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Diabetes Mellitus Tipo 2 , Leptina/análogos & derivados , Lipodistrofia , Proproteína Convertasa 9/sangre , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Estudios de Cohortes , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/uso terapéutico , Leptina/uso terapéutico , Lipodistrofia/sangre , Lipodistrofia/complicaciones , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
It is now recognized that the International System of Units (SI units) will be redefined in terms of fundamental constants, even if the date when this will occur is still under debate. Actually, the best estimate of fundamental constant values is given by a least-squares adjustment, carried out under the auspices of the Committee on Data for Science and Technology (CODATA) Task Group on Fundamental Constants. This adjustment provides a significant measure of the correctness and overall consistency of the basic theories and experimental methods of physics using the values of the constants obtained from widely differing experiments. The physical theories that underlie this adjustment are assumed to be valid, such as quantum electrodynamics (QED). Testing QED, one of the most precise theories is the aim of many accurate experiments. The calculations and the corresponding experiments can be carried out either on a boundless system, such as the electron magnetic moment anomaly, or on a bound system, such as atomic hydrogen. The value of fundamental constants can be deduced from the comparison of theory and experiment. For example, using QED calculations, the value of the fine structure constant given by the CODATA is mainly inferred from the measurement of the electron magnetic moment anomaly carried out by Gabrielse's group. (Hanneke et al. 2008 Phys. Rev. Lett. 100, 120801) The value of the Rydberg constant is known from two-photon spectroscopy of hydrogen combined with accurate theoretical quantities. The Rydberg constant, determined by the comparison of theory and experiment using atomic hydrogen, is known with a relative uncertainty of 6.6×10(-12). It is one of the most accurate fundamental constants to date. A careful analysis shows that knowledge of the electrical size of the proton is nowadays a limitation in this comparison. The aim of muonic hydrogen spectroscopy was to obtain an accurate value of the proton charge radius. However, the value deduced from this experiment contradicts other less accurate determinations. This problem is known as the proton radius puzzle. This new determination of the proton radius may affect the value of the Rydberg constant . This constant is related to many fundamental constants; in particular, links the two possible ways proposed for the redefinition of the kilogram, the Avogadro constant N(A) and the Planck constant h. However, the current relative uncertainty on the experimental determinations of N(A) or h is three orders of magnitude larger than the 'possible' shift of the Rydberg constant, which may be shown by the new value of the size of the proton radius determined from muonic hydrogen. The proton radius puzzle will not interfere in the redefinition of the kilogram. After a short introduction to the properties of the proton, we will describe the muonic hydrogen experiment. There is intense theoretical activity as a result of our observation. A brief summary of possible theoretical explanations at the date of writing of the paper will be given. The contribution of the proton radius puzzle to the redefinition of SI-based units will then be examined.
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An unusual but effective way to determine at threshold the dpi<-->NN transition strength alpha is to exploit the hadronic ground-state broadening Gamma(1s) in pionic deuterium, accessible by x-ray spectroscopy. The broadening is dominated by the true absorption channel dpi(-)-->nn, which is related to s-wave pion production pp-->dpi(+) by charge symmetry and detailed balance. Using the exotic atom circumvents the problem of Coulomb corrections to the cross section as necessary in the production experiments. Our dedicated measurement finds Gamma(1s)=(1171(-49)(+23)) meV yielding alpha=(252(-11)(+5)) microb.
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We have performed a systematic study of the bremsstrahlung emission from the electrons in the plasma of a commercial 14.5 GHz electron-cyclotron resonance ion source. The electronic spectral temperature and the product of ionic and electronic densities of the plasma are measured by analyzing the bremsstrahlung spectra recorded for several rare gases (Ar, Kr, and Xe) as a function of the injected power. Within our uncertainty, we find an average temperature of approximately 48 keV above 100 W, with a weak dependency on the injected power and gas composition. Charge state distributions of extracted ion beams have been determined as well, providing a way to disentangle the ionic density from the electronic density. Moreover x-ray emission from highly charged argon ions in the plasma has been observed with a high-resolution mosaic-crystal spectrometer, demonstrating the feasibility for high-precision measurements of transition energies of highly charged ions, in particular, of the magnetic dipole (M1) transition of He-like of argon ions.
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The (3p-1s) x-ray transition to the muonic hydrogen ground state was measured with a high-resolution crystal spectrometer. A Doppler effect broadening of the x-ray line was established which could be attributed to different Coulomb deexcitation steps preceding the measured transition. The assumption of a statistical population of the hyperfine levels of the muonic hydrogen ground state was directly confirmed by the experiment, and measured values for the hyperfine splitting can be reported. The results allow a decisive test of advanced cascade model calculations and establish a method to extract fundamental strong-interaction parameters from pionic hydrogen experiments.
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Spherically bent crystals are used as analyzers in high-resolution spectroscopy, in particular, in low count-rate applications such as exotic-atom research. The focal conditions are determined not only by the bending radius and the Bragg angle but also by the crystal cut angle between its surface and the reflecting crystal planes, along with their orientation with respect to the direction of dispersion. We describe a simple but precise method for measuring the cut angle and its orientation for mounted spherically bent crystals, by combining x-ray diffraction and laser optical alignment, which can be easily performed with standard x-ray laboratory equipment.
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We discuss a technique that permits branch points in the phase function to be localized in real-time adaptive-optics systems and that is unambiguous and robust in the presence of noise.
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The reconstruction of discontinuous light-phase functions is of major importance in adaptive optics. An efficient and simple algorithm that can reconstruct large arrays of phases from phase differences is presented. We prove that the algorithm yields a perfect result in the absence of noise, and we describe the function that it maximizes. We suggest a method that makes use of the reconstructed phase to measure the position of branch points. A simulation of the reconstruction of a 33x33 phase array is presented.
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A case control study was undertaken to compare the distribution of apolipoprotein (a) phenotypes in patients suffering from atherosclerosis and undergoing coronary bypass surgery with the distribution observed in adequately selected controls. Cases differed from controls for triglycerides (1.90 +/- 0.88 mmol l-1 and 1.16 +/- 0.79 mmol l-1, P < 0.0001, respectively), HDL cholesterol (1.15 +/- 0.34 mmol l-1 and 1.69 +/- 0.42 mmol l-1, P < 0.0001, respectively), apolipoprotein AI (1.31 +/- 0.24 g l-1 and 1.70 +/- 0.29 g l-1, P < 0.0001, respectively) and lipoprotein a (Lp(a)) (0.32 +/- 0.30 g l-1 and 0.19 +/- 0.20 g l-1, P < 0.0001, respectively). The apolipoprotein (a) phenotypes were distributed differently in cases and controls (chi 2 = 25.26, P < 0.0001) with a lower percentage of isoforms of larger size and a higher percentage of isoforms of smaller size in patients. The Lp(a) concentration remained significantly higher in patients than in controls for most of the phenotypes, suggesting that both a high Lp(a) concentration and a different apolipoprotein (a) size distribution could be involved in the development of atherosclerosis in this population. In addition, patients exhibiting the highest Lp(a) concentrations had higher levels of LDL cholesterol and apolipoprotein B than patients exhibiting the lowest Lp(a) concentrations. This feature was not observed in controls. By contrast, controls with the highest Lp(a) concentration had significantly higher triglyceride levels than controls with the lowest Lp(a) concentration. This feature was not observed in patients. Our results indicate that patients undergoing bypass surgery have higher Lp(a) concentrations than controls, this increase being not completely explained by the difference in apolipoprotein (a) phenotype distribution. The high Lp(a) concentration seems to be associated with different lipid profiles in patients than in controls.
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Puente de Arteria Coronaria , Lipoproteína(a)/sangre , Adulto , Anciano , Anciano de 80 o más Años , Apolipoproteínas/sangre , Arteriosclerosis/sangre , Arteriosclerosis/cirugía , Estudios de Casos y Controles , Femenino , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , FenotipoRESUMEN
A protocol using stable isotopes, developed to measure apolipoprotein B turnover in humans, was tested by intravenous infusion of [2H3]-leucine into 5 normolipidemic volunteers during a 14-h fast. Tracer-to-tracee ratio curves were analyzed by four different approaches: linear regression, monoexponential regression, a minimal compartmental model (3 compartments) and a complex model (4 compartments and two shunt pathways). The three-compartment model was validated by qualitative analysis of data obtained after injection of a [2H3]-leucine bolus. This simple model gave an FCR of 0.48 +/- 0.05 h-1 for VLDL, 0.62 +/- 0.08 h-1 for IDL and 0.022 +/- 0.002 h-1 for LDL. The total production rate of apolipoprotein B in plasma was 24.8 +/- 6.5 mg.kg-1.day-1. Kinetic parameters were similar for the complex model which showed no improvement in fit. Lower estimates were observed with the non-compartmental approaches.
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Apolipoproteínas B/análisis , Lipoproteínas/metabolismo , Adulto , Análisis de Varianza , Deuterio , Ayuno/sangre , Humanos , Infusiones Intravenosas , Cinética , Modelos Lineales , Lipoproteínas/química , Masculino , Valores de ReferenciaRESUMEN
BACKGROUND: Among patients with the idiopathic nephrotic syndrome who have focal and segmental glomerulosclerosis and undergo renal transplantation, 15 to 55 percent have recurrent nephrotic syndrome. The recurrence may be caused by a plasma factor or factors that increase glomerular permeability, because plasma exchange transiently decreases or abolishes proteinuria in some patients. We studied the effect on proteinuria of the removal of protein (mostly immunoglobulins) by adsorption onto protein A from the plasma of patients with recurrent nephrotic syndrome. METHODS: Eight patients were treated with one to three cycles of two to seven 1-day sessions of protein adsorption, and the patients' urinary protein excretion was measured repeatedly. Their immunosuppressive regimens were not changed during the treatment. The adsorbed proteins were eluted from the protein A and injected into rats, and the urinary albumin excretion of the rats was measured. RESULTS: The protein-adsorption treatment consistently decreased urinary protein excretion by an average of 82 percent at the end of a cycle (P < 0.001). In one patient proteinuria disappeared, and in another urinary protein excretion remained below 2.5 g per day with repeated cycles of protein adsorption. In all but one patient the effect of adsorption was limited in time, with a return to the preadsorption level of protein excretion within a maximum of two months. The administration to rats of material eluted from the protein A increased urinary albumin excretion 2.9- to 4.6-fold (P < 0.001 and P = 0.005, respectively). Although protein A primarily binds immunoglobulins, the active fraction of the eluted proteins had a molecular weight below 100,000, indicating that immunoglobulin was not directly involved. CONCLUSIONS: Adsorption of plasma protein decreases urinary protein excretion in patients with recurrence of the nephrotic syndrome after renal transplantation. Studies of the adsorbed proteins should provide information about the mechanism of this disease.
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Proteínas Sanguíneas/metabolismo , Trasplante de Riñón , Síndrome Nefrótico/terapia , Proteinuria/terapia , Adolescente , Adsorción , Adulto , Animales , Proteínas Sanguíneas/farmacología , Femenino , Glomerulonefritis/cirugía , Humanos , Masculino , Persona de Mediana Edad , Síndrome Nefrótico/cirugía , Intercambio Plasmático , Ratas , Recurrencia , Diálisis Renal , Proteína Estafilocócica A/metabolismoRESUMEN
Patients with end-stage renal failure secondary to idiopathic nephrotic syndrome are at risk of initial disease recurrence after kidney transplantation (30%). Selective proteinuria can appear immediately after transplantation and focal glomerular sclerosis with graft loss can occur in 10% of patients with recurrence. Current immunosuppressive protocols do not seem to influence the recurrence rate in adult patients and the efficacy of therapeutic plasma exchanges remains controversial. We have previously demonstrated that plasma exchanges, proposed early before glomerular sclerosis, were able to significantly reduce proteinuria without affecting albuminemia or glomerular filtration. We report here on three patients who suffered immediate recurrence after transplantation and were treated with plasma immunoadsorption onto protein A column (Excorim, Lund); these patients had prior histories of steroid-resistant focal glomerular sclerosis. This procedure is more specific than plasma exchange in that it cleared the serum of immunoglobulins, significantly decreased proteinuria in only two cases (from 14 to 5 g/d and 2.5 to 0.8 g/d) and eliminated it in the third case (from 3 to 0.1 g/d). The modifications of proteinuria levels appeared as early as the second immunoadsorption sequence and returned to pre-immunoadsorption values within 2 to 8 weeks. These observations argue for the protein A binding of plasmatic factor(s) involved in idiopathic, nephrotic syndrome and allow us to progress to the characterization of this(ese) factor(s).
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Técnicas de Inmunoadsorción , Trasplante de Riñón , Síndrome Nefrótico/terapia , Adulto , Creatinina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Recurrencia , Proteína Estafilocócica A , Factores de TiempoAsunto(s)
Calcimicina/farmacología , Ciclosporinas/farmacología , Proteínas/metabolismo , Linfocitos T/inmunología , Acetato de Tetradecanoilforbol/farmacología , Línea Celular , Células Cultivadas , Electroforesis en Gel Bidimensional , Rechazo de Injerto , Humanos , Trasplante de Riñón/inmunología , Activación de Linfocitos , Proteínas/aislamiento & purificación , Linfocitos T/efectos de los fármacosAsunto(s)
Glomerulonefritis/inmunología , Glomeruloesclerosis Focal y Segmentaria/inmunología , Trasplante de Riñón , Proteinuria/tratamiento farmacológico , Proteína Estafilocócica A/uso terapéutico , Adulto , Femenino , Humanos , Técnicas de Inmunoadsorción , Trasplante de Riñón/efectos adversos , Recurrencia , Factores de TiempoRESUMEN
The lipid and apolipoprotein states of 74 men (mean age 49.96 +/- 5.9 years) were studied 24 h before coronary bypass surgery and their results were compared with those of a control group of 78 men (mean age 48.88 +/- 5.41 years). Apolipoproteins C-III (apo C-III) and E (apo E) were determined in particles with (LpB) and without (nonLpB) apo B separated using a concanavalin A reagent. Apo C-III was significantly increased in LpB particles (P less than 0.001), and apo E in LpB (P less than 0.001) and nonLpB (P less than 0.001) particles. The significant variables selected in logistic discriminant stepwise analysis were total cholesterol/HDL-cholesterol, apo E-nonLpB and apo C-III-LpB. This last parameter, which is more discriminant than triglycerides, provides a more specific indication of dyslipoproteinemia in coronary bypass patients; in association with the other two variables, it significantly improved the percentage of correctly classified individuals.
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Apolipoproteínas/sangre , Puente de Arteria Coronaria , Lípidos/sangre , Adulto , Apolipoproteína C-III , Apolipoproteínas C/sangre , Apolipoproteínas E/sangre , Enfermedad Coronaria/sangre , Enfermedad Coronaria/cirugía , Análisis Discriminante , Humanos , Modelos Logísticos , Masculino , Persona de Mediana EdadRESUMEN
Third-generation cephalosporins such as ceftriaxone are often used alone; however, with Enterobacter (ENT), Citrobacter (CIT), Serratia (SER) and Morganella (MOR), a combination of two drugs is advisable. Aminoglycoside-beta-lactam combinations are often synergistic. However, results are not consistent with the new cephalosporins. We determined the killing kinetics of ceftriaxone (C) alone, amikacin (A) alone and both drugs in combination (AC). The antibiotics were tested in the following concentrations: 0.25, 1, 4 and 16 X MIC for C, 0.5, 2 and 8 X MIC for A, and, for AC, 0.5-0.25 X MIC (1), 0.5-1 X MIC (2) and 2-0.25 X MIC (3). Surviving bacteria were enumerated at 0 h, 1 h, 3 h, 5 h and 24 hours. Amikacin showed a strong, dose-dependent bactericidal activity. Maximal activity of ceftriaxone was observed at 1 or 4 X MIC. Time of contact had a significant influence, indicating a time-dependent activity. In 5 hours, the killing effect of the AC combination rarely exceeded that of each antibiotic alone. Higher killing rates were observed with AC and; the killing effect of AC (3) was similar to amikacin's maximal killing effect. In 24 hours, the AC (3) combination was clearly synergistic with inhibition of late regrowths.