DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF IMPURITIES FROM OLMESARTAN MEDOXIMIL AND HYDROCHLOROTHIAZIDE TABLET

Objective: To develop and validate stability indicating RP-HPLC gradient method for simultaneous estimation of impurities and degradation products from Olmesartan Medoximil and Hydrochlorothiazide tablet.Methods: The chromatographic separation was achieved by using Inertsil ODS (250 mm x 4.6 mm, 5μ) column. The mobile phase-A consists of 0.01M potassium dihydrogen phosphatebuffer pH 3.2 adjusted using orthophosphoric acids and acetonitrile as mobile phase-B. The flow rate was 1 ml/min, and chromatograms extracted at wavelength 225 nm.Results: The method was found linear from LOQ to 0.4% level with respect to target concentrations of Olmesartan Medoximil (1.6 mg/ml) and Hydrochlorothiazide (0.5 m/ml) for all impurities, with correlation coefficient found greater than 0.99. The method found robust in all deliberate variations of method parameters as a resolution between adjacent peaks found greater than 2.0. The % RSD results for precision and intermediate precision found less than 5.0%.Conclusion: The proposed analytical method was found to be robust, stability indicating and can be used for estimation of impurities and degradation products of Olmesartan Medoximil and Hydrochlorothiazide from tablet dosage form.Keywords: Stability indicating, RP-HPLC, ICH, Olmesartan Medoximil and Hydrochlorothiazid

Virulence Factors of Clinical and Fecal Isolates of Enterococci Species

Enterococci species are known commensals of the gastrointestinal flora; however, in recent years, they have emerged as important nosocomial pathogens that possess many virulence factors that are attributed to the pathogenesis of diseases caused by them. The study evaluated and compared the virulence factors of Enterococci isolated from fecal and clinical samples. From the obtained isolates, the clinical enterococcal isolates produced 35%, 20%, and 50%, and fecal isolates produced 23%, 13%, and 13% gelatinase, hemolysin, and biofilm, respectively. Biofilm production determined by the Congo Red agar, tube, and microtiter plate methods was 23%, 39%, and 49%, respectively. The sensitivity of the Congo Red agar and tube method compared to the microtiter plate method was 27% and 46%, respectively, whereas the specificity of both tests was 79%. This study showed that biofilm production plays a significant role in the pathogenesis of diseases caused by Enterococci. Detection of biofilm production using the microtiter plate method is more sensitive and specific than the Congo Red agar and tube method

Feasibility of MRI-guided large-core-needle biopsy of suspiscious breast lesions at 3 T

The feasibility of large-core-needle magnetic resonance imaging (MRI)-guided breast biopsy at 3 T was assessed. Thirty-one suspicious breast lesions shown only by MRI were detected in 30 patients. Biopsy procedures were performed in a closed-bore 3-T clinical MR system on a dedicated phased-array breast coil with a commercially available add-on stereotactic biopsy device. Tissue sampling was technically successful in 29/31 (94%) lesions. Median lesion size (n = 29) was 9 mm. Histopathological analysis showed 19 benign lesions (66%) and one inconclusive biopsy result (3%). At follow-up of these lesions, 15 lesions showed no malignancy, no information was available in three patients and two lesions turned out to be malignant (one lesion at surgical excision 1 month after biopsy and one lesion at a second biopsy because of a more malignant enhancement curve at 12-months follow-up MRI). Nine biopsy results showed a malignant lesion (31%) which were all surgically removed. No complications occurred. MRI-guided biopsy at 3 T is a safe and effective method for breast biopsy in lesions that are occult on mammography and ultrasound. Follow-up MRI at 6 months after the biopsy should be performed in case of a benign biopsy result

Breast MRI in nonpalpable breast lesions: a randomized trial with diagnostic and therapeutic outcome – MONET – study

<p>Abstract</p> <p>Background</p> <p>In recent years there has been an increasing interest in MRI as a non-invasive diagnostic modality for the work-up of suspicious breast lesions. The additional value of Breast MRI lies mainly in its capacity to detect multicentric and multifocal disease, to detect invasive components in ductal carcinoma in situ lesions and to depict the tumor in a 3-dimensional image. Breast MRI therefore has the potential to improve the diagnosis and provide better preoperative staging and possibly surgical care in patients with breast cancer. The aim of our study is to assess whether performing contrast enhanced Breast MRI can reduce the number of surgical procedures due to better preoperative staging and whether a subgroup of women with suspicious nonpalpable breast lesions can be identified in which the combination of mammography, ultrasound and state-of-the-art contrast-enhanced Breast MRI can provide a definite diagnosis.</p> <p>Methods/Design</p> <p>The MONET – study (<b><it>M</it></b>R mammography <b><it>O</it></b>f <b><it>N</it></b>onpalpable Br<b><it>E</it></b>ast <b><it>T</it></b>umors) is a randomized controlled trial with diagnostic and therapeutic endpoints. We aim to include 500 patients with nonpalpable suspicious breast lesions who are referred for biopsy. With this number of patients, the expected 12% reduction in surgical procedures due to more accurate preoperative staging with Breast MRI can be detected with a high power (90%). The secondary outcome is the positive and negative predictive value of contrast enhanced Breast MRI. If the predictive values are deemed sufficiently close to those for large core biopsy then the latter, invasive, procedure could possibly be avoided in some women. The rationale, study design and the baseline characteristics of the first 100 included patients are described.</p> <p>Trial registration</p> <p>Study protocol number NCT00302120</p

Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial

BACKGROUND There are limited data from randomized trials regarding whether volume-based, low-dose computed tomographic (CT) screening can reduce lung-cancer mortality among male former and current smokers. METHODS A total of 13,195 men (primary analysis) and 2594 women (subgroup analyses) between the ages of 50 and 74 were randomly assigned to undergo CT screening at T0 (baseline), year 1, year 3, and year 5.5 or no screening. We obtained data on cancer diagnosis and the date and cause of death through linkages with national registries in the Netherlands and Belgium, and a review committee confirmed lung cancer as the cause of death when possible. A minimum follow-up of 10 years until December 31, 2015, was completed for all participants. RESULTS Among men, the average adherence to CT screening was 90.0%. On average, 9.2% of the screened participants underwent at least one additional CT scan (initially indeterminate). The overall referral rate for suspicious nodules was 2.1%. At 10 years of follow-up, the incidence of lung cancer was 5.58 cases per 1000 personyears in the screening group and 4.91 cases per 1000 person-years in the control group; lung-cancer mortality was 2.50 deaths per 1000 person-years and 3.30 deaths per 1000 person-years, respectively. The cumulative rate ratio for death from lung cancer at 10 years was 0.76 (95% confidence interval [CI], 0.61 to 0.94; P = 0.01) in the screening group as compared with the control group, similar to the values at years 8 and 9. Among women, the rate ratio was 0.67 (95% CI, 0.38 to 1.14) at 10 years of follow-up, with values of 0.41 to 0.52 in years 7 through 9. CONCLUSIONS In this trial involving high-risk persons, lung-cancer mortality was significantly lower among those who underwent volume CT screening than among those who underwent no screening. There were low rates of follow-up procedures for results suggestive of lung cancer. (Funded by the Netherlands Organization of Health Research and Development and others; NELSON Netherlands Trial Register number, NL580.)

Appropriate training and retention of community doctors in rural areas: a case study from Mali

Background While attraction of doctors to rural settings is increasing in Mali, there is concern for their retention. An orientation course for young practicing rural doctors was set up in 2003 by a professional association and a NGO. The underlying assumption was that rurally relevant training would strengthen doctors' competences and self-confidence, improve job satisfaction, and consequently contribute to retention. Methods Programme evaluation distinguished trainees' opinions, competences and behaviour. Data were collected through participant observation, group discussions, satisfaction questionnaires, a monitoring tool of learning progress, and follow up visits. Retention was assessed for all 65 trainees between 2003 and 2007. Results and discussion The programme consisted of four classroom modules – clinical skills, community health, practice management and communication skills – and a practicum supervised by an experienced rural doctor. Out of the 65 trained doctors between 2003 and 2007, 55 were still engaged in rural practice end of 2007, suggesting high retention for the Malian context. Participants viewed the training as crucial to face technical and social problems related to rural practice. Discussing professional experience with senior rural doctors contributed to socialisation to novel professional roles. Mechanisms underlying training effects on retention include increased self confidence, self esteem as rural doctor, and sense of belonging to a professional group sharing a common professional identity. Retention can however not be attributed solely to the training intervention, as rural doctors benefit from other incentives and support mechanisms (follow up visits, continuing training, mentoring...) affecting job satisfaction. Conclusion Training increasing self confidence and self esteem of rural practitioners may contribute to retention of skilled professionals in rural areas. While reorientations of curricula in training institutions are necessary, other types of professional support are needed. This experience suggests that professional associations dedicated to strengthening quality of care can contribute significantly to rural practitioners' morale

Image-guided focused ultrasound ablation of breast cancer: current status, challenges, and future directions

Image-guided focussed ultrasound (FUS) ablation is a non-invasive procedure that has been used for treatment of benign or malignant breast tumours. Image-guidance during ablation is achieved either by using real-time ultrasound (US) or magnetic resonance imaging (MRI). The past decade phase I studies have proven MRI-guided and US-guided FUS ablation of breast cancer to be technically feasible and safe. We provide an overview of studies assessing the efficacy of FUS for breast tumour ablation as measured by percentages of complete tumour necrosis. Successful ablation ranged from 20% to 100%, depending on FUS system type, imaging technique, ablation protocol, and patient selection. Specific issues related to FUS ablation of breast cancer, such as increased treatment time for larger tumours, size of ablation margins, methods used for margin assessment and residual tumour detection after FUS ablation, and impact of FUS ablation on sentinel node procedure are presented. Finally, potential future applications of FUS for breast cancer treatment such as FUS-induced anti-tumour immune response, FUS-mediated gene transfer, and enhanced drug delivery are discussed. Currently, breast-conserving surgery remains the gold standard for breast cancer treatment

Modeling Stem Cell Induction Processes

Technology for converting human cells to pluripotent stem cell using induction processes has the potential to revolutionize regenerative medicine. However, the production of these so called iPS cells is still quite inefficient and may be dominated by stochastic effects. In this work we build mass-action models of the core regulatory elements controlling stem cell induction and maintenance. The models include not only the network of transcription factors NANOG, OCT4, SOX2, but also important epigenetic regulatory features of DNA methylation and histone modification. We show that the network topology reported in the literature is consistent with the observed experimental behavior of bistability and inducibility. Based on simulations of stem cell generation protocols, and in particular focusing on changes in epigenetic cellular states, we show that cooperative and independent reaction mechanisms have experimentally identifiable differences in the dynamics of reprogramming, and we analyze such differences and their biological basis. It had been argued that stochastic and elite models of stem cell generation represent distinct fundamental mechanisms. Work presented here suggests an alternative possibility that they represent differences in the amount of information we have about the distribution of cellular states before and during reprogramming protocols. We show further that unpredictability and variation in reprogramming decreases as the cell progresses along the induction process, and that identifiable groups of cells with elite-seeming behavior can come about by a stochastic process. Finally we show how different mechanisms and kinetic properties impact the prospects of improving the efficiency of iPS cell generation protocols.Fundação para a Ciência e a Tecnologia (BD 42942)MIT-Portugal ProgramNational Institutes of Health (U.S.) (CA112967)Singapore–MIT Alliance for Research and TechnologyIntel Corporatio