1,378 research outputs found
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
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
Modifying one’s hand’s trajectory when a moving target’s orientation changes
The path that the hand takes to intercept an elongated moving target depends on the target’s orientation. How quickly do people respond to changes in the moving target’s orientation? In the present study, participants were asked to intercept moving targets that sometimes abruptly changed orientation shortly after they started moving. It took the participants slightly more than 150 ms to adjust their hands’ paths to a change in target orientation. This is about 50 ms longer than it took them to respond to a 5-mm jump in the moving target’s position. It is only slightly shorter than it took them to initiate the movement. We propose that responses to changes in visually perceived orientation are not exceptionally fast, because there is no relationship between target orientation and direction of hand movement that is sufficiently general in everyday life for one to risk making an inappropriate response in order to respond faster
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
Do we use a priori knowledge of gravity when making elbow rotations?
In this study, we aim to investigate whether motor commands, emanating from movement planning, are customized to movement orientation relative to gravity from the first trial on. Participants made fast point-to-point elbow flexions and extensions in the transverse plane. We compared movements that had been practiced in reclined orientation either against or with gravity with the same movement relative to the body axis made in the upright orientation (neutral compared to gravity). For each movement type, five rotations from reclined to upright orientation were made. For each rotation, we analyzed the first trial in upright orientation and the directly preceding trial in reclined orientation. Additionally, we analyzed the last five trials of a 30-trial block in upright position and compared these trials with the first trials in upright orientation. Although participants moved fast, gravitational torques were substantial. The change in body orientation affected movement planning: we found a decrease in peak angular velocity and a decrease in amplitude for the first trials made in the upright orientation, regardless of whether the previous movements in reclined orientation were made against or with gravity. We found that these decreases disappeared after participants familiarized themselves with moving in upright position in a 30-trial block. These results indicate that participants used a general strategy, corresponding to the strategy observed in situations with unreliable or limited information on external conditions. From this, we conclude that during movement planning, a priori knowledge of gravity was not used to specifically customize motor commands for the neutral gravity condition
A Longitudinal Method for Simultaneous Whole-Brain and Lesion Segmentation in Multiple Sclerosis
In this paper we propose a novel method for the segmentation of longitudinal
brain MRI scans of patients suffering from Multiple Sclerosis. The method
builds upon an existing cross-sectional method for simultaneous whole-brain and
lesion segmentation, introducing subject-specific latent variables to encourage
temporal consistency between longitudinal scans. It is very generally
applicable, as it does not make any prior assumptions on the scanner, the MRI
protocol, or the number and timing of longitudinal follow-up scans. Preliminary
experiments on three longitudinal datasets indicate that the proposed method
produces more reliable segmentations and detects disease effects better than
the cross-sectional method it is based upon
Three-dimensional coherence of the conscious body image
We experience our body as a coherent object in the three-dimensional (3-D) world. In contrast, the body is represented in somatosensory cortex as a fragmented collection of two-dimensional (2-D) maps. Recent results have suggested that some forms of higher-level body representations maintain this fragmentation, for example by showing different patterns of distortion for two surfaces of a single body part, such as the palmar and dorsal hand surfaces. This study investigated the 3-D coherence of the conscious body image of the hand by comparing perceptual biases of perceived hand shape on the dorsal and palmar surfaces. Participants made forced-choice judgments of whether observed hand images were thinner or wider than their own left or right hand, and perceptual distortions of the hand image were assessed by fitting psychometric functions. The results suggested that the hand is consciously represented as a fully coherent, 3-D object. Specifically: (1) similar overall levels of distortion were found on the palmar and dorsal hand surfaces, (2) comparable laterality effects were found on both surfaces (left hand represented as wider than right hand), and (3) the magnitude of distortions were strongly correlated across the two surfaces. Whereas other recent results have suggested that perceptual abilities such as position sense, tactile size perception, and tactile localisation may rely on fragmented, 2-D representations of individual skin surfaces, the present results suggest that, in striking contrast, the conscious body image represents the body (or, at least the hand) as a coherent, 3-D object
The clinical response to infliximab in rheumatoid arthritis is in part dependent on pretreatment tumour necrosis factor α expression in the synovium
Objective: To determine whether the heterogeneous clinical response to tumour necrosis factor (TNF)alpha blocking therapy in rheumatoid arthritis (RA) can be predicted by TNF alpha expression in the synovium before initiation of treatment. Methods: Prior to initiation of infliximab treatment, arthroscopic synovial tissue biopsies were obtained from 143 patients with active RA. At week 16, clinical response was evaluated using the 28-joint Disease Activity Score (DAS28). Immunohistochemistry was used to analyse the cell infiltrate as well as the expression of various cytokines, adhesion molecules and growth factors. Stained sections were evaluated by digital image analysis. Student t tests were used to compare responders (decrease in DAS28 >= 1.2) with non-responders (decrease in DAS28 <1.2) and multivariable regression was used to identify the independent predictors of clinical response. Results: Synovial tissue analysis confirmed our hypothesis that the baseline level of TNF alpha expression is a significant predictor of response to TNF alpha blocking therapy. TNF alpha expression in the intimal lining layer and synovial sublining were significantly higher in responders than in non-responders (p = 0.047 and p = 0.008, respectively). The numbers of macrophages, macrophage subsets and T cells (all able to produce TNF alpha) were also significantly higher in responders than in non-responders. The expression of interleukin (IL)1 beta, IL6, IL18, IL10, E-selectin, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was not associated with response to anti-TNF alpha treatment. Conclusion: The effects of TNF alpha blockade are in part dependent on synovial TNF alpha expression and infiltration by TNF alpha producing inflammatory cells. Clinical response cannot be predicted completely, indicating involvement of other as yet unknown mechanism
Active wetting of epithelial tissues
Development, regeneration and cancer involve drastic transitions in tissue
morphology. In analogy with the behavior of inert fluids, some of these
transitions have been interpreted as wetting transitions. The validity and
scope of this analogy are unclear, however, because the active cellular forces
that drive tissue wetting have been neither measured nor theoretically
accounted for. Here we show that the transition between 2D epithelial
monolayers and 3D spheroidal aggregates can be understood as an active wetting
transition whose physics differs fundamentally from that of passive wetting
phenomena. By combining an active polar fluid model with measurements of
physical forces as a function of tissue size, contractility, cell-cell and
cell-substrate adhesion, and substrate stiffness, we show that the wetting
transition results from the competition between traction forces and contractile
intercellular stresses. This competition defines a new intrinsic lengthscale
that gives rise to a critical size for the wetting transition in tissues, a
striking feature that has no counterpart in classical wetting. Finally, we show
that active shape fluctuations are dynamically amplified during tissue
dewetting. Overall, we conclude that tissue spreading constitutes a prominent
example of active wetting --- a novel physical scenario that may explain
morphological transitions during tissue morphogenesis and tumor progression
Implementation of Early Intervention Protocol in Australia for 'High Risk' Injured Workers is Associated with Fewer Lost Work Days Over 2 Years Than Usual (Stepped) Care
The original version of this article unfortunately contained a spelling error in one of the co-authors's names. The family name of the co-author was incorrectly displayed as "James McCauley" instead of "James McAuley. The original article has been corrected
- …