RESUMO
Background/purpose. To evaluate the impact of intensity-modulated radiotherapy (IMRT) with intra-prostate fiducial markers image-guided radiotherapy (IGRT) on the incidence of late urinary toxicity compared to 3D conformal radiotherapy (3DCRT) for patients with prostate cancer (PC). Methods and materials. We selected 733 consecutive patients with localized PC treated with dose-escalation radiotherapy between 2001 and 2014. Eligibility criteria were radiation dose >72.0 Gy, no pelvic RT and minimum follow-up 24 months. 438 patients were treated with 3DCRT and 295 with IMRT. Acute and late urinary complications were assessed using the EORTC/RTOG and CTCAEs v3.0 definition. The Cox regression model was used to compare grade ≥2 urinary toxicity between both techniques. The median follow-up was 75 months (range 24-204). Results. The median isocenter radiation dose was 78.7 Gy for 3DCRT and 80.7 Gy for IMRT/IGRT (p < 0.001). The 5-year incidence of late grade ≥2 urinary toxicity was 6.4% for IMRT and 10.8% for 3DCRT [hazard ratio (HR) 0.575, p = 0.056]. The corresponding 5-year estimates of late grade ≥2 hematuria were 2% for IMRT and 5.3% for 3DCRT (HR 0.296, p = 0.024). On multivariate analysis, the antecedent of prior transurethral resection of the prostate was also a strong predictor of a higher risk of urinary complications (HR 2.464, p = 0.002) and of hematuria (HR 5.196, p < 0.001). Conclusion. Compared with 3DCRT, high-dose IMRT/IGRT is associated with a lower rate of late urinary complications in spite of higher radiation dose (AU)
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Humanos , Masculino , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/urina , Radioterapia de Intensidade Modulada/instrumentação , Radioterapia de Intensidade Modulada , Radioterapia Guiada por Imagem/métodos , Medidas de Toxicidade , Ressecção Transuretral da Próstata , Análise Multivariada , Radioterapia/métodosRESUMO
UNLABELLED: The aim of this study was to investigate vitamin D status and stress fracture risk during Royal Marine military training. Poor vitamin D status was associated with an increased risk of stress fracture. Vitamin D supplementation may help to reduce stress fracture risk in male military recruits with low vitamin D status. INTRODUCTION: Stress fracture is a common overuse injury in military recruits, including Royal Marine (RM) training in the UK. RM training is recognised as one of the most arduous basic training programmes in the world. Associations have been reported between serum 25-hydroxyvitamin D (25(OH)D) and risk of stress fracture, but the threshold of 25(OH)D for this effect remains unclear. We aimed to determine if serum 25(OH)D concentrations were associated with stress fracture risk during RM training. METHODS: We prospectively followed 1082 RM recruits (males aged 16-32 years) through the 32-week RM training programme. Troops started training between September and July. Height, body weight and aerobic fitness were assessed at week 1. Venous blood samples were drawn at weeks 1, 15 and 32. Serum samples were analysed for 25(OH)D and parathyroid hormone (PTH). RESULTS: Seventy-eight recruits (7.2 %) suffered a total of 92 stress fractures. Recruits with a baseline serum 25(OH)D concentration below 50 nmol L(-1) had a higher incidence of stress fracture than recruits with 25(OH)D concentration above this threshold (χ(2) (1) = 3.564, p = 0.042; odds ratio 1.6 (95 % confidence interval (CI) 1.0-2.6)). Baseline serum 25(OH)D varied from 47.0 ± 23.7 nmol L(-1) in February, to 97.3 ± 24.6 nmol L(-1) in July (overall mean 69.2 ± 29.2 nmol L(-1), n = 1016). There were weak inverse correlations between serum 25(OH)D and PTH concentrations at week 15 (r = -0.209, p < 0.001) and week 32 (r = -0.214, p < 0.001), but not at baseline. CONCLUSION: Baseline serum 25(OH)D concentration below 50 nmol L(-1) was associated with an increased risk of stress fracture. Further studies into the effects of vitamin D supplementation on stress fracture risk are certainly warranted.
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Fraturas de Estresse/etiologia , Militares/estatística & dados numéricos , Doenças Profissionais/etiologia , Condicionamento Físico Humano/efeitos adversos , Deficiência de Vitamina D/complicações , Vitamina D/análogos & derivados , Adolescente , Adulto , Antropometria/métodos , Estudos de Casos e Controles , Fraturas de Estresse/sangue , Humanos , Masculino , Doenças Profissionais/sangue , Hormônio Paratireóideo/sangue , Condicionamento Físico Humano/fisiologia , Aptidão Física/fisiologia , Estudos Prospectivos , Fatores de Risco , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Adulto JovemRESUMO
A stereotactic brain biopsy system that is magnetic resonance (MR) imaging-guided has not been validated in dogs. Our purpose was to determine the mean needle placement error in the caudate nucleus, thalamus, and midbrain of a canine cadaver brain using the modified Brainsight stereotactic system. Relocatable reference markers (fiducial markers) were attached to the cadaver head using a dental bite block. A T1-weighted gradient echo three-dimensional (3D) sequence was acquired using set parameters. Fiducial markers were used to register the head to the acquired MR images in reference to a 3D position sensor. This allowed the planning of trajectory path to brain targets in real time. Coordinates (X, Y, Z) were established for each target and 0.5 microl of diluted gadolinium was injected at each target using a 26-gauge needle to create a lesion. The center of the gadolinium deposition was identified on the postoperative MR images and coordinates (X', Y', Z') were established. The precision of this system in bringing the needle to target (needle placement error) was calculated. Seventeen sites were targeted in the brain. The mean needle placement error for all target sites was 1.79 +/- 0.87 mm. The upper bound of error for this stereotactic system was 3.31 mm. There was no statistically significant relationship between needle placement error and target depth (P = 0.23). The ease of use and precision of this stereotactic system support its development for clinical use in dogs with brain lesions > 3.31 mm.
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Biópsia por Agulha/veterinária , Encéfalo/patologia , Cães , Imagem por Ressonância Magnética Intervencionista/veterinária , Técnicas Estereotáxicas/veterinária , Animais , Biópsia por Agulha/métodos , Núcleo Caudado/patologia , Mesencéfalo/patologia , Tálamo/patologiaRESUMO
BACKGROUND: Previous studies have shown that plasma free choline concentrations are significantly decreased in many long-term home total parenteral nutrition (TPN) patients. Furthermore, low choline status has been associated with both hepatic morphologic and hepatic aminotransferase abnormalities. A preliminary pilot study suggested choline-supplemented TPN may be useful in reversal of these hepatic abnormalities. METHODS: Fifteen patients (10 M, 5 F) who had required TPN for > or =80% of their nutritional needs were randomized to receive their usual TPN (n = 8), or TPN to which 2 g choline chloride had been added (n = 7) for 24 weeks. Baseline demographic data were similar between groups. Patients had CT scans of the liver and spleen, and blood for plasma free and phospholipid-bound choline, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, gamma glutamyl transferase (GGT), bilirubin, serum lipids, complete blood count (CBC), and chemistry profile obtained at baseline, and weeks 2, 4, 6, 12, 16, 20, 24, and 34. CT scans were analyzed for Hounsfield unit (HU) densities. RESULTS: There were no significant differences in any measured parameters after 2 weeks. However, at 4 weeks, a significant difference in liver HU between groups was observed (13.3+/-5.0 HU [choline] vs 5.8+/-5.2 HU [placebo], p = .04). This significant trend continued through week 24. Recurrent hepatic steatosis and decreased HU were observed at week 34, 10 weeks after choline supplementation had been discontinued. A significant increase in the liver-spleen differential HU was also observed in the choline group (10.6+/-6.2 HU [choline] vs 1.3+/-3.3 HU [placebo], p = .01). Serum ALT decreased significantly (p = .01 to .05) in the choline group vs placebo at weeks 6,12, 20, and 24. Serum AST was significantly decreased in the choline group by week 24 (p = .02). The serum alkaline phosphatase was significantly reduced in the choline group at weeks 2, 12, 20, 24, and 34 (p = .02 to 0.07). Total bilirubin was normal in these patients and remained unchanged during the study. Serum GGT tended to decrease more in the choline group, but the greater decrease was not statistically significant. CONCLUSIONS: Choline deficiency is a significant contributor to the development of TPN-associated liver disease. The data suggest choline is a required nutrient for long-term home TPN patients.
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Deficiência de Colina/terapia , Colina/administração & dosagem , Lipotrópicos/administração & dosagem , Fígado/patologia , Nutrição Parenteral Total/efeitos adversos , Adulto , Colina/sangue , Suplementos Nutricionais , Emulsões Gordurosas Intravenosas , Feminino , Humanos , Lipotrópicos/sangue , Fígado/enzimologia , Masculino , Necessidades Nutricionais , Baço/patologia , Tomografia Computadorizada por Raios X , Transaminases/metabolismoRESUMO
BACKGROUND: Previous investigations have demonstrated that choline deficiency, manifested in low plasma-free choline concentration and hepatic injury, may develop in patients who require long-term total parenteral nutrition (TPN). Preliminary studies have suggested lecithin or choline supplementation might lead to improved visual memory in the elderly and reverse abnormal neuropsychological development in children. We sought to determine if choline-supplemented TPN would lead to improvement in neuropsychological test scores in a group of adult, choline-deficient outpatients receiving TPN. METHODS: Eleven subjects (8 males, 3 females) who received nightly TPN for more than 80% of their nutritional needs for at least 12 weeks before entry in the study were enrolled. Exclusion criteria included active drug abuse, mental retardation, cerebral vascular accident, head trauma, hemodialysis or peritoneal dialysis, (prothrombin time [PT] >2x control), or acquired immune deficiency syndrome (AIDS). Patients were randomly assigned to receive their usual TPN regimen (n = 6, aged 34.0 +/- 12.6 years) over a 12-hour nightly infusion or their usual TPN regimen plus choline chloride (2 g) (n = 5, aged 37.3 +/- 7.3 years). The following neuropsychological tests were administered at baseline and after 24 weeks of choline supplementation (or placebo): Weschler Adult Intelligence Scale-Revised (WAIS-R, intellectual functioning), Weschler Memory Scale-Revised (WMS-R, two subtests, verbal and visual memory), Rey-Osterrieth Complex Figure Test (visuospatial functioning and perceptual organization), Controlled Oral Word Association Test (verbal fluency), Grooved Pegboard (manual dexterity and motor speed), California Verbal Learning Test (CVLT, rote verbal learning ability), and Trail Making Parts A & B (visual scanning, psychomotor speed and set shifting). Scores were reported in terms of standard scores including z scores and percentile ranks. Mean absolute changes in raw scores were compared between groups using the Wilcoxon rank sum test, where p values < .05 constituted statistical significance. RESULTS: Significant improvements were found in the delayed visual recall of the WMS-R (7.0 +/- 2.7 vs -.33 +/- 5.7, p = .028), and borderline improvements in the List B subset of the CVLT (1.0 +/- 0.8 vs -2.0 +/- 2.4, p = .06) and the Trails A test (-3.8 +/- 8.1 vs 3.7 +/- 4.5 seconds, p = .067). No other statistically significant changes were seen. CONCLUSIONS: This pilot study indicates both verbal and visual memory may be impaired in patients who require long-term TPN and both may be improved with choline supplementation.
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Deficiência de Colina/complicações , Colina/farmacologia , Transtornos da Memória/prevenção & controle , Memória/efeitos dos fármacos , Nutrição Parenteral Total , Adulto , Colina/administração & dosagem , Colina/sangue , Deficiência de Colina/etiologia , Suplementos Nutricionais , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Transtornos da Memória/etiologia , Testes Neuropsicológicos , Nutrição Parenteral Total/efeitos adversos , Fatores de TempoRESUMO
BACKGROUND: Choline deficiency may develop in malnourished patients, those with cirrhosis, and those who require total parenteral nutrition. Previous data has suggested an important role for the kidneys in the maintenance of choline homeostasis. OBJECTIVE: This study was undertaken to determine the change in plasma choline during hemodialysis and to determine if it was lost in the dialysate. DESIGN: Thirteen adult patients (10 men, 3 women) who had required hemodialysis for a mean of 10.8 years were studied. Dialysis was performed 3 times weekly for 4 hours using either a cellulose acetate or polysulfone dialyzer membrane. Venous and arterial blood, and dialysate samples were taken for measurement of plasma free and phospholipid-bound choline concentration before beginning dialysis and after each hour of dialysis. An in vitro system was devised to determine if choline could bind to a significant degree to the dialysis membrane. RESULTS: Plasma free choline concentration was increased above normal (11.7 +/- 3.7 nmol/mL) at baseline and declined progressively during dialysis. In contrast, plasma phospholipid-bound choline concentration increased progressively during dialysis. The decrease in plasma free choline (-1.8 +/- 0.3 nmol/mL(-1)/h(-1); P = 1.6 x 10(-6)) was almost entirely related to that which was removed during dialysis, although the magnitude of the loss was not correlated with the increase in plasma phospholipid-bound choline concentration (125 +/- 20.5 nmol/mL(-1)/h(-1); P < 1.2 x 10(-6)). Patients lost a mean of 246 pmol of free choline during hemodialysis. Choline did not bind to the dialysis membrane. CONCLUSION: Plasma free choline concentration is elevated before dialysis, and choline is lost to a significant degree in the dialysate. Further investigation is necessary to determine whether a transient, dialysis-induced choline deficiency develops, and whether there is a role for choline supplementation in these patients. The choline homeostatic mechanism requires further investigation in renal failure patients.
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Deficiência de Colina/prevenção & controle , Colina/metabolismo , Soluções para Hemodiálise/química , Falência Renal Crônica/complicações , Fosfolipídeos/metabolismo , Diálise Renal , Adulto , Colina/sangue , Deficiência de Colina/dietoterapia , Feminino , Humanos , Técnicas In Vitro , Falência Renal Crônica/terapia , Masculino , Nutrição Parenteral Total , Fosfolipídeos/análiseRESUMO
BACKGROUND: Previous studies have shown that plasma and urinary free choline concentrations decrease significantly during a marathon, and that these decreases may be associated with decreased performance. OBJECTIVE: In a pilot study, we sought to determine whether lecithin supplementation prior to a marathon would maintain plasma free and urinary choline concentrations and improve performance versus placebo. METHODS: 12 accomplished marathon runners, males (7) and females (5), 21 to 50 years of age were randomized to receive lecithin (4 capsules BID; PhosChol 900) or placebo beginning one day prior to the 2000 Houston-Methodist Health Care Marathon. The lecithin supplement provided approximately 1.1 g of choline on a daily basis (2.2 g total). Runners estimated finish time based on recent performance and training. Fasting, pre- and post-marathon plasma and a five-hour urine collection were analyzed for free choline and plasma for phospholipid-bound choline. Pre-race predicted, as well as the actual finish time, were recorded. RESULTS: All subjects completed the marathon. Plasma free choline decreased significantly in the placebo group and increased significantly in the lecithin group (9.6 +/- 3.6 to 7.0 +/- 3.6 nmol/mL vs. 8.0 +/- 1.2 to 11.7 +/- 3.6 nmol/mL, p = 0.001 for the delta between groups). No significant changes in plasma phospholipid-bound choline concentration were observed. There was a non-significant decrease in urine free choline in both groups. Actual finish time was 256.3 +/- 46.3 minutes for the lecithin group vs. 240.8 +/- 62.0 for the placebo group and the actual:predicted time was 1.03 +/- 0.06 (lecithin) and 1.07 +/- 0.08 (placebo), p = 0.36. CONCLUSION: Short-term lecithin supplementation prior to a marathon maintains normal plasma free choline concentration during the race, but failed to improve performance.
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Colina/sangue , Fosfatidilcolinas/administração & dosagem , Corrida , Adulto , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Previous investigations have shown that plasma free choline decreases during long distance running. OBJECTIVE: This study was undertaken to determine if body choline status changes during a marathon run and whether performance is thereby adversely affected. DESIGN: Twenty-three accomplished marathon runners 25 to 49 years of age were studied before and after the 1997 Houston-Methodist Marathon. Fasting blood and five-hour urine samples were obtained in the morning, 14 days prior to the race, immediately after the race and approximately 48 hours after completion of the race. Runners were asked to predict their finish times two weeks prior to the race. Performance was indicated by the ratio of predicted to actual time. RESULTS: Both plasma free and phospholipid-bound choline concentrations as well as urinary free choline concentration decreased immediately following the race (19.2+/-4.5 to 14.6+/-4.2 nmol/mL, p=0.005, and 2565.2+/-516.4 to 2403.4+/-643.0 nmol/mL, p=0.068, respectively) and, except for the phospholipid-bound choline, rebounded towards baseline after 48 hours (15.6+/-3.2 and 2299.9+/-426.7 nmol/mL), although plasma concentrations remained significantly below baseline. Plasma free and phospholipid-bound choline concentrations were significantly correlated (r=0.46, p=0.0001), although urinary free choline concentration was not correlated with either. There was no correlation between plasma free, phospholipid-bound or urinary free choline concentration and actual finish time or the ratio of predicted to actual finish time. However, the percent decrease in urinary free choline concentration was significantly correlated with the ratio of predicted to actual time (r=0.47, p=0.036). No relationship was seen between this ratio and the percent decrease in either plasma free or phospholipid-bound choline concentrations immediately after the race. CONCLUSION: Our finding of both decreased free and phospholipid-bound choline suggests the decrease in choline status is related to accelerated choline metabolism or enhanced choline uptake by tissues rather than decreased hepatic choline release. The role of choline supplementation during endurance running requires further investigation.
Assuntos
Colina/sangue , Colina/urina , Fosfolipídeos/sangue , Corrida/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Patients receiving long-term total parenteral nutrition (TPN) develop hepatic steatosis as a complication. Our previous studies have shown this to be caused, at least in part, by choline deficiency. We studied four patients (1 man, 3 women) aged 50 +/- 13 years who had low plasma-free choline concentrations 4.8 +/- 1.7 (normal, 11.4 +/- 3.7 nmol/mL). The patients had received TPN for 9.7 +/- 4.7 years. They received parenteral nutrition solutions containing choline chloride (1 to 4 g/d) for 6 weeks. Abdominal computed tomography (CT) was performed at baseline, biweekly during the choline supplementation, and 4 weeks after discontinuation of choline. During choline administration, the plasma-free choline concentration increased into the normal range within 1 week in all four patients and remained at or above the normal range for all 6 weeks, but decreased back to baseline when choline supplementation was discontinued. Hepatic steatosis resolved completely, as estimated by CT. Liver density increased from -14.2 +/- 22.3 Hounsfield units (HU) to 8.4 +/- 10.3 HU at week 2 (P = .002); 9.6 +/- 10.7 HU at week 4 and 13.1 +/- 7.3 HU at week 6, as determined by the liver-spleen CT number difference obtained by the subtraction of the average spleen CT number (in HU) from the average liver CT number. This improvement continued up to 4 weeks after choline supplementation (13.8 +/- 2.8 HU). Hepatic steatosis was shown to have recurred in one patient after 10 weeks of return to choline-free parenteral nutrition. The hepatic steatosis associated with parenteral nutrition can be ameliorated, and possibly prevented, with choline supplementation. Therefore, choline may be an essential nutrient for patients who require long-term parenteral nutrition.
Assuntos
Deficiência de Colina/terapia , Colina/administração & dosagem , Fígado Gorduroso/etiologia , Nutrição Parenteral Total/efeitos adversos , Adulto , Idoso , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/tratamento farmacológico , Feminino , Humanos , Infusões Intravenosas , Lipotrópicos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada de EmissãoRESUMO
Plasma-free choline levels have previously been found below normal in patients receiving long term parenteral nutrition (TPN). In a group of 15 patients receiving home TPN who had low plasma free choline levels (6.3 +/- 0.8 mmol/L), we found 50% had hepatic steatosis. These patients were given oral lecithin or placebo in a double-blind randomized trial for 6 weeks. Lecithin supplementation led to an increase in plasma free choline of 53.4% +/- 15.4% at 2 weeks (P = 0.04), which continued at 6 weeks. The placebo group had no change in plasma-free choline at 2 weeks, but a significant decrease of 25.4% +/- 7.1% (P = 0.01) at 6 weeks. A significant and progressive decrease in hepatic fat was indicated by increased liver-spleen CT Hounsfield units at 2 and 6 weeks (7.5 +/- 1.7 units, P = 0.02; 13.8 +/- 3.5 units, P = 0.03) in the lecithin supplemental group. Nonsignificant changes were seen in the placebo group. It was concluded that hepatic steatosis in many patients receiving long term TPN is caused by plasma-free choline deficiency and may be reversed with lecithin supplementation. Choline is a conditionally essential nutrient in this population.