Patterns of platinum drug use in an acute care setting: a retrospective study.

PURPOSE: Platinum drugs have been in use in cancer treatment for more than 40 years, but little is known about the pattern of their use. The aim of this study was to examine the patterns of platinum drug use, with a secondary aim to describe the occurrence of dose reductions. METHODS: A retrospective analysis was conducted of oncology pharmacy dispensing records from a single hospital in Australia. Data related to drug choice, regimen and dose reductions were included in this study if the patient had received their last round of chemotherapy between November 2014 and July 2015. RESULTS: Of the 156 patients included in the study, 46% were dispensed a platinum drug during their treatment. The most commonly dispensed drugs were cisplatin (40%), carboplatin (40%) and oxaliplatin (15%), while some patients (5%) received more than one platinum drug. Dose reductions were more common in patients who were treated with a platinum drug (73%) compared with patients treated with non-platinum drugs (55%). The most common reason for a dose reduction was cytopenia. CONCLUSIONS: The findings suggest that platinum drugs remain one of the most commonly dispensed drugs to treat cancer patients and most patients receive a dose reduction during treatment.

Investigations into the electrochemical, surface, and electrocatalytic properties of the surface-immobilized polyoxometalate, TBA3K[SiW10O36(PhPO)2].

Surface anchoring of an organic functionalized POM, TBA3K[SiW10O36(PhPO)2] was carried out by two methods, the layer-by-layer (LBL) assembly technique by employing a pentaerythritol-based ruthenium(II) metallodendrimer as a cationic moiety and also by entrapping the POM in a conducting polypyrrole film. The redox behavior of the constructed films was studied by using cyclic voltammetry and electrochemical impedance spectroscopy. The surface morphologies of the constructed multilayers were examined by scanning electron microscopy and atomic force microscopy. X-ray photoelectron spectroscopy was conducted to confirm the elements present within the fabricated films. The multilayer assembly was also investigated for its catalytic efficiency towards the reduction of nitrite.

Surface immobilization of a tetra-ruthenium substituted polyoxometalate water oxidation catalyst through the employment of conducting polypyrrole and the layer-by-layer (LBL) technique.

A tetra Ru-substituted polyoxometalate Na10[{Ru4O4(OH)2(H2O)4}(γ-SiW10O36)2] (Ru4POM) has been successfully immobilised onto glassy carbon electrodes and indium tin oxide (ITO) coated glass slides through the employment of a conducting polypyrrole matrix and the layer-by-layer (LBL) technique. The resulting Ru4POM doped polypyrrole films showed stable redox behavior associated with the Ru centres within the Ru4POM, whereas, the POM's tungsten-oxo redox centres were not accessible. The films showed pH dependent redox behavior within the pH range 2-5 whilst exhibiting excellent stability towards redox cycling. The layer-by-layer assembly was constructed onto poly(diallyldimethylammonium chloride) (PDDA) modified carbon electrodes by alternate depositions of Ru4POM and a Ru(II) metallodendrimer. The resulting Ru4POM assemblies showed stable redox behavior for the redox processes associated with Ru4POM in the pH range 2-5. The charge transfer resistance of the LBL films was calculated through AC-Impedance. Surface characterization of both the polymer and LBL Ru4POM films was carried out using atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). Initial investigations into the ability of the Ru4POM LBL films to electrocatalytically oxidise water at pH 7 have also been conducted.

Transition metal ion-substituted polyoxometalates entrapped in polypyrrole as an electrochemical sensor for hydrogen peroxide.

A conducting polymer was used for the immobilization of various transition metal ion-substituted Dawson-type polyoxometalates (POMs) onto glassy carbon electrodes. Voltammetric responses of films of different thicknesses were stable within the pH domain 2-7 and reveal redox processes associated with the conducting polymer, the entrapped POMs and incorporated metal ions. The resulting POM doped polypyrrole films were found to be extremely stable towards redox switching between the various redox states associated with the incorporated POM. An amperometric sensor for hydrogen peroxide detection based upon the POM doped polymer films was investigated. The detection limits were 0.3 and 0.6 µM, for the Cu(2+)- and Fe(3+)-substituted POM-doped polypyrrole films respectively, with a linear region from 0.1 up to 2 mM H(2)O(2). Surface characterization of the polymer films was carried out using atomic force microscopy, X-ray photoelectron spectroscopy and scanning electron microscopy.

Comparison of COX-2, Ki-67, and BCL-2 expression in normal esophageal mucosa, Barrett's esophagus, dysplasia, and adenocarcinoma with postablation mucosa and implications for ablative therapies.

BACKGROUND: The neosquamous mucosa that replaces ablated esophageal endothelium after endoscopic mucosal ablation for Barrett's metaplasia or high-grade dysplasia (HGD) may retain buried glandular tissue. This study aimed to assess the neoplastic potential, cellular proliferation, and resistance to apoptosis of this buried glandular tissue by measuring COX-2, Ki-67, and BCL-2 expression in these tissues. METHODS: A prospectively collected database was sourced for esophageal biopsy specimens with normal histologic appearance, Barrett's metaplasia, HGD, adenocarcinoma, and postablation mucosa comprising ablated Barrett's and ablated HGD. Quantitative analysis of cellular markers was achieved immunohistochemically using monoclonal antibodies for the COX-2 enzyme (suggesting increased neoplastic potential), Ki-67 antigen (suggesting cellular proliferation), and BCL-2 oncoprotein (suggesting oncogenic resistance to apoptosis). Grading was performed by independent, blinded observers, and the pre- and postablation cellular disparities were subsequently noted. RESULTS: The buried glandular elements of postablation mucosa demonstrated universally greater COX-2, Ki-67, and BCL-2 expression than normal esophagus. Barrett's esophagus and adenocarcinoma expressed significantly greater COX-2 and Ki-67 at the deep glandular level than postablation mucosa. HGD demonstrated greater Ki-67 expression than the postablation tissue but only within the superficial glands. Overall, the expression of COX-2 correlated significantly with Ki-67 expression in deep glandular tissue. CONCLUSIONS: Ablation of pathologic mucosa in Barrett's esophagus and HGD reduces the expression of some markers of neoplastic behavior. However, the buried glandular tissue of the postablation mucosa still exhibits a higher expression than normal esophageal epithelium. This has potential implications for the follow-up treatment of these patients because it is unclear whether the true risk of neoplastic progression is adequately reduced. A more comprehensive study is required to address this issue.

Titania-silver and alumina-silver composite nanoparticles: novel, versatile synthesis, reaction mechanism and potential antimicrobial application.

Titania-silver (TiO(2)-Ag) and alumina-silver (Al(2)O(3)-Ag) composite nanoparticles were synthesised by a simple, reproducible, wet chemical method under ambient conditions. The surface of the oxides was modified with oleic acid, which acted as an intermediate between the oxide surface and the silver nanoparticles. The resulting composite nanoparticles were thoroughly characterised by XRD, TEM, XPS, FTIR and TGA to elucidate the mode of assembly of Ag nanoparticles on the oxide surfaces. Epoxy nanocomposites were formulated with TiO(2)-Ag and Al(2)O(3)-Ag to examine potential applications for the composite nanoparticles. Preliminary results from disc diffusion assays against Escherichia coli DH5α and Staphylococcus epidermidis NCIMB 12721 suggest that these TiO(2)-Ag and Al(2)O(3)-Ag composite nanoparticles have potential as antimicrobial materials.

Uterine innervation after hysterectomy for chronic pelvic pain with, and without, endometriosis.

OBJECTIVE: Chronic pelvic pain is associated with a wide range of clinical conditions that include endometriosis. The precise cause, mechanisms of pain, and natural history are imprecise. Patterns of uterine innervation have been studied after hysterectomy for chronic pelvic pain with and without endometriosis. STUDY DESIGN: Tissue blocks were taken from the lower one half of the uterus after hysterectomy for advanced endometriosis (n = 16 specimens; group 1) and for chronic pelvic pain without endometriosis (n = 15 specimens; group 2). The control group consisted of uteri that were removed for painless gynecologic conditions (n = 25 specimens; group 3). Tissue sections from the lower one half of the uterus were stained with anti-S100 to demonstrate patterns of innervation, and nerve fiber profiles were counted by standardized techniques; qualitative differences were also recorded. RESULTS: In uteri from women with advanced endometriosis, there were increased numbers of nerve fiber profiles compared with control specimens (group 1 vs group 3; P = .0013, Mann Whitney U test). There were also increased numbers of nerve fiber profiles in uteri that were associated with chronic pelvic pain without endometriosis (group 2 vs group 3; P = .04, Mann Whitney U test). There were no differences in nerve fiber count in uteri from groups 1 and 2 (P = .35, Mann Whitney U test). Comparing both groups of uteri with controls (groups 1 and 2 vs 3) demonstrated marked differences in nerve fiber counts (P = .002, Mann Whitney U test). Two distinctive patterns of reinnervation that were observed: disruption of nerve bundles (collateral sprouting with microneuroma formation) and ingrowth around blood vessels (perivascular nerve fiber proliferation). There were increased numbers of microneuromas (groups 1 and 2 vs 3; P = .001, chi-squared test with Yates correction) and perivascular nerve fiber proliferation (groups 1 and 2 vs 3; P = .008, chi-squared test with Yates correction) in the myometrium in chronic pelvic pain with, and without, endometriosis compared with the control group. CONCLUSION: Nerve fiber proliferation and other features of reinnervation have been observed in the isthmic regions of uteri that were removed at hysterectomy for chronic pelvic pain with and without endometriosis. There were no quantitative differences between the groups with chronic pelvic pain and endometriosis. These observations provide an alternative explanation for the source of pain and other clinical symptoms in these clinical settings.

Solid-state NMR study of ureidopyrimidinone model compounds.

High-resolution (1)H and (15)N{(1)H} solid-state NMR experiments were conducted on two ureidopyrimidinone model compounds: dimeric 2-butylureido-6-methyl-4-pyrimidinone (1) and its bifunctional analogue N,N-1,6-hexanediyl(2-ureido-6-methyl-4-pyrimidinone) (4). High magic angle spinning rates and (1)H decoupling schemes were used to increase the proton spectral resolution. Upon heating 1 to 440 K, an increase in mobility was observed for non-hydrogen-bonded protons; the dimer remained in keto tautomeric form, which is capable of much stronger intermolecular hydrogen bonding than the enol tautomer. From these findings, it was concluded that this ureidopyrimidinone moiety should allow the design of strongly bonded molecular assemblies whose thermal stability compares favourably with that of conventional engineering polymers.

A plasma membrane H+-ATPase is required for the formation of proanthocyanidins in the seed coat endothelium of Arabidopsis thaliana.

The plasma membrane in plant cells is energized with an electrical potential and proton gradient generated through the action of H+ pumps belonging to the P-type ATPase superfamily. The Arabidopsis genome encodes 11 plasma membrane H+ pumps. Auto-inhibited H+-ATPase isoform 10 (AHA10) is expressed primarily in developing seeds. Here we show that four independent gene disruptions of AHA10 result in seed coats with a transparent testa (tt) phenotype (light-colored seeds). A quantitative analysis of extractable flavonoids in aha10 seeds revealed an approximately 100-fold reduction of proanthocyanidin (PA), one of the two major end-product pigments in the flavonoid biosynthetic pathway. In wild-type seed coat endothelial cells, PA accumulates in a large central vacuole. In aha10 mutants, the formation of this vacuole is impaired, as indicated by the predominance of multiple small vacuoles observed by fluorescence microscopy using a vacuole-specific dye, 5-(and -6)-carboxy 2',7'-dichlorofluorescein diacetate. A similar vacuolar defect was also observed for another tt mutant, tt12, a proton-coupled multidrug and toxic compound extrusion transporter potentially involved in loading provacuoles with a flavonoid intermediate required for PA production. The endothelial cells in aha10 mutants are otherwise healthy, as indicated by the lack of a significant decrease in (i) the accumulation of other flavonoid pathway end products, such as anthocyanins, and (ii) mRNA levels for two endothelium-specific transcripts (TT12 and BAN). Thus, the specific effect of aha10 on vacuolar and PA biogenesis provides genetic evidence to support an unexpected endomembrane function for a member of the plasma membrane H+-ATPase family.

Argon beam plasma coagulation as therapy for high-grade dysplasia in Barrett's esophagus.

BACKGROUND & AIMS: Patients with high-grade dysplasia in Barrett's esophagus have a high chance of developing adenocarcinoma. Previously these patients have undergone resection, however, the management of patients unsuitable for surgical resection is unclear. We have studied the long-term outcome of patients who have undergone endoscopic Argon ablation for high-grade dysplasia in Barrett's. METHODS: Twenty-nine patients (median age, 64 yr; range, 43-85 yr) with high-grade dysplasia in Barrett's, who were unfit or had declined surgery, underwent Argon ablation and received follow-up evaluation over 7 years (mean follow-up, 37 mo; range, 7-78 mo). Treatment was stopped once there was no further histologic evidence of dysplasia. The patients then went on to receive a surveillance endoscopy at 3, 6, and 12 months after ablation, then annually thereafter. RESULTS: High-grade dysplasia responded to treatment in 25 patients (86%); 22 of these had complete regression to neosquamous esophageal mucosa. During follow-up evaluation, no patients died of esophageal adenocarcinoma. Four patients developed cancer, 3 of whom continue with ablation therapy. The fourth patient died of unrelated causes. A single esophageal perforation was the only significant adverse event attributable to therapy. No esophageal strictures occurred and patients returned to normal activity after 24 hours in the majority of cases. Patients who received Argon ablation showed no difference in survival to that of the general population. CONCLUSIONS: Argon beam ablation for high-grade dysplasia in Barrett's esophagus is an effective and safe treatment, especially in patients unfit for surgical resection.