A phase II study of high dose epirubicin in unresectable non small cell lung cancer.

Epirubicin (EPI), a doxorubicin analogue, is reported to have equal antitumour activity with lower cardiac and systemic toxicity. Recently, the maximum tolerated dose of this drug has been revised upwards with reported increased response rates in several malignancies. We initiated a phase II study of high-dose EPI as initial treatment for patients with advanced non-small cell lung cancer (NSCLC) (stage III and IV). Between May 1988 and November 1989, 25 patients were entered. The starting dose of EPI was 135 mg m-2, with dose attenuations and escalations of 15 mg m-2 based on mid-cycle evaluation of toxicity. Treatment was repeated every 3 weeks. Nine partial responses (36%, 95% CI: 18-57.5%) and 11 patients with disease stabilisation (44%) were observed. Median (range) time to progression was 19 (3-70) weeks. Median (range) survival is 32 (9-116+) weeks. There were no treatment related deaths. Major side effects were leukocytopenia WHO grade III/IV (23% of courses) and mucositis WHO grade II/III (15% of courses). In two patients left ventricular ejection fraction decreased greater than 15% compared to baseline values after a cumulative Epirubicin dose of 435 mg m-2, and therefore went off study. In none of the patients clinical signs of congestive heart failure were observed. We conclude from our data that high-dose EPI, contrary to previous negative studies using lower doses of EPI, ranks amongst the most active regimens against advanced NSCLC. Toxicity of high-dose EPI is moderate. Further evaluation of this compound in combination regimens is recommended

Effect of high temperature deposition on CoSi 2 phase formation

Abstract: This paper discusses the nucleation behaviour of the CoSi to CoSi2 transformation from cobalt silicide thin films grown by deposition at elevated substrate temperatures ranging from 375 °C to 600 °C. A combination of channelling, real-time Rutherford backscattering spectrometry, real-time x-ray diffraction, and transmission electron microscopy was used to investigate the effect of the deposition temperature on the subsequent formation temperature of CoSi2, its growth behaviour, and the epitaxial quality of the CoSi2 thus formed. The temperature at which deposition took place was observed to exert a significant and systematic influence on both the formation temperature of CoSi2 and its growth mechanism. CoSi films grown at the lowest temperatures were found to increase the CoSi2 nucleation temperature above that of CoSi2 grown by conventional solid phase reaction, whereas the higher deposition temperatures reduced the nucleation temperature significantly. In addition, a systematic change in growth mechanism of the subsequent CoSi2 growth occurs as a function of deposition temperature. First, the CoSi2 growth rate from films grown at the lower reactive deposition temperatures is substantially lower than that grown at higher reactive deposition temperatures, even though the onset of growth occurs at a higher temperature, Second, for deposition temperatures below 450 °C, the growth appears columnar, indicating nucleation controlled growth. Elevated deposition temperatures, on the other hand, render the CoSi2 formation process layer-by-layer which indicates enhanced nucleation of the CoSi2 and diffusion controlled growth. Our results further indicate that this observed trend is most likely related to stress and changes in microstructure introduced during reactive deposition of the CoSi film. The deposition temperature therefore provides a handle to tune the CoSi2 growth mechanism

Vaginal cuff dehiscence in laparoscopic hysterectomy: influence of various suturing methods of the vaginal vault

Vaginal cuff dehiscence (VCD) is a severe adverse event and occurs more frequently after total laparoscopic hysterectomy (TLH) compared with abdominal and vaginal hysterectomy. The aim of this study is to compare the incidence of VCD after various suturing methods to close the vaginal vault. We conducted a retrospective cohort study. Patients who underwent TLH between January 2004 and May 2011 were enrolled. We compared the incidence of VCD after closure with transvaginal interrupted sutures versus laparoscopic interrupted sutures versus a laparoscopic single-layer running suture. The latter was either bidirectional barbed or a running vicryl suture with clips placed at each end commonly used in transanal endoscopic microsurgery. Three hundred thirty-one TLHs were included. In 75 (22.7 %), the vaginal vault was closed by transvaginal approach; in 90 (27.2 %), by laparoscopic interrupted sutures; and in 166 (50.2 %), by a laparoscopic running suture. Eight VCDs occurred: one (1.3 %) after transvaginal interrupted closure, three (3.3 %) after laparoscopic interrupted suturing and four (2.4 %) after a laparoscopic running suture was used (p = .707). With regard to the incidence of VCD, based on our data, neither a superiority of single-layer laparoscopic closure of the vaginal cuff with an unknotted running suture nor of the transvaginal and the laparoscopic interrupted suturing techniques could be demonstrated. We hypothesise that besides the suturing technique, other causes, such as the type and amount of coagulation used for colpotomy, may play a role in the increased risk of VCD after TLH

2D-Based 3D Volume Retrieval Using Singular Value Decomposition of Detected Regions

In this paper, a novel 3D retrieval model to retrieve medical volumes using 2D images as input is proposed. The main idea consists of applying a multi–scale detection of saliency of image regions. Then, the 3D volumes with the regions for each of the scales are associated with a set of projections onto the three canonical planes. The 3D shape is indirectly represented by a 2D–shape descriptor so that the 3D–shape matching is transformed into measuring similarity between 2D–shapes. The shape descriptor is defined by the set of the k largest singular values of the 2D images and Euclidean distance between the vector descriptors is used as a similarity measure. The preliminary results obtained on a simple database show promising performance with a mean average precision (MAP) of 0.82 and could allow using the approach as part of a retrieval system in clinical routine

Activity of high-dose epirubicin combined with gemcitabine in advanced non-small-cell lung cancer: a multicenter phase I and II study

The aim of the study was to evaluate efficacy and tolerance of epirubicin and gemcitabine as first-line chemotherapy in patients with advanced non-small-cell lung cancer. A phase I study was performed with the combination of escalating doses of epirubicin intravenously on day 1 and a fixed dose of gemcitabine on days 1 and 8 of a 21-day cycle. Eighteen patients were included in the phase I part of the study before the maximum tolerated dose was found. Dose-limiting toxicity was febrile neutropenia. The phase II part of the study was continued with epirubicin 100 mg m−2on day 1 and gemcitabine 1125 mg m−2on days 1 and 8 of a 21-day cycle. Forty-three chemotherapy-naive patients were included. The median age of the patients was 60 years (range 26–75). Most patients (74%) were in stage IV. Granulocytopenia CTC grade 4 occurred in 32.5% and thrombocytopenia grade 4 in 11.6% of cycles. Febrile neutropenia occurred in six patients. Non-haematological toxicity was mainly mucositis CTC grade 2 and 3 in 35% of patients. The tumour response rate was 49% (95% confidence interval (CI) 35–63%). The median survival time for the patients was 42 weeks (95% CI 13–69). © 2000 Cancer Research Campaig

Doppler-free frequency modulation spectroscopy of atomic erbium in a hollow cathode discharge cell

The erbium atomic system is a promising candidate for an atomic Bose-Einstein condensate of atoms with a non-vanishing orbital angular momentum ($L \neq 0$) of the electronic ground state. In this paper we report on the frequency stabilization of a blue external cavity diode laser system on the 400.91 $nm$ laser cooling transition of atomic erbium. Doppler-free saturation spectroscopy is applied within a hollow cathode discharge tube to the corresponding electronic transition of several of the erbium isotopes. Using the technique of frequency modulation spectroscopy, a zero-crossing error signal is produced to lock the diode laser frequency on the atomic erbium resonance. The latter is taken as a reference laser to which a second main laser system, used for laser cooling of atomic erbium, is frequency stabilized

Amplitude and Frequency Spectrum of Thermal Fluctuations of A Translocating RNA Molecule

Using a combination of theory and computer simulations, we study the translocation of an RNA molecule, pulled through a solid-state nanopore by an optical tweezer, as a method to determine its secondary structure. The resolution with which the elements of the secondary structure can be determined is limited by thermal fluctuations. We present a detailed study of these thermal fluctuations, including the frequency spectrum, and show that these rule out single-nucleotide resolution under the experimental conditions which we simulated. Two possible ways to improve this resolution are strong stretching of the RNA with a back-pulling voltage across the membrane, and stiffening of the translocated part of the RNA by biochemical means.Comment: Significantly expanded compared to previous version, 13 pages, 4 figures, to appear in J. Phys.: Condens. Matte

Sonic hedgehog expression in zebrafish forebrain identifies the teleostean pallidal signaling center and shows preglomerular complex and posterior tubercular dopamine cells to arise from shh cells

Ventralization, a major patterning process in the developing vertebrate neural tube (central nervous system, CNS), depends on Sonic hedgehog (SHH) as a main signaling morphogen. We studied the CNS of late larval and young adult zebrafish in a transgenic shh‐GFP line revealing increased neuroanatomical detail due to the progressed differentiation state compared to earlier stages. Some major findings emerge from the present study. (a) shh –GFP is still expressed along the adult zebrafish CNS neuraxis in most locations seen in larvae. (b) We newly identify a ventroposterior shh pallidal domain representing the basal telencephalic signaling center important for basal ganglia development known in other vertebrates (i.e., the anterior entopeduncular area—basal medial ganglionic eminence of mammals). (c) We further show late‐emerging shh‐GFP positive radial glia cells in the medial zone of the dorsal telencephalon (i.e., the teleostan pallial amygdala). (d) Immunostains for tyrosine hydroxylase demonstrate that there is selective colocalization in adult dopamine cells with shh‐GFP in the posterior tuberculum, including in projection cells to striatum, which represents a striking parallel to amniote mesodiencephalic dopamine cell origin from shh expressing floor plate cells. (e) There is no colocalization of shh and islet1 as shown by respective shh‐GFP and islet1‐GFP lines. (f) The only radially far migrated shh‐GFP cells are located in the preglomerular area. (g) There are no adult cerebellar and tectal shh‐GFP cells confirming their exclusive role during early development as previously reported by our laboratory

Hot-water immersion does not increase postprandial muscle protein synthesis rates during recovery from resistance-type exercise in healthy, young males

The purpose of this study was to assess the impact of postexercise hot-water immersion on postprandial myofibrillar protein synthesis rates during recovery from a single bout of resistance-type exercise in healthy, young men. Twelve healthy, adult men (age: 23 ± 1 y) performed a single bout of resistance-type exercise followed by 20 min of water immersion of both legs. One leg was immersed in hot water [46°C: hot-water immersion (HWI)], while the other leg was immersed in thermoneutral water (30°C: CON). After water immersion, a beverage was ingested containing 20 g intrinsically L-[1-13C]-phenylalanine and L-[1-13C]-leucine labeled milk protein with 45 g of carbohydrates. In addition, primed continuous L-[ring-2H5]-phenylalanine and L-[1-13C]-leucine infusions were applied, with frequent collection of blood and muscle samples to assess myofibrillar protein synthesis rates in vivo over a 5-h recovery period. Muscle temperature immediately after water immersion was higher in the HWI compared with the CON leg (37.5 ± 0.1 vs. 35.2 ± 0.2°C; P < 0.001). Incorporation of dietary protein-derived L-[1-13C]-phenylalanine into myofibrillar protein did not differ between the HWI and CON leg during the 5-h recovery period (0.025 ± 0.003 vs. 0.024 ± 0.002 MPE; P = 0.953). Postexercise myofibrillar protein synthesis rates did not differ between the HWI and CON leg based upon L-[1-13C]-leucine (0.050 ± 0.005 vs. 0.049 ± 0.002%/h; P = 0.815) and L-[ring-2H5]-phenylalanine (0.048 ± 0.002 vs. 0.047 ± 0.003%/h; P = 0.877), respectively. Hot-water immersion during recovery from resistance-type exercise does not increase the postprandial rise in myofibrillar protein synthesis rates. In addition, postexercise hot-water immersion does not increase the capacity of the muscle to incorporate dietary protein-derived amino acids in muscle tissue protein during subsequent recovery