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1.
Acta Oncol ; 62(8): 915-922, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37504890

RESUMEN

BACKGROUND: Dose-surface maps (DSMs) are an increasingly popular tool to evaluate spatial dose-outcome relationships for the rectum. Recently, DSM addition has been proposed as an alternative method of dose accumulation from deformable registration-based techniques. In this study, we performed the first experimental investigation of the accuracy at which DSM accumulation can capture the total dose delivered to a rectum's surface in the presence of inter-fraction motion. MATERIAL AND METHODS: A custom PVC rectum phantom capable of representing typical rectum inter-fraction motion and filling variations was constructed for this project. The phantom allowed for the placement of EBT3 film sheets on the representative rectum surface to measure rectum surface dose. A multi-fraction prostate VMAT treatment was designed and delivered to the phantom in a water tank for a variety of inter-fraction motion scenarios. DSMs for each fraction were calculated in two ways using CBCT images acquired during delivery and summed to produce accumulated DSMs. Accumulated DSMs were then compared to film measurements using gamma analysis (3%/2 mm criteria). Similarity of isodose clusters between films and DSMs was also investigated. RESULTS: Baseline agreement between film measurements and accumulated DSMs for a stationary rectum was 95.6%. Agreement between film and accumulated DSMs in the presence of different types of inter.-fraction motion was ≥92%, and isodose cluster mean distance to agreement was within 1.5 mm for most scenarios. Overall, DSM accumulation performed the best when using DSMs that accounted for changes in rectum path orientation. CONCLUSION: Dose accumulation performed with DSMs was found to accurately replicate total delivered dose to a rectum phantom in the presence of inter-fraction motion.


Asunto(s)
Neoplasias de la Próstata , Recto , Masculino , Humanos , Recto/diagnóstico por imagen , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Pelvis , Fantasmas de Imagen
2.
Br J Dermatol ; 184(6): 1113-1122, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33236347

RESUMEN

BACKGROUND: The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials. OBJECTIVES: To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC. METHODS: One hundred and nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, in two rounds of Delphi exercises. Outcomes scored 'critically important' (score of 7, 8 or 9) by ≥ 70% of patients and ≥ 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants. RESULTS: A core set of seven outcomes was finalized at the consensus meeting: (i) serious or persistent adverse events, (ii) patient-reported quality of life, (iii) complete response, (iv) partial response, (v) recurrence-free survival, (vi) progression-free survival and (vii) disease-specific survival. CONCLUSIONS: In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Cutáneas , Carcinoma de Células Escamosas/terapia , Técnica Delphi , Humanos , Calidad de Vida , Proyectos de Investigación , Neoplasias Cutáneas/terapia , Resultado del Tratamiento
4.
Stem Cells ; 33(10): 2973-84, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26269433

RESUMEN

Cardiac hypertrophy is an abnormal enlargement of heart muscle. It frequently results in congestive heart failure, which is a leading cause of human death. Previous studies demonstrated that the nitric oxide (NO), cyclic GMP (cGMP), and protein kinase G (PKG) signaling pathway can inhibit cardiac hypertrophy and thus improve cardiac function. However, the underlying mechanisms are not fully understood. Here, based on the human embryonic stem cell-derived cardiomyocyte (hESC-CM) model system, we showed that Orai1, the pore-forming subunit of store-operated Ca(2+) entry (SOCE), is the downstream effector of PKG. Treatment of hESC-CMs with an α-adrenoceptor agonist phenylephrine (PE) caused a marked hypertrophy, which was accompanied by an upregulation of Orai1. Moreover, suppression of Orai1 expression/activity using Orai1-siRNAs or a dominant-negative construct Orai1(G98A) inhibited the hypertrophy, suggesting that Orai1-mediated SOCE is indispensable for the PE-induced hypertrophy of hESC-CMs. In addition, the hypertrophy was inhibited by NO and cGMP via activating PKG. Importantly, substitution of Ala for Ser(34) in Orai1 abolished the antihypertrophic effects of NO, cGMP, and PKG. Furthermore, PKG could directly phosphorylate Orai1 at Ser(34) and thus prevent Orai1-mediated SOCE. Together, we conclude that NO, cGMP, and PKG inhibit the hypertrophy of hESC-CMs via PKG-mediated phosphorylation on Orai1-Ser-34. These results provide novel mechanistic insights into the action of cGMP-PKG-related antihypertrophic agents, such as NO donors and sildenafil.


Asunto(s)
Canales de Calcio/genética , Cardiomegalia/genética , Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , Insuficiencia Cardíaca/genética , Calcio/metabolismo , Canales de Calcio/biosíntesis , Canales de Calcio/efectos de los fármacos , Cardiomegalia/patología , Diferenciación Celular/genética , GMP Cíclico/administración & dosificación , GMP Cíclico/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Insuficiencia Cardíaca/patología , Células Madre Embrionarias Humanas/efectos de los fármacos , Células Madre Embrionarias Humanas/metabolismo , Humanos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Óxido Nítrico/administración & dosificación , Óxido Nítrico/metabolismo , Proteína ORAI1 , Fenilefrina/administración & dosificación , Fosforilación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
5.
Diabet Med ; 33(4): 547-51, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26179569

RESUMEN

AIMS: To evaluate the effectiveness and feasibility of implementing a linguistically and culturally tailored Diabetes Prevention Program among Chinese immigrants with prediabetes living in New York City. METHODS: A total of 60 Chinese immigrants with prediabetes were randomized into either a Diabetes Prevention Program lifestyle intervention (n = 30) consisting of 12 bi-weekly core sessions and six monthly post-core sessions or the control intervention (n = 30), consisting of quarterly mailing of diabetes prevention information. Each Diabetes Prevention Program intervention session lasted 1.5-2 h and covered topics such as healthy eating, physical activity, stress reduction and problem-solving skills. Outcomes such as percent change in weight, BMI, and HbA1c concentration were assessed at baseline, 6 and 12 months. A mixed-effects linear regression was applied to test the intervention effect at months 6 and 12. Data were collected in the period 2012-2013 and analysed in 2014. RESULTS: The participant attrition rate was < 5% (2 out of 60) at 12 months. There was a significantly greater percent weight loss in the intervention group (-3.5 vs. -0.1%; P = 0.0001) at 6 months, which was largely maintained at 12 months (-3.3 vs. 0.3%; P = 0.0003). CONCLUSIONS: Participants in a Diabetes Prevention Program-based intervention achieved greater weight loss and improvements in HbA1c concentration than control participants. Evaluation of the Chinese Diabetes Prevention Program curriculum in a larger trial is warranted.


Asunto(s)
Asistencia Sanitaria Culturalmente Competente , Diabetes Mellitus Tipo 2/prevención & control , Estilo de Vida Saludable , Estado Prediabético/terapia , Anciano , Asiático , China/etnología , Investigación Participativa Basada en la Comunidad , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etiología , Emigrantes e Inmigrantes/educación , Estudios de Factibilidad , Femenino , Grupos Focales , Humanos , Lenguaje , Masculino , Persona de Mediana Edad , Ciudad de Nueva York/epidemiología , Sobrepeso/epidemiología , Sobrepeso/etnología , Sobrepeso/prevención & control , Sobrepeso/terapia , Educación del Paciente como Asunto , Proyectos Piloto , Estado Prediabético/etnología , Estado Prediabético/fisiopatología , Estado Prediabético/psicología , Riesgo , Estrés Psicológico/etnología , Estrés Psicológico/prevención & control
6.
Arch Dermatol Res ; 314(5): 417-425, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34047823

RESUMEN

BACKGROUND: Stromal vascular fraction (SVF), derived enzymatically or mechanically from adipose tissue, contains a heterogenous population of cells and stroma, including multipotent stem cells. The regenerative capacity of SVF may potentially be adapted for a broad range of clinical applications, including the healing of acute cutaneous wounds. OBJECTIVE: To evaluate the available literature on the efficacy and safety of autologous adipose-derived stromal vascular fraction (SVF) for the treatment of acute cutaneous wounds in humans. METHODS: A systematic review of the literature utilizing MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials was performed to identify published clinical trials of autologous adipose-derived SVF or similar ADSC-containing derivatives for patients with acute cutaneous wounds. This was supplemented by searches for ongoing clinical trials through ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. RESULTS: 872 records were initially retrieved. Application of inclusion and exclusion criteria yielded 10 relevant studies: two completed non-randomized controlled trials and eight ongoing clinical trials. Both completed studies reported a statistically significant benefit in percentage re-epithelialization and time to healing for the SVF treatment arms. Safety information for SVF was not provided. Ongoing clinical trials were assessing outcomes such as safety, patient and observer reported scar appearance, wound healing rate, and wound epithelization. CONCLUSION: In the context of substantial limitations in the quantity and quality of available evidence, the existing literature suggests that SVF may be a useful treatment for acute cutaneous wounds in humans. More clinical trials with improved outcome measures and safety assessment are needed.


Asunto(s)
Tejido Adiposo , Fracción Vascular Estromal , Cicatriz , Humanos , Repitelización , Cicatrización de Heridas
7.
ESMO Open ; 7(4): 100518, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35797737

RESUMEN

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of prostate cancer was published in 2020. It was therefore decided, by both the ESMO and the Singapore Society of Oncology (SSO), to convene a special, virtual guidelines meeting in November 2021 to adapt the ESMO 2020 guidelines to take into account the differences associated with the treatment of prostate cancer in Asia. These guidelines represent the consensus opinions reached by experts in the treatment of patients with prostate cancer representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with prostate cancer across the different regions of Asia.


Asunto(s)
Oncología Médica , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/terapia , Asia , Consenso , Europa (Continente) , Estudios de Seguimiento , Humanos , Masculino
8.
ESMO Open ; 6(6): 100304, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34864348

RESUMEN

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of renal cell carcinoma was published in 2019 with an update planned for 2021. It was therefore decided by both the ESMO and the Singapore Society of Oncology (SSO) to convene a special, virtual guidelines meeting in May 2021 to adapt the ESMO 2019 guidelines to take into account the ethnic differences associated with the treatment of renal cell carcinomas in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with renal cell carcinoma representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Asia , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/terapia , Estudios de Seguimiento , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Renales/terapia , Oncología Médica
9.
J Exp Clin Cancer Res ; 39(1): 78, 2020 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-32375866

RESUMEN

The majority of high-risk neuroblastomas can be divided into three distinct molecular subgroups defined by the presence of MYCN amplification, upstream TERT rearrangements or alternative lengthening of telomeres (ALT). The common defining feature of all three subgroups is altered telomere maintenance; MYCN amplification and upstream TERT rearrangements drive high levels of telomerase expression whereas ALT is a telomerase independent telomere maintenance mechanism. As all three telomere maintenance mechanisms are independently associated with poor outcomes, the development of strategies to selectively target either telomerase expressing or ALT cells holds great promise as a therapeutic approach that is applicable to the majority of children with aggressive disease.Here we summarise the biology of telomere maintenance and the molecular drivers of aggressive neuroblastoma before describing the most promising therapeutic strategies to target both telomerase expressing and ALT cancers. For telomerase-expressing neuroblastoma the most promising targeted agent to date is 6-thio-2'-deoxyguanosine, however clinical development of this agent is required. In osteosarcoma cell lines with ALT, selective sensitivity to ATR inhibition has been reported. However, we present data showing that in fact ALT neuroblastoma cells are more resistant to the clinical ATR inhibitor AZD6738 compared to other neuroblastoma subtypes. More recently a number of additional candidate compounds have been shown to show selectivity for ALT cancers, such as Tetra-Pt (bpy), a compound targeting the telomeric G-quadruplex and pifithrin-α, a putative p53 inhibitor. Further pre-clinical evaluation of these compounds in neuroblastoma models is warranted.In summary, telomere maintenance targeting strategies offer a significant opportunity to develop effective new therapies, applicable to a large proportion of children with high-risk neuroblastoma. In parallel to clinical development, more pre-clinical research specifically for neuroblastoma is urgently needed, if we are to improve survival for this common poor outcome tumour of childhood.


Asunto(s)
Neuroblastoma/terapia , Telómero/fisiología , Línea Celular Tumoral , Preescolar , Femenino , Humanos , Lactante , Masculino , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/genética , Telómero/efectos de los fármacos , Telómero/genética , Telómero/metabolismo
10.
Med Phys ; 36(5): 1848-58, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19544804

RESUMEN

A Monte Carlo (MC) study was carried out to evaluate the effects of the interseed attenuation and the tissue composition for two models of 125I low dose rate (LDR) brachytherapy seeds (Medi-Physics 6711, IBt InterSource) in a permanent breast implant. The effect of the tissue composition was investigated because the breast localization presents heterogeneities such as glandular and adipose tissue surrounded by air, lungs, and ribs. The absolute MC dose calculations were benchmarked by comparison to the absolute dose obtained from experimental results. Before modeling a clinical case of an implant in heterogeneous breast, the effects of the tissue composition and the interseed attenuation were studied in homogeneous phantoms. To investigate the tissue composition effect, the dose along the transverse axis of the two seed models were calculated and compared in different materials. For each seed model, three seeds sharing the same transverse axis were simulated to evaluate the interseed effect in water as a function of the distance from the seed. A clinical study of a permanent breast 125I implant for a single patient was carried out using four dose calculation techniques: (1) A TG-43 based calculation, (2) a full MC simulation with realistic tissues and seed models, (3) a MC simulation in water and modeled seeds, and (4) a MC simulation without modeling the seed geometry but with realistic tissues. In the latter, a phase space file corresponding to the particles emitted from the external surface of the seed is used at each seed location. The results were compared by calculating the relevant clinical metrics V85, V100, and V200 for this kind of treatment in the target. D90 and D50 were also determined to evaluate the differences in dose and compare the results to the studies published for permanent prostate seed implants in literature. The experimental results are in agreement with the MC absolute doses (within 5% for EBT Gafchromic film and within 7% for TLD-100). Important differences between the dose along the transverse axis of the seed in water and in adipose tissue are obtained (10% at 3.5 cm). The comparisons between the full MC and the TG-43 calculations show that there are no significant differences for V85 and V100. For V200, 8.4% difference is found coming mainly from the tissue composition effect. Larger differences (about 10.5% for the model 6711 seed and about 13% for the InterSource125) are determined for D90 and D50. These differences depend on the composition of the breast tissue modeled in the simulation. A variation in percentage by mass of the mammary gland and adipose tissue can cause important differences in the clinical dose metrics V200, D90, and D50. Even if the authors can conclude that clinically, the differences in V85, V100, and V200 are acceptable in comparison to the large variation in dose in the treated volume, this work demonstrates that the development of a MC treatment planning system for LDR brachytherapy will improve the dose determination in the treated region and consequently the dose-outcome relationship, especially for the skin toxicity.


Asunto(s)
Braquiterapia/instrumentación , Implantes de Mama , Neoplasias de la Mama/radioterapia , Modelos Biológicos , Radiometría/métodos , Braquiterapia/métodos , Simulación por Computador , Diseño Asistido por Computadora , Diseño de Equipo , Análisis de Falla de Equipo , Femenino , Humanos , Método de Montecarlo , Dosificación Radioterapéutica , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
11.
Int J Womens Dermatol ; 4(2): 80-82, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30023424

RESUMEN

OBJECTIVE: Although dermatologists strive to provide patient education on sun protection and skin cancer, approximately 90% of Americans have limited health literacy skills. Little has been written about the means to best teach all levels of learners to recognize common benign and malignant skin lesions. Earlier work found that with advancing age, adults were less able to identify concerning lesions, thus underscoring the need for accessible education. METHODS: We showed subjects a brief video (7th grade level) about common cutaneous growths, reducing the risk of skin cancer, and the importance of early detection. Subjects were asked about their skin cancer history, educational format preference, and the perceived impact of the video. Comprehension of symptoms of skin cancer and the benefits of sunscreen use and the ability to identify a melanoma, nevus, angioma, and seborrheic keratosis were also assessed. RESULTS: Of the 156 subjects, mean age 52.7 years (range, 18-88 years), 31% had a history of skin cancer. A total of 98.7% found the video to be helpful; 92% preferred having a video as part of their teaching versus 9% who preferred written materials alone, 99% knew that a new or changing lesion could signal skin cancer, and 100% correctly answered that wearing sunscreen is protective. Subjects correctly identified lesions as melanoma (99%), benign mole (97%), angiomas (96%), and seborrheic keratosis (91%). There was a nominal trend toward higher scores in people who preferred video learning, had no history of skin cancer, and were older than 60 years of age. CONCLUSION: In this study, we found that a brief, plain-language video was effective at conveying understandable content to help subjects learn to identify common cancerous and benign skin growths while also teaching them strategies to protect against skin cancer.

12.
Mol Cell Biol ; 19(3): 1617-26, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10022850

RESUMEN

Latent Epstein-Barr virus (EBV) is maintained as a nucleosome-covered episome that can be transcriptionally activated by overexpression of the viral immediate-early protein, Zta. We show here that reactivation of latent EBV by Zta can be significantly enhanced by coexpression of the cellular coactivators CREB binding protein (CBP) and p300. A stable complex containing both Zta and CBP could be isolated from lytically stimulated, but not latently infected RAJI nuclear extracts. Zta-mediated viral reactivation and transcriptional activation were both significantly inhibited by coexpression of the E1A 12S protein but not by an N-terminal deletion mutation of E1A (E1ADelta2-36), which fails to bind CBP. Zta bound directly to two related cysteine- and histidine-rich domains of CBP, referred to as C/H1 and C/H3. These domains both interacted specifically with the transcriptional activation domain of Zta in an electrophoretic mobility shift assay. Interestingly, we found that the C/H3 domain was a potent dominant negative inhibitor of Zta transcriptional activation function. In contrast, an amino-terminal fragment containing the C/H1 domain was sufficient for coactivation of Zta transcription and viral reactivation function. Thus, CBP can stimulate the transcription of latent EBV in a histone acetyltransferase-independent manner mediated by the CBP amino-terminal C/H1-containing domain. We propose that CBP may regulate aspects of EBV latency and reactivation by integrating cellular signals mediated by competitive interactions between C/H1, C/H3, and the Zta activation domain.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Herpesvirus Humano 4/fisiología , Proteínas Nucleares/metabolismo , Transactivadores/metabolismo , Activación Transcripcional , Proteínas Virales/metabolismo , Latencia del Virus/fisiología , Acetiltransferasas/biosíntesis , Acetiltransferasas/genética , Animales , Sitios de Unión , Proteína de Unión a CREB , Proteínas de Ciclo Celular/biosíntesis , Proteínas de Ciclo Celular/genética , Proteínas de Unión al ADN/genética , Proteína p300 Asociada a E1A , Regulación Viral de la Expresión Génica , Células HeLa , Herpesvirus Humano 4/crecimiento & desarrollo , Histona Acetiltransferasas , Humanos , Ratones , Proteínas Nucleares/biosíntesis , Proteínas Nucleares/genética , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Transactivadores/biosíntesis , Transactivadores/genética , Factores de Transcripción , Proteínas Virales/genética , Activación Viral , Factores de Transcripción p300-CBP
13.
Int J Antimicrob Agents ; 28(6): 545-50, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17097856

RESUMEN

Outpatient parenteral antibiotic therapy (OPAT) remains in its infancy in Singapore, with the first patients enrolled 4 years ago. Singapore's three largest hospitals, with over 3000 inpatient beds, now have designated and approved OPAT services. This study reviews the demographic, clinical and cost data of all patients enrolled in 2005 to facilitate benchmarking between services in Singapore and abroad and also to identify common needs for further development. In 2005, 225 OPAT enrollments in 208 different patients resulted in 4050 days of OPAT care. Orthopaedic diagnoses constituted 40% of admissions. Vancomycin was the most frequently used antibiotic (34%). The re-admission rate was 8.9%, but complications of OPAT care were only occasionally implicated. An estimated $207,200 was saved by patients despite there being significant financial disincentives to subsidised patients. OPAT is a safe, cost-efficient system that is becoming increasingly accepted in Singapore by patients, clinicians and management. Our three services have evolved independently into very similar practices. There is potential for further innovation, including outreach and carer-delivered dosing. However, major financial disincentives require review.


Asunto(s)
Atención Ambulatoria/economía , Antibacterianos/administración & dosificación , Antibacterianos/economía , Terapia de Infusión a Domicilio/economía , Infusiones Parenterales/economía , Pacientes Ambulatorios , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Atención Ambulatoria/métodos , Femenino , Humanos , Masculino , Resistencia a la Meticilina , Persona de Mediana Edad , Singapur , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/efectos de los fármacos , Vancomicina/administración & dosificación , Vancomicina/economía
14.
Diabetes Care ; 21(3): 431-7, 1998 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9540028

RESUMEN

OBJECTIVE: Genetic polymorphisms of the renin-angiotensin system (RAS) have been implicated in the pathogenesis of diabetic proteinuria. Ethnic differences in the frequencies of these genotypes have also been reported. To date, most of these studies have been performed in white and Japanese populations. In this study, we examined the associations between albuminuria and RAS genetic polymorphisms in Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: In a case-control study, the ACE insertion/deletion (I/D) gene, the angiotensinogen (AGT) gene (M235T), and the angiotensin II (AII) type 1 receptor gene (AT1 A1166C) were examined in 110 Chinese type 2 diabetic patients. Increased urinary albumin excretion (UAE) was defined as > or = 30 mg/day on at least two occasions during a 6-week study period. RESULTS: Compared with whites, there were high frequencies of the AGT TT genotype in Chinese control subjects (120/183 = 70%) and type 2 diabetic patients (74/110 = 67%). The frequencies of the MM genotype were 5 and 3%, respectively, and those of the ACE DD genotype were 13 and 10%, respectively. Although 9% of subjects carried the C allele, the AT1 CC genotype was not found in either group. Chinese type 2 diabetic patients with increased albuminuria (n = 56) had higher systolic blood pressure (160 +/- 26 mmHg vs 145 +/- 27 mmHg, P < 0.001) than the normoalbuminuric patients (n = 54). Both the AGT TT genotype (78.6% [44/56] vs. 55.6% [30/54], odds ratio [OR]: 3.0 [1.3-6.8]) and the T allele (88% [99/112] vs. 77% [83/108], OR: 2.5 [1.3-5.4]) were associated with an increased risk of albuminuria. Patients with the AGT TT genotype (n = 74) had higher 24-h UAE than those with the MT or MM genotypes (n = 36) (median: 37.8 mg/day vs. 17.8 mg/day, P < 0.01). This association remained significant in patients with normotension (56 mg/day [n = 19] for patients with the TT genotype vs. 22 mg/day [n = 14] for those with the MT/MM genotype, P = 0.03). The D allele carriers (DD or DI, n = 61) had higher serum ACE activities (75.5 +/- 29 U/l vs. 60.5 +/- 36.3 U/l, P < 0.01) than the noncarriers (II genotype). The median 24-h UAE also tended to be higher in the D allele carriers (38.9 mg/day vs. 21.4 mg/day, P = 0.07). The lowest UAE was observed in patients with the MM/MT/II genotype (16.3 mg/day [n = 18]) and the highest, in patients with the TT/DD/DI genotype (52.3 mg/day [n = 43]). No association was found between the TT genotype or D allele and hypertension. CONCLUSIONS: The high frequencies of the TT genotype and T allele in Chinese populations may contribute to the high prevalence of albuminuria in patients with type 2 diabetes. The possibility of synergism between the AGT TT genotype and the ACE D allele should also be explored.


Asunto(s)
Albuminuria/etnología , Albuminuria/genética , Angiotensinógeno/genética , Diabetes Mellitus Tipo 2/etnología , Diabetes Mellitus Tipo 2/genética , Peptidil-Dipeptidasa A/genética , Adulto , Factores de Edad , Anciano , Albuminuria/complicaciones , Alelos , Sustitución de Aminoácidos , Biomarcadores/sangre , Biomarcadores/orina , Presión Sanguínea/fisiología , Índice de Masa Corporal , Estudios de Casos y Controles , China/etnología , Colesterol/sangre , Elementos Transponibles de ADN , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Frecuencia de los Genes , Genes ras/genética , Genotipo , Hemoglobina Glucada/metabolismo , Hong Kong/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Receptor de Angiotensina Tipo 1 , Receptor de Angiotensina Tipo 2 , Receptores de Angiotensina/genética , Análisis de Regresión , Sistema Renina-Angiotensina/genética , Factores de Riesgo , Eliminación de Secuencia , Factores Sexuales , Factores de Tiempo
15.
Appl Clin Inform ; 6(1): 27-41, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25848411

RESUMEN

OBJECTIVE: To understand emergency department (ED) physicians' use of electronic documentation in order to identify usability and workflow considerations for the design of future ED information system (EDIS) physician documentation modules. METHODS: We invited emergency medicine resident physicians to participate in a mixed methods study using task analysis and qualitative interviews. Participants completed a simulated, standardized patient encounter in a medical simulation center while documenting in the test environment of a currently used EDIS. We recorded the time on task, type and sequence of tasks performed by the participants (including tasks performed in parallel). We then conducted semi-structured interviews with each participant. We analyzed these qualitative data using the constant comparative method to generate themes. RESULTS: Eight resident physicians participated. The simulation session averaged 17 minutes and participants spent 11 minutes on average on tasks that included electronic documentation. Participants performed tasks in parallel, such as history taking and electronic documentation. Five of the 8 participants performed a similar workflow sequence during the first part of the session while the remaining three used different workflows. Three themes characterize electronic documentation: (1) physicians report that location and timing of documentation varies based on patient acuity and workload, (2) physicians report a need for features that support improved efficiency; and (3) physicians like viewing available patient data but struggle with integration of the EDIS with other information sources. CONCLUSION: We confirmed that physicians spend much of their time on documentation (65%) during an ED patient visit. Further, we found that resident physicians did not all use the same workflow and approach even when presented with an identical standardized patient scenario. Future EHR design should consider these varied workflows while trying to optimize efficiency, such as improving integration of clinical data. These findings should be tested quantitatively in a larger, representative study.


Asunto(s)
Documentación/métodos , Registros Electrónicos de Salud , Medicina de Emergencia/métodos , Internado y Residencia , Médicos , Flujo de Trabajo , Servicio de Urgencia en Hospital , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo
16.
Am J Kidney Dis ; 33(6): 1064-70, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10352194

RESUMEN

The prevalence of diabetic nephropathy is greater in nonwhite patients with type II diabetes, including the Chinese, and genetic variation appears to have a role. We examined angiotensin-converting enzyme (ACE) DD/II and angiotensinogen (Atg) M235T polymorphism in a cohort of Chinese patients with type II diabetes with an average duration of diabetes of 14 years. Group A (n = 88) did not have significant diabetic nephropathy (creatinine levels 130 micromol/L [>1.48 mg/d], and those undergoing dialysis). The two groups were matched in different aspects, including age, duration of diabetes, blood pressure, and glycemic control. The results showed: (1) no difference of genotype distribution between groups A and B (DD:DI:II, 14%:45%:41% v 8%:38%:54%; P = 0.20; TT:TM/MM, 70%:30% v 76%:24%; P = 0.43), (2) no evidence of synergistic effect of ACE (DD/II) and Atg M235T gene polymorphisms, (3) no difference of allele frequencies between groups A and B (D:I, 36%:64% v 27%:73%; P = 0.20 and T:M, 86%:16% v 86%:14%; P = 0.73), and (4) ACE activity was greatest in patients with DD genotype and least in those with II genotype (DD:DI:II = 66. 9 +/- 13.3 U/L:61.5 +/- 19.9 U/L:45.0 +/- 17.0 U/L; P < 0.005). The data do not support a role of ACE (DD/II) or Atg M235T polymorphism in the development of diabetic nephropathy in Chinese patients with type II diabetes, and no synergistic effect was found between them. Greater ACE activity was associated with DD genotype, and its role in diabetic nephropathy remains to be elucidated.


Asunto(s)
Angiotensinógeno/genética , Diabetes Mellitus Tipo 2/genética , Nefropatías Diabéticas/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Anciano , Pueblo Asiatico/genética , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Peptidil-Dipeptidasa A/sangre
17.
Respir Med ; 95(11): 876-84, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11716201

RESUMEN

A retrospective study was carried out in a Hong Kong regional hospital with 24-h emergency service, to study the factors associated with shorter time to re-admission after acute exacerbation of chronic obstructive pulmonary disease (COPD). From 1 January 1997 to 31 December 1997, the first admission (index admission) of each patient through the emergency room with COPD/chronic bronchitis/emphysema was included. A total of 551 patients fulfilled the inclusion criteria. The total acute and rehabilitative length of stay (mean +/- SD) was 9.41+/-11.67 days. Within 1 year after discharge, 327 patients (59 35%) were re-admitted at least once. Median time to first re-admission after discharge was 240 days. By Cox regression analysis, the following factors were independently associated with shorter time to re-admission: hospital admission within 1 year before index admission, total length of stay in index admission > 5 days, nursing home residency, dependency in self-care activities, right heart strain pattern on electrocardiogram, on high dose inhaled corticosteroid and actual bicarbonate level > 25 mmol l(-1). These factors may be relevant in the future planning of healthcare utilization for COPD patients.


Asunto(s)
Readmisión del Paciente/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica , Actividades Cotidianas , Enfermedad Aguda , Factores de Edad , Anciano , Anciano de 80 o más Años , Intervalos de Confianza , Electrocardiografía , Femenino , Glucocorticoides/uso terapéutico , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/etiología , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Factores de Tiempo
18.
J Bone Joint Surg Am ; 80(7): 980-4, 1998 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9698002

RESUMEN

Fifty-seven revision total hip arthroplasties in fifty-six patients were performed with a Harris-Galante porous-coated acetabular component by one surgeon, and the patients were followed prospectively for a mean of seven years (range, five to twelve years). A trochanteric osteotomy was performed in forty hips, and a posterior approach with an extended anterior capsulectomy was used in the other seventeen. The acetabular defect was classified as segmental in seven hips, cavitary in twenty-three, and combined in twenty-one; six hips had no notable defect. A bulk allograft was used in eleven hips, and morseled cancellous-bone allograft or autogenous graft was used in thirty-four hips; twelve hips did not have bone-grafting. Both the femoral and the acetabular component were revised in forty-five hips, and only the acetabular component was revised in twelve. Thirty-nine hips (68 per cent) had a good or excellent clinical result according to the Harris hip score. The acetabular component was well fixed in the fourteen hips that had a fair result and the four hips that had a poor result. The acetabular component was considered to have migrated if there was a change in the angle of the cup of 5 degrees or more or a change in the horizontal or vertical position of the cup of more than three millimeters. Despite varying degrees of bone loss, no acetabular component had radiographic evidence of loosening at the latest follow-up examination. No component was revised and no revisions were scheduled. One hip was debrided for a late metastatic infection, but the component was well fixed and was not revised. There were no complications related to the use of screws for fixation. These mid-term results confirm the early success of acetabular revisions performed with fixation of a titanium fiber-metal-coated hemispherical component with multiple screws and no cement.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/efectos adversos , Trasplante Óseo , Cementación , Femenino , Estudios de Seguimiento , Articulación de la Cadera/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Porosidad , Estudios Prospectivos , Diseño de Prótesis , Radiografía , Reoperación , Propiedades de Superficie
19.
J Neuroimaging ; 8(1): 3-7, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9442583

RESUMEN

We intended to compare two-dimensional Fourier transform (2DFT) with three-dimensional Fourier transform (3DFT) multiple overlapping thin-slab acquisition (MOTSA) time-of-flight (TOF) magnetic resonance angiography for percent diameter stenosis, length of stenosis, and apparent occlusion at the carotid bifurcation. For that, 101 symptomatic patients (n = 202 carotid bifurcations) were evaluated with 3DFT MOTSA TOF and 2DFT TOF. Three observers measured the percent diameter stenosis from oblique axial multiplanar reformatted (MPR) images and length of stenosis from maximum intensity projection (MIP) images. Kappa analysis assessed interobserver agreement and the Wilcoxon signed rank test was used to compare the two MR angiographic techniques. There was a significant difference in the percent diameter stenosis (p < 0.01) and length of carotid stenosis (p < 0.01) between 2DFT and 3DFT MOTSA TOF magnetic resonance angiography. Stenosis was greater in 33% of carotid arteries and was upgraded (NASCET) in 17% of carotid arteries on the 2DFT TOF. The number of apparently occluded carotid arteries was equal with both MRA techniques. There was good agreement between the three observers (k = .50).


Asunto(s)
Estenosis Carotídea/diagnóstico , Angiografía por Resonancia Magnética/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador
20.
J Reprod Med ; 32(4): 280-4, 1987 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-3585872

RESUMEN

To investigate the role of Chlamydia trachomatis in puerperal endometritis, 72 patients with endometritis following vaginal or cesarean section delivery were studied. Blood, urine and endometrial cultures for aerobic and anaerobic bacteria and for C trachomatis were performed for all patients. C trachomatis was isolated in 25% of patients with endometritis. Patients with post-vaginal-delivery endometritis and a positive C trachomatis culture had a later onset of infection as well as a favorable clinical response to treatment despite persistence of C trachomatis in their endometrial cultures at the end of therapy. Cephalosporins failed to eradicate C trachomatis from endometrial cultures after five days of intravenous therapy.


Asunto(s)
Infecciones por Chlamydia/diagnóstico , Endometritis/etiología , Infección Puerperal/etiología , Adulto , Chlamydia trachomatis/aislamiento & purificación , Femenino , Humanos , Embarazo , Factores de Tiempo
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