End points for colon cancer adjuvant trials: observations and recommendations based on individual patient data from 20,898 patients enrolled onto 18 randomized trials from the ACCENT Group.

Purpose: The traditional end point for colon adjuvant clinical trials is overall survival (OS). We previously validated disease-free survival (DFS) after 3-year follow-up as an excellent predictor of 5-year OS results. Here we explore shorter term DFS and OS end points, as well as stage dependency.

How older Vietnamese Australian women manage their medicines.

Safe use of medicines is relevant to all, but especially older people, primarily because they have ageing bodies that require more medicines and are therefore more likely to experience complications, including adverse drug interactions. Australia has a rapidly growing migrant older population composed of people with different beliefs about, and practices using, medicines. This paper presents qualitative findings from interviews and focus groups conducted with older Vietnamese-Australian women living in Sydney, Australia.

Diagnosing primary ciliary dyskinesia.

A nationally funded diagnostic service should lead to improved outcome

Interpretive subgroup analysis extends modified grounded theory research findings in oncologic music therapy.

Following an investigation into oncologic patients' experiences of the helpfulness of music therapy (O'Callaghan & McDermott, 2004), it was considered that examining relationships between specific patient characteristics and their responses could yield further interesting understandings. "Interpretative subgroup analysis" is introduced, which adapts principles of subgroup analysis in quantitative research to textual data analysis. Anonymous written responses from 128 oncologic patients were analyzed to compare responses from (a) those that had one music therapy session with those who had more than one session, (b) males and females, and (c) middle and older aged respondents.

Practical problems and resource implications with the use of warfarin for venous thromboembolism in patients with cancer.

Background: Oral anticoagulants present multiple practical problems for patients undergoing chemotherapy. To assess the practice implications of anticoagulation therapy, a review was carried out.

Methods: A review of all patients with cancer treated with warfarin for venous thromboembolism (VTE) over a 1-year-period was carried out.

Primary ciliary dyskinesia: current state of the art.

Primary ciliary dyskinesia (PCD) is usually inherited as an autosomal recessive disorder and presents with upper and lower respiratory tract infection, and mirror image arrangement in around 50% of cases. Cilia dysfunction is also implicated in a wider spectrum of disease, including polycystic liver and kidney disease, central nervous system problems including retinopathy and hydrocephalus, and biliary atresia. Cilia are complex structures, containing more than 250 proteins; recent studies have begun to locate PCD genes scattered throughout the genome.

Regulation of ligands for the activating receptor NKG2D.

The outcome of an encounter between a cytotoxic cell and a potential target cell depends on the balance of signals from inhibitory and activating receptors. Natural Killer group 2D (NKG2D) has recently emerged as a major activating receptor on T lymphocytes and natural killer cells. In both humans and mice, multiple different genes encode ligands for NKG2D, and these ligands are non-classical major histocompatibility complex class I molecules.

Molecular chaperones regulate p53 and suppress senescence programs.

Many types of cancer cells constitutively express major molecular chaperones at high levels. Recent findings demonstrate that specific depletion of individual chaperones, including various members of the Hsp70 family, small heat shock proteins, or VCP/p97, leads to activation of p53 pathway and subsequently triggers cellular senescence. Here, we discuss a possibility that in cancer cells high levels of chaperones serve to keep the p53 signaling under control, thus allowing cancer cells to evade the default senescence and form tumors.

Structure of the fungal beta-glucan-binding immune receptor dectin-1: implications for function.

The murine molecule dectin-1 (known as the beta-glucan receptor in humans) is an immune cell surface receptor implicated in the immunological defense against fungal pathogens. Sequence analysis has indicated that the dectin-1 extracellular domain is a C-type lectin-like domain, and functional studies have established that it binds fungal beta-glucans. We report several dectin-1 crystal structures, including a high-resolution structure and a 2.

Intracerebroventricular antisense knockdown of G alpha i2 results in ciliary stasis and ventricular dilatation in the rat.

Background: In the CNS, the heterotrimeric G protein Galphai2 is a minor Galpha subunit with restricted localization in the ventricular regions including the ependymal cilia. The localization of Galphai2 is conserved in cilia of different tissues, suggesting a particular role in ciliary function. Although studies with Galphai2-knockout mice have provided information on the role of this Galpha subunit in peripheral tissues, its role in the CNS is largely unknown.

Music therapy as a non-pharmacological anxiolytic for paediatric radiotherapy patients.

Outpatient radiotherapy treatment in the paediatric cancer patient can be a traumatic and an anxiety-provoking experience for both the patient and the family. Music therapy has been widely reported to have psychosocial, educational and physical benefits for the paediatric cancer patient. Using individual case reports, this paper shows the successful use of music therapy as a non-pharmacological anxiolytic in the paediatric radiotherapy, outpatient waiting room setting, by providing the patient and the family with a means of communication, self-expression and creativity.

The crystal structure and mutational binding analysis of the extracellular domain of the platelet-activating receptor CLEC-2.

The human C-type lectin-like molecule CLEC-2 is expressed on the surface of platelets and signaling through CLEC-2 causes platelet activation and aggregation. CLEC-2 is a receptor for the platelet-aggregating snake venom protein rhodocytin. It is also a newly identified co-receptor for human immunodeficiency virus type 1 (HIV-1).

Enhanced delivery of nebulised salbutamol during non-invasive ventilation.

Non-invasive ventilation (NIV) is used to treat acute respiratory failure. Nebulised drugs can be delivered concurrently with NIV or during breaks from ventilatory support. We hypothesised that the amount of nebulised salbutamol inhaled when delivered via bi-level ventilation would be no different to the amount available directly from the same nebuliser.

The structure of the human allo-ligand HLA-B*3501 in complex with a cytochrome p450 peptide: steric hindrance influences TCR allo-recognition.

Virus-specific T cell populations have been implicated in allo-recognition. The subdominant T cell receptor JL12 recognizes both HLA-B*0801 presenting the Epstein-Barr virus-derived peptide FLRGRAYGL and also HLA-B*3501 presenting the cytochrome p450 self peptide KPIVVLHGY. This cross-reactivity could promote the rejection of HLA-B*3501-positive cells in Epstein-Barr virus-exposed HLA-B*0801 recipients.

Stroke care in long-term care facilities in southwestern Ontario.

Purpose: This study describes the current state of stroke care and rehabilitation in facility-based long-term care (LTC).

Method: LTC representatives, community partners (including physiotherapists and occupational therapists), stroke survivors, and family members were interviewed about stroke care provided in LTC facilities.

Results: Limitations of the current system were identified including inadequate provision of therapy, unequal access to specialized rehabilitation, lack of staff training to care for the specialized needs of residents with stroke, and the lack of coordinated and consistent care.

Has Ontario's Stroke System really made a difference?

The progress that has been made in preventing and treating stroke since 2000, when the Joint Stroke Strategy Working Group tabled its blueprint report, Towards an Integrated Stroke Strategy, is very encouraging. The evaluation results demonstrate that the Ontario Stroke System has had positive measurable impacts on access to stroke-related services, the integration and coordination of stroke care, treatment for stroke, and client and provider satisfaction.

Vector seasonality, host infection dynamics and fitness of pathogens transmitted by the tick Ixodes scapularis.

Fitness of tick-borne pathogens may be determined by the degree to which their infection dynamics in vertebrate hosts permits transmission cycles if infective and uninfected tick stages are active at different times of the year. To investigate this hypothesis we developed a simulation model that integrates the transmission pattern imposed by seasonally asynchronous nymphal and larval Ixodes scapularis ticks in northeastern North America, with a model of infection in white-footed mice (Peromyscus leucopus) reservoir hosts, using the bacteria Borrelia burgdorferi and Anaplasma phagocytophilum as examples. In simulations, survival of microparasites, their sensitivity to reduced rodent and tick abundance, and to 'dilution' by a reservoir-incompetent host depended on traits that allowed (i) highly efficient transmission from acutely-infected hosts, (ii) long-lived acute or 'carrier' host infections, and/or (iii) transmission amongst co-feeding ticks.

Defining the T cell antigen proteome of wasp venom.

Background: While modulation of T cell function is believed to be important in the successful acquisition of clinical tolerance during venom immunotherapy, little is known of the role of wasp venom specific T cell antigens.

Objective: We sought comprehensively to characterize the T cell proteome for wasp venom to facilitate the future development of T cell-based immunotherapeutic approaches.

Methods: Using peripheral blood mononuclear cells from wasp venom-allergic individuals and IL-4 ELISPOT analysis, we characterized T cell responses to whole venom and gel filtration/ion exchange-fractionated venom.

Functional status and health-related quality of life during inpatient stroke rehabilitation.

Objective: To examine changes in functional status and health-related quality of life (HRQOL) during inpatient stroke rehabilitation to examine the associations between changes in the two measures.

Design: Two independently collected databases were combined for a retrospective analysis. One contained the objectively assessed FIM score; the other contained the subjectively assessed Medical Outcomes Study 36-item short form (SF-36).

An exploration of the experience of gaining awareness of deficit in people who have suffered a traumatic brain injury.

Gaining awareness of deficits was explored in 10 people with moderate to severe traumatic brain injury (TBI) using a semi-structured interview and interpretative phenomenological analysis. Eight master themes emerged from the transcripts. Knowledge of deficits was acquired through personal discovery and the reactions of others, often outside the rehabilitation environment.

Reductions of circulating matrix metalloproteinase 2 and vascular endothelial growth factor levels after treatment with pegvisomant in subjects with acromegaly.

Background: Vascular endothelial growth factor (VEGF) is involved in activation of the matrix metalloproteinase (MMP) system; the latter is implicated in atherosclerosis and cardiovascular disease. Patients with acromegaly have reduced life expectancy primarily due to cardiac disease.

Aim: This study assessed plasma MMPs and VEGF levels in patients with active acromegaly (IGF-I > 130% upper limit of normal), and on treatment with pegvisomant.

Effect of sleeping position on nasal patency in newborns.

Sleeping posture has been implicated in the pathophysiology of sudden infant death syndrome. The effect of supine and lateral sleeping positions on nasal patency was investigated using acoustic rhinometry in 11 healthy newborns. The implications of the findings in sudden infant death syndrome are discussed.

[Renal manifestations of systemic autoimmune disease: diagnosis and therapy].

Renal involvement is relatively common in certain systemic autoimmune diseases, but can be clinically silent. Active surveillance is, therefore, essential because the early recognition of renal involvement may influence the extent of renal recovery. Blood pressure control is also essential, regardless of the underlying disease.

Effect of oropharyngeal length in drug lung delivery via suspension pressurized metered dose inhalers.

Purpose: To determine the effect of the oropharyngeal length in adults on the lung dose of a suspension pressurized metered dose inhaler, and whether employing small volume spacers can alter this role.

Methods: Depositions of Ventolin Evohaler (100) microg in the oropharyngeal models of two healthy adult subjects with 17.1 cm (short cast) and 19.

Effects of hormone replacement therapy type and route of administration on plasma matrix metalloproteinases and their tissue inhibitors in postmenopausal women.

Background: Matrix metalloproteinases (MMPs) are implicated in numerous disease states including cardiovascular disease and cancer. Because recent studies have shown a detrimental effect of hormone replacement therapy on cardiovascular disease and breast cancer, we investigated whether there are any differences in the concentrations of MMPs and their tissue inhibitors (TIMPs) in women receiving various forms of postmenopausal therapy.

Material And Methods: A total of 195 healthy postmenopausal women were assessed: 46 were taking tibolone, 47 were taking transdermal estradiol, 46 were taking conjugated equine estrogens (CEE), and 56 were not taking any menopausal therapy (CTR).