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1.
Clin Microbiol Infect ; 29(10): 1298-1305, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37348653

RESUMO

OBJECTIVES: To evaluate the efficacy and safety of short-course intravenous amphotericin B followed by sustained release posaconazole tablets for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis. METHODS: This prospective, pragmatic study included adults with diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis. Patients received short (7-14 days) or long (15-28 days) intravenous antifungal therapy (short intravenous antifungal treatment [SHIFT] or long intravenous antifungal treatment [LIFT], respectively) depending on the presence or absence of brain involvement. All patients received step-down posaconazole tablets, debridement, and glycemic control. The primary outcome was the treatment success at week 14, which was determined by assessing survival and the absence of disease progression through clinical evaluation and nasal endoscopy. Log-binomial regression analysis (risk ratio and 95% CI) was performed to assess factors associated with the primary outcome. RESULTS: Intravenous therapy was administered to 251 participants: SHIFT, 205 (median duration, 13 days); LIFT, 46 (median duration, 22 days). Treatment success at 3 months was 88% (217/248; 95% CI, 83-91%): SHIFT group, 93% (189/203; 89-96%); LIFT group, 62% (28/45; 47-76%). All-cause mortality was 12% (30/251): SHIFT group, 6% (13/205); LIFT group, 37% (17/46). Age (aRR [95% CI]: 1.02 [1.00-1.05]; p 0.027), diabetic ketoacidosis at presentation (2.32 [1.20-4.46]; p 0·012), glycated haemoglobin A1c (1.19 [1.03-1.39]; p 0.019), stroke (3.93 [1.94-7.95]; p 0·0001), and brain involvement (5.67 [3.05-10.54]; p < 0.0001) were independently associated with unsuccessful outcomes. DISCUSSION: Short intravenous amphotericin B with step-down posaconazole tablets should be further studied as primary treatment option for diabetes or COVID-19-associated mucormycosis in randomized controlled trials.


Assuntos
COVID-19 , Diabetes Mellitus , Mucormicose , Doenças Orbitárias , Adulto , Humanos , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Mucormicose/complicações , Estudos Prospectivos , Doenças Orbitárias/tratamento farmacológico , Doenças Orbitárias/microbiologia , COVID-19/complicações , Diabetes Mellitus/tratamento farmacológico
2.
Infect Dis Ther ; 12(5): 1319-1335, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37062023

RESUMO

INTRODUCTION: The objective of this study was to examine the evolution of carbapenem-resistant Klebsiella pneumoniae (CRKp) infections and their impact at a tertiary care hospital in South India. METHODS: A comparative analysis of clinical data from two prospective cohorts of patients with CRKp bacteremia (C1, 2014-2015; C2, 2021-2022) was carried out. Antimicrobial susceptibilities and whole genome sequencing (WGS) data of selected isolates were also analyzed. RESULTS: A total of 181 patients were enrolled in the study, 56 from C1 and 125 from C2. CRKp bacteremia shifted from critically ill patients with neutropenia to others (ICU stay: C1, 73%; C2, 54%; p = 0.02). The overall mortality rate was 50% and the introduction of ceftazidime-avibactam did not change mortality significantly (54% versus 48%; p = 0.49). Oxacillinases (OXA) 232 and 181 were the most common mechanisms of resistance. WGS showed the introduction of New Delhi metallo-ß-lactamase-5 (NDM-5), higher genetic diversity, accessory genome content, and plasmid burden, as well as increased convergence of hypervirulence and carbapenem resistance in C2. CONCLUSIONS: CRKp continues to pose a significant clinical threat, despite the introduction of new antibiotics. The study highlights the evolution of resistance and virulence in this pathogen and the impact on patient outcomes in South India, providing valuable information for clinicians and researchers.

3.
J Surg Case Rep ; 2022(1): rjab642, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35096370

RESUMO

We present the endoscopic management of two cases of complete ureteric occlusion at vesico-ureteral junction (VUJ) level following iatrogenic injury. Case 1 is a 60-year-old man who developed bilateral ureteric injury at the level of the VUJ following robot-assisted radical prostatectomy (RARP) for Gleason 3 + 4 = 7 T2bN0 prostate cancer. Case 2 is an 81-year-old man with history of recurrent G2pTa transitional cell carcinoma of the bladder originally diagnosed in 2005 and history of radical radiotherapy for prostate cancer. At his most recent transurethral resection of bladder tumour, the left ureteric orifice was not visualized. We describe step-by-step our technique in restoring continuity of the ureter with minimally invasive endoscopic approach, resulting in excellent long-term upper tract drainage for our patients. To our knowledge, combined utilization of a Collins knife to incise the area around the ureteric orifice to unearth them is not reported. We aim to report our technique and its outcomes.

5.
Am J Surg ; 216(3): 444-449, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-28890055

RESUMO

BACKGROUND: Our study aims to identify the minimum number of lymph nodes (LN) associated with improved survival in patients who underwent NRT for stage II-III rectal cancer. METHODS: Adults with clinical stage II and III rectal adenocarcinoma in the National Cancer Data Base were stratified by NRT. Multivariable Cox regression modeling with restricted cubic splines was used to determine the minimum number of LNs associated with improved survival. RESULTS: Of 38,363 patients, 76% received NRT. After adjustment, a LNY≥12 was associated with improved survival among patients receiving NRT (HR 0.79, p < 0.0001) and those without NRT (HR 0.88, p = 0.04). Among patients receiving NRT, factors independently associated with LNY≥12 were younger age, private insurance, low comorbidity score, a recent year of diagnosis, higher T stage and grade, APR resection, and academic institution. CONCLUSIONS: A minimum LNY of 12 confers a survival benefit for rectal cancer patients regardless of receiving neoadjuvant radiation therapy.


Assuntos
Adenocarcinoma/terapia , Colectomia/métodos , Linfonodos/patologia , Estadiamento de Neoplasias , Neoplasias Retais/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/secundário , Idoso , Quimiorradioterapia Adjuvante , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Retais/diagnóstico , Neoplasias Retais/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Estados Unidos/epidemiologia
6.
J Surg Res ; 200(1): 189-94, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26248478

RESUMO

BACKGROUND: Feeding tube placement is common among patients undergoing gastrectomy, and national guidelines currently recommend consideration of a feeding jejunostomy tube (FJT) for all patients undergoing resection for gastric cancer. However, data are limited regarding the safety of FJT placement at the time of gastrectomy for gastric cancer. METHODS: The 2005-2011 American College of Surgeons National Surgical Quality Improvement Program Participant User Files were queried to identify patients who underwent gastrectomy for gastric cancer. Subjects were classified by the concomitant placement of an FJT. Groups were then propensity matched using a 1:1 nearest neighbor algorithm, and outcomes were compared between groups. The primary outcomes of interest were overall 30-d overall complications and mortality. Secondary end points included major complications, surgical site infection, and early reoperation. RESULTS: In total, 2980 subjects underwent gastrectomy for gastric cancer, among whom 715 (24%) also had an FJT placed. Patients who had an FJT placed were more likely to be male (61.6% versus 56.6%, P = 0.02), have recent weight loss (21.0% versus 14.8%, P < 0.01), and have undergone recent chemotherapy (7.9% versus 4.2%, P < 0.01) and radiation therapy (4.2% versus 1.3%, P < 0.01). They were also more likely to have undergone total (compared with partial) gastrectomy (66.6% versus 28.6%, P < 0.01) and have concomitant resection of an adjacent organ (40.4 versus 24.1%, P < 0.01). After adjustment with propensity matching, however, all baseline characteristics and treatment variables were highly similar. Between groups, there were no statistically significant differences in 30-d overall complications (38.8% versus 36.1%, P = 0.32) or mortality (5.8 versus 3.7%, P = 0.08). There were also no differences in major complications, surgical site infection, or early reoperation. Operative time was slightly longer among patients with feeding tubes placed (median, 248 versus 233 min, P = 0.01), but otherwise there were no significant differences in any outcomes between groups. CONCLUSIONS: Concomitant placement of FJT at the time of gastrectomy may result in slightly increased operative times but does not appear to lead to increased perioperative morbidity or mortality. Further investigation is needed to identify the patients most likely to benefit from FJT placement.


Assuntos
Gastrectomia , Jejunostomia/mortalidade , Complicações Pós-Operatórias/etiologia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Nutrição Enteral/métodos , Feminino , Gastrectomia/mortalidade , Humanos , Intubação Gastrointestinal , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Avaliação de Resultados em Cuidados de Saúde , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/epidemiologia , Reoperação , Estudos Retrospectivos
7.
Drug Dev Ind Pharm ; 42(4): 611-23, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26146768

RESUMO

CONTEXT: Lipoidal systems have particularly shown potential for specific accumulation in areas with inflamed tissue increasing the selectivity of local drug delivery. OBJECTIVE: Formulation and evaluation of self-microemulsifying drug delivery system (SMEDDS) for colon-specific drug delivery for effective treatment of colonic diseases. METHOD: Ternary phase diagram was used to optimize level of oil, surfactant and co-surfactant to optimize SMEDDS and were evaluated for percent transmittance, emulsification time, in vitro release, myeloperoxidase (MPO) activity and intestinal accumulation. The spray dried SMEDDS were filled in capsules which were enteric coated with Eudragit S-100 at 10% weight gain to ensure SMEDDS delivery at colon. The spray dried SMEDDS were also evaluated for IR, DSC, XRD, SEM and stability study. RESULT: In ternary phase diagram, Capmul MCM C8 and Capmul PG12 NF with surfactant (Tween 20) and co-surfactant (PG) in ratio 2:1 and 3:1, respectively, showed maximum emulsification area. These liquid SMEDDS show maximum transmittance, globule size of 90-30 nm. The spray-dried SMEDDS with diluents show good flow property. The units of MPO activity show lower level as compared to pure drug and control group, histopathology results supports better healing with SMEDDS. This was attributed to accumulation of SMEDDS in inflammatory area as compared to drug which was further proved by accumulation study. Enteric-coated capsule containing SMEDDS are able to deliver drug, specifically at the colonic region. CONCLUSION: Higher accumulation of lipoidal drug in inflammatory area and specific release of liposomes by enteric-coated capsules provide better option for the treatment of colonic disease.


Assuntos
Colo/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Desenho de Fármacos , Emulsificantes/administração & dosagem , Emulsificantes/química , Microesferas , Animais , Química Farmacêutica , Colo/metabolismo , Colo/patologia , Emulsificantes/metabolismo , Masculino , Ratos , Ratos Wistar , Difração de Raios X
8.
Mol Pharm ; 10(5): 1683-94, 2013 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-23544801

RESUMO

Surgery, radiation and chemotherapy remain the mainstay of current cancer therapy. However, treatment failure persists due to the inability to achieve complete local control of the tumor and curtail metastatic spread. Vascular disrupting agents (VDAs) are a class of promising systemic agents that are known to synergistically enhance radiation, chemotherapy or thermal treatments of solid tumors. Unfortunately, there is still an unmet need for VDAs with more favorable safety profiles and fewer side effects. Recent work has demonstrated that conjugating VDAs to other molecules (polyethylene glycol, CNGRCG peptide) or nanoparticles (liposomes, gold) can reduce toxicity of one prominent VDA (tumor necrosis factor alpha, TNF-α). In this report, we show the potential of a gold conjugated TNF-α nanoparticle (NP-TNF) to improve multimodal cancer therapies with VDAs. In a dorsal skin fold and hindlimb murine xenograft model of prostate cancer, we found that NP-TNF disrupts endothelial barrier function and induces a significant increase in vascular permeability within the first 1-2 h followed by a dramatic 80% drop in perfusion 2-6 h after systemic administration. We also demonstrate that the tumor response to the nanoparticle can be verified using dynamic contrast-enhanced magnetic resonance imaging (MRI), a technique in clinical use. Additionally, multimodal treatment with thermal therapies at the perfusion nadir in the sub- and supraphysiological temperature regimes increases tumor volumetric destruction by over 60% and leads to significant tumor growth delays compared to thermal therapy alone. Lastly, NP-TNF was found to enhance thermal therapy in the absence of neutrophil recruitment, suggesting that immune/inflammatory regulation is not central to its power as part of a multimodal approach. Our data demonstrate the potential of nanoparticle-conjugated VDAs to significantly improve cancer therapy by preconditioning tumor vasculature to a secondary insult in a targeted manner. We anticipate our work to direct investigations into more potent tumor vasculature specific combinations of VDAs and nanoparticles with the goal of transitioning optimal regimens into clinical trials.


Assuntos
Antineoplásicos/administração & dosagem , Nanoconjugados/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Fator de Necrose Tumoral alfa/administração & dosagem , Animais , Linhagem Celular Tumoral , Terapia Combinada , Ouro , Humanos , Hipertermia Induzida , Masculino , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Camundongos , Camundongos Nus , Nanoconjugados/química , Neoplasias da Próstata/irrigação sanguínea , Neoplasias da Próstata/terapia , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Int J Hyperthermia ; 28(2): 105-12, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22335224

RESUMO

PURPOSE: To investigate simultaneous and sequential injection thermochemical ablation in a porcine model, and compare them to sham and acid-only ablation. MATERIALS AND METHODS: This IACUC-approved study involved 11 pigs in an acute setting. Ultrasound was used to guide placement of a thermocouple probe and coaxial device designed for thermochemical ablation. Solutions of 10 M acetic acid and NaOH were used in the study. Four injections per pig were performed in identical order at a total rate of 4 mL/min: saline sham, simultaneous, sequential, and acid only. Volume and sphericity of zones of coagulation were measured. Fixed specimens were examined by H&E stain. RESULTS: Average coagulation volumes were 11.2 mL (simultaneous), 19.0 mL (sequential) and 4.4 mL (acid). The highest temperature, 81.3°C, was obtained with simultaneous injection. Average temperatures were 61.1°C (simultaneous), 47.7°C (sequential) and 39.5°C (acid only). Sphericity coefficients (0.83-0.89) had no statistically significant difference among conditions. CONCLUSIONS: Thermochemical ablation produced substantial volumes of coagulated tissues relative to the amounts of reagents injected, considerably greater than acid alone in either technique employed. The largest volumes were obtained with sequential injection, yet this came at a price in one case of cardiac arrest. Simultaneous injection yielded the highest recorded temperatures and may be tolerated as well as or better than acid injection alone. Although this pilot study did not show a clear advantage for either sequential or simultaneous methods, the results indicate that thermochemical ablation is attractive for further investigation with regard to both safety and efficacy.


Assuntos
Técnicas de Ablação/métodos , Temperatura Alta/uso terapêutico , Fígado/cirurgia , Técnicas de Ablação/instrumentação , Ácido Acético/administração & dosagem , Animais , Hipertermia Induzida/métodos , Fígado/patologia , Modelos Animais , Suínos , Tomografia Computadorizada por Raios X
10.
Int J Hyperthermia ; 28(2): 113-21, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22335225

RESUMO

PURPOSE: To explore the effects of volume and concentration in thermochemical ablation using an in vivo porcine model. METHODS: Twelve swine 60-75 kg were used in this institutionally approved study. A needle design prototype coaxial device for reagent injections and a thermocouple were inserted into surgically exposed liver. Simultaneously, an acid and base (acetic acid and NaOH) were injected at 4 mL/min based on a 3 × 3 matrix with concentration (5, 10, and 15 mol/L) and volume on the axes (total volumes of 1, 2, and 4 mL). Three animals (centre grid position) strengthened the statistical analysis. Each animal received four identical injections (total 48). Temperatures and heart rate were recorded. Livers were formalin-fixed after sacrifice. After sectioning, coagulation zones were analysed by two observers. Area and slice thickness were used to calculate the volume, surface area, and sphericity for each treatment. RESULTS: Coagulation volumes ranged from 2.95 ± 0.29 to 14.72 ± 1.42 mL with a maximum of 18.3 mL. Highest peak temperature was 105°C with temperatures ranging 43.5 ± 2.6°C to 91.0 ± 6.5°C. There was no association between conditions and sphericity or heart rate. CONCLUSIONS: The method can be used successfully to ablate tissue in vivo. By neutralising acid in situ and releasing heat and a salt, this technique improves considerably upon the use of acetic acid used alone. Peak temperatures exceeded accepted coagulation thresholds even if the only mechanism operating was hyperthermia. Reagent concentrations and volumes increased the amount of the coagulum but not in a linear fashion.


Assuntos
Técnicas de Ablação/métodos , Temperatura Alta/uso terapêutico , Hipertermia Induzida/métodos , Técnicas de Ablação/instrumentação , Ácido Acético/química , Ácido Acético/uso terapêutico , Animais , Hipertermia Induzida/instrumentação , Fígado/patologia , Fígado/cirurgia , Modelos Animais , Necrose , Hidróxido de Sódio/química , Hidróxido de Sódio/uso terapêutico , Suínos
11.
J Assoc Physicians India ; 60: 50-2, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23777026

RESUMO

Oro-facial-digital syndrome type II (OFD-II) is characterized by frenulated tongue, midline cleft lip, high arched or cleft palate, micrognathia, syndactyly and polydactyly, bilateral reduplicated hallux, conductive hearing loss, choroidal coloboma and normal intelligence. There are nine forms of oro-facial-digital syndromes with different modes of inheritance. A young female with features of oro-facio-digital syndrome type-II is being reported.


Assuntos
Síndromes Orofaciodigitais/diagnóstico , Adulto , Fissura Palatina/genética , Feminino , Deformidades Congênitas do Pé/diagnóstico por imagem , Deformidades Congênitas do Pé/genética , Deformidades Congênitas da Mão/diagnóstico por imagem , Deformidades Congênitas da Mão/genética , Humanos , Síndromes Orofaciodigitais/classificação , Radiografia , Língua/anormalidades
12.
Nanomedicine (Lond) ; 6(3): 545-63, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21542691

RESUMO

Nanoparticles show tremendous promise in the safe and effective delivery of molecular adjuvants to enhance local cancer therapy. One important form of local cancer treatment that suffers from local recurrence and distant metastases is thermal therapy. In this article, we review a new concept involving the use of nanoparticle-delivered adjuvants to 'precondition' or alter the vascular and immunological biology of the tumor to enhance its susceptibility to thermal therapy. To this end, a number of opportunities to combine nanoparticles with vascular and immunologically active agents are reviewed. One specific example of preconditioning involves a gold nanoparticle tagged with a vascular targeting agent (i.e., TNF-α). This nanoparticle embodiment demonstrates preconditioning through a dramatic reduction in tumor blood flow and induction of vascular damage, which recruits a strong and sustained inflammatory infiltrate in the tumor. The ability of this nanoparticle preconditioning to enhance subsequent heat or cold thermal therapy in a variety of tumor models is reviewed. Finally, the potential for future clinical imaging to judge the extent of preconditioning and thus the optimal timing and extent of combinatorial thermal therapy is discussed.


Assuntos
Hipertermia Induzida/métodos , Nanopartículas/química , Neoplasias/terapia , Adjuvantes Farmacêuticos , Animais , Criocirurgia , Crioterapia , Coloide de Ouro/química , Humanos , Camundongos , Fator de Necrose Tumoral alfa/administração & dosagem , Fator de Necrose Tumoral alfa/uso terapêutico
13.
Ann Biomed Eng ; 38(3): 694-706, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20108044

RESUMO

Applications involving freeze-thaw, such as cryoplasty or cryopreservation can significantly alter artery biomechanics including an increase in physiological elastic modulus. Since artery biomechanics plays a significant role in hemodynamics, it is important to understand the mechanisms underlying these changes to be able to help control the biomechanical outcome post-treatments. Understanding of these mechanisms requires investigation of the freeze-thaw effect on arterial components (collagen, smooth muscle cells or SMCs), as well as the components' contribution to the overall artery biomechanics. To do this, isolated fresh swine arteries were subjected to thermal (freeze-thaw to -20 degrees C for 2 min or hyperthermia to 43 degrees C for 2 h) and osmotic (0.1-0.2 M mannitol) treatments; these treatments preferentially altered either the collagen matrix (hydration/stability) or smooth muscle cells (SMCs), respectively. Tissue dehydration, thermal stability and SMC functional changes were assessed from bulk weight measurements, analyses of the thermal denaturation profiles using Fourier transform infrared (FTIR) spectroscopy and in vitro arterial contraction/relaxation responses to norepinephrine (NE) and acetylcholine (AC), respectively. Additionally, Second Harmonic Generation (SHG) microscopy was performed on fresh and frozen-thawed arteries to directly visualize the changes in collagen matrix following freeze-thaw. Finally, the overall artery biomechanics was studied by assessing responses to uniaxial tensile testing. Freeze-thaw of arteries caused: (a) tissue dehydration (15% weight reduction), (b) increase in thermal stability (approximately 6.4 degrees C increase in denaturation onset temperature), (c) altered matrix arrangement observed using SHG and d) complete SMC destruction. While hyperthermia treatment also caused complete SMC destruction, no tissue dehydration was observed. On the other hand, while 0.2 M mannitol treatment significantly increased the thermal stability (approximately 4.8 degrees C increase in denaturation onset), 0.1 M mannitol treatment did not result in any significant change. Both 0.1 and 0.2 M treatments caused no change in SMC function. Finally, freeze-thaw (506+/-159 kPa), hyperthermia (268+/-132 kPa) and 0.2 M mannitol (304+/-125 kPa) treatments all caused significant increase in the physiological elastic modulus (Eartery) compared to control (185+/-92 kPa) with the freeze-thaw resulting in the highest modulus. These studies suggest that changes in collagen matrix arrangement due to dehydration as well as SMC destruction occurring during freeze-thaw are important mechanisms of freeze-thaw induced biomechanical changes.


Assuntos
Artérias/fisiologia , Colágeno/fisiologia , Matriz Extracelular/fisiologia , Músculo Liso Vascular/fisiologia , Miócitos de Músculo Liso/fisiologia , Adaptação Fisiológica/fisiologia , Animais , Apoptose/fisiologia , Células Cultivadas , Módulo de Elasticidade/fisiologia , Congelamento , Temperatura Alta , Técnicas In Vitro , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/citologia , Estresse Mecânico , Suínos
14.
Artigo em Inglês | MEDLINE | ID: mdl-19964027

RESUMO

Thermal therapies such as hyperthermia, radiofrequency ablation, cryoablation, etc. have shown great potential and are gaining increasing clinical acceptance in the treatment of solid tumors. However, these treatment modalities are limited by the size of tumor that can be treated, incomplete tumor kill, and damage to adjacent normal tissues. To address these limitations, the concept of adjuvant-assisted thermal therapies has been proposed and tested to enhance the tumor destructive effects of thermal therapies. CYT-6091, a pegylated colloidal gold nanoparticle containing TNF-alpha bound to its surface, has been extensively investigated in our lab as an adjuvant to enhance thermal therapies. This paper describes our investigations of nanoparticle enhanced thermal therapies in various preclinical and translational models of solid tumors.


Assuntos
Coloide de Ouro/uso terapêutico , Hipertermia Induzida , Nanopartículas/uso terapêutico , Animais , Feminino , Fibrossarcoma/terapia , Neoplasias Mamárias Experimentais/terapia , Camundongos , Camundongos Endogâmicos A , Neoplasias/terapia , Sarcoma Experimental/terapia , Fator de Necrose Tumoral alfa/uso terapêutico
15.
J Child Lang ; 16(2): 285-312, 1989 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2760128

RESUMO

Polysynthetic languages can present special extraction puzzles to children, due to the length of their words. A number of hypotheses concerning children's strategies for acquiring morphology, originally proposed on the basis of their approaches to somewhat simpler systems, are confirmed by observations of five children acquiring Mohawk. Among the Mohawk children, the earliest segmentation of words was phonological rather than morphological: stressed syllables, usually penultimate or antepenultimate, were extracted first. Ultimate syllables were then added, confirming the salience of the ends of words. During this time, distinctions expressed by adults in affixes were either omitted or expressed analytically. Acquisition then moved leftward by syllables. When most utterances were long enough to include pronominal prefixes as well as roots, morphological structure was apparently discovered. It is not surprising that the pronouns should trigger this awareness, since they are frequent, appearing with every verb and most nouns, they are functional, and they are semantically transparent. From this point on, the children acquired affixes primarily according to their utility and semantic transparency rather than their phonological shape or position.


Assuntos
Desenvolvimento da Linguagem , Linguística , Pré-Escolar , Feminino , Humanos , Indígenas Norte-Americanos , Masculino , Fonética , Semântica , Vocabulário
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