Search PubMed⌕ Search

Biomedical subjects

L A Laitinen

Publications and source records attributed to L A Laitinen.

At least 73 records · Page 4Linked to original sources
PubMed1996

Effect of regular nedocromil sodium or albuterol on bronchial inflammation in chronic asthma.

Nedocromil sodium is recommended for daily treatment of mild persistent asthma but its effect on cellular changes in asthmatic airways is poorly understood. We compared the antiinflammatory effects of nedocromil sodium and albuterol in 32 patients with asthma who received either nedocromil sodium 4 mg or albuterol 0.2 mg four times daily for 12 weeks according to a double-blind protocol. Patients underwent fiberoptic bronchoscopy, and lung function and bronchial responsiveness to histamine were measured. Numbers of inflammatory cells were studied by immunohistochemistry and image analysis. We were unable to identify any statistical differences between treatment groups for any of the variables measured. We conclude that our immunohistochemical study does not support the concept of nedocromil sodium as a potent/antiinflammatory drug.

Adult↗
PubMed1995

Altered regulation of breathing after bilateral lung transplantation.

In our previous animal studies on dogs, regulation of breathing was found to be altered after en bloc transplantation of the heart and both lungs. During carbon dioxide (CO2) inhalation the minute volume was increased due to an increase of tidal volume after transplantation whereas before transplantation both respiratory frequency and tidal volume increased. The success of the heart-lung transplantation was based on experiments on baboons as no long-term survivors were obtained in dogs. It was thought that the regulation of breathing is different in dogs and primates. We therefore decided to study the regulation of breathing in humans after bilateral lung transplantation during CO2 stimulation. The regulation of breathing was tested 2 to 4 months after bilateral lung transplantation in six patients. Six healthy subjects with intact lungs were tested as controls. The test persons were allowed to breathe first room air, then 5% CO2 in air for 4 min and then room air again. The frequency of respiration, tidal volume and minute ventilation were recorded using a phneumotachograph. Simultaneously samples of arterial blood were drawn from a cannulated brachial artery for analysis of pressure of arterial oxygen (PaO2), pressure of arterial carbon dioxide (PaCO2), base excess (BE) and pH. During inhalation of CO2 for 4 min the minute volume doubled in both transplant patients and in controls. The tidal volume of the transplant patients increased significantly more than that of the controls (P < 0.005) whereas respiratory frequency increased significantly only in the controls with intact lungs (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Transforming growth factor-beta regulates the expression of fibronectin and tenascin in BEAS 2B human bronchial epithelial cells.

We used monoclonal antibodies to study expression and extracellular matrix (ECM) incorporation of tenascin (Tn) and isoforms of fibronectin (Fn) in BEAS 2B immortalized human bronchial epithelial cells and the regulation of their synthesis by transforming growth factor (TGF)-beta 1 and -beta 2. In immunofluorescence microscopy, the control cells appeared negative for Tn. Extradomain A (EDA)-Fn was mainly seen in association with ECM fibers and, in a few cells, in an intracellular location. Immunoreactivity for oncofetal (onc)-Fn and extradomain B (EDB)-Fn was only seen in a few cells. In TGF-beta 1- and -beta 2-treated cells, a greatly enhanced immunostaining for Tn and three isoforms of Fn was seen both as to the number of positive cells and to the amount of immunoreactive material around them. In Western blotting of the untreated cells, EDA-Fn and onc-Fn were detected in the cell-free ECM and in the culture medium, whereas EDB-Fn was not detectable. An enhanced secretion and deposition of both EDA-Fn and onc-Fn and also secretion of EDB-Fn was seen upon treatment with TGF-beta s. In TGF-beta-treated cells, Tn was found exclusively in the ECM and not in the culture medium as shown by Western blotting of cell-free ECM and culture medium, respectively. Accentuation of tenascin staining in TGF-beta-treated cells was due to a greatly enhanced production of M(r) 280,000 and M(r) 190,000 isoforms of Tn.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Western↗
PubMed1994

Airway morphology: epithelium/basement membrane.

Morphologic studies have given important information about changes in the airways underlying the functional abnormalities in asthma. Recent biopsy studies have revealed that in asthma an airway inflammatory process is present even at a clinically early stage of the disease. This inflammatory response shows a particular cellular picture with concomitant vascular changes. It is widely thought that dramatic epithelial changes such as epithelial shedding are major mechanisms in the pathogenesis of asthma and bronchial hyper-responsiveness. Because of difficulties in obtaining proper biopsy specimens, it has not yet been established to what extent epithelial shedding really occurs in preterminal stages of asthma. Perhaps a more important aspect than epithelial shedding is a more continuous replacement of the ciliated epithelium by another type of epithelium in asthmatic patients' airways during the early disease stage. The airway epithelial cells, their surface receptors, and the underlying basement membrane seem to play an important role in maintaining the structural integrity of the epithelium and establishing functional permeability barriers. Disturbances in the structure may lead to events recognized as tissue damage and to the development of inflammation in asthma. We need to learn more about the adhesion mechanisms in asthma, both at the receptor and the ligand sites, to better assess the role of structural epithelial changes in this disease.

Asthma↗
PubMed1994

Modulation of bronchial inflammation: corticosteroids and other therapeutic agents.

We have shown that treatment with inhaled corticosteroid acts to improve asthma-induced changes in the airway mucosa to such an extent that cell type and structure are normalized. More specifically, such treatment increases the number of intraepithelial nerves, decreases the total number of inflammatory cells, and eliminates epithelial eosinophils, as well as decreasing the number of endothelial gaps in the postcapillary venules. In contrast, these effects do not seem to be found following treatment with beta 2-agonists.

Adrenal Cortex Hormones↗
PubMed1994

Seasonal variation in the function of blood monocytes obtained from healthy nonsmokers, asymptomatic smokers, and smokers with chronic bronchitis.

The present study focused on two questions: What effects do cigarette smoking and chronic bronchitis have on the function of the precursors of alveolar macrophages, the blood monocytes? Can seasonal variations affect the function of these cells? Phagocytic activity (the proportion of yeast-ingesting cells and the mean number of yeast particles per ingesting cell) and metabolism of arachidonic acid [secretion of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in zymosan-stimulated cultures] were studied as markers of monocyte function during three seasons: spring (May-June), autumn (November-December), and winter (February). Smokers with chronic bronchitis (SCBs) and asymptomatic smokers (ASs) had a lower proportion (p < 0.05) of ingesting monocytes than healthy nonsmokers (HNSs) during spring, but not during the other two seasons. The secretion of PGE2 was highest during autumn and lowest during spring in the monocytes of all three groups. In autumn, LTB4 secretion was increased in the monocytes of HNSs (p < 0.05) but not in those of ASs and SCBs. LTB4 secretion was similar in all groups during the other two seasons. Cigarette smoking and chronic bronchitis seem to impair the function of monocytes and may thereby affect the systemic host defense activity. Cells collected during autumn were generally more active than those sampled in spring, indicating marked seasonal variation in the function of monocytes from all three groups.

Arachidonic Acid↗
PubMed1994

Heart rate and cardiac arrhythmia during high-Gz flight.

Twenty-four pilots (age 20-32 years) were monitored with a Holter monitor during 26 hours including a high-Gz flight in order to evaluate heart rate (HR) and cardiac rhythm. Flight experience did not predict the mean in-flight HR (range 69-121 beats/minute), which decreased with increasing age and correlated to the maximum HR during sleep. We recorded maximally 27 ventricular and 97 supraventricular ectopic beats, 10 junctional rhythms, 5 gray-out, 1 vestibular symptom, and 1 instance of numbness of the feet during the flight. No causal relationship between HR, cardiac arrhythmia, or symptoms was found. Adaptation to in-flight +Gz stress takes place without significant arrhythmia and at a submaximal age-related HR.

Adaptation, Physiological↗
PubMed1993

Budesonide inhibits plasma extravasation induced by capsaicin and by substance P in the rat nasal mucosa.

We studied the effect of the locally administered glucocorticoid budesonide on plasma extravasation induced by capsaicin and by substance P (SP) in the nasal mucosa of pathogen-free rats. Using Evans blue dye as a tracer, we measured plasma extravasation induced by capsaicin (150 micrograms kg-1 i.v.) or SP (0.5 and 2.5 micrograms kg-1 i.v.) in the rat naso- and maxilloturbinates after pretreatment with budesonide (0.1-50 micrograms twice/day for 2 days in the right nostril; 50 micrograms only for SP) or its vehicle. We found that budesonide inhibits plasma extravasation induced by capsaicin in a dose-dependent fashion in the nasal cavity. After the highest dose (50 micrograms) of budesonide, the values of Evans blue in the nasal mucosa were not different from the values observed after capsaicin vehicle alone. Budesonide also reduced plasma extravasation induced by capsaicin in the trachea and the urinary bladder of the rats in a dose-dependent fashion. Budesonide (50 micrograms) delivered to the nose inhibited the plasma extravasation caused by 0.5 but not by 2.5 micrograms SP kg-1 in the nasal mucosa. We conclude that the postjunctional part of the neurogenic pathway is a target for glucocorticoid antiinflammatory action in the nasal mucosa, at least of the rat. Budesonide's effect on organs other than the nose can be explained by systemic absorption.

Administration, Topical↗
PubMed1993

Leukotriene E4 and granulocytic infiltration into asthmatic airways.

Sulphidopeptide leukotrienes are potent bronchoconstrictors and increase bronchial hyperreactivity, one of the hallmarks of asthma. We have demonstrated that leukotriene LTE4, the most stable of the sulphidopeptide leukotrienes, elicited an increase in the numbers of eosinophils and neutrophils in the lamina propria of the airway mucosa 4 h after inhalation in 4 asthmatic subjects. The numbers of eosinophils were, on average, 10-fold greater than those of neutrophils. There was no significant change in numbers of lymphocytes, plasma cells, mast cells, or macrophages. Since LTE4 recruits granulocytes, the potential of antisulphidopeptide leukotriene drugs as anti-inflammatory and "steroid-sparing" agents should be tested.

Adult↗
PubMed1993

Circadian variation in peripheral blood flow in relation to core temperature at rest.

The aim of the present study was to examine the circadian variation in skin blood flow and its relationship to the rhythm of rectal temperature. Eight young men were confined to continuous bed rest for 24 h in a thermoneutral environment. Rectal temperature, oxygen consumption, and peripheral blood flow (laser-Doppler flowmetry and plethysmography) were measured at intervals of 2 h, except at 2400 hours and 0600 hours. According to the cosinor-method, the mean rectal temperature displayed a statistically significant circadian variation with a minimum at 0400 hours. A significant circadian rhythm was also observed in total finger blood flow, finger laser-Doppler flow, and forearm laser-Doppler flow, but not in total forearm blood flow and forehead laser-Doppler flow. The rhythms of rectal temperature and extremity skin blood flow were phased differently, i.e. the decrease in rectal temperature was preceded by an increase in extremity skin blood flow with an average of 4-h time difference. The results would support the idea that circadian rhythm of core temperature is, at least in part, regulated by variation in extremity skin blood flow.

Adult↗
PubMed1993

Airway mucosal inflammation even in patients with newly diagnosed asthma.

We have studied bronchial biopsies from 14 patients with newly diagnosed asthma (four men and 10 women), who had had asthma symptoms, on average, 7.4 months (range, 2 to 12 months) and from four control subjects. The patients had not received corticosteroids, disodium cromoglycate, or theophylline before the study. The bronchial biopsies were taken, using a rigid-tube bronchoscope under local anaesthesia, from two different airway levels: (1) inside the right upper lobe bronchus, and (2) at the opening of the right middle lobe. The specimens were prepared for both light and electron microscopy. The use of Slot grids 1 x 2 mm enabled a large area of the thin sections to be photographed and analyzed by applying a graphic Autocad program. There was an increase in the numbers of mast cells (p < 0.001), eosinophils (p < 0.05), lymphocytes (p < 0.05), and macrophages (p < 0.05) in the epithelium of patients with newly diagnosed asthma as compared with those in control subjects. In the lamina propria, these asthmatic patients had more eosinophils (p < 0.001), lymphocytes (p < 0.001), macrophages (p < 0.001), and plasma cells (p < 0.001) than did the control subjects. We conclude that, in asthma, an airway inflammatory process is present even at a clinically early stage of the disease. In the asthmatic airways, there are signs of a general inflammatory response caused by more than one cell type.

Adult↗
PubMed1993

Airway inflammation in smokers with nonobstructive and obstructive chronic bronchitis.

To assess the manifestation and location of airway inflammation in smokers with chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD), we lavaged the airways of 12 smokers with CB and 11 smokers with COPD and coexisting CB (OCB). For comparison, the airways of 5 asymptomatic smokers (AS) and 10 healthy nonsmokers (HNS) were lavaged. In all cases, the first lavage aliquot, labeled "bronchial lavage" (BL), was processed separately from the four subsequent aliquots, which were combined and labeled "bronchoalveolar lavage" (BAL). The composition of BL and BAL fluids indicate an ongoing inflammatory process in the airways of all three groups of smokers. CB patients with obstruction had significantly lower concentrations of inflammatory cells in the BL and BAL fluids compared with subjects with nonobstructed CB. Furthermore, airway obstruction, indicated by a reduced FEV1, was significantly correlated with the concentrations of glutathione (p < 0.001), myeloperoxidase (MPO; p < 0.01), and eosinophil cationic protein (ECP; p < 0.01) in BAL fluids. Taken together, these findings suggest that the manifestations of inflammation present in the airways of smokers with CB are different in those who have developed obstruction compared with those who have not.

Adult↗
PubMed1992

A comparative study of the effects of an inhaled corticosteroid, budesonide, and a beta 2-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: a randomized, double-blind, parallel-group controlled trial.

We compared the effect of an inhaled corticosteroid, budesonide, and an inhaled beta 2-agonist, terbutaline, on clinical symptoms, lung function, and airway inflammation in 14 adult patients with newly diagnosed asthma. The study was conducted as a randomized, double-blind, parallel-group trial. Seven patients inhaled 600 micrograms, twice daily, of budesonide, the other seven patients inhaled 375 micrograms, twice daily, of terbutaline via identical metered-dose inhalers with a spacer. Bronchial biopsy specimens, obtained before randomization and after 3 months of treatment, were analyzed by electron microscopy. Both groups improved clinically budesonide was more effective than terbutaline in improving morning and evening peak expiratory flow rates, as well as bronchial responsiveness to inhaled histamine. Treatment with budesonide was accompanied by increased numbers of ciliated airway cells and intraepithelial nerves and fewer inflammatory cells, including eosinophils, especially in the epithelium, these changes were not observed in specimens from terbutaline-treated patients. We conclude that, in contrast to inhaled terbutaline, inhaled budesonide improved lung function and bronchial hyperreactivity in adult subjects with asthma treated for 3 months and that this corticosteroid was more effective in ameliorating abnormalities of the bronchial epithelium and decreasing inflammation in the airways.

Administration, Inhalation↗
PubMed1992

Exercise alters the pharmacokinetics of midazolam.

Six healthy volunteers received 15 mg midazolam, 50 mg ephedrine, or placebo orally before a 50-minute aerobic treadmill exercise and in a control session. Plasma drug concentrations for pharmacokinetic calculations were estimated from samples drawn up to 24 hours after drug intake. Heart rate, blood pressure, critical flicker fusion test, Maddox wing test, and visual analog scales relating to mood and feelings of tiredness were included in the sessions as pharmacodynamic measures. These tests were made at 35, 55, and 75 minutes and at 2, 2 1/2, 3 1/2, and 5 hours after drug intake. Exercise impaired the absorption of midazolam and counteracted the midazolam-induced decrement in flicker fusion threshold. Whether the effect on flicker fusion was caused mainly by the pharmacokinetic changes or by a general alerting effect of exercise cannot be verified by this experiment. The kinetics of ephedrine was not affected by exercise, but exercise enhanced the tachycardic response to ephedrine and abolished its pressor effect.

Adult↗