Eleven-year trends of stroke in Turku,Finland

The Turku Stroke Register included stroke events at all ages during the years 1982-1992. The incidence of stroke declined in all age groups, even in the oldest one. An even steeper decline was observed in mortality from stroke. Ischemic strokes contributed most to the observed decline, while subarachnoid and intracerebral hemorrhage showed mainly flat trends. Flat trends were also observed for recurrent strokes. The absolute number of strokes remained stable through the study years, but the population above 75 years of age doubled. More than half of the strokes occurred in people aged 75 years or older, and three fourths of them occurred in women. The incidence and mortality rate of ischemic stroke declined steeply in all age groups. Due to an increase in elderly people in the background population, the total number of strokes remained stable. Thus, in spite of the observed declining trends in incidence, the need for stroke care has not diminished.     

Neurological diseases and accidental falls of the aged

OBJECTIVE: To assess the influence of central and peripheral neurological diseases on the incidence of accidental falls of the aged. DESIGN: 1. Case-control study with cross-section at two years and 2. prospective study in a follow-up up to seven years thereafter. SETTING: Sample of a population study including all 589 inhabitants older than 70 years in three rural communities. PARTICIPANTS: 44 subjects with recurrent falls during two years' follow-up and 41 age and sex matched controls. MEASURES: Neurological diseases and evaluation, other diseases, and incidence of falls during the seven years' follow-up after the cross-section. RESULTS: Compared with the controls the fallers had more often multiple vascular lesions of the brain, extrapyramidal symptoms and signs as well as lumbar nerve root lesions. In the follow-up, cerebrovascular disease, especially with multiple lesions and residual signs of pyramidal tract lesion, Parkinson's disease, rigidity and hypokinesia were associated with increases risk of falling. In multivariate analysis signs of pyramidal tract lesion, rigidity and prior falls were predictors of falls. An increase in the incidence of falls was also associated with vascular lesion of the cerebellum, cerebral white matter hypodensity and cortical atrophy visible on CT. CONCLUSIONS: High incidence of falls was associated with chronic central nervous system diseases. Lumbar root lesions were more common among the fallers but did not increase the incidence of falls in the follow-up.Neurological diseases and evaluation, other diseases, and incidence of falls during the seven years' follow-up after the cross-section.Compared with the controls the fallers had more often multiple vascular lesions of the brain, extrapyramidal symptoms and signs as well as lumbar nerve root lesions. In the follow-up, cerebrovascular disease, especially with multiple lesions and residual signs of pyramidal tract lesion, Parkinson's disease, rigidity and hypokinesia were associated with increased risk of falling. In multivariate analysis signs of pyramidal tract lesion, rigidity, and prior falls were predictors of falls. An increase in the incidence of falls was also associated with vascular lesion of the cerebellum, cerebral white matter hypodensity and cortical atrophy visible on CT.     

Mortality from obstructive lung diseases and exposure to polycyclic aromatic hydrocarbons among asphalt workers

Work in the asphalt industry has been associated with nonmalignant respiratory morbidity and mortality, but the evidence is not consistent. A historical cohort of asphalt workers included 58,862 men (911,209 person-years) first employed between 1913 and 1999 in companies applying and mixing asphalt in Denmark, Finland, France, Germany, Israel, the Netherlands, and Norway. The relations between mortality from nonmalignant respiratory diseases (including the obstructive lung diseases: chronic bronchitis, emphysema, and asthma) and specific chemical agents and mixtures were evaluated using a study-specific exposure matrix. Mortality from obstructive lung diseases was associated with the estimated cumulative and average exposures to polycyclic aromatic hydrocarbons and coal tar (p values of the test for linear trend = 0.06 and 0.01, respectively). The positive association between bitumen fume exposure and mortality from obstructive lung diseases was weak and not statistically significant; confounding by simultaneous exposure to coal tar could not be excluded. The authors lacked data on smoking and full occupational histories. In conclusion, exposures to polycyclic aromatic hydrocarbons, originating from coal tar and possibly from bitumen fume, may have contributed to mortality from obstructive lung diseases among asphalt workers, but confounding and bias cannot be ruled out as an explanation for the observed associations.     

Adenoviral gene transfer restores lysyl hydroxylase activity in type VI Ehlers-Danlos syndrome

Type VI Ehlers-Danlos syndrome is a disease characterized by disturbed lysine hydroxylation of collagen. The disease is caused by mutations in lysyl hydroxylase 1 gene and it affects several organs including the cardiovascular system, the joint and musculoskeletal system, and the skin. The skin of type VI Ehlers-Danlos syndrome patients is hyperelastic, scars easily, and heals slowly and poorly. We hypothesized that providing functional lysyl hydroxylase 1 gene to the fibroblasts in and around wounds in these patients would improve healing. In this study we tested the feasibility of transfer of the lysyl hydroxylase 1 gene into fibroblasts derived from rats and a type VI Ehlers-Danlos syndrome patient (in vitro) and into rat skin (in vivo). We first cloned human lysyl hydroxylase 1 cDNA into a recombinant adenoviral vector (Ad5RSV-LH). Transfection of human type VI Ehlers-Danlos syndrome fibroblasts (about 20% of normal lysyl hydroxylase 1 activity) with the vector increased lysyl hydroxylase 1 activity in these cells to near or greater levels than that of wild type, unaffected fibroblasts. The adenoviral vector successfully transfected rat fibroblasts producing both beta-galactosidase and lysyl hydroxylase 1 gene activity. We next expanded our studies to a rodent model. Intradermal injections of the vector to the abdominal skin of rats produced lysyl hydroxylase 1 mRNA and elevated lysyl hydroxylase 1 activity, in vivo. These data suggest the feasibility of gene replacement therapy to modify skin wound healing in type VI Ehlers-Danlos syndrome patients.     

Tumour response and radiation-induced lung injury in patients with recurrent small cell lung cancer treated with radiotherapy and concomitant interferon-alpha

The aim of this study was to determine whether either natural or recombinant interferon (IFN)-alpha can improve the response to radiotherapy (RT) in patients with small cell lung cancer (SCLC), and to assess the role of IFN in radiation-induced lung injury. All patients had previously participated in a randomised trial of chemotherapy alone or in combination with IFN-alpha in three arms (arm O: no IFN, arm I: natural IFN-alpha, arm II: recombinant IFN-alpha). Patients with locally progressive disease in the lungs following chemotherapy were treated with RT and they continued with their concomitant IFN-alpha. The RT dose was 50 Gy. Radiation-induced lung injury was assessed by lung function tests, computed tomography and bronchoalveolar lavage fluid (BALF) analysis which included cell findings, Interleukin (IL)-1 alpha/-1 beta expression by alveolar macrophages and surfactant components. Seventeen patients were entered in the study, 16 of whom were evaluable. Response rates in Arms O, I and II were 50, 67 and 50%, respectively. Median survival was 18.5, 7 and 23 months respectively, and 1-year survival was 67, 29 and 75% respectively. Long-term survival as assessed by 2- and 3-year survival rates was 29% in patients receiving natural IFN-alpha as compared to 17% in patients not receiving IFN (not statistically significant findings). Every patient had abnormal results when assessed for radiation-induced lung injury. No statistically significant difference was found in toxicity between the treatment arms. A high surfactant protein (SP)-A/phospholipid ratio and a high level of SP-A in BALF before RT was associated with a high degree of radiation-induced lung injury measured by lung function tests and computed tomography in all arms of the study. Thus, we could not show that the combination of IFN-alpha and RT induced more lung toxicity than RT alone as we did in our previous study. The role of high SP-A/phospholipid ratios and high SP-A levels in BALF before RT as predictors of the development of lung injury after RT needs to be determined in the future.     

The 5-HT(2) receptor activation enhances impulsive responding without increasing motor activity in rats

The effects of 5-HT(2) receptor ligands on the performance of rats were investigated using a 5-choice serial reaction time (5-CSRT) task. Systemic administration of DOI (0.03 to 0.3 mg/kg subcutaneously [SC]), a 5-HT(2) receptor agonist, did not impair choice accuracy of well-performing rats under either baseline conditions or more demanding conditions of the task, in which the stimulus duration or intensity were reduced or the intertrial interval (ITI) was decreased. DOI (0.1 mg/kg or 0.15 mg/kg) increased premature responding (the probability of intertrial interval hole pokes) in all testing conditions, except under conditions of a short ITI when the rats did not make any hole responses. Ketanserin (0.1 to 0.3 mg/kg SC), a 5-HT(2A) receptor antagonist, had no marked effect on performance. When combined with ketanserin (0.2 mg/kg SC), however, DOI (0.1 mg/kg) did not increase premature responding. The lowest doses of DOI (0.05 and 0.1 mg/kg) that increase premature responding had no effect on open-field performance. Further, the effects of systemically administered DOI were not reproduced by bilateral administration of DOI into the anterior cingulate cortex. These data indicate that excessive activation of 5-HT(2A/2C) receptors interferes with response control rather than visual attention. Furthermore, the DOI-induced enhancement of impulsive responses are not due to locomotor hyperactivity, and the anterior cingulate cortex is not the primary site of action for this enhancement of premature responding.     

Phytosterols act as endocrine and metabolic disruptors in the European polecat (Mustela putorius).

Phytosterols or plant sterols (PS) are consumed as natural remedies and margarines by the general population in developed countries to lower elevated serum cholesterol levels. They are also present in high concentrations in pulp mill effluents. The aim of the study was to screen the endocrine and metabolic parameters of the European polecat (Mustela putorius) for the effects of PS. The results showed an increase in the plasma estradiol and TH levels with no effects on the hypophyseal regulatory hormones. The plasma ghrelin levels decreased. PS also affected intermediary metabolism. The liver glycogen content increased as did the kidney glucose-6-phosphatase activity. The liver lipase esterase activity, on the other hand, decreased due to PS. In serum lipids the total cholesterol did not change, but the low-density lipoprotein levels increased and the high-density lipoprotein-cholesterol ratio decreased. PS had widespread previously unreported effects on the physiology of the polecat. The multiple effects indicate the need of a thorough risk assessment of the effects and interactions of PS.