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      Diabetes: Changing the Fate of Diabetics in the Dialysis Unit

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          Abstract

          The prevalence of diabetes mellitus (DM) is very high worldwide. According to the World Health Organization in 2000 the worldwide prevalence of DM was 171,000,000. Diabetic nephropathy is a major vascular complication of DM. If DM is not treated early and adequately, many diabetic patients may reach end-stage renal disease (ESRD) secondary to advanced irreversible diabetic nephropathy. In many countries diabetic nephropathy has become the single most frequent cause of prevalent ESRD patients undergoing maintenance hemodialysis (MHD). In the early era of renal replacement therapy (RRT) by means of intermittent hemodialysis the prognosis of diabetic patients undergoing MHD was extremely poor and disappointing. While the prognosis of patients suffering from diabetic ESRD and maintained by chronic intermittent dialysis has greatly improved, the rehabilitation rate and survival of these patients continue to be worse than those of non-diabetic patients. A preexisting severely compromised cardiovascular condition, vascular access problems, diabetic foot disease, interdialytic weight gain, and intradialytic hypotension explain most of the less favorable outcome. Despite improved techniques and more aggressive medical therapy in recent years, a review of the fate of diabetics in dialysis units since 1972 reveals that these patients have had significant morbidity and mortality. We still have a long way to go in order to achieve more ideal outcomes for our patients. Most of the diabetic ESRD patients are still maintained by MHD, but they can choose other modalities of RRT such as chronic ambulatory peritoneal dialysis (CAPD), kidney and kidney plus pancreas transplantation. The results of different studies and national registries on the mortality and morbidity of ESRD patients being maintained on different modalities of dialysis are conflicting. It can be concluded that the two modalities of dialysis (CAPD and MHD) are almost comparable in terms of survival. The recent suggestions for nocturnal daily hemodialysis, short daily hemodialysis, and an integrative care approach for the management of diabetics with ESRD provides better promise for these patients.

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          Most cited references 21

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          Demography. Broken limits to life expectancy.

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            Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and II clinical trial.

            We administered recombinant human erythropoietin to 25 anemic patients with end-stage renal disease who were undergoing hemodialysis. The recombinant human erythropoietin was given intravenously three times weekly after dialysis, and transfusion requirements, hematocrit, ferrokinetics, and reticulocyte responses were monitored. Over a range of doses between 15 and 500 units per kilogram of body weight, dose-dependent increases in effective erythropoiesis were noted. At 500 units per kilogram, changes in the hematocrit of as much as 10 percentage points were seen within three weeks, and increases in ferrokinetics of three to four times basal values, as measured by erythron transferrin uptake, were observed. Of 18 patients receiving effective doses of recombinant human erythropoietin, 12 who had required transfusions no longer needed them, and in 11 the hematocrit increased to 35 percent or more. Along with the rise in hematocrit, four patients had an increase in blood pressure, and a majority had increases in serum creatinine and potassium levels. No organ dysfunction or other toxic effects were observed, and no antibodies to the recombinant hormone were formed. These results demonstrate that recombinant human erythropoietin is effective, can eliminate the need for transfusions with their risks of immunologic sensitization, infection, and iron overload, and can restore the hematocrit to normal in many patients with the anemia of end-stage renal disease.
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              The epidermal growth factor receptor/Erb-B/HER family in normal and malignant breast biology.

               S Eccles (2010)
              The EGFR/Erb-B receptor tyrosine kinases each play distinct and complementary roles in normal breast development. The four receptors form both homodimers and heterodimers in response to binding by ligands which show selectivity for one or more of the receptors (except Erb-B2). Together with the additional flexibility generated by the formation of different dimer pairs, these signalling networks play key roles in directing a variety of both autocrine and paracrine cellular responses. Complex two-way interactions between mammary epithelial cells and the surrounding stroma direct proliferation, duct formation, branching and terminal differentiation during puberty, pregnancy and lactation, with each receptor and ligand fulfilling distinct roles. Caricatures of the normal role of EGFR/Erb-B signalling resulting in aberrant cellular responses are seen in breast cancers, where over-expression and/or (less commonly) mutation of one or more of the receptors results in enhanced cell proliferation, motility, release of proteases and angiogenic factors. Given their importance in tumour progression, compared with most normal adult tissues and their links with resistance to chemotherapy and anti-endocrine therapy, Erb-B receptors (most notably Erb-B2) have been exploited as therapeutic targets. Monoclonal antibodies (e.g. trastuzumab, pertuzumab) and small molecule tyrosine kinase inhibitors (e.g. lapatinib, afatinib) have shown significant clinical responses in some breast cancer subtypes. Additional approaches include targeted toxins or drugs, peptide vaccines, immunRNase and chaperone inhibitors to deplete Erb-B2 protein levels. Greater understanding of the full spectrum of Erb-B-mediated signalling pathways and their misregulation in breast cancer will provide additional strategies to control malignant progression.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                978-3-8055-8237-7
                978-3-318-01434-1
                0253-5068
                1421-9735
                2007
                December 2006
                14 December 2006
                : 25
                : 1
                : 39-47
                Affiliations
                Iran University of Medical Sciences, Tehran, Iran
                Article
                96396 Blood Purif 2007;25:39–47
                10.1159/000096396
                17170536
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 6, Tables: 2, References: 46, Pages: 9
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/96396
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