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Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants.

Ambient air pollution has been associated with restricted fetal growth, which is linked with adverse respiratory health in childhood. We assessed the effect of maternal exposure to low concentrations of ambient air pollution on birthweight.

The association between physical activity, potential intermediate biomarkers and lung cancer risk was investigated in a study of 230 cases and 648 controls nested within the European Prospective Investigation of Cancer and Nutrition. Data on white blood cell aromatic-DNA adducts by 32P-post-labelling and glutathione (GSH) in red blood cells were available from a subset of cases and controls. Compared with the first quartile, the fourth quartile of recreational physical activity was associated with a lower lung cancer risk (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35–0.90), higher GSH levels (1.87 μmol GSH g−1haemoglobin, p 0.04) but not with the presence of high levels of adducts (OR 1.05, 95% CI 0.38–2.86). Despite being associated with recreational physical activity, in these small-scale pilot analyses GSH levels were not associated with lung cancer risk (OR 0.95, 95% CI 0.84–1.07 per unit increase in GSH levels). Household and occupational activity was not associated with lung cancer risk or biomarker levels.

GPX1 encoding the enzyme glutathione peroxidase 1 (GPX1) and hOGG1 encoding the 8-oxoguanine glycosylase 1 (OGG1) may counteract oxidative stress and resulting DNA damage associated with lifestyle-related exposures. We examined whether the polymorphisms GPX1 Pro198Leu and OGG1 Ser326Cys or low erythrocyte GPX enzyme activity in pre-diagnostic blood samples are associated with colorectal cancer risk, and assessed possible interactions between the polymorphisms or enzyme activity and various lifestyle factors in relation to colorectal cancer risk. Additionally, we studied whether the GPX1 Pro198Leu polymorphism and several lifestyle factors predict GPX activity in erythrocytes. The present study was nested within the prospective “Diet, Cancer and Health” study of 57,053 Danes including 375 colorectal cancer cases and a comparison group of 779 individuals matched on gender. Biomaterial was sampled and information on lifestyle factors was obtained from questionnaires filled in at enrolment in 1993–1997. GPX1 Pro198Leu, hOGG1 Ser326Cys and erythrocyte GPX enzyme activity were not associated with risk of colorectal cancer. We observed a higher risk associated with alcohol consumption and smoking among homozygous GPX1198Leu carriers, with incidence rate ratios for colorectal cancer of 1.45 (95% CI: 1.17–1.81, P=0.02) per 10g alcohol intake per day and 2.56 (95% CI: 0.99–6.61, P=0.02) among ever smokers compared with never smokers at enrolment. Erythrocyte GPX activity was influenced by the GPX1 Pro198Leu genotype, gender, smoking intensity, and intake of fruits and vegetables. Our results indicate that lifestyle-related oxidative stress may be a risk factor for colorectal cancer among subjects with a lowered defence.

Oxidative DNA damage is believed to be implicated in lung carcinogenesis. 8-OxodG is a mutagenic and abundant oxidative modification induced in DNA. OGG1, NEIL1 and MUTYH are all involved in the repair and prevention of 8-oxodG-derived mutations and may be up-regulated by oxidative stress. The polymorphism OGG1 Ser326Cys has in some studies been associated with risk of lung cancer.

Lung cancer risk was investigated in relation to single nucleotide polymorphisms in genes involved in the inflammatory response. The aim was to see if polymorphisms modifying the inflammatory response are associated with risk of lung cancer and if there were interactions between the same polymorphism and factors, which modify an inflammatory response, such as smoking status, duration, and intensity, and use of NSAID. The functional SNPs IL-1B T-31C, IL6 G-174C, IL8 T-251A, IL10 C-592T, COX2 C8473T, COX2 A-1195G and PPARγ2 Pro12Ala were included.

Oxidative damage to DNA may be important in carcinogenesis and a possible risk factor for lung cancer. The urinary excretion of products of damaged nucleotides in cellular pools or in DNA may be important biomarkers of exposure to relevant carcinogens reflecting the rate of damage in steady state and may predict cancer risk. Oxidation of guanine in DNA or the nucleotide pool may give rise to 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) for urinary excretion. Oxoguanine glycosylase (OGG1) is the base excision enzyme repairing 8-oxodG in DNA by release of 8-oxoguanine. In a nested case–cohort design we examined associations between urinary excretion of 8-oxodG and risk of lung cancer as well as potential interaction with the OGG1 Ser326Cys polymorphism in a population-based cohort of 25 717 men and 27 972 women aged 50–64 years with 3–7 years follow-up. We included 260 cases with lung cancer and a sub-cohort of 263 individuals matched on sex, age and smoking duration for comparison. Urine collected at entry was analysed for 8-oxodG by HPLC with electrochemical detection. The excretion of 8-oxodG was higher in current smokers, whereas OGG1 genotype had no effect. Overall the incidence rate ratio (IRR) (95% confidence interval) of lung cancer was 0.99 (0.80–1.22) per doubling of 8-oxodG excretion and there was no interaction with OGG1 genotype. However, among never-smokers (eight cases and eight sub-cohort members) the IRR was 11.8 (1.21–115) per doubling of 8-oxodG excretion. The association between 8-oxodG excretion and lung cancer risk among never-smokers suggests that oxidative damage to DNA nucleotides is important in this group.

Environmental carcinogens contained in air pollution, such as polycyclic aromatic hydrocarbons, aromatic amines or N-nitroso compounds, predominantly form DNA adducts but can also generate interstrand cross-links and reactive oxygen species. If unrepaired, such lesions increase the risk of somatic mutations and cancer. Our study investigated the relationships between 22 polymorphisms (and their haplotypes) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases (bladder cancer, 131; lung cancer, 134; oral–pharyngeal cancer, 41; laryngeal cancer, 47; leukaemia, 179; death from emphysema and chronic obstructive pulmonary disease, 84). The design was a case–control study nested within a prospective investigation. Among the many comparisons, few polymorphisms were associated with the diseases at the univariate analysis: XRCC1-399 Gln/Gln variant homozygotes [odds ratios (OR) = 2.20, 95% confidence intervals (CI) = 1.16–4.17] and XRCC3-241 Met/Met homozygotes (OR = 0.51, 95% CI = 0.27–0.96) and leukaemia. The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1-399Gln/Gln in lung cancer (OR = 0.22, 95% CI = 0.05–0.98), and confirmed an opposite effect (OR = 2.47, 95% CI = 1.02–6.02) in the leukaemia group. Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia (OR = 1.28, 95% CI = 1.02–1.61), bladder cancer (OR = 1.38, 95% CI = 1.06–1.79) and possibly other cancer risks. Further investigations of the combined effects of polymorphisms within these DNA repair genes, smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process.

Breast cancer may be related to oxidative stress. Breast cancer patients have been reported to have lower antioxidant enzyme activity than healthy controls and the polymorphism GPX1 Pro198Leu has been associated with risk of lung and breast cancer. The purpose of the present nested case-control study was to determine whether GPX1 Pro198Leu and glutathione peroxidase (GPX) activity in prospectively collected blood samples are associated with breast cancer risk among postmenopausal women and whether GPX activity levels are associated with other known breast cancer risk factors. We matched 377 female breast cancer cases with 377 controls all nested within the prospective ‘Diet, Cancer and Health’ study of 57 000 Danes. Carriers of the variant T-allele of GPX1 Pro198Leu were at 1.43-fold higher risk of breast cancer compared with non-carriers (95% CI = 1.07–1.92). Pre-diagnostic GPX activity tended to be lower in cases compared with controls. GPX activity was positively correlated with intake of alcohol (P < 0.0001) and the catalytic activity was lowered 5% for each additional copy of the variant T-allele (P = 0.0003). Alcohol intake was correlated with increased GPX activity for the C-allele but not for the T-allele. Results from this prospective study suggest that the GPX1 Pro198Leu-associated lowered GPX activity is associated with higher breast cancer risk among Danish women.

Low DNA-repair capacity has been associated with increased risk of several types of cancer. mRNA levels of the nucleotide excision repair genes ERCC1 and XPD have been shown to correlate with the DNA-repair capacity. Likewise, mRNA levels of several DNA-repair genes including ERCC1 have been shown to be lower in lymphocytes from patients with lung cancer and head and neck cancer compared with healthy persons. In these studies, the low DNA-repair gene expression levels could be either a risk factor for disease or a consequence of the same.

Epidemiological studies have found negative associations between human health and particulate matter in urban air. In most studies outdoor monitoring of urban background has been used to assess exposure. In a field study, personal exposure as well as bedroom, front door and background concentrations of PM2.5, black smoke (BS), and nitrogen dioxide (NO2) were measured during 2-day periods in 30 subjects (20–33 years old) living and studying in central parts of Copenhagen. The measurements were repeated in the four seasons. Information on indoor exposure sources such as environmental tobacco smoke (ETS) and burning of candles was collected by questionnaires. The personal exposure, the bedroom concentration and the front door concentration was set as outcome variable in separate models and analysed by mixed effect model regression methodology, regarding subject levels as a random factor. Seasons were defined as a dichotomised grouping of outdoor temperature (above and below 8°C). For NO2there was a significant association between personal exposure and both the bedroom, the front door and the background concentrations, whereas for PM2.5and BS only the bedroom and the front door concentrations, and not the background concentration, were significantly associated to the personal exposure. The bedroom concentration was the strongest predictor of all three pollution measurements. The association between the bedroom and front door concentrations was significant for all three measurements, and the association between the front door and the background concentrations was significant for PM2.5and NO2, but not for BS, indicating greater spatial variation for BS than for PM2.5and NO2. For NO2, the relationship between the personal exposure and the front door concentration was dependent upon the “season”, with a stronger association in the warm season compared with the cold season, and for PM2.5and BS the same tendency was seen. Time exposed to burning of candles was a significant predictor of personal PM2.5, BS and NO2exposure, and time exposed to ETS only associated with personal PM2.5exposure. These findings imply that the personal exposure to PM2.5, BS and NO2depends on many factors besides the outdoor levels, and that information on, for example, time of season or outdoor temperature and residence exposure, could improve the accuracy of the personal exposure estimation.Journal of Exposure Analysis and Environmental Epidemiology (2005) 15, 413–422. doi:10.1038/sj.jea.7500419; published online 26 January 2005

Lung cancer is the most common fatal cancer among Danish men, and the incidence rate is increasing among women. In a case-cohort study, we have investigated the occurrence of lung cancer in relation to a high-risk haplotype, previously identified for breast cancer among post-menopausal women, and in relation to the closely linked polymorphisms XPD Asp312Asn and Lys751Gln. Among 54,220 members of a Danish prospective cohort study aged 50-64 at entry, 265 lung cancer cases were identified and a sub-cohort comprising 272 individuals was used for comparison. Among women in the 50-55 year age interval, homozygous carriers of the high-risk haplotype were at increased risk of lung cancer ( RR =7.02 , 95% CI =1.88 -26.18). In the 56-60 year and 61-70 year age intervals, no associations were observed. Among men, no statistically significant associations were found in any age interval. Female homozygous carriers of the variant allele of XPD Lys751Gln were at significantly increased risk of lung cancer in the two younger age-intervals (50-55 years: RR =5.60 , 95% CI =1.18 -26.45, 56-60 years: RR =10.60 , 95% CI =1.50 -75.64). Among men, carriers of the variant allele of XPD Lys751Gln had a non-significantly increased risk of lung cancer in the youngest age interval ( RR =6.38 , 95% CI =0.74 -54.90). When the polymorphisms in XPD Asp312Asn and Lys751Gln were mutually adjusted, XPD Asp312Asn was not associated with increased risk of cancer. We found no interaction between genotypes and duration of smoking. In conclusion, two regions of chromosome 19q13.2-3 seem to be associated with risk of lung cancer.

This study examines blood pressure (BP) and independent factors related to BP in the acute phase of stroke. The study is part of the community-based Copenhagen Stroke Study. In a multivariate regression model we analyzed the impact of clinical and medical factors on admission BP. BP declined with increasing time from stroke onset with a total of 8/4 mm Hg. Independent factors related to diastolic BP were ischemic heart disease (–3.9 mm Hg), male gender (2.2 mm Hg), known hypertension prior to stroke (8.6 mm Hg), and primary hemorrhage (9.7 mm Hg). Independent factors related to systolic BP were age (3.6 mm Hg/10-year increase), atrial fibrillation (–7.2 mm Hg), ischemic heart disease (–6.0 mm Hg), intracerebral hemorrhage (13.3 mm Hg), and known hypertension prior to stroke (16.3 mm Hg). No independent relations were seen between BP and diabetes, claudication, previous stroke, smoking, daily alcohol consumption, initial stroke severity and lesion size. The increase in BP in the acute phase of stroke is a uniform response to the ischemic event per se. BP is not related to stroke severity. Several factors are independently related to the BP level in acute stroke. The clinical significance of this is yet to be tested, but these factors may contribute to the seemingly complex relation between BP and outcome.

In the Copenhagen Stroke Study, we evaluated the combined impact on stroke outcome of potentially treatable factors such as acute body temperature, blood glucose, and stroke in progression. The patients were stratified into two groups: (1) patients with ‘good’ prognostic parameters (body temperature on admission ≤37.0°C andplasma glucose on admission ≤6.5 mmol/l andwho did not develop stroke in progression) and (2) patients with correspondingly ‘poor’ prognostic parameters. A poor outcome was observed in 4% of the patients with good prognostic parameters versus in 49% of the patients with poor prognostic parameters (p < 0.01). In the multivariate analysis which also included stroke severity, blood glucose contributed significantly to poor outcome with an odds ratio (OR) of 1.2/1.0 mmol/l increase, body temperature with an OR of 2.2/1°C increase, and stroke in progression with an OR of 2.9. However, the combined effect of all three factors was more than additive with an OR of 10.0 (95% CI 1.5–56; p < 0.01). We have shown that in human stroke a strong and more than additive association exists between potentially reversible parameters and outcome. Intervention trials can prove whether these marked relations are causal.

Air pollution may have severe long-term as well as short-term health effects. The determination of possible links between pollution levels and impact on human health is, however, not a straightforward task. A key problem is the assessment of human exposure to ambient pollution levels. In later years, the possible role of particulate pollution as a health hazard has drawn major attention and is, therefore, the subject of research projects in many countries including Denmark. The present paper gives a review of recent and ongoing/planned Danish air pollution exposure studies. Furthermore, key results from Danish studies of ultrafine particles from urban traffic are outlined. The exposure studies show that air pollution models may be strong tools in impact assessment studies, especially when used in combination with personal exposure monitoring and application of biomarkers. Personal exposure measurements in Copenhagen indicate that indoor pollution levels may be very important for the personal exposure to fine fraction particles (PM2.5). Measurements with a differential mobility analyzer (DMA) in Danish urban areas show that number concentrations of ultrafine particles (&lt;100 nm) in busy streets are strongly correlated with classic traffic pollutants such as nitrogen oxides and carbon monoxide. The number concentrations in urban Danish streets have decreased considerably between two campaigns in 1999 and 2000, apparently as a result of reductions in sulfur contents in Danish diesel fuels that took place in July 1999.

This article examines the findings regarding the neurologic and functional recovery of patients from the Copenhagen Stroke Study. This article presents initial neurologic impairment and disability pattern and speed of recovery, final impairment and disability after completed rehabilitation, and prognostic factors in these stroke patients.

Leukocytosis is a common finding in the acute phase of stroke. A detrimental effect of leukocytosis on stroke outcome has been suggested, and trials aiming at reducing the leukocyte response in acute stroke are currently being conducted. However, the influence of leukocytosis on stroke outcome has not been clarified. Methods: In 763 unselected patients with stroke admitted within 24 hours from onset, we prospectively studied the relation between leukocyte count and outcome considering relevant confounders and predictors such as initial stroke severity, risk factor profile, body temperature, and infection. Results: Univariate, leukocyte count on admission was significantly related to initial stroke severity (assessed by the Scandinavian Stroke Scale), lesion size on computed tomography, mortality, and outcome in survivors. However, multivariate regression analysis revealed that only the relation between leukocytosis and initial stroke severity was independent of other factors, whereas the relations found univariately between leukocytosis and lesion size, mortality, and outcome in survivors disappeared when initial stroke severity was included in the multivariate model. Conclusion: Leukocytosis on admission was related to initial stroke severity but not to outcome. Leukocyte count on admission seems merely to reflect initial stroke severity and is most likely a stress response with no independent influence on outcome. Our study may suggest that attempts aimed merely at lowering leukocyte count in peripheral circulating blood in the acute phase of stroke cannot be expected to improve outcome.

OBJECTIVE: To determine the incidence, time course, and clinical importance of spontaneous reperfusion of cerebral infarcts in patients with acute stroke. DESIGN: Prospective, community based. SETTING: Department of Neurology, Bispebjerg Hospital, Copenhagen, Denmark. PATIENTS: Included in the incidence and time course study were 354 unselected patients with acute ischemic stroke. Clinical outcome was studied in a subgroup of 36 patients admitted on the day of stroke onset and in whom it was known whether spontaneous reperfusion occurred within the first week after stroke onset. MEASUREMENTS: Computed tomography and single photon emission computed tomography, with technetium Tc 99m exametazime used as a flow tracer. The Scandinavian Stroke Scale neurologic score was determined on admission, 1 and 2 weeks after stroke, and at discharge. RESULTS: The incidence of spontaneous reperfusion was 77% in patients with cortical infarcts. The frequency of reperfusion increased rapidly from zero at the time of onset to 60% on day 7 after stroke, reaching a maximum on day 14, at which time 77% showed reperfusion. Marked clinical improvement was observed in patients with spontaneous reperfusion (P=.001), while no improvement occurred in patients without reperfusion. Reperfusion was not observed in subcortical infarcts. CONCLUSIONS: The rate of spontaneous reperfusion increases gradually with time and occurs within the first 2 weeks after stroke onset in approximately four of five patients with cortical infarcts. Spontaneous reperfusion seemed to improve clinical outcome.

Many aspects of stroke-related headache, such as its incidence, pathophysiology, risk factors, and relation to stroke severity and outcome, are uncertain.

Summary

The aims of the study were to evaluate if the front-door concentrations of benzene, toluene, and xylenes can be used to classify the personal exposures of Danish children and to identify factors that affect their personal exposure. Average concentrations were measured over 1 week with diffusive samplers, and the personal exposures of 98 children and the concentrations outside the front doors of their homes were measured simultaneously. Time and activity patterns were noted in diaries. The front-door concentrations were significantly higher in Copenhagen than in rural areas (allP< 0.0001), but the personal exposures were only slightly higher. Even though the personal exposures were highly significantly associated with front-door concentrations in urban areas (allP< 0.004), use of the residential front-door concentration as an exposure surrogate would imply misclassification, as it cannot be used for rural children. Multiple regression analyses brought to light several factors that affect the exposure of children independently, including front-door concentration, riding in cars, and activities involving potential exposure to gasoline vapors like motocross, moped driving, and refueling of cars.

This study was undertaken to elucidate whether and how age influences stroke outcome.

We compared stroke severity, risk factors, and prognosis in patients with recurrent versus first-ever stroke. In the Copenhagen Stroke Study, we prospectively studied 1,138 unselected patients with acute stroke. Stroke was recurrent in 265 (23) despite most of these patients being given prophylactic treatment prior to recurrence. Only 12 of patients with atrial fibrillation were receiving anticoagulant treatment prior to recurrence. In multivariate analysis, recurrence was more frequently associated with a history of TIA, atrial fibrillation, male gender, and hypertension, but not with age, daily alcohol consumption, smoking, diabetes, ischemic heart disease, serum cholesterol, or hematocrit. Mortality was almost doubled compared with patients with a first-ever stroke. In survivors, however, both neurologic and functional outcomes and the speed of recovery were, in general, similar in the two groups. Despite similar neurologic impairments, patients with recurrence contralateral to their first stroke had markedly more severe functional disability after completed rehabilitation than patients with ipsilateral recurrence, implying that the ability to compensate functionally is decreased in patients with contralateral recurrence. Our findings emphasize the importance of consistent anticoagulant treatment for stroke patients with atrial fibrillation and close blood pressure control in stroke patients with hypertension. Other prophylactic measures are needed in patients in whom ASA fails to prevent recurrence. Patients with recurrent stroke have a markedly higher mortality than patients with a first-ever stroke, but those who survive recover as well and as fast as patients with a first-ever stroke. However, if recurrence is contralateral to the first stroke, functional recovery is poorer.

A recent study suggests that a high plasma level of tissue plasminogen activator (t-PA antigen) is a risk factor for stroke in men. Whether t-PA antigen is a risk factor for stroke in women is unknown. We measured plasma levels of t-PA antigen in 302 nonselected patients with acute ischemic stroke and in 138 healthy control subjects. In a subgroup of the patients, plasma t-PA antigen was remeasured 6 months after the stroke. Women with acute ischemic stroke (n=171) had median plasma t-PA antigen that was 39% higher than the healthy female control subjects (n=86): 10.3 (8.0 to 13.7) versus 7.4 (6.1 to 9.1) ng/mL (median [interquartile range]), P=.0001. At the reexamination of the patients after 6 months, plasma t-PA antigen was unchanged in the female patients. This suggests that the difference in plasma t-PA antigen between the female patients and the healthy control subjects did not result from an acute phase reaction. In a multivariate regression analysis, high t-PA antigen was an independent risk factor for stroke, and high plasma level of t-PA antigen was associated with severe stroke in women. The current data suggest that plasma t-PA antigen is elevated in women with ischemic stroke.

Orientation is an indicator of general intellectual function and is defined as the ability to report time, place, and personal data. Our knowledge of orientation in acute stroke is sparse. We examined the frequency of impaired orientation in acute stroke, its determinants, and recovery in 653 consecutive patients with acute stroke who were not unconscious and who were without severe aphasia. Prospective assessments of orientation and stroke severity were done by the Scandinavian Neurologic Stroke Scale at the time of acute admission and hereafter weekly until the end of rehabilitation. Impaired orientation was found in 23% of the patients on acute admission and in 12% of the survivors after completed rehabilitation. A stationary level of orientation was achieved by 80% of the patients within 2 weeks and by 95% within 6 weeks. A multiple linear regression analysis found neurological score (B = 0.027, SE(B) = 0.003), age (B = –0.013, SE(B) = 0.003), and comorbidity (B = –0.023, SE(B) = 0.078), but not sex, prior stroke, handedness, or side of stroke lesion to be significant independent determinants of orientation score on acute admission. Lesions involving the anterior and medial thalamus and/or any of the cerebral lobes were associated with impaired orientation. In conclusion, impaired orientation is frequent in acute stroke and the time-course of recovery is similar to what has been found in other neuropsychological impairments with the major part of recovery early after stroke onset.

The acute effect of opioid antagonists on volitional ethanol intake was studied in unselected Sprague‐Dawley rats using a two‐bottle, free‐choice model. The total daily intake of ethanol during saline treatment was 1.79 ± 0.4 g/kg/day (n= 136). The rats were deprived of fluids for the last 4 hr of the light period. Saline or drug was given intraperitoneally 20 to 30 min before the onset of dark, and the ethanol and water intakes were measured during the following hour. The ethanol intake during this hour was 0.75 ± 0.06 g/kg (n= 136). Naltrexone significantly reduced ethanol intake. There was also a signiflcant reduction in ethanol Intake following administration of ICI‐174,864. Naloxonazine and naloxone methiodide lacked effect. None of the treatments had any effect on the water or food intake. The resutts suggest that central bopioid receptors modulate volitional ethanol intake in the rat.

The gene coding for the filamentous hemagglutinin (FHA), one of the main factors involved in mediating adherence of Bordetella pertussis to ciliated host cells, was cloned in Escherichia coli, and the 3,500-base-pair nucleotide sequence encoding the amino-terminal region was determined. Molecular cloning, together with the characterization of recombinant FHA-related proteins produced in E. coli, revealed that the primary translation product is a protein of about 370 kilodaltons (kDa). The mature 220-kDa FHA polypeptide secreted by B. pertussis is most probably generated by proteolytic processing that eliminates a carboxy-terminal portion of about 150 kDa. The 1,087 amino-terminal residues of the predicted FHA sequence showed a number of remarkable features. Extensive homology to the Serratia marcescens and Proteus mirabilis hemolysin proteins was found between amino acids 91 and 205 of the FHA sequence, suggesting involvement of this FHA domain in host cell binding or secretion of FHA from B. pertussis. In addition, two regions containing repetitive amino acid sequences were identified. One region, extending from residues 382 to 664, was formed by six repeats, and a second, extending from residues 701 to 912, contained three repeats. The reactivities of several recombinant FHA-derived proteins with a panel of monoclonal antibodies identified at least four epitopes composing an immunoreactive domain present in the carboxy-terminal moiety of the mature FHA.

Medical treatment of acute stroke with tissue plasminogen activator (tPA) was recently approved in the United States, and neuroprotective agents are being developed. Should all patients with stroke, regardless of severity, receive such treatment? In the Copenhagen Stroke Study we studied the prognosis of stroke in 1,351 unselected patients from a well-defined catchment area treated in a community-based stroke unit from the time of acute admission to death or the end of rehabilitation. Outcome measures were mortality, discharge rates to the patients' own home or to a nursing home, length of hospital stay, and neurologic and functional outcomes. Prognosis was stratified according to initial stroke severity measured by the Scandinavian Neurological Stroke Scale (SSS) on admission. We estimated the effect of medical treatment on prognosis and health care utilization by assuming a medically induced decrease in initial stroke severity by 5 and 10 points in the initial SSS score. This mild and moderate decrease in initial stroke severity corresponded to an overall improvement in outcome and an overall cost reduction through shorter hospital stays. This was also true in patients with both mild and moderate stroke. However, in patients with severe stroke, survival increases expenses because of an increased discharge rate to a nursing home and an increase in the cost of acute care and rehabilitation. Future medical stroke trials should therefore focus on the effect and cost of treatment, especially in patients with severe stroke, and search for factors predictive of good clinical outcome in this group.

Anosognosia is a well-known symptom after stroke but its frequency following acute stroke is not known and knowledge of its impact on functional outcome is limited. This prospective study included 566 consecutive, unselected, acute stroke patients. Anoso gnosia was evaluated on acute admission using the test of Bisiach et al. (1986), stroke severity with the Scandinavian Neurological Stroke Scale (SNSS), and activities of daily living (ADLs) with the Barthel Index (BI). Multiple linear and logistic regres sion analyses were done to find the influence of anosognosia on the outcome of stroke per se. The frequency of anosognosia was 21% on acute admission. The lesion was located in the right hemisphere in 81% of the patients. Anosognosia was seen more frequently following cortical vs. subcortical lesions but showed no significant rela tionship to any of the four cortical lobes. The presence of anosognosia per se predicted 11.5 points less in discharge BI, increased the likelihood of death during the hospital stay by a factor of 4.4, and reduced the likelihood of discharge to independent living in survivors by 0.43. Anosognosia is common in acute stroke, has a profound influence on the prognosis, and indicates patients needing special encouragement and assistance with mobilization.

Specific neuropsychological symptoms like aphasia and neglect are well-known in stroke. General cognitive function in stroke patients has been given less attention. The Mini-Mental State Examination (MMSE) is widely used in different neurologic and psychiatric conditions. It has also been used in studies of depression with stroke and for validation of other instruments, but few studies have reported basic data con cerning MMSE in stroke. We assessed 541 unselected acute stroke patients prospec tively and consecutively with the MMSE. Its utility for functional prognosis was deter mined by multiple linear regression analyses of ADL function at discharge measured with the Barthel Index (BI), of length of rehabilitation, and by a logistic regression analysis of the rate of discharge to independent living. A considerable number of patients could not cooperate for the MMSE in the acute stage (42%, including uncon scious and aphasic patients). Reduced cognitive function was found to be common in stroke: a score below the cut-off level of 24 was found in 42%. General cognitive func tion per se had a slight influence on discharge ADL; a ten-point increase in MMSE score corresponded to a four-point increase (p = 0.0009) in BI outcome score. It had no influence on length of rehabilitation, but a ten-point increase in MMSE score increased the chance for discharge to independent living by a factor of 1.78 (95% CI 1.30 to 2.26). In spite of the limited number of stroke patients who can cooperate with the MMSE in the acute phase, a high incidence of reduced general cognitive func tion was found, and the level of general cognitive function was useful for prognosti cation and planning of rehabilitation. Key Words: Cerebrovascular disorders—Stroke— Mini-Mental State Examination—Intellectual function—Dementia—Rehabilitation.

We conducted this study to determine whether the presence of aphasia at the time of acute admission impedes functional improvement of stroke patients and if chronic aphasia aggravates the detrimental effects of stroke on daily life functioning. Six hun dred fifty consecutive stroke patients were examined at the time of admission to hos pital, at discharge after completed acute care and rehabilitation, and six months post- stroke followup. We used the aphasia subscale of the Scandinavian Neurologic Stroke Scale, the Barthel Index (BI), and the Frenchay Activity Index (FAI). Multiple lin ear and logistic regression analyses showed that initial aphasia had a small and clini cally irrelevant influence on functional improvement and it had no influence on dis charge to independent living when controlled for initial functional status, stroke severity, comorbidity, prior stroke, age, sex, and marital status. Similar analyses showed that chronic aphasia per se had no independent influence on either the BI score or the FAI six months post-stroke. Although aphasia is a significant handicap after stroke, it does not seem to affect functional independence after stroke, nor to be of impor tance for ADL and social functions as measured by BI and FAI in a more chronic stage following stroke.

In 12 non-icteric patients, changes in the pancreatic duct indicative of carcinoma were found during endoscopic retrograde cholangio-pancreatography (ERCP.). Percutaneous fine-needle biopsy was positive for cancer in six cases. Nine of the 12 patients were later proved to have carcinoma of the pancreas. There was one falsely negative biopsy but no false positives. In two cases no pancreatic cells were found in the smear. It seems that percutaneous fine-needle aspiration biopsy during ERCP is a feasible procedure and can be recommended in ductal changes indicative of carcinoma.

The purpose of the present study was to examine the effects of an insertion/deletion (ins/del) polymorphism in the promoter region of the plasminogen activator inhibitor-1 (PAI-1) gene on plasma PAI-1 antigen and activity levels and on stroke risk in the elderly. The ins/del genotype and PAI-1 antigen and activity plasma levels were determined in 177 patients with ischemic stroke (mean age, 75 years) and 93 healthy elderly subjects (mean age, 74 years). There was no difference in the frequencies of the ins and del alleles between stroke patients and healthy elderly subjects. The del/del genotype was associated with the highest plasma PAI-1 antigen levels in the healthy subjects: those with the ins/ins genotype had 36% lower plasma PAI-1 antigen levels than those with the del/del genotype (effect of genotype, P=0.3). In contrast, the ins/del genotype was not associated with plasma PAI-1 antigen and activity levels in 89 patients who had a stroke less than 10 days before blood sampling. However, an association of ins/del genotype with plasma PAI-1 activity levels could be demonstrated in 88 other patients more than 5 months after the stroke. This may suggest that PAI-1 metabolism is temporarily perturbed after a stroke. The present data suggest that an ins/del polymorphism in the PAI-1 promoter region affects plasma PAI-1 levels but has little or no effect on stroke risk in the elderly