Photodynamic therapy for inflammatory choroidal neovascularisation unresponsive to immunosuppression

Aim: To report on visual and angiographic outcomes of a consecutive series of patients with inflammatory choroidal neovascular membranes (CNV) unresponsive to systemic immunosuppression treated with photodynamic therapy (PDT). Methods: The medical records of six consecutive patients with inflammatory CNVs that failed to respond to systemic immunosuppression and that later underwent PDT were retrospectively reviewed. Patient demographics, visual acuity, and fluorescein angiographic findings were evaluated. Results: There were five females and one male with a mean age of 40.8 years (range 35-58 years). Four patients had clinical features consistent with punctate inner choroidopathy and two with presumed ocular histoplasmosis. In all cases clinical signs of CNV activity, including subretinal fluid, subretinal blood, hard exudates, and/or recent decrease in visual acuity were present prior to PDT. All patients had been treated with high dose systemic immunosuppressants, which failed to induce regression of the CNV and/or to improve vision. The CNVs were subfoveal in five patients and juxtafoveal in one; all were classified as predominantly classic. Following PDT an improvement in vision occurred in all cases (median improvement of 18 letters, range 3-42 letters). At last follow up, signs of decreased activity in the CNV were detected in all cases. Patients were followed for a median of 10 months (range 9-20 months). Conclusion: PDT appears to be a useful option in the management of patients with inflammatory CNVs unresponsive to immunosuppressive therapies.

Targeting EGFR Induced Oxidative Stress by PARP1 Inhibition in Glioblastoma Therapy

Despite the critical role of Epidermal Growth Factor Receptor (EGFR) in glioblastoma pathogenesis [1,2], EGFR targeted therapies have achieved limited clinical efficacy [3]. Here we propose an alternate therapeutic strategy based on the conceptual framework of non-oncogene addiction [4,5]. A directed RNAi screen revealed that glioblastoma cells overexpressing EGFRvIII [6], an oncogenic variant of EGFR, become hyper-dependent on a variety of DNA repair genes. Among these, there was an enrichment of Base Excision Repair (BER) genes required for the repair of Reactive Oxygen Species (ROS)-induced DNA damage, including poly-ADP ribose polymerase 1 (PARP1). Subsequent studies revealed that EGFRvIII overexpression in glioblastoma cells caused increased levels of ROS, DNA strand break accumulation, and genome instability. In a panel of primary glioblastoma lines, sensitivity to PARP1 inhibition correlated with the levels of EGFR activation and oxidative stress. Gene expression analysis indicated that reduced expression of BER genes in glioblastomas with high EGFR expression correlated with improved patient survival. These observations suggest that oxidative stress secondary to EGFR hyperactivation necessitates increased cellular reliance on PARP1 mediated BER, and offer critical insights into clinical trial design.

Hormone therapy and intraocular pressure in nonglaucomatous eyes

Objective: The influence of sex hormones on intraocular pressure (IOP) has been the focus of recent debate. Previous studies investigating the effects of hormone therapy (HT) on IOP in postmenopausal women have produced conflicting results but have been limited by small numbers of participants. The aim of our study was to compare IOP in women without glaucoma taking HT with those not taking HT. Methods: A prospective cross-sectional study of postmenopausal women visiting a single ophthalmic medical practitioner was conducted. All women with a history of intraocular disease, a family history of glaucoma, or refractive error exceeding ±5 diopters were excluded. Applanation tonometry was used to measure IOP, and participants were then asked if they were current HT users. Results: A total of 263 participants were recruited, of whom 91 reported current use of HT; 172 had never used HT. Within the HT group, 33 were taking an estrogen-therapy and 58 were taking a estrogen-progesterone therapy. Mean IOP in the HT group was significantly lower than that in the non-HT group; the mean difference was 1.41 mm Hg (P <0.001). This difference remained statistically significant after statistical correction for age, use of systemic ß-blockers, and time of IOP measurement. There was no significant difference in mean IOP between women taking combined versus those taking estrogen-only preparations. Conclusions: Our study showed that IOP was significantly lower in women taking HT than in those who had never taken HT, even after removing other possible influences on IOP. The IOP-lowering effect of HT deserves further investigation to explore whether it may represent a possible new therapeutic modality for glaucoma. © 2010 by The North American Menopause Society.

School-based counseling using systematic feedback: A cohort study evaluating outcomes and predictors of change

The outcomes of school-based counseling incorporating the Partners for Change Outcome Monitoring System (PCOMS) were evaluated using a cohort design, with multilevel modeling to identify predictors of change. Participants were 288 7-11 year olds experiencing social, emotional or behavioral difficulties. The intervention was associated with significant reductions in psychological distress, with a pre-post effect size (d) of 1.49 on the primary outcome measure and 88.7% clinical improvement. Greater improvements were found for disabled children, older children, and where CBT methods were used. The findings provide support for the use of systematic feedback in therapy with children.

Complementary Therapy: perceptions of older people with lung or colorectal cancer

Aim: To explore how older people with lung and colorectal cancer
view registered complementary therapy (CT) services in Northern
Ireland. Background: A literature review highlighted gaps around
information, access, and communication between patients and health
professionals regarding CT services. Methods: Using structured
interviews, a survey of 68 patients in one hospital and one hospice was
conducted in Belfast, Northern Ireland. Results: All respondents felt
that CT services should be better promoted and more easily
accessible to older people with cancer. Some patients were concerned
about the lack of written information provided regarding CT services,
which they believed led to poorer uptake and uncertainty regarding
the potential benefits. Others were concerned that engaging in or
disclosing CT usage might negatively affect existing relationships with
medical professionals. Conclusion: Patients should be offered high
quality written information on CT services to enable choice, improve
knowledge, and promote wider access. Increased physician education
may facilitate provision of such information.

A qualitative study of psychological, social and behavioral barriers to appropriate food portion size control

Background: Given the worldwide prevalence of overweight and obesity, there is a clear need for meaningful practical healthy eating advice - not only in relation to food choice, but also on appropriate food portion sizes. As the majority of portion size research to date has been overwhelmingly quantitative in design, there is a clear need to qualitatively explore consumers’ views in order to fully understand how food portion size decisions are made. Using qualitative methodology this present study aimed to explore consumers’ views about factors influencing their portion size selection and consumption and to identify barriers to appropriate portion size control.

Methods: Ten focus groups with four to nine participants in each were formed with a total of 66 persons (aged 19–64 years) living on the island of Ireland. The semi-structured discussions elicited participants’ perceptions of suggested serving size guidance and explored the influence of personal, social and environmental factors on their food portion size consumption. Audiotapes of the discussions were professionally transcribed verbatim, loaded into NVivo 9, and analysed using an inductive thematic analysis procedure.
Results: The rich descriptive data derived from participants highlight that unhealthy portion size behaviors emanate from various psychological, social and behavioral factors. These bypass reflective and deliberative control, and converge to constitute significant barriers to healthy portion size control. Seven significant barriers to healthy portion size control were apparent: (1) lack of clarity and irrelevance of suggested serving size guidance; (2) guiltless eating; (3) lack of self-control over food cues; (4) distracted eating; (5) social pressures; (6) emotional eating rewards;
and (7) quantification habits ingrained from childhood.

Conclusions: Portion size control strategies should empower consumers to overcome these effects so that the consumption of appropriate food portion sizes becomes automatic and habitual.
Keywords: Food portion size, Barriers, Obesity, Consumers, Qualitative study. © 2013 Spence et al.; licensee BioMed Central Ltd

Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes

An impaired glomerular filtration rate (GFR) leads to end-stage renal disease and increases the risks of cardiovascular disease and death. Persons with type 1 diabetes are at high risk for kidney disease, but there are no interventions that have been proved to prevent impairment of the GFR in this population.

ELIMED:A new hadron therapy concept based on laser driven ion beams

Laser accelerated proton beams have been proposed to be used in different research fields. A great interest has risen for the potential replacement of conventional accelerating machines with laser-based accelerators, and in particular for the development of new concepts of more compact and cheaper hadrontherapy centers. In this context the ELIMED (ELI MEDical applications) research project has been launched by INFN-LNS and ASCR-FZU researchers within the pan-European ELI-Beamlines facility framework. The ELIMED project aims to demonstrate the potential clinical applicability of optically accelerated proton beams and to realize a laser-accelerated ion transport beamline for multi-disciplinary user applications. In this framework the eye melanoma, as for instance the uveal melanoma normally treated with 62 MeV proton beams produced by standard accelerators, will be considered as a model system to demonstrate the potential clinical use of laser-driven protons in hadrontherapy, especially because of the limited constraints in terms of proton energy and irradiation geometry for this particular tumour treatment. Several challenges, starting from laser-target interaction and beam transport development up to dosimetry and radiobiology, need to be overcome in order to reach the ELIMED final goals. A crucial role will be played by the final design and realization of a transport beamline capable to provide ion beams with proper characteristics in terms of energy spectrum and angular distribution which will allow performing dosimetric tests and biological cell irradiation. A first prototype of the transport beamline has been already designed and other transport elements are under construction in order to perform a first experimental test with the TARANIS laser system by the end of 2013. A wide international collaboration among specialists of different disciplines like Physics, Biology, Chemistry, Medicine and medical doctors coming from Europe, Japan, and the US is growing up around the ELIMED project with the aim to work on the conceptual design, technical and experimental realization of this core beamline of the ELI Beamlines facility. © 2013 SPIE.

Predicting the need for insulin therapy in late onset (40-69 years) diabetes mellitus

A six-year prospective study of 144 newly diagnosed, symptomatic diabetic patients aged 40-69 years showed that 21 (15%) required insulin therapy, commencing 1-61 months after diagnosis. The plasma insulin response to oral glucose was assessed at the time of diagnosis. All 12 patients with very low peak insulin response (less than or equal to 6 mU/l) required insulin therapy. Thirty-six patients had an intermediate insulin response (greater than 6 less than or equal to 18 mU/l); of these, 7 with a mean weight 88% (range 73-96%) of average body weight required insulin, while 29 with a mean weight 117% (range 98-158%) of average body weight, did not. Ninety-six patients had a peak insulin response (greater than 18 mU/l); 2 patients whose weights were 96% and 100% of average body weight, required insulin, while the remainder did not. Consideration of initial body weight and peak insulin response provides a useful prediction of the eventual need for insulin.

The future of antimicrobial therapy in the era of antibiotic resistance in cystic fibrosis pulmonary infection

Cystic fibrosis (CF) is characterised by chronic polymicrobial airway infection and inflammation, which is the major cause of morbidity and mortality. Aggressive use of antimicrobials has been fundamental in increasing the life expectancy of CF patients in recent years. However, enhanced culture and non-culture based detection methods have identified bacteria in the CF lung not previously isolated from CF patients by routine diagnostic microbiology Coupled with increasing antimicrobial resistance, the future of antimicrobial therapy in CF respiratory infection remains challenging. New strategies are needed to address these problems and ensure improvements in life expectancy are maintained. Potential future strategies include the use of new antimicrobial agents and formulations currently in clinical trials, alternative methods of selecting appropriate therapeutic regimens, determination of the pathogenicity of species newly associated with CF and the development of new antimicrobials and adjuvants for use in clinical practice.