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.      

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.     

Prediction of inspiratory flow shapes during sleep with a mathematic model of upper airway forces

STUDY OBJECTIVES: To predict the airflow dynamics during sleep using a mathematic model that incorporates a number of static and dynamic upper airway forces, and to compare the numerical results to clinical flow data recorded from patients with sleep-disordered breathing on and off various treatment options. DESIGN: Upper airway performance was modeled in virtual subjects characterized by parameter settings that describe common combinations of risk factors predisposing to upper airway collapse during sleep. The treatments effect were induced by relevant changes of the initial parameter values. SETTING: Computer simulations at our website (http://www.utu.fi/ml/sovmat/bio/). PARTICIPANTS: Risk factors considered in the simulation settings were sex, obesity, pharyngeal collapsibility, and decreased phasic activity of pharyngeal muscles. INTERVENTIONS: The effects of weight loss, pharyngeal surgery, nasal continuous positive airway pressure, and respiratory stimulation on the inspiratory flow characteristics were tested with the model. MEASUREMENTS AND RESULTS: Numerical predictions were investigated by means of 3 measurable inspiratory airflow characteristics: initial slope, total volume, and flow shape. The model was able to reproduce the inspiratory flow shape characteristics that have previously been described in the literature. Simulation results also supported the observations that a multitude of factors underlie the pharyngeal collapse and, therefore, certain medical therapies that are effective in some conditions may prove ineffective in others. CONCLUSIONS: A mathematic model integrating the current knowledge of upper airway physiology is able to predict individual treatment responses. The model provides a framework for designing novel and potentially feasible treatment alternatives for sleep-disordered breathing.     

Ezrin immunoreactivity in relation to survival in serous ovarian carcinoma patients

OBJECTIVE: Ezrin is a membrane-cytoskeleton linker protein, which regulates cell polarity and signaling. Increased ezrin expression in astrocytomas and uveal melanomas is correlated with unfavorable prognostic factors and reduced patient survival. We investigated ezrin IR in normal ovarian surface epithelium and serous ovarian carcinomas, and its relation with clinical parameters and patient outcome. METHODS: Tissue microarray blocks were constructed of all serous ovarian carcinoma tissue samples removed at a primary operation in Helsinki University Central Hospital between 1964 and 1999 and of healthy ovarian tissue samples. Ezrin expression was assessed by indirect immunohistochemistry using a monoclonal 3C12 ezrin antibody. Tissue samples (n = 440) were scored for the intensity of ezrin immunoreactivity, and the scores were compared with patient age, the stage and grade of disease, and disease outcome. RESULTS: Healthy ovarian epithelium showed strong polarized ezrin immunoreactivity. In serous ovarian carcinoma, the reactivity varied from strong (15.0% of samples) to moderate (57.3%) or weak/negative (27.7%) and the subcellular distribution was typically diffuse. Weak or negative expression of ezrin was associated with shorter survival (P = 0.027) but also with an advanced age of the patients (P = 0.0001), and a higher histological grade of the disease (P = 0.032). In Cox multivariate survival analysis, ezrin immunoreactivity had no independent effect on survival, when controlling for the stage and grade of the disease, and patient age. CONCLUSIONS: In contrast with astrocytomas and uveal melanomas, negative or weak ezrin immunoreactivity in serous ovarian carcinoma correlates with poor patient outcome.     

Cephalometric evaluation of facial types in preschool children without sleep-related breathing disorder

OBJECTIVE: this study was aimed at characterizing the craniofacial structures, i.e. the facial skeleton, cranial base, dentition, pharyngeal airway space, and the hyoid bone position, in healthy preschool children without sleep-related breathing disorder. MATERIALS AND METHODS: from lateral cephalometric radiographs taken of 92 children for diagnostic purposes, 45 were selected for the present investigation on the basis of head position, and divided according to the classification of Siriwat and Jarabak (Angle Orthod. 55 (1985) 127) into groups representing counter-clockwise (CC), straight downward (SD), and clockwise (C) facial types. RESULTS: the findings showed that, in comparison with the other groups, CC is associated with larger facial taper and posterior facial height, smaller mandibular line angle, ramus position, lower facial height and cranial base angle. By a similar comparison, C is associated with larger mandibular line, gonial angles and convexity, and with a smaller L-1 to mandibular line angle. There were no significant differences in hyoid bone position among the three groups. However, the distance of the lower pharynx was smaller in CC than in C, while the tongue base of CC was noted to be in a posterior position. CONCLUSIONS: thus, the results indicate that there are significant differences in the madibular position and form among the present three groups of children. It is proposed that the objective of vertical facial control ought to be included in the treatment of preschool children with malocclusion and respiratory disorder.     

Termination of pregnancy with mifepristone and prostaglandin suppresses transiently circulating glucocorticoid bioactivity

Mifepristone is a potent antiglucocorticoid, the administration of which results in a dose-dependent activation of the hypothalamic-pituitary-adrenal axis. However, the net effect of this compound on circulating glucocorticoid activity is not known. We have used a recombinant cell bioassay to study glucocorticoid bioactivity (GBA), measured directly from serum, in 18 women undergoing medical termination of an early pregnancy with 200 mg mifepristone, followed by 0.8 mg misoprostol, a prostaglandin. Increased serum mifepristone was accompanied by an increase in serum cortisol that was insufficient to maintain circulating GBA within the normal (pre-mifepristone) range (34.7-93.8 nM cortisol equivalents); after approximately 43, 46, and 68 h of mifepristone ingestion, the mean serum GBA levels were much lower than the mean pre-mifepristone level (P < 0.0001). At the corresponding times, 16, 13, and 12 women displayed subnormal serum GBA levels (ranges, <15.6-23, <15.6-25.6, and <15.6-32.5 nM cortisol equivalents, respectively). Altogether 11 subjects displayed subnormal serum GBA (range, <15.6-32.5 nM cortisol equivalents) continuously in the presence of high concentrations of mifepristone. Two weeks after mifepristone administration, circulating GBA had returned to normal levels in all subjects. We conclude that 200 mg mifepristone elicits a significant suppression of serum GBA, to one third of the pretreatment value, despite the compensatory increase in the serum cortisol concentration.