Susceptibility of streptozotocin-induced diabetic rat retinal function and ocular blood flow to acute intraocular pressure challenge.

PURPOSE: To consider whether STZ-induced hyperglycemia renders rat retinal function and ocular blood flow more susceptible to acute intraocular pressure (IOP) challenge.

METHODS: Retinal function (electroretinogram, ERG) was measured during acute IOP challenge (10-100 mmHg, 5 mmHg increments, 3 min/step, vitreal cannulation) in adult Long-Evans rats (6-week old, citrate: n=6, STZ: n=10) 4 weeks after citrate buffer or streptozotocin (STZ, 65 mg/kg, blood glucose > 15 mmol/l) injection. At each IOP, dim and bright flash (-4.56, -1.72 log cd.s.m^-2) ERG responses were recorded to measure inner retinal and ON-bipolar cell function, respectively. Ocular blood flow (laser Doppler flowmetry, citrate; n=6, STZ; n=10) was also measured during acute IOP challenge. Retinae were isolated for qPCR analysis of nitric oxide synthase mRNA expression endothelial, eNos; inducible, iNos; neuronal, nNos).

RESULTS: STZ-induced diabetes increased the susceptibility of inner retinal (IOP at 50% response, 60.1, CI: 57.0-62.0 mmHg vs. citrate: 67.5, CI: 62.1-72.4 mmHg) and ON-bipolar cell function (STZ: 60.3, CI: 58.0-62.8 mmHg vs. citrate: 65.1, CI: 58.0-62.78 mmHg) and ocular blood flow (43.9, CI: 40.8-46.8 vs. citrate: 53.4, CI: 50.7-56.1 mmHg) to IOP challenge. Citrate eyes showed elevated eNos mRNA (+49.7%) after IOP stress, an effect not found in STZ-diabetic eyes (-5.7%, P<0.03). No difference was observed for iNos or nNos (P>0.05) following IOP elevation.

CONCLUSIONS: STZ-induced diabetes increased functional susceptibility during acute IOP challenge. This functional vulnerability is associated with a reduced capacity for diabetic eyes to upregulate eNOS expression and to autoregulate blood flow in response to stress.

Re-challenge chemotherapy with gemcitabine plus carboplatin in patients with non-small cell lung cancer

Despite recent improvements to current therapies and the emergence of novel agents to manage advanced non-small cell lung cancer (NSCLC), the patients' overall survival remains poor. Re-challenging with first-line chemotherapy upon relapse is common in the management of small cell lung cancer but is not well reported for advanced NSCLC. NSCLC relapse has been attributed to acquired drug resistance, but the repopulation of sensitive clones may also play a role, in which case re-challenge may be appropriate. Here, we report the results of re-challenge with gemcitabine plus carboplatin in 22 patients from a single institution who had previously received gemcitabine plus platinum in the first-line setting and had either partial response or a progression-free interval of longer than 6 months. In this retrospective study, the charts of patients who underwent second-line chemotherapy for NSCLC in our cancer center between January 2005 and April 2010 were reviewed. All the patients who received a combination of gemcitabine and carboplatin for re-challenge were included in the study. These patients were offered second-line treatment on confirmation of clear radiological disease progression. The overall response rate was 15% and disease control rate was 75%. The median survival time was 10.4 months, with 46% of patients alive at 1 year. These results suggest that re-challenge chemotherapy should be considered in selected patients with radiological partial response or a progression-free survival of longer than 6 months to the initial therapy.

The challenge to health professionals when carers resist truth telling at the end of life: a qualitative secondary analysis

Aims and objectives: To draw out the similar complexities faced by staff around
truth-telling in a children’s and adult population and to interrogate the dilemmas faced by staff when informal carers act to block truth-telling.

Background: Policy encourages normalisation of death, but carers may act to protect or prevent the patient from being told the truth. Little is known about the impact on staff.

Design: Secondary analysis of data using a supra-analysis design to identify commonality of experiences.

Methods: Secondary ‘supra-analysis’ was used to transcend the focus of two primary studies in the UK, which examined staff perspectives in a palliative children’s and a palliative adult setting, respectively. The analysis examined new theoretical questions relating to the commonality of issues independently derived in each primary study. Both primary studies used focus groups. Existing empirical data were analysed thematically and compared across the studies.

Results: Staff reported a hiding of the truth by carers and sustained use of activities aimed at prolonging life. Carers frequently ignored the advance of end of life, and divergence between staff and carer approaches to truth-telling challenged professionals. Not being truthful with patients had a deleterious effect on staff, causing anger and feelings of incompetence.

Conclusions: Both children’s and adult specialist palliative care staff found themselves caught in a dilemma, subject to policies that promoted openness in planning for death and informal carers who often prevented them from being truthful with patients about terminal prognosis. This dilemma had adverse psychological effects upon many staff.

Relevance to clinical practice: There remains a powerful death-denying culture in
many societies, and carers of dying patients may prevent staff from being truthful with their patients. The current situation is not ideal, and open discussion of this problem is the essential first step in finding a solution.

Belfast beyond violence: Flagging up a challenge to local government?

Northern Ireland is emerging from violence but still living with conflict. The recent flags protests in Belfast represent a challenge to public administration to transcend the contested politics of local government in Northern Ireland and to navigate a way through a symbolic legacy issue. This article draws on a longitudinal hermeneutic analysis of empirical research conducted on Northern Ireland local government over a decade, where these concerns dominated much debate. Additional analysis of the research findings reveals broader problems applicable to any public administration faced with managing situations in which good governance in public participation and procedural correctness operates alongside fundamental political disagreement and distrust. These conclusions are particularly pertinent for local administrations in societies transitioning from conflict.

Economic and social integration the challenge for EU constitutional law

'At a time of crisis and therefore a crucial juncture in European politics, Dagmar Schiek offers us an inspiring vision of the potential of the European Union. In her brilliant study, she exposes the obstacles that economic integration has posed for achievement of social justice, and provides a bold solution. Rejecting more limited models of constitutionalism, she presents a convincing alternative which is socially embedded, allowing space for action by manifold actors at multiple levels of governance.' - Tonia Novitz, University of Bristol, UK. © Dagmar Schiek 2012. All rights reserved.

Islamist Versus Islamist: Rising Challenge in Gaza

Islam's diversity is a direct result of centuries of schism and factionalism, and presents a challenge to the original spirit of unity as envisaged by its founder, the Prophet Mohammed. Rivalry within Islam undermines the precedent notion of unity through communal belonging (tawhid and ummah). Yet in the twenty-first century this diversity is ignored, and political Islam is represented as being more of a monolith than a spectrum of ideas and aspirations. Generally, the materialization of new Islamist groups is a challenge to those who hold that unity is all. In the Gaza Strip, specifically, the dominant Islamist actor, Hamas, is facing internal challenges from other Islamist elements. These rival Islamists are also influenced by events across their border in post-revolutionary Egypt where a plethora of new Islamist actors are vying for political space and power. This article deals with Hamas's Islamist rivals, and the effects they have had on Hamas's governance of the Gaza Strip, and political and religious legitimacy within it. It will focus on ideological and violent disputes between the Islamist elements in Gaza, and the means by which Hamas and its security elements have tackled newly emerging rivals.

Gerodontology--how big is the challenge in Ireland?

Population trends suggest that the Irish population is ageing, and that this population will have substantial treatment needs. These patients will be better informed than previous generations, and will demand treatment aimed at preserving a natural dentition. This will impact upon delivery of oral healthcare and manpower planning needs to consider how to address the increased demand for dental care. Poor oral health is associated with systemic health problems, including cardiovascular disease, respiratory disease and diabetes mellitus. It also has a negative impact upon quality of life, and the World Health Organisation has encouraged public healthcare administrators and decision makers to design effective and affordable strategies for better oral health and quality of life of older adults, which, in turn, are integrated into general health management programmes. Treatment concepts such as minimally invasive dentistry and the shortened dental arch concept are discussed in the context of these demographic changes and recommendations.

A review of the global pesticide legislation and the scale of challenge in reaching the global harmonization of food safety standards

Pesticide use is important in agriculture to protect crops and improve productivity. However, they have the potential to cause adverse human health or environmental effects, dependent on exposure levels. This review examines existing pesticide legislation worldwide, focusing on the level of harmonisation, and impacts of differing legislation on food safety and trade. Pesticide legislation varies greatly worldwide as countries have different requirements guidelines and legal limits for plant protection. Developed nations have more stringent regulations than developing countries, which lack the resources and expertise to adequately implement and enforce legislation. Global differences in pesticide legislation act as a technical barrier to trade. International parties such as the European Union (EU), Codex Alimentarius Commission (Codex), and North American Free Trade Agreement (NAFTA) have attempted to harmonise pesticide legislation by providing maximum residue limits (MRLs), but globally these limits remain variable. Globally harmonised pesticide standards would serve to increase productivity, profits and trade, and enhance the ability to protect public health and the environment.