Abstract-Increased renal restive index (RI) measured using Doppler ultrasonography has been shown to correlate with the degree of renal impairment in hypertensive patients. We investigated the prognostic role of RI in cardiovascular and renal outcomes. A total of 426 essential hypertensive subjects (mean age, 63 years; 50% female) with no previous cardiovascular disease were included in this study. Renal segmental arterial RI was measured by duplex Doppler ultrasonography. During follow-up (mean, 3.1 years), 57 participants developed the primary composite end points including cardiovascular and renal outcomes. In multivariate Cox regression analysis, RI was an independent predictor of worse outcome in total subjects (hazard ratio, 1.71 for 1 SD increase), as well as in patients with estimated glomerular filtration rate (eGFR) Ͻ60 mL/min per 1.73 m 2 (hazard ratio, 2.11 for 1 SD increase; PϽ0.01, respectively). When divided into 4 groups based on the respective sex-specific median levels of RI in the eGFR Ն60 and eGFR Ͻ60 mL/min per 1.73 m 2 groups, the group with eGFR Ͻ60 and high RI (male Ն0.73, female Ն0.72) had a significantly poorer event-free survival rate ( 2 ϭ126.4; PϽ0.01), and the adjusted hazard ratio by multivariate Cox regression analysis was 9.58 (95% CI, PϽ0.01). In conclusion, impairment of renal hemodynamics evaluated by increased RI is associated with an increased risk of primary composite end points, and the combination of high RI and low eGFR is a powerful predictor of these diseases in essential hypertension. In hypertensive patients with chronic kidney disease, RI evaluation may complement predictors of cardiovascular and renal outcomes. Key Words: cardiovascular disease Ⅲ renal hemodynamics Ⅲ ultrasonography Ⅲ hypertension Ⅲ predictor I n the past few years, there has been growing attention to markers of subclinical renal damage because they provide an accurate prediction of global cardiovascular outcome.1 Renal Doppler sonography permits noninvasive assessment of intrarenal hemodynamics in addition to evaluation of anatomic information. Intrarenal arterial waveforms recorded by Doppler sonography have been widely used to evaluate renal dysfunction.2,3 Previous studies have explored the capacity of resistive index (RI) calculated from blood flow velocity in vessels to predict the progression of renal function in patients with hypertension, 4 diabetes mellitus, 5 or chronic nephropathy. 6,7 In addition, histological studies demonstrated that RI not only reflects changes in intrarenal perfusion and renovascular resistance but was increased in several pathological conditions, such as renal atherosclerosis 8 and tubulointerstitial damage. 9,10 In previous studies, the prognostic value of RI was examined only in chronic nephropathy, 6 elderly, 11 or heart failure patients 12; however, the results obtained were inconsistent. Thus, the status of RI as an independent cardiovascular risk marker remains to be elucidated. Estimated glomerular filtration rate (eGFR), which is a measure of the kidneys' ...
The characterization of the transition state is a central issue in biophysical studies of protein folding. NMR is a multiprobe measurement technique that provides residuespecific information. Here, we used exchange spectroscopy to characterize the transition state of the two-state slow topological isomerization of a 27-residue lantibiotic peptide. The exchange kinetic rates varied on a per-residue basis, indicating the reduced kinetic cooperativity of the two-state exchange, as well as the previously observed reduced thermodynamic cooperativity. Furthermore, temperature-dependent measurements revealed large variations in the activation enthalpy and entropy terms among residues. Interestingly, we found a linear relationship between the logarithm of the equilibrium constants and that of the exchange rates. Because the data points are derived from amino acid residues in one polypeptide chain, we refer to the linear relationship as the residue-based linear free energy relationship (rbLFER). The rbLFER offers information about the transition state of the twostate exchange.
Multiprobe measurements, such as NMR and hydrogen exchange studies, can provide the equilibrium constant, K, and rate constants for forward and backward processes, k and k′, of the two-state structural changes of a polypeptide on a per-residue basis. We previously found a linear relationship between log K and log k and between log K and log k′ for the topological exchange of a 27-residue bioactive peptide. To test the general applicability of the residue-based linear free energy relationship (rbLEFR), we performed a literature search to collect residue-specific K, k, and k′ values in various exchange processes, including folding-unfolding equilibrium, coupled folding and binding of intrinsically disordered peptides, and structural fluctuations of folded proteins. The good linearity in a substantial number of the log–log plots proved that the rbLFER holds for the structural changes in a wide variety of protein-related phenomena. Among the successful cases, the hydrogen exchange study of apomyoglobin folding intermediates is particularly interesting. We found that the residues that deviated from the linear relationship corresponded to the α-helix, for which transient translocation had been identified by other experiments. Thus, the rbLFER is useful for studying the structures and energetics of the dynamic states of protein molecules.
We report the successful treatment with ultraviolet B phototherapy of a patient with HIV-associated eosinophilic pustular folliculitis. We were able to observe the clinical and therapeutic course for about one year and three months. This 35-year-old homosexual Japanese man presented with disseminated, discrete, follicular, erythematous papules with intense pruritus over his face, neck, chest wall, and upper back. Initially, the eruption responded to therapy with topical or oral indomethacin and oral H1 antihistamine. However, the eruption was highly prone to recurrence, and it gradually failed to respond to these therapies. The eruption became chronic and persistent and manifested the excoriated, prurigo-like nodules that are typical of reported pruritic papular eruption, suggesting that this skin disease and HIV-associated eosinophilic pustular folliculitis are two forms of the same disease entity. UVB phototherapy in small doses was very effective for the persistent eruption, and no recurrence of the eruption was noted during or since the six-month maintenance therapy (once a week at a dose equivalent to 0.75 of the minimal erythema dose) (9 months total). No unfavorable side effects have been observed during or after the UVB phototherapy (cumulative UVB doses of 2,320 mJ/cm2).
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