Satisfaction with the emergency department environment decreases with length of stay.

OBJECTIVE: To determine the emergency department (ED) environmental factors associated with patient satisfaction. METHODS: A prospective, observational study in a university-affiliated tertiary-referral ED and associated observation unit (OU). The ED environment was evaluated with a structured questionnaire, scored using a 100-mm visual analogue scale. Patients who stayed in the ED over 8 h (long-stay ED; LSED) were compared with those who stayed less than 4 h (short-stay ED; SSED) and with a control group admitted to the OU. RESULTS: A total of 233 patients was enrolled, overall satisfaction in SSED was 81% (95% CI 70.1 to 88.7), 69% in LSED (95% CI 57.4 to 78.7) and 84% in OU (95% CI 73.6 to 91.0). The most important environmental factors were cleanliness (median importance 95, interquartile range (IQR) 81-98) and communication with medical staff (94, IQR 80-98) and family (92, IQR 74-98). The least important factors were access to nature (38, IQR 19-65), a natural light source (50, IQR 24-74) and ability to sit out of bed (52, IQR 26-75). Factors rated high for importance but low for satisfaction were ED noise levels (median difference 40, IQR 3-70), ED trolley comfort (19, IQR 6-50) and food quality (12, IQR -4-29). CONCLUSION: Patients who spend over 8 h in the ED are less satisfied with their environment than either those who spend less than 4 h or patients in an OU. Importantly, distinct, amenable factors can be identified. These should be addressed to improve patients' overall ED management and satisfaction.

Febrile adults presenting to the emergency department: outcomes and markers of serious illness.

OBJECTIVES: To determine outcomes and markers of serious illness for febrile patients presenting to an adult emergency department. METHODS: A prospective cohort study of patients presenting to the emergency department with a temperature >or=38 degrees C. Medical staff obtained demographic data and risk factor profiles while assessing each febrile patient. All were followed up to determine death, admission to intensive care, length of stay in hospital, or subsequent admission to hospital within 30 days. Univariate and multivariate analysis determined which factors were markers of serious illness. RESULTS: For febrile adults admitted to hospital 3.0% died, 6.1% were admitted to intensive care, median length of stay in hospital was 7.2 days. Independent risk factors were-death: age (OR = 1.04), respiratory rate (OR = 1.06), white cell count (OR = 1.02), cardiac disease (OR = 3.3), and jaundice (OR = 21.4). Admission to intensive care: respiratory rate (OR = 1.1), pulse rate (OR = 1.03), and jaundice (OR = 5.1). Increased length of hospital stay: age (p<0.01), jaundice (p<0.01), respiratory rate (p = 0.01), focal neurological signs (p = 0.01), and changed mental state (p = 0.04). For febrile adults sent home 7.9% required admission to hospital within 30 days. Risk factors were respiratory rate (OR = 1.2), being female (OR = 5.36), malignancy (OR = 15.3), and cardiac disease (OR = 19.7). Initially having no focus of infection was protective (OR = 0.13). No febrile patient sent home from the emergency department died or required admission to intensive care. CONCLUSIONS: Few febrile adults presenting to the emergency department suffer an adverse outcome suggesting effective risk stratification is occurring. The identification of factors associated with adverse events may further improve this process.

Myocardial perfusion imaging in evaluation of undiagnosed acute chest pain.

Myocardial perfusion imaging is a relatively new technique in the emergency department management of acute chest pain. With improved sensitivity and specificity compared to traditional methods of risk stratification, an abnormal scan rapidly identifies individuals with acute perfusion abnormalities and allows the appropriate utilization of limited resources. Conversely, a normal scan allows prompt hospital discharge and is associated with excellent outcomes both in the short and medium terms. Acute chest pain myocardial perfusion imaging has been demonstrated to alter patient management and disposition and its routine use results in decreased costs in the intermediate risk population.

Stimulation of extracellular matrix components in the normal brain by invading glioma cells.

Malignant gliomas are characterized by an extensive invasion of tumor cells into the normal brain parenchyma. A substantial amount of data indicates that cell movement in general is regulated by specific interactions between extracellular matrix components and specific cell-surface receptors. In the present work, multicellular spheroids from 4 human glioma cell lines (U-373Mg, A-172Mg, U-251Mg and HF-66) were confronted with normal rat brain cell aggregates in vitro, which resulted in a progressive invasion of tumor cells into the brain aggregates. The co-cultures were then sectioned and immuno-stained for specific extracellular matrix components (laminin, fibronectin and collagen type IV) and for specific cell-surface receptors which bind to these components (integrins beta1, beta4, alpha3, alpha6). In addition, flow-cytometric measurements and Northern blot analyses showed expression of several different integrins within the cell lines. The alpha3 subunit was expressed strongly in all cell lines. Whereas the beta1 subunit was expressed weakly in exponentially growing monolayer cultures, it showed a pronounced expression in multicellular spheroids, indicating that the integrin expression may vary depending on the micro-environment within a tumor. Furthermore, normal brain tissue was able to produce laminin when confronted with the glioma cells, which also was observed for fibronectin and collagen type IV. The relevance of our observations to the in vivo situation was investigated further by immuno-staining 5 human glioma biopsy samples for laminin. In some areas of the tumors, specific deposits of laminin were observed. In conclusion, we have shown that normal brain tissue has the ability to produce extracellular matrix components, such as laminin, collagen type IV and fibronectin, when confronted with invading glioma cells. Our results show that the glioma cells express specific integrins which can interact with these extracellular matrix components. Such interactions may facilitate tumor cell migration and invasion.

Neutral glycolipid composition of primary human brain tumors.

Neutral glycolipids (NGL) were isolated and quantitated in 98 primary human brain tumors; 19 low grade astrocytomas (LGA), 12 anaplastic astrocytomas (AA), 37 high grade astrocytomas (HGA), 18 oligodendroglial tumors, and 12 primitive neuroectodermal tumors (PNET). In 38 of these, the nature of the hexose in the cerebroside was determined using immunothin-layer chromatographic techniques. Galactosylceramide (GalCer) was the major ceramide monohexoside (CMH), and glucosylcerebroside never comprised more than 6% of this fraction in any tumor type. Furthermore, there was no correlation between the proportion of glucosylcerebroside and histological diagnosis. AA had the most characteristic neutral glycolipid pattern, with high levels of total lipid, total neutral glycolipid, CMH, and ceramide dihexoside (CDH) but low water contents. Consistent with this glycolipid composition is the finding that AA usually had neither ceramide trihexoside (CTH) nor globoside. Oligodendrogliomas were somewhat similar to AA in having high levels of CMH and infrequently having CTH or globoside. However, oligodendrogliomas had low water and total lipid contents. PNET had low levels of total lipid, total NGL, and CMH, but frequently contained CTH and globoside. LGA had high water contents but low levels of total lipid and CMH. HGA tended to have intermediate levels of almost all constituents analyzed, probably reflecting the pronounced cellular heterogeneity of these tumors. The frequent presence of GalCer in astrocytomas raises the possibility that some of these contain a population of cells that are related to the oligodendroglial lineage. However, the low amounts of GalCer and infrequent presence of sulfatide in PNET is consistent with their lack of differentiation toward oligodendrocytes. It will be of interest to determine if the neutral glycolipid patterns reported here will correlate with patient survival and be of prognostic significance.

Growth factor modulation of surface ganglioside expression in cloned neoplastic glia.

Cloned neoplastic astrocytes from a human glioma-derived cell line (IPSB-18) were grown in fetal calf serum (FCS)-supplemented culture medium in the presence of three growth factors. Basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) but not platelet-derived growth factor (PDGF) induced an increase in the number of cells positive for the ganglioside-recognizing monoclonal antibody, A2B5. No such growth factor-mediated induction could be detected in cells maintained in plasma-derived serum (PDS)-supplemented medium. Small molecules, removed from PDS during dialysis, may, therefore, act synergistically with growth factors in the control of ganglioside synthesis.

A human glioma cell line retaining expression of GFAP and gangliosides, recognized by A2B5 and LB1 antibodies, after prolonged passage.

A malignant astrocytoma was cultured from a tissue biopsy taken at surgical resection, and serially passaged 65 times over a period of 4 years. Early culture cells showed a variety of morphological types, but were all positively labelled with a polyclonal antibody directed against glial fibrillary acidic protein (GFAP). As the number of passages increased small, GFAP-positive cells became the predominant cell type. Flow cytometry demonstrated changes in GFAP expression between early and late passages; early passages showing greater fluorescence intensity than those at later passages. All cells, however, remained positive for GFAP. In addition, this line (IPSB-18) was both vimentin and glutamine synthetase positive and no change in the expression of these two proteins was detectable on continued sequential passaging. Fibronectin was not detectable at any stage. As the number of passages increased, the population doubling time was shortened from 72 h at passage 5, to 28 h at passage 30. This line is unusual in its retention of GFAP expression through 65 sequential passages; the majority of astrocytoma lines lose this capacity after a few passages in vitro. The monoclonal antibody, A2B5, which recognizes surface gangliosides, has been previously shown to identify sub-set type 2 astrocytes in normal neural tissue in vitro. The expression of A2B5 gangliosides by 5-20% of GFAP-positive IPSB-18 cells, and their co-expression with the ganglioside GD3 identified by the LB1 monoclonal antibody, shows that cells with a similar phenotype to the type 1 and type 2 astrocytes of optic nerve are present in cultured gliomas, even after long term sequential passaging.

A2B5 surface ganglioside binding distinguishes between two GFAP-positive clones from a human glioma-derived cell line.

A human glioma-derived cell line which expresses both the astrocytic markers, glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) and cell surface gangliosides recognised by the A2B5 monoclonal antibody has been cloned. Two clones are described, which are A2B5-positive and A2B5-negative, respectively. These neoplastic clones may provide a suitable in vitro model with which to assess the significance of surface ganglioside expression in relation to function and lineage of mammalian glia.

Channels at the catalytic site of glycogen phosphorylase b: binding and kinetic studies with the beta-glycosidase inhibitor D-gluconohydroximo-1,5-lactone N-phenylurethane.

Regions of low packing density in the vicinity of the catalytic site of glycogen phosphorylase b are described with the aid of a computer program that generates a contour map in which the contour level is inversely proportional to the packing density in the protein. It is shown that, although there is no direct route from the catalytic site to the surface, there are two possible channels that could allow access for substrates following conformational changes in the enzyme. The first channel, channel 1, leads from the catalytic site to the surface close to the nucleoside inhibitor site and requires movements of residues 280-285 and Arg 569 in order to obtain access. Previous crystallographic experiments have shown that in the presence of substrates or R-state inhibitors these parts of the polypeptide chain undergo large conformational changes. The properties of the second channel (channel 2), which is the more extensive channel, have been investigated with the potent beta-glycosidase inhibitor D-gluconohydroximo-1,5-lactone N-phenylurethane (PUG). Crystallographic binding studies at 2.4-A resolution show that the compound binds neatly at the catalytic site of phosphorylase b. The glucopyranosylidene ring, in the half-chair conformation, occupies a similar but not identical position (shift about 0.6 A) to that occupied by other glucosyl compounds bound at the catalytic site.(ABSTRACT TRUNCATED AT 250 WORDS)