RESUMO
PURPOSE: Sleep impairment is reported to be a consequence of overweight and obesity. However, the weight-sleep relationship can alternately be explained by demographics (e.g. age) and covariates (i.e. mood/affect and behaviour in overweight/obese people; e.g. night-eating). Thus, we examined the weight-sleep quality relationship after controlling for the effects of affect and common behaviour (i.e. night-eating, insufficient exercise, alcohol and electronic device use). METHODS: Online questionnaires asked 161 overweight, obese or normal-weight participants about their sleep quality, night-eating, physical activity, alcohol use, electronic device use and anxiety and depression at T0 (baseline) and T1 (3 months later). Height and weight and waist and hip circumference were objectively measured at T0 and T1, and physical activity was assessed over 24 h (using actigraphy) at T0 and T1. Hierarchical multiple regression analyses evaluated whether the weight measures (i.e. body-mass-index [BMI], waist-to-hip ratio [WHR] and obesity category [overweight/obese vs. normal-weight]) predicted sleep quality and its components at T0 and T1, after controlling demographics (at step 1) and covariates (affective distress and behaviour) at step 2, and entering weight measures at step 3; maximum 8 variables in the analyses. RESULTS: High BMI predicted several aspects of sleep quality after taking into account co-existing behaviour, affect and demographics: sleep disturbances at T0 and lower sleep efficiency at T1. WHR and obesity category did not predict any aspects of sleep quality. Several co-existing behaviour were related to or predicted sleep quality score and aspects of sleep quality including night-eating, alcohol use and electronic device use and affective symptoms (i.e. anxiety, depression). CONCLUSION: Results suggest that a person's weight may impact on their sleep quality above and beyond the effects of their co-existing behaviour and affect, although their co-existing behaviour and affect may also adversely impact on sleep quality. LEVEL OF EVIDENCE: Level III, evidence obtained from well-designed cohort.
Assuntos
Sobrepeso , Qualidade do Sono , Índice de Massa Corporal , Humanos , Obesidade/complicações , Sobrepeso/complicações , Sobrepeso/psicologia , Sono , Relação Cintura-QuadrilRESUMO
BACKGROUND: Staff providing support to people with intellectual disabilities are exposed to stressful work environments which may put them at an increased risk of burnout. A small prior literature has examined predictors of burnout in disability support staff, but there is little consensus. In this study, we examined direct and indirect associations between work stressors (i.e. challenging client behaviour), staff emotional response to the behaviour (i.e. perceived stress, anxiety, depression), social and organisational support resources, and staff burnout. METHODS: A short survey examined client behaviour, staff psychological stress, anxiety, depression, social support (number, satisfaction), organisational support and burnout in 80 disability support staff in a community setting. RESULTS: Burnout levels were similar to or slightly lower than normed values for human services staff. Cross-sectional regression analyses indicated that depression symptoms and organisational support were related to worse emotional exhaustion and depersonalisation, whereas less social support was related to less personal accomplishment. Social support satisfaction (but not social support number or organisational support) moderated between high psychological stress to less emotional exhaustion. CONCLUSIONS: Taken together, these results suggest that depression symptoms and low organisational support were frequently concurrent with burnout symptoms. Furthermore, worker's personal and organisational supports may have helped bolster their sense of personal accomplishment, and buffered against the potential for emotional exhaustion.
Assuntos
Esgotamento Profissional/psicologia , Depressão/psicologia , Deficiência Intelectual/enfermagem , Apoio Social , Estresse Psicológico/psicologia , Adaptação Psicológica , Adulto , Esgotamento Profissional/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Pessoas com Deficiência Mental/reabilitação , Local de Trabalho/psicologiaRESUMO
OBJECTIVES: To develop a communication skills training (CST) module for health care professionals, particularly in the area of oncology, on how to conduct interviews using interpreters and to evaluate the module in terms of participant's self-efficacy and satisfaction. METHODS: Forty-seven multi-specialty health care providers from the New York Metropolitan Area attended a communication skills module at a Comprehensive Cancer Care Center about how to conduct clinical interviews utilizing interpreters. The development of this module was on the basis of current literature and followed the Comskil model previously utilized for other doctor-patient CSTs. Participants were given pre- and post-surveys to evaluate their own confidence as well as the helpfulness of the module. RESULTS: On the basis of a retrospective pre-post measure, participants reported an increase in their confidence about interviewing patients via translators. In addition, at least 80% of participants reported their satisfaction with the various components of the module by either agreeing or strongly agreeing with the different statements. CONCLUSIONS: We have developed a module that trains clinicians in effective collaboration with professional medical interpreters and shown its ability to increase the confidence of clinician's to work with limited English proficiency patients. Our approach intends to minimize not only the language barrier but also the cultural barriers that could potentially interfere with patients' care. PRACTICE IMPLICATIONS: This work has important practice implications in the oncology setting, where cultural sensitivity is paramount and empathic exchange with the patient optimizes their sense of being well supported by their health care team. We believe that this model is generalizable to many other medical settings where use needs to be made of a professional interpreter.
Assuntos
Barreiras de Comunicação , Educação Médica/métodos , Entrevistas como Assunto/métodos , Oncologia/educação , Tradução , Humanos , Relações Profissional-PacienteRESUMO
Phosgene is a chemical widely used in the plastics industry and has been used in warfare. It produces life-threatening pulmonary edema within hours of exposure; no antidote exists. This study examines pathophysiological changes seen following treatment with elevated inspired oxygen concentrations (Fi(O2)), in a model of phosgene-induced acute lung injury. Anesthetized pigs were exposed to phosgene (Ct 2500 mg min m(-3)) and ventilated (intermittent positive pressure ventilation, tidal volume 10 ml kg(-1), positive end-expiratory pressure 3 cm H(2)O, frequency 20 breaths min(-1)). The Fi(O2) was varied: group 1, Fi(O2) 0.30 (228 mm Hg) throughout; group 2, Fi(O2) 0.80 (608 mm Hg) immediately post exposure, to end; group 3, Fi(O2) 0.30 from 30 min post exposure, increased to 0.80 at 6 h post exposure; group 4, Fi(O2) 0.30 from 30 min post exposure, increased to 0.40 (304 mm Hg) at 6 h post exposure. Group 5, Fi(O2) 0.30 from 30 min post exposure, increased to 0.40 at 12 h post exposure. The current results demonstrate that oxygen is beneficial, with improved survival, arterial oxygen saturation, shunt fraction, and reduced lung wet weight to body weight ratio in all treatment groups, and improved arterial oxygen partial pressure in groups 2 and 3, compared to phosgene controls (group 1) animals. The authors recommend that treatment of phosgene-induced acute lung injury with inspired oxygen is delayed until signs or symptoms of hypoxia are present or arterial blood oxygenation falls. The lowest concentration of oxygen that maintains normal arterial oxygen saturation and absence of clinical signs of hypoxia is recommended.
Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/terapia , Oxigenoterapia/métodos , Fosgênio/toxicidade , Lesão Pulmonar Aguda/patologia , Administração por Inalação , Animais , Feminino , Oxigênio/administração & dosagem , Taxa de Sobrevida/tendências , Sus scrofa , Fatores de TempoRESUMO
OBJECTIVE: The purpose of this report is to extend the current understanding of patient satisfaction by examining expectations of a sample of breast cancer patients and concordance with their medical oncologists about the content of consultations and the importance of consultation items. METHODS: Three hundred and ninety-five female early stage breast cancer patients of 56 oncologists participated. Patients and oncologists completed a matched questionnaire measuring (a) met expectations, (b) concordance over content and item importance, and (c) satisfaction. RESULTS: Overall patient satisfaction was extremely high (x=91/100%) although expectations were not met at the stated level desired. Patients and physicians disagreed over what was conveyed and received. Higher overall satisfaction was predicted by levels of met expectations (unstandardized beta=0.69, p=0.008, SE=0.26) and concordance over (a) content (unstandardized beta=1.09, p=0.002, SE=0.34) and (b) importance (unstandardized beta=-0.78, p=0.006, SE 0.28). CONCLUSION: Although patient expectations were not well met and physician-patient discord was high about the content of consultations and the importance of consultation items, patients reported high levels of satisfaction. Expectation fulfillment and levels of concordance predicted satisfaction.
Assuntos
Neoplasias da Mama/terapia , Satisfação do Paciente , Relações Médico-Paciente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ohio , Educação de Pacientes como Assunto , Apoio Social , TexasRESUMO
OBJECTIVES: No longitudinal studies have concurrently evaluated predictors of anxiety, depression, and fatigue in people with multiple sclerosis (PwMS). This study determined factors that best predicted anxiety, depression, and fatigue in MS patients from a large pool of disease, cognitive, life-event stressor (LES), psychosocial, life-style, and demographic factors. DESIGN: A 2-year prospective longitudinal study evaluated predictors of psychological distress and fatigue in PwMS. METHODS: One hundred and one consecutive participants with MS were recruited from two MS clinics in Sydney, Australia. LES, anxiety, depression, and fatigue were assessed at baseline and at 3-monthly intervals for 2-years. Disease, cognitive, demographic, psychosocial, and life-style factors were assessed at baseline. Patient-reported relapses were recorded and corroborated by neurologists or evaluated against accepted relapse criteria. RESULTS: Depression strongly predicted anxiety and fatigue, and anxiety and fatigue strongly predicted later depression. Psychological distress (i.e. anxiety, depression) was also predicted by a combination of unhealthy behaviours (e.g. drug use, smoking, no exercise, or relaxation) and psychological factors (e.g. low optimism, avoidance coping), similar to the results of community-based studies. However, state-anxiety and fatigue were also predicted by immunotherapy status, and fatigue was also predicted by LES and demographics. CONCLUSIONS: These results suggest that similar factors might underpin psychological distress and fatigue in MS patients and community-well samples, although MS treatment factors may also be important. These results might assist clinicians in determining which MS patients are at greatest risk of developing anxiety, depression, or fatigue.
Assuntos
Transtornos de Ansiedade , Transtorno Depressivo , Fadiga/epidemiologia , Fadiga/psicologia , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/psicologia , Adaptação Psicológica , Adulto , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/etiologia , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/etiologia , Avaliação da Deficiência , Feminino , Seguimentos , Nível de Saúde , Humanos , Estilo de Vida , Masculino , Motivação , Estudos Prospectivos , Psicologia , Índice de Gravidade de Doença , Transtornos do Sono-Vigília/epidemiologia , Apoio Social , Inquéritos e QuestionáriosRESUMO
This study provides an analysis of the structure of the initial cancer consultation, the consultation styles of medical and radiation oncologists, and their effect on patient outcomes. One hundred and fifty-five cancer patients attending their first consultation with either a medical or radiation oncologist were audiotaped and the transcripts were analysed using the Cancode computer interaction analysis system. Findings revealed that medical oncologists allowed patients and their families more input into the consultation and were rated as warmer and more patient-centred compared with radiation oncologists. However, radiation oncologists spent a longer period discussing, and were more likely to bring up, social support issues with patients. Both medical and radiation oncologists varied their consultation style according to the patient's gender, age, anxiety levels, prognosis, and education. Patients seeing an oncologist who was rated as warmer and discussed a greater number of psychosocial issues had better psychological adjustment and reduced anxiety after consultation. These findings provide current evidence that may be used to inform improvements of communication skills training for oncologists and highlight the need for future communication research to separately consider oncologists from different disciplines.
Assuntos
Tomada de Decisões , Oncologia , Neoplasias/radioterapia , Satisfação do Paciente , Relações Médico-Paciente , Radioterapia (Especialidade) , Encaminhamento e Consulta , Gravação em Fita , Adaptação Psicológica , Ansiedade/diagnóstico , Atitude do Pessoal de Saúde , Competência Clínica , Comunicação , Empatia , Humanos , Médicos , Fatores de Tempo , Recursos HumanosRESUMO
ABSTRACT Although normally regarded as a vesicant, inhalation of sulphur mustard (HD) vapor can cause life-threatening lung injury for which there is no specific treatment. Novel therapies for HD-induced lung injury are best investigated in an in vivo model that allows monitoring of a range of physiological variables. HD vapor was generated using two customized thermostatically controlled glass flasks in parallel. The vapor was passed into a carrier flow of air (81 L. min(-1)) and down a length of glass exposure tube (1.75 m). A pig was connected to the midpoint of the exposure tube via a polytetrafluoroethylene-lined endotracheal tube, Fleisch pneumotachograph, and sample port. HD vapor concentrations (40-122.8 mg. m(-3)) up-and downstream of the point of exposure were obtained by sampling onto Porapak absorption tubes with subsequent analysis by gas chromatography-flame photometric detection. Real-time estimates of vapor concentration were determined using a photo-ionization detector. Lung function indices (respiratory volumes, lung compliance, and airway resistance) were measured online throughout. Trial runs with methylsalicylate (MS) and animal exposures with HD demonstrated that the exposure system rapidly reached the desired concentration within 1 min and maintained stable output throughout exposure, and that the MS/HD concentration decayed rapidly to zero when switched off. A system is described that allows reproducible exposure of HD vapor to the lung of anesthetized white pigs. The system has proved to be robust and reliable and will be a valuable tool in assessing potential future therapies against HD-induced lung injury in the pig. Crown Copyright (c) 2007 Dstl.
RESUMO
INTRODUCTION: Low rates of accrual of African-American (AA) patients with cancer to therapeutic clinical trials (CTs) represent a serious and modifiable racial disparity in healthcare that impedes the development of promising cancer therapies. Suboptimal physician-patient consultation communication is a barrier to the accrual of patients with cancer of any race, but communication difficulties are compounded with AA patients. Providing tailored health messages (THM) to AA patients and their physician about CTs has the potential to improve communication, lower barriers to accrual and ameliorate health disparities. OBJECTIVE: (1) Demonstrate the efficacy of THM to increase patient activation as measured by direct observation. (2) Demonstrate the efficacy of THM to improve patient outcomes associated with barriers to AA participation. (3) Explore associations among preconsultation levels of: (A) trust in medical researchers, (B) knowledge and attitudes towards CTs, (C) patient-family member congruence in decision-making, and (D) involvement/information preferences, and group assignment. METHODS AND ANALYSIS: First, using established methods, we will develop THM materials. Second, the efficacy of the intervention is determined in a 2 by 2 factorial randomised controlled trial to test the effectiveness of (1) providing 357 AA patients with cancer with THM with 2 different 'depths' of tailoring and (2) either providing feedback to oncologists about the patients' trial THM or not. The primary analysis compares patient engaged communication in 4 groups preconsultation and postconsultation. ETHICS AND DISSEMINATION: This study was approved by the Virginia Commonwealth University Institutional Review Board. To facilitate use of the THM intervention in diverse settings, we will convene 'user groups' at 3 major US cancer centres. To facilitate dissemination, we will post all materials and the implementation guide in publicly available locations. TRIAL REGISTRATION NUMBER: NCT02356549.
Assuntos
Comunicação , Educação em Saúde/métodos , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Neoplasias/terapia , Educação de Pacientes como Assunto/métodos , Relações Médico-Paciente , Negro ou Afro-Americano , Feminino , Humanos , Masculino , Neoplasias/etnologia , Encaminhamento e Consulta , Projetos de Pesquisa , Estados UnidosRESUMO
OBJECTIVES: The effect of dipyridamole on smooth muscle cell proliferation and prevention of intimal thickening after arterial injury was investigated. BACKGROUND: In addition to antiplatelet activity, dipyridamole also inhibits cell proliferation. We examined whether the antiproliferative action of dipyridamole on smooth muscle cells, as demonstrated here, has a direct effect on intimal thickening after vascular injury. METHODS: Cell proliferation was determined by measuring deoxyribonucleic acid (DNA) synthesis and by cell counting. The in vivo effect of locally delivered dipyridamole was determined in a rabbit model with carotid or femoral artery injury. RESULTS: Dipyridamole produced a dose-dependent inhibition of smooth muscle cell proliferation, producing 50% inhibition at 7 micrograms/ml. Structural analogues SH-869 and mopamidol were 10 to 100 times less effective than dipyridamole, suggesting that cell growth inhibition may be unrelated to the antiplatelet activity of dipyridamole. Inhibition of cell proliferation by dipyridamole was attenuated by increasing the serum concentration in the culture medium. Bypassing serum by local delivery of dipyridamole at the periadventitial site produced 63% inhibition (p < 0.05) of cell replication in balloon-injured arteries. Locally delivered dipyridamole also inhibited intimal thickening (20%, p < 0.05) after balloon injury. CONCLUSIONS: Dipyridamole inhibited smooth muscle cell proliferation in vitro. This activity was attenuated by serum proteins. Locally delivered dipyridamole inhibited cell replication in arteries and intimal thickening after balloon injury. These results suggest that although systemic treatment with dipyridamole may not be efficacious because of inadequate serum levels, its antiproliferative action on smooth muscle cells may reduce restenosis when the drug is delivered locally after coronary angioplasty.
Assuntos
Angioplastia com Balão , Dipiridamol/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Animais , Lesões das Artérias Carótidas , Artéria Carótida Primitiva/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Constrição Patológica/prevenção & controle , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/lesões , Masculino , Coelhos , Recidiva , Túnica Íntima/efeitos dos fármacosRESUMO
The preparation and biological evaluation of a series of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoximinoacetamido]cep halosporins, substituted at the 3'-position with monocyclic or bicyclic nitrogen-containing heterocycles are described. The resulting family of parenteral compounds displays a broad spectrum of antibacterial activity. Some compounds exhibit a similar level of Gram-negative activity to that of the "third-generation" cephalosporins with increased staphylococcal activity. The in vitro and in vivo antimicrobial activity, structure-activity relationships, beta-lactamase stability, and in vitro and in vivo pharmacological evaluations are presented.
Assuntos
Cefalosporinas/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Cefalosporinas/metabolismo , Cefalosporinas/farmacocinética , Fenômenos Químicos , Química , Cães , Enterobacter/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Feminino , Cobaias , Meia-Vida , Frequência Cardíaca/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Macaca mulatta , Masculino , Camundongos , Estrutura Molecular , Parassimpatolíticos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Ratos , Serratia marcescens/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Streptococcus/efeitos dos fármacos , Relação Estrutura-Atividade , beta-Lactamases/metabolismoRESUMO
Nine matched pairs of cephalosporins and their 1-carba-1-dethiacephalosporin analogues have been compared with regard to microbiological activity, beta-lactam carbonyl infrared absorption, and aqueous stability. In general the microbiological activity of the pairs of compounds were very similar across a broad range of bacteria. The infrared absorption bands for the beta-lactam carbonyls of the pairs indicated a general trend for the 1-carba-1-dethiacephalosporins to absorb at lower frequencies than the corresponding cephalosporins. All of the 1-carba-1-dethiacephalosporins did however present a striking stability enhancement over their cephalosporin counterparts at pH = 10 or 11 in water. This marked contrast of MIC similarity with the observed differences in chemical reactivity clearly demonstrates hydroxide ion catalyzed hydrolysis is not a good model for transpeptidase activity unless the compounds comprise a limited domain of structural type.
Assuntos
Cefalosporinas/farmacologia , Cefalosporinas/análise , Cefalosporinas/síntese química , Hidrólise , Testes de Sensibilidade Microbiana , Espectrofotometria InfravermelhoRESUMO
The authors provide an extensive and comprehensive review of dyslipoproteinemia in children. An effective program for CVD reduction in this population will include an accessible screening program to identify high-risk children, high-quality measurements of TC and LP-C, careful follow-up of screening results with multiple measurement to classify risk status and diagnose primary dyslipidemia, a key role for family and education, and consistent and long-term follow-up for diet and drug adherence, efficacy, and safety.
Assuntos
Hiperlipoproteinemias/prevenção & controle , Hipolipoproteinemias/prevenção & controle , Adolescente , Adulto , Arteriosclerose/etiologia , Arteriosclerose/prevenção & controle , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Criança , Pré-Escolar , Colesterol/sangue , Feminino , Humanos , Hiperlipoproteinemias/complicações , Hiperlipoproteinemias/diagnóstico , Hiperlipoproteinemias/terapia , Hipolipoproteinemias/complicações , Hipolipoproteinemias/diagnóstico , Hipolipoproteinemias/terapia , Lactente , Lipoproteínas/sangue , Masculino , Programas de RastreamentoRESUMO
The effects of inhaled zinc oxide/hexachloroethane smoke (11,580 mg x min/m3) and intratracheally instilled zinc chloride (2.5 mg/kg body weight) have been studied in rat lung. The effects of subsequent treatment with 70% oxygen have been studied after both procedures. Both the inhalation of the smoke and instillation of zinc chloride produced similar effects that included pulmonary edema, alveolitis and, at a later stage, some fibrosis. After zinc chloride instillation, the pathological changes largely spared the periphery of the lung, while following smoke inhalation they were more diffuse. Subsequent oxygen administration had little effect on the development or progression of the pathological changes.
Assuntos
Cloretos/toxicidade , Hexaclorofeno/toxicidade , Pneumopatias/patologia , Compostos de Zinco , Óxido de Zinco/toxicidade , Zinco/toxicidade , Administração por Inalação , Animais , Cloretos/administração & dosagem , Hexaclorofeno/administração & dosagem , Instilação de Medicamentos , Pneumopatias/induzido quimicamente , Pneumopatias/complicações , Macrófagos/patologia , Masculino , Oxigenoterapia , Edema Pulmonar/etiologia , Edema Pulmonar/patologia , Edema Pulmonar/terapia , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/patologia , Fibrose Pulmonar/terapia , Ratos , Ratos Endogâmicos , Fumaça/efeitos adversos , Zinco/administração & dosagem , Óxido de Zinco/administração & dosagemRESUMO
Cultures of murine erythroleukemic cells undergoing erythroid differentiation in response to induction by hexamethylene bisacetamide (HMBA) were exposed to 1180-MHz microwave (MW) radiation for 48 h while maintained at 37.4 degrees C by variable-temperature air flow. Exposures at 1180 MHz were at 5.5, 11, and 22 mW/cm2 with a normalized specific absorption rate of 3.32 W/kg per mW/cm2. HMBA-induced control cells were incubated in a 37.4 degrees C water bath. Mean cell doubling time was 16.5 h in both the irradiated cultures and the control cultures. About 65% of the cells of irradiated cultures and control cultures were benzidine-positive differentiated cells. Both the irradiated cultures and the control cultures contained approximately 58 micrograms of hemoglobin/mg total cytoplasmic protein. The absence of any change in these parameters suggests that MW radiation at 1180 MHz and similar frequencies exerts no effect on proliferation and differentiation of mammalian cells in the absence of hyperthermia.
Assuntos
Leucemia Eritroblástica Aguda/patologia , Micro-Ondas , Acetamidas/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/efeitos da radiação , Linhagem Celular , Vírus da Leucemia Murina de Friend , Técnicas In Vitro , CamundongosRESUMO
Pulmonary fibrosis is a common later sequel to damage to the lung caused by a wide variety of agents. Bleomycin is an antineoplastic drug used in the treatment of squamous cell carcinomas and lymphomas. It is known to cause pulmonary fibrosis is both man and experimental animals. Bleomycin, dissolved in saline, was given by intratracheal instillation (dose = 0.5 U/animal; dose vol. = 0.5 ml/animal) to groups of at least 5 rats. Groups received either a single dose or 2, 3 or 4 doses each given a week apart. They were then sacrificed at periods of up to 90 days after the last dose. Subsequent histology revealed varying degrees of alveolitis, type II pneumocyte hyperplasia, alterations to alveolar structure including obliteration, degeneration, collapse and enlargement with significant interstitial fibrosis. The lesion appeared to be diffusely distributed throughout the lung. After a single dose or 2 doses regression of the lesion was observed with time following dosing whereas with 3 or 4 doses of bleomycin the changes increased progressively in extent and severity. Three or more doses of intratracheal instilled bleomycin appear to be a good model of progressive pulmonary fibrosis in the rat.
Assuntos
Bleomicina/toxicidade , Fibrose Pulmonar/induzido quimicamente , Animais , Modelos Animais de Doenças , Pulmão/efeitos dos fármacos , Pulmão/patologia , Linfócitos/patologia , Masculino , Neutrófilos/patologia , Edema Pulmonar/induzido quimicamente , Ratos , Ratos EndogâmicosRESUMO
The penetration and distribution of T-2 toxin in excised human abdominal skin has been determined for a dose range of 1.0-2.6 micrograms/cm2 skin using an ethanol vehicle and a saline receptor solution. In all cases the overall percentage penetration of T-2 after 48 h was low, the greatest amounts of toxin being present in the stratum corneum with less in the epidermis and relatively little in the dermis. Vehicle: skin partition coefficients support this finding. Neither penetration nor distribution were changed by a rabbit serum receptor solution. Electron micrographs showed that at 1.8 micrograms/cm2 and above the contents of the intercellular space are leached out to leave the integument as a porous membrane. The distribution of T-2 within the skin after 48 h would suggest that for doses up to 2.6 micrograms/cm2 the irritative and inflammatory effects on the skin would be of more immediate concern than would systemic toxicity.
Assuntos
Sesquiterpenos/metabolismo , Absorção Cutânea , Toxina T-2/metabolismo , Difusão , Feminino , Humanos , Técnicas In Vitro , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Permeabilidade , Pele/efeitos dos fármacos , Pele/ultraestrutura , Solubilidade , Distribuição TecidualRESUMO
Zinc chloride which is formed by igniting a mixture of zinc oxide and hexachloroethane in the production of white smokes has been shown to produce oedema when given to rats as a single instillation. The oedematous reaction, as assessed by histopathology and measurements of alveolar surface protein in lavage fluid, is variable, dose-dependent, and maximal at 3 days but at sub-lethal doses it regresses after 7 days. The parent compound, zinc oxide, does not produce these effects. In some animals there is evidence of a fibrogenic response at 7 days post-exposure although it is currently unknown whether or not this effect is progressive.
Assuntos
Cloretos/toxicidade , Etano/análogos & derivados , Hidrocarbonetos Clorados/toxicidade , Edema Pulmonar/induzido quimicamente , Compostos de Zinco , Óxido de Zinco/toxicidade , Zinco/toxicidade , Animais , Interações Medicamentosas , Instilação de Medicamentos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Fumaça , TraqueiaRESUMO
Angiotensin-converting enzyme inhibitors have been shown to inhibit intimal thickening following balloon catheterization of rat carotid arteries. To assess the role of the renin-angiotensin pathway and the angiotensin type-I (AT1) receptor in this effect, the nonpeptide Ang II antagonist losartan (DuP 753) or vehicle was infused continuously i.v. in rats from two days before to two weeks after balloon injury to the left common carotid artery; drug effects upon intimal thickening were examined histologically. Losartan produced a dose-dependent reduction in cross-sectional area of intimal lesions determined two weeks post balloon injury. At 5 mg/kg/day a nonsignificant 23% reduction of intimal area was observed. At the higher dose of 15 mg/kg/day, losartan produced a 48% reduction in intimal area (P less than 0.05) compared to the vehicle-infused group. The cellular density of the neointima was not affected by losartan, indicating a probable effect of the drug upon migration and/or proliferation of smooth muscle cells. In separate groups of non-ballooned rats, losartan infusions of 5 and 15 mg/kg/day produced significant rightward shifts (averaging 6.4- and 55-fold, respectively) in curves relating increases in blood pressure to intravenous Ang II in pithed rats determined between 2 and 16 days following initiation of losartan infusion. Mean arterial blood pressure (determined under alpha-chloralose anesthesia) was reduced following continuous losartan infusion for 6 days from 128 +/- 8 mm Hg (vehicle) to 105 +/- 8 mm Hg at 5 mg/kg/day (P less than 0.05), and 106 +/- 4 mm Hg at 15 mg/kg/day (P less than 0.05). Thus, losartan attenuated the vascular response to balloon catheter injury, and this effect was associated with functional block of vascular AT1 receptors. The results support a role for Ang II, acting via AT1 receptors, in myointimal thickening subsequent to balloon injury of rat carotid arteries.
Assuntos
Angiotensina II/antagonistas & inibidores , Anti-Hipertensivos/farmacologia , Compostos de Bifenilo/farmacologia , Artérias Carótidas/efeitos dos fármacos , Imidazóis/farmacologia , Tetrazóis/farmacologia , Análise de Variância , Animais , Artérias Carótidas/patologia , Lesões das Artérias Carótidas , Cateterismo , Relação Dose-Resposta a Droga , Losartan , Masculino , Ratos , Ratos EndogâmicosRESUMO
Clinical trials have come to be regarded as the gold standard for treatment evaluation. However, many doctors and their patients experience difficulties when discussing trials, leading to poor accrual to trials and questionable quality of informed consent. We have previously developed a typology for ethical communication about Phase II and III clinical trials within four domains: (a) shared decision making, (b) sequencing information, (c) type and clarity of information, and (d) disclosure/coercion. The aim of this study was to compare current clinical practice when seeking informed consent with this typology. Fifty-nine consultations in which 10 participating oncologists sought informed consent were audiotaped. Verbatim transcripts were analysed using a coding system to (a) identify the presence or absence of aspects of the four domains and (b) rate the quality of aspects of two domains: (i) shared decision-making and (ii) type and clarity of information. Oncologists rarely addressed aspects of shared decision-making, other than offering to delay a treatment decision (78%). Moreover, many of these discussions scored poorly with respect to ideal content. The oncologists were rarely consistent with the sequence of information provision. A general rationale for randomising was only described in 46% of consultations. In almost one third of the consultations (28.8%) doctors made implicit statements favouring one option over another, either standard or clinical trial treatment. Doctors complied with some but not other aspects of a standard procedure for discussing clinical trials. This reflects the difficulty inherent in seeking ethical informed consent and the need for communication skills training for oncologists.