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1.
Ann R Coll Surg Engl ; 106(4): 369-376, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37642164

RESUMO

INTRODUCTION: Staging laparoscopy (SL) has become commonplace in the preoperative staging pathway for oesophagogastric (OG) cancer. SL is often performed before curative treatment to examine for macroscopic peritoneal metastases (PM) or positive peritoneal cytology (PPC). The aim of this study was to develop an objective risk scoring system to predict both PM and PPC at SL. METHODS: A prospectively collected and maintained database of all OG cancer patients treated between 2006 and 2020 was reviewed. Univariate and multivariate analyses were performed to identify risk factors for both PM and PPC at SL. A risk score was produced for both PM and PPC, and then validated internally. RESULTS: Among 968 patients who underwent SL, 96 (9.9%) had PM and 81 (8.4%) had PPC at SL. Tumour site (p < 0.001), computed tomography (CT) T stage (p < 0.001) and N stage (p = 0.029) were significantly associated with PM at SL (p < 0.001). Tumour site (p < 0.001), biopsy histology (p = 0.041), CT T stage (p < 0.001) and N stage (p < 0.001) were significantly associated with PPC. The risk scoring model for PM included cancer site and CT T stage. This was successfully tested on the validation set (area under the receiver operating characteristic [AUROC] = 0.730). The risk scoring model for PPC included cancer site, CT T and N stage. This was successfully tested on the validation set (AUROC = 0.773). CONCLUSIONS: The current risk scores are valid tools with which to predict the risk PM and PPC in patients undergoing SL for OG cancer and may help to avoid subjecting patients to unnecessary SL.


Assuntos
Laparoscopia , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Neoplasias Peritoneais/patologia , Estadiamento de Neoplasias , Neoplasias Gástricas/patologia , Laparoscopia/métodos , Peritônio/patologia , Estudos Retrospectivos
2.
BJS Open ; 4(3): 405-415, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32064788

RESUMO

BACKGROUND: Recent evidence suggests that complications after oesophagectomy may decrease short- and long-term survival of patients with oesophageal cancer. This study aimed to analyse the impact of complications on survival in a Western cohort. METHODS: Complications after oesophagectomy were recorded for all patients operated on between January 2006 and February 2017, with severity defined using the Clavien-Dindo classification. Associations between complications and overall and recurrence-free survival were assessed using univariable and multivariable Cox regression models. RESULTS: Of 430 patients, 292 (67·9 per cent) developed postoperative complications, with 128 (39·8 per cent) classified as Clavien-Dindo grade III or IV. No significant associations were detected between Clavien-Dindo grade and either tumour (T) (P = 0·071) or nodal (N) status (P = 0·882). There was a significant correlation between Clavien-Dindo grade and ASA fitness grade (P = 0·032). In multivariable analysis, overall survival in patients with Clavien-Dindo grade I complications was similar to that in patients with no complications (hazard ratio (HR) 0·97, P = 0·915). However, patients with grade II and IV complications had significantly shorter overall survival than those with no complications: HR 1·64 (P = 0·007) and 1·74 (P = 0·013) respectively. CONCLUSION: Increasing severity of complications after oesophagectomy was associated with decreased overall survival. Prevention of complications should improve survival.


Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Idoso , Fístula Anastomótica/mortalidade , Estudos de Coortes , Comorbidade , Inglaterra/epidemiologia , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/mortalidade , Análise de Sobrevida , Centros de Atenção Terciária
3.
Am J Transplant ; 18(6): 1397-1407, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29206349

RESUMO

Prior studies demonstrate that most living kidney donors (LKDs) report no adverse psychosocial outcomes; however, changes in psychosocial functioning at the individual donor level have not been routinely captured. We studied psychosocial outcomes predonation and at 1, 6, 12, and 24 months postdonation in 193 LKDs and 20 healthy controls (HCs). There was minimal to no mood disturbance, body image concerns, fear of kidney failure, or life dissatisfaction, indicating no incremental changes in these outcomes over time and no significant differences between LKDs and HCs. The incidence of any new-onset adverse outcomes postdonation was as follows: mood disturbance (16%), fear of kidney failure (21%), body image concerns (13%), and life dissatisfaction (10%). Multivariable analyses demonstrated that LKDs with more mood disturbance symptoms, higher anxiety about future kidney health, low body image, and low life satisfaction prior to surgery were at highest risk of these same outcomes postdonation. It is important to note that some LKDs showed improvement in psychosocial functioning from pre- to postdonation. Findings support the balanced presentation of psychosocial risks to potential donors as well as the development of a donor registry to capture psychosocial outcomes beyond the mandatory 2-year follow-up period in the United States.


Assuntos
Afeto , Imagem Corporal , Tomada de Decisões , Medo , Transplante de Rim , Doadores Vivos/psicologia , Satisfação Pessoal , Insuficiência Renal/psicologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
4.
Am J Transplant ; 16(3): 869-76, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26845630

RESUMO

Some living kidney donors (LKDs) incur costs associated with donation, although these costs are not well characterized in the United States. We collected cost data in the 12 mo following donation from 182 LKDs participating in the multicenter prospective Kidney Donor Outcomes Cohort (KDOC) Study. Most LKDs (n = 167, 92%) had one direct cost or more following donation, including ground transportation (86%), health care (41%), meals (53%), medications (36%), lodging (23%), and air transportation (12%). LKDs missed 33 072 total work hours, 40% of which were unpaid and led to $302 175 in lost wages (mean $1660). Caregivers lost $68 655 in wages (mean $377). Although some donors received financial assistance, 89% had a net financial loss in the 12-mo period, with one-third (33%) reporting a loss exceeding $2500. Financial burden was higher for those with greater travel distance to the transplant center (Spearman's ρ = 0.26, p < 0.001), lower household income (Spearman's ρ = -0.25, p < 0.001), and more unpaid work hours missed (Spearman's ρ = 0.52, p < 0.001). Achieving financial neutrality for LKDs must be an immediate priority for the transplant community, governmental agencies, insurance companies, nonprofit organizations, and society at large.


Assuntos
Gastos em Saúde/tendências , Falência Renal Crônica/cirurgia , Transplante de Rim/economia , Doadores Vivos , Nefrectomia/economia , Coleta de Tecidos e Órgãos/economia , Adulto , Custos e Análise de Custo , Feminino , Seguimentos , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Estudos Prospectivos
5.
Am J Transplant ; 15(9): 2387-93, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25943721

RESUMO

Limited information exists on the predonation costs incurred by eventual living kidney donors (LKDs). Expenses related to completion of the donation evaluation were collected from 194 LKDs participating in the multi-center, prospective Kidney Donor Outcomes Cohort (KDOC) Study. Most LKDs (n = 187, 96%) reported one or more direct costs, including ground transportation (80%), healthcare (24%), lodging (17%) and air transportation (14%), totaling $101 484 (USD; mean = $523 ± 942). Excluding paid vacation or sick leave, donor and companion lost wages totaled $35 918 (mean = $187 ± 556) and $14 378 (mean = $76 ± 311), respectively. One-third of LKDs used paid vacation or sick leave to avoid incurring lost wages. Few LKDs reported receiving financial support from the transplant candidate (6%), transplant candidate's family (3%), a nonprofit organization (3%), the National Living Donor Assistance Center (7%), or transplant center (3%). Higher total costs were significantly associated with longer distance traveled to the transplant center (p < 0.001); however, total costs were not associated with age, sex, race/ethnicity, household income, marital status, insurance status, or transplant center. Moderate predonation direct and indirect costs are common for adults who complete the donation evaluation. Potential LKDs should be advised of these possible costs, and the transplant community should examine additional strategies to reimburse donors for them.


Assuntos
Custos e Análise de Custo , Gastos em Saúde/tendências , Falência Renal Crônica/cirurgia , Transplante de Rim/economia , Doadores Vivos , Nefrectomia/economia , Obtenção de Tecidos e Órgãos/economia , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
6.
Ann Pharm Fr ; 71(4): 203-15, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23835018

RESUMO

The effect of oxygen on markers of oxidative stress has been partially elucidated. Volatile organic compounds (VOCs) are created during the oxidative burst and excreted in the human alveolar breath, which indeed contains biomarkers. A general concept including collection, separation, detection and clinical biomakers validation is presented in this article: (i) a method for the collection and GC-MS of halogenated VOCs in human alveolar breath is described: a transportable apparatus which sampled specifically alveolar breath; the VOCs were captured in a thermal desorption tube, Carbotrap 200® and each sample was thermally desorbed from the trap in an automated GC-MS apparatus; (ii) the inhibitory effects of halogenated alkanes on mitochondria are suspected likely to fight against oxidative stress deleterious reactions; (iii) two-dimensional gas chromatography occurs by the repeated and re-injection of effluent from one chromatographic column into a second column of orthogonal phase. A new commercial GCxGC system is presented; it is accomplished with a dual-stage, quad-jet thermal modulator positioned between the two columns; (iv) the affinity-based sensors usually used in connection with the GCxGC system face a difficulty to take into account different biases coming from different sources of drifting. Compared to other affinity-based sensing modes like electrical ones, gravimetric sensors enable a better decoupling. Nano Electro Mechanical Systems (NEMS)-based resonators are a particular type of gravimetric gas sensors. They are coated with a sensitive layer of polymer where gases of interest present in the atmosphere adsorb, generating an additional mass load which is measured through a frequency shift; (v) examination of exhaled breath has the potential to change the existing routine approaches in human medicine. Breath sampling to identify volatile biomarkers in diseases has been proposed in several respiratory diseases. Several VOCs have been identified in these patients by GC-MS. However, the use of traditional analytical instruments such as GC-MS to detect biomarkers of diseases has not become a routine for clinical applications. Consequently the electronic nose was the logical instrument of choice for disease diagnosis due to the capability of identifying complex mixtures of VOCs (as a whole) within sampled air using pattern-recognition algorithms.


Assuntos
Biomarcadores/análise , Testes Respiratórios/métodos , Alvéolos Pulmonares/metabolismo , Compostos Orgânicos Voláteis/análise , Alcanos/análise , Animais , Cromatografia Gasosa-Espectrometria de Massas , Halogênios/química , Humanos , Hidrocarbonetos Halogenados/análise , Hipertensão Pulmonar/diagnóstico
7.
Neurogastroenterol Motil ; 24(11): 990-e539, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22680279

RESUMO

BACKGROUND: Proximal displacement of the gastro-esophageal junction (GEJ) is present in hiatus hernia but also occurs transiently during transient lower esophageal sphincter relaxations (TLESRs) and swallows. Using a novel magnetic-based technique we have performed detailed examination of the GEJ movement during TLESRs and swallows in healthy subjects. METHODS: In 12 subjects, a magnet was endoscopically clipped to the GEJ and combined assembly of Hall-Effect locator probe and 36 channel high-resolution manometer passed nasally. After a test meal the subjects were studied for 90 min. KEY RESULTS: The median amplitude of proximal movement of GEJ during TLESRs was 4.3 cm (1.6-8.8 cm) and this was substantially greater than during swallowing at 1.2 cm (0.4-2.7 cm), P = 0.002. With both TLESRs and swallows proximal GEJ movement coincided with lower esophageal sphincter (LES) relaxation and return to its original position occurred 4 s after return of LES tone. Kinetic modeling of the movement of the GEJ during TLESRs indicated two return phases with the initial return phase having the greater velocity (0.9 cm s(-1) ) and being strongly correlated with amplitude of proximal movement (r = 0.8, P < 0.001). CONCLUSIONS & INFERENCES: The marked proximal GEJ migration during TLESRs represents very severe herniation of the GEJ. The rapid initial return of the GEJ following TLESRs when the crural diaphragm is relaxed and its correlation with amplitude suggest it is due to elastic recoil of the phreno-esophageal ligament. The marked stretching of the phreno-esophageal ligament during TLESRs may contribute to its weakening and development of established hiatus hernia.


Assuntos
Deglutição/fisiologia , Esfíncter Esofágico Inferior/fisiologia , Junção Esofagogástrica/fisiologia , Hérnia Hiatal/fisiopatologia , Complexo Mioelétrico Migratório/fisiologia , Adulto , Idoso , Endoscopia do Sistema Digestório , Feminino , Humanos , Cinética , Masculino , Manometria , Pessoa de Meia-Idade , Músculo Liso/fisiologia , Adulto Jovem
9.
Neurogastroenterol Motil ; 24(1): 61-4, e11, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22188326

RESUMO

BACKGROUND: The high resolution esophageal manometry system manufactured by Sierra Scientific Instruments is widely used. The technology is liable to 'thermal drift', a change in measured pressure due to change in temperature. This study aims to characterize 'thermal drift' and minimize its impact. METHODS: Response of the system to immediate temperature change (20 °C to 37 °C) was tested. Accuracy of pressure measurement over two hours at 37 °C was examined. Six repetitions were performed and median pressure change calculated for each sensor. Sensors were compared using Kruskal-Wallis test. Current correction processes were tested. KEY RESULTS: There was a biphasic response of the system to body temperature: an immediate change in recorded pressure, 'thermal effect' and an ongoing pressure change with time, 'baseline drift'. Median thermal effect for all 36 sensors was 7 mmHg (IQR 3.8 mmHg). Median baseline drift was 11.1 mmHg (IQR 9.9 mmHg). Baseline drift varied between sensors but for a given sensor was linear. Interpolated thermal compensation, recommended for prolonged studies, corrects data assuming a linear drift of pressures. When pressures were corrected in this way, baseline pressure was almost restored to zero (Median 0.3 mmHg, IQR 0.3). The standard thermal compensation process did not address the error associated with baseline drift. CONCLUSIONS & INFERENCES: Thermal effect is well compensated in the current operation of the system but baseline drift is not well recognized or addressed. Incorporation of a linear correction into current software would improve accuracy without impact on ease of use.


Assuntos
Temperatura Corporal , Esôfago/fisiologia , Manometria/instrumentação , Manometria/métodos , Manometria/normas , Desenho de Equipamento , Esôfago/anatomia & histologia , Humanos , Pressão , Reprodutibilidade dos Testes , Transdutores de Pressão
10.
Am J Transplant ; 11(2): 356-60, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21272238

RESUMO

Optimizing the possibilities for kidney-paired donation (KPD) requires the participation of donor-recipient pairs from wide geographic regions. Initially it was envisaged that donors would travel to the recipient center; however, to minimize barriers to participation and simplify logistics, recent trends have involved transporting the kidneys rather than the donors. The goal of this study was to review outcomes of this practice. KPD programs throughout the United States were directly queried about all transplants involving live donor kidney transport. Early graft function was assessed by urine output in the first 8 h, postoperative serum creatinine trend, and incidence of delayed graft function. Between April 27, 2007 and April 29, 2010, 56 live donor kidneys were transported among 30 transplant centers. Median CIT was 7.2 h (IQR 5.5-9.7, range 2.5-14.5). Early urine output was robust (>100 cc/h) in all but four patients. Creatinine nadir was <2.0 mg/dL in all (including the four with lower urine output) but one patient, occurring at a median of 3 days (IQR 2-5, range 1-49). No patients experienced delayed graft function as defined by the need for dialysis in the first week. Current evidence suggests that live donor kidney transport is safe and feasible.


Assuntos
Doação Dirigida de Tecido , Transplante de Rim/métodos , Doadores Vivos , Meios de Transporte , Adulto , Idoso , Creatinina/sangue , Função Retardada do Enxerto/etiologia , Feminino , Humanos , Transplante de Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos , Fatores de Tempo , Obtenção de Tecidos e Órgãos , Estados Unidos
11.
Nano Lett ; 10(10): 3899-903, 2010 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-20795729

RESUMO

Miniaturized gas chromatography (GC) systems can provide fast, quantitative analysis of chemical vapors in an ultrasmall package. We describe a chemical sensor technology based on resonant nanoelectromechanical systems (NEMS) mass detectors that provides the speed, sensitivity, specificity, and size required by the microscale GC paradigm. Such NEMS sensors have demonstrated detection of subparts per billion (ppb) concentrations of a phosphonate analyte. By combining two channels of NEMS detection with an ultrafast GC front-end, chromatographic analysis of 13 chemicals was performed within a 5 s time window.

12.
J Hum Nutr Diet ; 17(2): 117-9, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15023191

RESUMO

INTRODUCTION: The long-term effects on diet of dietary advice to eat fruit and vegetables or fatty fish are not well described. MATERIALS AND METHODS: From 1990 to 1996 3114 men aged 37-70 with treated angina were recruited from general practices in South Wales. A dietitian randomly allocated the eligible men to receive advice to eat more fruit and vegetables, or advice to eat more fatty fish, or both these types of advice or neither. In 2000, a brief self-completion questionnaire was sent to a sample of 1191 of the men known to be alive at the end of March 1999. RESULTS: The questionnaire was returned by 944 of the 1036 men alive at the time the questionnaire was sent. Those given fish advice were consuming more fatty fish but the difference was modest 21.9 g day(-1) vs. 14.0 g day(-1) (P < 0.01). The differences in fruit and vegetables intake between those given fruit advice and those not given fruit advice were small 373.2 g day(-1) vs. 351.7 g day(-1) (P = 0.05). DISCUSSION: Men of this age group may be particularly resistant to fruit and vegetables advice; population-based interventions or interventions targeted at women might be more effective.


Assuntos
Angina Pectoris/dietoterapia , Dieta , Adulto , Idoso , Animais , Gorduras na Dieta/administração & dosagem , Dietética , Óleos de Peixe/administração & dosagem , Peixes , Frutas , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Verduras , País de Gales
13.
Eur J Clin Nutr ; 57(3): 483-9, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12627187

RESUMO

BACKGROUND: Various mechanisms have been proposed to explain the association between plasma total homocysteine (tHcy) and risk of cardiovascular disease, including oxidative activity of homocysteine. OBJECTIVE: To explore the putative role of reactive oxygen species in the association between plasma tHcy and risk of cardiovascular disease in healthy individuals. DESIGN: A double-blind, placebo-controlled crossover intervention to increase folate intake through diet (increased consumption of folate-rich foods) and supplement (400 micro g folic acid) was carried out in 126 healthy men and women. Measurements were made of antioxidant activity in red blood cells and plasma, and products of oxidant damage in plasma. RESULTS: Diet and supplement-based interventions led to an increase in measures of folate status and a reduction in plasma tHcy. This was not associated with any significant change in measures of antioxidant activity (plasma and red blood cell glutathione peroxidase activity and red blood cell superoxide dismutase activity) or oxidant damage (plasma malondialdehyde), although an improvement in plasma total antioxidant capacity just failed to reach significance. CONCLUSIONS: In healthy individuals lowering plasma tHcy does not have any functional implications regarding oxidative damage.


Assuntos
Antioxidantes/metabolismo , Doenças Cardiovasculares/sangue , Ácido Fólico/administração & dosagem , Homocisteína/sangue , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Ácido Fólico/sangue , Ácido Fólico/metabolismo , Glutationa Peroxidase/metabolismo , Homocisteína/metabolismo , Humanos , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Estado Nutricional , Oxirredução , Espécies Reativas de Oxigênio , Fatores de Risco , Método Simples-Cego , Superóxido Dismutase/metabolismo
14.
Eur J Clin Nutr ; 57(2): 316-23, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12571666

RESUMO

OBJECTIVE: To assess and compare the effects of natural folate (100 micro g) with those of folic acid from fortified sources (100 micro g/day) on plasma folate and homocysteine. DESIGN: Randomized controlled trial (parallel groups). SETTING: Men and women living in South Wales, UK. SUBJECTS: A total of 135 healthy individuals recruited from the local workforce and blood donor sessions. All subjects possessed the 'wild-type' CC genotype for C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR). INTERVENTIONS: Subjects underwent one of the following dietary interventions for 4 months: (1) fortified diet-usual diet plus 100 microg/day folic acid from fortified foods; (2) natural folate diet-usual diet plus 100 microg/day folate from natural sources; (3) control-usual diet. RESULTS: The fortified group increased reported intake of folic acid from fortified foods compared to other groups (P<0.001) achieving an extra 98 microg/day (95% CI 88-108). The natural folate group increased reported intake of natural source folates compared with the other two groups (P<0.001), but achieved a mean increase of only 50 microg/day (95% CI 34-66). Plasma folate increased (P<0.01) by a similar amount in both intervention groups compared to controls (fortified group 2.97, 95% CI 0.8-5.1; natural group 2.76, 95% CI 0.6-4.9. Plasma homocysteine, vitamins B(6) and B(12) were not significantly changed. CONCLUSIONS: Subjects achieved increases in folate intake using fortified foods more easily than by folate-rich foods, however both sources increased plasma folate by a similar amount. These levels of intake were insufficient to reduce homocysteine concentrations in MTHFR CC homozygotes, but may be more effective in other genotypes.


Assuntos
Ácido Fólico/sangue , Ácido Fólico/farmacologia , Alimentos Fortificados , Frutas , Homocisteína/sangue , Política Nutricional , Verduras , Adolescente , Adulto , Idoso , Registros de Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reino Unido
15.
Z Kardiol ; 91(8): 614-9, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12426824

RESUMO

BACKGROUND: Clinical trials suggest an increased frequency of restenosis after coronary intervention in left anterior descending (LAD) compared to the left circumflex or right coronary arteries. Experimental studies correlate stent-induced arterial injury and the extent of neointima formation. This study investigates whether the coronary artery affects the relationship between arterial injury and neointima hyperplasia in the porcine stent model. METHODS: Non-lipemic farm pigs underwent stent placement in the LAD (n = 26) and the right coronary artery (RCA; n = 30). Quantitative coronary angiography (QCA) was performed before and after stent placement, and at follow-up; quantitative histomorphometry and injury score were analyzed at 30-day follow-up. RESULTS: Initial procedure balloon/artery ratios (LAD 1.17 +/- 0.11 vs RCA 1.17 +/- 0.09, P = NS), and minimal stent lumen diameters (MLD; LAD 2.91 +/- 0.31 vs RCA: 2.93 +/- 0.28 mm, P = NS) were similar suggesting no difference in deployment technique. At follow-up there was more restenosis in the LAD (diameter stenosis: 55.0 +/- 26.4% vs 37.3 +/- 18.1%, and MLD: 1.24 +/- 0.78 mm vs. 1.71 +/- 0.57 mm, P < 0.05 for both comparisons). No differences were seen for injury score (1.09 +/- 0.51 vs 1.01 +/- 0.57; LAD vs RCA) or stent area (6.13 +/- 0.99 vs 6.55 +/- 1.42 mm2). Histomorphometry demonstrated smaller lumen area (2.15 +/- 0.94 vs 2.96 +/- 1.29 mm2) and thicker neointima (0.63 +/- 0.25 vs 0.51 +/- 0.17 mm; all P < 0.05) in the LAD. Multiple linear regression analysis identified the LAD as an independent predictive factor for increased neointima formation. CONCLUSIONS: These observations establish an animal model that is consistent with clinical experience showing that restenosis after stenting is more common in the LAD. The findings may be useful for understanding and developing systemic and local antirestenotic strategies.


Assuntos
Angioplastia Coronária com Balão/instrumentação , Reestenose Coronária/patologia , Vasos Coronários/lesões , Stents , Túnica Íntima/lesões , Animais , Angiografia Coronária , Reestenose Coronária/diagnóstico por imagem , Vasos Coronários/patologia , Modelos Animais de Doenças , Displasia Fibromuscular/diagnóstico por imagem , Displasia Fibromuscular/patologia , Processamento de Imagem Assistida por Computador , Modelos Lineares , Suínos , Túnica Íntima/patologia
16.
Br J Cancer ; 86(12): 1864-70, 2002 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-12085177

RESUMO

This randomised, double-blind, placebo-controlled study was designed to evaluate the ability of the orally administered matrix metalloproteinase inhibitor, marimastat, to prolong survival in patients with non-resectable gastric and gastro-oesophageal adenocarcinoma. Three hundred and sixty-nine patients with histological proof of adenocarcinoma, who had received no more than a single regimen of 5-fluorouracil-based chemotherapy, were randomised to receive either marimastat (10 mg b.d.) or placebo. Patients were treated for as long as was tolerable. The primary endpoint was overall survival with secondary endpoints of time to disease progression and quality of life. At the point of protocol-defined study completion (85% mortality in the placebo arm) there was a modest difference in survival in the intention-to-treat population in favour of marimastat (P=0.07 log-rank test, hazard ratio=1.23 (95% confidence interval 0.98-1.55)). This survival benefit was maintained over a further 2 years of follow-up (P=0.024, hazard ratio=1.27 (1.03-1.57)). The median survival was 138 days for placebo and 160 days for marimastat, with 2-year survival of 3% and 9% respectively. A significant survival benefit was identified at study completion in the pre-defined sub-group of 123 patients who had received prior chemotherapy (P=0.045, hazard ratio=1.53 (1.00-2.34)). This benefit increased with 2 years additional follow-up (P=0.006, hazard ratio=1.68 (1.16-2.44)), with 2-year survival of 5% and 18% respectively. Progression-free survival was also significantly longer for patients receiving marimastat compared to placebo (P=0.009, hazard ratio=1.32 (1.07-1.63)). Marimastat treatment was associated with the development of musculoskeletal pain and inflammation. Events of anaemia, abdominal pain, jaundice and weight loss were more common in the placebo arm. This is one of the first demonstrations of a therapeutic benefit for a matrix metalloproteinase inhibitor in cancer patients. The greatest benefit was observed in patients who had previously received chemotherapy. A further randomised study of marimastat in these patients is warranted.


Assuntos
Adenocarcinoma/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adulto , Idoso , Estudos de Casos e Controles , Método Duplo-Cego , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/farmacocinética , Feminino , Humanos , Ácidos Hidroxâmicos/efeitos adversos , Ácidos Hidroxâmicos/farmacocinética , L-Lactato Desidrogenase/metabolismo , Masculino , Metaloendopeptidases/antagonistas & inibidores , Pessoa de Meia-Idade , Segurança , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Distribuição Tecidual , Resultado do Tratamento
17.
Gut ; 50(3): 378-81, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11839718

RESUMO

BACKGROUND: A large proportion of patients attending open access endoscopy have histological and gross pathological findings that are potentially premalignant. The proportion of these patients who go on to develop malignancies and the timescale over which this occurs are uncertain. AIMS: This study aims to discover the incidence of gastric cancers in this "high risk" group and to examine the potential for their early diagnosis and treatment. PATIENTS: A total of 1753 patients attended open access endoscopy. From these, 166 patients with dysplasia, intestinal metaplasia, atrophic gastritis, foveolar hyperplasia, regenerative changes, polyps, or ulcers who agreed to undergo annual surveillance endoscopy were studied. METHODS: Patients were endoscoped annually. Additionally, patients with ulcers were re-examined at two monthly intervals until ulcer healing. Cancers detected were treated by gastrectomy. RESULTS: Twenty two of 1753 patients attending open access endoscopy had gastric cancer (1.3%). In the study population, 14 cancers were detected over 10 years (8.4 %). These were of an earlier stage than those detected at open access (stage I and II 67% v 23%; p<0.05) and five year survival was significantly higher (50% v 10%; p=0.006). In atrophic gastritis and intestinal metaplasia the risk of malignancy was 11%. CONCLUSIONS: In patients with atrophic gastritis or intestinal metaplasia, annual surveillance can detect most new tumours at an early stage with a major improvement in survival. Potential benefits of such a surveillance programme are large and warrant further investigation in a multicentre randomised controlled trial.


Assuntos
Vigilância da População , Lesões Pré-Cancerosas/diagnóstico , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Inglaterra , Seguimentos , Gastrite Atrófica/diagnóstico , Gastroscopia , Humanos , Metaplasia/diagnóstico , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estômago/patologia , Neoplasias Gástricas/patologia , Úlcera Gástrica/diagnóstico , Taxa de Sobrevida
18.
J Am Coll Cardiol ; 38(7): 1799-805, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11738277

RESUMO

OBJECTIVES: We sought to study the effect of low-dose folic acid supplementation or optimization of dietary folate intake on plasma homocysteine and endothelial function in healthy adults. BACKGROUND: Elevated homocysteine is associated with cardiovascular disease, but it is not known whether this relationship is causal. Individuals homozygous (TT) for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene ( approximately 12% of the population) have increased homocysteine levels, particularly in association with suboptimal folate intake. METHODS: Healthy subjects (n = 126; 42 of each MTHFR genotype) were included in this cross-over study of three interventions of four months each: 1) placebo plus natural diet; 2) daily 400-microg folic acid supplement plus natural diet; and 3) increased dietary folate intake to 400 microg/day. RESULTS: At baseline, homocysteine was inversely related to plasma folate and was higher in TT homozygotes. For the whole group, plasma folate increased by 46% after dietary folate and by 79% after supplementation, with reductions of homocysteine of 14% and 16%, respectively. Within the genotype, TT homozygotes exhibited the most marked changes in these variables. Brachial artery endothelial function, as determined by a change in end-diastolic diameter in response to increased flow, was not changed by increased folate intake (98 +/- 73 microm at baseline, 110 +/- 69 microm after a high-folate diet, 114 +/- 59 microm after supplementation and 118 +/- 68 microm after placebo). Plasma von Willebrand factor antigen was unaltered. CONCLUSIONS: Optimization of dietary folate or low-dose folic acid supplementation reduces plasma homocysteine but does not enhance endothelial function, irrespective of the MTHFR (C667T) genotype.


Assuntos
Endotélio Vascular/efeitos dos fármacos , Ácido Fólico/administração & dosagem , Genótipo , Homocisteína/sangue , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Adolescente , Adulto , Idoso , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Ácido Fólico/sangue , Homozigoto , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2) , Pessoa de Meia-Idade , Necessidades Nutricionais , Valores de Referência , Resistência Vascular/genética , Resistência Vascular/fisiologia
19.
IEEE Trans Med Imaging ; 20(10): 990-8, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11686445

RESUMO

Layer decomposition is a promising method for obtaining accurate densitometric profiles of diseased coronary artery segments. This method decomposes coronary angiographic image sequences into moving densitometric layers undergoing translation, rotation, and scaling. In order to evaluate the accuracy of this technique, we have developed a technique for embedding realistic simulated moving stenotic arteries in real clinical coronary angiograms. We evaluate the accuracy of layer decomposition in two ways. First, we compute tracking errors as the distance between the true and estimated motion of a reference point in the arterial lesion. We find that noise-weighted phase correlation and layered background subtraction are superior to cross correlation and fixed mask subtraction, respectively. Second, we compute the correlation coefficient between the true vessel profile and the raw and processed images in the region of the stenosis. We find that layer decomposition significantly improves the correlation coefficient.


Assuntos
Simulação por Computador , Angiografia Coronária/métodos , Vasos Coronários/patologia , Densitometria/métodos , Algoritmos , Humanos , Modelos Anatômicos , Reprodutibilidade dos Testes , Processamento de Sinais Assistido por Computador
20.
Anal Chem ; 73(19): 4668-75, 2001 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-11605845

RESUMO

Vacuum-outlet GC with atmospheric-pressure air as the carrier gas is implemented at outlet pressures up to 0.8 atm using a low-dead-volume polymer-coated surface acoustic wave (SAW) detector. Increases in the system outlet pressure from 0.1 to 0.8 atm lead to proportional increases in detector sensitivity and significant increases in column efficiency. The latter effect arises from the fact that optimal carrier gas velocities are lower in air than in more conventional carrier gases such as helium or hydrogen due to the smaller binary diffusion coefficients of vapors in air. A 12-m-long, 0.25-mm-i.d. tandem column ensemble consisting of 4.5-m dimethyl polysiloxane and 7.5-m trifluoropropylmethyl polysiloxane operated at an outlet pressure of 0.5 atm provides up to 4 x 10(4) theoretical plates and a peak capacity of 65 (resolution, 1.5) for a 3-min isothermal analysis. At 30 degrees C, mixtures of vapors ranging in vapor pressure from 8.6 to 76 Torr are separated in this time frame. The SAW detector cell has an internal volume of < 2 microL, which allows the use of higher column outlet pressures with minimal dead time. The sensor response is linear with solute mass over at least 2-3 decades and provides detection limits of 20-50 ng for the vapors tested. The combination of atmospheric-pressure air as carrier gas, modest operating pressures, and SAW sensor detection is well-suited for field instrumentation since it eliminates the need for support gases, permits smaller, low-power pumps to be used, and provides sensitivity to a wide range of vapor analytes.


Assuntos
Cromatografia Gasosa/instrumentação , Acústica , Ar , Poluentes Atmosféricos/análise , Pressão do Ar , Cromatografia Gasosa/métodos , Compostos Orgânicos/análise , Vácuo , Volatilização
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