Embolism in acute middle cerebral artery stenosis

OBJECTIVE: To investigate the frequency of middle cerebral artery (MCA) stenosis in a series of nonselected patients and the coexistence of microembolic signals with stenosis. METHODS: MCA stenosis was sought by transcranial Doppler (TCD) in 387 patients admitted consecutively with acute ischemic cerebrovascular disease within the first 48 hours of the onset of symptoms and again at 6 months. TCD monitoring for microembolic signals was performed on all patients with MCA stenosis. RESULTS: MCA stenoses were found in 29 patients (7%), although in only 20 patients (5%) was the stenosis symptomatic. Microembolic signals were detected in five of 14 symptomatic stenoses (36%) monitored at the acute phase, but none were found in the chronic phase or in asymptomatic stenosis. Despite one third of symptomatic patients having had a further source of emboli, microembolic signals were detected only distally to the MCA stenosis. In the symptomatic group, 25% of stenoses had completely disappeared 6 months after stroke. Microembolic signal detection at the acute phase was associated with the subsequent disappearance of the stenosis. CONCLUSIONS: The frequency of symptomatic MCA stenosis in acute ischemic stroke was 5% in the population studied. Many stenoses are transient, and microembolic signals are often detectable at the poststenotic segment in the acute phase. The origin of at least 25% of symptomatic acute MCA stenoses may be embolic rather than atherosclerotic.     

Atherosclerotic aortic arch plaques in cryptogenic stroke: a microembolic signal monitoring study

BACKGROUND AND PURPOSE: To find out the prevalence of relevant atherosclerotic plaques in the aortic arch and their potential role as a source of embolism in cryptogenic stroke. METHODS: We performed a transoesophageal echocardiography (TEE) on 49 patients with cryptogenic stroke from a total series of 212 non-selected patients with acute ischaemic stroke studied prospectively by cranial computed tomography (CT), colour-duplex and transcranial Doppler (TCD) sonography with micro-embolic signal (MES) monitoring. Cryptogenic stroke was diagnosed in those patients without carotid or intracranial stenosis > 50%, nor lacunar or cardio-embolic strokes. We defined relevant plaques as those > or = 4 mm thick located in the ascending aorta or proximal arch. RESULTS: Twenty-three patients (46.9%) had atherosclerotic aortic plaques (AAP): 3 in the ascending aorta (in 1 > or = 4 mm), 11 in the proximal aortic arch (in 4 > or = 4 mm) and 9 in the descending aorta (in 5 > or = 4 mm). Hence, 5 patients (10.2%) had relevant plaques. Aortic plaques were significantly related to older age (p < 0.001) and male gender (p = 0.042). A carotid artery stenosis < 50% was found in 39% of patients with AAP and in 8% of those without AAP (p = 0.009). MES were detected in 3 patients with plaques > or = 4 mm thick, but not in those without AAP or with AAP < 4 mm thick (p = 0.006). CONCLUSION: Although few patients with cryptogenic stroke had relevant plaques in our non-selected population, our results support the hypothesis that relevant aortic plaques have embolic potential.     

Surface adsorption of recombinant human interferon-gamma in lyophilized and spray-lyophilized formulations

Recombinant human interferon-gamma (rhIFN-gamma) was lyophilized or spray-lyophilized in 9.5% trehalose, +/- 0.12% polysorbate 20 in 10 mM potassium phosphate, pH 7.5. We measured recovery of soluble protein after spraying, freeze-thawing, and drying and reconstitution. Infrared spectroscopy showed rhIFN-gamma secondary structure to be native-like in all dried powders. Powders were characterized using electron spectroscopy for chemical analysis, time-of-flight secondary ion mass spectroscopy, X-ray diffraction, and gas adsorption isotherms. rhIFN-gamma adsorbed at air/liquid interfaces during spraying, and to ice/liquid interfaces during lyophilization. The concentration of rhIFN-gamma at ice/liquid interfaces was approximately one-fourth that adsorbed at air/liquid interfaces. Addition of 0.12% polysorbate 20 reduced the concentration of rhIFN-gamma at both interfaces. Time-of-flight secondary ion mass spectroscopy detected polysorbate 20 on surfaces of lyophilized powders. Lyophilized samples dried more slowly but reconstituted more quickly than spray-lyophilized samples. rhIFN-gamma aggregated after nebulization, but aggregation decreased in 0.12% polysorbate 20. Addition of 0.12% polysorbate 20 reduced protein surface adsorption and decreased but did not completely prevent aggregation. Insignificant aggregation occurred after exposure to ice/liquid interfaces, but subsequent drying and reconstitution caused aggregation. The majority of the aggregation is due to adsorption at air-liquid and solid-air interfaces formed during spray-lyophilization or lyophilization.     

Rhabdomyosarcoma of the head and neck region: experience at the pediatric unit of the Istituto Nazionale Tumori, Milan

OBJECTIVE: This study aims to describe the clinical features and outcome of pediatric patients with head and neck rhabdomyosarcoma (RMS), which can be divided into parameningeal, orbital, or nonorbital, nonparameningeal. DESIGN: This is a retrospective single-institution analysis. SETTING: The study was performed at the Istituto Nazionale Tumori, Milan, Italy. METHODS: The study considered 142 consecutive patients < 21 years treated from 1973 to 2003. MAIN OUTCOME MEASURES: Patients were treated using a multimodality approach: complete conservative surgery was performed at diagnosis in only two patients, all patients received chemotherapy, and most (91%) also had radiotherapy. Disease-free survival and overall survival were estimated according to the Kaplan-Meier method. RESULTS: For the series as a whole, the 5-year disease-free and overall surival rates were 49% and 57%, respectively. The 5-year overall survival rate improved over the years from 38% before 1980 to 78% after 1990; it was 44% for parameningeal, 79% for orbital, and 77% for nonorbital, nonparameningeal RMS. CONCLUSIONS: The treatment of head and neck RMS is complex and necessarily multidisciplinary. Complete surgery is rarely feasible in the head and neck region. This study confirms that orbital RMS has a favourable outcome, whereas therapeutic results are generally unsatisfactory in parameningeal cases, although recent progress in radiotherapeutic techniques and in the efficacy of chemotherapy would suggest clear improvements in survival.     

Keratinocyte growth factor receptors

Modulation of the number of functional growth factor receptors on the epithelial cell surface that is exposed to the action of cognate ligands represents a key strategy in cellular physiology to regulate the proliferation rate and the differentiation process. The keratinocyte growth factor receptor (KGFR) and the epidermal growth factor receptor (EGFR), among the growth factor receptors expressed on keratinocytes, are believed to play a unique crucial role in controlling epithelial proliferation. KGFR and EGFR appear to also contribute to the cell differentiation process. Modulation of KGFR and EGFR on the proliferation rate and differentiation process has been reported either in in vivo or in vitro conditions. This article reviews the architecture, the ligand binding activated-signaling pathways, and the biologic effects of KGFR and EGFR on keratinocytes.     

Hereditary diffuse gastric cancer: association with lobular breast cancer

Hereditary diffuse gastric cancer (HDGC) has been shown to be caused by germline mutations in the gene CDH1 located at 16q22.1, which encodes the cell–cell adhesion molecule, E-cadherin. Not only does loss of expression of E-cadherin account for the morphologic differences between intestinal and diffuse gastric cancer (DGC) variants, but it also appears to lead to distinct cellular features which appear to be common amongst related cancers that have been seen in the syndrome. As in most hereditary cancer syndromes, multiple organ sites may be commonly affected by cancer, in HDGC, lobular carcinoma of the breast (LBC) and possibly other organ sites have been shown to be associated with the familial cancer syndrome. Given the complexity of HDGC, not only with regard to the management of the DGC risk, but also with regard to the risk for other related cancers, such as LBC, a multi-disciplinary approach is needed for the management of individuals with known CDH1 mutations.