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Showing papers by "Rambam Health Care Campus published in 2009"


Journal ArticleDOI
TL;DR: Data collected demonstrate that there is a strong association between GBA mutations and Parkinson's disease, and those with a GBA mutation presented earlier with the disease, were more likely to have affected relatives, and were morelikely to have atypical clinical manifestations.
Abstract: Background Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency of which causes Gaucher's disease, among patients with Parkinson's disease. We aimed to ascertain the frequency of GBA mutations in an ethnically diverse group of patients with Parkinson's disease. Methods Sixteen centers participated in our international, collaborative study: five from the Americas, six from Europe, two from Israel, and three from Asia. Each center genotyped a standard DNA panel to permit comparison of the genotyping results across centers. Genotypes and phenotypic data from a total of 5691 patients with Parkinson's disease (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic-regression models and the Mantel–Haenszel procedure used to estimate odds ratios across centers. Results All 16 centers could detect two GBA mutations, L444P and N370S. Among Ashkenazi Jewish subjects, either mutation was found in 15% of p...

1,629 citations



Journal ArticleDOI
TL;DR: It is shown that an array of sensors based on gold nanoparticles can rapidly distinguish the breath of lung cancer patients from the Breath of healthy individuals in an atmosphere of high humidity.
Abstract: Conventional diagnostic methods for lung cancer 1,2 are unsuitable for widespread screening 2,3 because they are expensive and occasionally miss tumours. Gas chromatography/mass spectrometry studies have shown that several volatile organic compounds, which normally appear at levels of 1–20 ppb in healthy human breath, are elevated to levels between 10 and 100 ppb in lung cancer patients 4–6 . Here we show that an array of sensors based on gold nanoparticles can rapidly distinguish the breath of lung cancer patients from the breath of healthy individuals in an atmosphere of high humidity. In combination with solidphase microextraction 7 , gas chromatography/mass spectrometry was used to identify 42 volatile organic compounds that represent lung cancer biomarkers. Four of these were used to train and optimize the sensors, demonstrating good agreement between patient and simulated breath samples. Our results show that sensors based on gold nanoparticles could form the basis of an inexpensive and non-invasive diagnostic tool for lung cancer. Lung cancer accounts for 28% of cancer-related deaths.

1,088 citations


Journal ArticleDOI
TL;DR: The combination of radiotherapy plus 6 months of androgen suppression provides inferior survival as compared with radiotherapyplus 3 years of androgens suppression in the treatment of locally advanced prostate cancer.
Abstract: Background The combination of radiotherapy plus long-term medical suppression of androgens (≥2 years) improves overall survival in patients with locally advanced prostate cancer We compared the use of radiotherapy plus short-term androgen suppression with the use of radiotherapy plus long-term androgen suppression in the treatment of locally advanced prostate cancer Methods We randomly assigned patients with locally advanced prostate cancer who had received external-beam radiotherapy plus 6 months of androgen suppression to two groups, one to receive no further treatment (short-term suppression) and the other to receive 25 years of further treatment with a luteinizing hormone–releasing hormone agonist (long-term suppression) An outcome of noninferiority of short-term androgen suppression as compared with long-term suppression required a hazard ratio of more than 135 for overall survival, with a one-sided alpha level of 005 An interim analysis showed futility, and the results are presented with an a

836 citations


Journal ArticleDOI
TL;DR: In young adults with AML, intensifying induction therapy with a high daily dose of daunorubicin improved the rate of complete remission and the duration of overall survival, as compared with the standard dose.
Abstract: Background In young adults with acute myeloid leukemia (AML), intensification of the anthracycline dose during induction therapy has improved the rate of complete remission but not of overall survival. We evaluated the use of cytarabine plus either standard-dose or high-dose daunorubicin as induction therapy, followed by intensive consolidation therapy, in inducing complete remission to improve overall survival. Methods In this phase 3 randomized trial, we assigned 657 patients between the ages of 17 and 60 years who had untreated AML to receive three once-daily doses of daunorubicin at either the standard dose (45 mg per square meter of body-surface area) or a high dose (90 mg per square meter), combined with seven daily doses of cytarabine (100 mg per square meter) by continuous intravenous infusion. Patients who had a complete remission were offered either allogeneic hematopoietic stem-cell transplantation or high-dose cytarabine, with or without a single dose of the monoclonal antibody gemtuzumab ozog...

755 citations



Journal ArticleDOI
TL;DR: This document sets out the current Consensus reached by a group of international experts in the fields of endoscopy and IBD at a meeting held in Brussels, 12-13th December 2008, organised jointly by the European Crohn's and Colitis Organisation (ECCO) and the Organisation Mondiale d'Endoscopie Digestive (OMED).
Abstract: Crohn's disease and ulcerative colitis are lifelong diseases seen predominantly in the developed countries of the world. Whereas ulcerative colitis is a chronic inflammatory condition causing diffuse and continuous mucosal inflammation of the colon, Crohn's disease is a heterogeneous entity comprised of several different phenotypes, but can affect the entire gastrointestinal tract. A change in diagnosis from Crohn's disease to ulcerative colitis during the first year of illness occurs in about 10 % - 15 % of cases. Inflammatory bowel disease (IBD) restricted to the colon that cannot be characterized as either ulcerative colitis or Crohn's disease is termed IBD-unclassified (IBDU). The advent of capsule and both single- and double-balloon-assisted enteroscopy is revolutionizing small-bowel imaging and has major implications for diagnosis, classification, therapeutic decision making and outcomes in the management of IBD. The role of these investigations in the diagnosis and management of IBD, however, is unclear. This document sets out the current Consensus reached by a group of international experts in the fields of endoscopy and IBD at a meeting held in Brussels, 12-13th December 2008, organised jointly by the European Crohn's and Colitis Organisation (ECCO) and the Organisation Mondiale d'Endoscopie Digestive (OMED). The Consensus is grouped into seven sections: definitions and diagnosis; suspected Crohn's disease; established Crohn's disease; IBDU; ulcerative colitis (including ileal pouch-anal anastomosis [IPAA]); paediatric practice; and complications and unresolved questions. Consensus guideline statements are followed by comments on the evidence and opinion. Statements are intended to be read in context with qualifying comments and not read in isolation.

312 citations


Journal ArticleDOI
TL;DR: The new second-generation colon capsule endoscopy is a safe and effective method for visualizing the colon and detecting colonic lesions and has a potential for improved accuracy compared with the first-generation system.
Abstract: Background and study aims A second-generation capsule endoscopy system, using the PillCam Colon 2, was developed to increase sensitivity for colorectal polyp detection compared with the first-generation system. The performance of this new system is reported. Patients and methods In a five-center feasibility study, second-generation capsule endoscopy was prospectively compared with conventional colonoscopy as gold standard for the detection of colorectal polyps and other colonic disease, in a cohort of patients scheduled for colonoscopy and having known or suspected colonic disease. Colonoscopy was independently performed within 10 hours after capsule ingestion. Capsule-positive but colonoscopy-negative cases were counted as false-positive. Results 104 patients (mean age 49.8 years) were enrolled; data from 98 were analyzed. Patient rate for polyps of any size was 44 %, 53 % of these patients having adenomas. No adverse events related to either procedure were reported. The capsule sensitivity for the detection of patients with polyps >or= 6 mm was 89 % (95 % confidence interval [CI] 70 - 97) and for those with polyps >or= 10 mm it was 88 % (95 %CI 56 - 98), with specificities of 76 % (95 %CI 72 - 78) and 89 % (95 %CI 86 - 90), respectively. Both polyps missed by colonoscopy and mismatch in polyp size by study definition lowered specificity. Overall colon cleanliness for capsule endoscopy was adequate in 78 % of patients (95 %CI 68 - 86). Conclusions The new second-generation colon capsule endoscopy is a safe and effective method for visualizing the colon and detecting colonic lesions. Sensitivity and specificity for detecting colorectal polyps appear to be very good, suggesting a potential for improved accuracy compared with the first-generation system. Further prospective and comparative studies are needed.

281 citations


Journal ArticleDOI
TL;DR: In this population of infants with advanced disease, biweekly infusions with alglucosidase alfa prolonged survival and invasive ventilation-free survival and improved indices of cardiomyopathy, motor skills, and functional independence.

261 citations


Journal ArticleDOI
TL;DR: The diagnostic performance of DNM is comparable to that of S-SPECT on a per-patient basis, however, superior image quality can be achieved with significantly shorter acquisition times with DNM because of improved count sensitivity and image contrast over S- SPECT.

242 citations


Journal ArticleDOI
TL;DR: Patients with rheumatoid arthritis receiving anti-TNF-alpha medication had lower periodontal indices and GCF TNF- alpha levels, suggesting suppression of proinflammatory cytokines might prove beneficial in suppressingperiodontal diseases.
Abstract: Background: The aim of this study was to evaluate the influence of anti-tumor necrosis factor-alpha (TNF-a) therapy on the clinical and immunologic parameters of the periodontium. Methods: Ten patients with rheumatoid arthritis (RA) who routinely received infusions of infliximab, 200 mg (RA+), 10 patients with RA without anti-TNF-a therapy (RA-), and 10 healthy controls (C) were included. Clinical parameters, including the plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment loss (AL), and bleeding on probing (BOP), were assessed, and total gingival crevicular fluid (GCF) TNF-a level was determined using enzyme-linked immunosorbent assay. Analysis of variance with Scheffe modification and the Pearson correlation test were used for statistical analysis. Results: The ages of the patients ranged from 22 to 76 years (mean, 50.73 – 9.1 years). The mean PI was similar among the groups. However, mean inflammatory parameters in the three groups varied significantly; GI was greater in the RA- group compared to RA+ and C groups (P = 0.0042). The RA+ group exhibited less BOP than RA- and C groups (21.1% – 3.0%, 45.9% – 6.2%, and 39.1% – 7.2%, respectively; P = 0.0146). The mean PD in the RA+ group was shallower than in RA- and C groups (3.22 – 0.13 mm, 3.85 – 0.22 mm, and 3.77 – 0.20 mm, respectively; P = 0.055). Clinical AL in the RA+ group was lower than in RA- and C groups (3.68 – 0.11 mm, 4.52 – 0.26 mm, and 4.35 – 0.24 mm, respectively; P = 0.0273). TNF-a levels in the GCF of the RA+ group were the lowest compared to RA- and C groups (0.663, 1.23, and 0.949 ng/site, respectively; P = 0.0401). A significant positive correlation was found between TNF-a levels in the GCF and clinical AL (r = 0.448; P = 0.0283). Conclusions: Patients with RA receiving anti-TNF-a medication had lower periodontal indices and GCF TNF-a levels. Thus, suppression of proinflammatory cytokines might prove beneficial in suppressing periodontal diseases. J Periodontol 2009;80:1414-1420.

Journal ArticleDOI
TL;DR: It is demonstrated, for the first time, that the addition of nicotine concentrations analogous to those acquired by a light to moderate smoker yields increased osteoblast proliferation and bone metabolism, whereas the addition to heavy smokers leads to the opposite effect.
Abstract: Smoking has a broad range of physiological effects, such as being a risk factor in osteoporosis, bone fracture incidence, and increased nonunion rates. Recent studies showed that nicotine has effects at the cellular level in human osteoblast cells. To identify possible mechanisms underlying nicotine-induced changes in osteogenic metabolism, we defined changes in proliferation and osteocalcin, type I collagen, and alkaline phosphatase gene expression after treating human osteosarcoma cells (MG63), with various concentration of nicotine. Nicotine affects cell proliferation in a biphasic manner, including toxic and antiproliferative effects at high levels of nicotine and stimulatory effects at low levels. Moreover, low levels of nicotine upregulated osteocalcin, type I collagen, and alkaline phosphatase gene expression. The increased cell proliferation and gene upregulation induced by nicotine were inhibited by addition of the nicotinic receptor antagonist d-tubocurarine. High nicotine concentrations downregulated the investigated genes. Our results demonstrate, for the first time, that the addition of nicotine concentrations analogous to those acquired by a light to moderate smoker yields increased osteoblast proliferation and bone metabolism, whereas the addition of nicotine concentrations analogous to heavy smokers leads to the opposite effect. The inhibition of these effects by d-tubocurarine suggests that nicotine acts via the nicotinic acetylcholine receptor (nAChR).

Journal ArticleDOI
TL;DR: The role of pain temporal summation assessed preoperatively as a significant psychophysical predictor for acute postoperative pain intensity is proposed and individual susceptibility toward a greater summation response may characterize patients who are potentially vulnerable to augmented POP.

Journal ArticleDOI
TL;DR: The GIWP-ROG defined guidelines for preoperative irradiation of adenocarcinomas of the GEJ and the stomach to reduce variability in the framework of future clinical trials.

Journal ArticleDOI
TL;DR: New findings which characterize the haemostatic balance of microparticles are presented, and a method that may potentially serve to predict a state of hypercoagulability in cancer patients is suggested.

Journal ArticleDOI
Antonis C. Antoniou1, Olga M. Sinilnikova2, Lesley McGuffog1, Sue Healey3, Heli Nevanlinna4, Tuomas Heikkinen4, Jacques Simard5, Amanda B. Spurdle3, Jonathan Beesley3, Xiaoqing Chen3, Susan L. Neuhausen6, Yuan C. Ding6, Fergus J. Couch7, Xianshu Wang7, Zachary S. Fredericksen7, Paolo Peterlongo, Bernard Peissel, Bernardo Bonanni, Alessandra Viel, Loris Bernard, Paolo Radice, Csilla Szabo7, Lenka Foretova, Michal Zikan8, Kathleen Claes9, Mark H. Greene10, Phuong L. Mai10, Gad Rennert11, Flavio Lejbkowicz11, Irene L. Andrulis12, Irene L. Andrulis13, Hilmi Ozcelik12, Gord Glendon13, Anne-Marie Gerdes14, Mads Thomassen14, Lone Sunde15, Maria A. Caligo16, Yael Laitman, Tair Kontorovich, Shimrit Cohen, Bella Kaufman17, Efrat Dagan18, Ruth Gershoni Baruch18, Eitan Friedman17, Katja Harbst19, Gisela Barbany-Bustinza20, Johanna Rantala20, Hans Ehrencrona21, Per Karlsson22, Susan M. Domchek23, Katherine L. Nathanson23, Ana Osorio24, Ignacio Blanco, Adriana Lasa25, Javier Benitez24, Ute Hamann26, Frans B. L. Hogervorst27, Matti A. Rookus27, J. Margriet Collée28, Peter Devilee29, Marjolijn J. L. Ligtenberg30, Rob B. van der Luijt31, Cora M. Aalfs32, Quinten Waisfisz33, Juul T. Wijnen29, Cornelis E. P. van Roozendaal34, Susan Peock1, Margaret Cook1, Debra Frost1, Clare Oliver1, Radka Platte1, D. Gareth Evans, Fiona Lalloo, Rosalind A. Eeles35, Louise Izatt36, Rosemarie Davidson, Carol Chu, Diana Eccles37, Trevor Cole, Shirley Hodgson38, Andrew K. Godwin39, Dominique Stoppa-Lyonnet40, Bruno Buecher41, Méanie Léoné2, Brigitte Bressac-de Paillerets42, Audrey Remenieras42, Olivier Caron42, Gilbert M. Lenoir42, Nicolas Sevenet43, Michel Longy43, Sandra Fert Ferrer, Fabienne Prieur, David E. Goldgar44, Alexander Miron45, Esther M. John46, Esther M. John47, Saundra S. Buys44, Mary B. Daly39, John L. Hopper48, Mary Beth Terry49, Yosuf Yassin45, Christian F. Singer50, Daphne Gschwantler-Kaulich50, Christine Staudigl50, Thomas Hansen51, Rosa B. Barkardottir, Tomas Kirchhoff52, Prodipto Pal52, Kristi Kosarin52, Kenneth Offit52, Marion Piedmonte53, Gustavo C. Rodriguez54, Katie Wakeley55, John F. Boggess56, Jack Basil, Peter E. Schwartz57, Stephanie V. Blank58, Amanda E. Toland59, Marco Montagna, Cinzia Casella, Evgeny N. Imyanitov, Anna Allavena60, Rita K. Schmutzler61, Beatrix Versmold61, Christoph Engel62, Alfons Meindl63, Nina Ditsch64, Norbert Arnold65, Dieter Niederacher65, Helmut Deißler66, Britta Fiebig67, Christian Suttner68, Ines Schönbuchner69, Dorothea Gadzicki70, Trinidad Caldés71, Miguel de la Hoya71, Karen A. Pooley1, Douglas F. Easton1, Georgia Chenevix-Trench3 
University of Cambridge1, University of Lyon2, QIMR Berghofer Medical Research Institute3, University of Helsinki4, Laval University5, University of California, Irvine6, Mayo Clinic7, Charles University in Prague8, Ghent University9, National Institutes of Health10, Technion – Israel Institute of Technology11, University of Toronto12, Cancer Care Ontario13, University of Southern Denmark14, Aarhus University15, University of Pisa16, Tel Aviv University17, Rambam Health Care Campus18, Lund University19, Karolinska Institutet20, Uppsala University21, University of Gothenburg22, University of Pennsylvania23, Carlos III Health Institute24, Autonomous University of Barcelona25, German Cancer Research Center26, Netherlands Cancer Institute27, Erasmus University Rotterdam28, Leiden University29, Radboud University Nijmegen30, Utrecht University31, University of Amsterdam32, VU University Amsterdam33, Maastricht University34, The Royal Marsden NHS Foundation Trust35, Guy's and St Thomas' NHS Foundation Trust36, Princess Anne Hospital37, University of London38, Fox Chase Cancer Center39, University of Paris40, Curie Institute41, Institut Gustave Roussy42, University of Bordeaux43, University of Utah44, Harvard University45, Cancer Prevention Institute of California46, Stanford University47, University of Melbourne48, Columbia University49, Medical University of Vienna50, University of Copenhagen51, Memorial Sloan Kettering Cancer Center52, Roswell Park Cancer Institute53, University of Chicago54, Tufts University55, University of North Carolina at Chapel Hill56, Yale University57, New York University58, Ohio State University59, University of Turin60, University of Cologne61, Leipzig University62, Technische Universität München63, Ludwig Maximilian University of Munich64, University of Düsseldorf65, University of Ulm66, University of Regensburg67, Heidelberg University68, University of Würzburg69, Hannover Medical School70, Complutense University of Madrid71
TL;DR: The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers and there was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not.
Abstract: Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 x 10(-4)]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not.


Journal ArticleDOI
TL;DR: The data suggest that the incorporation of dental implants into removable partial dentures could be an optional treatment plan for the partially edentulous patient to improve function and patient satisfaction.

Journal ArticleDOI
TL;DR: The effects of SrR on bone remodeling and cell activity were modest, indicating that its effects on fracture reduction may be predominantly mediated through a different mechanism than that observed with anabolic or more potent antiresorptive agents.
Abstract: We assessed the effects on bone remodeling and histomorphometry after daily subcutaneous injections of teriparatide (n = 39, 20 microg/d) or oral strontium ranelate (SrR, n = 40, 2 g/d) in postmenopausal women with osteoporosis. Evaluable biopsies were obtained from 29 patients in the teriparatide group and 22 in the SrR group after 6 mo of treatment. The mean +/- SD mineralization surfaces as a percent of bone surfaces (MS/BS, %) at the trabecular level were 7.73 +/- 1.48% for teriparatide and 5.25 +/- 1.15% for SrR (p = 0.219) and at the endocortical level were 17.22 +/- 3.06% and 9.70 +/- 2.07%, respectively (p = 0.052). Cortical porosity was 5.40 +/- 0.41% in the teriparatide and 4.14 +/- 0.40% in the SrR group (p = 0.037). Teriparatide induced significant increases from baseline in bone formation and resorption markers, reaching statistical significance for amino-terminal propeptide of type I collagen (PINP) after 1 mo (+57%, p < 0.001). SrR induced small, but statistically significant, reductions from baseline in PINP at 3 (-14%, p = 0.005) and 6 mo (-19%, p < 0.001) and in serum beta-C-terminal telopeptide of type I collagen (beta-CTX) at 1 and 3 mo (-11%, for both, p < 0.05). There were more patients with adverse events after SrR (70%) than teriparatide (41%) treatment (p = 0.013). In conclusion, the changes in biochemical markers of bone formation confirmed bone-forming activity of teriparatide but not of SrR treatment. The effects of SrR on bone remodeling and cell activity were modest, indicating that its effects on fracture reduction may be predominantly mediated through a different mechanism than that observed with anabolic or more potent antiresorptive agents.

Journal ArticleDOI
TL;DR: Improved diagnostic accuracy is reflected by improving image quality of SPECT and PET, detection of more clinically relevant lesions, better localization of disease and differentiation between physiologic and pathologic uptake, characterization of disease by its functional and morphologic appearance before and after therapy and accurate delineation of disease, optimizing biopsy and therapy planning.

Journal ArticleDOI
01 Nov 2009-Bone
TL;DR: A critical-sized gap platform was established in sheep tibiae to test whether blood-derived progenitor cells that have endothelial characteristics (EPC) would promote bone regeneration, and on the contrary, EPC transplantation led to formation of dense and massive woven bone all throughout the defect.

Journal ArticleDOI
TL;DR: The results demonstrate that porcine E-42 embryonic pancreatic tissue can normalize blood glucose levels in primates, and strongly suggest that this approach could offer an attractive replacement therapy for diabetes.
Abstract: Xenotransplantation of pig tissues has great potential to overcome the shortage of organ donors. One approach to address the vigorous immune rejection associated with xenotransplants is the use of embryonic precursor tissue, which induces and utilizes host vasculature upon its growth and development. Recently, we showed in mice that embryonic pig pancreatic tissue from embryonic day 42 (E42) exhibits optimal properties as a β cell replacement therapy. We now demonstrate the proof of concept in 2 diabetic Cynomolgus monkeys, followed for 393 and 280 days, respectively. A marked reduction of exogenous insulin requirement was noted by the fourth month after transplantation, reaching complete independence from exogenous insulin during the fifth month after transplantation, with full physiological control of blood glucose levels. The porcine origin of insulin was documented by a radioimmunoassay specific for porcine C-peptide. Furthermore, the growing tissue was found to be predominantly vascularized with host blood vessels, thereby evading hyperacute or acute rejection, which could potentially be mediated by preexisting anti-pig antibodies. Durable graft protection was achieved, and most of the late complications could be attributed to the immunosuppressive protocol. While fine tuning of immune suppression, tissue dose, and implantation techniques are still required, our results demonstrate that porcine E-42 embryonic pancreatic tissue can normalize blood glucose levels in primates. Its long-term proliferative capacity, its revascularization by host endothelium, and its reduced immunogenicity, strongly suggest that this approach could offer an attractive replacement therapy for diabetes.

Journal ArticleDOI
TL;DR: Evidence is provided that SOD may play an essential role in EPCs, and the important role of antioxidant therapy in type 2 diabetic patients is emphasized.
Abstract: Background: The function of endothelial progenitor cells (EPCs), which are key cells in vascular repair, is impaired in diabetes mellitus. Nitric oxide (NO) and reactive oxygen species can regulate EPC functions. EPCs tolerate oxidative stress by upregulating superoxide dismutase (SOD), the enzyme that neutralizes superoxide anion (O 2 -). Therefore, we investigated the roles of NO and SOD in glucose-stressed EPCs. Methods: The functions of circulating EPCs from patients with type 2 diabetes were compared to those from healthy individuals. Healthy EPCs were glucose-stressed, and then treated with insulin and/or SOD. We assessed O2 - generation, NO production, SOD activity, and their ability to form colonies. Results: EPCs from diabetic patients generated more O2 - , had higher NAD(P)H oxidase and SOD activity, but lower NO bioavailability, and expressed higher mRNA and protein levels of p22-phox, and manganese SOD and copper/zinc SOD than those from the healthy individuals. Plasma glucose and HbA1c levels in the diabetic patients were correlated negatively with the NO production from their EPCs. SOD treatment of glucose-stressed EPCs attenuated O2 - generation, restored NO production, and partially restored their ability to form colonies. Insulin treatment of glucosestressed EPCs increased NO production, but did not change O2 - generation and their ability to form colonies. However, their ability to produce NO and to form colonies was fully restored after combined SOD and insulin treatment. Conclusion: Our data provide evidence that SOD may play an essential role in EPCs, and emphasize the important role of antioxidant therapy in type 2 diabetic patients.

Journal ArticleDOI
27 Apr 2009-ACS Nano
TL;DR: The excellent discrimination between the various breath states obtained in this study provides expectations for future capabilities for diagnosis, detection, and screening various stages of kidney disease, especially in the early stages of the disease, where it is possible to control blood pressure and protein intake to slow the progression.
Abstract: In this study, we use an experimental model of bilateral nephrectomy in rats to identify an advanced, yet simple nanoscale-based approach to discriminate between exhaled breath of healthy states and of chronic renal failure (CRF) states. Gas chromatography/mass spectroscopy (GC-MS) in conjugation with solid-phase microextraction (SPME) of healthy and CRF breath, collected directly from the trachea of the rats, identified 15 common volatile organic compounds (VOCs) in all samples of healthy and CRF states and 27 VOCs that appear in CRF but not in healthy states. Online breath analysis via an array of chemiresistive random network of single-walled carbon nanotubes (SWCNTs) coated with organic materials showed excellent discrimination between the various breath states. Stepwise discriminate analysis showed that enhanced discrimination capacity could be achieved by decreasing the humidity prior to their analysis with the sensors' array. Furthermore, the analysis showed the adequacy of using representative simulated VOCs to imitate the breath of healthy and CRF states and, therefore, to train the sensors' array the pertinent breath signatures. The excellent discrimination between the various breath states obtained in this study provides expectations for future capabilities for diagnosis, detection, and screening various stages of kidney disease, especially in the early stages of the disease, where it is possible to control blood pressure and protein intake to slow the progression.

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TL;DR: TFU can improve medical treatment by increasing satisfaction and compliance and a trend towards decreased readmission rates was observed, which may lead to a reduction in the burden on the medical system.

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TL;DR: RIN2 deficiency was found to be associated with paucity of dermal microfibrils and deficiency of fibulin-5, which may underlie the abnormal skin phenotype displayed by the patients.
Abstract: Inherited disorders of elastic tissue represent a complex and heterogeneous group of diseases, characterized often by sagging skin and occasionally by life-threatening visceral complications. In the present study, we report on an autosomal-recessive disorder that we have termed MACS syndrome (macrocephaly, alopecia, cutis laxa, and scoliosis). The disorder was mapped to chromosome 20p11.21-p11.23, and a homozygous frameshift mutation in RIN2 was found to segregate with the disease phenotype in a large consanguineous kindred. The mutation identified results in decreased expression of RIN2, a ubiquitously expressed protein that interacts with Rab5 and is involved in the regulation of endocytic trafficking. RIN2 deficiency was found to be associated with paucity of dermal microfibrils and deficiency of fibulin-5, which may underlie the abnormal skin phenotype displayed by the patients.

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TL;DR: A population‐based cross‐sectional study to assess prevalence of cardiovascular risk factors in subjects with and without restless legs syndrome (RLS), it was found that female gender and HDL/LDL cholesterol were significantly associated with RLS compared with subjects without RLS.
Abstract: We conducted a population-based cross-sectional study to assess prevalence of cardiovascular risk factors in subjects with and without restless legs syndrome (RLS). Adults attending their annual checkup completed the International RLS Study Group questionnaire and underwent an interview by a neurologist. Data from the annual checkup were compared between subjects with and without RLS. The prevalence of RLS was 6.7% (95% CI 5.45–7.95) among 1,537 responders. RLS subjects' blood tests showed significantly higher fasting blood glucose level (P = 0.029), higher prevalence of hypercholesterolemia (P = 0.029) and reduced renal function (P = 0.013), and increased prevalence of low hematocrit (P = 0.008). RLS subjects weighed more (P = 0.029), had a higher BMI (P = 0.033), larger hip circumference (P = 0.033), and were less fit (P = 0.010). To control for interactions among statistical predictors, we also employed multivariate logistic regression models adjusted for age, gender, smoking, BMI, hemoglobin, glucose, HDL/LDL cholesterol, triglycerides, and creatinine. We found that female gender (OR 2.16; 95% CI 1.11–4.17), smoking (OR 1.82; 95% CI, 1.10–3.00), and HDL/LDL cholesterol (OR 0.18; 95% CI 0.034–0.90) were significantly associated with RLS compared with subjects without RLS. RLS was associated with cardiovascular risk factors. © 2009 Movement Disorder Society

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TL;DR: Aortic valve stenosis causes differential changes in longitudinal and circumferential mechanics that partially normalize after AVR, providing new insights into the mechanical adaptation of the LV to chronic afterload elevation and its response to unloading.

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TL;DR: The outcome of pregnant or postpartum women with VTE is similar to that in contraceptive users, even though the treatment is different, and the non-specific nature of PE signs may have caused some delay in PE diagnosis.
Abstract: Venous thromboembolism (VTE) is a leading cause of maternal death during pregnancy or postpartum, and in women using hormonal contraceptives. However, important issues concerning its natural history and therapy remain unsolved, and most of the protocols for treatment of VTE in this patient population are based on data extrapolated from other populations. RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic, acute VTE. We examined the clinical characteristics and three-month outcome of all enrolled women with pregnancy, postpartum or using hormonal contraceptives. As of December 2008, 173 pregnant women, 135 postpartum, and 798 contraceptive users were enrolled. Of these, 438 (40%) presented with pulmonary embolism (PE) and 668 with deep-vein thrombosis (DVT). Most women with acute PE had dyspnea (72%) or chest pain (75%), but only 2.0% had hypoxaemia. During the three-month study period, five women (0.45%; 95% CI: 0.17–1.00) died (3 had fatal PE), 13 (1.18%; 95% CI: 0.66–1.95) had VTE recurrences, and seven (0.63%; 95% CI: 0.28–1.25) major bleeding. Two of the three women with fatal PE died during the first few hours after arriving at the emergency ward, with no time to start any therapy. The outcome of pregnant or postpartum women with VTE is similar to that in contraceptive users, even though the treatment is different. The non-specific nature of PE signs may have caused some delay in PE diagnosis.

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TL;DR: Although rare, incidental focal abnormal FDG uptake in the breast may represent malignant lesions in up to 57% of patients and warrant further assessment including tissue sampling.
Abstract: Purpose The aim of this study was to evaluate the frequency and clinical significance of unexpected focal 18F-fluorodeoxyglucose (FDG) uptake localized by PET/CT within the breast.