96 research outputs found

    26 Ocena wyników pooperacyjnej radioterapii skojarzonej z 5-fluorouracylem u chorych na raka odbytnicy

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    Celem pracy była ocena wyników leczenia uzupełniającego z udziałem chemio- i radioterapii chorych po radykalnym zabiegu operacyjnym z powodu raka odbytnicy, ze szczególnym uwzględnieniem tolerancji leczenia. Materiał obejmuje 64 chorych leczonych w Klinice Onkologii i Radioterapii w Iatach1991–1995. Głównymi powikłaniami w czasie leczenia były biegunki (58%), nudności i wymioty (15%), objawy dyżuryczne (6%), leukopenia (33%) i niedokrwistość (5%). Do ostrych powikłań doszło ogółem 43 chorych (66%) w tym u 15 (23%) miały one charakter ciężki (stopień III i IV). Troje chorych nie ukończyło leczenia z powodu znacznego nasilenia objawów niepożądanych leczenia i pogorszenia stanu ogólnego.Późne powikłania, przede wszystkim w obrębie jelit i dróg moczowych, wystąpiły ogółem u 22 chorych (34%) w tym u 6 (9%)- w stopniu ciężkim. Spośród ocenionych 64 chorych dotychczas zmarło 19 (30%). Mediana czasu przeżycia w całej grupie wynosiła 37 miesięcy (11–60 miesięcy). Do wznowy miejscowej doszło u 15 chorych (23%) natomiast przerzuty odległe wystąpiły u 18 chorych (28%). Przedstawione wyniki, wskazujące na wysoki odsetek nawrotów oraz dużą liczbę powikłań popromiennych, skłoniły nas do zmiany techniki napromieniania. Efekty tych modyfikacji będzie można ocenić dopiero za kilka lat

    The role of biological rhythms in cancer chemotherapy

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    Adjuvant treatment of patients with rectal cancer

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    Adjuvant postoperative radiotherapy combined with chemotherapy is considered a standard management of rectal cancer patients with increased risk of local recurrence. In this study we evaluated the results of adjuvant chemo- and radiotherapy after radical surgery in 64 patients with rectal carcinoma with special reference to tolerance of treatment. All patients underwent radical surgery: anterior abdominal resection in 26, abdominoperineal resection in 19 and Hartman resection in one. Thirty three patients were postoperatively staged as Dukes B2 and 31 patients – as Dukes C. All patients received postoperative chemo-radiotherapy. Treatment included megavoltage irradiation with two parallel opposed fields to small pelvis at a dose of 45 Gy in 23–25 fractions and concomitant chemotherapy with 5-Fluorouracil during first three and last three days of irradiation.Main early complications from chemoradiation included diarrhea (58%), nausea and vomiting (15%), dysuria (6%), leukopenia (31%) and anaemia (4%). In total, acute side effects occured in 42 patients (66%) and in 16 of them (25%) were of grade 3 or 4. Three patients did not complete the treatment due to exacerbation of side effects and/or serious deterioration of performance status. Late complications, mainly from bowels and urinary bladder, occured in 19 patients (30%) and six of then (9%) were severe.Nineteen of the 64 evaluated patients have deceased ill now. Median survival was 29 months (4 to 50 months). Local recurrence was seen in 14 patients (22%) and distant metastases – in 18 (28%).Results of our study show that postoperative radiochemotherapy in rectal cancer patients is accompanied by a large number of acute and late complications. Literature data demonstrate that better tolerance of treatment may be achieved with the use of special surgical techniques preventing the replacement of small intestines to the pelvis after rectal amputation. Further improvement may be achieved with the use of multiple radiation fields, computerized treatment planning and customized blocking. Another option is an application of preoperative radiotherapy – the approach becoming recently more commonly used

    37. Multicenter, randomized study assessing the impact of amifostine on normal tissue radiation tolerance during head and neck cancer radiotherapy

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    A prospective, randomized multicenter study was conducted to assess the value of amifostine (Ethyol®) as a radioprotectant in head and neck cancer radiotherapy. The aim of the study was to evaluate the impact of the addition of daily amifostine (150 mg/m2) on the degree of early (mucositis, dysphagia, xerostomia) and late (mucosal, cutaneous, salivary gland, mandible and spinal cord) radiation reactions. Assessed were also patients’ quality of life, local control and overall survival. Sixty two patients from five Polish institutions were randomly assigned to radiotherapy alone (Arm A – 28 patients) or radiotherapy + amifostine (Arm B – 34 patients). There were 43 men and 19 women. Primary tumor was located in the oral cavity (27 patients), oropharynx (25 patients), nasopharynx (2 patients) and larynx/hypopharynx (8 patients). In 43 patients radiotherapy was used as the sole modality of treatment and 19 patients were irradiated postoperatively. The side effects of amifostine were manageable. In 6 patients amifostine infusion had to be temporarily stopped due to hypotension and in 5 patients its administration was permanently terminated due to hypotension, nausea and vomiting, septicemia or fever and visual disturbances. The early results of the study, focusing on early radiation reactions, will be presented at the conference

    Inhibition of indole production increases the activity of quinolone antibiotics against E. coli persisters

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    Abstract: Persisters are a sub-population of genetically sensitive bacteria that survive antibiotic treatment by entering a dormant state. The emergence of persisters from dormancy after antibiotic withdrawal leads to recurrent infection. Indole is an aromatic molecule with diverse signalling roles, including a role in persister formation. Here we demonstrate that indole stimulates the formation of Escherichia coli persisters against quinolone antibiotics which target the GyrA subunit of DNA gyrase. However, indole has no effect on the formation of E. coli persisters against an aminocoumarin, novobiocin, which targets the GyrB subunit of DNA gyrase. Two modes of indole signalling have been described: persistent and pulse. The latter refers to the brief but intense elevation of intracellular indole during stationary phase entry. We show that the stimulation of quinolone persisters is due to indole pulse, rather than persistent, signalling. In silico docking of indole on DNA gyrase predicts that indole docks perfectly to the ATP binding site of the GyrB subunit. We propose that the inhibition of indole production offers a potential route to enhance the activity of quinolones against E. coli persisters

    The emergence and diversification of a zoonotic pathogen from within the microbiota of intensively farmed pigs

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    The expansion and intensification of livestock production is predicted to promote the emergence of pathogens. As pathogens sometimes jump between species, this can affect the health of humans as well as livestock. Here, we investigate how livestock microbiota can act as a source of these emerging pathogens through analysis of Streptococcus suis, a ubiquitous component of the respiratory microbiota of pigs that is also a major cause of disease on pig farms and an important zoonotic pathogen. Combining molecular dating, phylogeography, and comparative genomic analyses of a large collection of isolates, we find that several pathogenic lineages of S. suis emerged in the 19th and 20th centuries, during an early period of growth in pig farming. These lineages have since spread between countries and continents, mirroring trade in live pigs. They are distinguished by the presence of three genomic islands with putative roles in metabolism and cell adhesion, and an ongoing reduction in genome size, which may reflect their recent shift to a more pathogenic ecology. Reconstructions of the evolutionary histories of these islands reveal constraints on pathogen emergence that could inform control strategies, with pathogenic lineages consistently emerging from one subpopulation of S. suis and acquiring genes through horizontal transfer from other pathogenic lineages. These results shed light on the capacity of the microbiota to rapidly evolve to exploit changes in their host population and suggest that the impact of changes in farming on the pathogenicity and zoonotic potential of S. suis is yet to be fully realized.This work was primarily funded by an EU Horizon 2020 grant “PIGSs” (727966) and a ZELS BBSRC award “Myanmar Pigs Partnership (MPP)” (BB/L018934/1). G.G.R.M., E.L.M., and L.A.W. were supported by a Sir Henry Dale Fellowship to L.A.W. jointly funded by the Wellcome Trust and the Royal Society (109385/Z/15/Z). N.H. was supported by a Challenge grant from the Royal Society (CH16011) and an Isaac Newton Trust Research Grant [17.24(u)]. G.G.R.M. was also supported by a Research Fellowship at Newnham College. S.B. is supported by the Medical Research Council (MR/V032836/1). PIC North America provided part of the funds for the sequencing of the isolates from the USA. A.J.B. and M.M. were funded by Medical Research Council and Biotechnology and Biological Sciences Research Council studentships respectively, and M.M. was co-funded by the Raymond and Beverly Sackler Fund. We would like to acknowledge Susanna Williamson at the APHA for providing samples, Oscar Cabezón for sampling of the wild boar population in Spain, Mark O’Dea for access to sequence data from Australian isolates, the PIGSs and MPP consortiums for providing samples and helpful discussions, Julian Parkhill and John Welch for helpful discussions, and two anonymous reviewers for their valuable suggestions for improving the manuscript. This research was funded in whole or in part by the Wellcome Trust. For the purpose of Open Access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript (AAM) version arising from this submission.info:eu-repo/semantics/publishedVersio

    Quorum Sensing Primes the Oxidative Stress Response in the Insect Endosymbiont, Sodalis glossinidius

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    quorum sensing system relies on the function of two regulatory proteins; SogI (a LuxI homolog) synthesizes a signaling molecule, characterized as N-(3-oxohexanoyl) homoserine lactone (OHHL), and SogR1 (a LuxR homolog) interacts with OHHL to modulate transcription of specific target genes. and SOPE. and SOPE indicates the potential for neofunctionalization to occur during the process of genome degeneration
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