RESUMO
Background: Patient-reported outcomes (pros) are essential to capture the patient's perspective and to influence care. Although pros and pro measures are known to have many important benefits, they are not consistently being used and there is there no Canadian pros oversight. The Position Statement presented here is the first step toward supporting the implementation of pros in the Canadian health care setting. Methods: The Canadian pros National Steering Committee drafted position statements, which were submitted for stakeholder feedback before, during, and after the first National Canadian Patient Reported Outcomes (canpros) scientific conference, 14-15 November 2019 in Calgary, Alberta. In addition to the stakeholder feedback cycle, a patient advocate group submitted a section to capture the patient voice. Results: The canpros Position Statement is an outcome of the 2019 canpros scientific conference, with an oncology focus. The Position Statement is categorized into 6 sections covering 4 theme areas: Patient and Families, Health Policy, Clinical Implementation, and Research. The patient voice perfectly mirrors the recommendations that the experts reached by consensus and provides an overriding impetus for the use of pros in health care. Conclusions: Although our vision of pros transforming the health care system to be more patient-centred is still aspirational, the Position Statement presented here takes a first step toward providing recommendations in key areas to align Canadian efforts. The Position Statement is directed toward a health policy audience; future iterations will target other audiences, including researchers, clinicians, and patients. Our intent is that future versions will broaden the focus to include chronic diseases beyond cancer.
Assuntos
Atenção à Saúde/estatística & dados numéricos , Oncologia/estatística & dados numéricos , Neoplasias/terapia , Medidas de Resultados Relatados pelo Paciente , Assistência Centrada no Paciente/estatística & dados numéricos , Canadá , Atenção à Saúde/métodos , Atenção à Saúde/normas , Humanos , Oncologia/métodos , Oncologia/normas , Neoplasias/diagnóstico , Assistência Centrada no Paciente/métodos , Assistência Centrada no Paciente/normas , Qualidade de VidaRESUMO
BACKGROUND: Whilst epidemiological studies have provided evidence of associations between certain risk factors and glioma onset, inferring causality has proven challenging. Using Mendelian randomization (MR), we assessed whether associations of 36 reported glioma risk factors showed evidence of a causal relationship. METHODS: We performed a systematic search of MEDLINE from inception to October 2018 to identify candidate risk factors and conducted a meta-analysis of two glioma genome-wide association studies (5739 cases and 5501 controls) to form our exposure and outcome datasets. MR analyses were performed using genetic variants to proxy for candidate risk factors. We investigated whether risk factors differed by subtype diagnosis (either glioblastoma (n = 3112) or non-glioblastoma (n = 2411)). MR estimates for each risk factor were determined using multiplicative random effects inverse-variance weighting (IVW). Sensitivity analyses investigated potential pleiotropy using MR-Egger regression, the weighted median estimator, and the mode-based estimator. To increase power, trait-specific polygenic risk scores were used to test the association of a genetically predicated increase in each risk factor with glioma onset. RESULTS: Our systematic search identified 36 risk factors that could be proxied using genetic variants. Using MR, we found evidence that four genetically predicted traits increased risk of glioma, glioblastoma or non-glioblastoma: longer leukocyte telomere length, liability to allergic disease, increased alcohol consumption and liability to childhood extreme obesity (> 3 standard deviations from the mean). Two traits decreased risk of non-glioblastoma cancers: increased low-density lipoprotein cholesterol (LDLc) and triglyceride levels. Our findings were similar across sensitivity analyses that made allowance for pleiotropy (genetic confounding). CONCLUSIONS: Our comprehensive investigation provides evidence of a causal link between both genetically predicted leukocyte telomere length, allergic disease, alcohol consumption, childhood extreme obesity, and LDLc and triglyceride levels, and glioma. The findings from our study warrant further research to uncover mechanisms that implicate these traits in glioma onset.
Assuntos
Glioma/epidemiologia , Glioma/genética , LDL-Colesterol/sangue , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/genética , Análise da Randomização Mendeliana , Obesidade/epidemiologia , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Homeostase do Telômero/genética , Triglicerídeos/sangueRESUMO
OBJECTIVE: This study investigates the factors associated with higher doses for both single-plane and biplane procedures and establishes centre-specific 75th percentile levels. METHODS: 602 patients undergoing coronary angiography in a large hospital at Sydney were recruited to the study, and causal agents for high radiation doses were investigated: gender, procedural complexity, severity of coronary artery disease, presence of coronary bypass grafts, entry approach (radial or femoral), level of operator experience; and a single-plane or a biplane imaging system was employed. RESULTS: The 75th percentile levels were calculated. The results demonstrated that, for both systems, higher exposures were associated with patients who were male (p<0.001), had coronary vessel disease (p<0.001) and had a history of coronary bypass grafts (p<0.001). In addition, for biplane systems, procedural complexity (p<0.001), types of entry approach (p<0.001) and levels of operator experience (p<0.001) significantly impacted upon the dose. Biplane examinations recorded higher doses than single-plane procedures (p<0.001) and the inclusion of left-sided ventriculography contributed to the overall dose by up to 10%. CONCLUSION: The 75th percentile levels in this study represent the tentative reference levels and are 48.9, 44.2 and 56 Gy cm(2) for all exposures, single-plane- and biplane-specific exposures, respectively, and compare favourably with the diagnostic reference level values established elsewhere internationally, with only the UK and Irish data being lower. ADVANCES IN KNOWLEDGE: Specific agents have been identified for dose-reducing strategies and the importance of operator training is highlighted. The assumption that biplane procedures may reduce the patient dose should be treated with caution.
Assuntos
Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doses de Radiação , Radiografia Intervencionista/métodos , Ponte de Artéria Coronária/estatística & dados numéricos , Feminino , Artéria Femoral/diagnóstico por imagem , Humanos , Masculino , Artéria Radial/diagnóstico por imagem , Fatores de RiscoRESUMO
The purpose of this inquiry was to evaluate the efficacy of prostate cancer education sessions. Implementation of 3-h patient educational sessions was intended to provide men newly diagnosed with localized prostate cancer, who face difficult and complex decisions, information about potential treatment options. Fifty-seven men completed the distress thermometer assessment before the education session to assess baseline levels of distress. Seven of the men were interviewed post-educational session to determine the degree of knowledge transfer from the session. This study explored the efficacy of the patients' learning experience using an interpretive phenomenological research approach. Resulting data revealed that these patients, as adult learners, were distressed and that, despite the availability of pertinent medical content, the subject material was not learned as intended or readily understood. The conclusion drawn from this preliminary applied educational research study was that the education model used was less than efficacious at ensuring that sufficient knowledge transfer was achieved for medical treatment decision-making processes. These findings suggest a need for future research to explore the application of adult learning theories and approaches that may offer enhanced knowledge translation and transfer for prostate cancer education programs.
Assuntos
Educação de Pacientes como Assunto , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/psicologia , Estresse Psicológico/psicologia , Tomada de Decisões , Humanos , Conhecimento , Masculino , Pessoa de Meia-IdadeRESUMO
Despite improvements in treatment of localized prostate cancer, local recurrence remains a significant problem. A total of 46 patients with proven local cancer recurrence following external beam radiotherapy entered a prospective clinical trial using ultrasound-guided cryosurgery to ablate the residual prostate gland. Persistent complications included one urethra-rectal fistula, incontinence (2), retention (3), and treatment induced erectile dysfunction (7). Using the PSA definitions for biochemical failure as PSA>or=0.3 ng/ml, the Kaplan-Meier plots showed the incidence of patients to be free of biochemical recurrence at 51 and 44% at 1 and 2 y, respectively. For a PSA>or=1.0, the values at 1 and 2 y were 72 and 58%.
Assuntos
Criocirurgia/métodos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Radioterapia/métodos , Idoso , Braquiterapia , Meios de Contraste/farmacologia , Crioterapia , Disfunção Erétil , Seguimentos , Gadolínio DTPA/farmacologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Recidiva Local de Neoplasia , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/metabolismo , Antígeno Prostático Específico/biossíntese , Neoplasias da Próstata/diagnóstico por imagem , Recidiva , Terapia de Salvação , Fatores de Tempo , UltrassonografiaRESUMO
Twenty-five samples of soft plaque and calcified plaque deposits from human hearts or aorta were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS). The determined elements were Ca, P, Na, K, Mg, Zn, Cu, Ba, Pb, Fe, Al, Si, and S. Results showed that the concentration of all elements in the soft plaque was at the micromolar level. In the calcified deposits, the concentrations of Ca and P were at least an order of magnitude higher than the soft plaque, but the other elements were at the same order of magnitude. In the calcified plaque the molar ratios of Ca/P suggested that a significant portion existed as hydroxyapatite Ca10(PO4)6(OH)3. However, their absolute concentrations indicated that this compound was not a major component of the plaque although it may play a major role in determining the crystal structure of the deposit. In some samples the Ca/P ratio was too high to conform to hydroxyapatite. In others it was too low. This indicated that both the calcium and phosphorus existed in other chemical forms which varied from sample to sample. In the soft tissue the P level was high indicating it existed primarily in chemical forms other than hydroxyapatite. The presence of homocysteine is often associated with heart disease. However, the low levels of sulfur indicate that although it may be present, it is not a major component of the plaque, but may nevertheless play an important role in its formation.
Assuntos
Aorta/química , Vasos Coronários/química , Metais Pesados/análise , Oligoelementos/análise , Arteriosclerose/fisiopatologia , Cadáver , Calcinose , Humanos , Espectrometria de MassasRESUMO
OBJECTIVES: To determine in a prospective pilot study the safety and efficacy of cryosurgical ablation for localized prostate carcinoma. METHODS: A total of 87 cryosurgical procedures were performed on 76 consecutive patients between December 1994 and February 1998. All patients had histologically proved adenocarcinoma of the prostate, with prostate-specific antigen (PSA) readings of less than 30 ng/mL. Clinical evaluations, PSA determinations, and patient self-reported quality-of-life questionnaires (functional assessment of cancer treatment-prostate; FACT-P) were used to determine biochemical and clinical disease-free status and complications. Patients had a mean follow-up of 50 months (minimum 36). RESULTS: Follow-up biopsies were performed in 73 patients, and 72 were negative for malignancy after one or more treatments. Ten patients required two treatments and 1 patient required three treatments. The 5-year overall and cancer-specific survival rate was 89% (95% confidence interval, 83% to 97%) and 98.6% (95% confidence interval, 96% to 100%), respectively. The undetectable PSA rate (less than 0.3 ng/mL) for low-risk patients (n = 13) was 60% at 5 years; for moderate-risk patients (n = 23), it was 77%, and for high-risk patients (n = 40), 48%. The corresponding percentage of patients with a PSA level less than 1.0 ng/mL at 5 years was 75%, 89%, and 76%. Sloughing occurred in 3 patients (3.9%), incontinence in 1 (1.3%), and testicular abscess in 1 (1.3%). At 3 years, 18 (47%) of 38 patients capable of unassisted intercourse at the time of cryosurgery had resumed sexual intercourse, 5 spontaneously and 13 with sildenafil or prostaglandin. CONCLUSIONS: The results of this prospective evaluation show cryosurgery to be both a safe and an effective option in the treatment of localized prostate cancer.
Assuntos
Adenocarcinoma/cirurgia , Criocirurgia , Neoplasias da Próstata/cirurgia , Adenocarcinoma/sangue , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The objective of this research was to evaluate the outcomes and costs of alternative approaches to managing patients previously treated for peptic ulcer disease and Helicobacter pylori infection. MATERIALS AND METHODS: A decision-analytic model was used to compare (1a) urease breath testing (UBT) for assessment of H. pylori status versus (1b) observation without further testing or treatment, among patients who were symptom-free following initial antimicrobial and antisecretory therapy for endoscopically demonstrated ulcer and H. pylori infection; and (2a) UBT versus (2b) repeat endoscopy with H. pylori testing, and versus (2c) repeat antimicrobial and antisecretory therapy without further testing, among patients who remained symptomatic following initial therapy. RESULTS: Among patients who were symptom free after initial therapy, 6.1% receiving UBT had symptomatic ulcer at one year, compared to 18.2% of those simply observed. The expected first-year cost per symptom-free patient following initial therapy was $591 for UBT compared to $480 for observation. Among patients with persistent symptoms after initial therapy, 21% receiving repeat therapy had symptomatic ulcer at one year, compared to 23.8% receiving repeat endoscopy, and 23.3% receiving UBT. Corresponding medical costs per patient were, respectively, $766, $1787 and $1122. CONCLUSIONS: The optimal approach to managing patients following initial treatment for ulcer and H. pylori infection depends on symptom status following initial therapy. For symptomatic patients, the preferred approach is to prescribe a repeat course of antimicrobial and antisecretory therapy. For patients without symptoms following initial therapy, UBT is the preferred approach because it is associated with a threefold lower risk of symptomatic ulcer at one year, although it costs an additional $110 per patient, compared with observation.
Assuntos
Custos de Cuidados de Saúde , Infecções por Helicobacter/economia , Helicobacter pylori , Úlcera Péptica/economia , Testes Respiratórios , Estudos de Coortes , Dispepsia/diagnóstico , Dispepsia/tratamento farmacológico , Dispepsia/economia , Dispepsia/microbiologia , Endoscopia Gastrointestinal , Feminino , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Humanos , Masculino , Modelos Teóricos , Úlcera Péptica/diagnóstico , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/microbiologia , Urease/análiseRESUMO
OBJECTIVE: A descriptive study was performed to evaluate the variables which influence the quality of life of women with ovarian cancer undergoing chemotherapy treatment. METHODS: The study involved a chart review of 60 women with ovarian cancer and analysis of their compiled EORTC QLQ-C30 Quality of Life (QoL) questionnaires. Analyses were performed using SPSS software to test the relationship of a number of biomedical variables with QoL outcomes. RESULTS: In comparing QoL scores between newly diagnosed women receiving first-line (cisplatin) chemotherapy and women receiving palliative (carboplatin) therapy for recurrent disease, those receiving first-line therapy had more appetite disturbance, diarrhea, and nausea than women in the latter group. Over time, global QoL declined for newly diagnosed patients, while it improved for those with recurrent disease. A third finding was that younger women reported more fatigue over the course of their treatment than older women. Finally, lower QoL was found to be able to predict death within 12 months after starting treatment. CONCLUSIONS: The EORTC QLQ-C30 can be used to test clinical assumptions and to influence treatment programs of women with ovarian cancer undergoing chemotherapy. The results confirmed the assumption that carboplatin has less of an impact on QoL than cisplatin. Also, the finding of improvements in QoL over time, for the women with recurrent disease, supports the use of carboplatin as palliative treatment. The differences observed in QoL between survivors and nonsurvivors 12 months after starting treatment may help identify high-risk patients for closer monitoring. Brief, structured QoL assessments before clinic appointments may be useful for improving the overall care of ovarian cancer patients.
Assuntos
Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/psicologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/psicologia , Qualidade de Vida , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/cirurgia , Paclitaxel/administração & dosagem , Valor Preditivo dos Testes , Inquéritos e Questionários , Resultado do TratamentoRESUMO
BACKGROUND: Cryosurgery was introduced as an alternative to radiotherapy or radical prostatectomy in the mid-1960s. Although it met the primary objective of achieving local control, it was largely abandoned due to a high incidence of complications. Technologic advances in the areas of imaging and urethral warming have renewed interest in this treatment methodology. The aim of the current study was to determine the quality of life of men enrolled in a Phase II clinical trial of cryosurgery for the treatment of localized prostate carcinoma. METHODS: Men were administered the Functional Assessment of Cancer Treatment-Prostate (FACT-P) prior to their treatment and at 6 weeks and 3, 6, and 12 months posttreatment. RESULTS: By 12 months after cryosurgery, most of the FACT-P subscales had returned to pretreatment levels, following a decline in well-being immediately after cryosurgery. There were two exceptions to this general trend: At 12 months, impairments in social/family well-being and sexual function still remained. The average time to return to work after therapy was 3 weeks. Stay in hospital after treatment was limited to 1 day for 94% of the participants. Compared with men who received the standard treatments of radical prostatectomy and radical radiotherapy, men treated with cryosurgery appeared to have a similar quality of life, with perhaps the exception of decreased sexual function. CONCLUSIONS: The quality-of-life outcomes of this study support the current renewed interest in cryosurgery. The severe impairments reported in other studies were not seen in this sample. In fact, it appeared that all aspects of the participants' well-being had returned to pretreatment levels by 12 months, with the exception of sexual function.
Assuntos
Criocirurgia/efeitos adversos , Neoplasias da Próstata/psicologia , Neoplasias da Próstata/cirurgia , Qualidade de Vida , Idoso , Apetite , Defecação , Humanos , Masculino , Pessoa de Meia-Idade , Dor/psicologia , Relações Médico-Paciente , Estudos Prospectivos , Comportamento Sexual/psicologia , Fatores de Tempo , MicçãoRESUMO
PURPOSE: The association between radiotherapy for gynecological carcinoma and sexual dysfunction is well established. Regular vaginal dilation is widely recommended to these women as a way for them to maintain vaginal health and good sexual functioning. However, the compliance rate with this recommendation is low. The purpose of this study was to test the effectiveness of a group psychoeducational program based on the "information-motivation-behavioral skills" model of behavior change in increasing the rate of compliance. METHODS AND MATERIALS: Thirty-two women with Stage I or II cervical or endometrial carcinoma who were being treated with radiotherapy were randomized and received either the experimental group program or the control intervention that consisted of written information and brief counseling. Outcome measures included global sexual health, knowledge about sexuality and cancer, fears about sexuality after cancer, and vaginal dilation compliance. RESULTS: Younger women attending the experimental program (44.4%) were significantly more likely to follow recommendations for vaginal dilation than those who received the control intervention (5.6%). Women, regardless of age, who received the experimental intervention reported less fear about sex after cancer treatment. The older women who received the experimental intervention gained more sexual knowledge. There was no evidence that the experimental intervention improved global sexual health. CONCLUSIONS: This is the first controlled study to provide evidence of an intervention's effectiveness 1. in increasing women's vaginal dilation following radiotherapy for gynecological carcinoma and 2. in reducing their fears about sex after cancer. Most women, particularly younger women, are unlikely to follow the recommendation to dilate unless they are given assistance in overcoming their fears and taught behavioral skills.
Assuntos
Coito/psicologia , Dispareunia/psicologia , Neoplasias do Endométrio/psicologia , Medo/psicologia , Lesões por Radiação/psicologia , Neoplasias do Colo do Útero/psicologia , Vagina/efeitos da radiação , Adulto , Fatores Etários , Idoso , Análise de Variância , Dilatação , Dispareunia/terapia , Neoplasias do Endométrio/radioterapia , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Cooperação do Paciente , Educação de Pacientes como Assunto/métodos , Avaliação de Programas e Projetos de Saúde , Lesões por Radiação/terapia , Neoplasias do Colo do Útero/radioterapiaRESUMO
Family physicians can be instrumental in helping their patients adjust to changes in sexuality subsequent to treatment for cancer, only if they break the silence surrounding sexuality. Cancer, like other illnesses, can interfere with intimate relationships. Many patients want to discuss changes in their sexuality with their family physician. However, few will raise the issue themselves but wait for their physician to broach the subject. This article summarises the P-LI-SS-IT Model which provides practical guidance on assessing the sexual concerns of cancer patients and on developing helpful interventions.
Assuntos
Neoplasias/psicologia , Educação de Pacientes como Assunto , Sexualidade , Coito , Feminino , Fertilidade , Humanos , Masculino , Relações Médico-PacienteRESUMO
BACKGROUND: Published reports of complication rates, such as erectile dysfunction, associated with treatments for prostate carcinoma are often used to guide patient decision-making and develop clinical guidelines. Unfortunately, the published data are largely comprised of case series from single institutions. Meta-analysis is a methodology for combining findings from several studies to produce a better result. METHODS: A comprehensive literature review and subsequent meta-analysis of the rates of erectile dysfunction associated with external beam radiotherapy and radical prostatectomy was conducted. A simple logistic regression model was used to combine the data from 40 articles that met selection criteria. RESULTS: The probability of maintaining erectile functioning after radiotherapy is 0.69. The probability after surgery is 0.42. This difference is significant. Analysis of the effects of variables such as patient age and stage of disease on erectile functioning could not be performed due to inconsistencies across studies and the limited number of studies reporting such variables. CONCLUSIONS: The published data indicate that men with normal erectile functioning are more likely to retain this function after radiotherapy than after surgery. Attention is drawn to the weaknesses in the reviewed studies in the hope that the clinical trials of emerging treatments, such as cryotherapy, brachytherapy, three-dimensional conformal radiotherapy, and neoadjuvant hormones can be strengthened to reflect more accurately the rate of treatment-associated erectile dysfunction.
Assuntos
Disfunção Erétil/etiologia , Ereção Peniana , Prostatectomia/efeitos adversos , Neoplasias da Próstata/fisiopatologia , Neoplasias da Próstata/terapia , Bases de Dados Factuais , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Ereção Peniana/efeitos da radiação , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgiaRESUMO
Very little is known about the distribution of hepatitis C virus (HCV) within South America. To assess the exposure of the general population to this virus, a number of sera obtained from three distinct geographical and racial groups were screened using a combination of immunoassays. Initial screening was undertaken with an inhouse immunoassay (core-ELISA) using synthetic peptides based on the N-terminus of the HCV core protein. Sera which were repeatedly positive by core-ELISA were also assessed using a commercial third-generation assay. The highest prevalence rate (2.3%) was seen in sera taken from the Tumaco region of Colombia. Lower rates were found in sera taken from La T, Ecuador (0.7%) and Las Majadas, Venezuela (0.7%). This indicates significantly different prevalence in different racial and geographical groups within the region.
Assuntos
Hepacivirus/isolamento & purificação , Anticorpos Anti-Hepatite C/sangue , Antígenos da Hepatite C/imunologia , Hepatite C/virologia , Proteínas do Core Viral/imunologia , Sequência de Aminoácidos , Ensaio de Imunoadsorção Enzimática , Hepacivirus/imunologia , Hepatite C/epidemiologia , Hepatite C/imunologia , Humanos , Indígenas Sul-Americanos , Programas de Rastreamento , Dados de Sequência MolecularRESUMO
The neutralizing activity and fusion-inhibition activity per unit weight of immunoglobulin were determined for each of a panel of 20 monoclonal antibodies (MAbs) to the fusion (F) protein of respiratory syncytial (RS) virus. Neutralization did not correlate with fusion-inhibiting activity, suggesting that the F protein plays at least two independent, antibody-sensitive roles in viral infection. Antibodies with the highest biological activity against A2, a subgroup A strain of RS virus, neutralized a subgroup B strain (8/60) poorly, suggesting a degree of antigenic variation that may be important in human infection. All but one fusion-inhibiting MAb bound to protein blots and binding was mapped to two areas on overlapping F protein fragments. One MAb with relatively poor fusion-inhibiting activity bound only to fragments C-terminal of amino acid 384, the remainder bound only to fragments containing residues 253 to 289. MAbs directed to the latter site were heterogeneous in neutralizing activity, subgroup specificity and fusion-inhibiting activity. These variations between MAbs could not be accounted for by differences in their binding avidities. We suggest that this binding site is not the complete antibody epitope which probably includes conformation-dependent elements.
Assuntos
Anticorpos Monoclonais/metabolismo , Vírus Sinciciais Respiratórios/metabolismo , Proteínas Virais de Fusão/metabolismo , Animais , Anticorpos Monoclonais/farmacologia , Sítios de Ligação de Anticorpos , Ensaio de Imunoadsorção Enzimática , Camundongos , Camundongos Endogâmicos BALB C/imunologia , Testes de Neutralização , Proteínas Recombinantes de Fusão/análise , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Virais de Fusão/análise , Proteínas Virais de Fusão/imunologiaRESUMO
Patients with cervical cancer were interviewed in a focus group format to obtain their retrospective views of quality of life (QL) in the context of cancer treatment. In addition, they were asked to evaluate the European Organization for Research and Treatment of Cancer's QL questionnaire (EORTC QLQ-C30) as an indicator of their QL. Ethnographic analysis of group transcripts revealed a number of dimensions of QL that these women did not believe were adequately addressed by the EORTC QLQ-C30. They were: (1) perceived control over one's body, (2) a sense of normalcy in one's life, (3) invasiveness experienced as a result of medical interventions, and (4) the degree of predictability of disease and treatment. Patients also indicated that QL was determined more by the meaning and value they placed on their experience than by the occurrence of specific functional changes, symptoms, or side effects. The results have implications for how QL is conceptualized. An alternative model of QL assessment, based on the patient as expert, is illustrated and described.
Assuntos
Qualidade de Vida , Inquéritos e Questionários/normas , Neoplasias do Colo do Útero/psicologia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Pesquisa Metodológica em Enfermagem , Neoplasias do Colo do Útero/terapiaAssuntos
Características Culturais , Indígenas Norte-Americanos , Planejamento de Assistência ao Paciente , Equipe de Assistência ao Paciente , Neoplasias do Colo do Útero/etnologia , Adulto , Arizona , Aconselhamento , Feminino , Identidade de Gênero , Humanos , Casamento/etnologia , Neoplasias do Colo do Útero/terapiaRESUMO
cDNA containing the entire coding sequence of the respiratory syncytial (RS) virus fusion (F) protein gene (574 amino acids) and two large PstI restriction fragments, encoding amino acids 18 to 212 and 214 to 574, were expressed in Escherichia coli as C-terminal chimeras with beta-galactosidase (beta-gal) in the pEX expression vector system. A further cDNA fragment, overlapping the PstI restriction site and encoding amino acids 190 to 289, was derived by PCR and expressed in a similar manner. Polyclonal rabbit serum raised against RS virus bound to all four chimeric proteins but most strongly to those containing C-terminal sequences. Two monoclonal antibodies (MAbs), 1E3 and RS348, capable of neutralizing the virus and inhibiting the viral fusion function, bound to all chimeras except that derived from the N-terminal PstI fragment, suggesting that their binding sites were located between amino acids 214 and 289. Further analysis of binding to expressed fragments from restriction enzyme digests and PCR amplification demonstrated that both antibodies bound to amino acids 253 to 289. MAb RS348 bound to 12-mer overlapping synthetic peptides containing the sequence 265 to 272 (PITNDQKK) but MAb 1E3 failed to bind to any 12-mer peptide derived from the F protein sequence. Immunization of mice with chimeric proteins containing the whole F protein coding sequence or amino acids 253 to 384, which includes the binding site of the two MAbs identified here, failed to induce antibodies that recognized the native RS virus F protein or could neutralize the virus. This suggests that either the beta-gal partner inhibits the immune response to the protein or that elements missing from the protein expressed in E. coli, perhaps conformational or added post-translation, contribute to the neutralizing antibody epitope.
Assuntos
Anticorpos Antivirais/imunologia , Proteína HN , Vírus Sinciciais Respiratórios/imunologia , Proteínas Virais de Fusão/imunologia , Proteínas Virais/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/sangue , Sequência de Bases , Epitopos , Escherichia coli/genética , Camundongos , Dados de Sequência Molecular , Testes de Neutralização , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/imunologia , Proteínas Recombinantes de Fusão/imunologia , Vírus Sinciciais Respiratórios/genética , Proteínas do Envelope ViralRESUMO
PURPOSE: To study the effects of iodinated radiographic contrast agents on proton relaxation in MR imaging. PATIENTS AND METHODS: Two patients were evaluated after the intrathecal administration of an iodinated nonionic contrast agent (Isovue) and five subjects with cranial tumors following the intravenous administration of an iodinated ionic contrast medium (Renografin). RESULTS: Both patients with subarachnoid iodinated contrast media demonstrated a relative reduction in T1 and/or T2 times using a spin-echo sequence, while four of five of the subjects with intracranial tumors (one glioma, one dural metastasis, three meningiomas) and intravenous enhancement revealed a visible MR effect. Confirmation of these in vivo observations was obtained by in vitro measurement of T1 and T2 while varying the concentration of the contrast media in saline. All iodinated contrast media showed progressively reduced relaxation times (T1 and T2) as the concentration of the agent was increased. The largest contributing relaxation mechanism is probably due to the binding and exchange of the surrounding water with the contrast molecules. CONCLUSION: The observed T1/T2 effects suggest that administration of iodinated contrast media in the period immediately prior to MR scanning may be contraindicated in selected cases due to the demonstrated alteration of MR signal intensity that may lead to diagnostic inaccuracies.