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1.
Br J Haematol ; 202(1): 65-73, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37082780

RESUMEN

Large B-cell lymphoma (LBCL) patients with comorbidities and/or advanced age are increasingly considered for treatment with CD19 CAR T, but data on the clinical benefit of CAR T in the less fit patient population are still limited. We analysed outcomes of consecutive patients approved for treatment with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) by the UK National CAR T Clinical Panel, according to fitness for autologous stem cell transplant (ASCT). 81/404 (20%) of approved patients were deemed unfit for ASCT. Unfit patients were more likely to receive tisa-cel versus axi-cel (52% vs. 48%) compared to 20% versus 80% in ASCT-fit patients; p < 0.0001. The drop-out rate from approval to infusion was significantly higher in the ASCT-unfit group (34.6% vs. 23.5%; p = 0.042). Among infused patients, response rate, progression-free and overall survival were similar in both cohorts. CAR T was well-tolerated in ASCT-unfit patients with an incidence of grade ≥3 cytokine release syndrome and neurotoxicity of 2% and 11%, respectively. Results from this multicentre real-world cohort demonstrate that CD19 CAR T can be safely delivered in carefully selected older patients and patients with comorbidities who are not deemed suitable for transplant.


Asunto(s)
Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Trasplantes , Humanos , Autoinjertos , Trasplante Autólogo , Proteínas Adaptadoras Transductoras de Señales , Antígenos CD19 , Síndrome de Liberación de Citoquinas , Linfoma de Células B Grandes Difuso/terapia , Inmunoterapia Adoptiva/efectos adversos
2.
Ann Oncol ; 31(9): 1251-1259, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32464282

RESUMEN

BACKGROUND: Outcomes for patients with high-risk diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP chemotherapy are suboptimal but, to date, no alternative regimen has been shown to improve survival rates. This phase 2 trial aimed to assess the efficacy of a Burkitt-like approach for high-risk DLBCL using the dose-intense R-CODOX-M/R-IVAC regimen. PATIENTS AND METHODS: Eligible patients were aged 18-65 years with stage II-IV untreated DLBCL and an International Prognostic Index (IPI) score of 3-5. Patients received alternating cycles of CODOX-M (cyclophosphamide, vincristine, doxorubicin and high-dose methotrexate) alternating with IVAC chemotherapy (ifosfamide, etoposide and high-dose cytarabine) plus eight doses of rituximab. Response was assessed by computed tomography after completing all four cycles of chemotherapy. The primary end point was 2-year progression-free survival (PFS). RESULTS: A total of 111 eligible patients were registered; median age was 50 years, IPI score was 3 (60.4%) or 4/5 (39.6%), 54% had a performance status ≥2 and 9% had central nervous system involvement. A total of 85 patients (76.6%) completed all four cycles of chemotherapy. There were five treatment-related deaths (4.3%), all in patients with performance status of 3 and aged >50 years. Two-year PFS for the whole cohort was 67.9% [90% confidence interval (CI) 59.9-74.6] and 2-year overall survival was 76.0% (90% CI 68.5-82.0). The ability to tolerate and complete treatment was lower in patients with performance status ≥2 who were aged >50 years, where 2-year PFS was 43.5% (90% CI 27.9-58.0). CONCLUSIONS: This trial demonstrates that R-CODOX-M/R-IVAC is a feasible and effective regimen for the treatment of younger and/or fit patients with high-risk DLBCL. These encouraging survival rates demonstrate that this regimen warrants further investigation against standard of care. TRIAL REGISTRATION: ClinicalTrials.gov (NCT00974792) and EudraCT (2005-003479-19).


Asunto(s)
Linfoma de Burkitt , Linfoma de Células B Grandes Difuso , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Burkitt/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Humanos , Ifosfamida/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Persona de Mediana Edad , Prednisona/uso terapéutico , Rituximab/uso terapéutico , Reino Unido , Vincristina/uso terapéutico , Adulto Joven
3.
J Intern Med ; 285(6): 681-692, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30811713

RESUMEN

BACKGROUND: The increasing incidence of diffuse large B-cell lymphoma (DLBCL) in ageing populations places a significant burden on healthcare systems. Co-morbidity, frailty, and reduced organ and physiological reserve contribute to treatment-related complications. The optimal dose intensity of R-CHOP to optimize outcome across different ages with variable frailty and comorbidity burden is unclear. OBJECTIVES AND METHODS: We examined the influence of intended (IDI) and relative (RDI) dose intensity of the combination of cyclophosphamide and doxorubicin, age and comorbidity on outcomes for DLBCL patients ≥70 years in a representative, consecutive cohort across eight UK centres (2009-2018). We determined predictors of survival using multivariable Cox regression, and predictors of recurrence before death using competing risks regression. RESULTS: Porgression-free survival (PFS) and overall survival (OS) were significantly inferior in patients ≥80 vs. 70-79 years (P < 0.001). In contrast, 2-year cumulative relapse incidence, when accounting for non-relapse mortality as a competing risk, was no different between 70-79 vs. ≥80 years (P = 0.27) or comorbidity status (CIRS-G: 0-6 vs. >6) (P = 0.27). In 70-79 years, patients with an IDI ≥80% had a significantly improved PFS and OS (P < 0.001) compared to IDI < 80%. Conversely, in patients ≥80 years, there was no difference in PFS (P = 0.88) or OS (P = 0.75) according to IDI <80% vs. ≥80%. On multivariable analysis, when comparing by age, there was a significantly higher cumulative relapse rate for patients aged 70-79 years with an IDI <80% (vs. >80%) (P = 0.04) but not for patients ≥80 years comparing IDI (P = 0.32). CONCLUSION: 'R-mini-CHOP' provides adequate lymphoma-specific disease control and represents a reasonable treatment option in elderly patients ≥80 years aiming for cure.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Distribución por Edad , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Comorbilidad , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Incidencia , Linfoma de Células B Grandes Difuso/epidemiología , Masculino , Prednisona/administración & dosificación , Recurrencia , Estudios Retrospectivos , Rituximab/administración & dosificación , Resultado del Tratamiento , Vincristina/administración & dosificación
4.
Opt Express ; 27(21): 30810-30818, 2019 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-31684324

RESUMEN

By exploiting the quantised nature of light, we demonstrate a sub-shot-noise scanning optical transmittance microscope. Our microscope demonstrates, with micron scale resolution, a factor of improvement in precision of 1.76(9) in transmittance estimation gained per probe photon relative to the theoretical model, a shot-noise-limited source of light, in an equivalent single-pass classical version of the same experiment using the same number of photons detected with a 90% efficient detector. This would allow us to observe photosensitive samples with nearly twice the precision, without sacrificing image resolution or increasing optical power to improve signal-to-noise ratio. Our setup uses correlated twin-beams produced by parametric down-conversion, and a hybrid detection scheme comprising photon-counting-based feed-forward and a highly efficient CCD camera.

6.
Ann Oncol ; 28(10): 2511-2516, 2017 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-28961838

RESUMEN

BACKGROUND: Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is associated with a dismal prognosis. Here, we report an analysis of CNS relapse for patients treated within the UK NCRI phase III R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) 14 versus 21 randomised trial. PATIENTS AND METHODS: The R-CHOP 14 versus 21 trial compared R-CHOP administered two- versus three weekly in previously untreated patients aged ≥18 years with bulky stage I-IV DLBCL (n = 1080). Details of CNS prophylaxis were retrospectively collected from participating sites. The incidence and risk factors for CNS relapse including application of the CNS-IPI were evaluated. RESULTS: 177/984 patients (18.0%) received prophylaxis (intrathecal (IT) methotrexate (MTX) n = 163, intravenous (IV) MTX n = 2, prophylaxis type unknown n = 11 and IT MTX and cytarabine n = 1). At a median follow-up of 6.5 years, 21 cases of CNS relapse (isolated n = 11, with systemic relapse n = 10) were observed, with a cumulative incidence of 1.9%. For patients selected to receive prophylaxis, the incidence was 2.8%. Relapses predominantly involved the brain parenchyma (81.0%) and isolated leptomeningeal involvement was rare (14.3%). Univariable analysis demonstrated the following risk factors for CNS relapse: performance status 2, elevated lactate dehydrogenase, IPI, >1 extranodal site of disease and presence of a 'high-risk' extranodal site. Due to the low number of events no factor remained significant in multivariate analysis. Application of the CNS-IPI revealed a high-risk group (4-6 risk factors) with a 2- and 5-year incidence of CNS relapse of 5.2% and 6.8%, respectively. CONCLUSION: Despite very limited use of IV MTX as prophylaxis, the incidence of CNS relapse following R-CHOP was very low (1.9%) confirming the reduced incidence in the rituximab era. The CNS-IPI identified patients at highest risk for CNS recurrence. CLINICALTRIALS.GOV: ISCRTN number 16017947 (R-CHOP14v21); EudraCT number 2004-002197-34.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Sistema Nervioso Central/patología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Esquema de Medicación , Femenino , Humanos , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Prednisona/administración & dosificación , Estudios Prospectivos , Rituximab/administración & dosificación , Vincristina/administración & dosificación
7.
Ann Oncol ; 28(7): 1540-1546, 2017 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-28398499

RESUMEN

BACKGROUND: There is an on-going debate whether 2- or 3-weekly administration of R-CHOP is the preferred first-line treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL). The UK NCRI R-CHOP14v21 randomized phase 3 trial did not demonstrate a difference in outcomes between R-CHOP-14 and R-CHOP-21 in newly diagnosed DLBCL patients aged 19-88 years, but data on elderly patients have not been reported in detail so far. Here, we provide a subgroup analysis of patients ≥60 years treated on the R-CHOP14v21 trial with extended follow-up. PATIENTS AND METHODS: Six hundred and four R-CHOP14v21 patients ≥60 years were included in this subgroup analysis, with a median follow-up of 77.7 months. To assess the impact of MYC rearrangements (MYC-R) and double-hit-lymphoma (DHL) on outcome in elderly patients, we performed a joint analysis of cases with available molecular data from the R-CHOP14v21 (N = 217) and RICOVER-60 (N = 204) trials. RESULTS: Elderly DLBCL patients received high dose intensities with median total doses of ≥98% for all agents. Toxicities were similar in both arms with the exception of more grade ≥3 neutropenia (P < 0.0001) and fewer grade ≥3 thrombocytopenia (P = 0.05) in R-CHOP-21 versus R-CHOP-14. The elderly patient population had a favorable 5-year overall survival (OS) of 69% (95% CI: 65-73). We did not identify any subgroup of patients that showed differential response to either regimen. In multivariable analysis including individual factors of the IPI, gender, bulk, B2M and albumin levels, only age and B2M were of independent prognostic significance for OS. Molecular analyses demonstrated a significant impact of MYC-R (HR = 1.96; 95% CI: 1.22-3.16; P = 0.01) and DHL (HR = 2.21; 95% CI: 1.18-4.11; P = 0.01) on OS in the combined trial cohorts, independent of other prognostic factors. CONCLUSIONS: Our data support equivalence of both R-CHOP application forms in elderly DLBCL patients. Elderly MYC-R and DHL patients have inferior prognosis and should be considered for alternative treatment approaches. TRIAL NUMBERS: ISCRTN 16017947 (R-CHOP14v21); NCT00052936 (RICOVER-60).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores de Tumor/genética , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-6/genética , Proteínas Proto-Oncogénicas c-myc/genética , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Esquema de Medicación , Femenino , Reordenamiento Génico , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Selección de Paciente , Medicina de Precisión , Prednisona/administración & dosificación , Prednisona/efectos adversos , Factores de Riesgo , Rituximab , Factores de Tiempo , Resultado del Tratamiento , Reino Unido , Vincristina/administración & dosificación , Vincristina/efectos adversos
8.
Ann Oncol ; 25(1): 236-40, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24356634

RESUMEN

BACKGROUND: Advanced GISTs are incurable, but often treatable for years with tyrosine kinase inhibitors (TKIs). The majority of GISTs harbor an oncogenic activating mutation in KIT or PDGFRA. Inhibition of this activating mutation with TKIs most often leads to durable disease control for many patients. However, almost all patients develop resistance to these TKIs, typically due to the development of secondary mutations, heralding the need for new therapeutic options. We conducted a phase II study evaluating the efficacy and toxicity of pazopanib, a broad spectrum TKI inhibiting KIT, VEGFRs (-1, -2, and -3), and PDGFR (-α and-ß) in patients with advanced GIST following failure of at least imatinib and sunitinib. METHODS: Patients received pazopanib 800 mg orally once daily. All patients were assessed for efficacy with CT scans every 8 weeks (two cycles). Patients continued pazopanib until progression or unacceptable toxicity. The primary end point was the 24-week nonprogression [complete response+partial response+stable disease (SD)] rate (NPR) per RECIST 1.1. Secondary end points included PFS, OS, and toxicity. RESULTS: Between August 2011 and September 2012, a total of 25 patients were treated at two institutions. Median number of prior therapy was 3 (range 2-7). A total of 90 cycles of pazopanib were administered, with a median of two cycles (range 1 to 17+) per patient. Best response of SD at any time was observed in 12 (48%) patients. The NPR was 17% [95% confidence interval (CI) 4.5-37]. All but one patient discontinued protocol either due to PD (n = 19) or intolerance (n = 4). One patient with succinate dehydrogenase (SDH)-deficient GIST exhibited continuing disease control after 17 cycles. The median PFS for the entire cohort was 1.9 months (95% CI 1.6-5.2), and the median OS was 10.7 months (95% CI 3.9-NR). CONCLUSIONS: Pazopanib was reasonably well tolerated with no unexpected toxicities. Pazopanib as a single agent has marginal activity in unselected heavily pretreated patients with advanced GIST.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias Gastrointestinales/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Adulto , Anciano , Inhibidores de la Angiogénesis/efectos adversos , Benzamidas/farmacología , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Femenino , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/patología , Tumores del Estroma Gastrointestinal/mortalidad , Tumores del Estroma Gastrointestinal/patología , Humanos , Mesilato de Imatinib , Indazoles , Indoles/farmacología , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Piperazinas/farmacología , Pirimidinas/efectos adversos , Pirimidinas/farmacología , Pirroles/farmacología , Sulfonamidas/efectos adversos , Sunitinib , Insuficiencia del Tratamiento , Carga Tumoral , Adulto Joven
9.
Phys Med Biol ; 69(13)2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38876111

RESUMEN

Objective.Active bone marrow (ABM) can serve as both an organ at risk and a target in external beam radiotherapy.18F-fluorothymidine (FLT) PET is the current gold standard for identifying proliferative ABM but it is not approved for human use, and PET scanners are not always available to radiotherapy clinics. Identifying ABM through other, more accessible imaging modalities will allow more patients to receive treatment specific to their ABM distribution. Multi-energy CT (MECT) and fat-fraction MRI (FFMRI) show promise in their ability to characterize bone marrow adiposity, but these methods require validation for identifying proliferative ABM.Approach.Six swine subjects were imaged using FFMRI, fast-kVp switching (FKS) MECT and sequential-scanning (SS) MECT to identify ABM volumes relative to FLT PET-derived ABM volumes. ABM was contoured on FLT PET images as the region within the bone marrow with a SUV above the mean. Bone marrow was then contoured on the FFMRI and MECT images, and thresholds were applied within these contours to determine which threshold produced the best agreement with the FLT PET determined ABM contour. Agreement between contours was measured using the Dice similarity coefficient (DSC).Main results.FFMRI produced the best estimate of the PET ABM contour. Compared to FLT PET ABM volumes, the FFMRI, SS MECT and FKS MECT ABM contours produced average peak DSC of 0.722 ± 0.080, 0.619 ± 0.070, and 0.464 ± 0.080, respectively. The ABM volume was overestimated by 40.51%, 97.63%, and 140.13% by FFMRI, SS MECT and FKS MECT, respectively.Significance.This study explored the ability of FFMRI and MECT to identify the proliferative relative to ABM defined by FLT PET. Of the methods investigated, FFMRI emerged as the most accurate approximation to FLT PET-derived active marrow contour, demonstrating superior performance by both DSC and volume comparison metrics. Both FFMRI and SS MECT show promise for providing patient-specific ABM treatments.


Asunto(s)
Médula Ósea , Estudios de Factibilidad , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Médula Ósea/diagnóstico por imagen , Animales , Imagen por Resonancia Magnética/métodos , Porcinos , Proliferación Celular , Tomografía de Emisión de Positrones , Procesamiento de Imagen Asistido por Computador/métodos , Tejido Adiposo/diagnóstico por imagen
10.
Infect Immun ; 80(4): 1606-14, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22311924

RESUMEN

Vaccines have been at the forefront of global research efforts to combat malaria, yet despite several vaccine candidates, this goal has yet to be realized. A potentially effective approach to disrupting the spread of malaria is the use of transmission-blocking vaccines (TBV), which prevent the development of malarial parasites within their mosquito vector, thereby abrogating the cascade of secondary infections in humans. Since malaria is transmitted to human hosts by the bite of an obligate insect vector, mosquito species in the genus Anopheles, targeting mosquito midgut antigens that serve as ligands for Plasmodium parasites represents a promising approach to breaking the transmission cycle. The midgut-specific anopheline alanyl aminopeptidase N (AnAPN1) is highly conserved across Anopheles vectors and is a putative ligand for Plasmodium ookinete invasion. We have developed a scalable, high-yield Escherichia coli expression and purification platform for the recombinant AnAPN1 TBV antigen and report on its marked vaccine potency and immunogenicity, its capacity for eliciting transmission-blocking antibodies, and its apparent lack of immunization-associated histopathologies in a small-animal model.


Asunto(s)
Anticuerpos/inmunología , Antígenos CD13/inmunología , Insectos Vectores/enzimología , Vacunas contra la Malaria/inmunología , Plasmodium vivax/inmunología , Animales , Anopheles/enzimología , Anopheles/inmunología , Anopheles/parasitología , Femenino , Humanos , Insectos Vectores/inmunología , Insectos Vectores/parasitología , Malaria/inmunología , Malaria/prevención & control , Malaria/transmisión , Ratones , Ratones Endogámicos BALB C , Plasmodium berghei/inmunología , Vacunas Sintéticas/inmunología
11.
Community Dent Health ; 29(1): 110-6, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22482261

RESUMEN

OBJECTIVE: The study investigated the experience of orofacial pain (OFP) symptoms and associated disability and psychosocial impact in community dwelling and institutionalized elderly people in Hong Kong. METHODS: A community-based cross-sectional survey involving elders aged 60 years and above. Participants were recruited at social centres for the elderly and homes for the aged throughout Hong Kong. Elders who reported OFP symptoms in the previous four weeks took part. Standard questions were asked about OFP conditions in the previous month and the Manchester Orofacial Pain Disability Scale (MOPDS), the Oral Health Impact Profile (OHIP-14) and the General Health Questionnaire (GHQ-12) were administered. The MOPDS was translated and validated for use in Chinese elders. RESULTS: 200 community dwelling and 200 institutionalized elders participated. Toothache was the most common symptom (62.0%) and burning sensation in the tongue was least common (0.5%). The distribution of pain symptoms, pain duration and severity and pain ratings were similar in both groups. The MOPDS (Chinese elders version) had good reliability and construct validity. The MOPDS and OHIP-14 summary scores was significantly higher in the institutionalized elderly (p < 0.001 and p < 0.013, respectively). Psychological distress (GHQ-12 score > or = 4) was more common among the institutionalized elderly (11%) than the community dwelling elderly (4.0%, p = 0.002). CONCLUSIONS: Orofacial pain symptoms were associated with significant disability and had a detrimental impact on psychological distress level and quality of life, particularly in the institutionalized elderly. There is a need to improve access to professional care and health-related outreach services generally for elderly people in Hong Kong.


Asunto(s)
Dolor Facial/psicología , Vida Independiente , Institucionalización , Calidad de Vida , Estrés Psicológico/psicología , Anciano , Anciano de 80 o más Años , Analgésicos/uso terapéutico , Síndrome de Boca Ardiente/psicología , Estudios Transversales , Escolaridad , Femenino , Hogares para Ancianos , Hong Kong , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Aceptación de la Atención de Salud , Autocuidado , Seguridad Social , Trastornos de la Articulación Temporomandibular/psicología , Factores de Tiempo , Enfermedades de la Lengua/psicología , Odontalgia/psicología
14.
J Oral Rehabil ; 37(1): 2-10, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19919620

RESUMEN

The study investigated the experience of widespread pain (WP) symptoms and psychological distress in southern Chinese with orofacial pain (OFP). A community-based, cross-sectional case-control study involving people aged 35-70 registered with the Hospital Authority/University of Hong Kong Family Medicine Clinic served as the sampling frame. People with recent OFP symptoms and a group without OFP took part. Standard questions were asked about OFP conditions in the previous month. Psychological status was evaluated through depression, and non-specific physical symptoms (NPS) scores were measured with depression and somatization sub-scales of the Symptom Checklist-90. Widespread pain was determined using body outline drawings to identify painful sites prior to a standard clinical examination. Two hundred people with OFP and 200 without OFP participated. Compared with 5.0% in the comparison group (P = 0.005), 13.5% of participants with OFP had WP (OFP/WP). Multiple OFP symptoms were more common in the OFP/WP sub-group than the OFP sub-group without WP (OFP/No WP) (P < 0.002). Sixty-three percent of the OFP/WP sub-group had moderate/severe depression scores compared with 26.0% in the OFP/No WP sub-group (P < 0.001). When pain items were included and excluded, 92.6% and 88.9% of the OFP/WP sub-group had moderate/severe NPS scores, respectively compared with 68.5% and 65.0% in the OFP/No WP sub-group (P = 0.004). Co-morbid WP occurred relatively often in southern Chinese with OFP. Psychological distress was common in OFP sufferers, particularly those with WP. A multidisciplinary approach to treatment including cognitive/behavioural therapy should be considered in Chinese people with OFP as part of a WP pattern.


Asunto(s)
Dolor Facial/psicología , Dolor/psicología , Trastornos Somatomorfos/psicología , Estrés Psicológico/psicología , Adulto , Anciano , Estudios de Casos y Controles , China , Enfermedad Crónica , Costo de Enfermedad , Estudios Transversales , Depresión/complicaciones , Depresión/psicología , Dolor Facial/complicaciones , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Dolor/complicaciones , Trastornos Somatomorfos/complicaciones , Estrés Psicológico/complicaciones
15.
Phys Med Biol ; 65(19): 19NT01, 2020 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-32975219

RESUMEN

Over the last 30 years, there have been dramatic changes in phased array coil technology leading to increasing channel density and parallel imaging functionality. Current receiver array coils are rigid and often mismatched to patient's size. Recently there has been a move towards flexible coil technology, which is more conformal to the human anatomy. Despite the advances of so-called flexible surface coil arrays, these coils are still relatively rigid and limited in terms of design conformability, compromising signal-to-noise ratio (SNR) for flexibility, and are not designed for optimum parallel imaging performance. The purpose of this study is to report on the development and characterization of a 15-channel flexible foot and ankle coil, rapidly designed and constructed using highly decoupled radio-frequency (RF) coil elements. Coil performance was evaluated by performing SNR and g-factor measurements. In vivo testing was performed in a healthy volunteer using both the 15-channel coil and a commercially available 8-channel foot coil. The highly decoupled elements used in this design allow for extremely rapid development and prototyping of application-specific coils for different patient sizes (adult vs child) with minimal additional design consideration in terms of coil overlap and geometry. Image quality was comparable to a commercially available RF coil.


Asunto(s)
Imagen por Resonancia Magnética/instrumentación , Imagen por Resonancia Magnética/métodos , Fantasmas de Imagen , Relación Señal-Ruido , Adulto , Niño , Diseño de Equipo , Voluntarios Sanos , Humanos
16.
Biochim Biophys Acta ; 1784(7-8): 1098-105, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18474266

RESUMEN

The human gene for catechol O-methyltransferase has a common single-nucleotide polymorphism that results in substitution of methionine (M) for valine (V) 108 in the soluble form of the enzyme (s-COMT). 108M s-COMT loses enzymatic activity more rapidly than 108V s-COMT at physiological temperature, and the 108M allele has been associated with increased risk of breast cancer and several neuropsychiatric disorders. We used circular dichroism (CD), dynamic light scattering, and fluorescence spectroscopy to examine how the 108V/M polymorphism affects the stability of the purified, recombinant protein to heat and guanidine hydrochloride (GuHCl). COMT contains two tryptophan residues, W143 and W38Y, which are located in loops that border the S-adenosylmethionine (SAM) and catechol binding sites. We therefore also studied the single-tryptophan mutants W38Y and W143Y in order to dissect the contributions of the individual tryptophans to the fluorescence signals. The 108V and 108M proteins differed in the stability of both the tertiary structure surrounding the active site, as probed by the fluorescence yields and emission spectra, and their global secondary structure as reflected by CD. With either probe, the midpoint of the thermal transition of 108M s-COMT was 5 to 7 degrees C lower than that of 108V s-COMT, and the free energy of unfolding at 25 degrees C was smaller by about 0.4 kcal/mol. 108M s-COMT also was more prone to aggregation or partial unfolding to a form with an increased radius of hydration at 37 degrees C. The co-substrate SAM stabilized the secondary structure of both 108V and 108M s-COMT. W143 dominates the tryptophan fluorescence of the folded protein and accounts for most of the decrease in fluorescence that accompanies unfolding by GuHCl. While replacing either tryptophan by tyrosine was mildly destabilizing, the lower stability of the 108M variant was retained in all cases.


Asunto(s)
Catecol O-Metiltransferasa/química , Mutación , Catecol O-Metiltransferasa/genética , Catecol O-Metiltransferasa/aislamiento & purificación , Dicroismo Circular , Humanos , Modelos Moleculares , Conformación Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Dispersión de Radiación , Espectrometría de Fluorescencia
17.
Opt Express ; 17(8): 6156-65, 2009 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-19365438

RESUMEN

An all-fibre heralded single photon source operating at 1570 nm has been demonstrated. The device generates correlated photon pairs, widely spaced in frequency, through four-wave mixing in a photonic crystal fibre. Separation of the pair photons and narrowband filtering is all achieved in fibre. The output heralded single photon rate was 9.2 x 10(4) per second, with a counts-to-accidentals ratio of 10.4 and a heralding fidelity of 52 %. Furthermore, narrowband filtering ensured that the output single photon state was near time-bandwidth limited with a coherence length of 4 ps. Such a source is well suited to quantum information processing applications.


Asunto(s)
Diseño Asistido por Computadora , Tecnología de Fibra Óptica , Iluminación/instrumentación , Modelos Teóricos , Simulación por Computador , Diseño de Equipo , Análisis de Falla de Equipo , Fotones , Teoría Cuántica , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
18.
Science ; 290(5493): 966-9, 2000 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-11062125

RESUMEN

Methyl halide gases are important sources of atmospheric inorganic halogen compounds, which in turn are central reactants in many stratospheric and tropospheric chemical processes. By observing emissions of methyl chloride, methyl bromide, and methyl iodide from flooded California rice fields, we estimate the impact of rice agriculture on the atmospheric budgets of these gases. Factors influencing methyl halide emissions are stage of rice growth, soil organic content, halide concentrations, and field-water management. Extrapolating our data implies that about 1 percent of atmospheric methyl bromide and 5 percent of methyl iodide arise from rice fields worldwide. Unplanted flooded fields emit as much methyl chloride as planted, flooded rice fields.


Asunto(s)
Hidrocarburos Halogenados/metabolismo , Metano/metabolismo , Oryza/crecimiento & desarrollo , Oryza/metabolismo , Atmósfera , California , Hidrocarburos Bromados/metabolismo , Hidrocarburos Yodados/metabolismo , Cloruro de Metilo/metabolismo , Estaciones del Año , Suelo , Microbiología del Suelo
19.
Int J STD AIDS ; 20(1): 16-8, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19103887

RESUMEN

Rectal infection with Chlamydia trachomatis affects approximately 7% of men having sex with men (MSM), attending departments of Genito-Urinary (GU) Medicine [Manavi et al. Int J STD AIDS 2004;15:162-4], and the British Association for Sexual Health and HIV (BASHH) guidelines for the treatment of uncomplicated genital C. trachomatis infection include 1 g of single-dose oral azithromycin as a recommended regimen [BASHH 2006]. A retrospective analysis was performed on case-notes from all patients diagnosed with rectal C. trachomatis infection in the department of GU Medicine, Edinburgh for the one-year period from 1 June 2005. Of 101 new episodes of rectal chlamydial infection, only 9% were associated with anorectal symptoms. Excluding these, 85% of asymptomatic patients were treated with a single dose of azithromycin 1 g orally, with a calculated treatment failure rate of 13% (nine of 68). This suggests that single-dose azithromycin may be a less than effective treatment in asymptomatic rectal C. trachomatis infection. The potential treatment failure rate with this regimen emphasizes the need for a test of cure at the appropriate interval following treatment to ensure clearance of infection.


Asunto(s)
Antibacterianos , Azitromicina , Infecciones por Chlamydia/tratamiento farmacológico , Chlamydia trachomatis/efectos de los fármacos , Enfermedades del Recto/tratamiento farmacológico , Adulto , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Azitromicina/administración & dosificación , Azitromicina/uso terapéutico , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/microbiología , Infecciones por Chlamydia/fisiopatología , Femenino , Humanos , Masculino , Enfermedades del Recto/epidemiología , Enfermedades del Recto/microbiología , Enfermedades del Recto/fisiopatología , Insuficiencia del Tratamiento , Resultado del Tratamiento , Reino Unido , Adulto Joven
20.
J Oral Rehabil ; 36(4): 264-70, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19220712

RESUMEN

This study aimed to assess agreement between patient and proxy assessment of patients' oral health-related quality of life (OHRQoL) during the acute stroke phase and 6 months after hospital discharge. As part of an observational longitudinal study, 161 consecutive patients hospitalized after stroke and their caregivers (CGs) were monitored during acute stroke and 6 months after hospital discharge. Patient-CG agreement of health-related quality of life as assessed by the General Oral Health Assessment Index (GOHAI) and Medical Outcomes Study 12-item Short Form (SF-12) which comprises physical (PCS-12) and mental component summaries (MCS-12) was determined by comparison and correlation analyses. Complete data were available for 65 patients and CGs. Compared with acute stroke, there were improvements in GOHAI and SF-12 scores from patient's and CG's perspective at 6-month follow-up. Caregivers overestimated the impact of stroke on MCS-12 over a period of time (P < 0.01) and underestimated the impact on GOHAI during acute stroke (P < 0.001) and on PCS-12 6 months later (P < 0.05). Patient-CG agreement was substantial to excellent during acute stroke [intra-class correlation coefficient (ICC 0.69-0.86)] and fair-to-moderate 6 months later (ICC 0.28-0.60). Agreement was adequate between patients' and CGs' assessment of patient OHRQoL during acute stroke but it was less reliable 6 months after hospital discharge. These findings suggest that proxy assessment of OHRQoL after stroke is effective in assessing stroke-related oral impairments that affect life quality without placing additional burden on stroke patients themselves to assess OHRQoL.


Asunto(s)
Salud Bucal/normas , Apoderado , Calidad de Vida , Autocuidado/normas , Accidente Cerebrovascular , Anciano , Cuidadores , Femenino , Hong Kong , Humanos , Estudios Longitudinales , Masculino , Calidad de Vida/psicología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/psicología , Rehabilitación de Accidente Cerebrovascular , Encuestas y Cuestionarios , Factores de Tiempo
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