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Morbidity, hospitalizations, and costs for the treatment of individuals with end-stage renal disease are simply not improving at a rate that is acceptable to many physicians and dialysis providers in the United States. Various conferences and papers have suggested what processes need to become part of the dialysis prescription to accelerate change. Controlling cardiovascular disease is a part of that change, and controlling extra-cellular volume (ECV) is necessary to accomplish this. Three dialysis providers joined in a quality initiative to objectively assess the ultrafiltration process and measure "normalized" ECV, with the outcome objective to decrease ECV-related hospitalizations. The results show a decrease in ECV-related hospitalizations by 50%. The model of dialysis prescription needs to now change to Kt/V + objective ECV control.
Frequently, bevacizumab is combined with chemotherapeutics such as irinotecan, motivated by studies showing improved clinical outcomes compared with historical controls. However, no systematic studies have been performed to determine if and how these drugs should be combined for optimal therapeutic response. The purpose of this study was to characterize the temporal combinations of bevacizumab and irinotecan by measuring the contrast-agent enhanced tumor volumes and relative cerebral blood volume using dynamic susceptibility contrast imaging. The studies, performed in the U87 brain tumor model, show a vascular normalization window with bevacizumab monotherapy and are consistent with clinical indications of no additional benefit in the addition of irinotecan to bevacizumab therapy.
Copyright © 2011 Wiley Periodicals, Inc.
Several studies recognized an overlap between CFS (chronic fatigue syndrome) and POTS (postural tachycardia syndrome). We compared the autonomic and neurohormonal phenotype of POTS patients with CFS (CFS-POTS) to those without CFS (non-CFS-POTS), to determine whether CFS-POTS represents a unique clinical entity with a distinct pathophysiology. We recruited 58 patients with POTS, of which 47 were eligible to participate. A total of 93% of them reported severe fatigue [CIS (Checklist of Individual Strength), fatigue subscale >36], and 64% (n=30) fulfilled criteria for CFS (CFS-POTS). The prevalence of CFS symptoms (Centers for Disease Control and Prevention criteria) was greater in the CFS-POTS group, but the pattern of symptoms was similar in both groups. Physical functioning was low in both groups (RAND-36 Health Survey, 40±4 compared with 33±3; P=0.153), despite more severe fatigue in CFS-POTS patients (CIS fatigue subscale 51±1 compared with 43±3; P=0.016). CFS-POTS patients had greater orthostatic tachycardia than the non-CFS-POTS group (51±3 compared with 40±4 beats/min; P=0.030), greater low-frequency variability of BP (blood pressure; 6.3±0.7 compared with 4.8±1.0 mmHg2; P=0.019), greater BP recovery from early to late phase II of the Valsalva manoeuvre (18±3 compared with 11±2 mmHg; P=0.041) and a higher supine (1.5±0.2 compared with 1.0±0.3 ng/ml per·h; P=0.033) and upright (5.4±0.6 compared with 3.5±0.8 ng/ml per h; P=0.032) PRA (plasma renin activity). In conclusion, fatigue and CFS-defining symptoms are common in POTS patients. The majority of them met criteria for CFS. CFS-POTS patients have higher markers of sympathetic activation, but are part of the spectrum of POTS. Targeting this sympathetic activation should be considered in the treatment of these patients.
The purpose of this study was to determine whether there are differences in postisometric contraction blood volume and oxygenation responses among groups of type 2 diabetes mellitus (T2DM), obese, and lean individuals detectable using MRI. Eight T2DM patients were individually matched by age, sex, and race to non-T2DM individuals with similar body mass index (obese) and lean subjects. Functional MRI was performed using a dual-gradient-recalled echo, echo-planar imaging sequence with a repetition time of 1 s and at two echo times (TE = 6 and 46 ms). Data were acquired before, during, and after 10-s isometric dorsiflexion contractions performed at 50 and 100% of maximal voluntary contraction (MVC) force. MRI signal intensity (SI) changes from the tibialis anterior and extensor digitorum longus muscles were plotted as functions of time for each TE. From each time course, the difference between the minimum and the maximum postcontraction SI (ΔSI) were determined for TE = 6 ms (ΔSI(6)) and TE = 46 ms (ΔSI(46)), reflecting variations in blood volume and oxyhemoglobin saturation, respectively. Following 50% MVC contractions, the mean postcontraction ΔSI(6) values were similar in the three groups. Following MVC only, and in the EDL muscle only, T2DM and obese participants had ∼56% lower ΔSI(6) than the lean individuals. Also following MVC only, the ΔSI(46) response in the EDL was lower in T2DM subjects than in lean individuals. These data suggest that skeletal muscle small vessel impairment occurs in T2DM and body mass index-matched subjects, in muscle-specific and contraction intensity-dependent manners.
Despite the early promising results with the anti-angiogenic agent, bevacizumab, to prolong time to progression in patients with brain tumors, the optimal dose and drug combinations have not yet been defined. The purpose of this study was to characterize the bevacizumab dose-response relationship for brain tumors by measuring the contrast-agent enhanced tumor volumes and relative cerebral blood volume (rCBV) using dynamic susceptibility contrast (DSC) imaging. The studies, performed in the U87 brain tumor model using doses of bevacizumab ranging from 0 to 10 mg/kg, demonstrate that tumor growth and vascularity are inhibited at all doses used, compared to untreated controls. However, only the maximum dose showed a statistically significant difference in growth rate. Conversely tumor vascularity, as measured with rCBV, was inhibited equally well for all doses used with no clear indication that higher doses are more effective.
Previous studies show that transient increases in both blood flow and magnetic resonance image signal intensity (SI) occur in human muscle after brief, single contractions, and that the SI increases are threefold larger in physically active compared with sedentary subjects. This study examined the relationship between these transient changes by measuring anterior tibial artery flow (Doppler ultrasound), anterior muscle SI (3T, one-shot echo-planar images, TR/TE = 1,000/35), and muscle blood volume and hemoglobin saturation [near-infrared spectroscopy (NIRS)] in the same subjects after 1-s-duration maximum isometric ankle dorsiflexion contractions. Arterial flow increased to a peak 5.9 ± 0.7-fold above rest (SE, n = 11, range 2.6-10.2) within 7 s and muscle SI increased to a peak 2.7 ± 0.6% (range 0.0-6.0%) above rest within 12 s after the contractions. The peak postcontractile SI change was significantly correlated with both peak postcontractile flow (r = 0.61, n = 11) and with subject activity level (r = 0.63, n = 10) estimated from 7-day accelerometer recordings. In a subset of 7 subjects in which NIRS data acquisition was successful, the peak magnitude of the postcontractile SI change agreed well with SI calculated from the NIRS blood volume and saturation changes (r = 0.80, slope = 1.02, intercept = 0.16), confirming the blood-oxygenation-level-dependent (BOLD) mechanism underlying the SI change. The magnitudes of postcontractile changes in blood saturation and SI were reproduced by a simple one-compartment muscle vascular model that incorporated the observed pattern of postcontractile flow, and which assumed muscle O(2) consumption peaks within 2 s after a brief contraction. The results show that muscle postcontractile BOLD SI changes depend critically on the balance between O(2) delivery and O(2) consumption, both of which can be altered by chronic physical activity.
The purpose of this study was to assess the repeatability of a dual gradient-recalled echo (GRE) muscle functional MRI technique. On 2 days, subjects (n = 8) performed 10 s isometric dorsiflexion contractions under conditions of: (1) maximal voluntary contraction (MVC), (2) 50% MVC (50% MVC), or (3) 50% MVC with concurrent proximal arterial cuff occlusion (50% MVC(cuff)). Functional MRI data were acquired using single-slice dual GRE (TR/TE = 1000/6, 46 ms)-echo planar imaging for 20 s before, during, and for 180 s after each contraction. The mean signal intensity (SI) time courses at each TE (SI(6) and SI(46), reflecting variations in blood volume and %HbO(2), respectively) from the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles were characterized with the post-contraction change in SI and the time-to-peak SI (DeltaSI and TTP, respectively). DeltaSI(6) following an MVC was 36% higher than that obtained after a 50% MVC (p = 0.048). For DeltaSI(6), the highest intraclass correlation coefficients (ICCs) were observed for the TA muscle in the 50% MVC and MVC conditions, with values of 0.83 (p = 0.01) and 0.88 (p = 0.005), respectively. Bland-Altman plots revealed repeatability coefficients (RCs) for the 50% MVC and MVC conditions in the TA muscle of 1.9 and 1.4, respectively. The most repeatable measures for DeltaSI(46) were obtained for the 50% MVC and MVC conditions in the EDL muscle (p = 0.01 and p = 0.04, respectively). Bland-Altman plots revealed RC's for 50% MVC and MVC conditions in the EDL muscle of 3.9 and 5.7, respectively. DeltaSI(6) and DeltaSI(46) increased as a function of the contraction intensity. The repeatability of the method depends on the muscle and contraction condition being evaluated, and in general, is higher following an MVC.
2009 John Wiley & Sons, Ltd.
A vascular term was incorporated into a reference region (RR) model analysis of DCE-MRI data, and its effect on the accuracy of the model in estimating tissue kinetic parameters in a tissue of interest (TOI) was systematically investigated through computer simulations. Errors in the TOI volume transfer constant (K(trans,TOI)) and TOI extravascular extracellular volume (v(e,TOI)) that result when the fractional plasma volume (v(p)) was included in (1) neither region, (2) TOI only (3) both regions were investigated. For nominal values of tumor kinetic parameters (v(e,TOI) = 0.40 and K(trans,TOI) = 0.25 min(-1)), if the vascular term was included in neither region or the TOI only, K(trans,TOI) error was within 20% for 0.03 < v(p,TOI) < 0.10, and v(e,TOI) error was within 20% for the range of v(p,TOI) studied (0.01-0.10). The effects of temporal resolution were shown to be complex, and in some cases errors increased with increasing temporal resolution.
Body fluid regulation is affected by gravity. The primary mechanisms of the etiology of hypovolemia found in simulation studies on earth and after space flight are different. The increased diuresis after increase of central blood volume postulated by Henry Gauer could not be found. Based on recent findings, new hypotheses about fluid volume regulation during space flight have emerged. The reduced blood volume in space is the result of 1) a negative balance of decreased fluid intake and smaller reduction of urine output; 2) fast fluid shifts from the intravascular to interstitial space as the result of lower transmural pressure after reduced compression of all tissue by gravitational forces especially of the thorax cage; and 3) fluid shifts from intravascular to muscle interstitial space because of less muscle tone required to maintain body posture. Additionally, loss of erythrocytes reduces blood volume. The attenuated diuresis during space flight can be explained by increased retention after stress-mediated sympathetic activation during initial phase of space flight, stimulation caused by reduced red cell mass, and activation after fast blood volume contraction. Additionally, the relation between plasma osmolarity and vasopressin release might be disturbed in microgravity.