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Blood sampling was carried out on day 1 of the first cycle. The activity of dihydropyrimidine dehydrogenase in mononuclear cells was lower in the index patient 5. Our results indicate that the inactivation of one dihydropyrimidine dehydrogenase allele can result in a strong reduction in 5-fluorouracil clearance, causing severe 5-fluorouracil induced toxicity. British Journal of Cancer 86 , —
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State government said that all economic activities, not specifically prohibited, will be permitted outside the containment zones. Large congregations including, social, political, sports, entertainment, academic, cultural, religious functions or processions will remain banned during the period. Educational institutions, including schools, colleges, training and coaching institutions will continue to remain closed.
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OJ L , Avis juridique important. Having regard to the Treaty establishing the European Community, and in particular Article a thereof,. In accordance with this Directive, Member States shall protect the fundamental rights and freedoms of natural persons, and in particular their right to privacy with respect to the processing of personal data. Member States shall neither restrict nor prohibit the free flow of personal data between Member States for reasons connected with the protection afforded under paragraph 1.
This Directive shall apply to the processing of personal data wholly or partly by automatic means, and to the processing otherwise than by automatic means of personal data which form part of a filing system or are intended to form part of a filing system. Each Member State shall apply the national provisions it adopts pursuant to this Directive to the processing of personal data where:.
In the circumstances referred to in paragraph 1 c , the controller must designate a representative established in the territory of that Member State, without prejudice to legal actions which could be initiated against the controller himself. Member States shall, within the limits of the provisions of this Chapter, determine more precisely the conditions under which the processing of personal data is lawful.
Further processing of data for historical, statistical or scientific purposes shall not be considered as incompatible provided that Member States provide appropriate safeguards;.
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DPD deficiency has been associated with severe 5-FU toxicity. Syndrome of DPD deficiency manifests as diarrhea, stomatitis, mucositis, and neurotoxicity and in some cases death. This is a true pharmacogenetic syndrome, with symptoms being unrecognizable until exposure to the drug. A year-old patient with metastatic pancreatic adenocarcinoma developed grade 4 thrombocytopenia, grade 3 coagulopathy, and grade 3 neurologic toxicity with a fatal outcome following administration of 5-FU.
Due to pancytopenia, DPD activity could not be determined in peripheral blood mononuclear cells PBMC using a previously described radioassay. Therefore, screening and genotypic analysis of homozygous and heterozygous, known and unknown sequence variants, in the DPYD gene were performed using DHPLC as previously described. Fluorouracil 5-FU , an analog of uracil, is one of the most commonly used chemotherapeutic agents and constitutes the mainstay of chemotherapy for most gastrointestinal tumors [ 1 ].
The most common 5-FU toxicities include neutropenia, mucositis, diarrhea, and hand—foot syndrome, with the latter two adverse effects predominating when 5-FU is administered as a continuous intravenous IV infusion [ 3 ]. Like other conventional cytotoxic antineoplastic agents, 5-FU has a relatively narrow therapeutic index. Its toxicity often limits the dose that can be administered, limiting its overall therapeutic usefulness.
Furthermore, since the late s, there have been multiple case reports demonstrating unanticipated fatal and near fatal toxicities in patients with dihydrpyrimidine dehydrogenase DPD deficiency following intravenous and oral fluoropyrimidines [ 4 — 8 ]. As DPD catalyzes the rate limiting step in the catabolic pathway of 5-FU, a deficiency of DPD can produce the clinical syndrome of 5-FU toxicity including mucositis, granulocytopenia, neuropathy, and death [ 3 ].
Van Kuilenburg et al. Johnson et al.
DPYD*2A mutation: the most common mutation associated with DPD deficiency
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DPD-based adaptive dosing of 5-FU in patients with head and neck cancer: impact on treatment Mita AC, Denis LJ, Rowinsky EK, et al.
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Date of admission. Status. Rank. Ky. C.. 17, 3, 97 50 D. dpd. 3, 6, 17,. ”. 97 N. Y. Inf 2 U. S. V. R. Cps. Smith, William A. EK: 16 Ky. Inf.
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