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Phil Attard Several variational principles that have been proposed for nonequilibrium systems are analyzed. These include the principle of minimum rate of entropy production due to Prigogine [Introduction to Thermodynamics of Irreversible Processes (Interscience, New York, 1967)], the principle of maximum rate... ( view more ) of entropy production, which is common on the internet and in the natural sciences, two principles of minimum dissipation due to Onsager [Phys. Rev. 37, 405 (1931)] and to Onsager and Machlup [Phys. Rev. 91, 1505 (1953)], and the principle of maximum second entropy due to Attard [J. Chem.. Phys. 122, 154101 (2005); Phys. Chem. Chem. Phys. 8, 3585 (2006)]. The approaches of Onsager and Attard are argued to be the only viable theories. These two are related, although their physical interpretation and mathematical approximations differ. A numerical comparison with computer simulation results indicates that Attard's expression is the only accurate theory. The implications for the Langevin and other stochastic differential equations are discussed. ( view less ) E Attard,H AttardThe antitrypsin activity of extracts obtained from two different seed types of Ecballium elaterium, was tested in vitro. The presence of trypsin inhibitors in three chromatographed samples for each extract, showed a strong and specific antitrypsin activity. Rosienne Farrugia,Christian A Scerri,Simon Attard Montalto,Raymond Parascandolo,Brian G R Neville,Alex E Felice Deficient activity of the Dihydropteridine Reductase enzyme (DHPR; EC 1.5.1.34; OMIM 261630) is due to mutations in the Quinoid Dihydropteridine Reductase gene on 4p15.3 (QDPR; RefSeq NM_000320). It results in defective recycling of tetrahydrobiopterin (BH(4)) and homozygotes have a rare form of at... ( view more )ypical Hyperphenylalaninaemia and Phenylketonuria (aPKU). The heterozygote frequency in the Maltese population is high at 3.3%. The more recently described and rarer type of BH(4) deficiency due to Sepiapterin Reductase enzyme deficiency (SR; EC 1.1.1.153; OMIM 182125), which presents as an atypical form of Dopa Responsive Dystonia (DRD) [L. Bonafe, B. Thony, J.M. Penzien, B. Czarnecki, N. Blau, Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia, Am. J. Hum. Genet. 69 (2001) 269-277; B.R.G. Neville, R. Parascandalo, S. Attard Montalto, R. Farrugia, A.E. Felice, A congenital dopa responsive motor disorder: a Maltese variant due to sepiapterin reductase deficiency, Brain 128 (Pt10) (2005) 2291-2296.] has also been identified at high frequency (4.6%) in this population. Two mutations, the c.68G>A in QDPR (p.G23D), and the new SPR, IVS2-2A>G mutation at the splice site consensus sequence in intron 2 of the Sepiapterin Reductase gene (SPR; RefSeq NM_003124) on 2p14-p12, were found to be the sole causative mutations in all the patients with DHPR deficiency and SR deficiency studied. All parents were heterozygotes for the corresponding mutation and showed no clinical symptoms. Three polymorphisms, c.96C>T (p.A32A), c. 345G>A (p.S115S) and c. 396G>A (p.L132L), have also been identified in the QDPR gene, defining four wild-type frameworks, useful in molecular epidemiology studies. The c. 68G>A mutation in QDPR was found only on framework I, suggesting a founder effect. In contrast no additional sequence diversity was found in the SPR gene whether in wild-type or mutant alleles which is also consistent with a founder effect. ( view less ) Songnian He,Phil Attard A formally exact Kirkwood-Buff virial formula for the surface tension of a supersaturated interface is derived. A modified Gibbs ensemble method is given that allows the creation of interacting supersaturated phases of equal chemical potential, and which enables the Kirkwood-Buff formula to be appl... ( view more )ied. The methods are tested by Monte Carlo simulation of a supersaturated Lennard-Jones fluid with a planar liquid-vapor interface. The Kirkwood-Buff results for the supersaturated surface tension are found to be in reasonable agreement with new results obtained here using the recently developed, formally exact, ghost interface method, [M. P. Moody and P. Attard, J. Chem. Phys., 2002, 117, 6705]. The surface tension is obtained as a function of supersaturation at four temperatures, and it is found to decrease with increasing supersaturation, and to vanish at the vapor spinodal. The relevance of the present results to the nucleation of droplets in a supersaturated vapor is discussed. ( view less ) A E Attard The principle that the coupling of light between two fiber waveguides can be controlled by the resonant interference of a third waveguide has been developed [Attard, Appl. Opt. 37, 2296-2302 (1998)]. Here significant details concerning the operation of a photonic switch are obtained, and a more com... ( view more )plete analysis is presented. Multiple-resonant conditions are identified for slab and fiber control waveguides at large indices of refraction. Thus a selection of materials with an appropriate refractive index and a Kerr coefficient is rendered more easily. Furthermore it is shown that the light used to control the index of refraction in the control waveguide does not enter the output of the photonic switch but remains confined to the control waveguide, for either a slab or a multimode fiber control waveguide. Spatial fluctuations of the control light beam in the control waveguide do not affect the operation of the photonic switch. Tolerances have been determined for the spacing between the control waveguide and the photonic coupler and also for the index of refraction of the control waveguide. ( view less ) Kishor B Taori,Ritu S Chaudhary,Vinod Attarde,Suresh Dhakate,Virender Sheorain,Prashant Nimbalkar,Preetam N WasnikOBJECTIVE: The purpose of our study was to detect changes in renovascular resistance through renal Doppler indexes in young sickle cell disease patients with normal routine urine laboratory tests. CONCLUSION: Renal Doppler sonography resistive index and pulsatility index values can serve as early r... ( view more )adiologic predictors of renovascular changes in sickle cell disease. Thereby, these findings can guide clinicians in the use of more intensive monitoring of laboratory values and initiating adequate treatment at an early stage. ( view less ) Christopher J Shepherd,Siân Rizzo,Ioanna Ledaki,Melissa Davies,Daniel Brewer,Gerhardt Attard,Johann de Bono,David L Hudson BACKGROUND: Recent evidence suggests that prostate stem cells in benign and tumor tissue express the cell surface marker CD133, but these cells have not been well characterized. The aim of our study was to gene expression profile CD133-expressing cells. METHODS: We analyzed CD133-positive (CD133+) ... ( view more )and -negative (CD133-) sub-populations of high-integrin expressing epithelial cells isolated from benign human prostate tissue and hormone-refractory prostate cancer (HRPC). RESULTS: CD133+ cells freshly isolated from benign prostate tissue exhibited an expression profile characteristic of a putative stem/progenitor cell population, with transcripts involved in biological processes ranging from development and ion homeostasis to cell communication. The profile of CD133- cells was consistent with that of a transit amplifying population, suggesting up-regulated proliferation and metabolism. Comparison of benign populations to those from HRPC showed some similarities between CD133+ profiles but also revealed significant differences that provide a tumor-specific pattern, which included evidence of increased metabolic activity and active proliferation. Subsequently, we demonstrated protein expression of a number of candidate genes in these cell populations and in benign tissue. In a novel observation we also found expression of some of these markers in prostate tumors, including the oligodendrocyte lineage transcription factor OLIG1. CONCLUSIONS: This study provides a unique genome-wide molecular signature of CD133+ and CD133- human prostate epithelial cells. This will provide a valuable resource for prostate stem cell biology research and the identification of novel therapeutic targets for the treatment of prostate cancer. ( view less ) Josephine Corsi,Marcus K Dymond,Oscar Ces,Joscha Muck,Daniele Zink,George S AttardWe report that a 4.3 kbp linearised T7 DNA plasmid is actively transcribed when it is dispersed in the hexagonal liquid crystalline phase of dioleoylphosphoethanolamine (DOPE). Jason Beard,George S Attard,Matthew J Cheetham The homeostatic control of membrane lipid composition appears to be of central importance for cell functioning and survival. However, while lipid biosynthetic reaction networks have been mapped in detail, the underlying control architecture which underpins these networks remains elusive. A key prob... ( view more )lem in determining the control architectures of lipid biosynthetic pathways, and the mechanisms through which control is achieved, is that the compositional complexity of lipid membranes makes it difficult to determine which membrane parameter is under homeostatic control. Recently, we reported that membrane stored elastic energy provides a physical feedback signal which modulates the activity in vitro of CTP:phosphocholine cytidylyltransferase (CCT), an extrinsic membrane enzyme which catalyses a key step in the synthesis of phosphatidylcholine lipids in the Kennedy pathway (Kennedy 1953 J. Am. Chem. Soc. 75, 249-250). We postulate that stored elastic energy may be the main property of membranes that is under homeostatic control. Here we report the results of simulations based on this postulate, which reveal a possible control architecture for lipid biosynthesis networks in vivo. ( view less ) Daniel T Grima,Lawrence A Leiter,Shaun G Goodman,Cheryl L Attard,Chi-Ming Chow,Anatoly Langer BACKGROUND: Strong evidence exists to support the use of statins, acetylsalicylic acid (ASA) and angiotensin-converting enzyme inhibitors (ACEI) in patients at high risk of cardiovascular (CV) events; however, current practice pattern data indicate that a significant care gap exists between evidenc... ( view more )e and practice. OBJECTIVES: To quantify the reduction in CV events that may be obtained with the optimal use of vascular protection therapy in Canadians at high risk of cardiovascular events. METHODS: Canadian Community Health Survey data from 2003 were used to estimate the prevalence of heart disease and/or diabetes, which were applied to an age-specific population in Canada to calculate the total number of high-risk patients. The number of events over 10 years was estimated using a state transition model, published risk equations, practice pattern data from Canadian registries and published therapy efficacy from clinical trials. RESULTS: Among 2.2 million high-risk Canadians, current care with statin, ASA and ACEI therapy has reduced the estimated occurrence of CV events over the next 10 years by approximately 400,000 from 1.01 million. Universal use of combination statin, ASA and ACEI therapy for high-risk patients, compared with current care, would prevent as many as 143,000 more CV events over the next 10 years. CONCLUSIONS: Great advances in the management of CV disease have been made; however, CV disease remains a substantial burden to patients and to the Canadian health care system. Canadian physicians have the opportunity to further reduce this burden through optimal management of high-risk patients based on clinical guidelines. ( view less ) J Clark,G Attard,S Jhavar,P Flohr,A Reid,J De-Bono,R Eeles,P Scardino,J Cuzick,G Fisher,M D Parker,C S Foster,D Berney,G Kovacs,C S Cooper An ERG gene 'break-apart' fluorescence in situ hybridization (FISH) assay has been used to screen whole-mount prostatectomy specimens for rearrangements at the ERG locus. In cancers containing ERG alterations the observed pattern of changes was often complex. Different categories of ERG gene altera... ( view more )tion were found either together in a single cancerous region or within separate foci of cancer in the same prostate slice. In some cases the juxtaposition of particular patterns of ERG alterations suggested possible mechanisms of tumour progression. Prostates harbouring ERG alterations commonly also contained cancer that lacked rearrangements of the ERG gene. A single trans-urethral resection of the prostate specimen examined harboured both ERG and ETV1 gene rearrangements demonstrating that the observed complexity may, at least in part, be explained by multiple ETS gene alterations arising independently in a single prostate. In a search for possible precursor lesions clonal ERG rearrangements were found both in high grade prostatic intraepithelial neoplasia (PIN) and in atypical in situ epithelial lesions consistent with the diagnosis of low grade PIN. Our observations support the view that ERG gene alterations represent an initiating event that promotes clonal expansion initially to form regions of epithelial atypia. The complex patterns of ERG alteration found in prostatectomy specimens have important implications for the design of experiments investigating the clinical significance and mechanism of development of individual prostate cancers. ( view less ) Phil Attard,Angus Gray-Weale A Brownian particle subject to a time- and space-varying force is studied with the second entropy theory for nonequilibrium statistical mechanics. A fluctuation expression is obtained for the second entropy of the path, and this is maximized to obtain the most likely path of the particle. Two appro... ( view more )aches are used, one based on the velocity correlation function and one based on the position correlation function. The approaches are a perturbation about the free particle result and are exact for weak external forces. They provide a particularly simple way of including memory effects in time-varying driven diffusion. The theories are tested against computer simulation data for a Brownian particle trapped in an oscillating parabolic well. They accurately predict the phase lag and amplitude as a function of drive frequency, and they account quantitatively for the memory effects that are important at high frequencies and that are missing in the simplest Langevin equation. ( view less ) F Frasca,C Nucera,G Pellegriti,P Gangemi,M Attard,M Stella,M Loda,V Vella,C Giordano,F Trimarchi,E Mazzon,A Belfiore,R Vigneri BRAF((V600E)) mutation is the most frequent genetic alteration in papillary thyroid carcinomas (PTCs) that are 80-90% of all thyroid cancers. We evaluated the relationship between BRAF((V600E)) and tumor, host, and environmental factors in PTCs from all geographical areas of Sicily. By PCR, BRAF((V... ( view more )600E)) was investigated in a series of 323 PTCs diagnosed in 2002-2005. The correlation between clinicopathological tumor, host, and environmental characteristics and the presence of BRAF((V600E)) were evaluated by both univariate and multivariate analyses. BRAF((V600E)) was found in 38.6% PTCs, with a 52% frequency in the classical PTCs and 26.4% in the tall cell variant. Univariate analysis indicated that BRAF((V600E)) was associated with greater tumor size (P=0.0048), extra-thyroid invasion (P<0.0001), and cervical lymph nodal metastases (P=0.0001). Multivariate logistic regression analysis confirmed that BRAF((V600E)) was an independent predictor of extra-thyroid invasion (P=0.0001) and cervical lymph nodal metastasis (P=0.0005). The association between BRAF((V600E)) and extra-thyroid invasion was also found in micro-PTCs (P=0.006). In 60 classical PTCs, BRAF((V600E)) was positively correlated with matrix metalloproteinase-9 expression (P=0.0047), suggesting a possible mechanism for BRAF((V600E)) effect on PTC invasiveness. No association was found between BRAF((V600E)) and patient age, gender, or iodine intake. In contrast, a strong association was found with residency in Eastern Sicily (P<0.0001 compared with Western Sicily). These results indicate that BRAF((V600E)) mutation is a marker of aggressive disease in both micro- and macro-PTCs. Moreover, for the first time, a possible link between BRAF((V600E)) mutation and environmental carcinogens is suggested. ( view less ) Kishor Taori,Parag Patil,Vinod Attarde,Arpita Singh,Varsha RangankarChorioangioma is a benign vascular tumor of the placenta arising from primitive chorionic mesenchyme. Large (>4 cm) chorioangiomas are much rarer and are often associated with maternal and/or fetal complications. We describe the sonographic features of a large placental chorioangioma with normal ou... ( view more )tcome. ( view less ) Thomas M Attard,Tanya Tajouri,Kristin D Peterson,Susan Tinley,Alan G Thorson,Henry T Lynch PURPOSE: Children with familial adenomatous polyposis have a greater mortality and morbidity in the first decade of life compared with the general population. Some children with a more severe disease phenotype present early with colorectal adenomata and may require colectomy at an early age. We pre... ( view more )sent our multidisciplinary clinic experience with familial adenomatous polyposis in children younger than age ten years at the time of presentation. METHODS: A cross-sectional analysis was performed on all patients with suspected or confirmed familial adenomatous polyposis presenting in the first decade of life and followed by the multidisciplinary Pediatric Hereditary Polyposis Clinic at our institutions. Analysis included demographics, clinical presentation and course, gene mutation testing, endoscopic-histologic findings, and surgical outcome. RESULTS: Twenty-two children (11 males) presented with suspected or confirmed familial adenomatous polyposis. Two were discharged from follow-up after negative adenomatous polyposis coli gene mutation testing. The rest underwent annual hepatoblastoma surveillance through age ten years with negative findings. Twelve patients presented with symptoms: six had de novo familial adenomatous polyposis. Seven had gastrointestinal hemorrhage and went on to colonoscopy. Four patients with adenomatous polyposis coli gene mutation at codon 1309 were referred for colectomy before age ten years. Referral to colectomy was earlier in patients with 1309 mutation and with de novo familial adenomatous polyposis. CONCLUSIONS: Children with familial adenomatous polyposis younger than age ten years may present presymptomatically for disease surveillance. Familial adenomatous polyposis with adenomatous polyposis coli gene mutation at codon 1309 entails a risk of a more aggressive phenotype; early colectomy may be indicated in children harboring this gene mutation. ( view less ) Xavier Le Roux,Franck Poly,Pauline Currey,Claire Commeaux,Brigitte Hai,Graeme W Nicol,James I Prosser,Michael Schloter,Eléonore Attard,Katja Klumpp The influence of switches in grassland management to or from grazing on the dynamics of nitrifier activity, as well as the abundance of ammonia-oxidizing bacteria, AOB and ammonia-oxidizing archeae, AOA, was analyzed for two years after changing management. Additionally community structure of AOB w... ( view more )as surveyed. Four treatments were compared in mesocosms: grazing on previously grazed grassland (G-G); no grazing on ungrazed grassland (U-U); grazing on ungrazed grassland (U-G) and cessation of grazing on grazed grassland (G-U). Nitrifier activity and abundance were always higher for G-G than U-U treatments and AOB community structure differed between these treatments. AOA abundance was in the same range as AOB abundance and followed the same trend. Grazing led to a change in AOB community structure within <5 months and a subsequent (5-12 months) increase in nitrifier activity and abundance. In contrast, cessation of grazing led to a decrease in nitrifier activity and abundance within <5 months and to a later (5-12 months) change in AOB community structure. Activity in G-U and U-G was similar to that in U-U and G-G, respectively, after 12 months. Sequence analysis of 16S rRNA gene clones showed that AOB retrieved from soils fell within the Nitrosospira lineage and percentages of AOB related to known Nitrosospira groups were affected by grazing. These results demonstrate that AOB and AOA respond quickly to changes in management. The selection of nitrifiers adapted to novel environmental conditions was a prerequisite for nitrification enhancement in U-G, whereas nitrification decrease in G-U was likely due to a partial starvation and decrease in the abundance of nitrifiers initially present. The results also suggest that taxonomic affiliation does not fully infer functional traits of AOB. ( view less ) G Attard,J Clark,L Ambroisine,G Fisher,G Kovacs,P Flohr,D Berney,C S Foster,A Fletcher,W L Gerald,H Moller,V Reuter,J S De Bono,P Scardino,J Cuzick,C S Cooper,Transatlantic Prostate Group  New predictive markers for managing prostate cancer are urgently required because of the highly variable natural history of this disease. At the time of diagnosis, Gleason score provides the gold standard for assessing the aggressiveness of prostate cancer. However, the recent discovery of TMPRSS2 ... ( view more )fusions to the ERG gene in prostate cancer raises the possibility of using alterations at the ERG locus as additional mechanism-based prognostic indicators. Fluorescence in situ hybridization (FISH) assays were used to assess ERG gene status in a cohort of 445 prostate cancers from patients who had been conservatively managed. The FISH assays detected separation of 5' (labelled green) and 3' (labelled red) ERG sequences, which is a consequence of the TMPRSS2-ERG fusion, and additionally identify interstitial deletion of genomic sequences between the tandemly located TMPRSS2 and ERG gene sequences on chromosome 21. Cancers lacking ERG alterations exhibited favourable cause-specific survival (90% survival at 8 years). We identify a novel category of prostate cancers, characterized by duplication of the fusion of TMPRSS2 to ERG sequences together with interstitial deletion of sequences 5' to ERG (called '2+Edel'), which by comparison exhibited extremely poor cause-specific survival (hazard ratio=6.10, 95% confidence ratio=3.33-11.15, P<0.001, 25% survival at 8 years). In multivariate analysis, '2+Edel' provided significant prognostic information (P=0.003) in addition to that provided by Gleason score and prostate-specific antigen level at diagnosis. Other individual categories of ERG alteration were associated with intermediate or good prognosis. We conclude that determination of ERG gene status, including duplication of the fusion of TMPRSS2 to ERG sequences in 2+Edel, allows stratification of prostate cancer into distinct survival categories. ( view less ) Henry T Lynch,Jane F Lynch,Patrick M Lynch,Thomas Attard Hereditary forms of colorectal cancer, as is the case with virtually all forms of hereditary cancer, show extensive phenotypic and genotypic heterogeneity, a phenomenon discussed throughout this special issue of Familial Cancer. Clearly, the family physician, oncology specialist, genetic counselor,... ( view more ) and cancer geneticist must know fully the complexity of hereditary cancer syndromes, their differential diagnosis, in order to establish a diagnosis, direct highly-targeted surveillance and management, and then be able to communicate effectively with the molecular geneticist so that an at-risk patient's DNA can be tested in accord with the syndrome of concern. Thus, a family with features of the Lynch syndrome will merit microsatellite instability testing, consideration for immunohistochemistry evaluation, and mismatch repair gene testing, while, in contrast, a patient with FAP will require APC testing. However, other germline mutations, yet to be identified, may be important should testing for these mutations prove to be absent and, therein, unrewarding to the patient. Nevertheless, our position is that if the patient's family history is consistent with one of these syndromes, but a mutation is not found in the family, we still recommend the same surveillance and management strategies for patients from families with an established cancer-causing germline mutation. Our purpose in this paper is to provide a concise coverage of the major hereditary colorectal cancer syndromes, to discuss genetic counseling, molecular genetic evaluation, highly targeted surveillance and management, so that cancer control can be maximized for these high hereditary cancer risk patients. ( view less ) Peter Karran,Natalie AttardThiopurines have diverse clinical applications and their long-term use as anti-rejection drugs in transplant patients has been associated with a significantly increased risk of various types of cancer. Although they are slowly being replaced by a new generation of non-thiopurine immunosuppressants,... ( view more ) it is anticipated that their use in the management of inflammatory and autoimmune diseases will continue to increase. Therapy-related cancer will remain a potential consequence of prolonged treatment for these generally non-life-threatening conditions. Understanding how thiopurines contribute to the development of cancer will facilitate clinical decisions about the potential risks to patients of long-term treatment for chronic inflammatory disorders. ( view less ) Agnès Attard,Mathieu Gourgues,Eric Galiana,Franck Panabières,Michel Ponchet,Harald Keller Oomycetes from the genus Phytophthora are fungus-like plant pathogens that are devastating for agriculture and natural ecosystems. Due to their particular physiological characteristics, no efficient treatments against diseases caused by these microorganisms are presently available. To develop such ... ( view more )treatments, it appears essential to dissect the molecular mechanisms that determine the interaction between Phytophthora species and host plants. Available data are scarce, and genomic approaches were mainly developed for the two species, Phytophthora infestans and Phytophthora sojae. However, these two species are exceptions from, rather than representative species for, the genus. P. infestans is a foliar pathogen, and P. sojae infects a narrow range of host plants, while the majority of Phytophthora species are quite unselective, root-infecting pathogens. To represent this majority, Phytophthora parasitica emerges as a model for the genus, and genomic resources for analyzing its interaction with plants are developing. The aim of this review is to assemble current knowledge on cytological and molecular processes that are underlying plant-pathogen interactions involving Phytophthora species and in particular P. parasitica, and to place them into the context of a hypothetical scheme of co-evolution between the pathogen and the host. ( view less ) Vittorio Gebbia,Carlo Di Gregorio,Marco Attard ABSTRACT: INTRODUCTION: Thyroglossal duct carcinoma is a very rare finding and its presentation is similar to that of a benign cyst, which is a relatively common developmental abnormality that may manifest as a midline, neck mass. In general the diagnosis of thyroglossal duct carcinoma is based on ... ( view more )the pathologic examination of the mass, but needle aspiration cytology, ultrasound and computed tomography play a role in the differential diagnosis of malignancy. CASE PRESENTATION: A further case of thyroglossal duct carcinoma and concurrent thyroid carcinoma with locoregional lymph node metastases affecting a 40-year-old woman followed up for 4 years is presented and discussed. CONCLUSION: Sistrunk's surgical technique must always be the initial treatment, but in case of carcinoma further surgery, that is, thyroidectomy with or without lymph node dissection, and treatment with radioactive iodine have to be considered according to the microscopic and clinical findings. Accurate pre-operative clinical and radiological evaluation should be performed in order to plan surgical strategy. ( view less ) V Grech,T Buttigieg,A Portelli,S Kotes,G Attard,P Huhn,C Gauci,M Schembri-WismayerKawasaki disease (KD) presenting with an acute hepatitic picture is exceedingly rare. A 3.5-year-old girl presented with acute hepatitis and went on to satisfy the criteria for the diagnosis of KD for which she was treated. There were no cardiac abnormalities or sequelae. G Attard,J Kitzen,S P Blagden,P C Fong,L C Pronk,J Zhi,G Zugmaier,J Verweij,J S de Bono,M de Jonge Pertuzumab represents the first in a new class of targeted therapeutics known as HER dimerisation inhibitors. We conducted a phase Ib study to determine the maximum-tolerated dose, the dose limiting toxicities (DLT), and pharmacokinetic (PK) interaction of docetaxel when administered in combination... ( view more ) with pertuzumab. Initially, two dose levels of docetaxel (60 and 75 mg m(-2)) were explored in combination with a fixed dose of 1050 mg of pertuzumab; then two dose levels of docetaxel (75 and 100 mg m(-2)) were explored in combination following a fixed dose of 420 mg of pertuzumab with a loading dose of 840 mg. Both drugs were administered intravenously every 3 weeks. The latter dose of pertuzumab was allowed after an amendment to the original protocol when phase II data suggesting no difference in toxicity or activity between the 2 doses became available. Two patients out of two treated at docetaxel 75 mg m(-2) in combination with pertuzumab 1050 mg suffered DLT (grade 3 diarrhoea and grade 4 febrile neutropaenia). Two out of five patients treated at docetaxel 100 mg m(-2) in combination with pertuzumab 420 mg with a loading dose of 840 mg suffered DLT (grade 3 fatigue and grade 4 febrile neutropaenia). Stable disease was observed at four cycles in more than half of the patients treated and a confirmed radiological partial response with a >50% decline in PSA in a patient with hormone refractory prostate cancer were observed. There were no pharmacokinetic drug-drug interactions. The recommended phase II dose of this combination was docetaxel 75 mg m(-2) and 420 mg pertuzumab following a loading dose of 840 mg. ( view less ) K Taori,P Patil,V Attarde,S Chandanshive,V Rangankar,N RewatkarMesenchymal chondrosarcomas, although very rare compared with conventional chondrosarcomas, are one of the few primary malignant tumours of bone that sometimes also arise in the soft tissues. Here we present a rare case of retroperitoneal extraskeletal mesenchymal chondrosarcoma (ESMC) in a 50-year... ( view more )-old female that showed characteristic extensive calcification. In this report, we discuss CT features of ESMC with pathological correlation. ( view less ) Danilo Attard Barbini,Fabiana Vanni,Silvana Girolimetti,Roberto Dommarco The development of an analytical method for the determination of four selected pyrethroid insecticides at residue level in beef meat is presented. Acetone and petroleum ether at 40-60 degrees C were chosen as extraction solvents. A two-step clean-up was performed using an Extrelut NT3-C(18) system ... ( view more )followed by a Florisil column, with disposable, ready-to-use cartridges. Instrumental analysis was carried out on a gas chromatograph equipped with an electron capture detector (GC-ECD), using matrix-matched and internal standard calibration techniques. Confirmatory analysis by GC-MS was performed. Recoveries at the EU Maximum Residue Limit (MRL), 0.5 x MRL and 1.5 x MRL levels and the repeatabilities were widely satisfactory. The main advantage of the method was the reduction of analysis time as compared with previously published works. The applicability of the method to different matrices and pesticide classes will be investigated. ( view less )
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