Warts in general practice

Eight hundred and ninety seven patients referred by their general practitioner to Health Centre Wart Clinics were interviewed. Seventy one patients (7.9%) were found to have lesions other than cutaneous warts. Females were significantly more likely to have plantar warts on their toes (p less than 0.002) and non-plantar warts on their fingers (p less than 0.03) and less likely to have non-plantar warts on the palms of their hands (p less than 0.03) than males. Patients living in large households (5+ persons) were more likely than patients living in smaller households (2-4 persons) to report an infected co-habitant (p less than 0.001). Patients with periungual warts were significantly more likely to be nailbiters. (p less than 0.001). Patients presenting with warts greater than two years in duration were more likely to have multiple warts than those with warts less than one month in duration (p less than 0.001). Patients who frequently immersed their hands in water were more likely to present with multiple warts on the hands (p less than 0.001). Multiple plantar warts were associated with moist or macerated feet (p less than 0.001). The role of the family doctor in diagnosing and preventing the spread of this infection is discussed.

Digoxin toxicity in the aged. Characterising and avoiding the problem

Digoxin is one of the most frequently prescribed drugs, particularly in the elderly population where there is an increased prevalence of atrial fibrillation and cardiac failure. The drug has a narrow therapeutic range and has gained a reputation for producing adverse effects in older patients. The more frail elderly patients with coexistent disease, often taking other treatments, are more at risk from digoxin toxicity due to inappropriate dosing, noncompliance, or increased sensitivity to digoxin resulting from pharmacokinetic or pharmacodynamic interactions. Application of basic pharmacological principles may be helpful in anticipating these problems. Elderly patients more commonly receive digoxin than younger patients, which in part accounts for the higher rates of toxicity in this group. Numerous components contribute to the development of toxicity, and diagnosis of toxicity is difficult in this age group. The measurement of serum concentrations can contribute to the clinical diagnosis. A major problem is the accurate diagnosis of digoxin toxicity which may have numerous nonspecific clinical manifestations, many of which are related to coexisting disease in elderly patients. This diagnostic imprecision is well recognised but has been helped by the introduction of serum digoxin measurement. However, reliance on serum concentrations should not replace clinical judgement, since these do not always correlate with toxicity. The apparently decreasing incidence of toxicity over recent years probably reflects several factors: the improvement in digoxin formulations, awareness of digoxin pharmacology, utilisation of serum concentrations, and the realisation that digoxin withdrawal is a viable proposition in elderly patients. Greater knowledge about the causes and prevention of digoxin toxicity should further reduce the morbidity and mortality arising from digoxin overdose, especially in the elderly population.

Antineutrophil cytoplasmic antibodies in myelodysplasia

Antibodies to neutrophil cytoplasmic antigens (ANCA) are good serological markers for patients with mainly vasculitic conditions. Two main types of ANCAs have been detected, the first termed cytoplasmic antineutrophil cytoplasmic antibody (cANCA) are mainly associated with patients with Wegener's granulomatosis, the other termed perinuclear antineutrophil cytoplasmic antibody (pANCA) are mainly associated with patients with renal vasculitis, rheumatic and collagen disorders. These antibodies are against various constituents of neutrophil granules. In patients with myelodysplasia, defects in normal granulocyte development are seen. We report a series of twelve patients with myelodysplasia of whom at least four showed a low titre and one a high titre of pANCA. Two of these patients also had demonstrable activity against myeloperoxidase (MPO). None of these patients had any evidence of systemic or cutaneous vasculitis or of any autoimmune disorder. There was no pANCA positivity in an age matched control group.

Do perinatal and early life exposures influence the risk of malignant melanoma?:A Northern Ireland birth cohort analysis

Aim: Intrauterine, early life and maternal exposures may have important consequences for cancer development in later life. The aim of this study was to examine perinatal and birth characteristics with respect to Cutaneous malignant melanoma (CMM) risk. Methods: The Northern Ireland Child Health System database was used to examine gestational age adjusted birth weight, infant feeding practices, parental age and socioeconomic factors at birth in relation to CMM risk amongst 447,663 infants delivered between January 1971 and December 1986. Follow-up of histologically verified CMM cases was undertaken from the beginning of 1993 to 31st December 2007. Multivariable adjusted unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) of CMM risk. Results: A total of 276 CMM cases and 440,336 controls contributed to the final analysis. In reference to normal (gestational age-adjusted) weight babies, those heaviest at birth were twice as likely to develop CMM OR 2.4 (95% CI 1.1-5.1). Inverse associations with CMM risk were observed with younger (

Skin Dendritic Cell Targeting via Microneedle Arrays Laden with Antigen-Encapsulated Poly-D, L-lactide-co-Glycolide Nanoparticles Induces Efficient Antitumor and Antiviral Immune Responses

The efficacious delivery of antigens to antigen-presenting cells (APCs), in particular, to dendritic cells (DCs), and their subsequent activation remains a significant challenge in the development of effective vaccines. This study highlights the potential of dissolving microneedle (MN) arrays laden with nanoencapsulated antigen to increase vaccine immunogenicity by targeting antigen specifically to contiguous DC networks within the skin. Following in situ uptake, skin-resident DCs were able to deliver antigen-encapsulated poly-d,l-lactide-co-glycolide (PGLA) nanoparticles to cutaneous draining lymph nodes where they subsequently induced significant expansion of antigen-specific T cells. Moreover, we show that antigen-encapsulated nanoparticle vaccination via microneedles generated robust antigen-specific cellular immune responses in mice. This approach provided complete protection in vivo against both the development of antigen-expressing B16 melanoma tumors and a murine model of para-influenza, through the activation of antigen-specific cytotoxic CD8(+) T cells that resulted in efficient clearance of tumors and virus, respectively. In addition, we show promising findings that nanoencapsulation facilitates antigen retention into skin layers and provides antigen stability in microneedles. Therefore, the use of biodegradable polymeric nanoparticles for selective targeting of antigen to skin DC subsets through dissolvable MNs provides a promising technology for improved vaccination efficacy, compliance, and coverage.

“Boundary-setting as a core activity in complex public systems”

Title: Boundary-setting as a core activity in complex public systems
Authors: Joanne Murphy & Mary Lee Rhodes

The definition of the boundary of a system is at the core of any systems approach (Midgley 2000; 2003). By defining boundaries we enable – and delimit – the range of outcomes sought and the actions and resources that can be brought to bear. In complex adaptive systems (CAS) analysis, the conceptualisaion and definition of boundaries is particularly challenging as they are constantly undergoing redefinition through agent action, interaction and entry/exit. (Rhodes et al 2011). The concept of ‘boundaries’ appears regularly in a wide range of literature around public management, administration, geopolitics, regeneration and organisational development. Discussions around boundaries focus on many things from concrete physical manifestations and barriers, to virtual interfaces between one organisational unit and another, or even entirely theoretical demarcations between different schools of thought (Kaboolian, 1998, Levi-Faur, 2004, Agranoff & McGuire, 2004).

However, managing ‘beyond’ such boundaries is a routinely recurring aspiration that transcends sectors and local concerns. Unsurprisingly then, there is an increasing understanding of the need to acknowledge and manage such boundaries (whether they be physical, social or organisational) within public management as a discipline (Currie et al 2007, Fitzsimmons and White, 1997, Murtagh, 2002). This paper explores the impact of boundaries on public management strategic decision-making in the sectors of urban regeneration and healthcare. In particular, it focuses on demarcations to physical space, communal identity and within professional relationships in these sectors.

The first section describes the research that gave rise to the paper and the cases examined. Next we briefly define what we mean by boundaries. We explore issues that have emerged from our analysis of urban regeneration and health care singularly, before looking at how the concept of boundaries is a recurrent concern across the sectors. The main contribution of the paper is an exploration of how a CAS lens can bring a new insight into the concept of boundaries and decision-making in the two sets of case studies. This discussion will concentrate on initial conditions, bifurcation and adaptation as key CAS factors in relation to boundaries. We conclude with a brief discussion on the benefits of a CAS lens to an analysis of boundaries in public management decision-making.
References:

Agranoff, R. and McGuire, M. (2003) Collaborative Public Management: Strategies for Local Government. Washington, DC: Georgetown Univ. Press.

Currie, G., Lockett, A. (2007) “A critique of transformational leadership: moral, professional & contingent dimensions of leadership within public services organizations”. Human Relations 60: 341-370.

Fitzsimmons and White, (1997) "Crossing boundaries: communication between professional groups", Journal of Management in Medicine, Vol. 11 Iss: 2, pp.96 – 101

Kaboolian, L. (1998) “The New Public Management: Challenging the Boundaries of the Management vs. Administration Debate” Public Administration Review Vol. 58, No. 3 pp.189-193

Levi-Faur D. and Vigoda-Gadot Eran (eds) (2004) International Public Policy and Management: Policy Learning Beyond Regional, Cultural and Political Boundaries, Marcel Dekker,
Midgley, G. (ed) (2003) Systems Thinking. London: Sage Publications

Midgley, G. (2000) Systemic Intervention: Philosophy, Methodology and Practice. New York, NY: Kluwer.

Murtagh, B. (2002). The Politics of Territory: Policy and Segregation in Northern Ireland. Basingstoke, Palgrave.

Rhodes, ML, Joanne Murphy, Jenny Muir, John Murray (2011) Public Management & Complexity Theory: Richer Decision Making in Irish Public Services, UK: Routledge

Immunophenotypic shift in a case of mycosis fungoides with vitreous invasion

The case of an 82-year-old man who developed intraocular extension from mycosis fungoides, a cutaneous T-cell lymphoma, is presented. The patient died soon after intra-ocular involvement occurred. Immunohistochemistry of a skin biopsy, taken early in the course of the disease, disclosed a predominance of T cells with a helper/inducer phenotype (CD4). However, an intraocular infiltrate obtained 7 years later contained mostly T cells with a suppressor/cytotoxic phenotype (CD8). The occurrence of ocular invasion, the change in immunophenotype, and the predominant proliferation of CD8 lymphocytes may have been related to the poor outcome in this patient.

Clinical trials in cystic fibrosis

In patients with cystic fibrosis (CF), clinical trials are of paramount importance. Here, the current status of drug development in CF is discussed and future directions highlighted. Methods for pre-clinical testing of drugs with potential activity in CF patients including relevant animal models are described. Study design options for phase II and phase III studies involving CF patients are provided, including required patient numbers, safety issues and surrogate end point parameters for drugs, tested for different disease manifestations. Finally, regulatory issues for licensing new therapies for CF patients are discussed, including new directives of the European Union and the structure of a European clinical trial network for clinical studies involving CF patients is proposed.

Crime, justice and the legitimacy of military power in the international sphere

This article examines how a discourse of crime and justice is beginning to play a significant role in justifying international military operations. It suggests that although the coupling of war with crime and justice is not a new phenomenon, its present manifestations invite careful consideration of the connection between crime and political theory. It starts by reviewing the notion of sovereignty to look then at the history of the criminalisation of war and the emergence of new norms to constrain sovereign states. In this context, it examines the three ways in which military force has recently been authorised: in Iraq, in Libya and through drones in Yemen, Pakistan and Somalia. It argues the contemporary coupling of military technology with notions of crime and justice allows the reiteration of the perpetration of crimes by the powerful and the representation of violence as pertaining to specific dangerous populations in the space of the international. It further suggests that this authorises new architectures of authority, fundamentally based on military power as a source of social power.

Antioxidants and diabetic retinopathy

The biochemical perturbations in diabetes mellitus (DM) create the conditions for the production of free radicals, the consequence of which is increased oxidative stress. Evidence has accrued over the past 2 decades that suggests that oxidative stress is an important pathogenetic factor in the development of diabetic retinopathy (DR). Experimental data show that the use of strategies that ameliorate oxidative stress can prevent and retard the development of DR in the animal model. Clinical observations also suggest that reducing oxidative stress may help to reverse pathological manifestations of DR. The present article constitutes an examination of the role of antioxidants in the management of DR and the current state of clinically relevant knowledge. © 2013 Springer Science+Business Media New York.

Microneedle-Iontophoresis Combinations for Enhanced Transdermal Drug Delivery

It has recently been proposed that the combination of skin barrier impairment using microneedles (MNs) coupled with iontophoresis (ITP) may broaden the range of drugs suitable for transdermal delivery as well as enabling the rate of delivery to be achieved with precise electronic control. However, few reports exist on the combination of ITP with in situ drug-loaded polymeric MN delivery systems. Our in vitro permeation studies revealed that MN enhances transdermal drug delivery. The combination of dissolving MN and ITP did not further enhance the extent of delivery of the low molecular weight drug ibuprofen sodium after short application periods. However, the extent of peptide/protein delivery was significantly enhanced when ITP was used in combination with hydrogel-forming MN arrays. As such, hydrogel-forming MN arrays show promise for the electrically controlled transdermal delivery of biomacromolecules in a simple, one-step approach, though further technical developments will be necessary before patient benefit is realized.

The sympathetic release test: a test used to assess thermoregulation and autonomic control of blood flow

When a subject is heated, the stimulation of temperature-sensitive nerve endings in the skin, and the raising of the central body temperature, results in the reflex release of sympathetic vasoconstrictor tone in the skin of the extremities, causing a measurable temperature increase at the site of release. In the sympathetic release test, the subject is gently heated by placing the feet and calves in a commercially available foot warming pouch or immersing the feet and calves in warm water and wrapping the subject in blankets. Skin blood flow is estimated from measurements of skin temperature in the fingers. Normally skin temperature of the fingers is 65-75 degrees F in cool conditions (environmental temperature: 59-68 degrees F) and rises to 85-95 degrees F during body heating. Deviations in this pattern may mean that there is abnormal sympathetic vasoconstrictor control of skin blood flow. Abnormal skin blood flow can substantially impair an individual's ability to thermoregulate and has important clinical implications. During whole body heating, the skin temperature from three different skin sites is monitored and oral temperature is monitored as an index of core temperature. Students determine the fingertip temperature at which the reflex release of sympathetic activity occurs and its maximal attainment, which reflects the vasodilating capacity of this cutaneous vascular bed. Students should interpret typical sample data for certain clinical conditions (Raynaud's disease, peripheral vascular disease, and postsympathectomy) and explain why there may be altered skin blood flow in these disorders.

The Postmodernist Critique of Evidence-Based Practice

In this paper, we examine the postmodernist argument that evidence-based practice (EBP) should be rejected by nurses because it restricts the sources of knowledge used by practitioners. Three main postmodernist criticisms are identified and discussed. First, that the notion of ‘best evidence’ implies a hierarchical and exclusivist approach to knowledge. We accept this argument, noting that such a hierarchy is accepted and justified by many of its proponents. Second, that the hierarchy embraced by the evidence-based practice movement damages health care because it excludes other forms of evidence that are needed to understand the complexity of care. We accept that some manifestations of EBP, notably the Cochrane Collaboration, have devalued qualitative evidence. Using our previous experience of conducting Cochrane reviews (McGaughey et al. 2007), we argue that this limits explanatory scope. Third, that it fails to take account of individuals or their experience. Here, we use evidence of the use by midwives of EBP policies and protocols to the detriment of including women in decision-making processes (Porter et al. 2007) to accept that there is also some merit to this critique. We conclude that, while it is not necessary to concur with the total rejection of EBP that postmodernists advocate, it is necessary to address the issues they raise in order to ensure that EBP better fits the requirements of nursing.
McGaughey, J., Alderdice, F., Fowler, R., Kapila, A., Mayhew, A., Moutray, M., 2007. Outreach and Early Warning Systems (EWS) for the prevention of Intensive Care admission and death of critically ill adult patients on general hospital wards. Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD005529. DOI: 10.1002/14651858.CD005529.pub2.
Porter, S., Crozier, K., Sinclair, M., Kernohan, W., 2007. New midwifery? A qualitative analysis of midwives’ decision-making strategies. Journal of Advanced Nursing 60 (6), 525-534.

Resemblance of psychotic symptoms and syndromes in affected sibling pairs from the Irish Study of High-Density Schizophrenia Families:evidence for possible etiologic heterogeneity

The authors sought to determine whether the clinical manifestations of schizophrenia and other psychotic disorders are correlated in affected sibling pairs.

Microneedles for intradermal and transdermal drug delivery

The formidable barrier properties of the uppermost layer of the skin, the stratum corneum, impose significant limitations for successful systemic delivery of broad range of therapeutic molecules particularly macromolecules and genetic material. Microneedle (MN) has been proposed as a strategy to breach the stratum corneum barrier function in order to facilitate effective transport of molecules across the skin. This strategy involves use of micron sized needles fabricated of different materials and geometries to create transient aqueous conduits across the skin. MN, alone or with other enhancing strategies, has been demonstrated to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo experiments. This suggested the promising use of MN technology for various possible clinical applications such as insulin delivery, transcutaneous immunisations and cutaneous gene delivery. MN has been proved as minimally invasive and painless in human subjects. This review article focuses on recent and future developments for MN technology including the latest type of MN design, challenges and strategies in MNs development as well as potential safety aspects based on comprehensive literature review pertaining to MN studies to date. (C) 2013 Elsevier B.V. All rights reserved.