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1.
Emerg Infect Dis ; 30(6): 1133-1143, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38781927

RESUMEN

We describe an unusual mortality event caused by a highly pathogenic avian influenza (HPAI) A(H5N1) virus clade 2.3.4.4b involving harbor (Phoca vitulina) and gray (Halichoerus grypus) seals in the St. Lawrence Estuary, Quebec, Canada, in 2022. Fifteen (56%) of the seals submitted for necropsy were considered to be fatally infected by HPAI H5N1 containing fully Eurasian or Eurasian/North American genome constellations. Concurrently, presence of large numbers of bird carcasses infected with HPAI H5N1 at seal haul-out sites most likely contributed to the spillover of infection to the seals. Histologic changes included meningoencephalitis (100%), fibrinosuppurative alveolitis, and multiorgan acute necrotizing inflammation. This report of fatal HPAI H5N1 infection in pinnipeds in Canada raises concerns about the expanding host of this virus, the potential for the establishment of a marine mammal reservoir, and the public health risks associated with spillover to mammals.Nous décrivons un événement de mortalité inhabituelle causé par un virus de l'influenza aviaire hautement pathogène A(H5N1) clade 2.3.4.4b chez des phoques communs (Phoca vitulina) et gris (Halichoerus grypus) dans l'estuaire du Saint-Laurent au Québec, Canada, en 2022. Quinze (56%) des phoques soumis pour nécropsie ont été considérés comme étant fatalement infectés par le virus H5N1 de lignées eurasiennes ou de réassortiment eurasiennes/nord-américaines. Un grand nombre simultané de carcasses d'oiseaux infectés par le H5N1 sur les sites d'échouement a probablement contribué à la contamination de ces phoques. Les changements histologiques associés à cette infection incluaient : méningo-encéphalite (100%), alvéolite fibrinosuppurée et inflammation nécrosante aiguë multi-organique. Cette documentation soulève des préoccupations quant à l'émergence de virus mortels, à la possibilité d'établissement de réservoirs chez les mammifères marins, et aux risques pour la santé publique associés aux propagations du virus chez les mammifères.


Asunto(s)
Brotes de Enfermedades , Subtipo H5N1 del Virus de la Influenza A , Animales , Subtipo H5N1 del Virus de la Influenza A/genética , Subtipo H5N1 del Virus de la Influenza A/patogenicidad , Quebec/epidemiología , Brotes de Enfermedades/veterinaria , Estuarios , Gripe Aviar/epidemiología , Gripe Aviar/virología , Gripe Aviar/historia , Phocidae/virología , Filogenia , Infecciones por Orthomyxoviridae/veterinaria , Infecciones por Orthomyxoviridae/virología , Infecciones por Orthomyxoviridae/epidemiología , Aves/virología
2.
Emerg Infect Dis ; 29(10): 2145-2149, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37735770

RESUMEN

Wholly Eurasian highly pathogenic avian influenza H5N1 clade 2.3.4.4b virus was isolated from 2 free-ranging black bears with meningoencephalitis in Quebec, Canada. We found that isolates from both animals had the D701N mutation in the polymerase basic 2 gene, previously known to promote adaptation of H5N1 viruses to mammal hosts.


Asunto(s)
Subtipo H5N1 del Virus de la Influenza A , Virus de la Influenza A , Gripe Humana , Ursidae , Animales , Humanos , Quebec/epidemiología , Subtipo H5N1 del Virus de la Influenza A/genética , Canadá
3.
Proc Natl Acad Sci U S A ; 111(26): E2703-10, 2014 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-24912178

RESUMEN

Understanding the origins of gut microbial community structure is critical for the identification and interpretation of potential fitness-related traits for the host. The presence of community clusters characterized by differences in the abundance of signature taxa, referred to as enterotypes, is a debated concept first reported in humans and later extended to other mammalian hosts. In this study, we provide a thorough assessment of their existence in wild house mice using a panel of evaluation criteria. We identify support for two clusters that are compositionally similar to clusters identified in humans, chimpanzees, and laboratory mice, characterized by differences in Bacteroides, Robinsoniella, and unclassified genera belonging to the family Lachnospiraceae. To further evaluate these clusters, we (i) monitored community changes associated with moving mice from the natural to a laboratory environment, (ii) performed functional metagenomic sequencing, and (iii) subjected wild-caught samples to stable isotope analysis to reconstruct dietary patterns. This process reveals differences in the proportions of genes involved in carbohydrate versus protein metabolism in the functional metagenome, as well as differences in plant- versus meat-derived food sources between clusters. In conjunction with wild-caught mice quickly changing their enterotype classification upon transfer to a standard laboratory chow diet, these results provide strong evidence that dietary history contributes to the presence of enterotype-like clustering in wild mice.


Asunto(s)
Alimentación Animal/análisis , Bacterias/genética , Dieta , Intestinos/microbiología , Ratones/microbiología , Microbiota/genética , Análisis de Varianza , Animales , Secuencia de Bases , Isótopos de Carbono/análisis , Análisis por Conglomerados , Cartilla de ADN/genética , Heces/microbiología , Francia , Alemania , Hígado/química , Metagenómica/métodos , Datos de Secuencia Molecular , Músculo Esquelético/química , Isótopos de Nitrógeno/análisis , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Especificidad de la Especie
4.
New Phytol ; 212(1): 259-68, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-26847468

RESUMEN

This paper presents highly unexpected paleobotanical data. Eight (14) C-accelerator mass spectrometry (AMS) dates of soil macrocharcoal pieces, identified taxonomically, indicate the presence of oak and beech in the Younger Dryas, and pine in the Allerød, in the northernmost low mountain range of Central Europe, the Harz Mountains, in Germany. If the presence of pine at such latitude and periods is not surprising, the presence of temperate-adapted trees is highly improbable, because they are assumed to have reached the area from a southern location several thousand years later. Two hypotheses are postulated to explain this record. Both are related to the warm periods of the Bølling and Allerød: the classically 'short' duration of this warm period makes the migration of the temperate trees from the identified refuge areas in the southern location implausible, and so the presence of intermediary microrefugia at a medium latitude in Central Europe is postulated; recent data reveal that the warm period of the Late Glacial phase was much longer than considered in the classical view and, thus, would be long enough for a northward migration of temperate-adapted trees. Although our dataset does not permit disentanglement of these hypotheses, it provides significant innovative insights for the biogeography of Central Europe.


Asunto(s)
Ecosistema , Árboles/fisiología , Clima , Europa (Continente) , Sedimentos Geológicos/química , Filogeografía , Suelo/química , Factores de Tiempo , Árboles/anatomía & histología
5.
Anesth Analg ; 122(1): 273-8, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26516803

RESUMEN

BACKGROUND: Single-injection ultrasound-guided infraclavicular block is a simple, reliable, and effective technique. A simplified double-injection ultrasound-guided axillary block technique with a high success rate recently has been described. It has the advantage of being performed in a superficial and compressible location, with a potentially improved safety profile. However, its effectiveness in comparison with single-injection infraclavicular block has not been established. We hypothesized that the double-injection ultrasound-guided axillary block would show rates of complete sensory block at 30 minutes noninferior to the single-injection ultrasound-guided infraclavicular block. METHODS: After approval by our research ethics committee and written informed consent, adults undergoing distal upper arm surgery were randomized to either group I, ultrasound-guided single-injection infraclavicular block, or group A, ultrasound-guided double-injection axillary block. In group I, 30 mL of 1.5% mepivacaine was injected posterior to the axillary artery. In group A, 25 mL of 1.5% mepivacaine was injected posteromedial to the axillary artery, after which 5 mL was injected around the musculocutaneous nerve. Primary outcome was the rate of complete sensory block at 30 minutes. Secondary outcomes were the onset of sensory and motor blocks, surgical success rates, performance times, and incidence of complications. All outcomes were assessed by a blinded investigator. The noninferiority of the double-injection ultrasound-guided axillary block was considered if the limits of the 90% confidence intervals (CIs) were within a 10% margin of the rate of complete sensory block of the infraclavicular block. RESULTS: At 30 minutes, the rate of complete sensory block was 79% in group A (90% CI, 71%-85%) compared with 91% in group I (90% CI, 85%-95%); the upper limit of CI of group A is thus included in the established noninferiority margin of 10%. The rate of complete sensory block was lower in group A (proportion difference of 12% [95% CI, 2-22]; P = 0.0091), as was surgical success rate (82% [95% CI, 74%-89%] vs 93% [95% CI, 86%-97%]; proportion difference of 11% [95% CI 1-20]; P = 0.0153). Sensory block onset also was slower in group A (log rank test P = 0.0020). Performance times were faster in group I (231 seconds [95% CI, 213-250]) than in group A (358 seconds [95% CI, 332-387]; P < 0.0001). No statistically significant difference was observed for vascular puncture, paresthesia during block performance, or procedure-related pain. No neurologic complication was noted at follow-up. CONCLUSIONS: We failed to demonstrate that the rate of complete sensory block of the double-injection axillary block is noninferior to the single-injection infraclavicular block. However, the rate of complete sensory block at 30 minutes is statistically significantly lower with the axillary block. The ultrasound-guided single-injection infraclavicular block thus seems to be the preferred technique over the axillary for upper arm anesthesia.


Asunto(s)
Anestésicos Locales/administración & dosificación , Axila/inervación , Clavícula/inervación , Mepivacaína/administración & dosificación , Bloqueo Nervioso/métodos , Ultrasonografía Intervencional , Adulto , Anciano , Anestésicos Locales/efectos adversos , Axila/diagnóstico por imagen , Clavícula/diagnóstico por imagen , Femenino , Humanos , Inyecciones , Masculino , Mepivacaína/efectos adversos , Persona de Mediana Edad , Actividad Motora/efectos de los fármacos , Bloqueo Nervioso/efectos adversos , Estudios Prospectivos , Quebec , Umbral Sensorial/efectos de los fármacos , Método Simple Ciego , Factores de Tiempo , Resultado del Tratamiento
6.
BMC Cancer ; 15: 479, 2015 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-26104798

RESUMEN

BACKGROUND: Valosin containing protein (VCP) is a critical mediator of protein homeostasis and may represent a valuable therapeutic target for several forms of cancer. Overexpression of VCP occurs in many cancers, and often in a manner correlating with malignancy and poor outcome. Here, we analyzed VCP expression in canine lymphoma and assessed its potential as a therapeutic target for this disease. METHODS: VCP expression in canine lymphomas was evaluated by immunoblotting and immunohistochemistry. The canine lymphoma cell lines CLBL-1, 17-71 and CL-1 were treated with the VCP inhibitor Eeyarestatin 1 (EER-1) at varying concentrations and times and were assessed for viability by trypan blue exclusion, apoptosis by TUNEL and caspase activity assays, and proliferation by propidium iodide incorporation and FACS. The mechanism of EER-1 action was determined by immunoblotting and immunofluorescence analyses of Lys48 ubiquitin and markers of ER stress (DDIT3), autophagy (SQSTM1, MAP1LC3A) and DNA damage (γH2AFX). TRP53/ATM-dependent signaling pathway activity was assessed by immunoblotting for TRP53 and phospho-TRP53 and real-time RT-PCR measurement of Cdkn1a mRNA. RESULTS: VCP expression levels in canine B cell lymphomas were found to increase with grade. EER-1 treatment killed canine lymphoma cells preferentially over control peripheral blood mononuclear cells. EER-1 treatment of CLBL-1 cells was found to both induce apoptosis and cell cycle arrest in G1. Unexpectedly, EER-1 did not appear to act either by inducing ER stress or inhibiting the aggresome-autophagy pathway. Rather, a rapid and dramatic increase in γH2AFX expression was noted, indicating that EER-1 may act by promoting DNA damage accumulation. Increased TRP53 phosphorylation and Cdkn1a mRNA levels indicated an activation of the TRP53/ATM DNA damage response pathway in response to EER-1, likely contributing to the induction of apoptosis and cell cycle arrest. CONCLUSIONS: These results correlate VCP expression with malignancy in canine B cell lymphoma. The selective activity of EER-1 against lymphoma cells suggests that VCP will represent a clinically useful therapeutic target for the treatment of lymphoma. We further suggest a mechanism of EER-1 action centered on the DNA repair response that may be of central importance for the design and characterization of VCP inhibitory compounds for therapeutic use.


Asunto(s)
Adenosina Trifosfatasas/antagonistas & inhibidores , Antineoplásicos/farmacología , Proteínas de Ciclo Celular/antagonistas & inhibidores , Daño del ADN/efectos de los fármacos , Linfoma/genética , Linfoma/metabolismo , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Perros , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos , Expresión Génica , Ganglios Linfáticos/patología , Linfoma/patología , Transducción de Señal/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Proteína que Contiene Valosina
7.
Am J Phys Anthropol ; 158(2): 325-340, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26175210

RESUMEN

OBJECTIVES: The island cemetery site of Ostorf (Germany) consists of individual human graves containing Funnel Beaker ceramics dating to the Early or Middle Neolithic. However, previous isotope and radiocarbon analysis demonstrated that the Ostorf individuals had a diet rich in freshwater fish. The present study was undertaken to quantitatively reconstruct the diet of the Ostorf population and establish if dietary habits are consistent with the traditional characterization of a Neolithic diet. METHODS: Quantitative diet reconstruction was achieved through a novel approach consisting of the use of the Bayesian mixing model Food Reconstruction Using Isotopic Transferred Signals (FRUITS) to model isotope measurements from multiple dietary proxies (δ13 Ccollagen , δ15 Ncollagen , δ13 Cbioapatite , δ34 Smethione , 14 Ccollagen ). The accuracy of model estimates was verified by comparing the agreement between observed and estimated human dietary radiocarbon reservoir effects. RESULTS: Quantitative diet reconstruction estimates confirm that the Ostorf individuals had a high protein intake due to the consumption of fish and terrestrial animal products. However, FRUITS estimates also show that plant foods represented a significant source of calories. Observed and estimated human dietary radiocarbon reservoir effects are in good agreement provided that the aquatic reservoir effect at Lake Ostorf is taken as reference. CONCLUSIONS: The Ostorf population apparently adopted elements associated with a Neolithic culture but adapted to available local food resources and implemented a subsistence strategy that involved a large proportion of fish and terrestrial meat consumption. This case study exemplifies the diversity of subsistence strategies followed during the Neolithic. Am J Phys Anthropol 158:325-340, 2015. © 2015 Wiley Periodicals, Inc.

10.
Can J Anaesth ; 60(3): 304-20, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23377861

RESUMEN

PURPOSE: The purpose of this module is to review the main ultrasound-guided approaches used for regional anesthesia of the upper limb. PRINCIPAL FINDINGS: The anatomical configuration of the upper limb, with nerves often bundled around an artery, makes regional anesthesia of the arm both accessible and reliable. In-depth knowledge of upper limb anatomy is required to match the blocked territory with the surgical area. The interscalene block is the approach most commonly used for shoulder surgery. Supraclavicular, infraclavicular, and axillary blocks are indicated for elbow and forearm surgery. Puncture techniques have evolved dramatically with ultrasound guidance. Instead of targeting the nerves directly, it is now recommended to look for diffusion areas. Typically, local anesthetics are deposited around vessels, often as a single injection. Phrenic nerve block can occur with the interscalene and supraclavicular approaches. Ulnar nerve blockade is almost never achieved with the interscalene approach and not always present with a supraclavicular block. If ultrasound guidance is used, the risk for pneumothorax with a supraclavicular approach is reduced significantly. Nerve damage and vascular puncture are possible with all approaches. If an axillary approach is chosen, the consequences of vascular puncture can be minimized because this site is compressible. CONCLUSIONS: Upper limb regional anesthesia has gained in popularity because of its effectiveness and the safety profile associated with ultrasound-guided techniques.


Asunto(s)
Anestesia de Conducción/métodos , Anestésicos Locales/administración & dosificación , Bloqueo Nervioso/métodos , Anestesia de Conducción/efectos adversos , Humanos , Bloqueo Nervioso/efectos adversos , Ultrasonografía Intervencional , Extremidad Superior/anatomía & histología , Extremidad Superior/cirugía
11.
Can J Anaesth ; 60(3): 244-52, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23212697

RESUMEN

INTRODUCTION: In recent studies on ultrasound-guided infraclavicular block (ICB), the authors have favoured a single injection posterior to the axillary artery rather than multiple injections; however, procedural complications and success rates associated with single-injection ultrasound-guided ICB are not well known. We undertook an observational study to evaluate the success rates of experienced and non-experienced operators performing ICBs and to identify the complications associated with ultrasound-guided single-injection ICB. METHODS: We conducted an observational cohort study of all ultrasound-guided single-injection ICBs performed over a two-year period (2008-2010). We identified the subjects for our study using a local database and excluded patients younger than 18 yr and those who received a continuous ICB. Complications (non-neurological and neurological) and ICB success rates were the primary and secondary end points, respectively. We collected the following data from patients' charts: patient demographics, types of complications and their respective frequencies, and the experience of the clinician performing the ICBs, and we identified potential late complications by telephone interview. Using a seven-point Likert scale, two experts in regional anesthesia evaluated the likelihood of a relationship between the identified neurological signs or symptoms and the ICB. A neurologist then evaluated the complications identified as being potentially related to the ICB. Summary data were collated, and 95% confidence intervals (CI) were calculated. RESULTS: We reviewed 627 ICB procedures, and 496 (79%) patients received telephone interviews. Most patients were males who had undergone either plastic or orthopedic surgery. Mepivacaine 1.5% was used in 96% of cases with a median volume of 30 mL [interquartile range 30-38]. We identified 131 cases of neurological signs or symptoms. Four cases were retained as possible links to the ICB, but they underwent complete resolution of symptoms at the time of evaluation. Two possible cases of local anesthetic toxicity were observed. There was a 93% success rate (95% CI 91 to 95) and the results were comparable between the experienced and the non-experienced operators (94% vs 93%, respectively). DISCUSSION: We observed few complications associated with a single-injection ultrasound-guided ICB and a high success rate regardless of the operator's expertise. The technique appears to be reliable, easy to perform, and safe.


Asunto(s)
Anestésicos Locales/administración & dosificación , Bloqueo Nervioso/métodos , Ultrasonografía Intervencional/métodos , Adulto , Anciano , Anestésicos Locales/efectos adversos , Plexo Braquial , Estudios de Cohortes , Femenino , Humanos , Inyecciones , Masculino , Mepivacaína/administración & dosificación , Mepivacaína/efectos adversos , Persona de Mediana Edad , Bloqueo Nervioso/efectos adversos , Procedimientos Ortopédicos/métodos , Procedimientos de Cirugía Plástica/métodos , Factores de Tiempo , Resultado del Tratamiento
12.
Can Vet J ; 54(4): 387-91, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24082168

RESUMEN

A 12-year-old, spayed female, Labrador dog was presented for evaluation of polyphagia, polyuria, polydipsia, weight loss of 2 months duration, and multiple cutaneous and subcutaneous masses. The dog was diagnosed with malignant pilomatrixoma with renal, lung, and lumbar metastases. This report describes an atypical presentation of malignant pilomatrixoma.


Pilomatrixoma malin avec métastases, améloblastome acanthomateux et tumeur hépatique chez une chienne avec polyphagie, polyurie, polydipsie et amaigrissement. Une chienne Labrador, âgée de 12 ans, était présentée pour l'évaluation d'une polyphagie, polyurie, polydipsie et d'un amaigrissement durant depuis 2 mois, ainsi que de multiples masses cutanées et sous-cutanées. Elle présentait un pilomatrixoma avec métastases aux reins, aux poumons et à une vertèbre lombaire. Ce rapport de cas décrit une présentation atypique de pilomatrixoma malin.(Traduit par les auteurs).


Asunto(s)
Ameloblastoma/veterinaria , Enfermedades de los Perros/patología , Neoplasias Hepáticas/veterinaria , Pilomatrixoma/veterinaria , Poliuria/veterinaria , Neoplasias Cutáneas/veterinaria , Ameloblastoma/clasificación , Animales , Perros , Femenino , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , Mucosa Bucal/patología , Neoplasias de la Boca/patología , Neoplasias de la Boca/veterinaria , Pilomatrixoma/complicaciones , Polidipsia , Poliuria/etiología , Neoplasias Cutáneas/patología , Pérdida de Peso
13.
JMIR Public Health Surveill ; 9: e39236, 2023 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-37494097

RESUMEN

The COVID-19 pandemic triggered unprecedented expansion of telemedicine, including in the delivery of opioid agonist treatment (OAT) for people with opioid use disorder (OUD). However, many people with OUD lack the technological resources necessary for remote care, have complex needs, and are underserved, with precarious access to mainstream services. To address the needs of these individuals, we devised a unique program to deliver OAT via telemedicine with the support of community outreach workers in Montreal (Quebec, Canada). The program was co-constructed by the service de médecine des toxicomanies of the Centre hospitalier de l'Université de Montréal (CHUM-SMT)-a hospital-based addiction medicine service-and CACTUS Montréal-a community-based harm reduction organization known and trusted by its clientele. All procedures were jointly developed to enable flexible and rapid appointment scheduling. CACTUS Montréal workers promoted the program, facilitated private on-site telemedicine connections to the CHUM-SMT, accompanied patients during web-based appointments if requested, and provided ongoing holistic support and follow-up. The CHUM-SMT offered individualized OAT regimens and other health services as needed. Overall, our experience as clinicians and community-based workers intimately involved in establishing and running this initiative suggests that participants found it to be convenient, nonjudgmental, and responsive to their needs, and that the implication of CACTUS Montréal was highly valued and integral to patient engagement and retention. Beyond the context of the COVID-19 pandemic, similar programs may present a flexible and accessible means to deliver alternative treatment options for people with OUD disengaged from traditional care, bridge gaps between communities and health providers, and improve access to care in rural or remote settings.


Asunto(s)
COVID-19 , Trastornos Relacionados con Opioides , Telemedicina , Humanos , Pandemias , Tratamiento de Sustitución de Opiáceos/métodos , Servicios de Salud Comunitaria , Telemedicina/métodos , Trastornos Relacionados con Opioides/epidemiología , Trastornos Relacionados con Opioides/tratamiento farmacológico
14.
R Soc Open Sci ; 10(9): 230741, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37711146

RESUMEN

Taxonomic identification of whale bones found during archaeological excavations is problematic due to their typically fragmented state. This difficulty limits understanding of both the past spatio-temporal distributions of whale populations and of possible early whaling activities. To overcome this challenge, we performed zooarchaeology by mass spectrometry on an unprecedented 719 archaeological and palaeontological specimens of probable whale bone from Atlantic European contexts, predominantly dating from ca 3500 BCE to the eighteenth century CE. The results show high numbers of Balaenidae (many probably North Atlantic right whale (Eubalaena glacialis)) and grey whale (Eschrichtius robustus) specimens, two taxa no longer present in the eastern North Atlantic. This discovery matches expectations regarding the past utilization of North Atlantic right whales, but was unanticipated for grey whales, which have hitherto rarely been identified in the European zooarchaeological record. Many of these specimens derive from contexts associated with mediaeval cultures frequently linked to whaling: the Basques, northern Spaniards, Normans, Flemish, Frisians, Anglo-Saxons and Scandinavians. This association raises the likelihood that early whaling impacted these taxa, contributing to their extirpation and extinction. Much lower numbers of other large cetacean taxa were identified, suggesting that what are now the most depleted whales were once those most frequently used.

15.
Carcinogenesis ; 33(11): 2283-92, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22871496

RESUMEN

Few targeted therapies have been developed for ovarian granulosa cell tumor (GCT), even though it represents 5% of all malignant ovarian tumors in women. As misregulation of PI3K/AKT signaling has been implicated in GCT development, we hypothesized that the AKT signaling effector mammalian target of rapamycin (mTOR) may play a role in the pathogenesis of GCT and could represent a therapeutic target. Analyses of human GCT samples showed an increase in protein levels of mTOR and its downstream effectors RPS6KB1, RPS6, eIF4B and PPARG relative to normal granulosa cells, suggestive of an increase in mTOR pathway activity and increased translational activity and/or protein stability. We next sought to evaluate mTOR as a GCT therapeutic target using the Pten (tm1Hwu/tmiHwu);Ctnnb1 (tm1Mmt/+);Amhr2 (tm3(cre)Bhr/+) (PCA) mouse model, in which mTOR, RPS6KB1, eIF4B and PPARG are upregulated in tumor cells in a manner similar to human GCT. Treatment of PCA mice with the mTOR-specific inhibitor everolimus reduced tumor growth rate (1.5-fold; P < 0.05) and also reduced total tumor burden (4.7-fold; P < 0.05) and increased survival rate (78 versus 44% in the vehicle group) in a PCA surgical model of GCT peritoneal carcinomatosis. Everolimus decreased tumor cell proliferation and tumor cell volume relative to controls (P < 0.05), whereas apoptosis was unaffected. Phosphorylation of RPS6KB1 and RPS6 were decreased (P < 0.05) by everolimus, but RPS6KB1, RPS6, eIF4B and PPARG expressions were not affected. These results suggest that mTOR is a valid and clinically useful pharmacological target for the treatment of GCT, although its inhibition does not reverse all consequences of aberrant PI3K/AKT signaling in the PCA model.


Asunto(s)
Proliferación Celular , Tumor de Células de la Granulosa/prevención & control , Inmunosupresores/uso terapéutico , Neoplasias Peritoneales/prevención & control , Sirolimus/análogos & derivados , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Adulto , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Factores Eucarióticos de Iniciación/genética , Factores Eucarióticos de Iniciación/metabolismo , Everolimus , Femenino , Tumor de Células de la Granulosa/mortalidad , Tumor de Células de la Granulosa/patología , Humanos , Técnicas para Inmunoenzimas , Ratones , Ratones Transgénicos , Fosfohidrolasa PTEN/fisiología , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/secundario , Fosforilación , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Quinasas S6 Ribosómicas 70-kDa/genética , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Transducción de Señal , Sirolimus/uso terapéutico , Tasa de Supervivencia , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , beta Catenina/fisiología
16.
Anesth Analg ; 114(1): 233-5, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22003214

RESUMEN

BACKGROUND: The optimal site for local anesthetic injection during ultrasound-guided sciatic popliteal block remains controversial. METHODS: Patients were randomized to receive 25 mL ropivacaine 0.75% around the sciatic nerve cephalad to the peroneal-tibial division in group A (n = 51) or caudad to the division in group B (n = 51). The sensory and motor blocks were evaluated every 5 minutes up to 30 minutes. RESULTS: Rates of complete sensory block and surgical anesthesia were superior in group B (P < 0.0001). CONCLUSION: The caudad technique provided better surgical anesthesia.


Asunto(s)
Amidas/administración & dosificación , Anestésicos Locales/administración & dosificación , Bloqueo Nervioso/métodos , Nervio Ciático/diagnóstico por imagen , Ultrasonografía Intervencional , Adulto , Femenino , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Actividad Motora/efectos de los fármacos , Neuronas Motoras/efectos de los fármacos , Estudios Prospectivos , Quebec , Análisis de Regresión , Ropivacaína , Sensación/efectos de los fármacos , Células Receptoras Sensoriales/efectos de los fármacos
17.
Can Vet J ; 53(5): 511-7, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-23115363

RESUMEN

The aim of this study was to determine whether or not canine lymphoma could be associated with a clinically relevant type B hyperlactatemia (> 2.5 mmol/L). The medical database from the University of Montreal Veterinary Medical Teaching Hospital was searched for confirmed cases of canine lymphoma with a blood lactate measurement. Information retrieved included stage, clinical observations compatible with causes of type A and B hyperlactatemia other than cancer, hepatic involvement, and drugs administered. Twenty (40%) dogs were hyperlactatemic. Five dogs (10%) were classified as having cancer-related hyperlactatemia. Seventy-five percent of hyperlactatemic dogs had clinical evidence of type A hyperlactatemia. In addition to lymphoma, 70% of hyperlactatemic dogs had evidence of an additional cause of type B hyperlactatemia. A significant association (P = 0.01) was identified between corticosteroid administration and hyperlactatemia. Cytological, echographic, and/or biochemical tests revealed hepatic changes in all hyperlactatemic dogs. Lymphoma alone may not be sufficient to explain clinically relevant hyperlactatemia in dogs.


Asunto(s)
Desequilibrio Ácido-Base/veterinaria , Enfermedades de los Perros/sangre , Lactatos/sangre , Linfoma/veterinaria , Neoplasias/veterinaria , Desequilibrio Ácido-Base/diagnóstico , Desequilibrio Ácido-Base/epidemiología , Desequilibrio Ácido-Base/etiología , Animales , Enfermedades de los Perros/diagnóstico , Perros , Femenino , Linfoma/sangre , Linfoma/diagnóstico , Masculino , Neoplasias/sangre , Neoplasias/diagnóstico , Estudios Retrospectivos
18.
Can Vet J ; 53(10): 1071-8, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23543925

RESUMEN

The objective of this study was to estimate the prevalence of mycoplasma, Staphylococcus aureus, and Streptococcus agalactiae in bulk tank milk (BTM) in Québec dairy herds. BTM was sampled 3 times a month in 117 randomly selected dairy herds. Samples were submitted for S. aureus, S. agalactiae, and mycoplasma and for direct mycoplasma detection by polymerase chain reaction (PCR). Mycoplasma spp. was identified at least once in 3 herds (2.6%) by primary culture and/or PCR and in 4 herds (3.4%) by enrichment culture and/or PCR. Staphylococcus aureus was isolated at least once in 99 (84.6%) and 112 (95.7%) herds in primary culture and after enrichment, respectively. Streptococcus agalactiae was isolated at least once in 9 (7.7%) and 10 (8.6%) herds in primary culture and after enrichment, respectively. Herd prevalence of mycoplasma was similar to that previously reported in Canada. Staphylococcus aureus is still by far the most important contagious mastitis pathogen.


Prévalence dans le lait de réservoir des agents pathogènes responsables de mammites contagieuses au Québec. L'objectif de cette étude était d'évaluer la prévelance de mycoplasmes, Stapylococcus aureus et Streptococcus agalactiae dans le lait de réservoir des troupeaux laitiers québécois. Dans 117 troupeaux sélectionnés aléatoirement, le lait de réservoir a été prélevé une fois par mois 3 mois de suite. Les prélèvements ont été soumis pour la recherche par culture de S. aureus, S. agalactiae et mycoplasmes ainsi que pour recherche directe par PCR pour mycoplasmes. Mycoplasma spp. a été identifié au moins une fois dans 3 troupeaux (2,6 %) en culture primaire ou PCR et dans 4 troupeaux (3,4 %) par enrichissement ou PCR. Staphylococcus aureus a été isolé au moins une fois dans 99 (84,6 %) et 112 (95,7 %) troupeaux en culture primaire et après enrichissement, respectivement. Streptococcus agalactiae a été isolé au moins une fois dans 9 (7,7 %) et 10 (8,6 %) troupeaux en culture primaire et après enrichissement, respectivement. La prévalence de troupeau de mycoplasmes est similaire à celle rapportée précédemment au Canada. Staphylococcus aureus est de loin le plus fréquent pathogène de mammite contagieuse.(Traduit par les auteurs).


Asunto(s)
Mastitis Bovina/microbiología , Leche/microbiología , Mycoplasma/aislamiento & purificación , Staphylococcus aureus/aislamiento & purificación , Streptococcus agalactiae/aislamiento & purificación , Animales , Bovinos , Industria Lechera , Femenino , Mastitis Bovina/epidemiología , Reacción en Cadena de la Polimerasa/veterinaria , Prevalencia , Quebec/epidemiología
20.
Can Vet J ; 52(9): 994-8, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22379200

RESUMEN

This retrospective study compared the efficacy of surgery alone versus surgery in combination with chemotherapy in the treatment of canine thyroid carcinoma; potential prognostic factors were evaluated. Forty-four dogs with biopsy-confirmed thyroid carcinoma met the inclusion criteria. Twenty-eight dogs were treated with surgery alone and 16 with surgery and chemotherapy. The median survival of dogs treated with surgery and chemotherapy was 518 d, which was not statistically different from that of the dogs treated with surgery alone. The number of thyroid lobes removed at surgery was prognostic with respect to survival. Despite an overall metastatic rate of 48%, the addition of chemotherapy to surgical excision did not improve survival; however, this finding may be due to inadequate power to demonstrate a difference.


Asunto(s)
Terapia Combinada/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/cirugía , Neoplasias de la Tiroides/veterinaria , Animales , Protocolos de Quimioterapia Combinada Antineoplásica , Enfermedades de los Perros/mortalidad , Perros , Femenino , Masculino , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/cirugía , Tiroidectomía/veterinaria , Resultado del Tratamiento
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