2 pmol/min) caused a 0.5-fold decrease in the sensitivity for noradrenaline. Although functional interactions between NPY or VIP and noradrenaline could be demonstrated, the dosages of the peptides required were high. Thus our results indicate that neither NPY nor VIP exert a major direct or noradrenaline-modulating effect on human veins.

Bronchial reactivity in hyperresponsive patients and healthy individuals: demonstration with high resolution computed tomography.

OBJECTIVE: High resolution computed tomography (HRCT) was used to assess the extent of bronchial reactivity after inhalative bronchoprovocation and dilation in hyperresponsive patients and healthy subjects. PATIENTS AND METHODS: Patients with mild intermittent asthma, 15 with a >20% decrease in FEV1 and a >10 mmHg (PC20+) in PaO2, 12 with a <20% decrease in FEV1 and a >10 mmHg (PC20-) in PaO2 after provocation, and eight healthy humans were included in the study. Changes in cross-sectional area in a total of 1256 bronchi and in bronchial wall area (792 bronchi) were evaluated after histamine-triggered bronchoprovocation and salbutamol-induced bronchodilation at high lung volumes (FVC 80%). Data were compared with the results of pulmonary function tests (FEV1, PaO2, PaCO2). RESULTS: In all groups, a significant decrease in bronchial cross-sectional area (P<0.001) and a significant increase in bronchial wall area (P<0.001) were observed subsequent to bronchoprovocation. After bronchodilation, the increase in cross-sectional area (P<0.001) and the further increase in airway wall area (P<0.01) were significant in all groups. In PC20+ and PC20- asthmatics, significant differences (P<0.05) in PaO2, >10 mmHg between baseline and provocation were observed. In healthy persons, the PaO2 decrease was <10 mmHg (P>0.05). After histamine provocation, the decrease in FEV1 was measured in the PC20+ group, whereas a <20% FEV1 decrease was found in the PC20- and the control groups, respectively. No significant correlations were observed between radiological data and the results of pulmonary function tests. CONCLUSIONS: HRCT demonstrated bronchial reactivity in hyperresponsive patients and, unexpectedly, in healthy subjects. The applied pulmonary function tests failed to characterize bronchial reactions in the healthy subjects. Based on these results, HRCT is a useful tool by which to achieve a comprehensive understanding of the pathophysiological processes in asthmatic patients.

[HRCT and bronchial asthma: visualization of the pathophysiologic changes of the pulmonary parenchyma after inhalation provocation]. / HRCT und Asthma bronchiale: Visualisierung pathophysiologischer Veränderungen des Lungenparenchyms nach inhalativer Provokation.

PURPOSE: To characterize parenchymal lung affections morphologically in patients with asthma and healthy subjects by high -resolution computed tomography (HRCT) subsequent to histamine-triggered inhalation bronchoprovocation and salbutamol-induced broncholysis, and to compare the results with pulmonary function tests. MATERIALS AND METHODS: Fifteen asthmatics with bronchial hyperreactivity, with a > 20% decrease in FEV1 and a > 10 mmHg decrease in PaO(2) after bronchoprovocation (PC20%+), twelve asthmatics with a < 20% decrease in FEV1 and a > 10 mmHg decrease in PaO(2) after bronchoprovocation (PC20%-), and eight healthy persons without bronchial hyperreactivity underwent inhalation bronchoprovocation and broncholysis. Spirometer-triggered HRCT at high lung volumes was performed, and total and peripheral lung densities and the amount of solid lung structures, representing predominantly vessels, were measured. RESULTS: After bronchoprovocation, we observed significant decreases in total and peripheral lung densities in all groups (p < 0.0005), and a significant increase in lung densities subsequent to bronchodilation (p < 0.0002). The morphological alterations in solid lung structure were not significantly different after bronchoprovocation or broncholysis (p > 0.05), as compared to the baseline measurements. In hyperreactive patients, PaO(2) significantly decreased after provocation and significantly increased after lysis (p < 0.05). In PC20%+ asthmatics, a mean reduction of 27.8% in FEV1 was observed, which was < 20% in the other groups. No significant correlations were observed between radiological data and the results of pulmonary function tests. In healthy persons, we demonstrated highly significant parenchymal response to bronchoprovocation and broncholysis, which was not otherwise documented by pulmonary function tests. CONCLUSION: In both PC20%+ and PC20%- patients as well as in healthy individuals, HRCT was efficient in the evaluation of pathoanatomical alterations of the lung parenchyma subsequent to inhalation provocation. In healthy individuals, these parenchymal alterations were not documented by pulmonary function tests.

[Complications of the central venous feeding of mobilized patients with an all-in-one solution]. / Komplikationen der zentralvenösen Ernährung mobilisierter Patienten mit Gesamtnährlösung.

35 mobilized patients received continuous parenteral nutrition consisting of an all-in-one solution mixed together in this department right before use over a total period of 1155 days (mean per patient 33 days). The primary complication rate was: second puncture in 14%, pneumothorax in 11% and haemothorax in 3% of cases. Secondary complications: catheter-related sepsis was documented in 8.5%. Metabolic complications were not seen. The all-in-one solution is a satisfactory nutrient for long-term, low-risk administration by the route, suitable even in the case of mobilized patients, without the necessity of intensive metabolic monitoring.

[Gluten-sensitive enteropathy and intestinal non-Hodgkin lymphoma (author's transl)]. / Gluteninduzierte Enteropathie und intestinales Non-Hodgkin-Lymphom.

The case report is presented of a patient with gluten sensitive enteropathy who subsequently developed an intestinal non-Hodgkin lymphoma. When steatorrhoea or diarrhoea develops in a patient with abdominal lymphoma, these symptoms are often attributed to progression of the lymphoma or to chemotherapy of the lymphoma. Since there is an established relationship between gluten-sensitive enteropathy and intestinal lymphoma, the differential diagnosis of steatorrhoea or diarrhoea developing in the course of malignant intestinal lymphoma must include gluten-sensitive enteropathy as well. In the investigation for gluten-sensitive enteropathy HLA typing can be used as a screening test in addition to routine malabsorption tests and small bowel biopsy

Effects of prednisolone on beta-adrenergic desensitization of normal peripheral lymphocytes: an in vitro model for steroid-controlled tachyphylaxis.

In vitro culture of human peripheral blood lymphocytes with the beta-adrenergic catecholamine isoproterenol for 24 hours, induced homologous beta-adrenergic desensitization, i.e. a large decrease in the number of beta-adrenergic binding sites and loss of the adenylate cyclase response to isoproterenol, without altering the effectiveness of prostaglandin E1 to stimulate the enzyme. Lymphocyte cultures pulsed for 24 hours with isoproterenol, washed free of the agent and cultured in hormone-free medium for 48 hours still showed marked suppression of the beta-adrenergic adenylate cyclase response and a lack of beta-receptors. When prednisolone was added to the isoproterenol-depleted resuspension medium of desensitized lymphocytes, however, the beta-adrenergic system recovered fully within 48 hours. Treatment of desensitized lymphocytes with prednisolone in the continuous presence of isoproterenol failed to restore beta-adrenergic responsiveness of the cells. The results are discussed with respect to the reconstituting effect of prednisolone on beta-adrenergic responsiveness in bronchial asthma after therapy induced tachyphylaxis.

Pirenzepin does not alter the pharmacokinetics of theophylline.

The possible pharmacokinetic interactions between pirenzepin and theophylline were investigated in an open single blind trial. Aminophylline (6.5 mg/kg body weight) was administered intravenously in five healthy male volunteers before and after chronic oral pirenzepin therapy (50 mg twice daily 5 days before to 2 days after giving aminophylline). To study the theophylline pharmacokinetics, serum and urine samples were collected up to 48 hours after aminophylline administration. It was demonstrated, that pirenzepin does not affect theophylline pharmacokinetics. Therefore, pirenzepin may be combined with aminophylline or theophylline without the risk of an interaction, which usually affect the coadministration of other antiulcer drugs, e.g. cimetidine, with theophylline.

[How dangerous is splenectomy in Hodgkin's disease? (author's transl)]. / Wie gefährlich ist die Splenektomie bei Morbus Hodgkin?

Serious complications aetiologically connected with the operation were found in 8 out of 51 patients (19 females, 32 males) who had undergone splenectomy for Hodgkin's disease. Weighing potential complications against the expected beneficial effects, clear indications for splenectomy are only found in stages I and IIa. In all more progressed clinical stages splenectomy should only be performed when 1) platelet deficiency existed prior to treatment, 2) additional irradiation of the splenic area is to be avoided, 3) oophoropexy is to be performed at the same time. When discussing the indication for splenectomy one should remember that a delay of treatment by approximately three weeks will result.

Substance P receptors in rat spleen: characterization and autoradiographic distribution.

The interaction of substance P with intact lymphatic tissue was quantified and autoradiographically visualized, using slide-mounted tissue sections of rat spleen. Radiolabeled substance P binds rapidly to an apparently single class of noninteracting high affinity sites (Kd = 2.4 nmol/L; Bmax = 9.4 fmol/mg protein). The ligand selectivity pattern suggests that substance P binding sites are similar to substance P receptors found in other tissues, including the brain, T lymphocytes, and macrophages. Substance P receptors are highly concentrated in the antigen-trapping spleen marginal zone, with low densities being found in the red pulp. No specific binding of radiolabel to T cell-dependent immunologic domains of the spleen is seen. The distribution of substance P receptors suggests that substance P is probably involved in the control of sensory functions of the immune system.

Effect of solution and suspension type aerosol of formoterol on tremor response and airways in patients with asthma.

BACKGROUND: Aerosol delivery and deposition to the oropharynx and the lungs have been found to be different for solution-type and suspension-type metered-dose aerosols used for treatment of asthma. We investigated possible differences in clinical effects between solution and suspension metered-dose formoterol aerosols. METHODS: A total of 24 patients with asthma (forced expiratory volume in 1 second, < or = 70% predicted) inhaled single doses (12 micrograms or 24 micrograms) of formoterol solution and suspension so that we could investigate the immediate tremor, airway, and cardiovascular responses in a randomized, double-blind, crossover trial. Fenoterol suspension aerosol (400 micrograms) was used for comparison (single-blind, poststudy, nonrandomized administration). Fenoterol (400 micrograms) as a rescue medication was inhaled after 120 minutes on each of the 5 study days. RESULTS: The order of mean (+/- SEM) maximum tremor acceleration was as follows: 12 micrograms formoterol solution (67.92 +/- 4.54 cm x sec-2) < 24 micrograms solution (73.46 +/- 4.51 cm x sec-2) < 12 micrograms suspension (80.87 +/- 5.08 cm x sec-2) < fenoterol (84.13 +/- 4.21 cm x sec-2) < 24 micrograms formoterol suspension 88.54 +/- 6.26 cm x sec-2). Maximum increase in specific airway conductance ranged from 0.48 +/ 0.03 to 0.55 +/- 0.04 sec-1 x kPa-1 for all drugs (p > 0.05). No change in cardiovascular parameters occurred (p > 0.05). CONCLUSION: No difference in the bronchial response to either formulation of formoterol was found. Tremor response to suspension aerosol (24 micrograms > 12 micrograms) was higher than that to solution aerosol (24 micrograms > 12 micrograms), indicating possible differences in systemic absorption because of a different deposition pattern. Rescue medication demonstrated systemic effects on tremor that were additive to those of formoterol.

High-affinity substance P binding sites in rat esophagus plexus submucosus.

Substance P receptors were investigated in rat esophagus using 125I-Bolton-Hunter substance P as a labeling probe. Autoradiographic studies show that esophageal submucosa contains clusters of high-affinity substance P binding sites [maximum binding (Bmax) 4.2 +/- 0.28 fmol/mg protein; dissociation constant (Kd) 0.1 +/- 0.01 X 10(9) M]. The receptor distribution pattern is typical for submucous neurons. These data suggest that substance P may act as a neurotransmitter in rat esophagus.

Effects of the sauna on diffusing capacity, pulmonary function and cardiac output in healthy subjects.

The present study examined possible short-term effects of the heat stress during sauna bathing on gas exchange, especially in correlation with changes in cardiac output. The results obtained are as follows: (1) The heat stress of sauna bathing caused a slight but not significant increase in diffusion capacity (p = 0.239) and no change in other pulmonary function parameters. (2) Cardiac output and cardiac index increased slightly but not significantly (p = 0.2455 and p = 0.2719). We conclude that heat stress in sauna neither influences gas exchange nor does it cause a significant increase in cardiac output.

Prediction of sensitization to flour allergens.

The purpose of the present study was to investigate the factors that may contribute to the sensitization to flour in baker's apprentices, and to predict this type of sensitization with a stepwise logistic regression model. Of the total of 258 baker's apprentices, 54 (20.9%) exhibited specific IgE development against flour allergens (wheat, rye, and/or barley). Allergologic variables, such as the total IgE level and IgE specific to grass pollen, tree pollen, weed pollen, molds, and animal dander, were found to correlate strongly with the sensitization to flour. However, the correlation between the presence of other manifest allergies and the sensitization to flour was weak. The presence of shadowing of the paranasal sinuses on the radiograph (mucosal thickening, opacity, air/fluid levels, and/or polypous shadowing) correlated with flour sensitization as well as with the leukocyte and lymphocyte counts in peripheral blood. Of the lung function data, only total lung capacity (in percentage of the predicted values) weakly correlated with the sensitization to flour. We were able to predict flour sensitization with a sensitivity of 63%, a specificity of 90%, and an efficiency of 84% by using the parameters that allow for the presence or absence of IgE specific to grass pollen and tree pollen, the presence or absence of radiographic shadowing, and total lung capacity in percentage of the predicted values.