A new parafocusing paradigm for X-ray diffraction.

A new approach to parafocusing X-ray diffraction implemented with an annular incident beam is demonstrated for the first time. The method exploits an elliptical specimen path on a flat sample to produce relatively high intensity maxima that can be measured with a point detector. It is shown that the flat-specimen approximation tolerated by conventional Bragg-Brentano geometries is not required. A theoretical framework, simulations and experimental results for both angular- and energy-dispersive measurement modes are presented and the scattering signatures compared with data obtained with a conventional pencil-beam arrangement.

Development of quality metrics for ambulatory pediatric cardiology: Infection prevention.

INTRODUCTION: In 2012, the American College of Cardiology's (ACC) Adult Congenital and Pediatric Cardiology Council established a program to develop quality metrics to guide ambulatory practices for pediatric cardiology. The council chose five areas on which to focus their efforts; chest pain, Kawasaki Disease, tetralogy of Fallot, transposition of the great arteries after arterial switch, and infection prevention. Here, we sought to describe the process, evaluation, and results of the Infection Prevention Committee's metric design process. METHODS: The infection prevention metrics team consisted of 12 members from 11 institutions in North America. The group agreed to work on specific infection prevention topics including antibiotic prophylaxis for endocarditis, rheumatic fever, and asplenia/hyposplenism; influenza vaccination and respiratory syncytial virus prophylaxis (palivizumab); preoperative methods to reduce intraoperative infections; vaccinations after cardiopulmonary bypass; hand hygiene; and testing to identify splenic function in patients with heterotaxy. An extensive literature review was performed. When available, previously published guidelines were used fully in determining metrics. RESULTS: The committee chose eight metrics to submit to the ACC Quality Metric Expert Panel for review. Ultimately, metrics regarding hand hygiene and influenza vaccination recommendation for patients did not pass the RAND analysis. Both endocarditis prophylaxis metrics and the RSV/palivizumab metric passed the RAND analysis but fell out during the open comment period. Three metrics passed all analyses, including those for antibiotic prophylaxis in patients with heterotaxy/asplenia, for influenza vaccination compliance in healthcare personnel, and for adherence to recommended regimens of secondary prevention of rheumatic fever. CONCLUSIONS: The lack of convincing data to guide quality improvement initiatives in pediatric cardiology is widespread, particularly in infection prevention. Despite this, three metrics were able to be developed for use in the ACC's quality efforts for ambulatory practice.

Phase II study of second-line gemcitabine in sensitive or refractory small cell lung cancer.

UNLABELLED: Small cell lung cancer (SCLC) is highly sensitive to chemotherapy. Despite a dramatic initial response, however, most patients relapse. Given the activity of gemcitabine in non-small cell lung cancer (NSCLC), and early clinical trials suggesting activity of gemcitabine in chemo-naive SCLC patients, we conducted a phase II study to determine the efficacy and toxicities of gemcitabine in SCLC patients who have failed first-line chemotherapy. Gemcitabine 1250 mg/m(2) was given intravenously on days 1 and 8, every 3 weeks. Eligibility criteria included prior treatment with only one chemotherapy regimen and Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Patients with brain metastases were eligible. RESULTS: Between April 1998 and October 2001, 27 patients were enrolled: 15 patients with sensitive (S) disease (recurred>3 months after first-line chemotherapy) and 12 patients with refractory (R) disease (failed<3 months after first-line chemotherapy). Median age was 61 (range 45-74). All patients had received prior platinum-based therapy involving etoposide and either cisplatin or carboplatin. There were one early death and two early withdrawals because of toxicity. No responses were observed. Of 24 patients who received at least two cycles of gemcitabine, only three achieved stable disease after six cycles while 21 progressed. The median time to progression (TTP) was 6 weeks in S group, 5.6 weeks in R group, and 6 weeks overall. After a minimum potential follow-up of almost 1 year for all patients, the median survival was 8.8 months in S group, 4.2 months in R group, and 6.4 months for the whole group. One-year survival rate was 33.3% in S group, 16.7% in R group, and 25.4% for all patients. Myelosuppression was the most commonly observed adverse effect, with grade 3/4 neutropenia in 30%, and grade 3 thrombocytopenia in 30%. One patient (3.7%) developed neutropenic fever. Respiratory failure and death, possibly related to pulmonary toxicity, was observed in one patient (3.7%). CONCLUSION: monotherapy gemcitabine as second-line agent has limited activity in previously treated SCLC.

Bioadhesive, non-drug-loaded nanoparticles as modulators of candidal adherence to buccal epithelial cells: a potentially novel prophylaxis for candidosis.

Adherence of microorganisms, such as Candida albicans, represents the initial step in the establishment of infection and, accordingly, modification of this step represents a method by which the incidence of infection may be reduced. Therefore, this study uniquely examined the effects of polymeric nanoparticles on the adherence of blastospores of C. albicans to human buccal epithelial cells (BEC) in vitro. Poly(propylcyanoacrylate) nanoparticles were produced by emulsion polymerisation using a range of anionic, cationic and non-ionic surfactants, their particle size and zeta potential characterised and incubated with stationary phase blastospores of C. albicans for a defined period. Following this, the surface properties and size of blastospores with adsorbed nanoparticles were characterised. phosphate buffered saline-treated and nanoparticle-treated blastospores were incubated with human BEC for 2 h, following which the number of adherent blastospores was enumerated by light microscopy. The size and zeta potential of the nanoparticles were dependent on the surfactant employed in the manufacture process. Following nanoparticle adsorption, alteration of the zeta potential and an increase in the diameter of blastospores were observed. However, as this increase in diameter was indirectly related to the size of the nanoparticles, this may indicate a preference for the adsorption of smaller particles. In addition, following nanoparticle adsorption, the cell surface hydrophobicity (CSH) of C. albicans blastospores was increased and, importantly, the subsequent adherence to BEC in vitro was reduced. Most notably, the adherence of blastospores that had been treated with nanoparticles (stabilised with docusate sodium) was circa 73% lower than that of untreated blastospores. A moderate correlation between increased CSH and reduced adherence and a low correlation between blastospore zeta potential and adherence were observed, inferring that other mechanisms, most likely stearic hindrance, are responsible for the antiadherent properties of adsorbed nanoparticles. In light of their ability to reduce candidal adherence to BEC, it is suggested that polymeric nanoparticles may be useful in the prophylaxis of candidosis of the oral cavity.

Phase I/II study of gemcitabine and exisulind as second-line therapy in patients with advanced non-small cell lung cancer.

BACKGROUND: The study was designed to evaluate the safety and efficacy of exisulind, a selective apoptotic antineoplastic drug, in combination with gemcitabine as second-line therapy in patients with progressing advanced non-small cell lung cancer. METHODS: Patients whose disease progressed more than 3 months from completion of first-line chemotherapy were eligible for this phase I/II trial. Primary end points were maximally tolerated dose and time to progression. Patients in the phase I portion of the study were treated with gemcitabine (1250 mg/m) in combination with three escalated dose levels of exisulind. Treatment involved six cycles of gemcitabine and exisulind followed by exisulind maintenance. The study was subsequently expanded to phase II. RESULTS: Thirty-nine patients (15 in phase I and 24 in phase II) were treated. The regimen was well tolerated with grade 3 fatigue and grade 3 constipation being dose-limiting toxicities. The maximally tolerated dose was not reached. Dose level 3 of exisulind (250 mg twice daily) in combination with gemcitabine was used for phase II. The overall response rates were 7% (phase I), 17% (phase II), and 13% (all). Median time to progression and median and 1-year survival, respectively, were 3.7 and 9.7 months and 33% (phase I); 4.3 and 9.4 months and 41% (phase II); and 4.1 and 9.4 months and 39% (all). CONCLUSION: Although the study met its primary end point of improving time to progression (more than 4.1 months in phase II), we did not observe a clear survival advantage and thus do not plan to further investigate this schedule of gemcitabine and exisulind.

Phase II study of weekly low-dose paclitaxel for relapsed and refractory non-Hodgkin's lymphoma: a Wisconsin Oncology Network Study.

This study was performed to determine the clinical activity and safety of weekly low-dose paclitaxel (90 mg/m2) given as a 1-hour infusion in patients with relapsed and refractory non-Hodgkin's lymphoma (NHL). Thirty patients were treated on a phase II protocol conducted at the University of Wisconsin Comprehensive Cancer Center and within the Wisconsin Oncology Network (WON). A cycle of therapy was defined as paclitaxel at 90 mg/m2 weekly for 6 consecutive weeks followed by a 2-week rest period. Cycles were repeated as long as there was no disease progression or unacceptable toxicity. In general, the patients were heavily pretreated with a median of 4 prior therapies (range 2-11), and 73% were refractory to the most recent systemic therapy. The median age was 70 (range 44-97). All NHL histological subtypes were eligible. Of the 30 eligible patients enrolled, 26 were evaluable for response and 28 for toxicity. The overall response rate was 23% (95% confidence interval (CI) 9.0-43.7%). One patient had a complete response, and 5 patients had partial responses. The median response duration was 3.2 months (range 1.4-11.8 months). The median event-free survival was 1.9 months. The major toxicity was neuropathy. Despite the limited marrow reserve in this patient population, myelosuppression was minimal. Paclitaxel given in this dose and schedule has modest activity in previously treated non-Hodgkin's lymphoma. The response rate appears similar to other reports using different doses and schedules. Myelosuppression appears less with this schedule than with other schedules.

Physicochemical characterization of hexetidine-impregnated endotracheal tube poly(vinyl chloride) and resistance to adherence of respiratory bacterial pathogens.

PURPOSE: Ventilator-associated pneumonia is a frequent cause of mortality in intensive care patients. This study describes the physicochemical properties of hexetidine-impregnated poly(vinyl chloride) (PVC) endotracheal tube (ET) biomaterials and their resistance to microbial adherence (Staphylococcus aureus and Pseudomonas aeruginosa). METHODS: PVC emulsion was cured in the presence of hexetidine (0-20% w/w) and was characterized in terms of drug release, surface properties (i.e., microrugosity/contact angle), mechanical (tensile) properties, and resistance to microbial adherence. RESULTS: Under sink conditions, hexetidine release from PVC was diffusion-controlled. Increasing the concentration of hexetidine from 1% to 10% (w/w) (but not from 10% to 20% w/w) increased the subsequent rate of drug release. In general, increasing the concentration of hexetidine decreased both the tensile properties and hydrophobicity, yet increased PVC microrugosity. Following hexetidine release (21 days), the surface properties were similar to those of native PVC. The resistance of hexetidine-containing PVC (1% or 5%) to microbial adherence (following defined periods of drug release) was greater than that of native PVC and was constant over the examined period of hexetidine release. CONCLUSIONS: ET PVC containing 1% (w/w) hexetidine offered an appropriate balance between suitable physicochemical properties and resistance to microbial adherence. This may offer an approach with which to reduce the incidence of ventilator-associated pneumonia.

Phase II trial of perillyl alcohol (NSC 641066) administered daily in patients with metastatic androgen independent prostate cancer.

OBJECTIVE: We conducted a phase II multicenter trial of perillyl alcohol in patients with advanced hormone refractory prostate cancer (HRPC). The primary endpoint was to evaluate the 6-month progression-free survival given the potential cytostatic nature of the drug. Secondary objectives included assessing acute and chronic toxicities, as well as measuring objective response rates. METHODS: Patients with metastatic androgen-independent prostate cancer that failed at least one prior chemotherapeutic or experimental regimen were eligible. Perillyl alcohol was administered orally at 1200 mg/m2/dose four times daily and continued until disease progression or development of unacceptable toxicity. RESULTS: Fifteen patients were eligible. Six patients received less than one cycle (4 weeks) of drug, four of which stopped because of drug intolerance. Only six patients received more than two cycles of therapy and were considered evaluable for response. Main toxicity included grade 1-2 gastrointestinal intolerance (nausea/vomiting in 60% of the patients) and fatigue (47%). One patient developed a grade 4 hypokalemia that was felt likely attributable to the drug. No objective responses were seen. All patients either progressed or withdrew from the study secondary to drug intolerance before the 6-month time period. CONCLUSION: Perillyl alcohol administered at this dose and formulation did not have any objective clinical activity in this patient population.