1,667 research outputs found

    Endothelial Dysfunction and Microvascular Complications in Type 1 Diabetes Mellitus

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    We examined whether alterations in vascular endothelial function and early structural changes in atherosclerosis are associated with microvascular complications in patients with type 1 diabetes mellitus (DM). Flow-mediated dilation (FMD) of the brachial artery and carotid intima-media thickness (IMT) measurement were performed in 70 young adults (aged 19 to 35 yr), 48 with type 1 DM, and 22 normal controls. Patients with diabetes had a lower peak FMD response (7.8±3.9 vs. 11.1±1.9%, p<0.001) and increased IMT (0.51±0.10 vs. 0.42±0.07 mm, p<0.001) compared with controls. Twenty (41.7%) of the patients had microvascular complications including neuropathy, nephropathy, or retinopathy. In these complicated diabetic patients, we found a lower FMD response (6.1±2.5 vs. 9.9±3.5%, p=0.001) compared with diabetics without microvascular complications. The presence of microvascular complications was also associated with older age and longer duration of the disease. However, no differences were observed in IMT, body size, blood pressure, HbA1c, C-reactive protein, low-density lipoprotein or high-density lipoprotein cholesterol levels between complicated and non-complicated patients. Endothelial dysfunction and early structural atherosclerotic changes are common manifestations in type 1 DM, and endothelial dysfunction is thought to be an early event in the atherosclerotic process and important in the pathogenesis of microvascular complications

    Modified FOLFOX-6 chemotherapy in advanced gastric cancer: Results of phase II study and comprehensive analysis of polymorphisms as a predictive and prognostic marker

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    <p>Abstract</p> <p>Background</p> <p>The objective of this study was to evaluate the efficacy and toxicity of infusional 5-fluorouracil (5-FU), folinic acid and oxaliplatin (modified FOLFOX-6) in patients with advanced gastric cancer (AGC), as first-line palliative combination chemotherapy. We also analyzed the predictive or prognostic value of germline polymorphisms of candidate genes associated with 5-FU and oxaliplatin.</p> <p>Methods</p> <p>Seventy-three patients were administered a 2 hour infusion of oxaliplatin (100 mg/m<sup>2</sup>) and folinic acid (100 mg/m<sup>2</sup>) followed by a 46 hour continuous infusion of 5-FU (2,400 mg/m<sup>2</sup>). Genomic DNA from the patients' peripheral blood mononuclear cells was extracted. Ten polymorphisms within five genes were investigated including TS, GSTP, ERCC, XPD and XRCC.</p> <p>Results</p> <p>The overall response rate (RR) was 43.8%. Median time to progression (TTP) and overall survival (OS) were 6.0 months and 12.6 months, respectively. Toxicities were generally tolerable and manageable. The RR was significantly higher in patients with a 6-bp deletion homozygote (-6 bp/-6 bp) in TS-3'UTR (55.0% <it>vs</it>. 30.3% in +6 bp/+6 bp or +6 bp/-6 bp, <it>p </it>= 0.034), and C/A or A/A in XPD156 (52.0% <it>vs</it>. 26.1% in C/C, <it>p </it>= 0.038). The -6 bp/-6 bp in TS-3'UTR was significantly associated with a prolonged TTP and OS. In a multivariate analysis, the 6-bp deletion in TS-3'UTR was identified as an independent prognostic marker of TTP (hazard ratio = 0.561, <it>p </it>= 0.032).</p> <p>Conclusion</p> <p>Modified FOLFOX-6 chemotherapy appears to be active and well tolerated as first line chemotherapy in AGC patients. The 6-bp deletion in TS-3'UTR might be a candidate to select patients who are likely to benefit from 5-FU based modified FOLFOX-6 in future large scale trial.</p

    Skeletal Adaptation to Intramedullary Pressure-Induced Interstitial Fluid Flow Is Enhanced in Mice Subjected to Targeted Osteocyte Ablation

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    Interstitial fluid flow (IFF) is a potent regulatory signal in bone. During mechanical loading, IFF is generated through two distinct mechanisms that result in spatially distinct flow profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While the former generates IFF primarily within the lacunar-canalicular network, the latter generates significant flow at the endosteal surface as well as within the tissue. This gives rise to the intriguing possibility that loading-induced IFF may differentially activate osteocytes or surface-residing cells depending on the generating mechanism, and that sensation of IFF generated via intramedullary pressurization may be mediated by a non-osteocytic bone cell population. To begin to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation mouse model and a microfluidic system for modulating intramedullary pressure (ImP) to assess whether structural adaptation to ImP-driven IFF is altered by partial osteocyte depletion. Canalicular convective velocities during pressurization were estimated through the use of fluorescence recovery after photobleaching and computational modeling. Following osteocyte ablation, transgenic mice exhibited severe losses in bone structure and altered responses to hindlimb suspension in a compartment-specific manner. In pressure-loaded limbs, transgenic mice displayed similar or significantly enhanced structural adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite up to ∌50% of trabecular lacunae being uninhabited following ablation. Interestingly, regression analysis revealed relative gains in bone structure in pressure-loaded limbs were correlated with reductions in bone structure in unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was potentiated by increases in osteoclastic activity and/or reductions in osteoblastic activity incurred independently of pressure loading. Collectively, these studies indicate that structural adaptation to ImP-driven IFF can proceed unimpeded following a significant depletion in osteocytes, consistent with the potential existence of a non-osteocytic bone cell population that senses ImP-driven IFF independently and potentially parallel to osteocytic sensation of poroelasticity-derived IFF

    Measurement of Mass and Width of the W Boson at LEP

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    We report on measurements of the mass and total decay width of the W boson with the L3 detector at LEP. W-pair events produced in e+e−\mathrm{e^+e^-} interactions between 161 GeV and 183 GeV centre-of-mass energy are selected in a data sample corresponding to a total luminosity of 76.7 pb−1^{-1}. Combining all final states in W-pair production, the mass and total decay width of the W boson are determined to be MW=80.61±0.15\mathrm{M_W}=80.61\pm0.15 GeV and ΓW=1.97±0.38\Gamma_{\mathrm{W}}=1.97\pm0.38 GeV, respectively

    Search for Heavy Neutral and Charged Leptons in e+^+e−^- Annihilation at s\sqrt{s} = 183 and 189 GeV

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    A search for unstable neutral and charged heavy leptons as well as for stable charged heavy leptons is performed at center-of-mass energies s\sqrt{s} = 183 and 189 GeV with the L3 detector at LEP. No evidence for their existence is found. We exclude neutral heavy leptons which couple to the electron, muon or tau family, of the Dirac type for masses below 92.4, 93.3 and 83.3 GeV, and of the Majorana type for masses below 81.8, 84.1 and 73.5 GeV, respectively. We exclude unstable charged heavy leptons for masses below 93.9 GeV for a wide range of the associated neutral heavy lepton mass. If the unstable charged heavy lepton decays to a light neutrino, we exclude masses below 92.4 GeV. The production of stable charged heavy leptons with mass less than 93.5 GeV is also excluded

    Formation of the ηc\eta_c in Two-Photon Collisions at LEP

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    The two-photon width Γγγ\Gamma_{\gamma\gamma} of the ηc\eta_c meson has been measured with the L3 detector at LEP. The ηc\eta_c is studied in the decay modes π+π−π+π−\pi^+\pi^-\pi^+\pi^-, π+π−\pi^+\pi^-K+^+K−^-, Ks0_s^0K±π∓^\pm\pi^\mp, K+^+K−π0^-\pi^{0}, π+π−η\pi^+\pi^-\eta, π+π−ηâ€Č\pi^+\pi^-\eta', and ρ+ρ−\rho^+\rho^- using an integrated luminosity of 140 pb−1^{-1} at s≃91\sqrt{s} \simeq 91 GeV and of 52 pb−1^{-1} at s≃183\sqrt{s} \simeq 183 GeV. The result is Γγγ(ηc)=6.9±1.7(stat.)±0.8(sys.)±2.0\Gamma_{\gamma\gamma}(\eta_c) = 6.9 \pm 1.7 (stat.) \pm 0.8 (sys.) \pm 2.0(BR) keV. The Q2Q^2 dependence of the ηc\eta_c cross section is studied for Q2<9Q^2 < 9 GeV2^{2}. It is found to be better described by a Vector Meson Dominance model form factor with a J-pole than with a ρ\rho-pole. In addition, a signal of 29±1129 \pm 11 events is observed at the χc0\chi_c0 mass. Upper limits for the two-photon widths of the χc0\chi_c0, χc2\chi_c2, and ηcâ€Č\eta_c' are also given

    Measurement of an Elongation of the Pion Source in Z Decays

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    We measure Bose-Einstein correlations between like-sign charged pion pairs in hadronic Z decays with the L3 detector at LEP. The analysis is performed in three dimensions in the longitudinal center-of-mass system. The pion source is found to be elongated along the thrust axis with a ratio of transverse to longitudinal radius of 0.81±0.02−0.19+0.030.81\pm 0.02 ^{+0.03}_{-0.19}

    Search for Charginos with a Small Mass Difference with the Lightest Supersymmetric Particle at \sqrt{s} = 189 GeV

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    A search for charginos nearly mass-degenerate with the lightest supersymmetric particle is performed using the 176 pb^-1 of data collected at 189 GeV in 1998 with the L3 detector. Mass differences between the chargino and the lightest supersymmetric particle below 4 GeV are considered. The presence of a high transverse momentum photon is required to single out the signal from the photon-photon interaction background. No evidence for charginos is found and upper limits on the cross section for chargino pair production are set. For the first time, in the case of heavy scalar leptons, chargino mass limits are obtained for any \tilde{\chi}^{+-}_1 - \tilde{\chi}^0_1 mass difference
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