Six-second spirometry for detection of airway obstruction: a population-based study in Austria

RATIONALE: The presence of airway obstruction is currently defined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines on the basis of the post-bronchodilator (BD) FEV(1)/FVC. It has been proposed that the traditional FVC can be replaced with the shorter and less demanding FEV(6) for detecting airway obstruction. OBJECTIVES: A comparison of FEV(1)/FVC and FEV(1)/FEV(6) for the detection of airway obstruction in population-based post-bronchodilator spirometry data. METHODS: A population-based sample of 1,349 adults participated in the Burden of Obstructive Lung Disease study in Austria. Specially trained and certified technicians conducted pre-BD and post-BD spirometry according to American Thoracic Society guidelines and administered standardized questionnaires. A total of 93% of the post-BD test sessions were acceptable, and were included in this analysis. The Third National Health and Nutrition Examination Survey reference equations were used to calculate predicted values and lower limits of normal (LLN) for FEV(1), FEV(6), FVC, FEV(1)/FVC, and FEV(1)/FEV(6). MEASUREMENTS AND MAIN RESULTS: The post-BD FEV(1)/FVC was below the LLN in 199 (15.8%) subjects. The sensitivity of the FEV(1)/FEV(6) for airway obstruction depended greatly on the threshold of percent predicted FEV(1) also used in the definition. The overall sensitivity of FEV(1)/FEV(6) for a diagnosis of airway obstruction, as defined by FEV(1)/FVC (including participants with an FEV(1) above the LLN), was 72.9%, with 98.8% specificity. The sensitivity increased to 98.0% when a low FEV(1) was also required to diagnose post-BD airway obstruction. The discordant cases had long forced expiratory times, often showed a flow-volume curve pattern consistent with two-compartment emptying, and were more often never-smokers. CONCLUSIONS: Six-second spirometry maneuvers (which measure FEV(6)) are as sensitive and specific for post-BD airway obstruction as traditional (prolonged exhalation time) FVC maneuvers only when the definition of airway obstruction includes a low FEV(1).     

Inhibition of prolyl 4-hydroxylase prevents left ventricular remodelling in rats with thoracic aortic banding

BACKGROUND: Pressure overload leads to myocardial remodelling with collagen accumulation, left ventricular hypertrophy (LVH), neurohormonal activation and myocardial dysfunction. Prolyl 4-hydroxylases (P4H) are involved in collagen maturation. Inhibition of P4H has been shown to prevent LV remodelling and improve survival post-myocardial infarction. AIM: To evaluate the role of P4H in pressure overload-induced myocardial remodelling. METHODS: Male Wistar rats underwent thoracic aortic banding (AoB) and were treated with a P4H inhibitor (P4HI) or vehicle (control). Echocardiography and haemodynamic measurements were performed after 4 weeks. Collagens, matrix metalloproteinases (MMP), tissue inhibitors of MMPs (TIMP), growth factors and neurohormonal markers were quantitated in LV samples. RESULTS: AoB led to LVH, increased LV enddiastolic pressure (LVEDP) and decreased contractility compared to sham. P4HI reversed these effects. AoB increased collagen I and III expression, which was normalized by P4HI. AoB led to deregulation of matrix remodelling enzymes, enhanced expression of growth factors and activation of the endothelin system. P4HI partially prevented deregulation of the MMP/TIMP system, inhibited upregulation of growth factors and normalized AoB-induced ECE-1 and ETB expression. CONCLUSIONS: P4HI leads to an improvement of AoB-associated LV dysfunction and reduces imbalance of extracellular matrix turnover and hypertrophy-associated gene expression. P4H inhibition could therefore be of value in treatment of myocardial remodelling accompanying pressure overload hypertrophy.     

Rituximab for acute plasma-refractory thrombotic thrombocytopenic purpura. A case report and concise review of the literature

Thrombotic thrombocytopenic purpura (TTP) is a rare disease which responds well to plasma exchange treatment in the majority of patients. We report on a patient with acute TTP caused by severe autoantibody-mediated ADAMTS-13 deficiency, in whom remission was not achieved by initial treatment consisting of plasma exchange (PE), plasma infusion and corticosteroids, followed by vincristine and splenectomy. In view of the ongoing activity of TTP, treatment was initiated with rituximab, a chimaeric monoclonal antibody directed against the CD 20 antigen present on B lymphocytes. The patient received 4 weekly infusions of 375 mg/m2, each administered after the daily PE session and withholding PE until 48 hours later. Three weeks after the last infusion of rituximab a complete clinical and laboratory remission of this first episode of acute refractory TTP was documented. A concise review of the literature on the role of rituximab in patients with a first episode of acute plasma-refractory TTP suggests that rituximab in that situation may produce clinical remission in a significant proportion of patients, result in a lowered plasma requirement and avoid the complications of salvage immunosuppressive therapy. The use of rituximab in acute refractory TTP appears to be safe, with no excess infectious complications. We conclude that rituximab should be considered in TTP patients with acquired ADAMTS-13 deficiency who fail to respond clinically after 7-14 days of standard treatment with daily PE and glucocorticoids.     

Radiofrequency ablation of complex fractionated atrial electrograms (CFAE): preferential sites of acute termination and regularization in paroxysmal and persistent atrial fibrillation

Introduction: Complex fractionated atrial electrograms (CFAE) have been described as a new target for ablation of atrial fibrillation (AF). This prospective study evaluates the acute effects of CFAE ablation in patients with paroxysmal or persistent AF and analyzes the preferential anatomic sites where these effects occur.
Methods and Results: Ablation of CFAE was performed in 66 symptomatic patients (mean age of 58 ± 12 years) with paroxysmal (n = 36) or persistent AF (n = 30). Termination or regularization of AF during ablation of CFAE was achieved in 56 of 66 patients (84%), with termination in 28 of 66 patients (42%) and regularization of AF in 28 of 66 patients (42%). Ablation of CFAE showed no effect in 10 of 66 patients (16%). Termination of AF occurred at 53 sites and AF regularization at 81 sites. The preferential sites of AF termination or regularization were found around the pulmonary veins (termination n = 15; regularization n = 22), at the anterior wall (termination n = 14; regularization n = 19) and at the interatrial septum (termination n = 8; regularization n = 17).
Conclusion: Termination or regularization of AF was achieved acutely in 84% of patients by ablation of CFAE. The preferential sites of AF termination or regularization were found around the pulmonary veins, at the anterior wall of the LA and at the interatrial septum. These findings may have implications for future ablation concepts.     

Activation-flow coupling differentiates between vascular and Alzheimer type of dementia

The activation-flow coupling describes a mechanism, which adapts local cerebral blood flow in accordance with the underlying neuronal activity. It was suggested that the mechanism helps in differentiation between Alzheimer and vascular type of dementia. We combined EEG and Doppler techniques and assessed integrity of the activation-flow coupling in the occipital cortex utilizing a visual stimulation task. Alzheimer patients (MMSE: 18+/-8 points, DemTect 5+/-4 points) without signs of vascular lesions on a MRI scan and vascular demented patients (MMSE: 20+/-6 points, DemTect 6+/-3 points; MRI Fazekas score 7+/-3 points) were compared with data from an age-matched control group. Evoked flow velocity responses in the posterior cerebral artery were analysed according to a control system model specifying the parameters gain, attenuation, natural frequency and rate time. Evoked potentials were analysed for the N(75)-P(100) amplitude difference. Vascular demented patients exhibited a significant decreased gain parameter and increased attenuation parameter indicating severe cerebrovascular dysfunction. Also, the potential amplitudes were significantly decreased indicating neuronal damage due to the vascular disease process. Alzheimer patients did not differ in parameters as compared to the control group supporting other reports of intact occipital function at this stage of disease. Simultaneous assessment of electrical as well as vascular integrity might help in differentiating the most frequent forms of dementia.     

Extracranial-intracranial bypass surgery to reduce the risk of haemodynamic stroke in cerebroocclusive atherosclerotic disease of the anterior cerebral circulation - a systematic review

BACKGROUND AND PURPOSE: Selected patients with acute or continual ischaemic symptoms from occlusions or inaccessible stenotic lesions of the internal carotid artery or middle cerebral artery have been considered candidates for an extracranial-intracranial (EC-IC) bypass procedure. Hitherto, no effectiveness of this surgical therapeutic option for various patient subgroups could be found in a large international randomized trial, and therefore various guidelines give negative recommendations for its usefulness. The aim of the present report was to analyze clinical effectiveness of EC-IC bypass for cerebral revascularization in haemodynamic subgroups of patients with advanced occlusive cerebrovascular disease in the anterior cerebral circulation. MATERIAL AND METHODS: A computerized database search from November 1985 to November 2001 was performed. Language restriction was done for English, French and German. Reports dealing with EC-IC bypass surgery for cerebral revascularization in case of advanced cerebrovascular disease in the anterior cerebral circulation were reviewed when appropriate. Studies were included if they contained valuable data on clinical state, pre- and postoperative haemodynamic state, surgical outcome and follow-up. RESULTS: The postoperative outcome related to death or stroke depended mainly on preoperative haemodynamic subgroups (CBF/CBV; OEF). The final functional status was worse the more the CBF/CBV ratio and OEF increased. Perioperative risk for death (0.6%) or stroke (2%) during the first month after surgery was similar to the death or stroke rate during the following 2 to 12 months after surgery. The overall risk profile for subsequent death or stroke of surgically treated patients is significantly better within the first 12 months than that of conservatively treated patients (1.3% vs. 3.6% per year). Neurological function was improved over the preoperative state in 84% of the patients and was unchanged in 6%. Postoperatively, modified Rankin scale score was 0-1 in 90% of patients and 2 in 1% of patients. Long-term patency was excellent, with 1% failure rate per year following the first year after surgery. CONCLUSION: Neurological function and subsequent stroke attributable to haemodynamic insufficiency in patients with symptomatic carotid occlusion or severe stenosis are improved significantly by EC-IC bypass surgery if the brain area corresponding to the impaired neurological function remains viable. The haemodynamic parameters observed for patients who experience improved neurological function or diminished stroke risk profile after EC-IC-bypass surgery contain both significantly elevated OEF and CBF/CBV. Therefore haemodynamic profile represents an important indicator for EC-IC bypass surgery and gives a good rationale for new trials conducted in a subgroup of patients selected on the basis of their haemodynamic profile.     

Spontaneous eyeblink rate predicts the strength of visuomotor binding

The primate cortex represents the external world in a distributed way, which requires for a mechanism that integrates the features of a processed event. Animal and patients studies suggest that feature binding in the visual cortex is under muscarinic-cholinergic control, whereas visuomotor integration is driven by the dopaminergic system. Consistent with this picture, we present evidence that the binding of visual and action features is modulated by spontaneous eyeblink rate (EBR), which is a functional marker of central dopaminergic function. Remarkably, the impact of EBR was restricted to the task-relevant visuomotor binding, suggesting that dopamine increased the maintenance of task-relevant information.