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1.
Chem Soc Rev ; 49(14): 4953-5007, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32538382

RESUMO

The past decade has witnessed tremendous advances in synthesis of metal halide perovskites and their use for a rich variety of optoelectronics applications. Metal halide perovskite has the general formula ABX3, where A is a monovalent cation (which can be either organic (e.g., CH3NH3+ (MA), CH(NH2)2+ (FA)) or inorganic (e.g., Cs+)), B is a divalent metal cation (usually Pb2+), and X is a halogen anion (Cl-, Br-, I-). Particularly, the photoluminescence (PL) properties of metal halide perovskites have garnered much attention due to the recent rapid development of perovskite nanocrystals. The introduction of capping ligands enables the synthesis of colloidal perovskite nanocrystals which offer new insight into dimension-dependent physical properties compared to their bulk counterparts. It is notable that doping and ion substitution represent effective strategies for tailoring the optoelectronic properties (e.g., absorption band gap, PL emission, and quantum yield (QY)) and stabilities of perovskite nanocrystals. The doping and ion substitution processes can be performed during or after the synthesis of colloidal nanocrystals by incorporating new A', B', or X' site ions into the A, B, or X sites of ABX3 perovskites. Interestingly, both isovalent and heterovalent doping and ion substitution can be conducted on colloidal perovskite nanocrystals. In this review, the general background of perovskite nanocrystals synthesis is first introduced. The effects of A-site, B-site, and X-site ionic doping and substitution on the optoelectronic properties and stabilities of colloidal metal halide perovskite nanocrystals are then detailed. Finally, possible applications and future research directions of doped and ion-substituted colloidal perovskite nanocrystals are also discussed.

2.
Angew Chem Int Ed Engl ; 59(3): 1030-1046, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31087754

RESUMO

In recent years, there have been rapid advances in the synthesis of lead halide perovskite nanocrystals (NCs) for use in solar cells, light emitting diodes, lasers, and photodetectors. These compounds have a set of intriguing optical, excitonic, and charge transport properties, including outstanding photoluminescence quantum yield (PLQY) and tunable optical band gap. However, the necessary inclusion of lead, a toxic element, raises a critical concern for future commercial development. To address the toxicity issue, intense recent research effort has been devoted to developing lead-free halide perovskite (LFHP) NCs. In this Review, we present a comprehensive overview of currently explored LFHP NCs with an emphasis on their crystal structures, synthesis, optical properties, and environmental stabilities (e.g., UV, heat, and moisture resistance). In addition, strategies for enhancing optical properties and stabilities of LFHP NCs as well as the state-of-the-art applications are discussed. With the perspective of their properties and current challenges, we provide an outlook for future directions in this rapidly evolving field to achieve high-quality LFHP NCs for a broader range of fundamental research and practical applications.

3.
Breast J ; 25(6): 1090-1096, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31338929

RESUMO

Day-case mastectomy surgery provides benefits to both patients and hospitals. Key barriers are the use of a drain and the risk of postoperative seroma formation. We introduced the use of a tissue sealant (Artiss) into the surgical site (post-mastectomy without immediate reconstruction and postaxillary clearance) and evaluated its effect on our practice, particularly day-case rates. A prospective audit of 177 patients who underwent a simple mastectomy with or without axillary surgery, or axillary node clearance with or without breast-conserving surgery was conducted at a single surgical center in the UK between November 2015 and November 2016. Artiss was used in all operations and, where appropriate, the drain was omitted to facilitate day-case surgery. The clinical outcomes were compared between patients undergoing different operations and duration of hospital stay. There was no statistically significant difference between day-case patients and inpatients in seroma aspiration rates (24.5% and 21.7%, respectively; P = 0.381) or other complications (22.4% and 16.1%, respectively; P = 0.106). The day-case mastectomy rate increased from 3.9% in the first quarter to 45.5% in the final quarter, which was a significant increase reaching well beyond the national target. The use of Artiss enabled us to increase the drain-free day-case surgery rates over a 1-year period, exceeding the 30% target recommended by the British Association of Day Surgery. We did not observe any increase in patient morbidity, and the change was cost-effective. We have now implemented the routine use of Artiss in women undergoing simple mastectomy with or without axillary surgery and stand-alone axillary node clearances as part of enhanced recovery clinical pathways.


Assuntos
Adesivo Tecidual de Fibrina/uso terapêutico , Mastectomia/métodos , Seroma/prevenção & controle , Idoso , Procedimentos Cirúrgicos Ambulatórios/métodos , Neoplasias da Mama/cirurgia , Drenagem/efeitos adversos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Seroma/epidemiologia , Reino Unido , Cicatrização/efeitos dos fármacos
4.
HIV Med ; 19(4): 290-298, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29368401

RESUMO

OBJECTIVES: The incremental costs of expanding antiretroviral (ARV) drug treatment to all HIV-infected patients are substantial, so cost-saving initiatives are important. Our objectives were to determine the acceptability and financial impact of de-simplifying (i.e. switching) more expensive single-tablet formulations (STFs) to less expensive generic-based multi-tablet components. We determined physician and patient perceptions and acceptance of STF de-simplification within the context of a publicly funded ARV budget. METHODS: Programme costs were calculated for patients on ARVs followed at the Southern Alberta Clinic, Canada during 2016 (Cdn$). We focused on patients receiving Triumeq® and determined the savings if patients de-simplified to eligible generic co-formulations. We surveyed all prescribing physicians and a convenience sample of patients taking Triumeq® to see if, for budgetary purposes, they felt that de-simplification would be acceptable. RESULTS: Of 1780 patients receiving ARVs, 62% (n = 1038) were on STF; 58% (n = 607) of patients on STF were on Triumeq®. The total annual cost of ARVs was $26 222 760. The cost for Triumeq® was $8 292 600. If every patient on Triumeq® switched to generic abacavir/lamivudine and Tivicay® (dolutegravir), total costs would decrease by $4 325 040. All physicians (n = 13) felt that de-simplifying could be safely achieved. Forty-eight per cent of 221 patients surveyed were agreeable to de-simplifying for altruistic reasons, 27% said no, and 25% said maybe. CONCLUSIONS: De-simplifying Triumeq® generates large cost savings. Additional savings could be achieved by de-simplifying other STFs. Both physicians and patients agreed that selective de-simplification was acceptable; however, it may not be acceptable to every patient. Monitoring the medical and cost impacts of de-simplification strategies seems warranted.


Assuntos
Antirretrovirais/economia , Redução de Custos , Didesoxinucleosídeos/economia , Medicamentos Genéricos/economia , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/economia , Lamivudina/economia , Cooperação do Paciente/psicologia , Adulto , Antirretrovirais/uso terapêutico , Canadá , Estudos de Coortes , Didesoxinucleosídeos/uso terapêutico , Combinação de Medicamentos , Quimioterapia Combinada/economia , Medicamentos Genéricos/uso terapêutico , Feminino , Infecções por HIV/psicologia , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Padrões de Prática Médica , Piridonas , Comprimidos
5.
Br J Psychiatry Suppl ; 55: s58-63, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23553696

RESUMO

BACKGROUND: Research suggests that levels of discrimination against people using mental health services are high; however, reports of these people's experiences are rare. AIMS: To determine whether the Time to Change (TTC) programme target of 5% reduction in discrimination has been achieved. METHOD: Separate samples of people using mental health services were interviewed annually from 2008 to 2011 using the Discrimination and Stigma Scale to record instances of discrimination. RESULTS: Ninety-one per cent of participants reported one or more experiences of discrimination in 2008 compared with 88% in 2011 (z = -1.9, P = 0.05). The median negative discrimination score was 40% in 2008 and 28% in 2011 (Kruskal-Wallis χ(2) = 83.4, P<0.001). CONCLUSIONS: The proportion of participants experiencing no discrimination increased significantly over the course of TTC but by less than the initial target. The overall median discrimination score fell by 11.5%. Data from 2010 and 2011 suggest that these gains may be hard to maintain during economic austerity.


Assuntos
Transtornos Mentais/psicologia , Discriminação Social/estatística & dados numéricos , Estigma Social , Adolescente , Adulto , Idoso , Inglaterra , Feminino , Humanos , Masculino , Serviços de Saúde Mental/estatística & dados numéricos , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
6.
Clin Oncol (R Coll Radiol) ; 35(1): e60-e66, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36379836

RESUMO

AIMS: Anaplastic thyroid cancer (ATC) is a rare but aggressive form of thyroid cancer with a median survival of 4 months. Recent advances in molecular profiling have shown that up to half of ATCs harbour the BRAF-V600E mutation. The aim of this study was to provide real-world data and experience on the use of combination therapy dabrafenib and trametinib in patients with BRAF-V600E-mutated advanced ATC. MATERIALS AND METHODS: We retrospectively evaluated patients with confirmed BRAF-V600E-mutated ATC, defined as patients with locally advanced or metastatic ATC with no locoregional, radical treatment options. Outcomes measured were overall survival, progression-free survival, response rate, discontinuation rate, dose reduction rate and toxicity data. RESULTS: Seventeen patients were evaluated and the mean age was 68 years. Ten patients died by the time of censoring. The median duration of follow-up was 12 months (3-43 months). The estimated median overall survival was 6.9 months (95% confidence interval 2.46 months - upper confidence interval not reached) and the median progression-free survival was 4.7 months (95% confidence interval 1.4-7.8 months). Dose interruptions and/or reductions were common, but none of the patients had to permanently discontinue treatment because of toxicities. Severe toxicities (grades 3 and 4) were uncommon. CONCLUSIONS: This study supports the indication of dabrafenib and trametinib in BRAF-V600E-mutated ATC as an effective and well-tolerated treatment in an historically difficult to treat cancer.


Assuntos
Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Idoso , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/genética , Carcinoma Anaplásico da Tireoide/patologia , Estudos Retrospectivos , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Reino Unido , Mutação , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
7.
Nat Med ; 7(4): 465-70, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11283674

RESUMO

Using a novel flow chamber assay system and whole blood, we show that leukocytes from septic individuals have a four-fold elevation of adhesion, but not rolling, on a P-selectin/beta2-integrin substrate. Most leukocytes from septic patients (but not healthy controls) that bound vascular cell adhesion molecule 1 (VCAM-1) were neutrophils. All adhesion was inhibited with an antibody specific for the VCAM-1 ligand alpha4-integrin. The alpha4-integrin was present on neutrophils from septic patients but not on neutrophils from patients with localized bacterial infections. The plasma milieu of septic patients was sufficient to induce neutrophils from healthy subjects to bind VCAM-1 under flow conditions. This is the first description of alpha4-integrin/VCAM-1 pathway of neutrophil recruitment in human disease. This pathway may provide a new therapeutic target to reduce inappropriate neutrophil adhesion without altering the normal yet critical beta2-integrin-mediated adhesive function of neutrophils.


Assuntos
Antígenos CD/fisiologia , Neutrófilos/fisiologia , Choque Séptico/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD18/metabolismo , Estudos de Casos e Controles , Adesão Celular , Movimento Celular , Feminino , Humanos , Técnicas In Vitro , Integrina alfa4 , Leucócitos/fisiologia , Ligantes , Masculino , Pessoa de Meia-Idade , Selectina-P/fisiologia , Choque Séptico/etiologia , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Molécula 1 de Adesão de Célula Vascular/fisiologia
8.
Adv Mater ; 32(12): e1906457, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32048359

RESUMO

Thermoelectric (TE) research is not only a course of materials by discovery but also a seedbed of novel concepts and methodologies. Herein, the focus is on recent advances in three emerging paradigms: entropy engineering, phase-boundary mapping, and liquid-like TE materials in the context of thermodynamic routes. Specifically, entropy engineering is underpinned by the core effects of high-entropy alloys; the extended solubility limit, the tendency to form a high-symmetry crystal structure, severe lattice distortions, and sluggish diffusion processes afford large phase space for performance optimization, high electronic-band degeneracy, rich multiscale microstructures, and low lattice thermal conductivity toward higher-performance TE materials. Entropy engineering is successfully implemented in half-Huesler and IV-VI compounds. In Zintl phases and skutterudites, the efficacy of phase-boundary mapping is demonstrated through unraveling the profound relations among chemical compositions, mutual solubilities of constituent elements, phase instability, microstructures, and resulting TE properties at the operation temperatures. Attention is also given to liquid-like TE materials that exhibit lattice thermal conductivity at lower than the amorphous limit due to intensive mobile ion disorder and reduced vibrational entropy. To conclude, an outlook on the development of next-generation TE materials in line with these thermodynamic routes is given.

9.
Clin Oncol (R Coll Radiol) ; 31(4): 219-224, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30744934

RESUMO

AIMS: The 2014 British Thyroid Association thyroid cancer guidelines recommend lifelong follow-up of thyroid cancer patients. This is probably unnecessary, can cause patient anxiety, is time consuming and places significant demand on National Health Service resources. It has been suggested that low-risk differentiated thyroid cancer (DTC) patients could be discharged to primary care once they are 5 years from diagnosis and treatment. The aim of this study was to investigate the potential safety of this practice. MATERIALS AND METHODS: In total, 756 patients with dynamically risk-stratified (DRS) low-risk/excellent response to treatment DTC treated over 2001-2013 in the Leeds region were followed after diagnostic surgery and the recurrence rate calculated. RESULTS: The median follow-up time was nearly 10 years (5-17 years). Radiological recurrence occurred in 13/756 (1.7%) patients and was always preceded by raised thyroglobulin/ thyroglobulin antibody levels. In all 13 patients elevation of thyroglobulin occurred within 5 years of diagnosis. Two additional patients were found to have rising thyroglobulin at almost 9 and 10.5 years from diagnosis, although to date radiological recurrence has not been detected. Assuming these two patients developed recurrence with longer duration of follow-up, then 0.26% (2/756) of patients would not have their recurrence discovered within 5 years of diagnosis. To detect 100% of patients with a putative recurrence in our cohort would require 10.5 years of follow-up. Four patients had transiently raised thyroglobulin, which became undetectable within 2 years (in three patients), without any treatment and radiological recurrence was not discovered. CONCLUSION: Discharge of DRS low-risk DTC patients to primary care after 5 years of secondary care follow-up is reasonable, accepting that late recurrence may occur in a very small minority of individuals (0.26%, ∼1:400). A more cautious approach would be to continue monitoring for 10 years, although the frequency of assessments could be reduced with increasing duration of follow-up.


Assuntos
Neoplasias da Glândula Tireoide/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Estudos Retrospectivos , Assunção de Riscos
10.
Clin Oncol (R Coll Radiol) ; 31(6): 385-390, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30878210

RESUMO

AIMS: To obtain an overview of the management and outcomes of children aged 18 years or younger diagnosed with differentiated thyroid carcinoma of follicular cell origin across the UK, by collecting and analysing data from the limited number of centres treating these patients. This multicentre data might provide a more realistic perspective than single-institution series. MATERIALS AND METHODS: Six centres submitted data extracted from historical records on patients aged 18 years or younger, diagnosed between 1964 and 2017. The univariate and multivariable Cox proportional hazard model was used to identify potential predictors of progression-free survival, using national data as a control. RESULTS: Data on 166 patients were available for analysis. Females (74%) were predominant, and the age ranged from 3 to 19 years at diagnosis, mean 14.1 years. Nodal metastases were present in 51%; 12% had distant metastases. After surgery, 95% received radioactive iodine (39% on more than one occasion) and 4% received external beam radiotherapy. With a median follow-up duration of 5 years, 69% are alive with no evidence of disease; 20% are alive with a raised thyroglobulin level as the only evidence of residual disease; 6% have residual structural disease detectable on imaging; 2% have died, from cerebral metastases. CONCLUSION: Despite most patients having advanced disease at presentation, outcomes are very good. A national prospective registry should allow systematic collection of good-quality data and may facilitate research to further improve outcomes.


Assuntos
Adenocarcinoma Folicular , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Adenocarcinoma Folicular/epidemiologia , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Modelos de Riscos Proporcionais , Câncer Papilífero da Tireoide/epidemiologia , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/terapia , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Reino Unido/epidemiologia
11.
Sci Adv ; 5(11): eaax4424, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31819900

RESUMO

The past few years have witnessed rapid advances in the synthesis of high-quality perovskite nanocrystals (PNCs). However, despite the impressive developments, the stability of PNCs remains a substantial challenge. The ability to reliably improve stability of PNCs while retaining their individual nanometer size represents a critical step that underpins future advances in optoelectronic applications. Here, we report an unconventional strategy for crafting dual-shelled PNCs (i.e., polymer-ligated perovskite/SiO2 core/shell NCs) with exquisite control over dimensions, surface chemistry, and stabilities. In stark contrast to conventional methods, our strategy relies on capitalizing on judiciously designed star-like copolymers as nanoreactors to render the growth of core/shell NCs with controlled yet tunable perovskite core diameter, SiO2 shell thickness, and surface chemistry. Consequently, the resulting polymer-tethered perovskite/SiO2 core/shell NCs display concurrently a stellar set of substantially improved stabilities (i.e., colloidal stability, chemical composition stability, photostability, water stability), while having appealing solution processability, which are unattainable by conventional methods.

12.
Sci Rep ; 9(1): 15569, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31700005

RESUMO

Climate change-driven alterations in Arctic environments can influence habitat availability, species distributions and interactions, and the breeding, foraging, and health of marine mammals. Phocine distemper virus (PDV), which has caused extensive mortality in Atlantic seals, was confirmed in sea otters in the North Pacific Ocean in 2004, raising the question of whether reductions in sea ice could increase contact between Arctic and sub-Arctic marine mammals and lead to viral transmission across the Arctic Ocean. Using data on PDV exposure and infection and animal movement in sympatric seal, sea lion, and sea otter species sampled in the North Pacific Ocean from 2001-2016, we investigated the timing of PDV introduction, risk factors associated with PDV emergence, and patterns of transmission following introduction. We identified widespread exposure to and infection with PDV across the North Pacific Ocean beginning in 2003 with a second peak of PDV exposure and infection in 2009; viral transmission across sympatric marine mammal species; and association of PDV exposure and infection with reductions in Arctic sea ice extent. Peaks of PDV exposure and infection following 2003 may reflect additional viral introductions among the diverse marine mammals in the North Pacific Ocean linked to change in Arctic sea ice extent.


Assuntos
Organismos Aquáticos/virologia , Cetáceos/virologia , Vírus da Cinomose Focina/metabolismo , Cinomose , Aquecimento Global , Gelo , Lontras/virologia , Animais , Regiões Árticas , Cinomose/epidemiologia , Cinomose/transmissão , Vírus da Cinomose Focina/patogenicidade
13.
Clin Oncol (R Coll Radiol) ; 29(5): 310-315, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28132755

RESUMO

AIMS: When a fixed activity of radioiodine is given for differentiated thyroid cancer (DTC), absorbed doses of radioiodine can vary widely and are not usually measured. Leeds Cancer Centre has routinely used a form of lesion-specific dosimetry for radioiodine patients. This study investigated if the results of dosimetry influenced treatment decisions for patients with advanced DTC. MATERIALS AND METHODS: Since 2005, patients with regionally advanced/metastatic DTC, who underwent radioiodine treatment together with dosimetry, were included in this study. Patients were excluded if their radioiodine post-treatment scan showed no abnormal uptake. Dosimetry was calculated using images taken 2, 3 and 7 days post-radioiodine. Regions of interest were drawn around lesions that required dosimetry and a time-dose activity curve was created. The total cumulative activity was equal to the area under the curve. Each patient's results were prospectively assessed by their oncologist regarding the usefulness of dosimetry in making management decisions. RESULTS: Thirty patients were studied and underwent 102 admissions of radioiodine between them. Dosimetry was carried out during 83 of 102 admissions. An absorbed dose of >20 Gy was taken as significant from dosimetry calculations, following which further radioiodine was considered. In 80% of patients, dosimetry was found to be useful when making treatment decisions. Only on 1/19 admissions did dosimetry calculate a minimum dose above 20 Gy in patients who had a total of four or more admissions for radioiodine. Ten per cent (3/30) had a complete response to radioiodine, both biochemically and radiologically, with a median follow-up of 6.7 months. Thirty-three per cent had a partial response/stable disease to radioiodine. The remainder had progressive disease. The decision to discontinue radioiodine therapy was often based on dosimetry and thyroglobulin results. Dosimetry was very useful for patients with thyroglobulin antibodies. CONCLUSION: Only 10% had a complete response. Therefore, a significant number of patients became refractory to radioiodine during a course of repeat admissions for treatment. Dosimetry (often together with thyroglobulin and anatomical scans) helped to identify these patients to avoid further futile radioiodine therapy.


Assuntos
Radioisótopos do Iodo/uso terapêutico , Radiometria/métodos , Neoplasias da Glândula Tireoide/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Cintilografia/métodos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Resultado do Tratamento , Reino Unido , Adulto Jovem
14.
J Clin Oncol ; 13(1): 165-76, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7799016

RESUMO

PURPOSE: To compare the efficacy of ceftazidime and imipenem monotherapy for fever and neutropenia, and to determine whether fewer antimicrobial modifications (additions or changes) are required by the broader-spectrum agent, imipenem. PATIENTS AND METHODS: Adult and pediatric patients undergoing chemotherapy for solid tumors, leukemias, or lymphomas were randomized to receive open-label ceftazidime or imipenem on presentation with fever and neutropenia. Success with or without modifications of the initial antibiotic was defined as survival through neutropenia; failure was death due to infection. Comparisons were based on numbers of modifications made to each monotherapy during the course of neutropenia, in patients stratified as having unexplained fever or a documented infection. RESULTS: Among 204 ceftazidime and 195 imipenem recipients, the overall success rate with or without modification was more than 98%, regardless of initial antibiotic regimen. Modifications occurred in half of all episodes, primarily in patients with documented infections on either monotherapy. Antianaerobic agents were more frequently added to ceftazidime (P < .001), but addition of other antibiotics, including vancomycin and aminoglycosides, was similar between the two monotherapy groups. Imipenem therapy was associated with significantly greater toxicity, manifested by Clostridium difficile-associated diarrhea and by nausea and vomiting, which required discontinuation of imipenem in 10% of recipients. CONCLUSION: Ceftazidime and imipenem are both effective in the management of fever and chemotherapy-related neutropenia, provided that modifications are made in response to clinical and microbiologic data that emerge during the course of neutropenia. Imipenem, despite its broader antimicrobial spectrum, does not significantly decrease the overall need for antibiotic modifications and is more often complicated by gastrointestinal toxicity.


Assuntos
Infecções Bacterianas/tratamento farmacológico , Ceftazidima/uso terapêutico , Febre/tratamento farmacológico , Imipenem/uso terapêutico , Neoplasias/complicações , Neutropenia/tratamento farmacológico , Aciclovir/uso terapêutico , Adolescente , Adulto , Idoso , Infecções Bacterianas/microbiologia , Causas de Morte , Ceftazidima/efeitos adversos , Criança , Pré-Escolar , Feminino , Febre/etiologia , Febre/mortalidade , Febre de Causa Desconhecida/tratamento farmacológico , Humanos , Imipenem/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Neutropenia/mortalidade , Estudos Prospectivos , Vancomicina/uso terapêutico
15.
J Clin Oncol ; 8(2): 222-9, 1990 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2299367

RESUMO

Twenty-four cancer patients with diffuse interstitial pneumonitis (DIP) were randomized to undergo an open lung biopsy (OLB) within 8 hours of presentation (12 patients) or to receive empiric antimicrobial therapy (ET) with trimethoprim-sulfamethoxazole (TMP-SMX) erythromycin for a minimum of 4 days (12 patients). Patients whose condition deteriorated underwent an OLB on day 4. Eight of 12 patients (67%) having OLB survived versus 10 of 12 (83%) receiving ET (P = .64). Morbidity occurred in nine of 12 (75%) having OLB versus eight of 12 (67%) receiving ET (P = 1.0). Concurrently, there were 14 additional cancer patients with DIP who were not randomized (nine refused, three had a coagulopathy contraindicating surgery, two were excluded by primary care physicians) and who were comparable demographically to the randomized group. Two received OLB and 12 ET. Combining the randomized and nonrandomized groups, eight of 14 (57%) having an initial OLB survived versus 18 of 24 (75%) of ET-treated patients (P2 = .19). Results of the OLB were seven Pneumocystis carinii pneumonia (PCP), five nonspecific pneumonitis (NSP), one cytomegalovirus, and one lymphoma. Results of OLB led to discontinuation of antibiotics in three patients. Of the 24 ET patients, eight failed to improve by day 4 and had an OLB. Results were two NSP, two PCP, two cancer, one blastomycosis, and one Candida pneumonia. Complications were seen in 10 of 14 (72%) initial OLB patients versus 14 of 24 (58%) patients on the ET arm (P = .65). When the complication rate between patients receiving only empiric antibiotics was compared with all patients having an OLB (initially or on day 4), the difference was greater in patients undergoing OLB (37% v 72%, respectively) (P2 = .14). ET with TMP-SMX plus erythromycin and broad spectrum antibiotics in granulocytopenic patients appeared to be as successful and potentially less toxic than an OLB in this study. Although the number of patients in this study was small, these data suggest that a trial of empiric antibiotic management may be reasonable in cancer patients presenting with DIP, especially if they are nonneutropenic.


Assuntos
Biópsia/métodos , Eritromicina/uso terapêutico , Neoplasias , Fibrose Pulmonar/patologia , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adulto , Agranulocitose/complicações , Diagnóstico Diferencial , Quimioterapia Combinada/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/patologia , Estudos Prospectivos , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/fisiopatologia , Distribuição Aleatória
16.
J Pharmacol Toxicol Methods ; 51(2): 153-7, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15767209

RESUMO

INTRODUCTION: Increased methylglyoxal formation due to insulin resistance has been implicated in the development of essential hypertension and in type-2 diabetic complications in animal models. Methylglyoxal is a highly reactive aldehyde, which binds sulfhydryl and amino groups of membrane proteins forming conjugates, advanced glycation end products (AGEs), which alter membrane function, leading to increased blood pressure and oxidative stress. We have shown elevated aldehyde conjugates in tissues of hypertensive rats which may be formed primarily from methylglyoxal. Our objective was to develop a specific method to measure methylglyoxal in rat tissues. METHOD: This method involves preparation of plasma, blood and tissue homogenates, solid phase extraction of methylglyoxal, derivitization using o-phenylenediamine, further purification of derivatized products by solid phase extraction and quantification by electrospray ionization liquid chromatography mass spectrometry (ESI/LC/MS). RESULTS: Methylglyoxal was highest in aorta followed by heart, liver, kidney and blood in that order in Sprague-Dawley rats. Levels of methylglyoxal in plasma were about an order of magnitude lower than that in tissues, but above the concentration used for the lowest calibration standard. DISCUSSION: We have successfully developed an ESI/LC/MS method for quantification of methylglyoxal in rat tissues. The high selectivity of this method offers an advantage over other methods based on fluorescence. This method will allow the evaluation of methylglyoxal in essential hypertension and type-2 diabetes.


Assuntos
Cromatografia Líquida , Espectrometria de Massas , Aldeído Pirúvico/análise , Aldeído Pirúvico/sangue , Espectrometria de Massas por Ionização por Electrospray , Animais , Aorta/química , Rim/química , Fígado/química , Masculino , Estrutura Molecular , Miocárdio/química , Aldeído Pirúvico/química , Ratos , Ratos Sprague-Dawley , Sensibilidade e Especificidade
17.
J Food Prot ; 68(9): 1823-30, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16161680

RESUMO

Frankfurters inoculated with Listeria monocytogenes were treated with 1% cetylpyridinium chloride (CPC) or with 1% CPC followed by a water rinse at various combinations of spray temperatures (25, 40, and 55 degrees C), spray pressures (20, 25, and 35 psi), and times of exposure (30, 40, and 60 s). No significant differences (P > 0.05) were observed in the reductions achieved by 1% CPC + water wash and those achieved with 1% CPC treatment alone. L. monocytogenes populations were reduced by ca. 1.7 log CFU/g immediately following treatment, with no differences (P > 0.05) observed for different spray temperatures, pressures, or exposure times. The effectiveness of 1% CPC spray treatment (at 25 degrees C, 20 psi, and 30 s of exposure) against L. monocytogenes on vacuum-packaged frankfurters stored at 0 and 4 degrees C for 42 days was then evaluated. Application of a 1% CPC surface spray to frankfurters immediately prior to packaging reduced L. monocytogenes concentrations by 1.4 to 1.7 log CFU/g and further restricted growth of the pathogen during 42 days of refrigerated storage, thereby meeting U.S. Department of Agriculture alternatives 1 and 2 criteria for Listeria control. CPC treatment reduced aerobic plate counts, lactic acid bacteria, yeasts and molds, total coliforms, and Escherichia coli populations on noninoculated frankfurters to below detectable limits. The 1% CPC treatment did not affect the color (L*, a*, and b* values) of frankfurters stored for 42 days at 0 or 4 degrees C (P > 0.05). The effect of 1% CPC treatment on the firmness of frankfurters was also negligible.


Assuntos
Anti-Infecciosos Locais/farmacologia , Cetilpiridínio/farmacologia , Conservação de Alimentos/métodos , Listeria monocytogenes/efeitos dos fármacos , Produtos da Carne/microbiologia , Produtos da Carne/normas , Contagem de Colônia Microbiana , Microbiologia de Alimentos , Embalagem de Alimentos , Pressão , Controle de Qualidade , Temperatura , Fatores de Tempo
18.
West Indian Med J ; 54(3): 210-2, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16209229

RESUMO

The colon responds monomorphically to a variety of insults thus making it difficult to differentiate invasive amoebic colitis and inflammatory bowel disease (IBD). The authors present a case with chronic dysentery, haematochezia, anaemia and hypoproteinaemia. The endoscopic findings were suggestive of IBD. The stool examination was negative for trophozoites or cysts of parasites. The recto-colonic biopsy specimens showed mucosal inflammation with exudates containing amoebic trophozoites. The patient was successfully treated with metronidazole and iodoquinol. He recovered within two weeks and repeat colonoscopy four weeks after the treatment showed a normal rectum and colon. Clinicians should have a high level of suspicion for amoebic colitis in cases of colitis especially in regions where amoebiasis is still present. Efforts should be made to find the amoebic trophozoites in multiple stool and colonic biopsy specimens.


Assuntos
Disenteria Amebiana/diagnóstico , Adulto , Amebicidas/uso terapêutico , Diagnóstico Diferencial , Quimioterapia Combinada , Disenteria Amebiana/tratamento farmacológico , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Iodoquinol/uso terapêutico , Masculino , Metronidazol/uso terapêutico
19.
FEBS Lett ; 383(3): 150-4, 1996 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-8925886

RESUMO

Exposure of HeLa cells in monolayer culture to increasing concentrations of exogenously added H2O2 causes damage to cellular DNA. When the DNA is subsequently isolated from the non-apoptotic cells remaining in such cultures, evidence was obtained to suggest that the DNA damage elicited in intact cells was non-random and that certain nucleotide sequences associated with, or related to, the genes for heat shock protein 60 and catalase were more susceptible to damage than others. In contrast, these particular sequences were not specifically susceptible to damage when naked human DNA was exposed directly to H2O2 in vitro. On an overall comparative basis, sequences in the genes encoding catalase, alpha-1 antitrypsin and beta-actin appear more vulnerable to H2O2 in vivo, than sequences in H-ras and the P53 gene which seem surprisingly resistant.


Assuntos
Dano ao DNA , DNA de Neoplasias/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Actinas/genética , Sequência de Bases , Catalase/genética , DNA/química , DNA/efeitos dos fármacos , DNA/isolamento & purificação , Sondas de DNA , DNA de Neoplasias/química , DNA de Neoplasias/isolamento & purificação , Relação Dose-Resposta a Droga , Eletroforese em Gel de Ágar , Feminino , Genes p53 , Genes ras , Células HeLa , Humanos , Placenta , Gravidez , alfa 1-Antitripsina/genética
20.
Am J Med ; 81(4): 596-600, 1986 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3766589

RESUMO

Although usually considered a non-pathogen, Clostridium tertium was isolated from 10 immunosuppressed patients including seven patients with bacteremia. This organism can grow aerobically and can be easily disregarded as a contaminant. It also has a somewhat unusual susceptibility pattern, with significant resistance to the penicillins, cephalosporins, and clindamycin, possibly explaining its emergence in immunocompromised patients already receiving multiple antibiotics.


Assuntos
Infecções por Clostridium/fisiopatologia , Clostridium/patogenicidade , Adulto , Anemia Aplástica/complicações , Antibacterianos/uso terapêutico , Criança , Clostridium/isolamento & purificação , Infecções por Clostridium/complicações , Infecções por Clostridium/tratamento farmacológico , Feminino , Humanos , Leucemia/complicações , Masculino , Pessoa de Meia-Idade
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