GPU-accelerated Monte Carlo simulation of electron and photon interactions for radiotherapy applications.

Objective. The Monte Carlo simulation software is a valuable tool in radiation therapy, in particular to achieve the needed accuracy in the dose evaluation for the treatment plans optimisation. The current challenge in this field is the time reduction to open the way to many clinical applications for which the computational time is an issue. In this manuscript we present an innovative GPU-accelerated Monte Carlo software for dose valuation in electron and photon based radiotherapy, developed as an update of the FRED (Fast paRticle thErapy Dose evaluator) software.Approach. The code transports particles through a 3D voxel grid, while scoring their energy deposition along their trajectory. The models of electromagnetic interactions in the energy region between 1 MeV-1 GeV available in literature have been implemented to efficiently run on GPUs, allowing to combine a fast tracking while keeping high accuracy in dose assessment. The FRED software has been bench-marked against state-of-art full MC (FLUKA, GEANT4) in the realm of two different radiotherapy applications: Intra-Operative Radio Therapy and Very High Electron Energy radiotherapy applications.Results. The single pencil beam dose-depth profiles in water as well as the dose map computed on non-homogeneous phantom agree with full-MCs at 2% level, observing a gain in processing time from 200 to 5000.Significance. Such performance allows for computing a plan with electron beams in few minutes with an accuracy of ∼%, demonstrating the FRED potential to be adopted for fast plan re-calculation in photon or electron radiotherapy applications.

Inter-fractional monitoring of [Formula: see text]C ions treatments: results from a clinical trial at the CNAO facility.

The high dose conformity and healthy tissue sparing achievable in Particle Therapy when using C ions calls for safety factors in treatment planning, to prevent the tumor under-dosage related to the possible occurrence of inter-fractional morphological changes during a treatment. This limitation could be overcome by a range monitor, still missing in clinical routine, capable of providing on-line feedback. The Dose Profiler (DP) is a detector developed within the INnovative Solution for In-beam Dosimetry in hadronthErapy (INSIDE) collaboration for the monitoring of carbon ion treatments at the CNAO facility (Centro Nazionale di Adroterapia Oncologica) exploiting the detection of charged secondary fragments that escape from the patient. The DP capability to detect inter-fractional changes is demonstrated by comparing the obtained fragment emission maps in different fractions of the treatments enrolled in the first ever clinical trial of such a monitoring system, performed at CNAO. The case of a CNAO patient that underwent a significant morphological change is presented in detail, focusing on the implications that can be drawn for the achievable inter-fractional monitoring DP sensitivity in real clinical conditions. The results have been cross-checked against a simulation study.

Mixed secondary bacterial infection is associated with severe lesions of chromoblastomycosis in a neglected population from Brazil.

Chromoblastomycosis (CBM) is a chronic subcutaneous infection caused by melanotic fungi, affecting mainly rural workers in tropical and subtropical regions. Secondary bacterial infections (SBIs) in CBM lesions bring complications to the disease, but little is known about the agents involved. Fungal and bacterial identification and epidemiological profile of 50 patients with CBM were analyzed in this study. Bacteria were tested for susceptibility to antibacterial drugs. Fonseacea pedrosoi and Rhinocladiella aquaspersa were the fungal agents isolated. 88% of the patients presented SBI. Gram-positive bacteria coinfected mainly upper limbs, and Gram-negative bacteria were more isolated from lower limbs. Streptococcus pyogenes and mixed bacterial microbiota were associated with severe lesions. Staphylococcus aureus was associated with mixed infections and consequently with the severity of the infection. Resistance to ß-lactams and methicillin was detected. Our results emphasize the necessity of bacterial culture and susceptibility testing as part of routine monitoring CBM cases.

Esterification reactions catalyzed by lipases immobilized in organogels: effect of temperature and substrate diffusion.

Rhizomucor miehei lipase was immobilized in hydroxy(propylmethyl) cellulose or agar gels containing lecithin or AOT microemulsions. The effect of the diffusion of substrates and products to this catalyst was studied, as well as the effect of temperature on the initial rate of ester synthesis. The composition of the gel affects the reaction rate due to mass transport phenomena. The apparent activation energies were higher for the systems based on agar, independently of the microemulsion used, and lower for the systems based on AOT microemulsions, independently of the polymer used.

Unexpected reaction profile observed in the synthesis of propyl laurate when using Candida rugosa lipases immobilized in microemulsions based organogels.

1-Propyl laurate synthesis should not be used as standard reaction test of immobilized enzymes in microemulsion-based organogels (MBGs) prepared using lecithin/1-propanol as surfactant when extremely active enzymes with high load are used. In these cases, an anomalous kinetic reaction constant value is observed over short reaction times. Such an anomalous profile is strongly dependent on the concentration of catalyst in the crude powder and, consequently, is not appreciated when either commercial or low activity lipase samples are employed.

Exercise testing as a predictor of surgical risk after pneumonectomy for bronchogenic carcinoma.

The aim of the present investigation was to evaluate the predictive value of a symptom-limited exercise test in predicting postoperative morbidity and mortality in patients submitted to pneumonectomy. The study was conducted in 150 patients (mean age, 57.1). Forty-four patients (29.3%) had postoperative complications. Four patients (2.7%) died within one month of the pneumonectomy. Patients with complications had significantly lower VO2max. The incidence of complications in relation to the amount of oxygen consumption showed that with the progressive decrease of oxygen consumption there was a progressive increase in frequency of complications. In particular patients with VO2max < 50% of predicted should be considered at high risk of morbidity and mortality from cardiopulmonary causes. This predictive capacity of VO2max was more evident in patients with a preoperative FEV1 less than 70% of predicted. The present data support the suggestion that exercise testing could be a useful adjunt in the evaluation of postoperative risk for pneumonectomy, especially in patients with obstructive pulmonary disease.

Formation of micelles and liposomes from carnitine amphiphiles.

Esterification of the carboxy and/or the hydroxy groups of (R)-carnitine (3-hydroxy-4-trimethylammonium butanoate) produces interesting classes of (cationic or zwitterionic) surfactants whose CMC values are in general predictable from their molecular structure. In fact similar relationships between CMC and the number of carbon atoms, Cn, have been found for three classes of such surfactants. However the sensitivity of CMC to Cn for the diesters is considerably lower than that calculated from literature values for the monoesters (either in their cationic or zwitterionic forms). The CMC values for the diesters have been determined by tensiometric, conductimetric and spectrophotometric methods, both in pure water and in 0.154 M NaCl solutions, at 25 degrees C. In particular the tensiometric results provide evidence that double-chain diesters undergo self assembly into structures more complex than simple micelles if the two chains are of comparable length. EPR and electron microscopy experiments show that the aggregates spontaneously formed by these surfactants are a mixture of multilamellar vescicles.

Late pulmonary effects in favorable stage I and IIA Hodgkin's disease treated with radiotherapy alone.

Radiotherapy (RT) in patients with favorable-stage Hodgkin's disease can induce clinical and subclinical evidence of pulmonary damage lasting over the years. In this study, we monitored 36 patients with stage IA-IIA Hodgkin's disease treated with subtotal nodal RT. The planned dose of RT was 40 Gy to 44 Gy to the involved areas and 36 Gy to the adjacent uninvolved areas. Pulmonary function was evaluated by chest radiograph, spirometric parameters, arterial blood gas analysis, and single-breath CO transfer factor (DLCO). The tests were performed before and at the end of irradiation, and during the follow-up 1 and 3 to 5 years after the treatment. At the end of RT, we found a significant decrease of total lung capacity, vital capacity, forced expiratory volume in 1 second, residual volume, and DLCO. Spirometric parameters improved during the follow-up period, whereas the decline of DLCO (-6.4%) was persistent. No correlation was found between mantle RT dose and DLCO changes. Four patients showed a decline of DLCO of >20% from pretreatment values but only one was symptomatic. Our study confirms that RT induces a pulmonary-restrictive disease at a subclinical level that seems to be reversible in the majority of patients.

Lung function and serum concentration of tumor necrosis factor-alpha, interleukin-6 and fibronectin in patients treated with ABVD chemotherapy followed by radiotherapy for mediastinal Hodgkin's disease.

UNLABELLED: Mediastinal radiotherapy and polychemotherapy regimens can produce late toxicity leading to pulmonary fibrosis. There is evidence for the involvement of various cytokines in this process. We evaluated lung function in 20 patients with stage I-IIA Hodgkin's disease and submitted to chemotherapy including bleomycin (ABVD) and radiotherapy. Lung function tests were performed before, at the end of treatment and after a median of 12 months from the end of therapy. Tumor necrosis factor-alpha (TNF-alpha), fibronectin and interleukin-6 (IL-6) were determined on serum samples collected at the same time intervals. A modification of tests indicative of a restrictive lung disease was observed at end of treatment, whereas a persistent decline of transfer lung factor for carbon monoxide (DLCO) was documented. TNF-alpha constantly decreased, fibronectin increased and IL-6 showed a decline after treatment and a rise during the follow-up but the differences were not statistically significant. No significant correlations were observed between changes of lung function tests and serum cytokine concentration. CONCLUSIONS: This lack of correlation could be due to: a) incorrect selection of serum collection time, or b) to the fact that cytokine plasma concentration does not reflect events occurring in the alveolar phase.

Effect of dietary supplementation with polyunsaturated fatty acids on bronchial hyperreactivity in subjects with seasonal asthma.

Dietary supplementation with omega-3 essential fatty acids results in the production of uniqe 5-lipoxygenase and cyclooxygenase products which are biologically less active and may inhibit the production, or actions, of the eicosanoids produced when arachidonic acid is the substrate for 5-lipoxygenase and cyclooxygenase, rather than omega-3 essential fatty acids. Since airway inflammation may play a central role in the pathophysiology of asthma, we studied the effect of omega-3 essential fatty acids on bronchial responsiveness in 7 atopic patients suffering from seasonal asthma due to airborne allergens, and positive to intracutaneous skin reaction to two or more allergens. Bronchial responsiveness to ultrasonically nebulized distilled water (UNDW) was determined 30 days from the initial ingestion of 3 g/day of omega-3 essential fatty acids and 30 days after stopping dietary supplementation. Flow volume curves and Raw were recorded before the provocation test, at the end of inhalation, and at 10-, 20-, 30- and 60-min intervals. The maximum fall in forced expiratory volume in 1 s (FEV1) and the maximum increase in airway resistance (Raw) were chosen as the main outcome parameters. After 30 days of dietary supplementation, bronchial responsiveness to UNDW was significantly improved (in fact maximum fall in FEV1 was -11% vs. -28% before treatment, and maximum increase in Raw was +37% vs. +265% before treatment). The challenge test repeated 30 days after stopping dietary supplementation was the same as that recorded before treatment. The present data strongly suggest the hypothesis that dietary supplementation with omega-3 essential fatty acids could decrease bronchial hyperreactivity in atopic patients.

[The evaluation of the efficacy of artesunate combined with tetracycline in the therapy of falciparum malaria]. / Avaliação da eficácia do artesunato associado à tetraciclina na terapêutica da malária falciparum.

A controlled clinical therapeutic study in hospitalized patients compared artesunate with quinine and mefloquine in patients with uncomplicated falciparum malaria. Forty two patients entered the trial and the follow up was for 28 days with thick blood film taken every 12 hours until became negative. Laboratory examinations included haematological and biochemical tests before and after treatment. Patients had a mean parasitaemia of 42.568 per microliter. Twenty six patients completed 28 days of follow up but 16 did not fulfil this protocol. One in each of the therapeutic groups showed delayed R I resistance. A further patient in the quinine group showed R III resistance. The cure rate was 88.8% for artesunate. 85.7% for mefloquine and 81.8% for quinine; no significant difference was found, the same occurring with the clearance of fever. The artesunate group had a quicker parasitaemia clearance time (37.3 +/- 11.5 hours) when compared with quinine (65.2 +/- 17.4) showing a significant difference (p = 0.0016). Parasite clearance with mefloquine, was intermediate (58.9 +/- 16.6 ours) between the artesunate and quinine. No important side effects were observed with any of the therapeutic regimens and no deaths registered.

Oral doxophylline in patients with chronic obstructive pulmonary disease.

Doxophylline, or 2-(7'-theophyllinemethyl)1,3-dioxolane, is a theophylline derivative which has shown interesting bronchodilating activity, and it appears to determine few adverse effects. The aim of the present investigation was to evaluate clinical therapeutic effects of the drug in the treatment of 2 groups of patients suffering from moderate to severe chronic obstructive pulmonary disease differing in acute response to the inhaled beta 2-agonist salbutamol and to compare changes of lung function tests to serum concentration of doxophylline. We studied 67 patients with chronic obstructive pulmonary disease (median age 63 years, 9 females and 58 males) who were all clinically stable at the time of the study. Patients were separated into 2 groups on the basis of their reaction to inhalation of 200 micrograms of salbutamol: those with an increased FEV1 of more than 20% from baseline value (group 1), and those with no increase (group 2). Doxophylline was administered orally at the dose of 400 mg 3 times daily. Serum levels of doxophylline were determined by high-pressure liquid chromatography. Spirometry and blood gas analysis were performed before and 10 days after treatment. Four patients stopped drug assumption because of side effects (3 for dyspepsia and 1 for anxiety). In group 1 (34 patients), a significant increase in SVC, FVC, FEV1, FEF 25-75% and PEFR was observed. In group 1 (29 patients), only PEFR significantly increased. No modifications in blood gas analysis were observed. The mean serum level of doxophylline was 14 micrograms/ml in group 1 and 9 micrograms/ml in group 2: the difference was statistically significant. The relation between serum levels of doxophylline and FVC showed an increase in the parameter up to the concentration of 12-13 micrograms/ml, after which a plateau phase was observed. On the basis of our data, doxophylline appears to have an interesting bronchodilating effect in patients responsive to the inhaled beta 2-agonist salbutamol. The lower limit of the therapeutic range seems to be 12-13 micrograms/ml. The upper limit of the therapeutic range was not determined because it was not possible to obtain serum samples when side effects occurred.

Late pulmonary toxicity after treatment for Hodgkin's disease.

The combination of mediastinal radiotherapy (RT) with chemotherapy (CT) including bleomycin is associated with an increased risk of pulmonary toxicity. The aim of the present investigation was to evaluate late pulmonary effects of RT plus CT consisting of the ABVD regimen in patients suffering from early stage Hodgkin's disease. For this purpose pulmonary function was serially evaluated before, at the end and at least 1 year after therapy in 32 patients (median age 28 years) with Hodgkin's disease stages IA,B-IIA. Treatment consisted of four cycles of ABVD chemotherapy followed by mediastinal irradiation at the median dose of 36 Gy (range 30.6-43.2). At the end of treatment, resting mean pulmonary function tests showed a significant decline of forced expiratory volume in 1 second (FEV1), forced expiratory flow at 25-75%, (FEF25-75%), total lung capacity (TLC), vital capacity (VC) and carbon monoxide diffusing capacity (DLCO). The decline of TLC, VC and DLCO, indicative of a pulmonary defect of restrictive type, persisted 1 year from the end of therapy. Only seven patients developed symptoms of cough and mild shortness of breath with effort. These data confirm that RT combined with short term ABVD result in pulmonary dysfunction that does not seem to have clinical significance.

Spontaneous regional healing of extensive skin lesions in diffuse cutaneous leishmaniais (DCL)

The authors report a case of diffuse cutaneous leishimaniasis, with longstanding evolution and presenting with diffuse infiltrated lesions rich in amastigotes in the absence of mucosal involvement. In situ characterization with inonoclonal antibodies revealed Leishmania amazonensis. Large regional lesions have presented spontaneous healing without specific therapy. Considering that DCI presents with a defect in the cellular immune response, this fact demonstrate that this patient may develop a regional cellular immune response enough to destroy the parasites and to produce clearing of some lesions.

O babaçu (Orbignya phalerata martins) como provável fator de risco de infecçäo humana pelo agente da cromoblastomicose no estado do Maranhäo, Brasil / The coconut babaçu (Orbignya phalerata martins) as a probable risk of human infection by the agent of chromoblastomycosis in the State of Maranhäo, Brazil

Após estudo de 3O pacientes portadores de cromoblastomicose, acompanhados no hospital dos servidores do Estado do Maranhao, verificou-se em 2 (6,6 por cento) lesoes na regiao glútea, diferindo do que geralmente se observa, pois na cromoblastomicose existe sempre história de microtraumatismo sofridos durante o trabalho na lavoura, propiciando o desenvolvimento mais freqüente das lesoes nas extremidades, principalmente dos membros inferiores. Ambos pacientes, doentes há 10 anos, apresentavam lesoes modulares e verrugo-confluentes em placas coalescentes na regiao glútea direita. O diagnóstico etiológico foi firmado através de exame histopatológico e cultura, com isolamento de Fonsecaea pedrosoi. Na investigaçao epidemiológica do tipo de exposiçao verificou-se que os mesmos desempenhavam a profissao de quebradores de coco-babaçú, atividade relativamente comum no Estado. Parece evidente a relaçao entre o tipo de atividade profissional e o desenvolvimento da infecçao.

Associaçäo de cromoblastomicose e hanseníase: relato de dois casos / Chromoblastomycosis associated with leprosy: report of 2 cases

Ao estudar 30 casos de cromoblastomicose diagnosticados no Hospital dos Servidores do Estado do Maranhao, no período de novembro de 1988 a março de 1993, os autores observaram 2 (6,6 por cento) casos, que apresentaram associaçao desta doença com hanseníase. O primeiro paciente desenvolveu as duas doenças concomitantemente, apresentando espessamento no nervo cubital bilateral, mal perfurante plantar em pé direito e lesoes em placas verrucóides na perna esquerda, com biópsia de nervo cubital direito positiva para hanseníase dimorfa T e biópsia da lesao em placa, positiva para Fonsecaea pedrosoi. O segundo caso, paciente com história de hanseníase virchowiana há 30 anos, em pausa terapêutica por "cura", com lesoes verrugo-confluentes em cotovelo direito há 12 meses, histopatológico e cultura positiva, para cromoblastomicose. Os possíveis fatores para o desenvolvimento da cromoblastomicose nestes pacientes sao discutidos.

Effect of the addition of electrolytes on the partition coefficients, activity coefficients, and acid dissociation constants of carnitine and its acetyl and propionyl derivatives.

The partition coefficients, P, between n-octanol and water of carnitine, acetylcarnitine, propionylcarnitine, and tetraethylammonium pentacyanopropenides have been determined spectrophotometrically at 20 degrees C. The value of P increases upon addition of electrolytes, the increase produced by LiCl being particularly high. The carnitine cations are 'salted-out' by electrolytes as shown by the variation of their 'single-ion' activity coefficients (relative to that of the tetraethylammonium ion) with electrolyte concentration. These cations are appreciably more hydrated than the reference tetraethylammonium ion. The considered carnitine cations are at least one pKa (where Ka is the acid dissociation constant) unit more acidic than butanoic acid in water at 25 degrees C. Electrolyte addition somewhat increases the pKa of these cationic acids.