Pharmacogenetics : the science of predictive clinical pharmacology

The study of pharmacogenetics has expanded from what were initially casual family-based clinical drug response observations, to a fully-fledged science with direct therapeutic applications, all within a time-span of less than 60 years. A wide spectrum of polymorphisms, located within several genes, are now recognised to influence the pharmacokinetics and pharmacodynamics of the majority of drugs within our therapeutic armamentarium. This information forms the basis for the new development of pharmacogenetic genotyping tests, which can be used to predict the therapeutic and/or adverse effects of a specific drug in a particular patient. Pharmacogenetic-guided, patient targeted therapy has now become the developing fulcrum of personalized medicine, as it provides the best means to optimize benefit/risk ratio in pharmacological management.peer-reviewe

Biotech drugs : biological therapeutic agents

The recent years has seen significant growth in a new therapeutic approach to the management of disease. Biological therapeutic agents, constitute a broad category of drugs, usually generated by recombinant techniques from living organisms. These therapies revolutionise the traditional approaches to drug design and development, and regulatory agencies have been swift in developing the necessary structures to ensure their optimal use.peer-reviewe

Pentalogy of Cantrell : the first Maltese case with successful outcome

Pentalogy of Cantrell is a rare disorder which was first described by Cantrell and his colleagues in 1958. It is comprised of congenital heart disease and midline defects. Surgical treatment is possible with internalisation of the heart, repair of associated intracardiac anomalies and repair of the thoraco-abdominal defect. In this article the authors describe the first Maltese case, with a successful outcome.peer-reviewe

Pension reforms since the financial crisis could have a serious impact on the future retirement incomes of young Europeans

What effect has the financial crisis had on pension systems in EU countries? Aaron G. Grech notes that prior to the crisis there was a significant divergence in pensions across the EU, with some states having relatively generous systems in comparison to others. He writes that following the crisis, southern European states have had to substantially cut back on pensions, while other states in northern Europe have remained relatively unscathed. He argues that although it should still be possible for these systems to keep pensioners out of poverty, European policymakers will need to ensure a properly functioning labour market that provides opportunities for young Europeans

Coherent forward stimulated Brillouin scattering of a spatially incoherent laser beam in a plasma and its effect on beam spray

A statistical model for forward stimulated Brillouin scattering (FSBS) is developed for a spatially incoherent, monochromatic, laser beam propagating in a plasma. A threshold for the average power in a speckle is found, well below the self-focusing one, above which the laser beam spatial incoherence can not prevent the coherent growth of FSBS. Three-dimensional simulations confirm its existence and reveal the onset of beam spray above it. From these results, we propose a new figure of merit for the control of the propagation through a plasma of a spatially incoherent laser beam.Comment: submitted to PR

The relationship between infecting organisms and underlying structural anomalies in children with urinary tract infections

Introduction: Urinary tract infections (UTIs) are a common cause of morbidity in childhood with potential for renal scarring and reflux nephropathy which can lead to hypertension and end-stage renal failure. Aim: The aim of this study was to investigate the relationship between the infecting organism and any underlying anomalies of the urinary tract which may predispose to the development of infections and which may alter the management of children with UTIs. Methods and results: A total of 72 cases of UTI were recorded retrospectively (in- and outpatients), with ages ranging from 3 days to 48 months (mean 9.5, median 5 months). Fifty seven (79%) of patients had their first reported urinary tract infection under the age of 1 year.. Fifty eight (80.6%) were E. coli infections. These presented at an older age than non-E. coli infections. Investigations were abnormal in 31 (43%) cases. The mean age for first infection in patients with abnormal investigations was 7.7 months (median 2 months), younger than those with no renal tract abnormalities. Organisms other than E. coli were rarely found when no significant abnormalities were detected with investigation by US and MCUG and this was a statistically significant difference (p<0.001). Renal scarring was identified in 10 (13.9%) patients. Discussion: This study confirms that non-E. coli UTI is associated with underlying renal pathology and that early infections with any organism are more likely to be associated with underlying abnormalities. We also outline an algorithm based on the recent NICE 2007 guidelines which will be adopted by the Paediatric Department, Mater Dei Hospital for the investigation of UTI.peer-reviewe

A comparison of clinical paediatric murmur assessment with echocardiography

Objective: To compare the clinical acumen of paediatric cardiovascular examination between various hospital paediatrician grades. Design: Prospective data collection of clinical and echocardiography findings on paediatric echocardiography referrals. Setting and patients: All paediatric patients (birth - 14 years) referred for echocardiography, in a regional hospital catering for the island population of Malta. Echocardiography was carried out by three paediatricians with tertiary training in this technique. Main outcome measures: Pre-echocardiography clinical diagnoses were compared with echocardiography results according to grade of referring hospital doctor (ranging from houseman to consultant). Both normal and abnormal hearts at echocardiography were included. Results: Echocardiographers had the highest clinical accuracy and the highest attempts at reaching a clinical diagnosis. Accuracy and attempts at diagnosis decreased as doctor's hospital grade decreased, from consultant to houseman. Ventricular septal defect was the most easily diagnosed lesion. Atrial septal defect was often misdiagnosed as pulmonary stenosis.peer-reviewe

Pharmacogenetics and personalized medicine : does gender have a role?

The study of the role of genetic polymorphisms in drug responses, is now a firmly established field of pharmacology research. It has robust applications in predicting drug effect, and therefore contributes to the process of optimum selection of drug and dose for specific patients. Since the last 10 years, the FDA as well as the EMA have set up their own pharmacogenomics advisory groups, and have flagged an increasing number of medicinal products with specific genotyping recommendations in order to reap their greatest benefit. The contribution of gender to therapeutic outcomes has long been recognised, but recent research suggests that gender influence may not only occur via well recognised hormonal pathways, but also via direct non-hormone-mediated mechanisms. This influence may confound pharmacogenetic predictors, and gender stratification may therefore be an important consideration in pharmacogenetic-based drug trials.peer-reviewe