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1.
Ann Oncol ; 31(11): 1526-1535, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32828825

RESUMO

BACKGROUND: In EMBRACA, talazoparib prolonged progression-free survival versus chemotherapy (hazard ratio [HR] 0.542 [95% confidence interval (CI) 0.413-0.711]; P < 0.0001) and improved patient-reported outcomes (PRO) in germline BRCA1/2 (gBRCA1/2)-mutated advanced breast cancer (ABC). We report final overall survival (OS). PATIENTS AND METHODS: This randomized phase III trial enrolled patients with gBRCA1/2-mutated HER2-negative ABC. Patients received talazoparib or physician's choice of chemotherapy. OS was analyzed using stratified HR and log-rank test and prespecified rank-preserving structural failure time model to account for subsequent treatments. RESULTS: A total of 431 patients were entered in a randomized study (287 talazoparib/144 chemotherapy) with 412 patients treated (286 talazoparib/126 chemotherapy). By 30 September 2019, 216 deaths (75.3%) occurred for talazoparib and 108 (75.0%) chemotherapy; median follow-up was 44.9 and 36.8 months, respectively. HR for OS with talazoparib versus chemotherapy was 0.848 (95% CI 0.670-1.073; P = 0.17); median (95% CI) 19.3 months (16.6-22.5 months) versus 19.5 months (17.4-22.4 months). Kaplan-Meier survival percentages (95% CI) for talazoparib versus chemotherapy: month 12, 71% (66% to 76%)/74% (66% to 81%); month 24, 42% (36% to 47%)/38% (30% to 47%); month 36, 27% (22% to 33%)/21% (14% to 29%). Most patients received subsequent treatments: for talazoparib and chemotherapy, 46.3%/41.7% received platinum and 4.5%/32.6% received a poly(ADP-ribose) polymerase (PARP) inhibitor, respectively. Adjusting for subsequent PARP and/or platinum use, HR for OS was 0.756 (95% bootstrap CI 0.503-1.029). Grade 3-4 adverse events occurred in 69.6% (talazoparib) and 64.3% (chemotherapy) patients, consistent with previous reports. Extended follow-up showed significant overall improvement and delay in time to definitive clinically meaningful deterioration in global health status/quality of life and breast symptoms favoring talazoparib versus chemotherapy (P < 0.01 for all), consistent with initial analyses. CONCLUSIONS: In gBRCA1/2-mutated HER2-negative ABC, talazoparib did not significantly improve OS over chemotherapy; subsequent treatments may have impacted analysis. Safety was consistent with previous observations. PRO continued to favor talazoparib.


Assuntos
Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteína BRCA1/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Células Germinativas , Mutação em Linhagem Germinativa , Humanos , Ftalazinas , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Qualidade de Vida
2.
J Biomed Sci ; 27(1): 96, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008372

RESUMO

BACKGROUND: A lung transplant is the last resort treatment for many patients with advanced lung disease. The majority of donated lungs come from donors following brain death (BD). The endothelin axis is upregulated in the blood and lung of the donor after BD resulting in systemic inflammation, lung damage and poor lung graft outcomes in the recipient. Tezosentan (endothelin receptor blocker) improves the pulmonary haemodynamic profile; however, it induces adverse effects on other organs at high doses. Application of ex vivo lung perfusion (EVLP) allows the development of organ-specific hormone resuscitation, to maximise and optimise the donor pool. Therefore, we investigate whether the combination of EVLP and tezosentan administration could improve the quality of donor lungs in a clinically relevant 6-h ovine model of brain stem death (BSD). METHODS: After 6 h of BSD, lungs obtained from 12 sheep were divided into two groups, control and tezosentan-treated group, and cannulated for EVLP. The lungs were monitored for 6 h and lung perfusate and tissue samples were processed and analysed. Blood gas variables were measured in perfusate samples as well as total proteins and pro-inflammatory biomarkers, IL-6 and IL-8. Lung tissues were collected at the end of EVLP experiments for histology analysis and wet-dry weight ratio (a measure of oedema). RESULTS: Our results showed a significant improvement in gas exchange [elevated partial pressure of oxygen (P = 0.02) and reduced partial pressure of carbon dioxide (P = 0.03)] in tezosentan-treated lungs compared to controls. However, the lungs hematoxylin-eosin staining histology results showed minimum lung injuries and there was no difference between both control and tezosentan-treated lungs. Similarly, IL-6 and IL-8 levels in lung perfusate showed no difference between control and tezosentan-treated lungs throughout the EVLP. Histological and tissue analysis showed a non-significant reduction in wet/dry weight ratio in tezosentan-treated lung tissues (P = 0.09) when compared to control. CONCLUSIONS: These data indicate that administration of tezosentan could improve pulmonary gas exchange during EVLP.


Assuntos
Antagonistas dos Receptores de Endotelina/farmacologia , Pulmão/efeitos dos fármacos , Piridinas/farmacologia , Testes de Função Respiratória , Tetrazóis/farmacologia , Vasodilatadores/farmacologia , Animais , Modelos Animais de Doenças , Pulmão/fisiologia , Perfusão , Carneiro Doméstico , Doadores de Tecidos
3.
Equine Vet Educ ; 31(10): 517-522, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33041530

RESUMO

Silicate associated osteoporosis (SAO) was diagnosed post mortem in an adult horse with the shortest documented exposure to cytotoxic silicates of 2 years. The horse was evaluated for a 6-months history of progressive back tenderness and acute onset of lameness. The horse had a marked (4/5) [American Association of Equine Practitioners scale] left forelimb lameness, moderate (2/5) hindlimb ataxia and weakness, and cervical pain upon palpation. Physical examination did not reveal clinical skeletal deformities or respiratory compromise. Radiographs revealed widespread, discrete, sharply delineated, osteolytic lesions in the skull, vertebral column, ribs, scapulae and middle phalanx (P2) of the left forelimb and a diffuse bronchointerstitial lung pattern. The presumptive clinical diagnosis was widespread, metastatic osteolytic neoplasia. Due to the poor quality of life and grave prognosis, the horse was humanely euthanised. Post mortem examination revealed pulmonary silicosis in the lungs and hilar lymph nodes and osteolytic lesions with numerous, large osteoclasts and disorganised bone remodeling both consistent with SAO. SAO should be included as a differential diagnosis for horses with widespread, multifocal, discrete osteolysis and history of exposure to endemic regions with possible cytotoxic silicate inhalation. Exposure time of 2 years is potentially sufficient to develop SAO.

4.
Vet Pathol ; 54(1): 155-158, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27312367

RESUMO

West Nile virus (WNV) infection has been detected in many species of birds and mammals, but scant information is available about the disease in small ruminants. West Nile virus was diagnosed in 6 sheep with neurological signs and encephalitis, in California between 2002 and 2014. All sheep had severe lymphoplasmacytic meningoencephalitis. Lymphoplasmacytic myelitis was also detected in 2 sheep where the spinal cord was examined. Brain tissue was positive for WNV detected by polymerase chain reaction in 6 of 6 sheep and by immunohistochemistry (IHC) in 5 of 6 sheep. Viral antigen was not detected by IHC in extraneural tissues in the 3 sheep examined. West Nile virus RNA was sequenced from 2 of 6 sheep, and each one clusters closely with WNV isolated from mosquito pools from nearby locations at similar times. West Nile virus was the most common cause of viral encephalitis in sheep diagnosed at this laboratory between 2002 and 2014, accounting for 6 of 9 sheep.


Assuntos
Doenças dos Ovinos/virologia , Febre do Nilo Ocidental/veterinária , Vírus do Nilo Ocidental , Animais , Encéfalo/patologia , Encéfalo/virologia , Feminino , Masculino , Reação em Cadeia da Polimerase/veterinária , Análise de Sequência de RNA/veterinária , Ovinos/virologia , Doenças dos Ovinos/patologia , Febre do Nilo Ocidental/patologia , Vírus do Nilo Ocidental/genética
5.
Vet Pathol ; 52(1): 189-92, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24686386

RESUMO

Mortality of 20% of a flock of 1000 chukar partridge chicks occurred over a 6-week period in Northern California from August to September 2012. Affected birds were 2 to 42 days old and died without premonitory clinical signs or after showing ruffled feathers and anorexia for 24 to 72 hours. Three carcasses were submitted for necropsy, 2 birds had hemorrhagic tracheitis grossly, and all 3 had lymphoplasmacytic and histiocytic myocarditis with myocardial necrosis microscopically. The differential diagnoses and the diagnostic workup to achieve a final diagnosis are discussed. The detection of 2 zoonotic agents in these birds makes this an interesting case from a public health perspective.


Assuntos
Doenças das Aves/patologia , Salmonelose Animal/patologia , Salmonella typhimurium/isolamento & purificação , Febre do Nilo Ocidental/veterinária , Vírus do Nilo Ocidental/isolamento & purificação , Animais , Doenças das Aves/mortalidade , California , Diagnóstico Diferencial , Plumas , Feminino , Galliformes , Masculino , Salmonelose Animal/mortalidade , Febre do Nilo Ocidental/mortalidade , Febre do Nilo Ocidental/patologia
6.
Vet Pathol ; 52(6): 1148-56, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25648965

RESUMO

Equine coronavirus (ECoV) is a Betacoronavirus recently associated clinically and epidemiologically with emerging outbreaks of pyrogenic, enteric, and/or neurologic disease in horses in the United States, Japan, and Europe. We describe the pathologic, immunohistochemical, ultrastructural, and molecular findings in 2 horses and 1 donkey that succumbed to natural infection with ECoV. One horse and the donkey (case Nos. 1, 3) had severe diffuse necrotizing enteritis with marked villous attenuation, epithelial cell necrosis at the tips of the villi, neutrophilic and fibrinous extravasation into the small intestinal lumen (pseudomembrane formation), as well as crypt necrosis, microthrombosis, and hemorrhage. The other horse (case No. 2) had hyperammonemic encephalopathy with Alzheimer type II astrocytosis throughout the cerebral cortex. ECoV was detected by quantitative polymerase chain reaction in small intestinal tissue, contents, and/or feces, and coronavirus antigen was detected by immunohistochemistry in the small intestine in all cases. Coronavirus-like particles characterized by spherical, moderately electron lucent, enveloped virions with distinct peplomer-like structures projecting from the surface were detected by negatively stained transmission electron microscopy in small intestine in case No. 1, and transmission electron microscopy of fixed small intestinal tissue from the same case revealed similar 85- to 100-nm intracytoplasmic particles located in vacuoles and free in the cytoplasm of unidentified (presumably epithelial) cells. Sequence comparison showed 97.9% to 99.0% sequence identity with the ECoV-NC99 and Tokachi09 strains. All together, these results indicate that ECoV is associated with necrotizing enteritis and hyperammonemic encephalopathy in equids.


Assuntos
Encefalopatias/veterinária , Infecções por Coronavirus/veterinária , Coronavirus/imunologia , Enterite/veterinária , Equidae , Doenças dos Cavalos/patologia , Animais , Sequência de Bases , Encefalopatias/patologia , Encefalopatias/virologia , Coronavirus/genética , Coronavirus/isolamento & purificação , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Enterite/patologia , Enterite/virologia , Fezes/virologia , Feminino , Doenças dos Cavalos/virologia , Cavalos , Hiperamonemia/veterinária , Intestino Delgado/patologia , Intestino Delgado/virologia , Dados de Sequência Molecular , Necrose/veterinária , Análise de Sequência de DNA/veterinária
7.
Invest New Drugs ; 31(1): 115-25, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22415798

RESUMO

BACKGROUND: This phase I study evaluated the safety, tolerability and preliminary efficacy of sorafenib combined with vorinostat in patients with solid tumors. PATIENTS AND METHODS: Patients were treated with sorafenib 400 mg po bid daily and vorinostat 200-400 mg po days 1-14 of a 21 day cycle to establish the recommended phase II dose (RP2D). The tolerability and efficacy of the RP2D was further tested in two cohorts of 6-12 patients each with advanced RCC and NSCLC. RESULTS: 17 patients were treated in the dose escalation phase that established the RP2D at sorafenib 400 mg po bid daily, vorinostat 300 mg po days 1-14. Dose limiting toxicities (DLT) included intolerable grade 2 hand-foot syndrome and multiple grade 1 toxicities causing dose interruption for more than 14 days. Despite good tolerance in the all-comers population, the RP2D was poorly tolerated in the RCC and NSCLC cohorts with the majority being unable to finish 2 full cycles of therapy. Although there were no confirmed responses, 1 patient each with NSCLC adenocarcinoma and renal sarcoma had unconfirmed partial responses and 5 of 8 patients with RCC having durable minor responses (11-26 %), including 2 who were on treatment for nearly a year. CONCLUSIONS: Although tolerable in other tumor types, sorafenib 400 mg po bid with vorinostat 300 mg po daily days 1-14 of a 21-day cycle is not tolerable without dose reductions/delays in RCC and NSCLC patients. These patients may require lower doses than the RP2D explored within this study. No confirmed responses were seen but minor responses particularly in RCC were observed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Inibidores de Histona Desacetilases/administração & dosagem , Humanos , Ácidos Hidroxâmicos/administração & dosagem , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Sorafenibe , Vorinostat
8.
Vet Pathol ; 50(6): 1028-36, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23686768

RESUMO

Clostridium difficile is commonly associated with diarrhea and colitis in humans and other mammals, including horses. To this date, the epidemiologic, microbiologic, clinical, and diagnostic aspects of C. difficile-associated disease (CDAD) in horses have been thoroughly described. However, reports describing the enteric pathology of this disease in horses are limited. This study presents a comprehensive description of the pathologic characteristics of CDAD in 21 horses and discusses the criteria for the diagnosis of the disease. Case selection was based on C. difficile A/B toxins detection (enzyme-linked immunosorbent assay) in intestinal content samples accompanied by compatible gross and microscopic enteric lesions. Grossly, multifocal, segmental, or diffuse hemorrhage; congestion; and/or marked gelatinous edema of the intestinal wall with abundant bloody or green watery contents were observed. Histologically, the most common lesion was severe necrotizing or necrohemorrhagic enteritis, colitis, or typhlocolitis, with mucosal and/or submucosal thrombosis and marked submucosal edema. The pathology of CDAD in horses is similar to that caused by other equine enteric pathogens; therefore, a definitive diagnosis requires detection of C. difficile A/B toxins in the intestinal contents.


Assuntos
Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/veterinária , Colite/veterinária , Enterite/veterinária , Doenças dos Cavalos/diagnóstico , Animais , Animais Recém-Nascidos , Proteínas de Bactérias/isolamento & purificação , Toxinas Bacterianas/isolamento & purificação , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/microbiologia , Colite/diagnóstico , Colite/microbiologia , Diarreia/veterinária , Enterite/diagnóstico , Enterite/microbiologia , Enterotoxinas/isolamento & purificação , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Doenças dos Cavalos/microbiologia , Cavalos , Intestinos/patologia , Masculino , Estudos Retrospectivos
9.
Vet Pathol ; 50(3): 530-3, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23355516

RESUMO

A group of 342 beef calves, corralled in the Patagonia region of Argentina, were fed alfalfa hay that had been inadvertently contaminated with Wedelia glauca. A total of 147 (43%) calves died within 4 days. Pathologic findings in 2 calves were diffuse centrilobular hepatic necrosis and hemorrhage with edema in the gallbladder, common bile duct, and choledochoduodenal junction. Epidermal fragments of W. glauca were identified in rumen contents by microscopy. Intact W. glauca plants and leaf fragments were found in the hay. Patches of defoliated W. glauca were also identified in the alfalfa pasture from which the hay had been baled.


Assuntos
Doenças dos Bovinos/etiologia , Intoxicação por Plantas/veterinária , Wedelia/intoxicação , Ração Animal , Animais , Argentina/epidemiologia , Doenças dos Ductos Biliares/etiologia , Doenças dos Ductos Biliares/patologia , Doenças dos Ductos Biliares/veterinária , Bovinos , Doenças dos Bovinos/economia , Doenças dos Bovinos/patologia , Surtos de Doenças/veterinária , Diterpenos/intoxicação , Edema/etiologia , Edema/patologia , Edema/veterinária , Feminino , Doenças da Vesícula Biliar/etiologia , Doenças da Vesícula Biliar/patologia , Doenças da Vesícula Biliar/veterinária , Hemorragia/etiologia , Hemorragia/patologia , Hemorragia/veterinária , Fígado/patologia , Hepatopatias/etiologia , Hepatopatias/patologia , Hepatopatias/veterinária , Masculino , Medicago sativa , Necrose/veterinária , Intoxicação por Plantas/mortalidade , Intoxicação por Plantas/patologia , Plantas Tóxicas/química , Plantas Tóxicas/intoxicação , Rúmen/patologia , Wedelia/química
10.
Hernia ; 27(4): 873-881, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36959525

RESUMO

INTRODUCTION: Surgical site occurrence (SSO) and surgical site infection (SSI) are common concerns with incisional hernia repair. Intraoperative drain placement is a common practice aiming to reduce SSO and SSI rates. However, literature on the matter is very poor. The aim of this study is to investigate the role of subcutaneous and periprosthetic drain placement on postoperative outcomes and SSO and SSI rates with incisional hernia repair. METHODS: A non-randomised pilot study was performed between January 2018 and December 2020 and included patients with elective midline or lateral incisional hernia repair with sublay mesh placement. Patients were prospectively included, followed for 1 month and divided into three groups: group 1 without drainage, group 2 with subcutaneous drainage, and group 3 with subcutaneous and periprosthetic drains. Drains were placed at surgeon's discretion. All patients were included in the enhanced recovery program. RESULTS: One hundred and four patients were included. Twenty-four patients (23.1%) did not have drains (group 1), 60 patients (57.7%) had a subcutaneous drain (group 2) and 20 patients (19.2%) had both a subcutaneous and a periprosthetic drains (group 3). SSO rates were significantly different between the 3 groups: 20.8% in group 1, 20.7% in group 2 and 50% in group 3 (p = 0.03). There was no significant difference in deep and superficial SSI rates between the 3 groups. Subgroup analysis revealed that adding a drain in direct contact with the mesh significantly increased SSO rate but did not influence SSI rate. Length of stay was also significantly increased by the presence of a drain, 3.1 ± 1.9 days for group 1; 5.9 ± 4.8 for group 2 and 5.9 ± 2.5 days for group 3 (p < 0.005). CONCLUSION: Drain placement in direct contact with the mesh might increase SSO rate. More studies are necessary to evaluate the actual benefits of drainage after incisional hernia repair.


Assuntos
Hérnia Ventral , Hérnia Incisional , Humanos , Projetos Piloto , Hérnia Incisional/etiologia , Hérnia Incisional/cirurgia , Telas Cirúrgicas/efeitos adversos , Herniorrafia/efeitos adversos , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Drenagem/efeitos adversos , Hérnia Ventral/cirurgia
11.
Vet Pathol ; 49(2): 255-63, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21502373

RESUMO

Clostridium perfringens type C is an important cause of enteritis and enterocolitis in foals and occasionally in adult horses. The disease is a classic enterotoxemia, and the enteric lesions and systemic effects are caused primarily by beta toxin, 1 of 2 major toxins produced by C. perfringens type C. Until now, only sporadic cases of C. perfringens type C equine enterotoxemia have been reported. We present a comprehensive description of the lesions in 8 confirmed cases of type C enterotoxemia in foals and adult horses. Grossly, multifocal to segmental hemorrhage and thickening of the intestinal wall were most common in the small intestine, although the colon and cecum were also frequently affected. All horses had variable amounts of fluid, often hemorrhagic intestinal contents. The most characteristic microscopic lesion was necrotizing or necrohemorrhagic enteritis, with mucosal and/or submucosal thrombosis. Numerous gram-positive rods were occasionally seen in affected mucosa. A definitive diagnosis of C. perfringens type C enterotoxemia in all 8 cases was based on the clinical history, gross and histologic lesions, and detection of the beta toxin in intestinal contents.


Assuntos
Toxinas Bacterianas/metabolismo , Clostridium perfringens/isolamento & purificação , Enterotoxemia/patologia , Doenças dos Cavalos/patologia , Animais , Animais Recém-Nascidos , Clostridium perfringens/genética , Clostridium perfringens/metabolismo , Enterotoxemia/microbiologia , Enterotoxemia/mortalidade , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Doenças dos Cavalos/microbiologia , Doenças dos Cavalos/mortalidade , Cavalos , Imuno-Histoquímica/veterinária , Intestinos/microbiologia , Intestinos/patologia , Masculino , Reação em Cadeia da Polimerase/veterinária , Estudos Retrospectivos
12.
Biomed J ; 45(5): 776-787, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34666219

RESUMO

INTRODUCTION: Organs procured following brain stem death (BSD) are the main source of organ grafts for transplantation. However, BSD is associated with inflammatory responses that may damage the organ and affect both the quantity and quality of organs available for transplant. Therefore, we aimed to investigate plasma and bronchoalveolar lavage (BAL) pro-inflammatory cytokine profiles and cardiovascular physiology in a clinically relevant 6-h ovine model of BSD. METHODS: Twelve healthy female sheep (37-42 Kg) were anaesthetized and mechanically ventilated prior to undergoing BSD induction and then monitored for 6 h. Plasma and BAL endothelin-1 and cytokines (IL-1ß, 6, 8 and tumour necrosis factor alpha (TNF-α)) were assessed by ELISA. Differential white blood cell counts were performed. Cardiac function during BSD was also examined using echocardiography, and cardiac biomarkers (A-type natriuretic peptide and troponin I were measured in plasma. RESULTS: Plasma concentrations big ET-1, IL-6, IL-8, TNF-α and BAL IL-8 were significantly (p < 0.01) increased over baseline at 6 h post-BSD. Increased numbers of neutrophils were observed in the whole blood (3.1 × 109 cells/L [95% confidence interval (CI) 2.06-4.14] vs. 6 × 109 cells/L [95%CI 3.92-7.97]; p < 0.01) and BAL (4.5 × 109 cells/L [95%CI 0.41-9.41] vs. 26 [95%CI 12.29-39.80]; p = 0.03) after 6 h of BSD induction vs baseline. A significant increase in ANP production (20.28 pM [95%CI 16.18-24.37] vs. 78.68 pM [95%CI 53.16-104.21]; p < 0.0001) and cTnI release (0.039 ng/mL vs. 4.26 [95%CI 2.69-5.83] ng/mL; p < 0.0001), associated with a significant reduction in heart contractile function, were observed between baseline and 6 h. CONCLUSIONS: BSD induced systemic pro-inflammatory responses, characterized by increased neutrophil infiltration and cytokine production in the circulation and BAL fluid, and associated with reduced heart contractile function in ovine model of BSD.


Assuntos
Cardiopatias , Fator de Necrose Tumoral alfa , Ovinos , Animais , Feminino , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-8 , Citocinas/metabolismo , Tronco Encefálico
13.
Artigo em Inglês | MEDLINE | ID: mdl-34026237

RESUMO

BACKGROUND: There is a scarcity of evaluated tools to assess whether non-specialist providers achieve minimum levels of competency to effectively and safely deliver psychological interventions in low- and middle-income countries. The objective of this study was to evaluate the reliability and utility of the newly developed Working with children - Assessment of Competencies Tool (WeACT) to assess service providers' competencies in Gaza, Palestine. METHODS: The study evaluated; (1) psychometric properties of the WeACT based on observed role-plays by trainers/supervisors (N = 8); (2) sensitivity to change among service provider competencies (N = 25) using pre-and-post training WeACT scores on standardized role-plays; (3) in-service competencies among experienced service providers (N = 64) using standardized role-plays. RESULTS: We demonstrated moderate interrater reliability [intraclass correlation coefficient, single measures, ICC = 0.68 (95% CI 0.48-0.86)] after practice, with high internal consistency (α = 0.94). WeACT assessments provided clinically relevant information on achieved levels of competencies (55% of the competencies were scored as adequate pre-training; 71% post-training; 62% in-service). Pre-post training assessment saw significant improvement in competencies (W = -3.64; p < 0.001). CONCLUSION: This study demonstrated positive results on the reliability and utility of the WeACT, with sufficient inter-rater agreement, excellent internal consistency, sensitivity to assess change, and providing insight needs for remedial training. The WeACT holds promise as a tool for monitoring quality of care when implementing evidence-based care at scale.

14.
Vet Pathol ; 47(1): 108-15, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20080490

RESUMO

During the 12 months of 2006, zygomycotic lymphadenitis was diagnosed in 194 of 198 feedlot steers (0.04% of cattle slaughtered during that period) in a California slaughterhouse as part of bovine tuberculosis surveillance. Mesenteric lymph nodes were involved in 190 cases. Affected lymph nodes were enlarged (2 to 42 cm in greatest dimension), firm, and mottled gray-white to yellow with multiple granular or caseocalcareous foci. Histologically, nodal architecture was effaced by necrosis, granulomatous inflammation, and fibrosis. In approximately 20% of the cases, granulomas were mainly restricted to subcapsular sinuses and afferent lymphatic vessels, causing granulomatous lymphangitis. Nonseptate, irregularly branching hyphae with nonparallel walls and bulbous enlargements were common in necrotic areas and within the cytoplasm of multinucleated giant cells. Fungal cultures were performed on 124 affected lymph nodes using 7 media, but no zygomycetes were cultured. Fungal DNA was amplified from 20 lymph nodes. Amplicons from 16 nodes had nearly 100% homology with sequences for Rhizomucor pusillus; 4 amplicons had (> 98%) homology with Absidia corymbifera sequences. Zygomycosis should be considered in the differential diagnosis for granulomatous lymphadenitis in feedlot steers.


Assuntos
Doenças dos Bovinos/microbiologia , Linfadenite/veterinária , Zigomicose/veterinária , Animais , Bovinos , Doenças dos Bovinos/patologia , DNA Fúngico/isolamento & purificação , Fungos/genética , Granuloma/microbiologia , Granuloma/patologia , Granuloma/veterinária , Linfonodos/patologia , Linfadenite/microbiologia , Linfadenite/patologia , Masculino , Filogenia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Zigomicose/patologia
15.
Equine Vet J ; 41(9): 903-7, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20383989

RESUMO

REASONS FOR PERFORMING STUDY: There is increasing anecdotal evidence among horse owners, trainers and equine clinicians of a high prevalence of subepiglottic ulcers, suggested to have a negative effect on racing performance. OBJECTIVES: To provide a prevalence study and pathological characterisation of laryngopharyngeal lesions with emphasis in the subepiglottic area and, in particular, subepiglottic ulcers. METHODS: The study was carried out on 91 Thoroughbred racehorses received for post mortem examination from 4 major Southern California racetracks. The most common reason for submission was catastrophic musculoskeletal injury, but others include sudden death, laminitis, colic, colitis, neurological disorders, pleuropneumonia and arytenoid chondropathy. Laryngopharyngeal specimens were collected and examined grossly; selected cases were also examined histopathologically. RESULTS: Thirteen horses (143%) had at least one type of laryngopharyngeal abnormality, 7 horses (7.7%) had lesions in the subepiglottic soft tissues, including 4 subepiglottic ulcers, 2 soft palate 'kissing lesions' and one 'subepiglottic scar'. Eight horses (8.8%) had lesions elsewhere in the laryngopharynx, including mucosal ulcerations, arytenoid chondropathy, epiglottic entrapment and partial absence of arytenoid cartilage. CONCLUSIONS AND POTENTIAL RELEVANCE: Lesions in the subepiglottic area were among the most prevalent in this study, suggesting that an important percentage of laryngopharyngeal abnormalities may be missed during routine endoscopy of the standing horse, which often does not include the examination of subepiglottic tissues. Pathologically, subepiglottic ulcers were chronic-active with viable hyperplastic epithelial margins, suggesting that proper healing and re-epithelialisation should occur with appropriate treatment. In most cases, the lesions observed do not necessarily indicate a clinical problem and more extensive prevalence studies and correlation between abnormalities found and performance are needed to assess the clinical relevance of subepiglottic soft tissue lesions accurately.


Assuntos
Doenças dos Cavalos/patologia , Hipofaringe/patologia , Úlcera/veterinária , Animais , California/epidemiologia , Doenças dos Cavalos/epidemiologia , Cavalos , Úlcera/epidemiologia , Úlcera/patologia
16.
Eur Respir J ; 31(4): 854-9, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18094005

RESUMO

Lung carcinoma with a basaloid pattern (BC) is classified as either a basaloid variant of squamous cell carcinoma (SCC) or as variant of large cell carcinoma (LCC) depending on the presence of a squamous component. In a previous study of 37 cases, the present authors showed that BC presented with a shorter median and overall survival. In order to confirm its clinical significance in a larger series, 90 BC, including 46 basaloid variants of LCC and 44 basaloid variants of SCC, were compared with 1,328 other nonsmall cell lung carcinoma (NSCLC) with regard to clinical features and survival. The survival of basaloid variants of LCC and SCC was comparable. Median and overall survival were significantly lower for BC than for NSCLC in stage I-II patients, with a median survival of 29 and 49 months, respectively, and 5-yr survival rates of 27 and 44% for BC and NSCLC. When disease-specific survival was considered, BC had a shorter survival than both NSCLC and SCC. Basaloid pattern confers a poor prognosis in nonsmall cell lung carcinoma, especially in stage I-II patients, suggesting that lung carcinoma with a basaloid pattern is not only a variant of squamous cell carcinoma or large cell carcinoma, but is a unique entity with a significantly poor prognosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Neoplasias de Células Escamosas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida
17.
Avian Dis ; 52(3): 426-32, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18939630

RESUMO

Seven psittacine birds and a toucan (Ramphastos toco) were diagnosed as infected with Coxiella-like bacteria, based on polymerase chain reaction and bacterial 16S rRNA gene sequence obtained from each bird's liver tissue. Most of the birds exhibited lethargy and weakness for several days prior to death. Gross lesions included mild to moderate emaciation and severely enlarged and mottled pale livers and spleens. Microscopically, there was multifocal necrosis of hepatocytes with infiltration of a mixed population of inflammatory cells, including lymphocytes, heterophils, plasma cells, and macrophages randomly scattered throughout in most birds. In several birds within the macrophages there were vacuoles containing basophilic small cocco-bacilli organisms measuring about 0.5-1 microm. The spleens had increased numbers of mononuclear phagocytic system cells, some of which had vacuoles that contained similar organisms, as observed in the liver. There was inflammation in the epicardium and endocardium, interstitium of the lungs, kidney, adrenal and thyroid glands, lamina propria of the intestine, and in occasional birds in the brain, bursa of Fabricius, and bone marrow associated with similar organisms in the macrophages. Transmission electron microscopy of the liver and lungs in most birds and in the thyroid glands of one bird revealed pleomorphic round to elongated bacteria measuring about 0.45 microm in diameter and more than 1.0 microm in length. Most of these organisms contained a peripheral zone of loosely arranged electron dense material that was located immediately beneath a trilaminar membrane. Occasional organisms contained nucleoids. This is the first documentation of disease presumptively associated with Coxiella-like bacteria in birds.


Assuntos
Doenças das Aves/microbiologia , Doenças das Aves/patologia , Coxiella/genética , Infecções por Bactérias Gram-Negativas/veterinária , Fígado/ultraestrutura , Psittaciformes , Animais , Sequência de Bases , Primers do DNA/genética , Evolução Fatal , Infecções por Bactérias Gram-Negativas/patologia , Imuno-Histoquímica , Microscopia Eletrônica , Dados de Sequência Molecular , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
18.
Rev Pneumol Clin ; 64(5): 250-6, 2008 Oct.
Artigo em Francês | MEDLINE | ID: mdl-18995155

RESUMO

INTRODUCTION: Lung cancer is a disease with a poor prognosis. Therapeutic innovations in oncology and the optimisation of intensive care patient management have improved the prognosis of lung cancer presenting with acute life-threatening respiratory or cardiac emergencies. OBSERVATION: We reported on the case of a patient with lung cancer presenting with mildly abundant haemoptysis, who was hospitalised in intensive care. After multidisciplinary discussion, the patient was intubated following recurrent haemorrhage that resulted in respiratory failure. The outcome was favourable. Four months later, this patient was still alive and autonomous. DISCUSSION: After years of pessimism, the medical literature has revealed an improvement in lung cancer patients' survival. Respiratory failure and shock are the main reasons for admission to the intensive care unit. The mortality risk factors depend more on acute conditions than on the underlying lung cancer. The patient's admission must be made before multiorgan failure occurs, along with the implementation of non invasive therapies. The use of intensive care as a bridge to overcome an acute event is a possible means of caring for the patient. CONCLUSION: Consideration of the acute event is important when deciding whether to hospitalise a patient with lung cancer in intensive care. An early admission, if indicated, is desirable. The course in the first 72hours provides a good estimation of the patient's prognosis and helps to achieve better treatment.


Assuntos
Carcinoma de Células Escamosas/terapia , Cuidados Críticos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , APACHE , Fatores Etários , Idoso , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Interpretação Estatística de Dados , Humanos , Avaliação de Estado de Karnofsky , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Radiografia Torácica , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Rev Mal Respir ; 24(3 Pt 1): 343-7, 2007 Mar.
Artigo em Francês | MEDLINE | ID: mdl-17417173

RESUMO

INTRODUCTION: Surgery remains the only curative treatment for primary non-small cell bronchial carcinoma. It is mainly appropriate for small, localised tumours. Some patients have contra-indications to surgery and radiofrequency offers a minimally invasive alternative with few complications. It is performed under general anaesthesia by a percutaneous approach. The main complications are mechanical, primarily pneumothorax, and infections are uncommon and generally mild. CASE REPORT: We report the case of a man treated by radiofrequency for a small bronchial carcinoma. The procedure was rapidly complicated by infection of the area treated, spreading throughout both lung fields and requiring intensive and prolonged antibiotic treatment. Resolution of the infection was slow despite appropriate treatment. The rapid onset and spread are explained by the immunosuppressed state of the patient. CONCLUSION: Radiofrequency is a recent treatment for bronchial carcinoma that is developing rapidly. Though it is associated with low morbidity and mortality the possibility of potentially fatal infective complications in certain patients should be recognised.


Assuntos
Neoplasias Brônquicas/radioterapia , Carcinoma/radioterapia , Infecções Oportunistas/etiologia , Pneumonia Bacteriana/etiologia , Idoso , Humanos , Hospedeiro Imunocomprometido , Masculino
20.
J Natl Cancer Inst ; 92(7): 550-6, 2000 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-10749910

RESUMO

BACKGROUND: The number of elderly patients with breast cancer is increasing. Limited age-related information available about this disease prompted this study. PATIENTS AND METHODS: The study population was derived from 50828 and 256287 patients with invasive breast cancer in San Antonio breast cancer databases and the Surveillance, Epidemiology, and End Results (SEER) registry, respectively. Tumor biologic and clinical characteristics, local and systemic therapies, and survival according to the patient's age were analyzed. Survival was also compared with that of age-matched women from the general population. RESULTS: In patients 55 years old or older, there was an association between increasing age at diagnosis and the presence of more favorable biologic characteristics of the tumor, including more tumors that express steroid receptors, lower proliferative rates, diploidy, normal p53, and absence of the expression of epidermal growth factor receptor and c-erbB2. In older patients with lymph node-negative disease and/or small tumors, the observed and expected survivals were almost identical. In the SEER registry, the 8-year survival of lymph node-negative patients relative to the expected survival of age-matched women from the general population was 1.01 (95% confidence interval [CI] = 0.98-1. 04) for patients 70-74 years old, 1.06 (95% CI = 1.01-1.11) for patients 75-79 years old, and 1.09 (95% CI = 0.98-1.20) for patients 80-84 years old. CONCLUSION: In women 55 years old or older, advancing age is associated with more favorable tumor biology, and breast cancer survival in older women is similar to survival in the general population irrespective of disease status. This favorable outcome should be considered when making clinical decisions in older patients.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/química , Neoplasias da Mama/epidemiologia , Terapia Combinada , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ploidias , Prognóstico , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Fatores de Risco , Programa de SEER , Análise de Sobrevida , Resultado do Tratamento , Proteína Supressora de Tumor p53/análise , Estados Unidos/epidemiologia
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