Aspects of cancer chemotherapy

A total of 107 cases (62 male and 45 female),with histologically proven malignant disease and all receiving cytotoxic therapy were studied.A brief review of the history of cancer chemotherapy is given > together with a detailed account of the principal agents currently available, methods and routes of administration, means of assessing response to treatment and the necessary routines of investigation.The results obtained are presented,mainly in tabular form. Assessment of response, incidence, severity, significance, mechanisms and management of toxic effects, the significance of hepatic metas¬ tases and causes of death in relation to oancer chemotherapy, are discussed in detail.Finally, the conclusions derived from the study of these cases are presented

Topical clobetasol for the treatment of toxic epidermal necrolysis: study protocol for a randomized controlled trial.

BackgroundToxic epidermal necrolysis (TEN) is a rare systemic allergic drug eruption with high patient mortality. Currently, no established treatments have been shown to be effective for TEN beyond supportive care. Prior studies of systemic corticosteroids have yielded conflicting data, with some showing a possible benefit and others reporting in increased mortality. However, topical steroids have shown promise for treatment of ocular sequelae of TEN, such as scarring and vision loss. We have designed a randomized controlled trial to evaluate topical clobetasol for treatment of the epidermal manifestations of TEN. In addition, we propose genetic studies to characterize the TEN transcriptome and alterations in cutaneous gene expression that might occur following topical steroid treatment.Methods/designThis split-body randomized, double-blind, placebo-controlled Phase IIa proof-of-concept trial will evaluate the safety and efficacy of once-daily topical clobetasol applied to the skin of patients with TEN. This multicenter trial will recruit a total of 15 patients between the ages of 12 and 85 from the University of California Davis Medical Center and Shriners Hospital for Children inpatient burn units. Designated treatment areas on opposite sides of the body will be treated with blinded clobetasol 0.05% ointment or control petrolatum ointment daily for 14 days. On day 3 of therapy, a biopsy will be taken from the treated area for genetic studies. The primary study aims will be to establish the safety of topical clobetasol treatment and determine the time to cessation of skin detachment for the control and clobetasol-treated areas. Secondary endpoints will evaluate efficacy using parameters such as time to 90% re-epithelialization and percentage of affected skin at 0, 3, 6, 9, 12 and 15 days. Genomic DNA and RNA will be obtained from biopsy samples, to characterize the TEN transcriptome and identify changes in gene expression after topical steroid treatment.DiscussionTopical steroids have shown promise for treating ocular complications of TEN, but to date have not been evaluated for cutaneous manifestations of the disease. This trial will investigate clinical and molecular outcomes of topical clobetasol application and hopefully provide insight into the disease pathophysiology.Trial registrationClinicalTrials.gov NCT02319616. https://clinicaltrials.gov/ct2/show/NCT02351037

Impurity-assisted Andreev reflection at a spin-active half-metal-superconductor interface

The Andreev reflection amplitude at a clean interface between a half-metallic ferromagnet (H) and a superconductor (S) for which the half metal's magnetization has a gradient perpendicular to the interface is proportional to the excitation energy $\varepsilon$ and vanishes at $\varepsilon=0$ [B\'{e}ri {\em et al.}, Phys.\ Rev.\ B {\bf 79}, 024517 (2009)]. Here we show that the presence of impurities at or in the immediate vicinity of the HS interface leads to a finite Andreev reflection amplitude at $\varepsilon=0$. This impurity-assisted Andreev reflection dominates the low-bias conductance of a HS junction and the Josephson current of an SHS junction in the long-junction limit.Comment: 12 pages, 2 figure

Precision spectroscopy of the 3s-3p fine structure doublet in Mg+

We apply a recently demonstrated method for precision spectroscopy on strong transitions in trapped ions to measure both fine structure components of the 3s-3p transition in 24-Mg+ and 26-Mg+. We deduce absolute frequency reference data for transition frequencies, isotope shifts and fine structure splittings that are in particular useful for comparison with quasar absorption spectra, which test possible space-time variations of the fine structure constant. The measurement accuracy improves previous literature values, when existing, by more than two orders of magnitude

Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma

Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. Curcumin has been used extensively in Ayurvedic medicine for centuries, as it is nontoxic and has a variety of therapeutic properties including anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer activities via its effect on a variety of biological pathways involved in mutagenesis, oncogene expression, cell cycle regulation, apoptosis, tumorigenesis and metastasis. Curcumin has shown anti-proliferative effect in multiple cancers, and is an inhibitor of the transcription factor NF-κB and downstream gene products (including c-myc, Bcl-2, COX-2, NOS, Cyclin D1, TNF-α, interleukins and MMP-9). In addition, curcumin affects a variety of growth factor receptors and cell adhesion molecules involved in tumor growth, angiogenesis and metastasis. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and treatment protocols include disfiguring surgery, platinum-based chemotherapy and radiation, all of which may result in tremendous patient morbidity. As a result, there is significant interest in developing adjuvant chemotherapies to augment currently available treatment protocols, which may allow decreased side effects and toxicity without compromising therapeutic efficacy. Curcumin is one such potential candidate, and this review presents an overview of the current in vitro and in vivo data supporting its therapeutic activity in head and neck cancer as well as some of the challenges concerning its development as an adjuvant chemotherapeutic agent

Comparison of walking overground and in a Computer Assisted Rehabilitation Environment (CAREN) in individuals with and without transtibial amputation

Background Due to increased interest in treadmill gait training, recent research has focused on the similarities and differences between treadmill and overground walking. Most of these studies have tested healthy, young subjects rather than impaired populations that might benefit from such training. These studies also do not include optic flow, which may change how the individuals integrate sensory information when walking on a treadmill. This study compared overground walking to treadmill walking in a computer assisted virtual reality environment (CAREN) in individuals with and without transtibial amputations (TTA). Methods Seven individuals with traumatic TTA and 27 unimpaired controls participated. Subjects walked overground and on a treadmill in a CAREN at a normalized speed. The CAREN applied optic flow at the same speed that the subject walked. Temporal-spatial parameters, full body kinematics, and kinematic variability were collected during all trials. Results Both subject groups decreased step time and control subjects decreased step length when walking in the CAREN. Differences in lower extremity kinematics were small (\u3c 2.5○) and did not exceed the minimal detectable change values for these measures. Control subjects exhibited decreased transverse and frontal plane range of motion of the pelvis and trunk when walking in the CAREN, while patients with TTA did not. Both groups exhibited increased step width variability during treadmill walking in the CAREN, but only minor changes in kinematic variability. Conclusions The results of this study suggest that treadmill training in a virtual environment should be similar enough to overground that changes should carry over. Caution should be made when comparing step width variability and step time results from studies utilizing a treadmill to those overground

Dietary supplementation with Bifidobacterium longum subsp. infantis (B. infantis) in healthy breastfed infants: study protocol for a randomised controlled trial.

BackgroundThe development of probiotics as therapies to cure or prevent disease lags far behind that of other investigational medications. Rigorously designed phase I clinical trials are nearly non-existent in the field of probiotic research, which is a contributing factor to this disparity. As a consequence, how to appropriately dose probiotics to study their efficacy is unknown. Herein we propose a novel phase I ascending dose trial of Bifidobacterium longum subsp. infantis (B. infantis) to identify the dose required to produce predominant gut colonisation in healthy breastfed infants at 6 weeks of age.Methods/designThis is a parallel-group, placebo-controlled, randomised, double-blind ascending dose phase I clinical trial of dietary supplementation with B. infantis in healthy breastfed infants. The objective is to determine the pharmacologically effective dose (ED) of B. infantis required to produce predominant (>50 %) gut colonisation in breastfed infants at 6 weeks of age. Successively enrolled infant groups will be randomised to receive two doses of either B. infantis or placebo on days 7 and 14 of life. Stool samples will be used to characterise the gut microbiota at increasing doses of B. infantis.DiscussionProbiotic supplementation has shown promising results for the treatment of a variety of ailments, but evidence-based dosing regimes are currently lacking. The ultimate goal of this trial is to establish a recommended starting dose of B. infantis for further efficacy-testing phase II trials designed to evaluate B. infantis for the prevention of atopic dermatitis and food allergies in at-risk children.Trial registrationClinicaltrials.gov # NCT02286999 , date of trial registration 23 October 2014

On the Nature of the Mesoscale Variability in Denmark Strait

AbstractTime series data from a mooring in the center of Denmark Strait and a collection of shipboard hydrographic sections occupied across the sill are used to elucidate the mesoscale variability of the dense overflow water in the strait. Two dominant, reoccurring features are identified that are referred to as a bolus and a pulse. A bolus is a large, weakly stratified lens of overflow water associated with cyclonic rotation and a modest increase in along-stream speed of 0.1 m s−1. When a bolus passes through the strait the interface height of the overflow layer increases by 60 m, and the bottom temperature decreases by 0.4°C. By contrast, a pulse is characterized by anticyclonic rotation, a strong increase in along-stream speed of &gt;0.25 m s−1, a decrease in interface height of 90 m, and no significant bottom temperature signal. It is estimated that, on average, boluses (pulses) pass through the strait every 3.4 (5.4) days with no seasonal signal to their frequency. Both features have the strongest along-stream signal in the overflow layer, while the strongest cross-stream velocities occur above the Denmark Strait overflow water (DSOW). In this sense neither feature can be characterized as a simple propagating eddy. Their dynamics appear to be similar to that ascribed to the mesoscale variability observed downstream in the deep western boundary current. Strong correlation of bottom temperatures between the mooring in Denmark Strait and a downstream array, together with a match in the frequency of occurrence of features at both locations, suggests a causal relationship between the mesoscale variability at the sill and that farther downstream.</jats:p

Observation and modeling of energetic particles at synchronous orbit on July 29, 1977

In the twelve hours following a worldwide storm, there was a series of at least four magnetospheric substorms, the last and largest of which exhibited an expansion phase onset at approximately 1200 UT. Data from six spacecraft in three general local time groupings (0300, 0700, and 1300 LT) were examined and vector magnetic field data and energetic electron and ion data from approximately 15 keV to 2 MeV were employed

Mechanical Properties of ZTO, ITO, and a-Si:H Multilayer Films for Flexible Thin Film Solar Cells

The behavior of bi- and trilayer coating systems for flexible a-Si:H based solar cells consisting of a barrier, an electrode, and an absorption layer is studied under mechanical load. First, the film morphology, stress, Young’s modulus, and crack onset strain (COS) were analyzed for single film coatings of various thickness on polyethylene terephthalate (PET) substrates. In order to demonstrate the role of the microstructure of a single film on the mechanical behavior of the whole multilayer coating, two sets of InSnOx (indium tin oxide, ITO) conductive coatings were prepared. Whereas a characteristic grain–subgrain structure was observed in ITO-1 films, grain growth was suppressed in ITO-2 films. ITO-1 bilayer coatings showed two-step failure under tensile load with cracks propagating along the ITO-1/a-Si:H-interface, whereas channeling cracks in comparable bi- and trilayers based on amorphous ITO-2 run through all constituent layers. A two-step failure is preferable from an application point of view, as it may lead to only a degradation of the performance instead of the ultimate failure of the device. Hence, the results demonstrate the importance of a fine-tuning of film microstructure not only for excellent electrical properties, but also for a high mechanical performance of flexible devices (e.g., a-Si:H based solar cells) during fabrication in a roll-to-roll process or under service