Osteosarcoma of the Pelvis: Outcome Analysis of Surgical Treatment

Risk factors to explain the poor survival of patients with osteosarcoma of the pelvis are poorly understood. Therefore, we attempted to identify factors affecting survival and development of local recurrence and metastasis. We retrospectively reviewed 43 patients who had high-grade pelvic tumors and were treated surgically. Twenty lesions were chondroblastic, 10 fibroblastic, 11 osteoblastic, and one each was giant cell-rich and small cell osteosarcomas. At a median of 3.5years (range, 0.3-21years) postoperatively, 13 patients were alive with no evidence of disease. The overall and disease-free 5-year survival rates were 38% and 29%, respectively, at 5years. Anatomic location, tumor size, and margin predicted survival. Fifteen patients (35%) had local recurrence. The 5-year cumulative incidence of recurrence with death as a competing risk factor was 34%. Location in the ilium and size of the tumor predicted local recurrence. Twenty-one (49%) of 43 patients had metastases develop. The cumulative incidence of metastasis with death as a competing risk factor was 48% at 5years. Six patients who presented with metastasis had a worse survival than patients who had no evidence of metastasis at presentation (2-year survival, 33% versus 76%). If distant metastasis is diagnosed subsequent to primary treatment, aggressive therapy may be justified. Level of Evidence: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidenc

Tracking motions from satellite water vapor imagery: Quantitative applications to hurricane track forecasting

Water vapor imagery from GOES satellites has been available for over a decade. These data are used extensively, mainly in a qualitative mode, by forecasters in the United States (Weldon and Holmes, 1991). Some attempts have been made at quantifying the data by tracking features in time sequences of the imagery (Stewart et al., 1985; Hayden and Stewart, 1987). For a variety of reasons, applications of this approach have produced marginal results (Velden, 1990). Recently, METEOSAT-3 (M-3) was repositioned at 50W by the European Space Agency, in order to provide complete coverage of the Atlantic Ocean. Data from this satellite are being transmitted to the U.S. for operational use. Compared with the GOES satellite, the M-3 has a superior resolution and signal-to-noise ratio in its water vapor channel, which translates into improved automated tracking capabilities. During a period in 1992 which included the Atlantic hurricane season, water vapor tracking algorithms were applied to the M-3 data in order to evaluate the coverage, accuracy and model impact of the derived vectors. Data sets were produced during several tropical cyclone cases, including Hurricane Andrew. In this paper, the M-3 water vapor wind sets are assessed, and their impact on a hurricane track forecast model is examined

Investigating the Reliability of Substance Toxicity Information Found on the Internet in Pediatric Poisonings

ObjectivesThe Internet may be the first source of information used by parents during a suspected poisoning of their children. Our primary aim was to assess the reliability of the Internet as a resource for information for parents to initially manage a suspected poisoning involving their child without outside consultation.MethodsWe distributed a self-administered survey to English-speaking parents to evaluate their Internet access behaviors so we could emulate their search strategies for a poisoning. A panel of clinical toxicologists performed an evaluation of Websites to determine the proportion that provided accurate and adequate information on common substances involved in poisonings.ResultsOf 21 parents surveyed, 15 (71%) used the Internet daily, with Google and Yahoo being the most commonly used search engines. Seven parents (39%) were somewhat to very likely to utilize the Internet during a poisoning scenario with prescription medications involving their child. Overall, only 27 (38%) of the Websites reviewed advised the user to call the poison center with the proper 800 telephone number, whereas no Website provided adequate information to manage the poisoning without outside consultation. Few Websites provided information on the toxic dose (13%), how to determine whether to manage the poisoning at home or in a hospital (22%), or first aid (28%).ConclusionsThe information provided on the Internet for substances involved in poisonings is variable and often incomplete. Reliance on the Internet for poisonings could create needless delays and inappropriate assessments and actions to manage a pediatric poisoning incident

Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

A descriptive exploratory study of how admissions caused by medication-related harm are documented within inpatients' medical records.

BACKGROUND: Adverse drug reactions, poor patient adherence and errors, here collectively referred to as medication-related harm (MRH), cause around 2.7-8.0% of UK hospital admissions. Communication gaps between successive healthcare providers exist, but little is known about how MRH is recorded in inpatients' medical records. We describe the presence and quality of MRH documentation for patients admitted to a London teaching hospital due to MRH. Additionally, the international classification of disease 10th revision (ICD-10) codes attributed to confirmed MRH-related admissions were studied to explore appropriateness of their use to identify these patients. METHODS: Clinical pharmacists working on an admissions ward in a UK hospital identified patients admitted due to suspected MRH. Six different data sources in each patient's medical record, including the discharge summary, were subsequently examined for MRH-related information. Each data source was examined for statements describing the MRH: symptom and diagnosis, identification of the causative agent, and a statement of the action taken or considered. Statements were categorised as 'explicit' if unambiguous or 'implicit' if open to interpretation. ICD-10 codes attributed to confirmed MRH cases were recorded. RESULTS: Eighty-four patients were identified over 141 data collection days; 75 met our inclusion criteria. MRH documentation was generally present (855 of 1307 statements were identified; 65%), and usually explicit (705 of 855; 82%). The causative agent had the lowest proportion of explicit statements (139 of 201 statements were explicit; 69%). For two (3%) discharged patients, the causal agent was documented in their paper medical record but not on the discharge summary. Of 64 patients with a confirmed MRH diagnosis at discharge, only six (9%) had a MRH-related ICD-10 code. CONCLUSIONS: Availability of information in the paper medical record needs improving and communication of MRH-related information could be enhanced by using explicit statements and documenting reasons for changing medications. ICD-10 codes underestimate the true occurrence of MRH

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

Differential cholinergic activation of G proteins in rat and mouse brainstem: Relevance for sleep and nociception

Murine models are increasingly used for investigations of sleep, yet no previous studies have characterized cholinergic activation of guanine nucleotide binding proteins (G proteins) in mouse brainstem nuclei known to regulate sleep. This study used in vitro [ 35 S]guanylyl-5′- O -(Γ-thio)-triphosphate ([ 35 S]GTPΓS) autoradiography to test the hypothesis that muscarinic cholinergic receptors activate G proteins in C57BL/6J (B6) mouse brainstem. The nuclei studied are homologous to those known in rat and cat to modulate sleep and nociception. In B6 mouse, carbachol significantly increased specific binding of [ 35 S]GTPΓS in the pontine reticular nucleus, caudal part (79%); pontine reticular nucleus, oral part (131%); laterodorsal tegmental nucleus (56%); pedunculopontine tegmental nucleus (86%); dorsal raphe nucleus (53%); dorsal medial periaqueductal gray (54%); and ventrolateral periaqueductal gray (52%) when compared with basal binding. Carbachol-induced G protein activation was concentration-dependent and blocked by atropine, demonstrating mediation by muscarinic receptors. G protein activation by carbachol was heterogeneous across B6 mouse brainstem nuclei. Comparison of [ 35 S]GTPΓS binding between mouse and rat revealed different magnitudes of G protein activation in the pontine reticular formation. In the same pontine reticular formation area of B6 mouse where in vitro treatment with carbachol activates G proteins, in vivo microinjection of cholinomimetics causes a rapid eye movement sleep-like state. These data provide the first direct measurement of muscarinic receptor-activated G proteins in B6 mouse brainstem nuclei known in other species to regulate sleep. J. Comp. Neurol. 457:175–184, 2003. © 2003 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34467/1/10548_ftp.pd

Myelin-mediated inhibition of oligodendrocyte precursor differentiation can be overcome by pharmacological modulation of Fyn-RhoA and protein kinase C signalling

Failure of oligodendrocyte precursor cell (OPC) differentiation contributes significantly to failed myelin sheath regeneration (remyelination) in chronic demyelinating diseases. Although the reasons for this failure are not completely understood, several lines of evidence point to factors present following demyelination that specifically inhibit differentiation of cells capable of generating remyelinating oligodendrocytes. We have previously demonstrated that myelin debris generated by demyelination inhibits remyelination by inhibiting OPC differentiation and that the inhibitory effects are associated with myelin proteins. In the present study, we narrow down the spectrum of potential protein candidates by proteomic analysis of inhibitory protein fractions prepared by CM and HighQ column chromatography followed by BN/SDS/SDS–PAGE gel separation using Nano-HPLC-ESI-Q-TOF mass spectrometry. We show that the inhibitory effects on OPC differentiation mediated by myelin are regulated by Fyn-RhoA-ROCK signalling as well as by modulation of protein kinase C (PKC) signalling. We demonstrate that pharmacological or siRNA-mediated inhibition of RhoA-ROCK-II and/or PKC signalling can induce OPC differentiation in the presence of myelin. Our results, which provide a mechanistic link between myelin, a mediator of OPC differentiation inhibition associated with demyelinating pathologies and specific signalling pathways amenable to pharmacological manipulation, are therefore of significant potential value for future strategies aimed at enhancing CNS remyelination

Co-Transplantation of Adipose Tissue-Derived Stromal Cells and Olfactory Ensheathing Cells for Spinal Cord Injury Repair

Patients suffering from spinal cord injury (SCI) still have a dismal prognosis. Despite all the efforts developed in this area, currently there are no effective treatments. Therefore, cell therapies have been proposed as a viable alternative to the current treatments used. Adipose tissue-derived stromal cells (ASCs) and olfactory ensheathing cells (OECs) have been used with promising results in different models of SCI, namely due to the regenerative properties of the secretome of the first, and the guidance capability of the second. Using an in vitro model of axonal growth, the dorsal root ganglia explants, we demonstrated that OECs induce neurite outgrowth mainly through cell-cell interactions, while ASCs' effects are strongly mediated by the release of paracrine factors. A proteomic analysis of ASCs' secretome revealed the presence of proteins involved in VEGF, PI3K, and Cadherin signaling pathways, which may be responsible for the effects observed. Then, the cotransplantation of ASCs and OECs showed to improve motor deficits of SCI-rats. Particular parameters of movement such as stepping, coordination, and toe clearance were improved in rats that received the transplant of cells, in comparison to nontreated rats. A histological analysis of the spinal cord tissues revealed that transplantation of ASCs and OECs had a major effect on the reduction of inflammatory cells close the lesion site. A slight reduction of astrogliosis was also evident. Overall, the results obtained with the present work indicate that the cotransplantation of ASCs and OECs brings important functional benefits to the injured spinal cord. Stem Cells 2018;36:696-708.This article is a result of the project (NORTE-01-0145-FEDER-000013), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); Cofinanciado pelo Programa Operacional Regional do Norte (ON.2 SR&TD Integrated Program – NORTE-07-0124-FEDER- 000021), ao abrigo do Quadro de Referência Estrategico Nacional (QREN), através do Fundo Europeu de Desenvolvimento Regional (FEDER); Projeto Estrategico – LA 26 – 2011–2012 and Projeto Estratégico – LA 26 – 2013-2014 cofinan- ciado por fundos nacionais, através da Fundação para a Ciência e a Tecnologia (PEst-C/SAU/LA0026/2011; PEst-C/SAU/LA0026/2013), e pelo Fundo Europeu de DesenvolvimentoRegional (FEDER), através do COMPETE (FCOMP-01-0124- FEDER-022724; FCOMP-01-0124-FEDER-037298 ). Support also from PTDC/NEU-SCC/7051/2014; POCI-01-0145-FEDER-007440; PTDC/NEU-NMC/0205/2012; UID/NEU/04539/2013; The National Mass Spectrometry Network (RNEM) (REDE/1506/ REM/2005). This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the pro- ject POCI-01-0145-FEDER-0070info:eu-repo/semantics/publishedVersio

Mesenchymal stromal-cell transplants induce oligodendrocyte progenitor migration and remyelination in a chronic demyelination model.

Demyelinating disorders such as leukodystrophies and multiple sclerosis are neurodegenerative diseases characterized by the progressive loss of myelin that may lead toward a chronic demyelination of the brain¿s white matter, impairing normal axonal conduction velocity and ultimately causing neurodegeneration. Current treatments modifying the pathological mechanisms are capable of ameliorating the disease; however, frequently, these therapies are not sufficient to repress the progressive demyelination into a chronic condition and permanent loss of function. To this end, we analyzed the effect that bone marrowderived mesenchymal stromal cell (BM-MSC) grafts exert in a chronically demyelinated mouse brain. As a result, oligodendrocyte progenitors were recruited surrounding the graft due to the expression of various trophic signals by the grafted MSCs. Although there was no significant reaction in the non-grafted side, in the grafted regions oligodendrocyte progenitors were detected. These progenitors were derived from the nearby tissue as well as from the neurogenic niches, including the subependymal zone and dentate gyrus. Once near the graft site, the cells matured to myelinating oligodendrocytes. Finally, electrophysiological studies demonstrated that axonal conduction velocity was significantly increased in the grafted side of the fimbria. In conclusion, we demonstrate here that in chronic demyelinated white matter, BM-MSC transplantation activates oligodendrocyte progenitors and induces remyelination in the tissue surrounding the stem cell graft