[Industry-funded therapy studies: what is in the pipeline?]. / Industriegeförderte Therapiestudien : Was ist in der Pipeline?

Several acute stroke trials are underway or have been recently completed. Among the latter are the ICTUS trial and the IST-3 trial. Several other approaches are being tested for thrombolytic therapy among them modern imaging-based patient selection and new thrombolytic agents, such as desmoteplase and tenecteplase. Other strategies include neuroprotection and neurorestoration, biophysical approaches, such as near infrared laser therapy, hemodynamic augmentation and sphenopalatine ganglion stimulation. Mechanical thrombectomy is practiced in many centers although randomized trials are pending and the IMS-3 trial was stopped. This overview will cover the very recently completed and currently recruiting acute ischemic stroke trials.

Characterization of solid and liquid sorbent materials for biogas purification by using a new volumetric screening instrument.

With the increasing utilization of biogas as an energy source the need for new materials and methods to purify and clean the corresponding gas mixtures is rising. In this regard, the application of ad- or absorptive gas purification methods has increased significantly over the last years. For fast and economic evaluation of the potential of different sorbent materials, a new volumetric screening instrument has been developed. First the measuring method and the new instrument design will be described. This instrument allows ad- and absorption, as well as desorption measurements in a technically relevant, wide pressure, and temperature range. It was used for the characterization of common sorbent materials such as activated carbons and zeolite molecular sieves. Additionally, new substances like metal-organic frameworks and ionic liquids were analyzed. Thereby the sorption of CO(2), CH(4), N(2), and H(2) was measured. The obtained data allow the direct comparison of the sorption properties of the different materials, the results of which will be presented in the second part of the paper.

Two-year vascular hospitalisation rates and associated costs in patients at risk of atherothrombosis in France and Germany: highest burden for peripheral arterial disease.

OBJECTIVES: To obtain Western European perspectives on the economic burden of atherothrombosis in patients with multiple risk factors only (MRF), cerebrovascular disease (CVD), coronary artery disease (CAD), and in the under-evaluated group of patients with peripheral arterial disease (PAD), we examined vascular-related hospitalisation rates and associated costs in France and Germany. DESIGN: The prospective REACH Registry enrolled 4693 patients in France, and 5594 patients in Germany (from December 2003 until June 2004). METHODS: For each country, 2-year rates and costs associated with cardiovascular events and vascular-related hospitalisations were examined for patients with MRF, CVD, CAD, and PAD. RESULTS: Two-year hospitalisation costs were highest for patients with PAD (3182.1€ for France; 2724.4€ for Germany) and lowest for the MRF group (749.1€ for France; 503.3€ for Germany). Peripheral revascularizations and amputations were the greatest contributors to costs for all risk groups. Across all PAD subgroups, peripheral procedures constituted approximately half of the 2-year costs. CONCLUSION: Hospitalisation rates and costs associated with atherothrombotic disease in France and Germany are high, especially so for patients with PAD.

[Epidemiology, clinical picture and management of atrial fibrillation]. / Epidemiologie, Klinik und Management des Vorhofflimmerns.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affects approximately 1% of adults and prevalence increases with age. Nine per cent of those aged 80 years and older have AF. AF is associated with increased cardiovascular mortality and morbidity, including stroke.Stroke in patients with AF is more severe and more likely to be fatal. Prevention of thromboembolism with oral anticoagulants and rate or rhythm control are the main therapeutic strategies for patients with AF. Vitamin K antagonists reduce the risk of stroke in patients with AF, however are underutilized. Dronedarone is the first antiarrhythmic drug that reduces the stroke rate.

Hemodynamic assessment of acute stroke using dynamic single-slice computed tomographic perfusion imaging.

BACKGROUND: Stroke management would benefit from a broadly available imaging tool that detects perfusion deficits in patients with acute stroke. OBJECTIVE: To determine the role of dynamic, single-slice computed tomographic (CT) perfusion imaging (CTP) in the assessment of acute middle cerebral artery stroke. DESIGN AND PATIENTS: Imaging with CTP and CT within the first 6 hours of symptom onset and before the start of treatment in a consecutive clinical series of 22 patients (mean age, 68.3 years; 14 women; studied within 143 +/- 96 minutes of stroke onset). SETTING: A stroke unit in a university hospital. MAIN OUTCOME MEASURES: Area of the perfusion deficit (nAP(0)) from time-to-peak maps, hemispheric lesion area from follow-up CT (HLA(F)), final infarct volume, and stroke recovery (National Institutes of Health Stroke Scale scores). RESULTS: Eighteen patients had perfusion deficits in the middle cerebral artery territory and corresponding hypoattenuation in follow-up CT. Three patients with normal CTP findings showed lacunar infarctions or normal findings on follow-up CT. In 1 patient, CTP did not reveal a territorial deficit above the imaging slice. The overall sensitivity and specificity of CTP for the detection of perfusion deficits in patients with proven territorial infarction (n = 18) on follow-up CT were 95% and 100%, respectively. The nAP(0) was significantly correlated with the National Institutes of Health Stroke Scale score at admission (P<.003) and the HLA(F) (P<.001). Different stroke patterns were identified in patients with follow-up CTP (n = 10): (1) initial perfusion deficit and partial nutritional reperfusion (nAP(0)>HLA(F); n = 6), (2) initial perfusion deficit and nonnutritional reperfusion (nAP( 0)>/=HLA(F); n = 2), and (3) initial perfusion deficit without reperfusion (nAP(0)>/=HLA(F); n = 2). CONCLUSIONS: Computed tomographic perfusion imaging detects major perfusion deficits in the middle cerebral artery territory. Because CTP is broadly available, it may play a role in acute stroke management. Arch Neurol. 2000;57:1161-1166

Magnetic resonance imaging assessment of cerebral hemodynamics during spreading depression in rats.

High-speed magnetic resonance imaging was used to perform simultaneous measurements of relative cerebral blood volume (rCBV) and water diffusion changes during spreading depression (SD) induced by cortical potassium chloride application. Rats were fitted epidurally with a rubber chamber. Potassium chloride was perfused through the chamber until SD was indicated by a negative direct current (DC) potential shift. Magnetic resonance imaging scans used echo planar diffusion and T2-weighted images. Iron dextran was injected as a blood pool contrast agent to make subsequent changes in T2 (or T2*) directly proportional to changes in CBV. Multislice maps of apparent diffusion coefficient (ADC) and rCBV were generated with 6- to 16-second time resolution, which revealed transient ADC and rCBV changes propagating over the cortex after potassium chloride application. Transient ADC declines appeared simultaneously with the DC shift, whereas rCBV increase followed with a delay of 16.4+/-14.9 seconds. Prolonged rCBV decrease was observed after the initial increase during the SD in half of the animals. The delayed rCBV response after the ADC change supports the observation of increased energy demand because of repolarization. Simultaneous DC potential recording and ADC measurements in corresponding sites of the cortex indicate that transient ADC decreases during SD reflect water shifts associated with cell depolarization.

Managed care: new challenges, new roles for the primary care physician. 2.

Managed care is revolutionizing health care, according to panelists in this roundtable discussion. Primary care physicians need to see patient care not as episodic but as a total, preventive package. In managed care, physicians hire nonphysician extenders for patient screening and function as a manager and consultant to an interdisciplinary team that extends beyond the four walls of the office practice. Patients need to know that primary care physicians can handle most of their problems; the specialist should be referred cases that are complicated and require procedures or second opinions. Outcome studies in managed care are lacking in important areas of geriatric medicine, such as treatment of psychiatric illnesses and Alzheimer's disease.

Managed care: what to expect as Medicare-HMO enrollment grows. 1.

Managed care is restructuring the American health care system and is beginning to make inroads into the Medicare-eligible population. Advantages of managed care for older patients include an emphasis on prevention, more flexibility in care delivery, and fewer restrictions and wider coverage (eg, prescriptions) than Medicare fee-for-service, and opportunities to develop measures for quality of care. Disadvantages include limitations on access and choice and a potential for professional conflict of interest. Early managed care enrollment favors the healthy "young-old;" questions remain about whether HMOs can provide quality care to the frail elderly with complicated and expensive health care needs.

Assessment of regional cerebral blood volume in acute human stroke by use of single-slice dynamic susceptibility contrast-enhanced magnetic resonance imaging.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the clinical usefulness of dynamic susceptibility contrast-enhanced MRI (DSC-MRI) in acute cerebral ischemia. METHODS: During bolus injection of gadolinium-diethylenetriamine pentaacetic acid, a series of rapid T2*-weighted images was recorded from one slice. Concentration-time curves and images of regional cerebral blood volume (rCBV) were calculated from this data set. DSC-MRI, MR angiography, conventional spin-echo MRI (SE-MRI), and CT were performed in 11 patients within 6 hours after stroke onset and before thrombolytic or anticoagulant treatment was begun. A follow-up MRI examination was performed 24 to 48 hours after stroke onset. RESULTS: In 7 of 11 patients (group 1) with territorial infarcts of the middle (n = 6) or posterior cerebral artery (n = 1), DSC-MRI showed reduced rCBV in the affected territory before conventional SE-MRI displayed ischemic lesions. DSC-MRI was helpful to differentiate severely ischemic tissue from peri-infarct parenchyma. Partial reperfusion (n = 3), unchanged reduction of rCBV (n = 2), and progressive reduction of rCBV (n = 2) were observed in the follow-up study. Normal DSC-MRI findings were present in 4 of 11 patients (group 2) with lacunar infarcts. CONCLUSIONS: DSC-MRI accomplished the detection of the ischemic territory in the very early stage (< 6 hours) before SE-MRI delivered unequivocal results. DSC-MRI might be helpful to discriminate completely ischemic tissue from potentially salvageable ischemic parenchyma at risk and may play an important role in stroke therapy and evaluation.

Assessment of cerebral blood volume with dynamic susceptibility contrast enhanced gradient-echo imaging.

OBJECTIVE: Dynamic susceptibility contrast (DSC) enhanced MRI was used to study relative cerebral blood volume (rCBV). MATERIALS AND METHODS: We examined 15 healthy subjects and 47 patients with vascular stenosis or occlusion, with brain infarctions, and with cerebral neoplasms. During bolus injection of Gd-diethylenetriamine pentaacetic acid, a series of rapid T2*-weighted fast low angle shot two-dimensional images were recorded from the same slice. From these images, changes in signal intensity during bolus passage were computed pixel-by-pixel and converted into contrast agent concentration curves. Applying the principles of indicator dilution theory, images of rCBV were calculated. RESULTS AND CONCLUSION: Regions of infarctions show almost zero rCBV. In patients with high-grade vascular stenosis or occlusion a bolus delay in comparison to the unaffected side and an increased mean transit time can be observed. Some of the affected areas show an increased rCBV, which is a well-known physiological mechanism that takes place to compensate for the reduced cerebral blood pressure. In brain tumors, rCBV imaging reveals focal or homogeneous areas of increased blood volume. This can even be observed in low-grade astrocytomas with unaffected blood-brain barrier. In CBV imaging, the effects of radiotherapy on tumor tissue can be monitored as a significant decrease of rCBV in tumor tissue after therapy.