bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensory and Histological Characteristics of Beef Rib Cuts Heated at Two Rates to Three End Point Temperatures
Authors: Bayne Barbara H. , Allen Mary B. , Large Nancy F. , Meyer Bernadine H. , Goertz Grayce E.
Published: January 2008

Beef rib cuts were oven roasted at 107° and 163°C. to end points of 60°, 70°, and 77°C. Cooking losses, tenderness, and other sensory properties were evaluated and related to histological changes in muscle components. Cooking times were longer and cooking losses usually lower at 107°C. than at 163°C. As end point temperature increased, cooking time and cooking loss increased and juiciness decreased. Shear values for cuts heated to end points of 70° and 77°C. at 107°C. were lower than for all other heat treatments. Roasts cooked at 107°C. to each end point and those cooked at 163°C. to 60°C. received higher tenderness scores than did all other heat treatments. Muscle fiber diameter decreased approximately the same extent with heating at either oven temperature. Fiber diameter decreased as end point temperature increased from 60° to 70°C., but diameter increased between 70° and 77°C. Quantity of collagenous connective tissue appeared to be greater in cuts heated at 163°C. to 60°, 70°, and 77°C. and at 107°C. to 70°C. than at other heat treatments. With increasing oven and end point temperatures, collagenous tissue changed from a banded to a granular appearance and fat became dispersed in the perimysial and endomysial collagenous tissue.
Educational ethnography as performance art: towards a sensuous feeling and knowing
Authors: Bagley Carl
Published: January 2008

The article methodologically positions and subsequently describes an ethnographic-based performance art piece staged as the author's keynote address at the UK's first international conference on Arts-Based Educational Research held at Queen's University Belfast. The article draws on existing arts-based research literature and a range of participant `voices' — including the voice of the author as `impresario' whose research provided the ethnographic data and facilitated the performance, the voices of the artists as `performers' who created and staged the piece, and the voices of the audience as `spec-actors' who made the journey through the performance — to make its case and hopefully encourage other qualitative researchers to a performative (re)presentational embrace.
Preoperative Psychosocial Evaluation of Penile Prosthesis Candidates
Authors: Ulloa Erin Winters , Silberbogen Amy K. , Brown Kirstin
Published: January 2008

Penile prosthesis surgery is a recommended treatment option for a subset of patients who present with erectile dysfunction (ED). Although treatment outcome research indicates that patients are generally satisfied with this intervention, it remains an invasive procedure with risk for complications. A review of the literature reveals general agreement for the importance of a thorough preoperative evaluation to determine appropriateness for a penile implant; however, there are no known descriptions of such an evaluation in the literature. This article provides an introduction to the domains that are most relevant to assess in a patient who is considering penile implant surgery: sexual history (including organic and psychogenic causes of ED), success and utilization of other treatment interventions, relationship functioning, and patient expectations for and knowledge of the procedure. The advantages to this approach are presented, particularly in enhancing patient satisfaction with treatment outcomes.
Npm1 is a haploinsufficient suppressor of myeloid and lymphoid malignancies in the mouse
Authors: Sportoletti Paolo , Grisendi Silvia , Majid Samia M. , Cheng Ke , Clohessy John G. , Viale Agnes , Teruya-Feldstein Julie , Pandolfi Pier Paolo
Published: January 2008

Nucleophosmin (NPM1) gene has been heavily implicated in cancer pathogenesis both as a putative proto-oncogene and tumor suppressor gene. NPM1 is the most frequently mutated gene in acute myeloid leukemia (AML), while deletion of 5q, where NPM1 maps, is frequent in patients with myelodysplastic syndromes (MDS). We have previously shown that mice heterozygous for Npm1 (Npm1+/−) develop a hematologic syndrome with features of human MDS. Here we analyzed Npm1+/− mutants to determine their susceptibility to cancer. Npm1+/− mice displayed a greater propensity to develop malignancies compared with Npm1+/+ mice. The Npm1+/− cohort frequently developed hematologic malignancies of both myeloid and lymphoid origin with myeloid malignancies displaying the highest incidence. Malignant cells retained the wild-type allele with normal localization and expression of Npm1 at the protein level, suggesting that complete Npm1 loss is not a prerequisite for tumorigenesis. Our results conclusively demonstrate that Npm1 acts as a haploinsufficient tumor suppressor in the hematopoietic compartment.
Antigen-induced clustering of surface CD38 and recruitment of intracellular CD38 to the immunologic synapse
Authors: Muñoz Pilar , Mittelbrunn María , de la Fuente Hortensia , Pérez-Martínez Manuel , García-Pérez Angélica , Ariza-Veguillas Adriana , Malavasi Fabio , Zubiaur Mercedes , Sánchez-Madrid Francisco , Sancho Jaime
Published: January 2008

During immunologic synapse (IS) formation, human CD38 redistributes to the contact area of T cell–antigen-presenting cell (APC) conjugates in an antigen-dependent manner. Confocal microscopy showed that CD38 preferentially accumulated along the contact zone, whereas CD3-ζ redistributed toward the central zone of the IS. APC conjugates with human T cells or B cells transiently expressing CD38–green fluorescent protein revealed the presence of 2 distinct pools of CD38, one localized at the cell membrane and the other in recycling endosomes. Both pools were recruited to the T/APC contact sites and required antigen-pulsed APCs. The process appeared more efficient in T cells than in APCs. CD38 was actively recruited at the IS of T cells by means of Lck-mediated signals. Overexpression of CD38 in T cells increased the levels of antigen-induced intracellular calcium release. Opposite results were obtained by down-regulating surface CD38 expression by means of CD38 siRNA. CD38 blockade in influenza HA-specific T cells inhibited IL-2 and IFN-γ production, PKCθ phosphorylation at Thr538, and PKCθ recruitment to the IS induced by antigen-pulsed APCs. These results reveal a new role for CD38 in modulating antigen-mediated T-cell responses during IS formation.
New evidence of risk factors for community-acquired pneumonia: a population-based study
Authors: Almirall J. , Bolíbar I. , Serra-Prat M. , Roig J. , Hospital I. , Carandell E. , Agustí M. , Ayuso P. , Estela A. , Torres A. ,   the Community-Acquired Pneumonia in Catalan Countries (PACAP) Study Group
Published: January 2008

The aim of the present study was to identify risk factors for community-acquired pneumonia (CAP), with special emphasis on modifiable risk factors and those applicable to the general population.

A population-based, case–control study was conducted, with a target population of 859,033 inhabitants aged >14 yrs. A total of 1,336 patients with confirmed CAP were matched to control subjects by age, sex and primary centre over 1 yr.

In the univariate analysis, outstanding risk factors were passive smoking in never-smokers aged >65 yrs, heavy alcohol intake, contact with pets, households with >10 people, contact with children, interventions on the upper airways and poor dental health. Risky treatments included amiodarone,N-acetylcysteine and oral steroids. Influenza and pneumococcal vaccine, and visiting the dentist were protective factors. Multivariable analysis confirmed cigarette smoking, usual contact with children, sudden changes of temperature at work, inhalation therapy (particularly containing steroids and using plastic pear-spacers), oxygen therapy, asthma and chronic bronchitis as independent risk factors.

Interventions for reducing community-acquired pneumonia should integrate health habits and lifestyle factors related to household, work and community, together with individual clinical conditions, comorbidities and oral or inhaled regular treatments. Prevention would include vaccination, dental hygiene and avoidance of upper respiratory colonisation.
Necrotising pneumonia is an increasingly detected complication of pneumonia in children
Authors: Sawicki G. S. , Lu F. L. , Valim C. , Cleveland R. H. , Colin A. A.
Published: January 2008

Necrotising pneumonia (NP) is a severe complication of community-acquired pneumonia characterised by liquefaction and cavitation of lung tissue. The present study describes the epidemiology, aetiology, management and outcomes of children hospitalised with NP over a 15-yr period.

A retrospective observational study of NP cases was conducted from January 1990 to February 2005 analysing clinical presentation, laboratory data, hospital course and long-term follow-up.

A total of 80 NP cases were identified, with the number of detected cases increasing from 12, in the period 1993–1996, to 40 in the period 2001–2004. In total, 69 (86%) cases had pleural effusion with a low pH (mean 7.08) and 38 (48%) patients had positive cultures, withStreptococcus pneumoniaeas the predominant organism. Recently, other organisms, most notably methicillin-resistantStaphylococcus aureus, emerged. Patients had prolonged hospitalisations (median 12 days). A total of 69 patients required pleural interventions and those receiving chest drainage alone had similar outcomes to those managed surgically. All patients had full clinical resolution within 2 months of presentation.

Necrotising pneumonia has increasingly been identified as a complication of paediatric pneumonia.Streptococcus pneumoniaeremains the predominant organism, but since 2002, different bacteria have been isolated and the age range of cases has broadened. Despite the serious morbidity, massive parenchymal damage and prolonged hospitalisations, long-term outcome following necrotising pneumonia is excellent.
Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE)
Authors: Vestbo J. , Anderson W. , Coxson H. O. , Crim C. , Dawber F. , Edwards L. , Hagan G. , Knobil K. , Lomas D. A. , MacNee W. , Silverman E. K. , Tal-Singer R. ,   on behalf of the ECLIPSE investigators
Published: January 2008

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and not well understood. The forced expiratory volume in one second is used for the diagnosis and staging of COPD, but there is wide acceptance that it is a crude measure and insensitive to change over shorter periods of time.

Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) is a 3-yr longitudinal study with four specific aims: 1) definition of clinically relevant COPD subtypes; 2) identification of parameters that predict disease progression in these subtypes; 3) examination of biomarkers that correlate with COPD subtypes and may predict disease progression; and 4) identification of novel genetic factors and/or biomarkers that both correlate with clinically relevant COPD subtypes and predict disease progression.

ECLIPSE plans to recruit 2,180 COPD subjects in Global Initiative for Chronic Obstructive Lung Disease categories II–IV and 343 smoking and 223 nonsmoking control subjects. Study procedures are to be performed at baseline, 3 months, 6 months and every 6 months thereafter. Assessments include pulmonary function measurements (spirometry, impulse oscillometry and plethysmography), chest computed tomography, biomarker measurement (in blood, sputum, urine and exhaled breath condensate), health outcomes, body impedance, resting oxygen saturation and 6-min walking distance.

Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points is the largest study attempting to better describe the subtypes of chronic obstructive pulmonary disease, as well as defining predictive markers of its progression.
Early effective drainage in the treatment of loculated tuberculous pleurisy
Authors: Chung C-L. , Chen C-H. , Yeh C-Y. , Sheu J-R. , Chang S-C.
Published: January 2008

The role of early effective drainage in loculated tuberculous (TB) pleurisy treatment remains unclear.

Consecutive patients with TB pleurisy subjected to anti-TB treatment and pigtail drainage (n = 64) were divided into three groups: 1) patients with free-flowing effusions irrigated with saline (free-flowing group; n = 20); 2) patients with loculated effusions irrigated with streptokinase (streptokinase group; n = 22); and 3) patients with loculated effusions irrigated with saline (saline group; n = 22). Pleural irrigation was performed for 3 days consecutively and the effusion drained as completely as possible. Outcomes were assessed for 12 months by clinical symptoms, effusion removed, radiological scores for effusion amount, lung function and occurrence of residual pleural thickening.

The total effusion volumes removed were significantly greater in the free-flowing (2.36±1.62 L) and streptokinase groups (2.59±1.77 L) than in the saline group (1.28±1.21 L). Compared with the saline group, the free-flowing and streptokinase groups showed significant improvement in radiological scores and forced vital capacity at different time-points during follow-up, and a significantly lower occurrence of residual pleural thickening. All outcome variables were comparable between the streptokinase and free-flowing groups.

In summary, early effective drainage and complete anti-tuberculosis treatment may hasten clearance of pleural effusion, reduce residual pleural thickening occurrence and accelerate pulmonary function recovery in patients with symptomatic loculated tuberculous pleurisy.
Decreased expression of haem oxygenase-1 by alveolar macrophages in idiopathic pulmonary fibrosis
Authors: Ye Q. , Dalavanga Y. , Poulakis N. , Sixt S. U. , Guzman J. , Costabel U.
Published: January 2008

Haem oxygenase (HO)-1 is an oxidative stress responsive protein that may be involved in the pathogenesis of interstitial lung disease.

HO-1 expression in alveolar macrophages from bronchoalveolar lavage was investigated in 24 patients with idiopathic pulmonary fibrosis (IPF), 16 with sarcoidosis, 14 with hypersensitivity pneumonitis (HP) and 13 controls. Using immunocytochemistry, HO-1 expression in macrophages was scored semiquantitatively from 0–3 according to increasing intensity. The mean score of 100 macrophages was calculated. Macrophages were cultured and levels of interleukin (IL)-12 and IL-18 in the culture supernatants were measured by ELISA.

The mean score of HO-1 was significantly lower in IPF (67) than in sarcoidosis (105), HP (106) or controls (106). There was no significant difference between sarcoidosis, HP and controls. The score of HO-1 correlated positively with the lymphocyte percentage in sarcoidosis and HP. Positive correlations were found between the score of HO-1 and the release of IL-12 and IL-18 by macrophages in IPF.

The expression of haem oxygenase-1, a critical defender against oxidative stress, is decreased in macrophages of idiopathic pulmonary fibrosis patients compared with those with granulomatous lung disorders. This supports the hypothesis of an oxidant–antioxidant imbalance in the pathogenesis of idiopathic pulmonary fibrosis.
Monocyte chemotactic protein-1 in the migration of differentiated leukaemic cells toward alveolar epithelial cells
Authors: Tsai W-H. , Shih C-H. , Lin C-C. , Ho C-K. , Hsu F-C. , Hsu H-C.
Published: January 2008

All-trans retinoic acid (ATRA) can induce acute respiratory distress syndrome in patients with acute promyelocytic leukaemia (APL). The current study investigated the role of monocyte chemotactic protein (MCP)-1 in the chemotactic transmigration of ATRA-treated NB4 (ATRA-NB4) APL cells toward A549 alveolar epithelial cells.

NB4 and A549 cells were separately cultured with ATRA and/or dexamethasone (DEX). ATRA-NB4 cells were then placed in an upper insert and co-incubated with A549 cells or their conditioned medium (CM) located in a lower plate to test their transmigration activity.

ATRA stimulated NB4 cells to transmigrate toward the A549 cells. The secretion of MCP-1 was enhanced by ATRA treatment in both A549 and NB4 cells. The binding assay demonstrated that ATRA-NB4 cells bound MCP-1. Pre-treatment of both CM-A549 cells with antibodies against MCP-1 and of ATRA-NB4 cells with antibodies against MCP-1 receptors reduced ATRA-NB4 cell transmigration. DEX did not suppress MCP-1 secretion and transmigration in ATRA-NB4 cells, although when applied to A549 cells, MCP-1 secretion was suppressed and ATRA-NB4 cell transmigration was attenuated.

Monocyte chemotactic protein-1 secreted from alveolar epithelial cells plays an important role in the cell–cell interaction involved in the chemotactic transmigration of all-trans retinoic acid-treated acute promyelocytic leukaemia cells toward alveolar epithelial cells.
Deletion of MyD88 markedly attenuates sepsis-induced T and B lymphocyte apoptosis but worsens survival
Authors: Peck-Palmer Octavia M , Unsinger Jacqueline , Chang Katherine C , Davis Christopher G , McDunn Jonathan E , Hotchkiss Richard S
Published: January 2008

Sepsis induces widespread lymphocyte apoptosis, resulting in impaired immune defenses and increased morbidity and mortality. There are multiple potential triggers or signaling molecules involved in mediating death signals. Elucidating the specific signaling pathways that are involved in mediating lymphocyte apoptosis may lead to improved therapies of this lethal disorder. We investigated a number of key cellular receptors and intracellular signaling pathways that may be responsible for apoptotic cell death. Specifically, we investigated the role of pathogen-associated molecular patterns (TLR2, TLR4, and IL-1R), intracellular signaling proteins (MyD88 and TRIF), cytoplasmic transcription factors (STAT1 and STAT4), and the MAPK pathway (JNK1) in sepsis-induced lymphocyte apoptosis. Studies were performed in the cecal ligation and puncture (CLP) model of sepsis using specific gene-targeted deletions. CLP-induced lymphocyte apoptosis was evaluated 20 h post-operation by active caspase-3 and TUNEL staining. Surprisingly, the only genetic construct that ameliorated T and B lymphocyte sepsis-induced apoptosis (∼80% and 85%, respectively) occurred in MyD88−/− mice. Despite the marked decrease in sepsis-induced apoptosis, MyD88−/− mice had a worsened survival. In conclusion, lymphocyte death in sepsis likely involves multiple pathogen-sensing receptors and redundant signaling pathways. MyD88 was effective in blocking apoptosis, as it is essential in mediating most pathogen recognition pathways; however, MyD88 is also critical for host survival in a model of severe peritonitis.
Patterns of neutrophil serine protease-dependent cleavage of surfactant protein D in inflammatory lung disease
Authors: Cooley Jessica , McDonald Barbara , Accurso Frank J , Crouch Erika C , Remold-O’Donnell Eileen
Published: January 2008

The manuscript presents definitive studies of surfactant protein D (SP-D) in the context of inflammatory lung fluids. The extent of SP-D depletion in bronchoalveolar lavage fluid (BALF) of children affected with cystic fibrosis (CF) is demonstrated to correlate best with the presence of the active neutrophil serine protease (NSP) elastase. Novel C-terminal SP-D fragments of 27 kDa and 11 kDa were identified in patient lavage fluid in addition to the previously described N-terminal, 35-kDa fragment by the use of isoelectrofocusing, modified blotting conditions, and region-specific antibodies. SP-D cleavage sites were identified. In vitro treatment of recombinant human SP-D dodecamers with NSPs replicated the fragmentation, but unexpectedly, the pattern of SP-D fragments generated by NSPs was dependent on calcium concentration. Whereas the 35- and 11-kDa fragments were generated when incubations were performed in low calcium (200 μM CaCl2), incubations in physiological calcium (2 mM) with higher amounts of elastase or proteinase-3 generated C-terminal 27, 21, and 14 kDa fragments, representing cleavage within the collagen and neck regions. Studies in which recombinant SP-D cleavage by individual NSPs was quantitatively evaluated under low and high calcium conditions showed that the most potent NSP for cleaving SP-D is elastase, followed by proteinase-3, followed by cathepsin G. These relative potency findings were considered in the context of other studies that showed that active NSPs in CF BALF are in the order: elastase, followed by cathepsin G, followed by proteinase-3. The findings support a pre-eminent role for neutrophil elastase as the critical protease responsible for SP-D depletion in inflammatory lung disease.
RNase A ribonucleases and host defense: an evolving story
Authors: Rosenberg Helene F
Published: January 2008

RNase A (bovine pancreatic RNase) is the founding member an extensive family of divergent proteins that share specific elements of sequence homology, a unique disulfide-bonded tertiary structure, and the ability to hydrolyze polymeric RNA. Among the more intriguing and perhaps counterintuitive findings, at the current state of the art, the connection between RNase activity and characterized host defense functions is quite weak; whether this is a scientific reality or more a reflection of what has been chosen for study remains to be determined. Several of the RNase A family RNases are highly cationic and have cytotoxic and bactericidal properties that are clearly (eosinophil cationic protein, leukocyte RNase A-2) or are probably (RNase 7) unrelated to their enzymatic activity. Interestingly, peptides derived from the leukocyte RNase A-2 sequence are nearly as bactericidal as the entire protein, suggesting that among other functions, the RNase A superfamily may be serving as a source of gene scaffolds for the generation of novel cytotoxic peptides. Other RNase A ribonucleases are somewhat less cationic (mouse angiogenin 4, zebrafish RNases) and have moderate bactericidal activities that have not yet been explored mechanistically. Additional host defense functions characterized specifically for the RNase eosinophil-derived neurotoxin include reducing infectivity of RNA viruses for target cells in culture, which does require RNase activity, chemoattraction of immature human dendritic cells via a G-protein-coupled receptor-dependent mechanism, and activation of TLR2. The properties of individual RNase A ribonucleases, recent experimental findings, and important questions for the near and distant future will be reviewed.
Phase II Study of Predictive Biomarker Profiles for Response Targeting Human Epidermal Growth Factor Receptor 2 (HER-2) in Advanced Inflammatory Breast Cancer With Lapatinib Monotherapy
Authors: Johnston Stephen , Trudeau Maureen , Kaufman Bella , Boussen Hamouda , Blackwell Kimberley , LoRusso Patricia , Lombardi Donald P. , Ben Ahmed Slim , Citrin Dennis L. , DeSilvio Michelle L. , Harris Jennifer , Westlund Ron E. , Salazar Vanessa , Zaks Tal Z. , Spector Neil L.
Published: January 2008

Purpose

Inflammatory breast cancer (IBC) is one of the most aggressive forms of breast cancer. Lapatinib, an oral reversible inhibitor of epidermal growth factor receptor (EGFR) and human EGFR 2 (HER-2), demonstrated clinical activity in four of five IBC patients in phase I trials. We conducted a phase II trial to confirm the sensitivity of IBC to lapatinib, to determine whether response is HER-2 or EGFR dependent, and to elucidate a molecular signature predictive of lapatinib sensitivity.

Patients and Methods

Our open-label multicenter phase II trial (EGF103009) assessed clinical activity and safety of lapatinib monotherapy in patients with recurrent or anthracycline-refractory IBC. Patients were assigned to cohorts A (HER-2–overexpressing [HER-2+]) or B(HER-2–/EGFR+) and fresh pretreatment tumor biopsies were collected.

Results

Forty-five patients (30 in cohort A; 15 in cohort B) received lapatinib 1,500 mg once daily continuously. Clinical presentation and biomarker analyses demonstrated a tumor molecular signature consistent with IBC. Lapatinib was generally well tolerated, with primarily grade 1/2 skin and GI toxicities. Fifteen patients (50%) in cohort A had clinical responses to lapatinib in skin and/or measurable disease (according to Response Evaluation Criteria in Solid Tumors) compared with one patient in cohort B. Within cohort A, phosphorylated (p) HER-3 and lack of p53 expression predicted for response to lapatinib (P < .05). Tumors coexpressing pHER-2 and pHER-3 were more likely to respond to lapatinib (nine of 10 v four of 14; P = .0045). Prior trastuzumab therapy and loss of phosphate and tensin homolog 10 (PTEN) did not preclude response to lapatinib.

Conclusion

Lapatinib is well tolerated with clinical activity in heavily pretreated HER-2+, but not EGFR+/HER-2–, IBC. In this study, coexpression of pHER-2 and pHER-3 in tumors seems to predict for a favorable response to lapatinib. These findings warrant further investigation of lapatinib monotherapy or combination therapy in HER-2+ IBC.
Recruitment ofDrosophilaPolycomb-group proteins by Polycomblike, a component of a novel protein complex in larvae
Authors: Savla Urmi , Benes Judith , Zhang Junyu , Jones Richard S.
Published: January 2008

Polycomb-group (PcG) proteins are highly conserved epigenetic transcriptional repressors that play central roles in numerous examples of developmental gene regulation. Four PcG repressor complexes have been purified from Drosophila embryos: PRC1, PRC2, Pcl-PRC2 and PhoRC. Previous studies described a hierarchical recruitment pathway of PcG proteins at the bxd Polycomb Response Element (PRE) of the Ultrabithorax(Ubx) gene in larval wing imaginal discs. The DNA-binding proteins Pho and/or Phol are required for target site binding by PRC2, which in turn is required for chromosome binding by PRC1. Here, we identify a novel larval complex that contains the PcG protein Polycomblike (Pcl) that is distinct from PRC1 and PRC2 and which is also dependent on Pho and/or Phol for binding to the bxd PRE in wing imaginal discs. RNAi-mediated depletion of Pcl in larvae disrupts chromosome binding by E(z), a core component of PRC2, but Pcl does not require E(z) for chromosome binding. These results place the Pcl complex(PCLC) downstream of Pho and/or Phol and upstream of PRC2 and PRC1 in the recruitment hierarchy.
Quantification of integrin receptor agonism by fluorescence lifetime imaging
Authors: Parsons Maddy , Messent Anthea J. , Humphries Jonathan D. , Deakin Nicholas O. , Humphries Martin J.
Published: January 2008

Both spatiotemporal analyses of adhesion signalling and the development of pharmacological inhibitors of integrin receptors currently suffer from the lack of an assay to measure integrin-effector binding and the response of these interactions to antagonists. Indeed, anti-integrin compounds have failed in the clinic because of secondary side effects resulting from agonistic activity. Here, we have expressed integrin-GFP and effector-mRFP pairs in living cells and quantified their association using fluorescence lifetime imaging microscopy (FLIM) to measure fluorescence resonance energy transfer (FRET). Association of talin with β1 integrin and paxillin with α4 integrin was dependent on both the ligand and receptor activation state, and was sensitive to inhibition with small molecule RGD and LDV mimetics, respectively. An adaptation of the assay revealed the agonistic activity of these small molecules, thus demonstrating that these compounds may induce secondary effects in vivo via integrin activation. This study provides insight into the dependence of the activity of small molecule anti-integrin compounds upon receptor conformation, and provides a novel quantitative assay for the validation of potential integrin antagonists.
Structural Characterizations of Charged Colloidal Silica Crystals Formed by Base Diffusion
Authors: Yamada Hiroshi , Sawada Tsutomu , Yamanaka Junpei , Yonese Masakatsu , Uchida Fumio
Published: January 2008

We examine the structures and orientation of charged colloidal silica crystals formed by the unidirectional diffusion of sodium hydrogencarbonate. Angular-dependent diffraction spectrometry is applied to centimeter-sized cubic crystals immobilized in polymer hydrogels. We find that the lattice planes of these crystals are not aligned with the container walls. This suggests that these large crystals are not formed by the wall effect, which has played a vital role in the formation of large crystals in previous studies.
Effect of Macroscopically Smooth Silver Substrate on the Surface-enhanced Raman Scattering of 4-Nitrobenzenethiol Adsorbed on Powdered Au
Authors: Shin Kuan Soo , Park Chan Seok , Kang Weekyung , Kim Kwan
Published: January 2008

Raman scattering measurements were conducted for 4-nitrobenzenethiol (4-NBT) assembled on gold μ-powders sparsely dispersed on smooth silver substrates. The SERS signals of 4-NBT were enhanced by using smooth Ag substrates caused by electromagnetic coupling of the surface plasmon polaritons of μAu powders and flat metal substrate. And 4-NBT adsorbed on Au powder is converted to 4-aminobenzenethiol (4-ABT) by the irradiation of visible light.
[5]Rotaxanes Composed of α-Cyclodextrin and Pd or Pt Complexes with Alkylbipyridinium Ligands
Authors: Taira Toshiaki , Suzaki Yuji , Osakada Kohtaro
Published: January 2008

[3]Pseudorotaxane, having two α-cyclodextrins and an N-alkylbipyridinium as the macrocyclic and axle components, reacts with M(NO3)2(en) (M = Pd and Pt, en = 1,2-ethylenediamine) in water to form new transition metal-containing [5]rotaxanes.
p-Nitrophenyl Triazenyl Purine: First Adenine-based Colorimetric Anion Sensor
Authors: Upadhyay K K , Kumar Ajit , Upadhyay Shalini , Mishra Rakesh K , Roychoudhuary P K
Published: January 2008

6-[(2E)-3-(4-Nitrophenyl)triaz-2-en-1-yl]-9H-purine (p-nitrophenyl triazenyl purine, PNTP) has been synthesized and evaluated for sensing the anions PF6−, HSO4−, ClO4−, and BF4− as their tetrabutylammonium salts in DMSO. This is the first example of any adenine-based anion sensor. The addition of 2 equivalents of PF6−, HSO4−, ClO4−, and BF4− to the 2×10−5 mol dm−3 DMSO solution of PNTP at room temperature produced visible color changes and perturbation of UV–vis spectral pattern of PNTP in terms of absorbance at 398 and 575 nm in reciprocal patterns. The sensing ability of PNTP was found to be best for PF6− among all the chosen anions.
Syntheses of Fluorescence-labeled Sphingosine 1-Phosphate Methylene and Sulfur Analogues as Possible Visible Ligands to the Receptor
Authors: Yamamoto Tetsuya , Hasegawa Hiroko , Hakogi Toshikazu , Katsumura Shigeo
Published: January 2008

The methylene and sulfur analogues of sphingosine 1-phosphate labeled with a fluorescent group at the terminus of the backbone skeleton were stereoselectively synthesized as possible nonhydrolyzable visible ligands to the sphingosine 1-phosphate receptor, S1P1.
The Ultimate Aberdeen Knot
Authors: Stott Philip M , Ripley Lionel G , Lavelle Michael A
Published: January 2008

INTRODUCTION

The Aberdeen knot has been shown to be stronger and more secure than a surgeon's knot for ending a suture line. No data exist as to the ideal configuration of the Aberdeen knot. The Royal College of Surgeons of England in their Basic Surgical Skills Course, 2002 recommended six throws. The aim of this experiment is to find the ideal combination of throws and turns.

MATERIALS AND METHODS

Aberdeen knots of various configurations were tied in O-PDS suture (Ethicon, Johnson and Johnson). Each configuration was tied 10 times. A materials testing machine was used to test the knots to destruction in a standardised manner.

RESULTS

The knots were seen to behave in two ways. They either slipped and unravelled, or broke. Knots tied with fewer than three throws were unreliable. Knots tied with three throws and two turns appear to be the strongest configuration. Adding further throws and turns does not increase the strength of an Aberdeen knot.

CONCLUSIONS

An Aberdeen knot tied with three throws and two turns is the ultimate Aberdeen knot.
Acute Appendicitis: Are we Over Diagnosing it?
Authors: Singhal V , Jadhav V
Published: January 2008

INTRODUCTION

Appendicectomy is by far the commonest major emergency general surgical operation and laparoscopic appendicectomy is now becoming common. The question of whether a normal-looking appendix should be removed laparoscopically is more pertinent than ever before.

PATIENTS AND METHODS

A retrospective study was undertaken to review the histopathology results and compare macroscopic with microscopic descriptions of all patients who underwent an appendicectomy, either by open surgery or laparoscopically, over a 1-year period from 1 September 2004 to 31 August 2005.

RESULTS

A total of 199 appendicectomies were carried out in the year of which histopathology results for 190 could be retrieved. Of the 190 who had an appendicectomy, 110 (57.9%) were female and 80 (42.1%) were male. While appendicitis was confirmed histologically in 65 of 80 (81.2%) male patients, it could only be confirmed histologically in 57 of 110 (51.8%) female patients. However, in a large number of female patients in whom macroscopically normal appendices had been removed, other findings were noted including fibro-obliterative changes in 10, luminal inflammation in 6, serositis in 5, lymphoid hyperplasia in 3, feacoliths in 2, and pinworm in 1, making another abdominal pathology a possibility.

CONCLUSIONS

The number of macroscopically normal appendices removed was much larger in female patients. However in 27 of 49 normal looking appendices in females, findings such as serositis, luminal inflammation, lymphoid hyperplasia, etc. were noted on histology, suggesting that another abdominal pathology may have been missed or the appendix may still have been the cause for pain. On the basis of these findings, we suggest that diagnostic laparoscopy should be performed at least in all female patients before an appendicectomy; if no other findings are noted on laparoscopy, it is likely to be worthwhile to remove the appendix.
Content and Design of Patient-Targeted Websites in Orthopaedic Surgery: The Example of Total Hip Replacement
Authors: Moran M , Oliver CW
Published: January 2008

INTRODUCTION

The Internet is frequently used as a source of medical information by patients. There is no shortage of quantity of information on the Internet. Most studies have concentrated on the content of information provided by orthopaedic websites. This study aims to assess all aspects of website construction, using total hip replacement (THR) as an example.

MATERIALS AND METHODS

Using the search term ‘total hip replacement’, we evaluated the top 50 results from 4 popular search engines. A detailed evaluation of these sites was carried out and data recorded on authorship, readability (Flesch score), authority, currency, information status, information value, information quality, graphics and design, navigation, speed and access. These were individually scored using the University of Michigan Consumer Health WebSite Checklist.

RESULTS

From the 200 web pages, 167 unique Uniform Resource Locators (URLs) were recorded. Of these, 55 provided patient information about THR and were evaluated fully. Of websites, 62% originated in the US. The authorship of the majority of websites was described as commercial (28%) or academic/physician (49%). Website evaluation showed that content, navigation, graphics and speed were good. However, authority, currency, information status, information quality and ease of reading scored poorly.

DISCUSSION

Most of the sites visited presented adequate information about THR. However, the manner in which this information was presented is poor.
Blood and Body Fluid Splashes During Surgery – The Need for Eye Protection and Masks
Authors: Davies CG , Khan MN , Ghauri ASK , Ranaboldo CJ
Published: January 2008

INTRODUCTION

While most surgeons make an effort to avoid needlestick injury, some can pay little attention to reduce the potential route of infection occurring when body fluids splash into the eye. It has been shown that transmission of HIV, hepatitis B or C can occur across any mucous membrane. This study aims to quantify how frequently body fluids splash the mask and lens of wrap around protective glasses thus potentially exposing the surgeon to infection.

PATIENTS AND METHODS

A prospective study was carried out by a single surgeon on all cases performed over a 1-year period. Protective mask and glasses were examined before and after operations.

RESULTS

A total of 384 operations were performed with 174 (45%) showing blood or body fluid splash on the lens. A high incidence of splashes was found in vascular surgical procedures (79%). All amputations showed splash on the protective lens. Interestingly, 50% of laparoscopic cases resulted in blood or body fluid splash on the protective lens.

CONCLUSIONS

This study has shown a high incidence (45%) of blood and body fluid splashes found on protective glasses and masks. There was a very high incidence (79%) during vascular surgical procedures. With the prevalence of HIV and hepatitis increasing, it seems prudent to protect oneself against possible routes of transmission.
Pulmonary Metastasectomy: A Common Practice Based on Weak Evidence
Authors: Treasure Tom
Published: January 2008

The resection of secondary metastases from the lungs is a wide-spread surgical practice. Patients are referred from coloproctology teams to thoracic surgeons specifically for this surgery. What is the expected benefit? I have explored the rationale and searched the literature in order to present these patients with a well-informed opinion for their consideration. I find only weak evidence based on uncontrolled retrospective series which have been interpreted as showing a survival benefit. This has been extrapolated to policy and practice that do not stand up to scrutiny. The practice has never been subjected to randomised trial and I will argue that the present evidence is insufficient to justify the uncontrolled use of an intervention with inescapable short-term morbidity, permanent loss of function, and major cost implications. I propose ways in which the evidence may be improved, including a trial in the areas of most uncertainty.
‘To have … or not to have’. Should Computed Tomography and Ultrasonography be Implemented as a Routine Work-Up for Patients with Suspected Acute Appendicitis in a Regional Hospital?
Authors: Chiang David T , Tan Elaine I , Birks David
Published: January 2008

INTRODUCTION

Appendicitis is a common diagnosis, but is by no means a simple one to establish. This retrospective study investigated the value of medical imaging (ultrasonography and/or computed tomography [CT]) for patients with suspected appendicitis. Negative appendicectomy rate and appendiceal perforation with or without medical imaging were used as end points for this investigation.

PATIENTS AND METHODS

This study retrospectively reviewed all patients admitted in one district general hospital with suspected acute appendicitis. The patient cohort was identified from the Unit Registry and an International Classification of Diseases-based Review of medical records. The medical records were analysed, and the outcome of patients were followed up.

RESULTS

Between 12 January 2004 to 27 May 2005, 168 patients' medical records were audited. The negative appendicitis rate was 6.7% and appendiceal perforation rate was 3.2%. Among them, only 20 in-patients (12%) had medical imaging (ultrasonography and/or CT scan) after clinical assessment for suspected acute appendicitis. Medical imaging had a 70% prediction rate for acute appendicitis, 20% false-negative rate, and 10% false-positive rate. Overall, the prediction rate for appendicitis by clinical assessment supplemented by laboratory tests and medical imaging at clinician's discretion was 93.2%.

CONCLUSIONS

Despite studies advocating routine use of medical imaging for patients with suspected acute appendicitis, this study showed that the clinical evaluation is still paramount to the management of patients with suspected acute appendicitis before considering medical imaging.
Trend towards Primary Closure Following Laparoscopic Exploration of the Common Bile Duct
Authors: Jameel M , Darmas B , Baker AL
Published: January 2008

INTRODUCTION

The aim of this study was the assessment of patient outcome, peri-operative complications, length of stay and duration of operation after laparoscopic primary closure of the common bile duct (CBD) compared with choledochotomy with T-tube drainage and trans-cystic exploration.

PATIENTS AND METHODS

Analysis of prospectively collected data on 71 explorations of the common bile duct between July 2001 and March 2006.

RESULTS

A total of 71 patients had exploration of the CBD. Within this group, 12 were referred after failed endoscopic retrograde cholangiopancreatography (ERCP). The methods of exploration included trans-cystic (9 cases), choledochotomy with Ttube (12), and choledochotomy with primary closure (50). CBD stones were found in 66 patients. In the remaining cases, we found a stricture in 1, debris in 2, and dilatation of the CBD without a stone in 2. There were 5 conversions to open technique and 3 patients required postoperative ERCP (1 with permanent stenting). Peri-operative complications included T-tube (3), primary closure group (9), and trans-cystic (0). There was no statistical significant difference (Chi-square test, P = 0.296) between the groups. There was a trend towards a shorter length of stay in the primary closure group as compared with the trans-cystic and T-tube groups of 4.16, 4.44, and 6.33 days, respectively. However, it did not reach statistical significance (one-way analysis of variance with Boneferroni correction, mean difference between groups 1.89, 0.28, 2,17, statistical significance at P < 0.05). The shortest operating time was in the primary closure group (95.92 min) which was statistically significant (P < 0.001). We did not use a biliary drain in the last 48 patients.

CONCLUSIONS

Primary laparoscopic closure of the CBD is safe and results in a reduction in operating time. Choledochoscopy ensures clearance of the CBD and eliminates the need for T-tube.
Comparison of the Short-Form Survey 12 and the MacNew Heart Disease Health-Related Quality of Life Survey Among Patients with Cardiac Disease
Authors: Sansgiry Sujit S , Chien Chloe , Jayawant Sujata S , Raju Aditya
Published: January 2008

Background:

Heallh-relaled quality or lire (HRQL) is an important outcome, especially for chronic diseases with no cure such as cardiovascular diseases.

Objective:

To investigate the comparability of 2 HRQL instalments, the Short Form-12 (SF-12) survey and the MacNew Heart Disease HRQL survey (MacNew) in patients with cardiac diseases.

Methods:

A nonexperimental cross-sectional study was conducted in a lipid clinic in the Houston metropolitan area. Patients with a prior cardiac disease were requested to complete the SF-12 and the MacNew scales while waiting to see the physician during their regular clinic visit, Cronbach's u values were estimated to evaluate internal consistency. Spearman's correlation was performed to examine the correlation between the SF-12 and the MacNew scale domains,

Results:

A total of 118 patients were enrolled in this study. High Cronbach's a (from 0.89 to 0.94) were observed from all component scores in the MacNew scales. Physical component scores from the SF-12 and from the MacNew were highly correlated (r = 0.74; p < 0.001), as were the mental component score from the SF-12 and the emotional component score from the MacNew (r = 0.68; p < 0.001).

Conclusions:

The SF-12 and the MacNew appeared to be strongfy correlated to each other for predicting a patient's HRQL in patients with a cardiac disease.
Amantadine Enhancement of Arousal and Cognition After Traumatic Brain Injury
Authors: Sawyer Elizabeth , Maura Laurie S , Ohlinger Martin J
Published: January 2008

Objective:

To determine the role of amantadine therapy tor early arousal and improved cognition in traumatic brain injury (TBI).

Data Sources:

Literature was accessed through MEDLINE (1950–August 2007) using the MeSH terms amantadine, brain injuries, cognition, and arousal. PubMed (through August 2007) terms included amantadine, traumatic brain injury, and cerebral injury.

Study Selection and Data Extraction:

All studies ol amantadine (used <6 mo after injury) for enhancement of arousal or cognition in patients with TBI were reviewed.

Data Synthesis:

Many cases of TBI are associated with frontal lobe injury. As a dopamine agonist, amantadine is thought to be involved in frontal lobe stimulation. Two case reports, 3 retrospective studies, and 2 randomized, double-blind, controlled trials of amantadine therapy for early arousal in TBI were identified and reviewed. Limitations of the available studies include open design, retrospective design, and heterogeneous brain injury types. Results have been inconsistent between studies, largely due to variability in designs, heterogeneity in patient populations, time following injury, and use of numerous different outcome measures. Despite these limitations, improvements in arousal and cognition, as documented by the Glasgow Coma Scale and olher measures, have been observed in patients with TBI when amantadine has been initiated 3 days to 5 months after injury.

Conclusions:

At doses of 200–400 mg/day, amantadine appears to safely improve arousal and cognition in patients with TBI. Additional prospective controlled studies with homogeneous patient populations will better define the role of amantadine for early arousal.
Treatment Options in Imatinib-Resistant Chronic Myelogenous Leukemia
Authors: Marshall Helen M , Hammond Julia M
Published: January 2008

Objective:

To discuss new therapeutic options available in the treatment of chronic myelogenous leukemia (CML) in patients who (ailed or were intolerant to imatinib therapy.

Data Sources:

Literature was accessed via MEDLINE (1966–May 2007). EMBASE (199l–3rd quarter 2007). the Proceedings of the American Society of Hematology (2000–2006), and the Proceedings of the American Society of Clinical Oncology (2000–2007). Search terms included imatinib, dasatinib, nilotinib. and chronic myelogenous leukemia.

Study Selection and Data Extraction:

Meeting abstracts and studies that reported preclinical and Phase 1, 2, and 3 trials published in English are included.

Data Synthesis:

Imatinib is the standard of care for CML; however, some patients develop resistance or are intolerant to the drug. Phase 1 and 2 clinical data for the more potent tyrosine kinase inhibitors, dasatinib and nilotinib, are promising. Hematologic and cytogenetic responses are reported with both. There does not appear to be cross-resistance between the drugs, although neither is effective against all mutations ol the hallmark molecular marker, the Philadelphia chromosome. Novel agents are also being examined for the treatment of patients with CML, including aurora kinase and farnesyl transferase inhibitors, as well as combination therapies.

Conclusions:

Dasatinib and nilotinib are second-tine options for patients who have CML and are resistant or intolerant to imatinib. Toxicity profiles between agents may differ. Clinical trials with these drugs and others are ongoing.