Long-term outcome after intravenous thrombolysis of basilar artery occlusion

Context  Basilar artery occlusion (BAO) is an infrequent disease with high morbidity and mortality. Intra-arterial thrombolysis is advocated for treatment but is limited to use at specialized centers. Objective  To evaluate outcomes for patients with BAO treated with intravenous thrombolytic therapy. Design, Setting, and Participants  During 1995 to 2003, 50 consecutive patients with angiographically proven BAO were treated according to an institutional therapy protocol based on intravenous thrombolysis with recombinant tissue plasminogen activator (alteplase). Patients were treated at an urban university teaching hospital receiving all patients with ischemic stroke who were considered for thrombolysis in a catchment area of 1.5 million inhabitants in Helsinki, Finland. Intervention  Intravenous administration of alteplase (0.9 mg/kg) during a 1-hour infusion. Main Outcome Measures  Basilar artery recanalization determined by magnetic resonance angiography and clinical outcomes at 3 months and at 1 year or longer determined by modified Rankin Scale and Barthel Index scores. Results  Recanalization was studied in 43 patients and verified in 26 (52%) of all patients. By 3 months, 20 patients (40%) had died while 11 had good outcomes (modified Rankin Scale score, 0-2); 12 (24%) reached independence in activities of daily living (Barthel Index score, 95-100), and 6 (16%) were severely disabled (Barthel Index score, 0-50). In the long term (median follow-up 2.8 years), 15 patients (30%) reached good outcomes (modified Rankin Scale score, 0-2) while 23 (46%) died. Conclusions  Intravenous administration of alteplase for patients with BAO appears to be associated with rates of survival, recanalization, and independent functional outcome comparable with those reported with endovascular approaches. These data suggest that a randomized trial is needed to compare these approaches for treatment of BAO.      

Effects of coronary artery bypass related conduction defects: a 10-year follow-up study

OBJECTIVES: The aim of this study is to determine the long-term prognostic significance of new permanent conduction defects (CDs) related to coronary artery bypass grafting (CABG), and to assess predisposing factors for increased mortality after CABG. DESIGN: One hundred and eighty patients who underwent an elective CABG without any evidence of preoperative CDs were followed on average for 9.6 years. Long-term outcome was observed in terms of Kaplan-Meier survival analysis, and several potential pre-, intra- and postoperative factors for increased mortality were analysed using the Cox regression model. RESULTS: Sixty-three (35.0%) of the patients developed a new CD (CD+ group) before hospital discharge. Early (<30 days) and long-term (>30 days) survival rates were 98.9 and 86.1%, respectively. The long-term survival in CD+ patients was significantly lower that in CD- patients (77.8% vs 90.4%, p = 0.02). However, cardiac survival in CD+ patients and CD- patients did not differ from each other (88.9% and 92.3%, respectively, p=NS). Five independent predictors for increased all cause mortality were identified: diabetes (relative risk ratio 5.99 [2.43-14.78]), number of distal anastomoses (3.20 [1.30-7.88]), a new intraoperative conduction defect (2.83 [95% CI 1.24-6.49]), preoperative ejection fraction <50% (2.60 [1.08-6.27]) and perfusion time (1.02 [1.01-1.03]). CONCLUSIONS: Excellent survival rates can be obtained 10 years after CABG. CDs were not related to increased cardiac mortality. The appearance of preoperative diabetes, intraoperative perfusion time, number of distal anastomoses performed, CABG derived permanent CDs and low preoperative ejection fraction are associated with higher all cause mortality during the long-term follow-up.     

Working conditions and health behaviours among employed women and men: the Helsinki Health Study

BACKGROUND: Working conditions influence health, but previous studies on the associations between work-related factors and health behaviours are scarce. The aim of this study was to analyse whether unfavourable working conditions are associated with diet, physical activity, alcohol consumption, and smoking. METHODS: The data derive from postal questionnaires collected in 2000-2001 from 40- to 60-year-old employees of the City of Helsinki (n=6243, response rate: 68%). Logistic regression analysis was used to examine health behaviours as outcomes. Job demands and job control, physically and mentally strenuous work, work fatigue, working overtime and satisfaction with work-home interface were independent variables, adjusted for age, education, occupational social class and marital status. RESULTS: Most of the examined associations between working conditions and health behaviours were not statistically significant. Among women, mentally strenuous work and high job control were associated with a healthy diet. Work fatigue was associated with physical inactivity, whereas physically strenuous work and satisfaction with work-home interface were more often reported by physically active women. Work fatigue was associated with high drinking among men. Low job strain was reported by nonsmoking women, whereas working overtime was associated with nonsmoking among men. CONCLUSIONS: Working conditions were only weakly associated with health behaviours, and the associations varied for different health behaviours.     

Cerebral palsy is characterized by protein mediators in cord serum

Cerebral palsy (CP) is a major neurodevelopmental disability in childhood. An association between intrauterine infection and CP has been reported. We examined the relationship between inflammatory mediators in cord serum and CP in term and preterm children. Regional multicenter study was conducted on 19 CP children and 19 gestation-matched paired controls. CP children (n = 27) were further compared with controls of similar gestation at birth (n = 25). Serum levels of 78 protein mediators were analyzed. Eleven analytes correlated with the length of gestation both in cases and controls. In paired analysis, B-lymphocyte chemoattractant, ciliary neurotrophic factor, epidermal growth factor, interleukin (IL)-5, IL-12, IL-13, IL-15, macrophage migration inhibitory factor, monocyte chemoattractant protein-3, monokine induced by interferon gamma, and tumor necrosis factor-related apoptosis-inducing ligand were higher in children with CP (p < or = 0.05). Preterm infants with CP showed higher epidermal growth factor and lower levels of granulocyte-macrophage colony-stimulating factor, IL-2, macrophage-derived chemokine, and pulmonary and activation-regulated chemokine than their paired controls. Inflammatory mediators and growth factors serve as a footprint of the fetal response to an insult manifesting after birth as a permanent brain damage. The cytokine patterns at birth differ between premature and term infants who develop CP.     

Interaction of gaze direction and facial expressions processing: ERP study

Event related potentials (ERPs) were recorded from 11 subjects watching photographs of angry and happy faces with different gaze directions. ERPs to right averted gaze differed from those to straight and left averted gaze at 85 and 460 ms whereas ERPs to happy and angry expressions differed at 115, 330 and 380 ms. We suggest that short-latency effects, maximal over occipital cortex, reflect the involvement of visual cortex in the early analysis of socially-relevant stimuli. Interaction of gaze and expressions was reflected in ERPs at 270 - 450 ms. We conclude that gaze and emotional expressions are analyzed in parallel at the early stages of visual processing. The interaction of these two processing streams starts no earlier than at 270 ms.     

Kainate down-regulates a subset of GABA<Subscript>A</Subscript> receptor subunits expressed in cultured mouse cerebellar granule cells

The effect of kainate, an agonist selective for ionotropic AMPA/kainate type of glutamate receptors, on GABAA receptor subunit expression in cultured mouse cerebellar granule cells was studied using quantitative RT-PCR, ligand binding and electrophysiology. Chronic kainate treatment, without producing excitotoxicity, resulted in preferential, dose- and time-dependent down-regulation of alpha1, alpha6 and beta2 subunit mRNA expression, the expression of beta3, gamma2 and delta subunit mRNAs being less affected. The down-regulation was reversed by DNQX, an AMPA/kainate-selective glutamate receptor antagonist. A 14-day kainate treatment resulted in 46% decrease of total [3H]Ro 15-4513 binding to the benzodiazepine sites. Diazepam-insensitive [3H]Ro 15-4513 binding was decreased by 89% in accordance with very low amount of alpha6 subunit mRNA present. Diazepam-sensitive [3H]Ro 154513 binding was decreased only by 40%, contrasting >90% decrease in alpha1 subunit mRNA expression. However, this was consistent with lower potentiation of GABA-evoked currents in kainate-treated than control cells by the alpha1-selective benzodiazepine site ligand zolpidem, suggesting compensatory expression of alpha5 (and/or alpha2 or alpha3) subunits producing diazepam-sensitive but zolpidem-insensitive receptor subtypes. In conclusion, chronic kainate treatment of cerebellar granule cells selectively down-regulates oil, alpha6 and beta2 subunits resulting in altered GABAA receptor pharmacology.     

Progression of brain damage after status epilepticus and its association with epileptogenesis: a quantitative MRI study in a rat model of temporal lobe epilepsy

PURPOSE: This study examined the hypothesis that neurodegeneration continues after status epilepticus (SE) ends and that the severity of damage at the early phase of the epileptogenic process predicts the outcome of epilepsy in a long-term follow-up. METHODS: SE was induced in rats by electrical stimulation of the amygdala, and the progression of structural alterations was monitored with multiparametric magnetic resonance imaging (MRI). Absolute T2, T1rho, and diffusion (Dav) images were acquired from amygdala, piriform cortex, thalamus, and hippocampus for < or = 4.5 months after SE. Frequency and type of spontaneous seizures were monitored with video-electroencephalography recordings. Histologic damage was assessed from Nissl, Timm, and Fluoro-Jade B preparations at 8 months. RESULTS: At the acute phase (2 days after SE induction), quantitative MRI revealed increased T2, T1rho, and Dav values in the primary focal area (amygdala), reflecting disturbed water homeostasis and possible early structural damage. Pathologic T2 and T1rho were observed in mono- or polysynaptically connected regions, including the piriform cortex, midline thalamus, and hippocampus. The majority of acute MRI abnormalities were reversed by 9 days after SE. In later time points (> 20 days after induction), both the T1rho and diffusion MRI revealed secondarily affected areas, most predominantly in the amygdala and hippocampus. At this time, animals began to have spontaneous seizures. The initial pathology revealed by MRI had a low predictive value for the subsequent severity of epilepsy and tissue damage. CONCLUSIONS: The results demonstrate progressive neurodegeneration after SE in the amygdala and the hippocampus and stress the need for continued administration of neuroprotectants in the treatment of SE even after electrographic seizure activity has ceased.     

Effects of short-term copper exposure on gill structure, metallothionein and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in rainbow trout (Oncorhynchus mykiss)

Rainbow trout (Oncorhynchus mykiss) were exposed to 1.65 microM of waterborne copper for 24 h. Fish were then transferred to metal-free water. Metallothionein mRNA induction in rainbow trout liver and gill tissue, hypoxia-inducible factor-1 (HIF-1alpha) accumulation in gill tissue and arithmetic mean thickness of gill epithelium (Har) were determined at 4 and 24h of exposure as well as 48 h after transfer to metal-free water. The arithmetic mean distance from water to blood was significantly elevated after both 4 and 24 h of exposure (Har was 4.67 and 4.66 microm, respectively in exposed fish, compared to 3.81 and 3.62 microm for the corresponding control fish). During the 48 h recovery Har returned towards the control values; the recovery value of 4.21 microm was significantly lower than values during exposures. There was also a significant increase in gill metallothionein mRNA levels after the 4 h exposure with MT/GAPDH ratio of 1.288 versus the control value of 0.988. In liver, metallothionein induction was not observed. HIF-1alpha protein showed an increased accumulation in gills after 4 h, with the HIF-1alpha/alpha-tubulin ratio of 0.562 being significantly higher than the 24 h exposure value of 0.232. These results suggest that exposure to copper for four hours causes hypoxia in the gill epithelium, which is adequate for the activation of HIF-1alpha.     

Characterization of the preferred orientation of delta-mannitol crystallites in tablets

The crystallographic texture, i.e. the preferred orientation of crystallites of delta-mannitol samples, has been experimentally determined by pole figure analysis. The pole figures were measured with an X-ray diffraction texture goniometer. It was found that already the uncompressed delta-mannitol powder sample was slightly texturized so that the (0 2 0) plane was parallel to the upper surface of the sample. The degree of preferred orientation was found to significantly increase when the powder was compressed to a tablet with the minimum (74MPa) compression pressure. Nevertheless, the direction of the texture remained parallel to the tablet surface. Maximum compression (740MPa) did not increase the degree of preferred orientation further. The compression time (0 or 60s) was not found to noticeably affect the strength or direction of the texture. The extent of the texture inside the tablet was determined with a tablet surface grinding experiment. The degree of preferred orientation was found to decrease under the surface while the orientation remained the same. The results were confirmed with orientation distribution function (ODF) calculations.