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1.
Pharm Pract (Granada) ; 19(2): 2353, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34221203

RESUMO

BACKGROUND: Patient satisfaction is one of the essential indicators for assessing the quality of healthcare services being delivered, including pharmacy ambulatory care service, as it determines the practicability and sustainability of the service provided. As such, pharmaceutical care services provided during medication therapy adherence clinic (MTAC) sessions need to be assessed to maximise its effectiveness and benefits to the patients. OBJECTIVE: This study aimed to assess the association between patient satisfaction and socio-demographic characteristics, as well as the predictors for patient satisfaction. METHODS: This was a cross-sectional study conducted at the medical outpatient department in Hospital Port Dickson from January until October 2019. Convenience sampling method was used to recruit potential study participants. Patient satisfaction was measured using Validated Patient Satisfaction with Pharmacist Services Questionnaire (PSPSQ2.0), consisted of quality of care and interpersonal relationship between pharmacist and patient domains. Descriptive data were presented as mean and standard deviation or numbers and percentages, while Independent Sample t-test, ANOVA and post-hoc analysis, and multiple linear regression were used for inferential data analysis. RESULTS: There were 37 (25%) diabetes MTAC, 36 (24.3%) respiratory MTAC, and 75 (50.7%) warfarin MTAC patients recruited. On average, the mean overall satisfaction score was 3.30(SD=0.43). The mean satisfaction score in the interpersonal relationship domain [3.35(SD=0.44)] was higher than the quality of care domain [3.26(SD=0.45)]. There was a significant association between gender, education level, and patient satisfaction towards pharmaceutical care service (p<0.05). Gender and education level statistically predicted respondents' satisfaction with MTAC services (p<0.001). CONCLUSIONS: The overall patient satisfaction towards MTAC services in this setting was high. Gender and education level were significant predictors for patient satisfaction. These findings could potentially contribute to the planning of MTAC services in the future.

2.
Pharm. pract. (Granada, Internet) ; 19(2)apr.- jun. 2021. tab
Artigo em Inglês | IBECS | ID: ibc-225537

RESUMO

Background: Patient satisfaction is one of the essential indicators for assessing the quality of healthcare services being delivered, including pharmacy ambulatory care service, as it determines the practicability and sustainability of the service provided. As such, pharmaceutical care services provided during medication therapy adherence clinic (MTAC) sessions need to be assessed to maximise its effectiveness and benefits to the patients. Objective: This study aimed to assess the association between patient satisfaction and socio-demographic characteristics, as well as the predictors for patient satisfaction. Methods: This was a cross-sectional study conducted at the medical outpatient department in Hospital Port Dickson from January until October 2019. Convenience sampling method was used to recruit potential study participants. Patient satisfaction was measured using Validated Patient Satisfaction with Pharmacist Services Questionnaire (PSPSQ2.0), consisted of quality of care and interpersonal relationship between pharmacist and patient domains. Descriptive data were presented as mean and standard deviation or numbers and percentages, while Independent Sample t-test, ANOVA and post-hoc analysis, and multiple linear regression were used for inferential data analysis. Results: There were 37 (25%) diabetes MTAC, 36 (24.3%) respiratory MTAC, and 75 (50.7%) warfarin MTAC patients recruited. On average, the mean overall satisfaction score was 3.30(SD=0.43). The mean satisfaction score in the interpersonal relationship domain [3.35(SD=0.44)] was higher than the quality of care domain [3.26(SD=0.45)]. There was a significant association between gender, education level, and patient satisfaction towards pharmaceutical care service (p<0.05). Gender and education level statistically predicted respondents' satisfaction with MTAC services (p<0.001) (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Satisfação do Paciente , Assistência Farmacêutica , Diabetes Mellitus/tratamento farmacológico , Estudos Transversais , Análise Multivariada , Fatores Sexuais , Fatores Etários , Malásia
3.
Ann R Coll Surg Engl ; 102(9): 737-743, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32820638

RESUMO

INTRODUCTION: Open thyroidectomy is the most common approach to thyroid surgery. However, 'scarless' (in the neck) endoscopic thyroidectomy, consisting of endoscopic and robotic surgery, is progressively being adopted for its perceived cosmetic benefits. This study aims to determine the patient's preferred surgical approach and to identify the factors that influence their decision. MATERIALS AND METHODS: A pilot study consisting of 100 patients with a surgical thyroid disorder were prospectively recruited from a single tertiary centre. An interviewer-administered survey was conducted. Demographic, socioeconomic status, scar perception and an adapted body image scale were evaluated to identify factors that shaped the patient's perception of the surgical approach. RESULTS: The mean age of participants was 54.5 ± 13.0 years; 72% were women and 87% Chinese. Of the 100 patients, 75 patients considered scarless endoscopic thyroidectomy as their preferred surgical approach while 25 patients opted for open thyroid surgery. Improvement in scar perception score between scarless endoscopic thyroidectomy and open thyroid surgery is associated with an increased willingness to choose scarless endoscopic thyroidectomy. The mean body image scale score was 6.9 ± 2.8, indicating no statistical difference between the surgical approaches. On multivariate analysis, improvement in scar perception score (odds ratio 3.38, 95% confidence interval 1.11-10.29) and having surgeon recommendation (odds ratio 6.38, 95% confidence interval 1.80-22.63) were independently associated with interest in scarless endoscopic thyroidectomy. CONCLUSION: Patients interest in undergoing scarless endoscopic thyroidectomy is driven by improved scar perception and surgeon's recommendation compared with open thyroid surgery.


Assuntos
Cicatriz/etiologia , Endoscopia/efeitos adversos , Preferência do Paciente/estatística & dados numéricos , Tireoidectomia/efeitos adversos , Atitude Frente a Saúde , Cicatriz/prevenção & controle , Cicatriz/psicologia , Estudos Transversais , Endoscopia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Preferência do Paciente/psicologia , Projetos Piloto , Estudos Prospectivos , Inquéritos e Questionários , Doenças da Glândula Tireoide/cirurgia , Tireoidectomia/métodos
4.
Mol Cancer Res ; 16(11): 1625-1640, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30037855

RESUMO

The most commonly utilized class of chemotherapeutic agents administered as a first-line therapy are antimitotic drugs; however, their clinical success is often impeded by chemoresistance and disease relapse. Hence, a better understanding of the cellular pathways underlying escape from cell death is critical. Mitotic slippage describes the cellular process where cells exit antimitotic drug-enforced mitotic arrest and "slip" into interphase without proper chromosome segregation and cytokinesis. The current report explores the cell fate consequence following mitotic slippage and assesses a major outcome following treatment with many chemotherapies, therapy-induced senescence. It was found that cells postslippage entered senescence and could impart the senescence-associated secretory phenotype (SASP). SASP factor production elicited paracrine protumorigenic effects, such as migration, invasion, and vascularization. Both senescence and SASP factor development were found to be dependent on autophagy. Autophagy induction during mitotic slippage involved the autophagy activator AMPK and endoplasmic reticulum stress response protein PERK. Pharmacologic inhibition of autophagy or silencing of autophagy-related ATG5 led to a bypass of G1 arrest senescence, reduced SASP-associated paracrine tumorigenic effects, and increased DNA damage after S-phase entry with a concomitant increase in apoptosis. Consistent with this, the autophagy inhibitor chloroquine and microtubule-stabilizing drug paclitaxel synergistically inhibited tumor growth in mice. Sensitivity to this combinatorial treatment was dependent on p53 status, an important factor to consider before treatment.Implications: Clinical regimens targeting senescence and SASP could provide a potential effective combinatorial strategy with antimitotic drugs. Mol Cancer Res; 16(11); 1625-40. ©2018 AACR.


Assuntos
Autofagia/fisiologia , Senescência Celular/fisiologia , Mitose/fisiologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Quinases Proteína-Quinases Ativadas por AMP , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Autofagia/efeitos dos fármacos , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Citocinas/metabolismo , Feminino , Células HCT116 , Células HEK293 , Xenoenxertos , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitose/efeitos dos fármacos , Neoplasias/metabolismo , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Proteínas Quinases/metabolismo , Transfecção , Peixe-Zebra
5.
J Colloid Interface Sci ; 465: 26-32, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26641561

RESUMO

Suppressing the Leidenfrost effect can significantly improve heat transfer from a heated substrate to a droplet above it. In this work, we demonstrate that by generating high frequency acoustic wave in the droplet, at sufficient vibration displacement amplitudes, the Leidenfrost effect can be suppressed due to the acoustic radiation pressure exerted on the liquid-vapor interface; strong capillary waves are observed at the liquid-vapor interface and subsequently leads to contact between the liquid and the heated substrate. Using this technique, with 10(5)Hz vibration frequency and 10(-6)m displacement amplitude of the acoustic transducer, a maximum of 45% reduction of the initial temperature (T0∼200-300°C) of the heated substrate can be achieved with a single droplet of volume 10(-5)l.

6.
Soft Matter ; 11(4): 775-84, 2015 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-25493924

RESUMO

The ability to suppress the Leidenfrost effect is of significant importance in applications that require rapid and efficient cooling of surfaces with temperature higher than the Leidenfrost point TSL. The Leidenfrost effect will result in substantial reduction in cooling efficiency and hence there have been a few different approaches to suppress the Leidenfrost effect. The majority of these approaches relies on fabricating micro/nano-structures on heated surfaces, others rely on inducing an electric field between the droplets and the heated surfaces. In this paper, we present an approach that induces low frequency vibrations (f∼10(2) Hz) on a heated surface to suppress the effect. By mapping the different magnitudes of surface acceleration [greek xi with two dots above]sversus different initial surface temperatures Ts of the substrate, three regimes that represent three distinct impact dynamics are analyzed. Regime-I represents gentle film boiling ([greek xi with two dots above]s∼10(2) m s(-2) and Ts∼TSL), which is associated with the formation of thin spreading lamella around the periphery of the impinged droplet; Regime-II ([greek xi with two dots above]s∼10(2) m s(-2) and Ts>TSL) represents film boiling, which is associated with the rebound of the impinged droplet due to the presence of a thick vapor layer; Regime-III ([greek xi with two dots above]s∼10(3) m s(-2) and Ts∼TSL) represents contact boiling, which is associated with the ejection of tiny droplets due to the direct contact between the droplet and the heated surface. The estimated cooling enhancement for Regime-I is between 10% and 95%, Regime-II is between 5% and 15%, and Regime-III is between 95% and 105%. The improvement in cooling enhancement between Regime-I (strong Leidenfrost effect) and Regime-III (suppressed Leidenfrost effect) is more than 80%, demonstrating the effectiveness of using low frequency vibrations to suppress the Leidenfrost effect.

7.
Clin Nephrol ; 74(5): 372-83, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20979946

RESUMO

This review of 2,586 renal biopsies over the past 3 decades in Singapore documents the changing pattern of glomerulonephritis (GN) from that of a third world country to that of a developed nation. In the 1st decade, mesangial proliferative glomerulonephritis was the most common form of primary GN, just as it was in the surrounding Asian countries. In the 2nd decade, the prevalence of mesangial proliferative GN decreased with a rise in membranous, GN which is also seen in China and Thailand. In the 3rd decade, there was a dramatic increase in focal sclerosing glomerulosclerosis. This increase reflects aging and obesity in keeping with more developed countries like Australia, India, Thailand and the United States of America. IgA nephritis remains the most common GN. Apart from the geographical influence, other socioeconomic factors play a significant role in the evolution of the renal biopsy pattern. Mesangial proliferative GN remains prevalent in many Asian countries, but in Singapore the prevalence is decreasing just as it is in Japan, Korea and Malaysia. Worldwide, the prevalence of focal sclerosing glomerulosclerosis continues to increase in many countries.


Assuntos
Glomerulonefrite/epidemiologia , Rim/patologia , Adolescente , Adulto , Idoso , Biópsia , Distribuição de Qui-Quadrado , Países Desenvolvidos/estatística & dados numéricos , Países em Desenvolvimento/estatística & dados numéricos , Feminino , Mesângio Glomerular/patologia , Glomerulonefrite/patologia , Glomerulonefrite por IGA/epidemiologia , Glomerulonefrite por IGA/patologia , Glomerulonefrite Membranoproliferativa/epidemiologia , Glomerulonefrite Membranoproliferativa/patologia , Glomerulonefrite Membranosa/epidemiologia , Glomerulonefrite Membranosa/patologia , Glomerulosclerose Segmentar e Focal/epidemiologia , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Medição de Risco , Fatores de Risco , Singapura/epidemiologia , Fatores de Tempo , Adulto Jovem
8.
Clin Rheumatol ; 29(5): 551-3, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20119843

RESUMO

An increase in reports of systemic lupus erythematosus (SLE) related to tumour necrosis factor inhibitor (TNFi) therapy has recently been highlighted. We report new-onset SLE in a 22-year-old woman after 13 months of infliximab for ankylosing spondylitis (AS). Lupus symptoms promptly resolved and serologic abnormalities improved after infliximab was ceased. A flare of AS symptoms after 2 months prompted cautious introduction of an alternative TNFi, etanercept. At 14 months follow-up, neither clinical nor serologic flare of lupus had occurred. To our knowledge, this is the third reported case of infliximab-related lupus that did not recur on switching to an alternative TNFi.


Assuntos
Anticorpos Monoclonais/farmacologia , Imunoglobulina G/farmacologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Antirreumáticos/farmacologia , Autoimunidade , DNA/metabolismo , Etanercepte , Feminino , Humanos , Inflamação , Infliximab , Lúpus Eritematoso Sistêmico/sangue , Qualidade de Vida , Receptores do Fator de Necrose Tumoral , Espondilite Anquilosante/sangue , Fatores de Tempo
9.
J Neurochem ; 99(2): 657-69, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17029606

RESUMO

The murine 1C11 cell line, derived from F9 pluripotent teratocarcinoma cells, exhibits features of a bipotential neuronal precursor as it converts into serotonergic or catecholaminergic neurons under appropriate induction. In order to point out molecular markers expressed in this early neuroectodermic commitment, we used a cDNA subtractive hybridization method. The 105 different isolated cDNAs represented 75 known genes, expressed sequence tags (EST) or genomic fragments. A majority of known proteins encoded by these sequences are involved in cellular mobility or migration. We characterized two sequences showing identities with ESTs and we called them Noxp20 and Noxp70. The Noxp20 transcript encodes a putative protein with a predicted caspase recruitment domain and the Noxp70 transcript encodes a putative protein displaying a Zn-finger domain. Consistent with their roles in neuronal cell development, in situ hybridization showed that Noxp20 and Noxp70 are over-expressed in brain. At embryonic days 12 and 15, Noxp20 is strongly expressed in the ventricular and intermediate zones of the brain and of the spinal cord. At embryonic day 15, Noxp70 was found to be strongly expressed in the ventricular zone around the telencephalic ventricle, and to a lower extent in the thalamus and hypothalamus. At post-natal day 10, Noxp20 mRNA was detected in the dentate gyrus, the hippocampus, the cerebellum and the olfactory bulb.


Assuntos
Proteínas de Transporte/metabolismo , Diferenciação Celular/fisiologia , Sistema Nervoso Central/embriologia , Ectoderma/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Células-Tronco/metabolismo , Sequência de Aminoácidos , Animais , Proteínas Relacionadas à Autofagia , Sequência de Bases , Biomarcadores/análise , Biomarcadores/química , Biomarcadores/metabolismo , Encéfalo/citologia , Encéfalo/embriologia , Encéfalo/metabolismo , Proteínas de Transporte/química , Proteínas de Transporte/isolamento & purificação , Linhagem Celular Transformada , Linhagem Celular Tumoral , Sistema Nervoso Central/citologia , Sistema Nervoso Central/metabolismo , Ectoderma/citologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Camundongos , Dados de Sequência Molecular , Células NIH 3T3 , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/isolamento & purificação , Estrutura Terciária de Proteína/fisiologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Medula Espinal/citologia , Medula Espinal/embriologia , Medula Espinal/metabolismo , Células-Tronco/citologia , Teratocarcinoma
10.
Int J Gynecol Cancer ; 15(4): 624-9, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16014116

RESUMO

Pelvic exenteration is used as therapeutic option for advanced or recurrent cancer in the pelvis. We determined the complications of and the survival after pelvic exenteration. The study was performed as a retrospective cohort (n = 62) study from January 1, 1989, until January 1, 2000. Descriptive statistics were used. Survival was estimated according to the Kaplan-Meier life table. The operative mortality was 1.6%. Seventy-five percent of the patients had postoperative complications of which ileus and urinary tract infection were the most common. Late complications occurred in 83% of the patients. Recurrent disease was observed in 38% of the women, whereas 50% had died on January 1, 2000. Five-years disease-free and overall survival were 42% (confidence interval [CI] +/- 14%) and 46% (CI +/- 14%), respectively. Elderly patients (> 70 years old) do not experience more complications. Despite considerable morbidity, pelvic exenteration is a therapeutic option for survival, even for patients of 70 years and older.


Assuntos
Neoplasias dos Genitais Femininos/cirurgia , Exenteração Pélvica , Complicações Pós-Operatórias , Neoplasias Urológicas/cirurgia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Morbidade , Exenteração Pélvica/efeitos adversos , Exenteração Pélvica/métodos , Estudos Retrospectivos , Resultado do Tratamento
11.
Gynecol Oncol ; 93(3): 610-4, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15196852

RESUMO

OBJECTIVES: Pelvic exenteration, for gynecological and urological cancer, is an extensive and mutilating procedure. The 5-year survival rate is fairly good (40-60%), but little is known about the long-term quality of life. METHODS: In this retrospective cohort study, the quality of life was assessed using the EORTC QLQ-C30 (version 3.0) and the EORTC QLQ-OV28 questionnaires. RESULTS: Healthy females and those who underwent pelvic exenteration for a gynecological or urological malignancy reported comparable levels of emotional functioning and general quality of life. More physical, sexual, and social problems were, however, noted after exenteration. Younger patients and patients who underwent total pelvic exenteration had the most difficulty in adapting to daily life, disease, and treatment. They also had a worse body image, and the influence of the operation on their sex life was greater compared to other patient groups of this study. CONCLUSION: Despite the immense effect of pelvic exenteration on physical, sexual, and social functioning, women who underwent this procedure reported similar levels of emotional functioning and general quality of life compared to healthy women. Adaptation and the mechanism of response shift presumably play an important role.


Assuntos
Neoplasias dos Genitais Femininos/cirurgia , Exenteração Pélvica , Qualidade de Vida , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Estudos de Coortes , Feminino , Neoplasias dos Genitais Femininos/psicologia , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Exenteração Pélvica/efeitos adversos , Exenteração Pélvica/métodos , Exenteração Pélvica/psicologia , Estudos Retrospectivos , Inquéritos e Questionários , Neoplasias da Bexiga Urinária/psicologia
12.
BJU Int ; 93(7): 1001-4, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15142151

RESUMO

OBJECTIVE: To estimate the effect of nocturia on quality of life (QoL) and to assess the associated effects of sleep problems. SUBJECTS AND METHODS: From a random sample of Dutch adults (>/= 18 years old) 1000 were selected after stratification to complete a written questionnaire. Respondents (819) were distributed over three groups: a target group (189, who felt bothered by >/= one void/night); a reference group 1 (120 reporting >/= two voids/night but with no bother); and reference group 2 (510, with 0-1 voids/night). Nocturia, other lower urinary tract symptoms and perceived impact on life were measured using the Bristol Lower Urinary Tract Symptoms Questionnaire (B-LUTS). Sleep problems were measured using the Sleep Wake Experience List (SWEL) and QoL using two subscales from the RAND-36, i.e. 'physical functioning' and 'mental health'. RESULTS: The perceived impact on life was highest in the target group (P < 0.05), which also had more sleep problems and scored lower on the QoL scores than both reference groups (P < 0.05). Statistically significant differences in mental health and physical functioning between the target and reference groups became insignificant after correcting for sleep problems, indicating that the effect of nocturia (with bother) is mediated by sleep problems. CONCLUSIONS: Nocturia may lead to sleep insufficiency and consequently to a decrease in mental and physical health. Patients who consult a doctor for nocturia should thus be treated adequately. In addition, it is worthwhile for doctors to routinely check if patients who contact them for sleep problems also have nocturia.


Assuntos
Qualidade de Vida , Transtornos do Sono-Vigília/etiologia , Transtornos Urinários/psicologia , Adulto , Idoso , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos
13.
Tissue Antigens ; 63(5): 453-7, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15104676

RESUMO

"Cancer germline" genes such as those of the MAGE family are expressed in many tumors and in male germline cells but are silent in normal tissues. They encode shared tumor-specific antigens that have been used in therapeutic vaccination trials of cancer patients. We report the identification of a new MAGE-1-encoded peptide that is recognized by a cytolytic T-lymphocyte (CTL) clone on human leukocyte antigen (HLA)-B*5701. The sequence of the peptide, corresponding to position 102-112 of the MAGE-1 protein sequence, is ITKKVADLVGF. When tumor cells expressing MAGE-1 were transfected with HLA-B*5701, they were lyzed by the CTL clone, indicating that the peptide is processed in tumor cells and can, therefore, be used as a target for anti-tumoral vaccination.


Assuntos
Antígenos de Neoplasias/imunologia , Antígenos HLA-B/imunologia , Proteínas de Neoplasias/imunologia , Peptídeos/imunologia , Linfócitos T Citotóxicos/imunologia , Antígenos de Neoplasias/genética , Sequência de Bases , Linhagem Celular Tumoral , Transformação Celular Viral , Herpesvirus Humano 4 , Humanos , Antígenos Específicos de Melanoma , Proteínas de Neoplasias/genética
14.
Tissue Antigens ; 62(5): 426-32, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14617050

RESUMO

'Cancer-germline' genes such as those of the MAGE family are expressed in many tumors and in male germline cells, but are silent in other normal tissues. They encode shared tumor-specific antigens, which have been used in small therapeutic vaccination trials of cancer patients. Gene MAGE-4, which is expressed in more than 50% of carcinomas of esophagus, head and neck, lung, and bladder, has two known alleles. Using PCR amplifications and digestions of the amplified product, we found that one third of the MAGE-4-positive samples expressed MAGE-4a. We folded HLA-A1 tetramers with peptide MAGE-4a169-177 EVDPASNTY, which is homologous to MAGE-1- and MAGE-3-encoded peptides recognized on HLA-A1 by cytolytic T lymphocytes. Blood lymphocytes from an individual without cancer were directly labelled with these A1/MAGE-4 tetramers. The very rare cells that were stained were sorted by flow cytometry and cloned. We isolated a cytolytic T-lymphocyte clone that lyzed specifically cells pulsed with this MAGE-4 peptide and HLA-A1 tumor cells expressing MAGE-4a, demonstrating that this antigenic peptide is processed efficiently in tumor cells. This peptide might therefore be useful for therapeutic antitumoral vaccination.


Assuntos
Proteínas de Neoplasias/imunologia , Peptídeos/imunologia , Linfócitos T Citotóxicos/imunologia , Antígenos de Neoplasias , Citometria de Fluxo , Antígeno HLA-A1/imunologia , Humanos , Proteínas de Neoplasias/metabolismo , Peptídeos/metabolismo , Linfócitos T Citotóxicos/metabolismo , Células Tumorais Cultivadas
15.
Int J Hyperthermia ; 19(5): 481-97, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12944164

RESUMO

A study was performed on regional hyperthermia for patients with locally advanced prostate carcinoma. The primary objective was to analyse the thermometry data with an emphasis on the possibility of replacing invasive thermometry by tumour-related intra-luminal thermometry. Fourteen patients were treated with a combination of conformal external beam radiotherapy (70 Gy) and hyperthermia. Hyperthermia was delivered using the Coaxial TEM system, one treatment per week, to a total of five treatments. Thermometry was performed in bladder, urethra, rectum and esophagus. Invasive thermometry in the prostate was carried out during one or two treatments for each patient by placing transperineally a central and a peripheral catheter. Heterogeneous temperature distributions were measured in the prostate. The mean average invasive temperature range was 1.1 degrees C. Due to the temperature heterogeneity and a limited number of thermometry sensors (mean 7, range 2-13), large variability between treatments and patients existed regarding achieved temperatures and dose. The mean invasive T90 was 40.2 +/- 0.6 degrees C and T50 was 40.8 +/- 0.6 degrees C. The mean Cum min T90>40.5 degrees C per treatment was 22 (range 0-50). Importantly, intra-luminal temperatures did not reliably predict invasively measured temperatures. Invasive thermometry, therefore, remains compulsory to calculate a thermal dose for an individual patient. Changes in temperature during treatment, measured by the urethral sensors, corresponded well with changes in temperature measured by the individual invasive sensors. Similar comparison of rectal temperature changes with intra-prostatic temperature changes was not as predictive. The similarity in temperature changes between the urethral and interstial sites, suggests that urethral temperatures are sufficient for treatment optimization. The SAR profile did not correspond with the temperature profile indicating heterogeneous perfusion. Although regional hyperthermia in combination with external beam radiotherapy for locally advanced prostate carcinoma is clinically feasible, the question on the importance of invasive thermometry remains.


Assuntos
Hipertermia Induzida/métodos , Neoplasias da Próstata/radioterapia , Radioterapia Conformacional , Termômetros , Idoso , Temperatura Corporal , Terapia Combinada , Esôfago , Estudos de Viabilidade , Temperatura Alta , Humanos , Masculino , Pessoa de Meia-Idade , Reto , Uretra
16.
Eur Urol ; 44(1): 51-6, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12814675

RESUMO

OBJECTIVE: Photodynamic diagnosis (PDD) for the detection of bladder cancer has become a diagnostic tool in several hospitals. Several studies have reported different rates of false positive biopsies using 5-aminolevulinic acid induced fluorescence. In this study we evaluated the effect of previous intravesical therapy on the false positive biopsy rate. METHODS: Two hours prior to endoscopy 1.5g ALA dissolved in 50ml 1.4% NaHCO(3) solution was instilled intravesically. For fluorescence excitation a blue light source (D-light, Karl Storz) was used. Under white and fluorescence light guidance, tumor locations were recorded, cold cup biopsies were taken and tumors were resected. Patients were divided into 3 groups, last intravesical therapy (IVT) less than 6 months prior to PDD, last IVT longer than 6 months before PDD and no previous IVT. RESULTS: In total 917 biopsies were taken in 249 procedures of fluorescent and non-fluorescent areas. White light endoscopy revealed 270 and PDD 378 of in total 390 tumors, resulting in a sensitivity of 97% and specificity of 49% for PDD. Pathologic evaluation considered 270 fluorescent biopsies as false positive. The rate of false positive biopsies was 25.7% in the group No IVT, 30.6% in the group PDD-IVT >6 months, whereas in the group "within 6 months after intravesical therapy" the rate was 39.6% (p<0.025). When premalignant lesions such as dysplasia II are considered tumor the difference between the groups is even more significant (p<0.001). CONCLUSIONS: The procedure has a high sensitivity for superficial bladder cancer and decreases the number of overlooked lesions. Recent intravesical therapy results in significantly more false positive fluorescent biopsies. Since patient outcome might predominantly be determined by the early detection and subsequent treatment of (pre)malignant tissue we suggest that PDD is justified even shortly after intravesical therapy.


Assuntos
Ácido Aminolevulínico , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/terapia , Mycobacterium bovis , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/diagnóstico , Estudos de Coortes , Cistoscopia/métodos , Reações Falso-Positivas , Feminino , Fluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes , Probabilidade , Estudos Prospectivos , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/diagnóstico
17.
J Urol ; 170(1): 264-7, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12796701

RESUMO

PURPOSE: We evaluated in vivo the role of muscarinic receptors on ureteral peristaltic frequency and contraction force in a large animal model using pharmacological manipulation. MATERIALS AND METHODS: A total of 12 female pigs weighing a mean +/- SEM of 72 +/- 4 kg were chronically instrumented using an electronic pressure monitoring catheter in the right ureter. Furthermore, nephrostomy, arterial, venous and cystostomy catheters were placed. Ureteral peristalsis was repeatedly recorded before and after the administration of atropine and carbachol. RESULTS: Systemic and local effects of the 2 agents were observed. Compared with controls we recorded an increase in mean ureteral peristaltic frequency (2.0 +/- 0.3 versus 1.6 +/- 0.6 minutes-1, p <0.05) and mean contraction force (50.1 +/- 1.4 versus 45.3 +/- 1.7 cm H(2)O, p <0.05) during renal pelvis perfusion with 0.25 ml per minute saline. Administration of atropine or carbachol modulated neither the force of contraction nor the frequency of ureteral peristalsis in vivo (p >0.05). CONCLUSIONS: Smooth muscle motor activity at the mid and distal ureter is not modulated by muscarinic receptors. Peristaltic frequency is directly related to the pyelocaliceal load during a rate of diuresis not exceeding animal normal diuresis plus 0.25 ml per minute. Ureteral contraction force increases only in the mid ureter with increased diuresis.


Assuntos
Músculo Liso/fisiologia , Receptores Muscarínicos/fisiologia , Ureter/fisiologia , Animais , Feminino , Modelos Animais , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Receptores Muscarínicos/efeitos dos fármacos , Suínos , Ureter/efeitos dos fármacos
18.
BJU Int ; 91(7): 627-30, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12699473

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of the Urolume endourethral self-expandable metallic stent (American Medical Systems, MI, USA) in treating urethral strictures, based on a follow-up of> 10 years. PATIENTS AND METHODS: Between November 1989 and June 1990, the Urolume stent was inserted into 15 patients (aged 25-77 years) who had recurrent urethral strictures. The mean duration of stricture before stent insertion was 10.9 years. The patients (all men) were followed using a questionnaire and uroflowmetry, and if necessary, retrograde cysto-urethrography and/or urethroscopy and/or X-ray urodynamics. RESULTS: Two failures were caused by excessive tissue proliferation in the stent, which ended in stent removal or a suprapubic catheter. Another two stents were removed because of discomfort or pain. Two patients developed stenosis in the stent after 7 and 9 years. In the final evaluation only two of the 15 patients were satisfied with their stent. The mean maximum urinary flow rate at the last follow-up was 15 mL/s, and half the patients noted 'stent' incontinence. Lower urinary tract infections, urge and stress incontinence, and discomfort with ejaculation, were all symptoms perceived at the last follow-up. CONCLUSION: The long-term results of the Urolume stent in this study weaken the optimistic early results. Only two of the 15 patients were satisfied with their stent.


Assuntos
Stents/efeitos adversos , Estreitamento Uretral/terapia , Adulto , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Disfunções Sexuais Fisiológicas/etiologia , Estreitamento Uretral/fisiopatologia , Cateterismo Urinário , Incontinência Urinária/etiologia , Urodinâmica
19.
Eur J Cancer ; 39(1): 70-7, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12504661

RESUMO

Fifty-seven patients with MAGE-3-positive measurable metastatic cancer, most of them with melanoma, were vaccinated with escalating doses of a recombinant MAGE-3 protein combined with a fixed dose of the immunological adjuvant SBAS-2, which contained MPL and QS21. The immunisation schedule included 4 intramuscular (i.m.) injections at 3-week intervals. Patients whose tumour stabilised or regressed after 4 vaccinations received 2 additional vaccinations at 6-week intervals. The vaccine was generally well tolerated. Among the 33 melanoma patients who were evaluable for tumour response, we observed 2 partial responses, 2 mixed responses and 1 stabilisation. Time to progression in these 5 patients varied from 4 to 29 months. In addition, a partial response lasting 10 months was observed in 1 of the 3 metastatic bladder cancer patients included. None of the tumour responses described above involved visceral metastases. Immunological responses to the vaccine will be reported separately.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Antígenos de Neoplasias/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas de Neoplasias/administração & dosagem , Neoplasias/terapia , Adulto , Idoso , Vacinas Anticâncer/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células de Transição/terapia , Feminino , Humanos , Imunização , Lipídeo A/administração & dosagem , Lipídeo A/análogos & derivados , Neoplasias Pulmonares/terapia , Masculino , Melanoma/terapia , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias/patologia , Proteínas Recombinantes/administração & dosagem , Saponinas/administração & dosagem , Neoplasias Cutâneas/terapia , Análise de Sobrevida , Resultado do Tratamento , Neoplasias da Bexiga Urinária/terapia
20.
Tissue Antigens ; 60(5): 365-71, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12492812

RESUMO

'Cancer-germline' genes such as those of the MAGE family are expressed in many tumors and in male germline cells, but are silent in normal tissues. They encode shared tumor-specific antigens, which have been used in therapeutic vaccination trials of cancer patients. MAGE-A4 is expressed in more than 50% of carcinomas of esophagus, head and neck, lung, and bladder. We report here the identification of a new MAGE-A4 encoded peptide, which is recognized by a cytolytic T lymphocyte (CTL) clone on HLA-B*3701. The sequence of the peptide is SESLKMIF. It corresponds to the MAGE-A4156-163 protein sequence. When tumor cells expressing MAGE-A4 were transfected with HLA-B*3701, they were recognized by the CTL clone, demonstrating that the peptide ought to be processed in tumor cells and could therefore serve as a target for therapeutic antitumoral vaccination.


Assuntos
Apresentação de Antígeno , Antígenos de Neoplasias/imunologia , Antígenos HLA-B/imunologia , Proteínas de Neoplasias , Neoplasias/imunologia , Linfócitos T Citotóxicos/imunologia , Apresentação de Antígeno/imunologia , Células Cultivadas , Células Dendríticas/imunologia , Antígeno HLA-B37 , Humanos
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