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Biomedical subjects

L A Laitinen

Publications and source records attributed to L A Laitinen.

At least 19 recordsLinked to original sources

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

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

Alertness and sleep in young men during military service.

Alertness and sleep in healthy young men conscripted into military service were examined by testing personality characteristics and by completing questionnaires at the beginning of military service about their civilian life alertness and sleep, and by using polygraphic recordings during their military service. Sleep-time during service was restricted to 8 hours a night; 236 men answered the questionnaire on civilian life alertness and sleep; 116 men a Minnesota multiphasic personality inventory; 7 underwent conventional, and 29 static charge-sensitive bed sleep recordings. Daytime latencies to Stage 2 sleep were 11 +/- 2 min. Sleep latencies were the shortest 6 h after waking. Night sleep was normal in conventional recordings. Nocturnal activities in static charge-sensitive bed recordings were: motor-active waking 4 +/- 3%, active sleep 24 +/- 11%, intermediate sleep 22 +/- 8%, quiet sleep 47 +/- 13%, and undefined 4 +/- 2%. Positive answers to questions on civilian life sleepiness were related to high scores on scales for hypochondria, psychasthenia and sense of reality, and night sleep longer than 10 h to high scores for psychasthenia and sense of reality, but not to polygraphic measures. Two men with complaints about civil-time irresistible sleep at the time of beginning the military service had short Stage 2 latencies at the daytime minimum of alertness during service (4 and 8 min). Although alertness and sleep during military service were normal on average, the findings suggest that all conscripted individuals may not have had enough sleep.

Adult

European Respiratory Society study on chronic obstructive pulmonary disease (EUROSCOP): hypothesis and design.

Chronic obstructive pulmonary disease (COPD) is a common disease in industrialised countries and responsible for a considerable morbidity and mortality. Cigarette smoking is the most important aetiological factor. The EUROSCOP trial aims at investigating the hypothesis that airway inflammation plays an important pathogenic role in the development of chronic obstructive airway disease in smokers. In cigarette smokers with poorly reversible airflow obstruction, the effect over 3 yrs of an inhaled glucocorticosteroid, budesonide 400 micrograms b.i.d., on the decline of lung function, measured as postbronchodilator forced expiratory volume in one second (FEV1), will be compared with that of placebo. The trial has been designed to detect a difference in yearly decline of at least 30 ml.year-1. The study is a parallel group, randomised, double-blind, multicentre study. Patients will be recruited from 47 centres in 12 countries in Europe. It will start with a run-in consisting of two 3 month periods. During the first 3 months, the patients will be offered a smoking cessation programme. All patients who have not stopped smoking during this period will enter the second half of the run-in where compliance with the dosage regimen will be tested. After these two periods, patients will be randomised to receive either inhaled budesonide, 400 micrograms b.i.d., or placebo for a period of 3 yrs.

Administration, Inhalation

Lung function impairment following mycoplasmal and other acute pneumonias.

We prospectively studied the lung function of 106 consecutive young patients with pneumonia. At the time of hospital admission we observed impaired spirometric function in 48% of the patients. During and following treatment, the frequency of abnormalities in pulmonary function tests decreased rapidly. However, at the 15th day of hospitalization, abnormal ventilatory function was still demonstrated in 21% of the patients. Such prolonged impairment of ventilatory function was significantly more likely to result from pneumonia caused by Mycoplasma pneumoniae than from forms caused by adenovirus or Streptococcus pneumoniae.

Adenovirus Infections, Human

Clinical testing of thermally stimulated cardiovascular oscillations in man.

STUDY OBJECTIVE: The study assessed the physiological validity of an automatic thermal stimulation method to induce synchronised oscillations in the neural cardiovascular control system. DESIGN: Automatic alternating rhythmic warm and cool immersion of different skin areas of 18 males was done at different frequencies and water temperatures. The neurally mediated responses to the periodic thermal stimulation were measured from skin blood flow and heart rate and compared to those of a sham stimulation. Respiration was monitored for control purposes. The reproducibility of the stimulation and responses was examined. SUBJECTS: 18 young males volunteered for the study. MEASUREMENTS AND MAIN RESULTS: The water bath method produced reproducible thermal stimulation and responses of skin blood flow and heart rate. Rhythmic thermal stimulation at 0.013-0.096 Hz synchronised the oscillations of the forearm skin blood flow when the thermal stimulus amplitude exceeded 10 degrees C. The increase in the stimulus amplitude or enlargement of the stimulus area did not further increase the oscillatory response of skin blood flow. Sham stimulation or mean temperature of the periodic thermal stimulation in the range 23-33 degrees C did not influence the oscillations of skin blood flow. Local cooling of the stimulated lower legs attenuated the response of skin blood flow. Both thermal stimulation and sham stimulation affected heart rate, but no stable synchronisation of the periodic heart rate variability was found at supine rest. Thermal stimulation of the sitting subjects' forearm instead of legs increased the synchronisation of the periodic heart rate variability. CONCLUSIONS: The response of skin blood flow agreed with the theory of the thermal entrainment. In a supine man, both thermal stimulation and non-specific central nervous influences induced significant and reproducible interactions with periodic heart rate variability and respiration.

Adult

Bronchial hyperresponsiveness in normal subjects during attenuated influenza virus infection.

Fourteen healthy male subjects with hemagglutination-inhibition antibody titers of 1:8 or less to homologous influenza A virus were studied. Six subjects received live, attenuated influenza virus by nasal drops and by aerosol. Although infection occurred in these six subjects, with the development of 4-fold or greater increases in hemagglutination-inhibition antibody titers, they remained asymptomatic. Eight subjects received placebo via the same route, and did not develop symptoms and showed no increase in antibody titer. Prior to administration of virus or placebo, histamine diphosphate aerosol increased airway resistance only slightly, and there was no difference between the virus and placebo groups. Two days after inoculation, bronchomotor responses in the placebo group were unchanged (p greater than 0.05), but in the virus-infected group, bronchomotor responses were significantly greater than in the preinfected state (p less than 0.01). Isoproterenol hydrochloride reversed and prevented the increase in airway resistance after histamine, suggesting that the bronchoconstriction was caused by smooth muscle contraction. Our findings indicate that transient, asymptomatic respiratory virus infection augments airway smooth muscle responses.

Adult

Eosinophilic airway inflammation during exacerbation of asthma and its treatment with inhaled corticosteroid.

We have compared the inflammatory changes in the bronchial mucosa and the increase in the airway hyperresponsiveness in an asthmatic patient during the deterioration of symptoms. A striking increase in the number of bronchial epithelial eosinophils was associated with an increase in both airway hyperresponsiveness and asthma symptoms. During 16 wk of treatment with the inhaled corticosteroid, budesonide, the patient's clinical status and airway hyperresponsiveness improved. This was accompanied by an improvement in the ultrastructure of bronchial mucosa and a decrease in the number of epithelial eosinophils.

Adrenal Cortex Hormones

Granulocytes and their secretory products, myeloperoxidase and eosinophil cationic protein, in bronchoalveolar lavage fluids from two lung lobes in normal subjects.

The interlobar variability of lavage neutrophils and eosinophils was studied in twelve healthy subjects. In addition, the interlobar variation of the neutrophil cell marker myeloperoxidase (MPO) and the eosinophil cell marker eosinophil cationic protein (ECP) was assessed. Bronchial washes (BW), as defined by the first aspirated lavage aliquot, and bronchoalveolar lavage (BAL) fluids were compared. One subsegment of the right middle lobe and one subsegment of the right lower lobe were lavaged in the same session. Interlobar consistency of neutrophil and eosinophil cell recoveries was observed but, in contrast, the levels of MPO or ECP did not correlate in lavage fluids aspirated from the two lobes. These results suggest that BAL cell content from a single lobe of the lung in healthy subjects does reflect the cell populations throughout the airways, while the levels of soluble proteins may differ between the lobes. Such a variation questions the correlation between cells and their secretory products or the correlation between levels of solutes in lavage fluid and in the underlying tissue. Further methodological studies appear warranted to elucidate whether cell and solute recoveries accurately reflect the underlying pathology.

Adult

Prevalence of asthma in Finnish young men.

OBJECTIVE: To determine the prevalence of asthma in cohorts of Finnish young men in the period 1926-89. DESIGN: A retrospective analysis using reports and statistics of Finnish defence forces. SETTING: Call up examinations of candidates for military conscription and examination of conscripts discharged because of poor health. SUBJECTS: Roughly 900,000 men--that is, 98% of men of conscription age--examined in 1966-89 and a proportional but unknown number examined in 1926-61. MAIN OUTCOME MEASURES: Asthma recognised at call up examination, exemption from military service, and discharge from military service because of asthma. RESULTS: During 1926-61 the prevalence of asthma recorded at call up examinations remained steady at between 0.02% and 0.08%. Between 1961 and 1966, however, a continuous, linear rise began, the prevalence increasing from 0.29% in 1966 to 1.79% in 1989--that is, representing a sixfold increase. Compared with 1961 the rise was 20-fold. From 1966 to 1989 the sum of exemptions and discharges from military service due to asthma increased analogously sixfold. CONCLUSIONS: If the apparent increase in asthma detected in Finnish young men was due entirely to improved diagnostic methods and other confounding effects then some 95% of cases must have gone undiagnosed in the years before 1966. This seems inconceivable, which suggests that much of the increase was real. This conclusion is strengthened by the observed rise in exemptions and discharges due to asthma.

Adult

Long-term cardiac sequelae after treatment of malignant tumors with radiotherapy or cytostatics in childhood.

A series of 41 individuals were restudied after childhood cancer with a median follow-up time of 17 years after chest irradiation or treatment with cyclophosphamide or Adriamycin (doxorubicin). Radiotherapy of the chest had been used in 21 patients, and in 13 of these irradiation was also directed at the heart. Thirty-five patients received cyclophosphamide and five received Adriamycin therapy. All patients were investigated by a pediatric cardiologist. Investigations included an electrocardiogram (ECG), a chest radiographic film, an echocardiogram, an exercise test, and a 24-hour ECG. Altogether 20 patients (49%) showed some abnormality in cardiac tests. Each additional year of follow-up was associated with a 1.3-fold (95% confidence limits, 1.04-1.66; P less than 0.05) increase in the risk for pathologic cardiac findings. The risk for an abnormal cardiac test result in the 13 patients who had received cardiac irradiation was 12.8-fold (95% confidence limits, 1.8-90.8; P less than 0.02) that of the other patients. However, abnormalities in cardiac function were mild.

Adolescent

Bronchial biopsies in drug intervention studies in CB and COAD.

So far, little information is available on the usefulness of the biopsy method in drug intervention studies in COAD and CB. Quantitation studies at electron microscopical level are time consuming. Comparative studies between and within the patient groups are needed to attain basic and clinically relevant information. Pathology studies may lead to a better understanding of basic pathophysiological mechanisms behind the diseases. The sequences of cellular events could be revealed so that morphology may be useful in intervention studies.

Biopsy

Effects of single doses of quinapril and atenolol on autonomic nervous function and exercise capacity in healthy volunteers.

The effects of single oral doses of the angiotensin converting enzyme (ACE) inhibitor quinapril (CI-906) 40 mg and the cardioselective beta-adrenoceptor blocker atenolol 100 mg on sympathetic and parasympathetic function and on exercise capacity have been studied in 8 healthy young men. The trial followed a double-blind, placebo controlled, randomized cross-over design, with at least one week between treatments. Blood pressure (BP) and heart rate (HR) at rest were slightly reduced by atenolol but were not affected by quinapril. Atenolol impaired the sympathetically mediated increases in HR and BP caused by standing, immersion of the hand into melting ice, the Valsalva manoeuvre and isometric forearm exercise. Quinapril did not influence those responses nor the vagally mediated bradycardia of the diving reflex. Atenolol, however, augmented the vagal bradycardia, presumably by sympathetic inhibition. In a dynamic bicycle ergometer test with a stepwise increasing work load, exercise performance was decreased by atenolol but not by quinapril. Inhibition of the renin-angiotensin system by quinapril was shown by a marked decrease in serum ACE activity and a several-fold increase in plasma renin activity (PRA). Atenolol produced a moderate reduction in PRA. Before or during exercise, plasma noradrenaline and adrenaline were not influenced by either drug. The results indicate that, unlike the atenolol-induced beta-adrenoceptor blockade, ACE inhibition by a single dose of quinapril had no clear effect on autonomic nervous function or exercise capacity.

Adult

Effect of posture on spontaneous and thermally stimulated cardiovascular oscillations.

STUDY OBJECTIVE: The aim of the study was to investigate the effect of posture on thermally stimulated cardiovascular oscillations. DESIGN: The effect of increased gravitational stress (rising from sitting to standing position) on the thermally stimulated cardiovascular oscillations was measured in young male volunteers. Extensive cardiovascular function data were obtained using a cardiovascular investigation protocol. SUBJECTS: The volunteers were five fit young men, aged 20-21 years. EXPERIMENTS AND MAIN RESULTS: Cardiovascular changes from sitting to standing indicated increased sympathetic and decreased parasympathetic influence on heart and skin blood vessels; mean heart rate increased, beat to beat heart rate variability diminished, high frequency periodic heart rate variability decreased, low frequency heart rate oscillations and ratio of low frequency to high frequency heart rate variability increased, mean skin blood flow and oscillations of skin blood flow decreased (all p less than 0.05). Thermal skin stimulation at 0.01-0.10 Hz frequency increased both sitting and standing 0.10 Hz periodic heart rate variability (p less than 0.05), and 0.10 Hz thermal stimulation entrained the heart rate oscillations in sitting and standing subjects (p less than 0.05). In contrast, skin blood flow oscillations in sitting subjects decreased, while in standing subjects it increased during 0.10 Hz thermal stimulation compared to the corresponding prestimulus values (p less than 0.04). CONCLUSIONS: On the basis of previous physiological experiments, these results suggest coupling between thermoregulatory and 0.10 Hz reflex activities.

Adult

Bronchial epithelial inflammation in children with chronic cough after early lower respiratory tract illness.

We studied the ultrastructural findings in biopsies from the main carina of seven school-aged children who had had chronic cough for at least 3 months and who all had a history of early lower respiratory illness (LRI). They had their first LRI between birth and 7 yr of age (range, 5 to 11 yr). The cross-sectional area of the epithelium was quantified by point counting for the percentage area of intercellular spaces (ICS) denoting edema, and the numbers of both inflammatory cells (leukocytes, including eosinophils, and mast cells) and ciliated cells. The children (excluding the one using inhaled steroids) demonstrated nearly 17- and more than sevenfold increases in the mean area of ICS and number of inflammatory cells per epithelial area, respectively, and a nearly three-fold decrease in the mean number of ciliated cells per epithelial area compared with the biopsy specimens from the orifice of the right upper lobe bronchus of two healthy adults. In the children, the increase in inflammatory cells (greater than 91% were lymphocytes) was more prominent in the children with two LRI before the age of 1 yr. Our findings imply a close association of early LRI and later epithelial inflammation during chronic cough. Allergic mechanisms in the epithelial inflammation cannot be ruled out as six of the patients had, either alone or in combination, signs of atopia, positive family history of allergic rhinitis or asthma, and eosinophils or mast cells in the epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Vascular beds in the airways of normal subjects and asthmatics.

In humans a rich network of capillaries runs subepithelially from the central airways to the level of the peripheral bronchioles, where it anastomoses with the alveolar capillaries. The tracheobronchial capillaries converge to form venules extending to a deeper plexus of larger venules and arterioles. Transmission electronmicroscopy shows capillaries very close to the epithelial basement membrane, but not in the epithelium itself. There are two main differences in the bronchial mucosal vascular bed between healthy controls and asthmatics. In 60% of asthmatics there are endothelial gaps in the bronchial mucosal microvasculature compared to none in controls. Half of asthmatics have eosinophils adhered in the bronchial mucosal venules and capillaries, but none are seen in controls. Neutrophils are even more common than eosinophils in the bronchial mucosal capillaries and venules, but they are also found in the venules of one control out of four. The finding of inflammatory cells in the bronchial vessels suggests possible chemotaxis in asthmatics.

Asthma