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Biomedical subjects

L Greiff

Publications and source records attributed to L Greiff.

83 records · Page 5Linked to original sources
PubMed1993

Mucosal exudation of fibrinogen in coronavirus-induced common colds.

We studied the mucosal exudation of plasma in relation to pathophysiological events during an induced common cold. Coronavirus 229E was inoculated nasally in 20 healthy volunteers under controlled conditions. Ten volunteers developed the common cold, determined by symptom scores and serology. The bulk plasma exudate was monitored, using fibrinogen (MW 340 kD) in nasal lavage fluids as an endogenous marker. Following inoculation, anterior rhinoscopy and objective registrations of nasal mucosal temperature, nasal discharge weight, and nasal blockage index by peak expiratory air flow, were followed twice daily for 6 days. Mucosal plasma exudation, as assessed by fibrinogen in lavage fluids, increased hundredfold after virus inoculation, concomitantly with the subjective symptoms and objective physiological changes. We propose that this exudation reflects the degree of subepithelial inflammation, and suggests that plasma bulk exudate, including all potent plasma protein systems may be involved in the resolution of acute viral rhinitis--common cold.

Adult↗
PubMed1991

Plasma exudation as a first line respiratory mucosal defence.

A great variety of provocations of the airway mucosa produce extravasation of plasma from the abundant subepithelial microvessels. A plasma exudate has important actions through its volume, its specific and unspecific binding proteins, its enzyme systems, and its potent peptides (of kinin, complement, coagulation, fibrinolysis and other systems). If allowed to operate on the surface of an intact mucosa the plasma exudate would have important roles in normal airway defence. Recent observations in guinea-pig tracheobronchial airways and in human nasal airways suggest that the mucosal exudation of plasma into the airway lumen is a non-injurious fully reversible process. Threshold exudative responses thus resulted in the appearance of an 'unfiltered' plasma exudate not only in the lamina propria but also on the surface of an undisrupted mucosa. Even after extensive luminal entry of exudate the epithelial lining was intact, as judged by light, fluorescence and electron microscopy. Hence, the epithelial barrier was reversibly permeable when approached from beneath by the plasma exudate. This was a distinct increase in outward permeability, because even during the exudation of plasma the mucosa remained a barrier to luminal solutes. It is possible that the exudate itself, by a slight compressive action on the basolateral aspect of epithelial cells, creates intercellular pathways for its entry into the lumen. Contrary to current beliefs, we propose that plasma exudation should be considered a first line respiratory defence mechanism operating together with other systems of the mucosal surface.

Absorption↗
PubMed1991

Effects of airway luminal concentration of albumin on histamine-induced mucosal exudation of radio-iodine labelled albumin.

In an in vivo study of guinea-pig airway barriers we have examined the effects of the luminal concentration of albumin on exudation (outward) and absorption (inward) permeabilities to radio-iodine labelled albumin. Previously validated techniques for superfusion of solutes onto the tracheobronchial mucosal surface and for subsequent tracheal lavage were employed. [125I]albumin was administered intravenously as plasma tracer and [131I]albumin was superfused topically as absorption tracer. Histamine (5.0 nmol) was superfused onto the mucosal surface together with the absorption tracer and in the presence of different albumin concentrations (0.3, 3.0 and 30 mg ml-1). The experiment was terminated 10 minutes after the tracheal mucosal superfusion and samples of plasma and tracheal lavage fluid were collected. The mucosal exudation response was calculated from the detection of [125I]albumin in the airway lumen. The absorption ability of the mucosa was determined by the detection of [131I]albumin in circulating plasma. Histamine induced a significant mucosal exudation of [125I]albumin. This effect was unaffected by the level of albumin on the mucosal surface. There was a small but significant absorption of [131I]albumin in the presence of 0.3 and 3.0 mg ml-1 of albumin in the luminal liquid. An albumin concentration of 30 mg ml-1 markedly increased the rate of absorption of [131I]albumin. However, the absorption rate was not affected by the histamine-induced mucosal exudation process at any level of luminal albumin. The present data further demonstrates that plasma exudation and mucosal absorption are independent processes. The data are in keeping with the view that an increased subepithelial hydrostatic pressure moves the plasma exudate across the mucosa as a distinct outward process.

Absorption↗
PubMed1991

Effects of histamine, ethanol, and a detergent on exudation and absorption across guinea pig airway mucosa in vivo.

This study examined effects of three substances that cause mucosal provocation (histamine, ethanol, and the detergent dioctylsodium sulphosuccinate (DOSS] on the flux of solutes across airway vascular mucosal barriers in anaesthetised guinea pigs. The inward flux was assessed as absorption of iodine-131 labelled albumin (MW 69,000) from the tracheobronchial surface into the circulation and the outward flux as the exudation of two intravenously administered plasma tracers--125I albumin (MW 69,000) and fluorescein isothiocyanate conjugated (FITC) dextran (MW 70,000)--into the airway. The absorption of technetium-99m labelled DTPA (MW 492) from the tracheobronchial airways was determined in separate experiments. Histamine (5.0 nmol) dissolved in 40 microliters saline and superfused on the tracheobronchial mucosal surface caused significant and similar entry of 125I albumin and FITC dextran into the airway lumen. This dose of histamine did not, however, alter the absorption of small (99mTc DTPA) or large (131I albumin) solutes across the airway mucosa. Ethanol (0.17 mumol), superfused in the same way, also caused significant exudation of the plasma tracers into the airway lumen. In addition, ethanol increased the absorption of 131I albumin without causing change in the disappearance rate of 99mTc DTPA. The detergent, DOSS (0.28 nmol), dissolved in ethanol (0.17 mumol), caused a pronounced increase in exudation and much increased absorption of small and large tracer solutes. Thus three patterns of change in airway mucosal barriers were found. The agents that are toxic to membranes, ethanol and DOSS, caused a bidirectional increase in permeability across the mucosa, whereas histamine caused only an outward exudative flux. The results obtained with histamine are similar to those seen previously with bradykinin, capsaicin, and allergen, suggesting that endogenous inflammatory mediators have a role in mucosal defence, producing entry of plasma exudates into the airway lumen without increasing the mucosal absorption of luminal material.

Absorption↗
PubMed1991

Absorption of 51Cr EDTA across the human nasal airway barriers in the presence of topical histamine.

Whether histamine, a mediator that causes exudation, affects the airway absorption of luminal solutes has been examined in a study of eight healthy volunteers. Fluid containing the absorption tracer chromium-51 labelled EDTA was instilled into one nasal cavity for 15 minutes, with a nasal pool-device (total volume 14 ml). The airway absorption of 51Cr EDTA determined by urinary recovery of radioactivity corresponded to 0.095 (SE 0.023) ml of the instillate in the absence of histamine. When histamine was added to the nasal instillate at a concentration of 2.0 mg/ml, which is known to produce substantial exudation of plasma into the airway lumen, the absorption of 51Cr EDTA was unchanged (0.093 (0.025) ml of the instillate). Separate experiments excluded the possibility that any swallowed portion of 51Cr EDTA could have contributed significantly to the amount absorbed. The present data agree with previous observations in guinea pig tracheobronchial airways, where histamine and other exudative agents did not increase the mucosal absorption of solutes from the airway lumen. These data suggest that the potent protein systems of blood plasma can transverse the endothelial-epithelial linings and operate on the surface of the airway mucosa without compromising its integrity as a barrier to luminal material.

Absorption↗
PubMed1991

125I-albumin may not be used as a tracer of absorption across the human nasal airway barriers.

This study set out to examine the effects of histamine on airway absorption of macromolecules. By employment of a novel "nasal pool" technique instillates containing 125I-albumin, with or without histamine, were kept for 15 min on human nasal mucosa. Unaffected by the presence of histamine, the instillations produced significant levels of plasma radioactivity, increasing for 60 min. However, gel-filtration data showed that only 30% of the plasma radioactivity was still bound to albumin. Incubation experiments indicated that radioiodine did not dissociate from albumin in nasal liquids nor in the blood. Further experiments involved oral ingestion of the entire nasal instillate. Prompt gastrointestinal absorption of radioactivity occurred, giving rise to plasma levels about two orders of magnitude higher than those recorded after the nasal applications. Moreover, only 25% of the plasma radioactivity was now bound to albumin. It must be considered unavoidable that a small portion (less than 1%) of the nasal instillate is swallowed. Hence, the plasma radioactivity detected in this study may largely reflect gastrointestinal break-down of 125I-albumin and subsequent absorption of radioiodine. We conclude that 125I-albumin may not be employed in studies addressing macromolecular absorption across the human nasal mucosa and that previous work and conclusions based on nasal absorption of 125I-albumin are invalid.

Absorption↗
PubMed1990

The 'nasal pool' device applies controlled concentrations of solutes on human nasal airway mucosa and samples its surface exudations/secretions.

A 'nasal pool' (NP) device, a compressible plastic container with an adapted nozzle, was used to perform a continuous 10-min nasal provocation and lavage. This novel technique brings known concentrations of agents into contact with a large and defined area of the nasal mucosal surface for extended periods of time. Simultaneously, the surface exudations/secretions of the same nasal mucosa are effectively sampled by the NP fluid. A concentration-response study of histamine (80, 400 and 2000 micrograms/ml) was performed in 12 normal subjects on three different occasions. Exudation of plasma albumin into the lavage fluid was measured to quantitate the histamine-induced airway inflammation. The effect of the dwell time on exudation was examined using histamine (400 micrograms/ml) instilled in the nasal cavity for time periods from 10 sec to 10 min. The time course of histamine-induced plasma exudation response was studied by exposing the mucosa to histamine (400 micrograms/ml) for 12 min, with the NP renewed every minute. Allergen-provocations were performed in subjects with hay fever and TAME-esterase activity in the returned lavage fluid was determined to indicate the degree of response. Histamine produced a concentration-dependent increase in albumin levels in the NP fluid; 123.3 +/- 25.6, 213.8 +/- 19.7 and 430.2 +/- 32.0 micrograms/ml (mean +/- s.e.m.), respectively. The time-course study demonstrated that plasma exudation into the lumen occurred promptly and that the exudation response reached a maximum after exposure to histamine for 6-10 min. The dwell-time experiments supported this finding. After 10 min the exudation appeared to decline despite the continued presence of histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Clearance of 99mTc DTPA from guinea pig nasal, tracheobronchial, and bronchoalveolar airways.

Technetium-99m labelled diethylenetriamine penta-acetate (99mTc-DTPA) was used to compare small solute absorption (clearance) from nasal, tracheobronchial, and bronchoalveolar airways in anaesthetised guinea pigs. 99mTc DTPA dissolved in saline was superfused through nasal and orolaryngeal catheters on to nasal and tracheobronchial airways; a small particle aerosol of nebulised 99mTc DTPA was delivered to the bronchoalveolar airways through a tracheostomy. Radioactivity over the appropriate region was then determined with a gamma camera. Mucociliary transport of 99mTc DTPA appeared not to contribute to the disappearance of 99mTc DTPA. Time-activity curves were obtained and half life values calculated by fitting a monoexponential equation to the experimental data. A progressive reduction in 99mTc DTPA was recorded from the nasal and tracheobronchial airways and from the bronchoalveolar airway, suggesting that absorption was occurring. The disappearance of 99mTc DTPA was fastest from the bronchoalveolar region, which also had the largest mucosal surface. The similar shape of the retention curves for the nasal and tracheobronchial regions suggests that the characteristics of nasal absorption of 99mTc DTPA could prove applicable to the tracheobronchial region. It is proposed that the present methods are suited for comparing the pharmacology of small solute absorption across nasal, tracheobronchial, and bronchoalveolar airway mucosa.

Absorption↗
PubMed1987

Symptoms and endoscopic findings in the diagnosis of gastroesophageal reflux disease.

Two hundred and twenty patients with symptoms suggestive of pathologic gastroesophageal reflux were investigated to elucidate the ability of symptoms and endoscopic findings in establishing a diagnosis of reflux disease as measured by ambulatory 24-h pH-monitoring. Daily occurrence of heartburn or acid regurgitation had positive predictive values of 59% and 66%, respectively. pH-monitoring showed pathologic reflux in 75% of patients with esophageal mucosal erosions. Endoscopic erythema of the distal esophagus predicted reflux disease in only 53%. Symptom registration during ambulatory 24-h pH-monitoring showed that about half of the symptomatic events reported by patients with pathologic reflux occurred within 5 min of a reflux episode. The corresponding figure for patients with normal pH-monitoring was less than 20%. We conclude that it is difficult to establish a diagnosis of gastroesophageal reflux disease by patient history alone, that erythema at endoscopy correlates poorly with pathologic reflux, and that reflux disease may be present even with normal endoscopy findings.

Adolescent↗
PubMedDate not supplied

Nasal mucosal endorgan hyperresponsiveness.

Nonspecific hyperresponsiveness of the upper and lower airways is a well-known characteristic of different inflammatory airway diseases but the underlying mechanisms have not yet been satisfactorily explained. In attempts to elucidate the relation of hyperresponsiveness to disease pathophysiology we have particularly examined the possibility that different airway endorgans may alter their function in allergic airway disease. The nose, in contrast to the bronchi, is an accessible part of the airways where in vivo studies of airway mucosal processes can be carried out in humans under controlled conditions. Different endorgans can be defined in the airway mucosa: subepithelial microvessels, epithelium, glands, and sensory nerves. Techniques may be applied further in the nose to determine selectively the responses/function of these endorgans. Topical challenge with methacholine will induce a glandular secretory response, and topical capsaicin activates sensory c-fibers and induces nasal smart. Topical histamine induces extravasation of plasma from the subepithelial microvessels. The plasma exudate first floods the lamina propria and then moves up between epithelial cells into the airway lumen. This occurs without any changes in the ultrastructure or barrier function of the epithelium. We have therefore forwarded the view of mucosal exudation of bulk plasma as a physiological airway tissue response with primarily a defense function. Since the exudation is specific to inflammation, we have also suggested mucosal exudation as a major inflammatory response among airway endorgan functions. Using a "nasal pool" device for concomitant provocation with histamine and lavage of the nasal mucosa we have assessed exudative responses by analyzing the levels of plasma proteins (e.g., albumin alpha 2-macroglobulin) in the returned lavage fluids. A secretory hyperresponsiveness occurs in both experimental and seasonal allergic rhinitis. This type of nasal hyperreactivity may develop already 30 minutes after allergen challenge. It is attenuated by topical steroids and oral antihistamines. We have demonstrated that exudative hyperresponsiveness develops in both seasonal allergic rhinitis and common cold, indicating significant changes of this important microvascular response in these diseases. An attractive hypothesis to explain airway hyperresponsiveness has been increased mucosal absorption permeability due to epithelial damage, possibly secondary to the release of eosinophil products. However, neither nonspecific nor specific endorgan hyperresponsiveness in allergic airways may be explained by epithelial fragility or damage since nasal absorption permeability (measured with 51CR-EDTA and dDAVP) was decreased or unchanged in our studies of allergic and virus-induced rhinitis, respectively. Thus, the absorption barrier of the airway mucosa may become functionally tighter in chronic eosinophilic inflammation.

Blood Vessels↗