Influence of the technique and comorbidities in hypofractionated radiotherapy for prostate cancer.

PURPOSE: To analyze the differences in toxicity and biochemical relapse-free survival with hypofractionated radiotherapy with three-dimensional radiotherapy (3D-CRT) or volumetric arc therapy (VMAT) for prostate cancer taking into account comorbidity measured using the Charlson Comorbidity Index (CCI). METHODS: From January 2011 to June 2016, 451 patients with prostate cancer were treated with 60 Gy (20 daily fractions). VMAT or 3D-CRT was used. Distribution by stage: 17% low-risk, 27.2% intermediate-risk; 39.2% high-risk, 16.6% very high-risk. Mean CCI was 3.4. RESULTS: With a median follow up of 51 months, most patients did not experience any degree of acute GI toxicity (80.9%) compared to 19.1%, who experienced some degree, mainly G-I /II. In the multivariate analysis, only technique was associated with acute GI toxicity ≥ G2. Patients treated with VMAT had greater acute GI toxicity compared with those who received 3D-CRT (23.9% vs. 13.5%, p = 0.005). With respect to acute GU toxicity, 72.7% of patients experienced some degree, fundamentally G-I/II. Neither age, CCI, nor androgen deprivation therapy (ADT) were associated with greater toxicity. Overall survival at 2, 5 and 7 years was 97%, 88% and 83% respectively. The only factor with statistical significance was CCI, with a greater number of events in individuals with a CCI ≥ 4 (p < 0.03). CONCLUSIONS: Hypofractionated radiotherapy for prostate cancer is an effective, well-tolerated treatment even for elderly patients with no associated comorbidity. Longer follow up is needed in order to report data on late toxicity.

Effect of a specific supplement enriched with n-3 polyunsaturated fatty acids on markers of inflammation, oxidative stress and metabolic status of ear, nose and throat cancer patients.

Malnutrition affects 40-50% of patients with ear, nose and throat (ENT) cancer. The aim of this study was to assess changes induced by a specific nutritional supplement enriched with n-3 polyunsaturated fatty acids, fiber and greater amounts of proteins and electrolytes, as compared with a standard nutritional supplement, on markers of inflammation, oxidative stress and metabolic status of ENT cancer patients undergoing radiotherapy (RT). Fourteen days after starting RT, 26 patients were randomly allocated to one of two groups, 13 supplemented with Prosure, an oncologic formula enriched with n-3 polyunsaturated fatty acids, fiber and greater amounts of proteins and electrolytes (specific supplement), and 13 supplemented with Standard-Isosource (standard supplement). Patients were evaluated before RT, and 14, 28 and 90 days after starting RT. The results showed that there were no significant differences between the groups, but greater changes were observed in the standard supplement group, such as a decline in body mass index (BMI), reductions in hematocrit, erythrocyte, eosinophil and albumin levels, and a rise in creatinine and urea levels. We concluded that metabolic, inflammatory and oxidative stress parameters were altered during RT, and began to normalize at the end of the study. Patients supplemented with Prosure showed an earlier normalization of these parameters, with more favorable changes in oxidative stress markers and a more balanced evolution, although the difference was not significant.

Efectos inmediatos de la manipulación occipito-atlo-axoidea en el apoyo podal: estudio baropodométrico / Immediate effects of occipito-atloaxoid manipulation on foot support: baropodometric study

Introducción: El equilibrio postural es mantenido gracias a un sistema de aferencias y eferencias en continua adaptación. El objetivo de estas adaptaciones es el mantenimiento de la horizontalidad de la mirada y los centros laberínticos. Para esto el raquis cervical superior tiene un rol importante asegurando la orientación de la cabeza en el espacio. Este estudio trata de evaluar el efecto sobre el apoyo de la normalización propioceptiva del raquis suboccipital. Objetivos: Evaluar cambios inmediatos en la distribución de presiones en el apoyo plantar tras la técnica de thrust occipitoatlo-axoidea (TOAA). Material y Métodos: Se realizó un estudio experimental controlado aleatorizado (ECCA) de carácter explicativo, simple ciego con estrategia de evaluador cegado. Se evaluó a cada sujeto antes y después de la intervención o placebo mediante plataforma de presión. Los sujetos fueron evaluados sin calzado y recibiendo órdenes protocolizadas. La muestra fue de 46 sujetos (25 hombres / 22 mujeres) con una edad media de 24,98±3,04 años. Se utilizó para la comparación intergrupal de la varianza el estadístico ANOVA para las variables paramétricas y la prueba U de Mann Whitney para las no paramétricas. Resultados: Se observó aumento de la «presión máxima» (p=0,044) y del «Porcentaje de carga sobre el pie izquierdo» (p=0,048) acercándolo al reparto equitativo bilateral. Conclusiones: La manipulación occipito-atlo-axoidea aumenta la presión máxima de apoyo y aproxima el porcentaje de carga al reparto equitativo bilateral en sujetos sanos. Los resultados inducen a pensar de cambios en el apoyo tras la técnica, lo cual debe ser comprobado en estudios posteriores con muestras más amplias (AU)

Introduction: Postural balance is maintained thanks to a continually changing system of inputs and outputs. The goal of these changes is to maintain the sight and labyrinthine centres horizontal. To do this, the upper cervical spine has an important role, ensuring the head’s direction within the area. This study is about assessing the effect on the support of proprioceptive normalisation of the suboccipital spine. Objectives: To assess immediate changes in pressure distribution on the arch support after occipito-atlo-axoid thrust (OAAT). Material and methods: A single blind randomised controlled trial (RCT) of an experimental explanatory nature was carried out using the strategy of a blind (no connection between the assessor and inspector) assessor. Each subject was assessed before and after the procedure or placebo using a pressure platform. The subjects were assessed without footwear receiving standardised orders. The sample had 46 subjects (25 men and 22 women) with an average age of 24.98±3.04. For comparison between groups of the variance for parametric variables, the ANOVA statistic was used and for the non-parametric variables the Mann Whitney U test was used. Results: An increase was seen in the «maximum pressure» (p=0.044) and in the «load percentage on the left foot» (p=0.048) coming close to equitable bilateral distribution. Conclusions: Occipito-atlo-axoid manipulation increases the maximum support pressure and approaches the percentage for equitable bilateral load distribution in healthy subjects. The results could lead to considering changes in support after the technique, which must be verified in later studies with larger samples (AU)

Multimodal treatment of desmoid tumours: the significance of local control

INTRODUCTION: Desmoid tumours are a rare group of tumours arising in the deep musculoaponeurotic structures and although they have no metastatic potential they can be locally aggressive with relapse rates of between 23-40%. Three sub-sites are reported: extra-abdominal, abdominal wall and intra-abdominal. The purpose of this study was to analyze patients with these tumours treated and followed at our institution and to determine factors influencing disease free survival. MATERIAL AND METHODS: We conducted a retrospective study of 20 patients treated between 1997 and 2009. Data was compiled to include age, gender, surgical history, familial adenomatous polyposis (FAP), contraceptives, tumour site, first-line treatment, positive margins and adjuvant radiotherapy. A descriptive and survival statistical analysis was also performed. RESULTS: Most patients were women, with a median age of 36 years, with abdominal wall involvement and treated with complete surgery without adjuvant radiotherapy. With a median follow-up of 35 months (range 0-188), local control at 5 years for any kind of treatment was 80%. Overall survival (OS) and 5-year progression-free survival (PFS) were 100% and 86%, respectively. CONCLUSION: Desmoid tumours are group of rare tumours. Although complete surgical resection remains the cornerstone of treatment for resectable lesions, there is still substantial risk of recurrence. Our outcomes are comparable to those reported in the few series published to date (AU)

Wortmannin enhances the induction of micronuclei by low and high LET radiation.

In mammalian cells, the repair of DNA double-strand breaks (DSBs) is mainly mediated by DNA non-homologous end joining. DNA-dependent protein kinase (DNA-PK), a nuclear serine-threonine kinase and a member of the phosphaditylinositol-3 kinase-related kinase family that is activated by DSBs, is a key component of this pathway. Wortmannin (WM) is known to be an irreversible and potent inhibitor of DNA-PK and has thus been proposed as an effective sensitizer for ionizing radiation and for radiomimetic compounds. The present study, using the cytokinesis block micronucleus assay, reports on the differential effect of WM on the repair of the DNA damage induced by low LET ((60)Co gamma-radiation) and high LET radiation by the boron neutron capture reaction (alpha and Li particles) in V79 Chinese hamster cells. Significant increases in the number of micronuclei per binucleated cell as well as in the frequency of micronucleated binucleated cells were observed in the presence of different concentrations of WM for high LET radiation from the boron neutron capture reaction. The increases observed reached a maximum of approximately 2-fold in comparison with the respective controls. WM, however, had a more pronounced effect on (60)Co gamma-radiation-induced micronuclei, increasing the genotoxic damage from this radiation by approximately 3- to 4-fold. These results are in general in agreement with the concept that DSBs induced by high LET radiation are not a more suitable substrate for the end joining processes mediated by DNA-PK, yet they do not preclude a role for DNA-PK in high LET-induced damage repair.

The effect of ethanol on acrylic bone cement.

Prosthesis loosening is a major problem associated with the use of poly(methyl methacrylate) (PMMA) bone cement that may be related to a peri-implant vacuolisation commonly observed at bone-cement interface. Methyl methacrylate (MMA) monomer may be one of the cement components partly responsible for the mentioned vacuolisation due to a cytotoxic effect associated to this compound. Alcoholism has been related to bone necrosis in predisposed individuals. Furthermore, ethanol has been shown to clean material with adherent cement debris during cleaning procedure in laboratory. Consequently, we have decided to study whether ethanol will also be related to an increased liberation of MMA from the polymer matrix. 'In vitro' release studies using PMMA plates were conducted to access the role of ethanol on the liberation of the monomer. Contact angle measurements and surface tension estimation were also carried out in order to find a possible effect of ethanol on surface cement properties. Results suggest that ethanol, even in small quantities, enhances the leaching of the monomer from the polymer matrix, but does not considerably change the wettability properties of the cement surface.

Evaluation of the genotoxic effects of the boron neutron capture reaction in human melanoma cells using the cytokinesis block micronucleus assay.

The present work reports on the genotoxicity of the boron neutron capture (BNC) reaction in human metastatic melanoma cells (A2058) assessed by the cytokinesis block micronucleus assay (CBMN) using p-borono-L-phenylalanine (BPA) as the boron delivery agent. Different concentrations of BPA (0.48, 1.2 and 2.4 mM) and different fluences of thermal neutrons were studied. Substantial genotoxic potential of alpha and lithium particles generated inside or near the malignant cell by the BNC reaction was observed in a dose-response manner as measured by the frequency of micronucleated binucleated melanoma cells and by the number of micronuclei (MN) per binucleated cell. The distribution of the number of MN per micronucleated binucleated cell was also studied. The BNC reaction clearly modifies this distribution, increasing the frequency of micronucleated cells with 2 and, especially, > or =3 MN and conversely decreasing the frequency of micronucleated cells with 1 MN. A decrease in cell proliferation was also observed which correlated with MN formation. A discrete genotoxic and anti-proliferative contribution from both thermal neutron irradiation and BPA was observed and should be considered secondary. Additionally, V79 Chinese hamster cells (chromosomal aberrations assay) and human lymphocytes (CBMN assay) incubated with different concentrations of BPA alone did not show any evidence of genotoxicity. The presented results reinforce the usefulness of the CBMN assay as an alternative method for assessment of the deleterious effects induced by high LET radiation produced by the BNC reaction in human melanoma cells.

The influence of vacuum mixing on methylmethacrylate liberation from acrylic cement powder.

Polymethylmethacrylate (PMMA) bone cement is a biomaterial used to anchor prostheses during joint replacement surgery. Residual methylmethacrylate monomer (MMA) may be related with the cytotoxic effect of PMMA. The aim of the present paper was to investigate the effect of two different cement mixing methods: hand stirring at atmospheric pressure and under partial vacuum (0.330 and 0.154 bar) on residual monomer liberation in phosphate buffer saline solution from acrylic cement powder. Residual MMA content was determined by high-performance liquid chromatography. Mathematical models were applied to experimental dissolution data revealing that monomer release was significantly reduced in bone cement powder obtained at 0.154 bar vacuum pressure compared to the other mixing conditions. The kinetic models applied are consistent with a simple diffusion mechanism of the monomer from the polymer matrix.

[Uremic myopathy]. / Miopatía urémica.

INTRODUCTION: The neurological features of chronic renal failure are very varied. Uremic myopathy is a controversial condition. In most cases it is related to the secondary hyperparathyroidism which these patients develop, and its characteristics are superimposed on their osteomalacia myopathy. CLINICAL CASES AND CONCLUSIONS: We report two patients with terminal chronic renal failure on hemodialysis who complained on difficulty with walking. The clinical findings, laboratory and neurophysiological investigations and the histopathological report of the muscle biopsy were similar to those of osteomalacia myopathy. The muscle weakness of patients with terminal chronic renal failure is related to many factors. The most important of these is the secondary hyperparathyroidism which leads to osteomalacia myopathy. On muscle biopsy there was isolated fibre necrosis of both types 1 and 2 (case 1) and of type 2 alone (case 2), which is considered to be the commonest finding. Although treatment with high doses of vitamin D3, or its hydroxylated metabolites, has been recommended, it was not effective in our patients.

In vitro release studies of methylmethacrylate liberation from acrylic cement powder.

Bone cement or polymethylmethacrylate (PMMA) is commonly used for anchoring cemented prosthesis to the bone. Cytotoxic effect of culture media exposed to PMMA powder may be related with long term problems associated with acrylic cement application, being the monomer (methylmethacrylate) one of the cement's component partly responsible for the cytotoxic effect. The present work reports the studies of monomer release from acrylic bone cement powder under different experimental conditions: setting time of PMMA (in solution and air) and different culture media composition. High-performance liquid chromatography was used for the determination of residual monomer. Mathematical models were applied to experimental dissolution data revealing that monomer release is lightly affected by the studied variables. The monomer release seems to be a surface phenomena, suggesting that the possible actions of monomer will mainly be due to the initial loss of non polymerized monomer rather than to further depolymerization of the already polymerized cement.

Nitric oxide and human thermal injury short term outcome.

Nitric oxide (NO) is an important mediator in numerous physiological and pathophysiological events. After thermal injury an increase in plasma and urinary levels has been observed. The real importance of this fact is unknown. The stable NO derivatives (NO2-/NO3-) plasma concentrations were determined in 27 burned patients admitted to the Burn Unit at Santa Maria Hospital in Lisbon at first, third, fifth, seventh, ninth and 15th days and the values were compared with healthy controls (n=9). A significant increase (P<0.05) in burn patient determinations upon admission was found. The patients with inhalation injury revealed greater values compared to the other patients with statistical significance at 5th day (P<0.05). The patients who died showed a NO increase (0.397+/-0.138 vs. 0.267+/-0.017, P> 0.1, day 1) with significance at day 5 (0.615+/-0.223 vs. 0.154+/-0.048, P<0.05). The determinations in patients with sepsis were higher than in the other patients (P<0.01) at day 3. No relation with total burned surface area (TBSA) was found. For the first time, considering burned patients, a significant increase of NO was found in patients who died, in patients with inhalation injury and in patients in sepsis. The possible role of NO in burn injury is discussed. The authors suggest the possible role of NO determination as an indicator of sepsis. The role of NO synthesis inhibitors is discussed. Further studies are needed to clarify these questions.

Dietary beta-adrenoceptor agonists have a persistent effect on nitric oxide synthesis in rat cultured smooth muscle cells.

Several compounds including lipopolysaccharide and sympathomimetics stimulate the expression of the inducible nitric oxide synthase in vascular smooth muscle cells. We evaluated the effect of clenbuterol on nitric oxide (NO) production by vascular smooth muscle cells of the rat aorta in culture. Wistar rats were divided into three diet groups (control, clenbuterol and washout). Aortic vascular smooth muscle cells from rats from these 3 diet groups were cultured in the presence and absence of lipopolysaccharide and/or beta-adrenoceptor agonists. NO release was measured by Griess reagent. Clenbuterol or salbutamol added to cells from control rats potentiated lipopolysaccharide-induced NO release. Cells from rats fed on clenbuterol, in a medium without beta-adrenoceptor agonists, showed a similar potentiation, even after a 10-day washout period. The addition of beta-adrenoceptor agonists to the latter cells did not increase NO production. NG-Nitro-L-arginine decreased nitrite production in lipopolysaccharide-stimulated cells. Our results demonstrate that dietary clenbuterol has a persistent 'ex vivo' effect on lipopolysaccharide-induced NO production by cultured vascular smooth muscle cells.

Acrylic bone cement induces the production of free radicals by cultured human fibroblasts.

Arthroplasty with poly(methyl methacrylate) (PMMA) bone cement induces late loosening phenomena that compromise the prosthetic stability. As free radicals are inflammatory mediators and cytotoxic, it seemed useful to investigate whether PMMA induces the liberation of free radicals and/or cytotoxicity. The effect of PMMA interaction on cultured human fibroblasts was accessed by the cell viability test (MTT), and by the measurement of lipoperoxides in the incubation medium. The incubation with the medium exposed to PMMA induced a significant reduction in the viability and a significant increase in lipoperoxide liberation (vs control). These data suggest that PMMA is cytotoxic. This effect seems to be mediated by lipoperoxide and possibly by other free radicals, and may explain the peri-implant loosening phenomena that compromise the prosthetic stability.

DL-propranolol augments production of NO induced by cytokines in cultured aortic smooth muscle of the rat.

The effect of DL-propranolol on the production of nitric oxide (NO.) by cultured arterial smooth muscle cells from normotensive (WKY) and spontaneously hypertensive rats (SHR) was studied before and after stimulation by lipopolysaccharide or interleukin-1 beta. The influence of L-arginine and NG-nitro-L-arginine on these events was also studied. Lipopolysaccharide-stimulated SHR-derived smooth muscle cells produced less NO. than WKY cells. However the amounts produced in response to interleukin-1 beta were similar for the two cell types. DL-propranolol increased the NO. production in both types of cells exposed to lipopolysaccharide, but had no significant effect on this parameter in WKY-derived cells exposed to interleukin-1 beta. Inclusion of L-arginine during incubations with propranolol had no effect on the levels of NO. produced by either cell type exposed to lipopolysaccharide. The basal production of NO. was enhanced in smooth muscle cells from both normotensive and hypertensive rats when the cells were treated with L-arginine after exposure to interleukin-1 beta. L-Arginine increased the response to DL-propranolol only in the WKY cells. NO. production was depressed by inclusion of NG-nitro-L-arginine during incubations in both cell types regardless of the treatment regime used to induce NO. synthase activity. The results suggest that DL-propranolol may induce the production of NO. by cultured smooth muscle cells exposed to cytokines.

Effect of Ca2+ modulators on acetylcholine-induced phasic and tonic contractions and A23187-induced contractions in ileal longitudinal muscle and IP3 production.

The influence of different sources of Ca2+ on the Emax and ED50 values of acetylcholine (ACh)-induced phasic and tonic contractions and on A23187-induced contractions was studied using different extracellular Ca2+ concentrations ([Ca2+]o) and the Ca2+ modulators TMB-8 and D600. IP3 production induced by both stimulants was also studied. The results are compatible with: (a) the mobilization of Ca2+ from an intracellular source as a primary event in the phasic response. (b) The primary involvement of a D600-sensitive inward Ca2+ current in the ACh-tonic response. (c) An inward D600-sensitive Ca2+ current associated with the ionophore transported ion. (d) The involvement of an IP3 independent, TMB-8 sensitive mechanism of Ca2+ mobilization involved in the A23187-induced responses.

[Left atrial thrombus. Its evolution with oral anticoagulation]. / Trombo auricular izquierdo. Evolución con anticoagulación oral.

UNLABELLED: Left ventricular thrombi were found in 25 patients by two-dimensional echocardiography. All patients were in atrial fibrillation, 16 had mitral or mitroaortic valve diseases and nine mitral or mitroaortic bioprosthetic valves. Nine patients (36%) had history of arterial embolism. At diagnostic time, oral anticoagulation with coumadin was instaured in all the patients. Periodic clinic and echocardiography follow-up was performed. Left atrial thrombi either disappeared (18 patients [72%]) or reduced their size (one patient). Six patients with mitral stenosis were considered as candidates to percutaneous mitral valvuloplasty, which was performed in 4 patients whose thrombi disappeared with anticoagulation therapy in 6 months. During the follow-up one patient had cerebral embolism without sequelae. CONCLUSIONS: 1st. Patients with left atrial thrombi have high risk for arterial embolism. 2nd. Left atrial thrombi disappear in a high proportion after prescribing oral anticoagulation, which has some important therapeutic implications.

Effect of DL-propranolol on nitric oxide production in perfused rat hindquarters.

The effect of DL-propranolol on NO release in perfused rat hindquarters was studied by using oxyhemoglobin as a capture system to allow the quantitative assay of NO production. In some experiments the stable prostacyclin metabolite 6-keto-PGF1 alpha (6-keto) was simultaneously assayed. We observed that: (1) DL-propranolol induced an increase in NO and 6-keto release. The dextro isomer was inactive; (2) DL-propranolol-induced NO release was only slightly reduced by acetylsalicylic acid in a concentration that inhibits prostacyclin synthesis, and was abolished by the chemical removal of the endothelium with 3-3 cholamidopropyl dimethylammonium 1-propane sulphonate (CHAPS) applied before or during stimulation; (3) NG-nitro-L-arginine blocked DL-propranolol-induced NO production, an effect that was antagonized by L-arginine but not by its dextro isomer.