Bioluminescent sensor proteins for point-of-care therapeutic drug monitoring.

For many drugs, finding the balance between efficacy and toxicity requires monitoring their concentrations in the patient's blood. Quantifying drug levels at the bedside or at home would have advantages in terms of therapeutic outcome and convenience, but current techniques require the setting of a diagnostic laboratory. We have developed semisynthetic bioluminescent sensors that permit precise measurements of drug concentrations in patient samples by spotting minimal volumes on paper and recording the signal using a simple point-and-shoot camera. Our sensors have a modular design consisting of a protein-based and a synthetic part and can be engineered to selectively recognize a wide range of drugs, including immunosuppressants, antiepileptics, anticancer agents and antiarrhythmics. This low-cost point-of-care method could make therapies safer, increase the convenience of doctors and patients and make therapeutic drug monitoring available in regions with poor infrastructure.

Mise en place d'un programme de prévention et de prise en charge du diabète en Suisse: le point de vue des patients et des professionnels de la santé [Implementation of a diabetes disease management program in Switzerland: patients' and healthcare professionals' point of view].

BACKGROUND: A reorganization of healthcare systems is required to meet the challenge of the increasing prevalence of chronic diseases, e.g. diabetes. In North-America and Europe, several countries have thus developed national or regional chronic disease management programs. In Switzerland, such initiatives have only emerged recently. In 2010, the canton of Vaud set up the "Diabetes Cantonal Program", within the framework of which we conducted a study designed to ascertain the opinions of both diabetic patients and healthcare professionals on the elements that could be integrated into this program, the barriers and facilitators to its development, and the incentives that could motivate these actors to participate. METHODS: We organized eight focus-groups: one with diabetic patients and one with healthcare professionals in the four sanitary areas of the canton of Vaud. The discussions were recorded, transcribed and submitted to a thematic content analysis. RESULTS: Patients and healthcare professionals were rather in favour of the implementation of a cantonal program, although patients were more cautious concerning its necessity. All participants envisioned a set of elements that could be integrated to this program. They also considered that the program could be developed more easily if it were adapted to patients' and professionals' needs and if it used existing structures and professionals. The difficulty to motivate both patients and professionals to participate was mentioned as a barrier to the development of this program however. Quality or financial incentives could therefore be created to overcome this potential problem. CONCLUSION: The identification of the elements to consider, barriers, facilitators and incentives to participate to a chronic disease management program, obtained by exploring the opinions of patients and healthcare professionals, should favour its further development and implementation.

Métabolisme du magnésium pour le clinicien : une mise au point actuelle et simple [Magnesium metabolism for clinical practioner : an up to date review]

La mesure de la fraction libre du magnésium circulant est désormais possible grâce aux électrodes sélectives. Lors d'une déplétion magnésique l'enquête étiologique est orientée par la comparaison de la magnésiurie et de la magnésémie. Les syndromes de Bortter, ou alcaloses hypokaliémiques d'origine rénale, sont des tubulopathies primitives définies par des signes simples: tension artérielle normale; alcalose hypokaliémiques; excrétion rénale conservée des chlorures et recherche de diurétiques négative dans les urines. Grâce à la mesure de la magnésémie et de la calciurie on distingue au moins deux alcaloses hypokaliémiques d'origine rénale, la maladie de Gitelman et le syndrome de Bartter au sens strict.

Choline-PET in prostate cancer management: The point of view of the radiation oncologist.

Among PET radiotracers, FDG seems to be quite accepted as an accurate oncology diagnostic tool, frequently helpful also in the evaluation of treatment response and in radiation therapy treatment planning for several cancer sites. To the contrary, the reliability of Choline as a tracer for prostate cancer (PC) still remains an object of debate for clinicians, including radiation oncologists. This review focuses on the available data about the potential impact of Choline-PET in the daily clinical practice of radiation oncologists managing PC patients. In summary, routine Choline-PET is not indicated for initial local T staging, but it seems better than conventional imaging for nodal staging and for all patients with suspected metastases. In these settings, Choline-PET showed the potential to change patient management. A critical limit remains spatial resolution, limiting the accuracy and reliability for small lesions. After a PSA rise, the problem of the trigger PSA value remains crucial. Indeed, the overall detection rate of Choline-PET is significantly increased when the trigger PSA, or the doubling time, increases, but higher PSA levels are often a sign of metastatic spread, a contraindication for potentially curable local treatments such as radiation therapy. Even if several published data seem to be promising, the current role of PET in treatment planning in PC patients to be irradiated still remains under investigation. Based on available literature data, all these issues are addressed and discussed in this review.

Routine use of point-of-care tests: usefulness and application in clinical microbiology.

Point-of-care (POC) tests offer potentially substantial benefits for the management of infectious diseases, mainly by shortening the time to result and by making the test available at the bedside or at remote care centres. Commercial POC tests are already widely available for the diagnosis of bacterial and viral infections and for parasitic diseases, including malaria. Infectious diseases specialists and clinical microbiologists should be aware of the indications and limitations of each rapid test, so that they can use them appropriately and correctly interpret their results. The clinical applications and performance of the most relevant and commonly used POC tests are reviewed. Some of these tests exhibit insufficient sensitivity, and should therefore be coupled to confirmatory tests when the results are negative (e.g. Streptococcus pyogenes rapid antigen detection test), whereas the results of others need to be confirmed when positive (e.g. malaria). New molecular-based tests exhibit better sensitivity and specificity than former immunochromatographic assays (e.g. Streptococcus agalactiae detection). In the coming years, further evolution of POC tests may lead to new diagnostic approaches, such as panel testing, targeting not just a single pathogen, but all possible agents suspected in a specific clinical setting. To reach this goal, the development of serology-based and/or molecular-based microarrays/multiplexed tests will be needed. The availability of modern technology and new microfluidic devices will provide clinical microbiologists with the opportunity to be back at the bedside, proposing a large variety of POC tests that will allow quicker diagnosis and improved patient care.

Ebstein's anomaly: one and a half ventricular repair.

Patients with Ebstein's anomaly can present after childhood or adolescence with cyanosis, arrhythmias, severe right ventricular dysfunction and frequently with left ventricular dysfunction secondary to the prolonged cyanosis and to the right ventricular interference. At this point conventional repair is accompanied by elevated mortality and morbidity and poor functional results. We report our experience with three patients (8, 16 and 35 years of age) with Ebstein's anomaly, very dilated right atrium, severe tricuspid valve regurgitation (4/4), bi-directional shunt through an atrial septal defect and reduced left ventricular function (mean ejection fraction = 58%, mean shortening fraction = 25%). All underwent one and a half ventricular repair consisting of closure of the atrial septal defect, tricuspid repair with reduction of the atrialised portion of the right ventricle and end-to-side anastomosis of the superior vena cava to the right pulmonary artery. All patients survived, with a mean follow-up of 33 months. In all there was complete regression of the cyanosis and of the signs of heart failure. Postoperative echocardiography showed reduced degree of tricuspid regurgitation (2/4) and improvement of the left ventricular function (mean ejection fraction = 77%, mean shortening fraction = 40%). In patients with Ebstein's anomaly referred late for surgery with severely compromised right ventricular function or even with reduced biventricular function, the presence of a relatively hypoplastic and/or malfunctioning right ventricular chamber inadequate to sustain the entire systemic venous return but capable of managing part of the systemic venous return, permits a one and a half ventricular repair with good functional results.

Traditional local medicines in the republic of Palau and non-communicable diseases (NCD), signs of effectiveness.

ETHNOPHARMACOLOGICAL RELEVANCE: The aim of this survey was to describe which traditional medicines (TM) are most commonly used for non-communicable diseases (NCD - diabetes, hypertension related to excess weight and obesity) in Pacific islands and with what perceived effectiveness. NCD, especially prevalent in the Pacific, have been subject to many public health interventions, often with rather disappointing results. Innovative interventions are required; one hypothesis is that some local, traditional approaches may have been overlooked. MATERIALS AND METHODS: The method used was a retrospective treatment-outcome study in a nation-wide representative sample of the adult population (about 15,000 individuals) of the Republic of Palau, an archipelago of Micronesia. RESULTS: From 188 respondents (61% female, age 16-87, median 48,), 30 different plants were used, mostly self-prepared (69%), or from a traditional healer (18%). For excess weight, when comparing the two most frequent plants, Morinda citrifolia L. was associated with more adequate outcome than Phaleria nishidae Kaneh. (P=0.05). In case of diabetes, when comparing Phaleria nishidae (=Phaleria nisidai) and Morinda citrifolia, the former was statistically more often associated with the reported outcome "lower blood sugar" (P=0.01). CONCLUSIONS: Statistical association between a plant used and reported outcome is not a proof of effectiveness or safety, but it can help select plants of interest for further studies, e.g. through a reverse pharmacology process, in search of local products which may have a positive impact on population health.