Cellular mediators in human leishmaniasis: Critical determinants in parasite killing or disease progression.

Data on cellular immunity mediators in the early phase of human leishmaniasis are still limited and controversial. In order to mimic the changes of humoral mediators during the early phase of human natural infection, some Th1, Th2, Treg, and Breg cytokines, MCP-1, and the nitric oxide (NO) from human PBMC, stimulated by Leishmania infantum, Leishmania major, Leishmania donovani and Leishmania tropica infective metacyclic promastigotes, were determined. After 4 h of L. major, L. donovani, and L. tropica challenge, TNFα, IL-1ß, IL-6 levels were significantly higher than negative control cultures with saline (SF) instead of Leishmania promastigotes, unlike L. infantum-stimulated TNFα and L. major-stimulated IL-1ß. We obtained higher levels of IL-4 and IL-10 cytokines after stimulation of human PBMCs by L. infantum and L. donovani, compared to those observed after the challenge of PBMCs by L. major and L. tropica. Regarding IL-35, such cytokine levels were significantly increased following infection with L. infantum and L. donovani, in contrast to L. major and L. tropica. Up to our knowledge, we are the first to study the effect of four different species of Leishmania on IL-35 levels in human cells. Our study highlights how several Leishmania species can up-regulate different groups of cytokines (Th1, Th2, Treg and Breg) and modulate NO release in a different way. This original aspect can be explained by different Leishmania cell products, such as LPG, obtained from different strains/species of live parasites. Our findings would contribute to the development of new therapeutics or vaccination strategies.

ß-Bi2O3 reduction by laser irradiation in a liquid environment.

This study reports the structural and stoichiometric modifications of bismuth oxide nanoparticles in the ß phase (ß-Bi2O3) by UV pulsed laser irradiation in water or ethanol solutions. Scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, UV-vis diffuse reflectance and high-resolution transmission electron microscopy were used to characterize the synthesized nanomaterials. The various analyses demonstrate that the laser irradiation of ß-Bi2O3 nanospheres is a green, fast and effective method to produce Bi2O2CO3 nanosheets or metallic Bi nanoparticles depending on the liquid environment used. Bi subcarbonate is obtained by laser irradiation in water, whereas metallic Bi is produced by laser irradiation in ethanol, and in particular the relative amount of metallic Bi is found to depend on the laser fluence. These typologies of materials find application in several fields, such as photocatalytic processes, light filters and environmental sensors.

SU-E-T-466: TCP and NTCP: Is That All?

PURPOSE: Concerns about the secondary cancer risks associated to the peripheral neutron and photon contamination in photon modern radiotherapy (RT) techniques (e.g., Intensity Modulated RT -IMRT- or Intensity Modulated Arc Therapy -IMAT) have been widely raised. Benefits in terms of better tumor coverage have to be balanced against the drawbacks of poorer organ at risk sparing and secondary cancer risk in order to make the decision on the optimum treatment technique. The aim of this study was to develop a tool which estimates treatment success taking into consideration the neutron secondary cancer probability. METHODS: A methodology and benchmark dataset for radiotherapy real time assessment of patient neutron dose and application to a novel digital detector (DD) has been carried out (submitted to PMB, 2011). Our DD provides real time neutron equivalent dose distribution in relevant organs along the patient. This information, together with TCP and NTCP estimated from the DVH of target and organs at risks, respectively, have been built into a general biological model which allows us to evaluate the success of the treatments (Sánchez-Nieto et al., ESTRO meeting 2012). This model has been applied to make estimation of treatment success in a variety of treatment techniques (3DCRT, forward and inverse IMRT, RapidArc, Volumetric Modulated Arc Therapy and Helical Tomotherapy) to low and high energy. RESULTS: MU-demanding techniques at high energies were able to deliver treatment plans with the highest complicated-free tumour control. Nevertheless, neutron peripheral dose must be taken into consideration as the associated risk could be of the same order of magnitude than the usually considered NTCPs. CONCLUSIONS: The methodology developed to provide an online organ neutron peripheral dose can be successfully combined with biological models to make predictions on treatment success taking into consideration secondary cancer risks.

A conditioned medium from a human liposarcoma-derived cell line induces p53-dependent apoptosis in several tumor cell lines.

A novel cell line, named LSA, has been obtained, stabilized, and characterized from a human liposarcoma. These cells have morphological and biochemical features strongly resembling the adipocytes and were able to grow in the Ham's F12 medium, in presence or absence of FCS. A conditioned medium (LSA-CM) was obtained by growing the LSA cells in the F12 medium in the absence of FCS. LSA-CM had cytostatic and cytotoxic effects (apoptosis and necrosis) associated with down-regulation of c-myc and upregulation of p53 in several human cell lines (breast, lung, glioblastoma, etc. ). The MCF-7 and glioblastoma cells were killed by LSA-CM in 5-6 days, whereas the same cells were killed by LSA-CM co-incubated with low doses of cisplatin in 30 h. LSA-CM peri-tumoral injections for 15 days in Balb-c-fc3H mice affected by mammary tumors, resulted in the rapid disruption of tumors and absence of metastases. In contrast, in the untreated animals the tumor masses were 4 times larger than initial lesions, and numerous metastases were found in the lungs. The toxicity analysis of LSA-CM, performed on three different animal species, showed that LSA-CM is absolutely free of acute, subacute, and subchronic toxicity. The possible use of LSA-CM/cisplatin for cancer treatment is discussed.

Parathyroid carcinoma--the Princess Margaret Hospital experience.

PURPOSE: Carcinoma of the parathyroid gland is a rare disease representing 0.5 to 4% of patients with primary hyperparathyroidism. We reviewed our experience with this disease, with special emphasis on the role of adjuvant postoperative radiotherapy. METHODS: A retrospective review was conducted of all cases of parathyroid carcinoma referred to the Princess Margaret Hospital (PMH) from 1958-1996. Ten patients were identified. Their clinical features, management details, and treatment outcome are described. RESULTS: There were 5 men and 5 women with a mean age of 53 years. Of these, 7 patients underwent en bloc resection; among them, 4 had neck dissection or lymph node sampling. The other 3 patients underwent only limited surgery to remove the tumor. Seven patients were referred for consideration of adjuvant radiation treatment. Six patients were given adjuvant radiation therapy for microscopic residual disease. All patients tolerated the radiation treatment well, with minimal side effects. The 7 patients have been followed regularly with no evidence of recurrence and normal serum calcium. The mean follow-up for the 6 patients who had adjuvant radiotherapy was 62.3 months (range 12 to 156 months). The remaining 3 patients had metastatic disease and were referred for palliative radiotherapy. CONCLUSIONS: Our results in a small number of patients suggest local radiation therapy to the tumor bed may have eliminated the strong predilection for local recurrence of this disease, as reported by other investigators.

[Magnetic resonance in the study of suprarenal neoplasms. Qualitative and quantitative analysis of signal intensity]. / La Risonanza Magnetica nello studio delle neoplasie surrenaliche. Analisi qualitativa e quantitativa dell'intensità del segnale.

INTRODUCTION: Magnetic Resonance Imaging (MRI) has been proposed as the diagnostic technique of choice to characterize adrenal tumors. However, the results of the current studies are controversial. MATERIAL AND METHODS: Forty-nine patients with unilateral adrenal masses were submitted to MRI for lesion characterization on the basis of MR signal intensity. Cytology and/or histology demonstrated 14 pheochromocytomas (pheos), 11 adenomas, 3 cysts, 2 myelolipomas, 4 carcinomas, 3 metastases and 1 fibrosarcoma; a clinical diagnosis of adenoma was made in the remaining 11 patients. MR studies were performed using spin-echo (SE) sequences with T1 (TR/TE = 600/17 ms) and T2 (TR/TE = 2000/15-90 ms) weighting. T1-weighted images were also acquired after Gadolinium-DTPA (Gd-DTPA) administration. MR studies were integrated with in- and out-of-phase (TR/TE = 100/4-6 ms) chemical-shift (CS) sequences. MR signal intensity (SI) was analyzed qualitatively and quantitatively; MR results were correlated with tumor type and hormone secretion. RESULTS: The qualitative analysis of T2 images showed high signal intensity in the majority (80%) of adrenal lesions (14 pheos, 12 adenomas, 3 cysts, 2 myelolipomas and 8 malignancies). The quantitative analysis of post-Gd-DTPA T1 images permitted to distinguish adenomas, cysts and myelolipomas from pheos and malignancies. The qualitative analysis of post-Gd-DTPA T2 and T1 images permitted to distinguish pheos and cysts from adenomas and malignancies (p < .05); however, pheos and cysts as well as adenomas and malignancies were not differentiated. MR SI was similar in secreting and nonsecreting adenomas from both a qualitative and a quantitative viewpoints. CS MRI permitted to distinguish adenomas (decreased signal intensity on out-phase relative to in-phase images) from other benign and malignant lesions (no signal change from out-phase to in-phase images). CONCLUSIONS: The qualitative analysis of MR SI on conventional T1 and T2 images does not permit to differentiate adrenal masses. The qualitative evaluation of T1 images after Gd-DTPA administration, the quantitative analysis and CS sequences are technical options improving lesion characterization.

Optimization of permanent 125I prostate implants using fast simulated annealing.

PURPOSE: Treatment planning of ultrasound-guided transperineal 125I permanent prostatic implants is a time-consuming task, due to the large number of seeds used and the very large number of possible source arrangements within the target volume. The goal of this work is to develop an algorithm based on fast simulated annealing allowing consistent and automatic dose distribution optimization in permanent 125I prostatic implants. METHODS AND MATERIALS: Fast simulated annealing is used to optimize the dose distribution by finding the best seed distribution through the minimization of a cost function. The cost function includes constraints on the dose at the periphery of the planned target volume and on the dose uniformity within this volume. Adjustment between peripheral dose and the dose uniformity can be achieved by varying the weight factor in the cost function. RESULTS: Fast simulated annealing algorithm finds very good seed distributions within 20,000 iterations. The computer time needed for the optimization of a typical permanent implant involving 60 seeds and 14 needles is approximately 15 min. An additional 5 min are necessary for isodose distribution computations and miscellaneous outputs. CONCLUSION: The use of fast simulated annealing allows for an efficient and rapid optimization of dose distribution. This algorithm is now routinely used at our institution in the clinical planning of 125I permanent transperineal prostate implants for early stage prostatic carcinoma.

[Scintigraphic characterization of expansive lesions located in the adrenals. Comparison with magnetic resonance imaging]. / Caratterizzazione scintigrafica delle lesioni espansive a sede surrenalica. Confronto con l'imaging a Risonanza Magnetica.

In this study, 35 patients (11 men and 24 women, mean age 47 +/- 16 years) with unilateral adrenal masses underwent nor-cholesterol (nor-Chol) (n = 11), metaiodobenzylguanidine (MIBG) (n = 15) or nor-Chol and MIBG (n = 9) radionuclide studies. In all patients Magnetic Resonance (MR) adrenal imaging was also performed. In 19 (54%) patients, no laboratory abnormalities of adrenal function were observed. In the other 16 (46%) patients, adrenal hyperfunction was found. In 21 lesions, histology showed 10 pheochromocytomas (Pheos), 6 adenomas, 3 metastases, 1 cyst and 1 nodular focal liver hyperplasia. In the remaining 14 lesions, increased cortisol (n = 4) or aldosterone (n = 2) levels and/or intense nor-Chol uptake (n = 14) were considered suggestive of adenoma. Diagnostic accuracy of both nor-Chol and MIBG radionuclide studies in correctly identifying adenoma or Pheos was 100%. Conversely, qualitative MR signal intensity (SI) analysis on T2-weighted images did not allow to accurately distinguish lesions of different nature. In particular, 10 Pheos, 8 adenomas, 3 mestastasis and 1 cyst clearly showed on T2-weighted images higher SI than the liver; 5 adenomas had a slight higher SI; the remaining lesions (7 adenomas and 1 liver hyperplasia) exhibited low SI. In conclusion, adrenal scintigraphy using nor-Chol or MIBG allows to identify adenomas and Pheos, respectively. Conversely, qualitative MR SI analysis cannot differentiate different adrenal lesion (Pheos, adenoma, metastasis and cyst) and yields heterogeneous results in adenomas.

[Design, development, and dosage control of individual compensatory filters for 6 MV X-ray radiotherapy]. / Progettazione, realizzazione e controllo dosimetrico di filtri compensatori individuali per radioterapia con raggi X da 6 MV.

An automated system for the design and manufacturing of individual compensators has been implemented. The system based on computed tomography enables 3D compensation of missing tissue and tissue heterogeneities. The relationship between Hounsfield numbers and electron densities was obtained empirically. Compensator design is based on the calculation of the water equivalent thicknesses between the compensation plane and the patient surface. After calculation a styrofoam mould is cut by a computer driven machine and filled with bee's wax or tin granules. Compensator thickness is calculated by means of the conversion ratio tau, which is defined as t/x, where t is the compensator thickness equivalent to the missing tissue in the treatment geometry. Relations between tau and field size, depth of compensation plane and focus-compensation plane distance were assessed. The conversion ratio is a linear function of the missing tissue and depends markedly on field size; for a 10-cm-deep compensation plane at 1 m from the accelerator target the tau value, calculated for bee's wax, decreases by 25% from 7 x 7 cm2 to 23 x 23 cm2 field size. Conversion ratio rises by approximately 10% for a 3-cm increase in compensation plane depth and reduces by about 5% when increasing the focus-compensation plane distance from 100 cm to 140 cm. It must be stressed that a 10% variation of tau, for bee's wax, involves only a 2% dose variation in the compensation plane. Therefore, for compensator design it is enough to consider tau as depending on field size only. Compensation effectiveness has been tested by a film-densitometric technique using phantoms with tilted incident surfaces and heterogeneities. The results show that the compensators reduce the flatness of the beam profile below 4% and increase the relative dose uniformity on the compensation plane from 18% to 60%.

[Stereotactic radiotherapy with linear accelerators. Dosage considerations on collimators and photon beam energy]. / La radioterapia stereotassica con acceleratori lineari. Considerazioni dosimetriche sui collimatori e sull'energia di fasci di fotoni.

The small X-ray beam profiles produced by linear accelerators and used in stereotactic radiosurgery were studied. Circular focusing and not-focusing beams outlined by additional collimators (diameter ranging 10 to 30 mm) and square field outlined by the jaws (field size 10 to 30 mm) were measured. 6 and 18-MV X-ray beams from a dual energy accelerator and 6 and 15-MV X-ray beams produced by 2 single-energy accelerators were used. Measurements were carried out with Kodak X Omat V films in a perspex phantom in the same conditions for all the fields. To study the profile characteristics we introduced the V80/V20 = (R80/R20)3 ratio where R80 and R20 are respectively the mean distance of the 80% and 20% isodose lines from the beams axis. Measurement results show that 6-MV X-ray beams have a higher V80/V20 ratio than the ones obtained with the other energies. There is no significant difference between the beams produced with focused collimators and those produced with not-focused collimators. Square fields outlined by the jaws have a V80/V20 ratio greatly dependent on the accelerator used. This ratio is generally worse than the ones obtained with beams outlined by additional collimators.

[Advantages of a system of positioning and localization made of thermo-conformable materials for irradiation of cervicofacial and encephalic lesions treated with stereotactic fractionated radiation]. / Vantaggi offerti da un sistema di posizionamento e localizzazione di materiale termoconformabile per l'irradiazione di lesioni cervico facciali ed encefaliche trattate con tecnica stereotassica in frazionamento.

In this work we first analyzed the reliability of materials supplied by the main firms, which must be considered when defining the lesion and planning target volume. The coordinates of specific target landmarks, i.e., bone, calcium deposition or catheters, on baseline CT scans were compared with those measured on control scans. Since the PLATO-SRS system yields 3 coordinates for each target, the final error is calculated by the evaluation of the shift of the different coordinates. The mean error reported for the first material (ORFIT) was 5 mm (13/23 patients). This margin of error is too high and was considered unacceptable; a second material was then tested. The latter, which is not recyclable and softens at higher temperatures, exhibited a mean error of 2.5 mm (10/23 patients), which allows daily repositioning of greater reliability. Treatment was repeated in 4/20 arcs in all, which number depended mainly on fraction size. Correct lesion location and patient positioning were allowed by laser landmarks on the mask made directly on the treatment couch. The laser too was checked before each treatment session, i.e., preferentially at the end of an ordinary working day.

Ultrasound diagnosis of Achilles tendon pathology in runners.

The great upsurge in popularity of running activities has increased the number of athletes presenting with pathology of the Achilles tendon. A clinical and ultrasonic study was performed on 47 middle and long distance runners referred to the Authors with such problems. The results of this study can be grouped as follows: 1. paratendonitis: enlargement of the antero-posterior diameter of the tendon, and hyperechogenicity of Kager's triangle; 2. tendonitis (with or without paratendonitis): thickening of the tendon, with the presence of degenerative nodules; 3. enthesopathy: thickening of the distal part of the tendon, enlargement of the hypoechogenic area behind the tendon itself and microcalcification.