Progressive myopia in early onset chronic angle closure glaucoma.

A 19-year-old girl presented with advanced unilateral chronic angle closure glaucoma and myopia with gross cupping and field loss in a previously hyperopic eye with a marked increase in corneal curvature. This emphasises that a marked myopic shift may be an important sign of glaucoma in a young patient.     

Effectiveness of alliances and partnerships for health promotion

This paper assesses the impact of alliances or partnerships for health promotion in northern and southern nations, as described in published papers and through contemporary accounts of best practice. The balance of evidence from published literature and case study accounts is clear. Alliance or partnership initiatives to promote health across sectors, across professional and lay boundaries and between public, private and non-government agencies, do work. They work in tackling the broader determinants of health and well-being in populations in a sustainable manner, as well as in promoting individual health-related behaviour change. The greater the level of local community involvement in setting agendas for action and in the practice of health promotion, the larger the impact. Volunteer activities, peer programmes and civic activities ensure the maximum benefit from community approaches. In addition, durable structures which facilitate planning and decision-making, such as local committees and councils, are key factors in successful alliances or partnerships for health promotion. Such mechanisms also support the sharing of power, responsibility and authority for change, the maintenance of order and of programmatic relevance, and allow local people one means of reflection and for dissent. At a national, regional, district, village and local community or neighbourhood level, this review found that the existence and implementation of policies for health promotion activities were also crucial to sustainability. The evidence from the review suggests the need for new 'social' indicators to measure the effects of health promotion. Indicators for success which focus only upon benefits for individuals cannot capture adequately the extent of the impact of the many and varied collective, collaborative health promotion initiatives, alliances or partnerships currently underway around the world. These have been shown to affect families, communities, institutions and aspects of the organisation of social and civic life. This paper posits the notion of social capital as one important new framework for organising our thinking about the broader determinants of health and how to influence them through community based approaches to reduce inequalities in health and well-being.Key words: alliances; health promotion; partnerships      

Monitoring plasma levels of fluphenazine during chronic therapy with fluphenazine decanoate

This study was conducted to examine the interpatient variability in steady–state plasma concentrations of fluphenazine by repeat depot intramuscular administration, and to determine the relationship between these concentrations and clinical state. Steady–state pre–dose concentrations of fluphenazine in plasma were measured using a sensitive and specific gas chromatography/mass spectrometry (GC/MS) assay in 24 patients with schizophrenia who were receiving continuous treatment with depot intramuscular fluphenazine decanoate. Clinical response was measured using the Andreasen Scale for positive and negative symptoms. Steady–state plasma concentrations of fluphenazine ranged from undetectable (< 0–l ng/ml) to 27-9 ng/ml, with a median of 0–5 ng/ml. No significant associations were found between plasma concentration and dosage, or age and sex of the patient. Steady–state plasma concentrations in patients taking anticholinergic agents were significantly higher than in patients not receiving such drugs (P < 0–05 by MannWhitney U–test). Poorer control, expressed as the sum of the negative symptom scores or the sum of the positive and negative symptom scores, was related to higher log transformed plasma concentrations of fluphenazine and higher fluphenazine decanoate dosage. The log transformed plasma concentrations of fluphenazine and the fluphenazine decanoate dosages were weakly related. Patients receiving another antipsychotic drug in addition to fluphenazine decanoate tended to have poorer clinical control and higher dosages of fluphenazine decanoate. These results indicate the useful role that plasma level monitoring can fulfil in identifying patients who are therapy–resistant despite high plasma levels.     

Radiation-induced chromosomal aberrations in human lymphocytes after partial-body exposure to 60Co gamma-irradiation and in vitro exposure to 230 kV X-irradiation.

Small yields of chromosome aberrations were present in lymphocytes from 12 patients observed at first metaphase in culbure. Blood samples were obtained at various times, up to three days, after single partial-body therapeutic exposure ranging from 75 to 400 rads of 60Co gamma-irradiation. When all patients were considered there was no correlation between treatment dose and aberration frequency, but on subdivision into two groups on the basis of whether the reticuloendothelial system was involved in the cancer, linear regression analysis could be fitted to the data for each group. An in vitro dose response curve for dicentrics induced by 230 kV X rays at a dose rate of 23.3 rads per minute was constructed for use as a standard calibration curve for 48 hour cultures. The yield of dicentric aberrations was best fitted by a power law model, Y = kDn in which k = (1.59 +/- 0.66) 10(-4) and n= 1.49 +/- 0.08, (P =0.96).     

Hypoxia-inducible factor-1alpha and the glycolytic phenotype in tumors

Metastatic tumors generally exhibit aerobic glycolysis (the Warburg effect). The advent of [18F]fluorodeoxyglucose positron emission tomography imaging, coupled with recent findings linking hypoxia-inducible factor (HIF-1alpha) overexpression to aggressive cancers, has rekindled an interest in this aspect of tumor metabolism. These studies explore the role of HIF-1alpha in human breast cancer lines and its relationship to glycolytic regulation. Here we demonstrate that, under normal oxygen conditions, nonmetastatic cells consume less glucose and express low HIF-1alpha, whereas metastatic cells constitutively express high glycolysis and HIF-1alpha, suggesting that dysregulation of HIF-1alpha may induce the Warburg effect. This hypothesis was tested by renormalizing HIF-1alpha levels in renal carcinoma cells, leading to inhibition of aerobic glycolysis.     

Dendrimers and dendritic polymers in drug delivery

The unique properties of dendrimers, such as their high degree of branching, multivalency, globular architecture and well-defined molecular weight, make them promising new scaffolds for drug delivery. In the past decade, research has increased on the design and synthesis of biocompatible dendrimers and their application to many areas of bioscience including drug delivery, immunology and the development of vaccines, antimicrobials and antivirals. Recent progress has been made in the application of biocompatible dendrimers to cancer treatment, including their use as delivery systems for potent anticancer drugs such as cisplatin and doxorubicin, as well as agents for both boron neutron capture therapy and photodynamic therapy.     

Meta-analysis of heterogeneously reported trials assessing change from baseline

This paper considers the quantitative synthesis of published comparative study results when the outcome measures used in the individual studies and the way in which they are reported varies between studies. Whilst the former difficulty may be overcome, at least to a limited extent, by the use of standardized effects, the latter is often more problematic. Two potential solutions to this problem are; sensitivity analyses and a fully Bayesian approach, in which pertinent external information is included. Both approaches are illustrated using the results of two systematic reviews and meta-analyses which consider the difference in mean change in systolic blood pressure and the difference in physical functioning between an intervention and control group. The two examples illustrate that by adopting a fully Bayesian approach, as opposed to undertaking sensitivity analyses assuming fixed values for unknown parameters, the overall intervention effect can be estimated with greater uncertainty, but that assessing the sensitivity of results to choice of prior distributions in such analyses is crucial.     

The case for strategic international alliances to harness nutritional genomics for public and personal health

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.