Towards automated detection of psychosocial risk factors with text mining.

BACKGROUND: Psychosocial risk factors influence early retirement and absence from work. Health checks by occupational health nurses (OHNs) may prevent deterioration of work ability. Health checks are documented electronically mostly as free text, and therefore the effect of psychological risk factors on working capacity is difficult to detect. AIMS: To evaluate the potential of text mining for automated early detection of psychosocial risk factors by examining health check free-text documentation, which may indicate medical statements recommending early retirement, prolonged sick leave or rehabilitation. Psychosocial risk factors were extracted from OHN documentation in a nationwide occupational health care registry. METHODS: Analysis of health check documentation and medical statements regarding pension, sick leave and rehabilitation. Annotations of 13 psychosocial factors based on the Prima-EF standard (PAS 1010) were used with a combination of unsupervised machine learning, a document search engine and manual filtering. RESULTS: Health check documentation was analysed for 7078 employees. In 83% of their health checks, psychosocial risk factors were mentioned. All of these occurred more frequently in the group that received medical statements for pension, rehabilitation or sick leave than the group that did not receive medical statement. Documentation of career development and work control indicated future loss of work ability. CONCLUSIONS: This study showed that it was possible to detect risk factors for sick leave, rehabilitation and pension from free-text documentation of health checks. It is suggested to develop a text mining tool to automate the detection of psychosocial risk factors at an early stage.

Health check documentation of psychosocial factors using the WAI.

BACKGROUND: Health checks in occupational health (OH) care should prevent deterioration of work ability and promote well-being at work. Documentation of health checks should reflect and support continuity of prevention and practice. AIMS: To analyse how OH nurses (OHNs) undertaking health checks document psychosocial factors at work and use the Work Ability Index (WAI). METHODS: Analysis of two consecutive OHN health check records and WAI scores with statistical analyses and annotations of 13 psychosocial factors based on a publicly available standard on psychosocial risk management: British Standards Institution specification PAS 1010, part of European Council Directive 89/391/EEC, with a special focus on work-related stress and workplace violence. RESULTS: We analysed health check records for 196 employees. The most frequently documented psychosocial risk factors were home-work interface, work environment and equipment, job content, workload and work pace and work schedule. The correlations between the number of documented risk and non-risk factors and WAI scores were significant: OHNs documented more risk factors in employees with lower WAI scores. However, documented psychosocial risk factors were not followed up, and the OHNs' most common response to detected psychosocial risks was an appointment with a physician. CONCLUSIONS: The number of psychosocial risk factors documented by OHNs correlated with subjects' WAI scores. However, the documentation was not systematic and the interventions were not always relevant. OHNs need a structure to document psychosocial factors and more guidance in how to use the documentation as a tool in their decision making in health checks.

Combining supervised and unsupervised named entity recognition to detect psychosocial risk factors in occupational health checks.

INTRODUCTION: In occupational health checks the information about psychosocial risk factors, which influence work ability, is documented in free text. Early detection of psychosocial risk factors helps occupational health care to choose the right and targeted interventions to maintain work capacity. In this study the aim was to evaluate if we can automate the recognition of these psychosocial risk factors in occupational health check electronic records with natural language processing (NLP). MATERIALS AND METHODS: We compared supervised and unsupervised named entity recognition (NER) to detect psychosocial risk factors from health checks' documentation. Occupational health nurses have done these records. RESULTS: Both methods found over 60% of psychosocial risk factors from the records. However, the combination of BERT-NER (supervised NER) and QExp (query expansion/paraphrasing) seems to be more suitable. In both methods the most (correct) risk factors were found in the work environment and equipment category. CONCLUSION: This study showed that it was possible to detect risk factors automatically from free-text documentation of health checks. It is possible to develop a text mining tool to automate the detection of psychosocial risk factors at an early stage.

Cardiac positron emission tomography/computed tomography imaging accurately detects anatomically and functionally significant coronary artery disease.

BACKGROUND: Computed tomography (CT) is increasingly used to detect coronary artery disease, but the evaluation of stenoses is often uncertain. Perfusion imaging has an established role in detecting ischemia and guiding therapy. Hybrid positron emission tomography (PET)/CT allows combination angiography and perfusion imaging in short, quantitative, low-radiation-dose protocols. METHODS AND RESULTS: We enrolled 107 patients with an intermediate (30% to 70%) pretest likelihood of coronary artery disease. All patients underwent PET/CT (quantitative PET with (15)O-water and CT angiography), and the results were compared with the gold standard, invasive angiography, including measurement of fractional flow reserve when appropriate. Although PET and CT angiography alone both demonstrated 97% negative predictive value, CT angiography alone was suboptimal in assessing the severity of stenosis (positive predictive value, 81%). Perfusion imaging alone could not always separate microvascular disease from epicardial stenoses, but hybrid PET/CT significantly improved this accuracy to 98%. The radiation dose of the combined PET and CT protocols was 9.3 mSv (86 patients) with prospective triggering and 21.8 mSv (21 patients) with spiral CT. CONCLUSIONS: Cardiac hybrid PET/CT imaging allows accurate noninvasive detection of coronary artery disease in a symptomatic population. The method is feasible and can be performed routinely with <10 mSv in most patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00627172.

A novel g.-1258G>A mutation in a conserved putative regulatory element of PAX9 is associated with autosomal dominant molar hypodontia.

Mutations in the transcription factor PAX9 which plays a critical role in the switching of odontogenic potential from the epithelium to the mesenchyme during tooth development cause autosomal dominant non-syndromic hypodontia primarily affecting molars. Linkage analysis on a family segregating autosomal dominant molar hypodontia with markers flanking and within PAX9 yielded a maximum multipoint LOD score of 3.6. No sequence variants were detected in the coding or 5'- and 3'-untranslated regions (UTRs) of PAX9. However, we identified a novel g.-1258G>A sequence variant in all affected individuals of the family but not in the unaffected family members or in 3088 control chromosomes. This mutation is within a putative 5'-regulatory sequence upstream of PAX9 highly conserved in primates, somewhat conserved in ungulates and carnivores but not conserved in rodents. Bioinformatics analysis of the sequence determined that there was no abolition or creation of a putative binding site for known transcription factors. Based on our previous findings that haploinsufficiency for PAX9 leads to hypodontia, we postulate that the g.-1258G>A variant reduces the expression of PAX9 which underlies the hypodontia phenotype in this family.

Allergic sensitization is associated with rhinovirus-, but not other virus-, induced wheezing in children.

BACKGROUND: Data on the link between atopy and viral wheeze are limited. AIM: To evaluate the association between IgE sensitization and viral infection in wheezing children. METHODS: This is an observational study in hospitalized wheezing children (n = 247; median age 1.6 ; interquartile range 1.1, 2.9). Eighteen respiratory viral infections were studied using all available methods. A specific immunoglobulin E (IgE) sensitization for common food and aeroallergens and other atopy-related variables including total IgE, blood and nasal eosinophils, exhaled nitric oxide, eczema and atopic eczema, parental allergy and asthma, number of wheezing episodes, positive asthma predictive index or asthma and use of inhaled corticosteroid were correlated with specific viral etiology. RESULTS: Atopy was closely associated with sole rhinovirus etiology (n = 58) but not with sole respiratory syncytial virus, sole enterovirus, sole human bocavirus, sole other virus, mixed viral, or virus negative etiology. The number of sensitizations was particularly associated with sole rhinovirus etiology (odds ratio 4.59; 95% confidence interval 1.78, 11.8; adjusted to age and sex), followed by aeroallergen sensitization (respectively; 4.18; 2.00, 8.72), total IgE level (2.06; 1.32, 3.21), food allergen sensitization (2.02; 1.08, 3.78), and nasal eosinophil count (1.52; 1.08, 2.13). CONCLUSIONS: According to our data, allergic sensitization is positively linked to rhinovirus-, but not other virus-, associated wheezing and calls attention for studies to test rhinovirus-associated wheezing as a part of asthma risk indices.

Twenty-four-month alpha-galactosidase A replacement therapy in Fabry disease has only minimal effects on symptoms and cardiovascular parameters.

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of alpha-galactosidase A enzyme activity. Decreased enzyme activity leads to accumulation of glycosphingolipids in different tissues including endothelial cells and smooth-muscle cells and cardiomyocytes, and cardiovascular complications are common in the disease. Since 2001, specific enzyme replacement therapy (ERT) with alpha-galactosidase A has been available. It has been reported to improve clinical symptoms and quality of life. However, limited and controversial data on its efficacy to cardiac involvement have been published. Nine patients (5 male) with Fabry disease were included in an open-label prospective follow-up study of 24-month ERT. Comprehensive cardiovascular evaluation was performed by MRI, stress echocardiography and quality of life assessment. Plasma globotriaosylceramide decreased from 6.2 to 1.4 microg/ml during ERT (p<0.05). The only other measured parameters that changed significantly were resting heart rate that decreased from 79 to 67 bpm (p<0.01) and end-systolic volume that decreased by 12.4 ml (p<0.05). The other parameters consisting of quality of life, self-estimated cardiovascular condition, diastolic function, exercise capacity, ECG parameters, ejection fraction and ventricular mass did not change. ERT has only minimal effect on symptoms and cardiovascular morphology and function in Fabry disease. Therefore, effective conventional medical therapy is still of major importance in Fabry disease. Larger ERT studies are warranted, especially in women, to solve current open questions, such as the age at which ERT should be started, optimal dosage and intervals between infusions. Furthermore, longer follow-up studies are needed to assess the effects of ERT on prognosis.

Increased aortic intima-media thickness: a marker of preclinical atherosclerosis in high-risk children.

BACKGROUND: Autopsy studies in children have shown that atherosclerotic lesions begin to develop first in the intima of the aorta. Recent developments in ultrasound techniques have made it possible to visualize the intima-medial thickness of the abdominal aorta directly (aIMT). Therefore, we examined the feasibility of measuring aIMT in children and studied its value in distinguishing high-risk children from healthy controls compared with a more established marker of subclinical atherosclerosis, the common carotid artery intima-medial thickness (cIMT). METHODS AND RESULTS: IMTs were measured using high-resolution (13 MHz) ultrasound in 88 children (aged 11+/-2 years); 16 had hypercholesterolemia (LDL cholesterol, 5.1+/-1.2 mmol/L), 44 had type 1 diabetes (mean duration, 4.4+/-3.1 years; LDL cholesterol, 2.3+/-0.7 mmol/L), and 28 were healthy (controls; LDL cholesterol, 2.5+/-0.8 mmol/L). High-risk children had significantly increased aIMTs and cIMTs (both P<0.001) compared with controls. In controls, aIMT was similar to cIMT (P=NS), but aIMT was higher than cIMT in the children with hypercholesterolemia and diabetes (both P<0.01). Both markers showed excellent and approximately equal between-observer (<4%) and between-subject variation (<5%). CONCLUSIONS: Children with hypercholesterolemia and diabetes show increased IMTs compared with healthy controls, with a relatively greater increase in the aIMT than in the cIMT. Because atherosclerosis begins first in the intima of the aorta, these data suggest that the aIMT might provide the best currently available noninvasive marker of preclinical atherosclerosis in children.

Quantification of mitral regurgitation by velocity-encoded cine nuclear magnetic resonance imaging.

OBJECTIVES: The feasibility of velocity-encoded cine nuclear magnetic resonance (NMR) imaging to measure regurgitant volume and regurgitant fraction in patients with mitral regurgitation was evaluated. BACKGROUND: Velocity-encoded cine NMR imaging has been reported to provide accurate measurement of the volume of blood flow in the ascending aorta and through the mitral annulus. Therefore, we hypothesized that the difference between mitral inflow and aortic systolic flow provides the regurgitant volume in the setting of mitral regurgitation. METHODS: Using velocity-encoded cine NMR imaging at a magnet field strength of 1.5 T and color Doppler echocardiography, 19 patients with isolated mitral regurgitation and 10 normal subjects were studied. Velocity-encoded cine NMR images were acquired in the short-axis plane of the ascending aorta and from the short-axis plane of the left ventricle at the level of the mitral annulus. Two independent observers measured the ascending aortic flow volume and left ventricular inflow volume to calculate the regurgitant volume as the difference between left ventricular inflow volume and aortic flow volume, and the regurgitant fraction was calculated. Using accepted criteria of color flow Doppler imaging and spectral analysis, the severity of mitral regurgitation was qualitatively graded as mild, moderate or severe and compared with regurgitant volume and regurgitant fraction, as determined by velocity-encoded cine NMR imaging. RESULTS: In normal subjects the regurgitant volume was -6 +/- 345 ml/min (mean +/- SD). In patients with mild, moderate and severe mitral regurgitation, the regurgitant volume was 156 +/- 203, 1,384 +/- 437 and 4,763 +/- 2,449 ml/min, respectively. In normal subjects the regurgitant fraction was 0.7 +/- 6.1%. In patients with mild, moderate and severe mitral regurgitation, the regurgitant fraction was 3.1 +/- 3.4%, 24.5 +/- 8.9% and 48.6 +/- 7.6%, respectively. The regurgitant fraction correlated well with the echocardiographic severity of mitral regurgitation (r = 0.87). Interobserver reproducibilities for regurgitant volume and regurgitant fraction were excellent (r = 0.99, SEE = 238 ml; r = 0.98, SEE = 4.1%, respectively). CONCLUSIONS: These findings suggest that velocity-encoded NMR imaging can be used to estimate regurgitant volume and regurgitant fraction in patients with mitral regurgitation and can discriminate patients with moderate or severe mitral regurgitation from normal subjects and patients with mild regurgitation. It may be useful for monitoring the effect of therapy intended to reduce the severity of mitral regurgitation.

Population-based twin study of the effects of migration from Finland to Sweden on endothelial function and intima-media thickness.

Finnish men have higher coronary heart disease (CHD) mortality than Swedish men do. To assess the impact of migration to a country with lower CHD mortality on subclinical atherosclerosis, we measured early functional and structural atherosclerotic vascular changes in twins discordant for migration from Finland to Sweden. Conventional CHD risk factors, flow-mediated dilatation (FMD) of the brachial artery, carotid intima-media thickness, and carotid artery compliance were measured in 74 male twin pairs (20 monozygous, 54 dizygous), aged 42 to 69 years, in which co-one twin had migrated more than 20 years ago permanently to Sweden. There were no significant differences in CHD risk factors except for diastolic blood pressure and body fat percentage, which were higher in Sweden. In all subjects, mean FMD was non-significantly higher in Sweden (5.7+/-4.3% vs 4.9+/-4.2%, P=0.22), but in monozygous twins the difference in FMD was highly significant (7.2+/-4.4 vs 3.7+/-2.9%, P=0.003). There was no significant difference in intima-media thickness or carotid artery compliance between Sweden and Finland. We conclude that in Finnish monozygous twins the endothelial function is better among the twins that have migrated to a country with lower CHD prevalence.

Diagnosis of infective endocarditis. Sensitivity of the Duke vs von Reyn criteria.

BACKGROUND: Because of the highly variable clinical manifestations of infective endocarditis (IE), different sets of diagnostic criteria have been used to standardize case definitions of IE. We evaluated the validity of the recently proposed Duke criteria, as compared with the older von Reyn criteria, in patients with no history of injecting drug abuse. METHODS: A total of 243 consecutive episodes of suspected IE in 222 patients treated during the years 1980 through 1995 in a Finnish teaching hospital were retrospectively evaluated for the likelihood of IE by means of these 2 classification schemes. RESULTS: Of all disease episodes, 114 were designated as definite IE by the Duke criteria, as compared with 64 episodes so classified by the von Reyn criteria (P < .001; Fisher exact test). Moreover, as many as 115 disease episodes were rejected by the von Reyn criteria, whereas only 37 episodes were rejected by the Duke criteria (P < .001). Of the cases rejected by the von Reyn criteria, the Duke clinical criteria designated 6 (5%) as definite IE and 72 (63%) as possible IE. Among histopathologically verified episodes, 46 were designated as definite IE by the Duke clinical criteria, as compared with a diagnosis of probable IE by the von Reyn criteria in 33 episodes (P = .02). Moreover, 26 pathologically proved cases would have been rejected by the von Reyn criteria had surgery not been performed, as compared with none being rejected by the Duke criteria (P < .001). CONCLUSIONS: Corroborating earlier findings, the higher sensitivity of the Duke criteria, as compared with the von Reyn criteria, was demonstrated in this study. These results confirm the validity of the Duke criteria in diagnosing IE in a non-drug-addict patient population.

Constantly low HDL-cholesterol concentration relates to endothelial dysfunction and increased in vivo LDL-oxidation in healthy young men.

To test the hypothesis that low HDL-C concentration interferes with vascular endothelial function and lipoprotein oxidation, we measured endothelium-dependent flow mediated dilatation (FMD, %) of the brachial artery in young men (n=20) classified prospectively into two groups on basis of having either low or high HDL-C concentration over the past 2 years. As an estimate of in vivo low-density lipoprotein oxidation (ox-LDL), we measured LDL diene conjugation. FMD was present in the group with high HDL-C concentration, but impaired in the group with low HDL-C (5.5+/-3.2 vs 0.2+/-1.2%, P<0. 001). The group with high HDL-C level had significantly lower levels of ox-LDL compared to low HDL-C group (18.0+/-1.8 vs 22.9+/-4.4, P

HMG CoA reductase inhibitors are related to improved systemic endothelial function in coronary artery disease.

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase (statins) may enhance vascular endothelial function independent of their cholesterol lowering effect. To test this hypothesis, we surveyed two groups of patients (age 55+/-7, mean+/-SD) with coronary artery disease that were matched for age, blood pressure and serum lipid levels. Group 1 comprised 23 men without lipid-lowering medication and Group 2 included 22 patients with ongoing HMG CoA reductase inhibitor medication. Flow-mediated (endothelium-dependent) arterial dilatation (FMD) and nitrate-mediated (smooth muscle dependent) dilatation (NMD) were measured in the brachial artery using high resolution ultrasound. FMD was considerably higher in group 2 (4.3+/-2.6 vs. 2.6+/-2.8%; P<0.05). In multivariate regression model, statin use was the only significant (P<0.05) predictor of FMD. In all subjects, FMD correlated with statin dose (P<0.05 for trend). NMD was non-significantly higher in group 2 (11.4+/-5.0 vs. 9.0+/-4.2%, P=0. 08). We conclude that patients with established coronary artery disease on HMG CoA reductase inhibitor therapy have better vascular endothelial function than similar patients without the medication. These data provide further support for the idea that HMG CoA reductase inhibitors enhance endothelial function independent of their lipid-lowering effects. This may suggest that these drugs could be beneficial in secondary prevention of coronary artery disease regardless of the serum cholesterol concentration.

Reduced myocardial flow reserve relates to increased carotid intima-media thickness in healthy young men.

Increased carotid artery wall thickness and lipoprotein oxidation are key early events in atherosclerosis. To test the hypothesis that reduced myocardial flow reserve is a marker of subclinical atherosclerosis, we examined the relationships between flow reserve and carotid artery intima-media thickness (IMT) in young men free from coronary heart disease. Basal and dipyridamole stimulated coronary blood flow was measured using positron emission tomography (PET) in 55 healthy men aged 36+/-4 years. Myocardial flow reserve was calculated as the ratio of stimulated flow to basal flow. The mean carotid artery IMT was measured using high-resolution ultrasound. Oxidised LDL was measured as baseline LDL diene conjugation. Myocardial flow reserve decreased across the quartiles of increasing IMT (P=0.006), and was 5.2+/-1.9 in the lowest quartile for IMT and 3.7+/-1.2 in the highest (P=0.04, I vs. IV quartile). In univariate analysis, oxidised LDL correlated inversely with flow reserve (r=-0.35, P=0.01) and directly with IMT (r=0.51, P<0.001). The association between flow reserve and IMT remained significant (P< or =0.01) in multivariate regression model including age, blood pressure, left ventricular mass, ox-LDL, total cholesterol, HDL-cholesterol and triglycerides as covariates. These data support the concept that reduced myocardial flow reserve reflects subclinical atherosclerosis in asymptomatic subjects, and suggest that increased lipoprotein oxidation is directly related to early structural and functional atherosclerotic vascular changes.

Enhancement of myocardial [fluorine-18]fluorodeoxyglucose uptake by a nicotinic acid derivative.

UNLABELLED: Recently, the euglycemic hyperinsulinemic clamp technique was shown to give excellent image quality during metabolic steady-state conditions. Acipimox is a new potent nicotinic acid derivative that rapidly reduces serum free fatty acid (FFA) levels by inhibiting lipolysis in peripheral tissue. METHODS: To compare the effects of acipimox administration and insulin clamp on [18F]fluorodeoxyglucose ([18F]FDG) uptake and myocardial glucose utilization, five nondiabetic and seven type II diabetic patients who had had previous myocardial infarctions were studied twice: once during a clamp study and once after the administration of acipimox (2 x 250 mg orally). All patients also underwent resting SPECT perfusion imaging prior to PET scans. RESULTS: The patients tolerated acipimox well. Although fasting plasma glucose levels were higher in diabetic patients (9.2 +/- 3.4 versus 5.5 +/- 0.3 mM, p = 0.03), they were decreased both during clamping and after acipimox; during imaging, no significant differences between the groups and approaches were detected. By visual analysis, the image quality and myocardial [18F]FDG uptake patterns were similar during clamping and after acipimox. Compared with the relative [18F]FDG uptake values obtained during clamping, acipimox yielded similar results in normal, mismatch and scar segments (r = 0.88, p = 0.0001). Similar rMGU values were also obtained during both approaches. CONCLUSION: Thus, PET imaging with [18F]FDG after the administration of acipimox is a simple and feasible method for clinical viability studies both in nondiabetic and diabetic patients. It results in excellent image quality and gives rMGU levels similar to the insulin clamp technique.

Reduced myocardial flow reserve does not impair exercise capacity in asymptomatic men.

We examined whether impaired coronary flow reserve in healthy men is associated with changes in cardiac performance and exercise-induced ischemia. A comparison between 7 asymptomatic men with low flow reserve (<3.5) and 8 men with normal flow reserve (>3.5) showed no differences in these parameters, suggesting that the mechanisms that control myocardial blood flow during exercise remain normal despite the alterations in the mechanisms that control the vasodilatory reaction to dipyridamole.

Effects of cigarette smoke on the metabolism of vasoactive hormones in rat isolated lungs.

1. The effects of exposure of rats to cigarette smoke have been studied on the metabolism of vasoactive hormones in isolated lungs from these animals. 2. Rats were exposed for 1 h per day to cigarette smoke for 1 day or for 10 days. 3. Angiotensin I conversion was increased after 1 day's exposure but after 10 days' exposure conversion returned to normal. 4. Inactivation of prostaglandin E2 was decreased after 1 day's exposure. After 10 days' exposure there was a further decrease which could not be attributed to smoke alone. 5. The inactivation of 5-hydroxytryptamine and bradykinin remained unchanged after both short and longer exposures to smoke. 6. The metabolic activity of the lung towards some vasoactive hormones in the pulmonary circulation is affected by exposure of the animal to cigarette smoke and such changes may be relevant to the initiation of cardiovascular changes consequent upon cigarette smoking.

Nicotine-induced respiratory effects of cigarette smoke in dogs.

We report that nicotine is responsible for both a blood-borne stimulation of the respiratory center and a direct effect on intrathoracic airway tone in dogs. We introduced cigarette smoke into the lungs of donor dogs and injected arterial blood obtained from them into the circulation of recipient dogs to show that a blood-borne material increased breathing and airway smooth muscle tone. Smoke from cigarettes containing 2.64 mg of nicotine was effective; that from cigarettes containing 0.42 mg of nicotine was not. Nicotine, in doses comparable to the amounts absorbed from smoke, also increased breathing and tracheal smooth muscle tension when injected into the vertebral circulation of recipient dogs. Finally, blockade of nicotine receptors in the central nervous system and in the airway parasympathetic ganglia inhibited the effects of inhaled cigarette smoke and intravenous nicotine on the respiratory center and on bronchomotor tone. We conclude that nicotine absorbed from cigarette smoke is the main cause of cigarette smoke-induced bronchoconstriction. It caused central respiratory stimulation, resulting in increased breathing and airway smooth muscle tension, and had a direct effect on airway parasympathetic ganglia as well.

Immunologic and nonimmunologic responsiveness in ragweed-sensitized dogs.

The relationship between airway responsiveness to inhaled antigen and histamine, immunologic release of lung histamine, immunologic responsiveness of skin, and specific immunoglobulin E (IgE) antibodies were examined in 11 inbred allergic dogs immunized with extracts of ragweed and grass and 5 nonimmunized control dogs from the same colony. Airway responsiveness to antigen and histamine was characterized by the doses that increased the airflow resistance of the total respiratory system to twice the control values (ED200). Highly significant correlations were found between airway responsiveness and cutaneous responsiveness to antigen and other immunologic characteristics (e.g., IgE and histamine released from lung by inhaled antigen) in all dogs. In ragweed-sensitized dogs, there was an inverse correlation between immunologic responsiveness (reflected by the cutaneous response to antigen and histamine released from lung by inhaled antigen) and nonimmunologic responsiveness of airways (histamine ED200: r = 0.73, P less than 0.05 and r = 0.75, P less than 0.01, respectively). Antigen ED200 was also correlated with histamine release from lung after antigen inhalation (r = 0.74; P less than 0.01). We conclude that airway reactions to inhaled antigen in allergic dogs are dependent not only on immunologic factors but also on the degree of nonimmunologic airway responsiveness to histamine and that these factors are correlated inversely.

Ambulatory blood pressure characteristics in normotensive and treated hypertensive older people.

The objective of this study was to determine the normal values and characteristics of 24-h ambulatory blood pressure (ABP) and to describe the ABP level of treated hypertensive subjects in an older Finnish population. ABP was measured in 502 randomly selected subjects aged 64 years or over living in a Finnish municipality (mean age 70 years, range 64-87 years). A total of 211 subjects did not have blood pressure (BP) affecting medication. ABP measurements were taken every 30 min for 24 h, and the day- and night-time periods were diary-based. The results were that in untreated subjects, the average office BP was 134/82 +/- 16/9 (s.d.) mm Hg for men and 140/81 +/- 18/8 mm Hg for women. The 24-h average BP was 120/75 +/- 14/8 mm Hg (95th percentile upper limit 145/93 mm Hg) for men and 125/75 +/- 15/7 (95th = 154/89 mm Hg) for women. The daytime averages were 127/78 +/- 12/7 mm Hg (95th = 154/99 mm Hg) and 131/78 +/- 15/7 mm Hg (95th = 158/91 mm Hg) for men and women, respectively. The ABP daytime value of 130/83 mm Hg corresponded best to the office BP value of 140/90 mm Hg. All BP values were significantly higher in the treated hypertensive group compared to the normotensive group. Night-time BP was markedly lower than daytime BP, and no difference in circadian variability was found between the normotensive and hypertensive subjects. Both office and ambulatory BPs were significantly higher in women than in men. This study provides sex-specific normal values for ABP in a 64 to 87-year-old age group. The normal values of ABP were markedly lower than the office BP values. Hypertensives, even when treated, tended to have elevated values.