Computerized tomography angiography in patients with subarachnoid hemorrhage: from aneurysm detection to treatment without conventional angiography.

OBJECT: The purpose of this study was to determine prospectively whether and to what extent computerized tomography (CT) angiography can serve as the sole imaging method for a preoperative workup in patients with ruptured intracranial aneurysms. METHODS: During a 1-year period, all patients who presented to the authors' hospital with subarachnoid hemorrhage demonstrated by unenhanced CT scanning or lumbar puncture underwent CT angiography. Two radiologists evaluated the CT angiography source images and maximum intensity projection slabs and arrived at a consensus. They categorized the quality of the CT angiography as adequate or inadequate and classified aneurysms that were detected as definitely or possibly present. The parent artery of anterior communicating artery aneurysms was identified by asymmetrical anterior cerebral artery size and asymmetrical aneurysm location. The parent artery was indicated by the larger A1 segment in cases of asymmetrical A1 size. Only CT angiograms of adequate quality that revealed aneurysms classified as definitely present and with an unequivocal parent artery were presented to the neurosurgeons, who decided whether preoperative digital subtraction (DS) angiography should still be performed. Forty-nine of the 100 studied patients did not undergo surgery because of poor clinical condition, nonaneurysmal cause of the hemorrhage, or endovascular treatment of the ruptured aneurysm. Of the 51 patients who underwent surgery, radiologists required DS angiography in 17 patients; the imaging technique provided greater certainty in 13 instances. The neurosurgeons required DS angiography 11 times; this provided additional information in two instances. Twenty-three (45%) of the 51 patients were surgically treated successfully on the basis of CT angiography findings alone. CONCLUSIONS: Computerized tomography angiography can replace DS angiography as the preoperative neuroimaging technique in a substantial proportion of patients with ruptured intracranial aneurysms.     

Supercritical fluid drying of carbohydrates: selection of suitable excipients and process conditions.

The processibility of 15 carbohydrates, more or less commonly used, was investigated as excipients in supercritical fluid drying. The focus was on the ability to produce amorphous powder, the stability of the powders towards crystallisation, and the residual water and ethanol content. The aqueous solutions were sprayed into a pressurised carbon dioxide-ethanol mixture flowing cocurrently through a coaxial two-fluid nozzle. The powder characteristics appeared to be influenced by the supersaturation level reached during the SCF-drying process and by the properties of the sugar species, such as water solubility and glass transition temperature, or the solution viscosities. The stability and the residual solvent content of a selected set of sugars and some mixtures were further analysed. The stability of amorphous powders was investigated at 4 degrees C, room temperature, 40 and 50 degrees C. Lactose, maltose, trehalose, raffinose, cyclodextrin, low-molecular-weight dextran and inulin could form free-flowing powders that remained amorphous during the 3-month stability study. Sucrose had to be mixed with other sugars to form a stable amorphous powder. Ethanol could be entrapped in supercritical fluid dried low-molecular-weight sugars, whereas polysaccharide powders were free of ethanol. Measures to prevent or overcome the presence of ethanol are discussed.     

Localization of nonpalpable breast lesions

The introduction of mammography screening and improvements in diagnostic tools resulted in a major increase of breast cancers detectable as small, nonpalpable lesions suitable for breast-conserving treatment. Accurate preoperative localization of these cancers is a necessity. Several methods are available for localization, of which wire-guided localization is considered the current gold standard. Promising techniques are radio-guided occult lesion localization, radioactive seed localization and ultrasound-guided surgery. In this article, an overview of the various localization techniques is provided, describing advantages, shortcomings and effectiveness.     

Medullary cone movement in subjects with a normal spinal cord and in patients with a tethered spinal cord.

PURPOSE: To compare movement of the normal medullary cone when the patient has changed from a supine to prone position with that in patients with known or suspected tethered spinal cord syndrome. MATERIALS AND METHODS: Fifty-six individuals divided into three groups were examined with lumbar spine magnetic resonance (MR) imaging performed with the patient in the prone and supine positions. Group 1 consisted of 15 healthy volunteers and six patients with a herniated disk; group 2, 25 patients clinically suspected of having a tethered cord; and group 3, 10 patients who previously had undergone tethered cord surgery. RESULTS: All group 1 subjects showed distinct and statistically significant medullary cone movement (range, 21%--41%); no patient in group 3 showed movement (Wilcoxon rank sum test, P <.001). In group 2, the 20 patients in whom a definite diagnosis of tethered cord syndrome was made on the basis of initial supine MR image findings showed no movement, whereas two of five patients with normal supine MR images had abnormal and decreased cone movement at prone imaging. CONCLUSION: Prone MR imaging has no additional value when the supine MR image has clearly shown the cause of tethering or in patients who have undergone tethered cord surgery, but it can provide additional information in patients clinically suspected of having a tethered cord and in whom supine MR imaging depicted no abnormalities.     

The β-adrenoceptor agonist clenbuterol is a potent inhibitor of the LPS-induced production of TNF-α and IL-6 in vitro and in vivo

OBJECTIVE AND DESIGN: To investigate the suppressive effects of the beta-agonist clenbuterol on the release of TNF-alpha and IL-6 in a lipopolysaccharide (LPS)-model of inflammation, both in vitro and in vivo. MATERIAL AND SUBJECTS: Human U-937 cell line (monocyte-derived macrophages), and male Wistar rats (200-250 g). TREATMENT: U-937 macrophages were incubated with LPS at 1 microg/ml, with or without 1.0 mM-0.1 nM test drugs (clenbuterol and other cAMP elevating agents) for 1-24 h. Rats were administered either 1 or 10 microg/kg clenbuterol (or saline) orally, 1 h before intraperitoneal administration of 2 mg/kg LPS. METHODS AND RESULTS: TNF-alpha and IL-6 time-concentration profiles were determined both in culture media and plasma, using ELISA' s and bioassays. LPS-mediated release of both cytokines was significantly suppressed by clenbuterol. CONCLUSIONS: The beta-agonist clenbuterol very potently suppresses the LPS-induced release of the pro-inflammatory cytokines TNF-alpha and IL-6 both in vitro and in vivo.     

White Matter Lesions and Encephalopathy in Patients Treated For Primary Central Nervous System Lymphoma

A retrospective analysis of the clinical presentations and neuroimaging characteristics of 33 patients with a primary central nervous system lymphoma (PCNL) who received cranial radiotherapy was performed to assess incidence of and risk factors for radiation-induced encephalopathy. CT and MRI scans were revised by a neurologist and a radiologist in conference. White matter abnormalities before and after radiotherapy on the last scan before recurrence were quantified according to a semi-quantitative scale. All available medical records were retrieved and reviewed with respect to demographic and tumor-related variables, treatment modalities, disease-free and overall survival and clinical symptoms and signs of encephalopathy. CT and MRI scans showed severe white matter lesions in 75% of 20 patients and in 86% of patients aged more than 60 years. Forty percent of patients presented with new clinical signs of cognitive impairment a median of 14.5 months after initial diagnosis (8.5 months after radiotherapy). The risk of white matter lesions appeared greater in patients aged > 60 (RR 1.2, 95% CI = 0.8–2.0), in patients with prior white matter lesions (RR 1.3, 95% CI = 0.8–2.1) and in patients with multifocal cerebral lymphoma (RR 1.5, 95% CI = 1.0–2.1). In conclusion, the risk of white matter lesions and clinical symptoms and signs of encephalopathy is high in patients treated by radiotherapy for PCNL. The risk appears to be greatest in older patients, patients with multifocal tumor and in those with prior white matter lesions on CT or MRI.     

Beta-adrenergic receptor agonists induce the release of granulocyte chemotactic protein-2, oncostatin M, and vascular endothelial growth factor from macrophages

Vascular endothelial growth factor (VEGF), oncostatin M (OSM), and granulocyte chemotactic protein-2 (GCP-2/CXCL6) are up-regulated in U937 macrophages and peripheral blood macrophages exposed to LPS, beta-adrenergic receptor (beta2-AR) agonists (e.g. zilpaterol, and clenbuterol) and some other agents that induce intracellular cAMP (prostaglandin E2, forskolin, and butyryl cAMP). LPS in combination with beta2-agonists and cAMP elevating agents had an additional effect on the release of VEGF, OSM, and CXCL6. These proteins are up-regulated after 16-24 h of exposure and this is mediated by the beta2-AR, as determined by time course experiments and the use of a specific beta2-AR antagonist (ICI 118551). Beta2-AR agonists are used as bronchodilators in the treatment of asthma, but appear to have no effect on the chronic inflammation of the disease. However, the up-regulation of VEGF, OSM, and CXCL6 may have adverse effects on the inflammatory process of asthma. These mediators are involved in the recruitment of neutrophils, airway remodelling and angiogenesis, known features of chronic inflammatory diseases. We propose that the up-regulation of these proteins could play a role in the adverse effects of prolonged excessive usage of beta2-AR agonists on the airways besides the desensitization of the beta2-AR.     

A standardised approach towards PROving the efficacy of foods and food constituents for health CLAIMs (PROCLAIM): providing guidance

Diet is well known to have beneficial health properties that extend beyond traditionally accepted nutritional effects. The approach involved in elucidating these beneficial physiological effects is becoming more important, as reflected by increasing research being undertaken. With growing consumer awareness of foods and food constituents and their relationship to health, the key questions for regulators, scientists and the food industry continue to relate to: (1) how consumers could be protected and have confidence that the health claims on foods are well supported by the evidence; (2) how research on physiological effects of food (constituents) and their health benefits could be stimulated and supported; (3) how research findings could be used in the development of innovative new food products. The objectives of this paper are to provide a set of recommendations on the substantiation of health claims for foods, to develop further guidance on the choice of validated markers (or marker patterns) and what effects are considered to be beneficial to the health of the general public (or specific target groups). Finally, the case for developing a standardised approach for assessing the totality of the available scientific data and weighing the evidence is proposed.