Science.gov

Sample records for renal clearance concepts

  1. Renal Clearance: Using an Interactive Activity to Visualize a Tricky Concept

    ERIC Educational Resources Information Center

    Hull, Kerry

    2016-01-01

    Renal clearance, the volume of blood cleared of a substance in a particular time period, is commonly recognized as one of the most difficult concepts in physiology. This difficulty may in part reflect the quantitative nature of renal clearance since many life sciences majors perceive that mathematics is irrelevant to their discipline. Students may…

  2. Acute effects of ethanol on renal folate clearance in rats

    SciTech Connect

    Eisenga, B.H.; McMartin, K.E.

    1986-03-05

    Studies of the renal clearance of folic acid in primates demonstrate net reabsorption of folate by a saturable system. The acute administration of ethanol to rats causes a significant increase in urinary folate excretion. The mechanism for this effect is unknown and thus the effect of acute administration of ethanol on the renal absorption and urinary clearance of folate was studied in rats. Folic acid was administered to male Sprague-Dawley rats via continuous intravenous infusion in doses ranging from 3-75 micromoles/kg and renal clearance relative to inulin was determined. The effects of various dose levels of ethanol on these parameters were then determined. At a dose of 15 micromoles/kg, the renal clearance of folate relative to that of inulin was about 0.65 mg/min. At a plasma ethanol level about 100 mg/dl, the renal clearance of folate was not markedly altered. These results suggests that there is net reabsorption of folate in the rat kidney and that moderate doses of ethanol have little effect on renal effect on renal folate reabsorption.

  3. Highly fluorescent resorcinarene cavitand nanocapsules with efficient renal clearance

    NASA Astrophysics Data System (ADS)

    Mahadevan, Kalpana; Patthipati, Venkata Suresh; Han, Sangbum; Swanson, R. James; Whelan, Eoin C.; Osgood, Christopher; Balasubramanian, Ramjee

    2016-08-01

    Nanomaterial based imaging approaches hold substantial promise in addressing current diagnostic and therapeutic challenges. One of the key requirements for the successful clinical translation of nanomaterials is their complete clearance from the body within a reasonable time period preferably via the renal filtration route. This article describes the synthesis of highly fluorescent, water soluble, resorcinarene cavitand nanocapsules and demonstrates their effective renal clearance in mice. The synthesis and functionalization of nanocapsules was accomplished in a one-pot operation via thiol-ene reactions without involving self-assembly, sacrificial templates or emulsions. Water soluble resorcinarene cavitand nanocapsules obtained by this approach were covalently functionalized with Alexa Fluor 750. Highly fluorescent nanocapsules with hydrodynamic diameters of 122 nm and 68 nm and extinction coefficients of 1.3 × 109 M-1 cm-1 and 1.5 × 108 M-1 cm-1 respectively were prepared by varying the reaction conditions. The in vivo biodistribution and clearance of these nanocapsules in mice followed by whole-body fluorescence imaging showed that they were both cleared renally within a few hours. Given the inherent encapsulation capabilities of nanocapsules, the renal clearance demonstrated in this work opens up new opportunities for their theranostic applications especially for targeting and treating the urinary tract.

  4. Highly fluorescent resorcinarene cavitand nanocapsules with efficient renal clearance.

    PubMed

    Mahadevan, Kalpana; Patthipati, Venkata Suresh; Han, Sangbum; Swanson, R James; Whelan, Eoin C; Osgood, Christopher; Balasubramanian, Ramjee

    2016-08-19

    Nanomaterial based imaging approaches hold substantial promise in addressing current diagnostic and therapeutic challenges. One of the key requirements for the successful clinical translation of nanomaterials is their complete clearance from the body within a reasonable time period preferably via the renal filtration route. This article describes the synthesis of highly fluorescent, water soluble, resorcinarene cavitand nanocapsules and demonstrates their effective renal clearance in mice. The synthesis and functionalization of nanocapsules was accomplished in a one-pot operation via thiol-ene reactions without involving self-assembly, sacrificial templates or emulsions. Water soluble resorcinarene cavitand nanocapsules obtained by this approach were covalently functionalized with Alexa Fluor 750. Highly fluorescent nanocapsules with hydrodynamic diameters of 122 nm and 68 nm and extinction coefficients of 1.3 × 10(9) M(-1) cm(-1) and 1.5 × 10(8) M(-1) cm(-1) respectively were prepared by varying the reaction conditions. The in vivo biodistribution and clearance of these nanocapsules in mice followed by whole-body fluorescence imaging showed that they were both cleared renally within a few hours. Given the inherent encapsulation capabilities of nanocapsules, the renal clearance demonstrated in this work opens up new opportunities for their theranostic applications especially for targeting and treating the urinary tract.

  5. Nitrazepam clearance unimpaired in patients with renal insufficiency.

    PubMed

    Ochs, H R; Oberem, U; Greenblatt, D J

    1992-06-01

    Eight patients with mild to moderate renal insufficiency (mean serum creatinine: 2.4 mg/100 ml) and 9 matched control subjects with normal renal function received a single 5-mg oral dose of nitrazepam, cleared mainly by hepatic nitroreduction. Serum nitrazepam levels were determined by gas chromatography during the 72 hours after dosage. Renal patients and controls were well-matched for age (74 vs. 63 years), height (165 vs. 164 cm), and weight (68 vs. 64 kg). Patients and control subjects did not differ significantly in nitrazepam elimination half-life (32 vs. 24 hour) or volume of distribution (4.2 vs. 3.6 liters/kg). Clearance was higher in patients than in controls (4.2 vs. 1.7 ml/min/kg), but the difference was not significant. Nitrazepam free fraction in serum was increased in renal patients (16.8 vs. 15.0% unbound, p = 0.08). After correction for individual values of free fraction, the two groups still did not differ in kinetic variables for nitrazepam. Thus, mild to moderate renal insufficiency does not alter the kinetics of nitrazepam.

  6. Further Characterization of an Active Clearance Control Concept

    NASA Technical Reports Server (NTRS)

    Taylor, Shawn C.; Steinetz, Bruce M.; Oswald, Jay J.

    2007-01-01

    A new test chamber and precision hydraulic actuation system were incorporated into an active clearance control (ACC) test rig at NASA Glenn Research Center. Using the improved system, a fast-acting, mechanically-actuated, ACC concept was evaluated at engine simulated temperatures and pressure differentials up to 1140 F and 120 psig, on the basis of secondary seal leakage and kinematic controllability. During testing, the ACC concept tracked a simulated flight clearance transient profile at 1140 F, 120 psig, with a maximum error of only 0.0012 in. Comparison of average dynamic leakage of the system with average static leakage did not show significant differences between the two operating conditions. Calculated effective clearance values for the rig were approximately 0.0002 in. at 120 psig, well below the industry specified effective clearance threshold of 0.001 in.

  7. High Temperature Evaluation of an Active Clearance Control System Concept

    NASA Technical Reports Server (NTRS)

    Taylor, Shawn C.; Steinetz, Bruce M.; Oswald, Jay J.

    2006-01-01

    A mechanically actuated blade tip clearance control concept was evaluated in a nonrotating test rig to quantify secondary seal leakage at elevated temperatures. These tests were conducted to further investigate the feasibility of actively controlling the clearance between the rotor blade tips and the surrounding shroud seal in the high pressure turbine (HPT) section of a turbine engine. The test environment simulates the state of the back side of the HPT shroud seal with pressure differentials as high as 120 psig and temperatures up to 1000 F. As expected, static secondary seal leakage decreased with increasing temperature. At 1000 F, the test rig's calculated effective clearance (at 120 psig test pressure) was 0.0003 in., well within the industry specified effective clearance goal.

  8. The biodistribution of gold nanoparticles designed for renal clearance

    NASA Astrophysics Data System (ADS)

    Alric, Christophe; Miladi, Imen; Kryza, David; Taleb, Jacqueline; Lux, François; Bazzi, Rana; Billotey, Claire; Janier, Marc; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier

    2013-06-01

    Owing to their tunable optical properties and their high absorption cross-section of X- and γ-ray, gold nanostructures appear as promising agents for remotely controlled therapy. Since the efficiency of cancer therapy is not limited to the eradication of the tumour but rests also on the sparing of healthy tissue, a biodistribution study is required in order to determine whether the behaviour of the nanoparticles after intravenous injection is safe (no accumulation in healthy tissue, no uptake by phagocytic cell-rich organs (liver, spleen) and renal clearance). The biodistribution of Au@DTDTPA nanoparticles which are composed of a gold core and a DTDTPA (dithiolated polyaminocarboxylate) shell can be established by X-ray imaging (owing to the X-ray absorption of the gold core) and by magnetic resonance imaging (MRI) since the DTDTPA shell was designed for the immobilization of paramagnetic gadolinium ions. However scintigraphy appears better suited for a biodistribution study owing to a great sensitivity. The successful immobilization of radioelements (99mTc, 111In) in the DTDTPA shell, instead of gadolinium ions, renders possible the follow up of Au@DTDTPA by scintigraphy which showed that Au@DTDTPA nanoparticles exhibit a safe behaviour after intravenous injection to healthy rats.Owing to their tunable optical properties and their high absorption cross-section of X- and γ-ray, gold nanostructures appear as promising agents for remotely controlled therapy. Since the efficiency of cancer therapy is not limited to the eradication of the tumour but rests also on the sparing of healthy tissue, a biodistribution study is required in order to determine whether the behaviour of the nanoparticles after intravenous injection is safe (no accumulation in healthy tissue, no uptake by phagocytic cell-rich organs (liver, spleen) and renal clearance). The biodistribution of Au@DTDTPA nanoparticles which are composed of a gold core and a DTDTPA (dithiolated polyaminocarboxylate

  9. Augmented renal clearance in critically ill patients: incidence, associated factors and effects on vancomycin treatment

    PubMed Central

    Campassi, María Luz; Gonzalez, María Cecilia; Masevicius, Fabio Daniel; Vazquez, Alejandro Risso; Moseinco, Miriam; Navarro, Noelia Cintia; Previgliano, Luciana; Rubatto, Nahuel Paolo; Benites, Martín Hernán; Estenssoro, Elisa; Dubin, Arnaldo

    2014-01-01

    Objective An augmented renal clearance has been described in some groups of critically ill patients, and it might induce sub-optimal concentrations of drugs eliminated by glomerular filtration, mainly antibiotics. Studies on its occurrence and determinants are lacking. Our goals were to determine the incidence and associated factors of augmented renal clearance and the effects on vancomycin concentrations and dosing in a series of intensive care unit patients. Methods We prospectively studied 363 patients admitted during 1 year to a clinical-surgical intensive care unit. Patients with serum creatinine >1.3mg/dL were excluded. Creatinine clearance was calculated from a 24-hour urine collection. Patients were grouped according to the presence of augmented renal clearance (creatinine clearance >120mL/min/1.73m2), and possible risk factors were analyzed with bivariate and logistic regression analysis. In patients treated with vancomycin, dosage and plasma concentrations were registered. Results Augmented renal clearance was present in 103 patients (28%); they were younger (48±15 versus 65±17 years, p<0.0001), had more frequent obstetric (16 versus 7%, p=0.0006) and trauma admissions (10 versus 3%, p=0.016) and fewer comorbidities. The only independent determinants for the development of augmented renal clearance were age (OR 0.95; p<0.0001; 95%CI 0.93-0.96) and absence of diabetes (OR 0.34; p=0.03; 95%CI 0.12-0.92). Twelve of the 46 patients who received vancomycin had augmented renal clearance and despite higher doses, had lower concentrations. Conclusions In this cohort of critically ill patients, augmented renal clearance was a common finding. Age and absence of diabetes were the only independent determinants. Therefore, younger and previously healthy patients might require larger vancomycin dosing. PMID:24770684

  10. Seal Investigations of an Active Clearance Control System Concept

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M.; Taylor, Shawn; Oswald, Jay; DeCastro, Jonathan A.

    2006-01-01

    In an effort to improve upon current thermal active clearance control methods, a first generation, fast-acting mechanically actuated, active clearance control system has been designed and installed into a non-rotating test rig. In order to harvest the benefit of tighter blade tip clearances, low-leakage seals are required for the actuated carrier segments of the seal shroud to prevent excessive leakage of compressor discharge (P3) cooling air. The test rig was designed and fabricated to facilitate the evaluation of these types of seals, identify seal leakage sources, and test other active clearance control system concepts. The objective of this paper is to present both experimental and analytical investigations into the nature of the face-seal to seal-carrier interface. Finite element analyses were used to examine face seal contact pressures and edge-loading under multiple loading conditions, varied E-seal positions and two new face seal heights. The analyses indicated that moving the E-seal inward radially and reducing face seal height would lead to more uniform contact conditions between the face seal and the carriers. Lab testing confirmed that moving the balance diameter inward radially caused a decrease in overall system leakage.

  11. Evaluation of an Active Clearance Control System Concept

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M.; Lattime, Scott B.; Taylor, Shawn; DeCastro, Jonathan A.; Oswald, Jay; Melcher, Kevin J.

    2005-01-01

    Reducing blade tip clearances through active tip clearance control in the high pressure turbine can lead to significant reductions in emissions and specific fuel consumption as well as dramatic improvements in operating efficiency and increased service life. Current engines employ scheduled cooling of the outer case flanges to reduce high pressure turbine tip clearances during cruise conditions. These systems have relatively slow response and do not use clearance measurement, thereby forcing cold build clearances to set the minimum clearances at extreme operating conditions (e.g., takeoff, reburst) and not allowing cruise clearances to be minimized due to the possibility of throttle transients (e.g., step change in altitude). In an effort to improve upon current thermal methods, a first generation mechanically-actuated active clearance control (ACC) system has been designed and fabricated. The system utilizes independent actuators, a segmented shroud structure, and clearance measurement feedback to provide fast and precise active clearance control throughout engine operation. Ambient temperature performance tests of this first generation ACC system assessed individual seal component leakage rates and both static and dynamic overall system leakage rates. The ability of the nine electric stepper motors to control the position of the seal carriers in both open- and closed-loop control modes for single and multiple cycles was investigated. The ability of the system to follow simulated engine clearance transients in closed-loop mode showed the system was able to track clearances to within a tight tolerance ( 0.001 in. error).

  12. Evaluation of an Active Clearance Control System Concept

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M.; Lattime, Scott B.; DeCastro, Jonathan A.; Oswald, Jay; Melcher, Kevin J.

    2005-01-01

    Reducing blade tip clearances through active tip clearance control in the high pressure turbine can lead to significant reductions in emissions and specific fuel consumption as well as dramatic improvements in operating efficiency and increased service life. Current engines employ scheduled cooling of the outer case flanges to reduce high pressure turbine tip clearances during cruise conditions. These systems have relatively slow response and do not use clearance measurement, thereby forcing cold build clearances to set the minimum clearances at extreme operating conditions (e.g., takeoff, reburst) and not allowing cruise clearances to be minimized due to the possibility of throttle transients (e.g., step change in altitude). In an effort to improve upon current thermal methods, a first generation mechanically-actuated active clearance control (ACC) system has been designed and fabricated. The system utilizes independent actuators, a segmented shroud structure, and clearance measurement feedback to provide fast and precise active clearance control throughout engine operation. Ambient temperature performance tests of this first generation ACC system assessed individual seal component leakage rates and both static and dynamic overall system leakage rates. The ability of the nine electric stepper motors to control the position of the seal carriers in both open- and closed-loop control modes for single and multiple cycles was investigated. The ability of the system to follow simulated engine clearance transients in closed-loop mode showed the system was able to track clearances to within a tight tolerance (0.001 in. error).

  13. Evaluation of circulating levels and renal clearance of natural amino acids in patients with Cushing's disease.

    PubMed

    Faggiano, A; Pivonello, R; Melis, D; Alfieri, R; Filippella, M; Spagnuolo, G; Salvatore, F; Lombardi, G; Colao, A

    2002-02-01

    Although the hypercortisolism-induced impairment of protein homeostasis is object of several studies, a detailed evaluation of the complete amino acid profile of patients with Cushing's syndrome (CS) has never been performed. The aim of the current open transversal controlled study was to evaluate serum and urinary concentrations as well as renal clearance of the complete series of natural amino acids and their relationship with glucose tolerance in patients with Cushing's disease (CD). Twenty patients with CD (10 active and 10 cured) and 20 sex- and age-matched healthy controls entered the study. Measurement of serum and urinary levels of the complete series of natural amino acids was performed in all patients analyzed by cationic exchange high performance liquid cromatography (HPLC) after 2 weeks of a standardized protein intake regimen. The renal clearance (renal excretion rate) of each amino acid was calculated on the basis of the serum and urinary concentrations of creatinine and the specific amino acid. Fasting glucose and insulin levels, glucose and insulin response to standard glucose load, insulinogenic and homeostasis model insulin resistance (Homa-R) indexes were also evaluated and correlated to the circulating levels and renal clearances of each amino acid. Significantly higher serum (p<0.01) and urinary (p<0.05) levels of alanine and cystine, lower serum and higher urinary levels of leucine, isoleucine and valine (p<0.05) and higher renal excretion rates of leucine, isoleucine and valine (p<0.01) were found in patients with active CD than in patients cured from the disease and in controls. No difference was found between cured patients and controls. Creatinine clearance was similar in active and cured patients and in controls. In patients with active CD, urinary cortisol levels were significantly correlated to urinary cystine levels (r=0.85; p<0.01) and renal excretion rate of leucine (r=-0.76; p<0.05), isoleucine (r=-0.76; p<0.05) and valine (r=-0

  14. [Study of age and sex dependance in renal clearances with radioisotopes (author's transl)].

    PubMed

    Schernthaner, G; Erd, W; Ludwig, H; Sinzinger, H; Höfer, R

    1976-03-01

    In 85 patients between 15 and 95 years of age (40 male patients and 45 females) without any signs of renal disease (concentration of serum creatinine below 1,4 mg/100ml, normal diastolic blood pressure and normal urine analysis) a highly significant negative correlation was found between glomerular filtration rate (GFR, determined by 51Cr-EDTA - slope-clearance) and renal plasma flow (RPF, determined by 131J-oJHS-iodinehippuricacid-totalclearance) on one side and age on the other. Beginning with a basic value of 160 ml in males and 144 ml in females for GFR, the average decrease per year was 1,2 ml/1,0 ml respectively. The basis value of RPF was 854 ml for males and 673 ml for females, the decrease per year was 5,4 ml in men and 2,9 ml in women. The importance of physiological diminution of clearance values in elderly patients and its consequences for therapy are discussed. The more exact and methodically simpler 51Cr-EDTA-slope-clearance without urine collection should be used instead of the somewhat inaccurate determination of endogenous creatinine clearance especially in older patients.

  15. Renal tubular receptor imaging with iodine-131-labeled peanut lectin: pharmacokinetics and renal clearance mechanism in animals

    SciTech Connect

    Boniface, G.R.; Suresh, M.R.; Willans, D.J.; Tam, Y.K.; Shysh, A.; Longenecker, B.M.; Noujaim, A.A.

    1986-05-01

    Intravenously administered peanut lectin (PNA), iodinated with /sup 131/I ((/sup 131/I)PNA), is rapidly cleared from the plasma by the kidneys in dogs (clearance (total body) = 17.52 +/- 8.74 ml/min). Dynamic gamma camera renal scintigraphy demonstrated renal accumulation and excretion phases of the (/sup 131/I)PNA renogram in dogs and rabbits (% injection dose-at-peak = 21.8 +/- 3.3% and 19.6 +/- 4.3%, time-to-peak = 44.6 +/- 4.8 min and 37.2 +/- 6.9 min, respectively). Immunoperoxidase staining of kidney sections, following i.v. administered PNA, demonstrated predominant accumulation by the proximal tubules of mice, rabbits, and dogs. The basement membrane was intensely stained at early times p.i. while intracellular and luminal PNA was evident within 1 hr. Urine analysis confirmed the presence of intact (/sup 131/I)PNA in the bladder contents, while protein degradation products, and a small percentage of the free iodide (less than 5%) were noted within 1 hr p.i. The relative proportion of free iodide increased at later times p.i. (greater than 6 hr). A receptor mediated excretion mechanism is proposed for the clearance of PNA and may be useful for the study of renal tubular function.

  16. Sub-10-nm Pd nanosheets with renal clearance for efficient near-infrared photothermal cancer therapy.

    PubMed

    Tang, Shaoheng; Chen, Mei; Zheng, Nanfeng

    2014-08-13

    Efficient renal clearance is of fundamentally important property of nanoparticles for their in vivo biomedical applications. In this work, we report the successful synthesis of ultra-small Pd nanosheets (SPNS) with an average diameter of 4.4 nm and their application in photothermal cancer therapy using a near infrared laser. The ultra-small Pd nanosheets have strong optical absorption in the NIR region and high photothermal conversion efficiency (52.0%) at 808 nm. After being surface-functionalized with reduced glutathione (GSH), the SPNS-GSH was administered to mice to investigate the biodistribution, photothermal efficacy and tumor ablation in vivo. The in vivo photothermal therapy studies clearly demonstrate that surface modification with GSH allows the nanosheets to exhibit prolonged blood circulation and thus high accumulation in tumors. Upon 808 nm NIR irradiation, the tumors can be completely ablated. More importantly, with the size below the renal filtration limit (<10 nm), the GSHylated Pd nanosheets can be nicely cleared from body through the renal excretion route and into urine. Together with the high efficacy of NIR photothermal therapy, the unique renal clearance properties make the ultra-small Pd nanosheets promising for practical use in photothermal cancer therapy.

  17. Comparison between the effects of indapamide and hydrochlorothiazide on creatinine clearance in patients with impaired renal function and hypertension.

    PubMed

    Madkour, H; Gadallah, M; Riveline, B; Plante, G E; Massry, S G

    1995-01-01

    The long-term effects of indapamide or hydrochlorothiazide on blood pressure and renal function were examined in patients with impaired renal function and moderate hypertension. Both drugs controlled hypertension and blood pressure remained normal during the 2 years of the study. Despite this comparable control of hypertension, indapamide therapy was associated with a 28.5 +/- 4.4% increase in creatinine clearance while treatment with hydrochlorothiazide was associated with a 17.4 +/- 3.0% decrease in creatinine clearance. The results of the study indicate that indapamide is superior to hydrochlorothiazide in the treatment of patients with impaired renal function and moderate hypertension.

  18. Gram-scale synthesis of coordination polymer nanodots with renal clearance properties for cancer theranostic applications

    NASA Astrophysics Data System (ADS)

    Liu, Fuyao; He, Xiuxia; Chen, Hongda; Zhang, Junping; Zhang, Huimao; Wang, Zhenxin

    2015-08-01

    An ultrasmall hydrodynamic diameter is a critical factor for the renal clearance of nanoparticles from the body within a reasonable timescale. However, the integration of diagnostic and therapeutic components into a single ultrasmall nanoparticle remains challenging. In this study, pH-activated nanodots (termed Fe-CPNDs) composed of coordination polymers were synthesized via a simple and scalable method based on coordination reactions among Fe3+, gallic acid and poly(vinylpyrrolidone) at ambient conditions. The Fe-CPNDs exhibited ultrasmall (5.3 nm) hydrodynamic diameters and electrically neutral surfaces. The Fe-CPNDs also exhibited pH-activatable magnetic resonance imaging contrast and outstanding photothermal performance. The features of Fe-CPNDs greatly increased the tumour-imaging sensitivity and facilitated renal clearance after injection in animal models in vivo. Magnetic resonance imaging-guided photothermal therapy using Fe-CPNDs completely suppressed tumour growth. These findings demonstrate that Fe-CPNDs constitute a new class of renal clearable nanomedicine for photothermal therapy and molecular imaging.

  19. Renal Drug Dosage Adjustment According to Estimated Creatinine Clearance in Hospitalized Patients With Heart Failure.

    PubMed

    Altunbas, Gokhan; Yazc, Mehmet; Solak, Yalcin; Gul, Enes E; Kayrak, Mehmet; Kaya, Zeynettin; Akilli, Hakan; Aribas, Alpay; Gaipov, Abduzhappar; Yazc, Raziye; Ozdemir, Kurtulus

    2016-01-01

    It is of clinical importance to determine creatinine clearance and adjust doses of prescribed drugs accordingly in patients with heart failure to prevent untoward effects. There is a scarcity of studies in the literature investigating this issue particularly in patients with heart failure, in whom many have impaired kidney function. The purpose of this study was to determine the degree of awareness of medication prescription as to creatinine clearance in patients hospitalized with heart failure. Patients hospitalized with a diagnosis of heart failure were retrospectively evaluated. Among screened charts, patients with left ventricular ejection fraction <40% and an estimated glomerular filtration rate (eGFR) of ≤50 mL/min were included in the analysis. The medications and respective doses prescribed at discharge were recorded. Medications requiring renal dose adjustment were determined and evaluated for appropriate dosing according to eGFR. A total of 388 patients with concomitant heart failure and renal dysfunction were included in the study. The total number of prescribed medications was 2808 and 48.3% (1357 medications) required renal dose adjustment. Of the 1357 medications, 12.6% (171 medications) were found to be inappropriately prescribed according to eGFR. The most common inappropriately prescribed medications were famotidine, metformin, perindopril, and ramipril. A significant portion of medications used in heart failure requires dose adjustment. Our results showed that in a typical cohort of patients with heart failure, many drugs are prescribed at inappropriately high doses according to creatinine clearance. Awareness should be increased among physicians caring for patients with heart failure to prevent adverse events related to medications.

  20. Megalin and cubilin are endocytic receptors involved in renal clearance of hemoglobin.

    PubMed

    Gburek, Jakub; Verroust, Pierre J; Willnow, Thomas E; Fyfe, John C; Nowacki, Wojciech; Jacobsen, Christian; Moestrup, Søren K; Christensen, Erik I

    2002-02-01

    The kidney is the main site of hemoglobin clearance and degradation in conditions of severe hemolysis. Herein it is reported that megalin and cubilin, two epithelial endocytic receptors, mediate the uptake of hemoglobin in renal proximal tubules. Both receptors were purified by use of hemoglobin-Sepharose affinity chromatography of solubilized renal brush-border membranes. Apparent dissociation constants of 1.7 microM for megalin and 4.1 microM for cubilin were determined by surface plasmon resonance analysis. The binding was calcium dependent in both cases. Uptake of fluorescence-labeled hemoglobin by BN-16 cells was inhibited by anti-megalin and anti-cubilin antibodies as well as by receptor-associated protein, a chaperone for LDL-receptor family proteins. Partial inhibition by myoglobin was observed, whereas bovine serum albumin, intrinsic factor-cobalamin complexes, and beta2-microglobulin did not affect the uptake. By use of immunohistochemistry, it was demonstrated that uptake of hemoglobin in proximal tubules of rat, mouse, and dog kidneys occurs under physiologic conditions. Studies on normal and megalin knockout mouse kidney sections showed that megalin is responsible for physiologic clearance of hemoglobin. Labeling intensities in kidneys from normal and cubilin-malexpressing dogs were similar, which suggests that, in the normal state, the role of cubilin in uptake of hemoglobin is rather limited. However, cubilin is likely to assist hemoglobin endocytosis in settings of hemoglobinuria. In conclusion, the study provides a molecular explanation for long-standing observations of hemoglobin uptake in renal proximal tubules that involve the endocytic receptors megalin and cubilin. The findings may prove to be essential for further research on the pathophysiology of hemoglobinuric acute renal failure and proteinuria-associated tubulointerstitial nephritis.

  1. Preliminary Diffusive Clearance of Silicon Nanopore Membranes in a Parallel Plate Configuration for Renal Replacement Therapy

    PubMed Central

    Kim, Steven; Heller, James; Iqbal, Zohora; Kant, Rishi; Kim, Eun Jung; Durack, Jeremy; Saeed, Maythem; Do, Loi; Hetts, Steven; Wilson, Mark; Brakeman, Paul; Fissell, William H.; Roy, Shuvo

    2015-01-01

    Silicon nanopore membranes (SNM) with compact geometry and uniform pore size distribution have demonstrated a remarkable capacity for hemofiltration. These advantages could potentially be used for hemodialysis. Here we present an initial evaluation of the SNM’s mechanical robustness, diffusive clearance, and hemocompatibility in a parallel plate configuration. Mechanical robustness of the SNM was demonstrated by exposing membranes to high flows (200ml/min) and pressures (1,448mmHg). Diffusive clearance was performed in an albumin solution and whole blood with blood and dialysate flow rates of 25ml/min. Hemocompatibility was evaluated using scanning electron microscopy and immunohistochemistry after 4-hours in an extra-corporeal porcine model. The pressure drop across the flow cell was 4.6mmHg at 200ml/min. Mechanical testing showed that SNM could withstand up to 775.7mmHg without fracture. Urea clearance did not show an appreciable decline in blood versus albumin solution. Extra-corporeal studies showed blood was successfully driven via the arterial-venous pressure differential without thrombus formation. Bare silicon showed increased cell adhesion with a 4.1 fold increase and 1.8 fold increase over polyethylene-glycol (PEG)-coated surfaces for tissue plasminogen factor (t-PA) and platelet adhesion (CD-41), respectively. These initial results warrant further design and development of a fully scaled SNM-based parallel plate dialyzer for renal replacement therapy. PMID:26692401

  2. Faster non-renal clearance of metoprolol in streptozotocin-induced diabetes mellitus rats.

    PubMed

    Lee, Unji; Lee, Inchul; Lee, Byung K; Kang, Hee E

    2013-11-20

    Metoprolol is a selective β1-adrenergic receptor antagonist metabolized by hepatic cytochrome P450s (CYPs). In this study, we evaluated pharmacokinetic changes following intravenous (i.v.) and oral metoprolol in rats with diabetes mellitus induced by streptozotocin (DMIS). Metoprolol has an intermediate hepatic extraction ratio in rats (0.586-0.617), and it is assumed that the liver is exclusively responsible for metoprolol metabolism. Thus, the hepatic clearance, CL(H) (the non-renal clearance, CL(NR)) of metoprolol depends on the hepatic blood flow rate (Q(H)), the free fraction in plasma (f(p)), and in vitro hepatic intrinsic clearance, CL(int). After i.v. administration of 1.5 mg/kg metoprolol to DMIS rats, its CLNR was 40.9% faster than control animals. This could be due to a significantly faster QH because hepatic CL(int) and fp were comparable between the two groups of rats due to unchanged hepatic CYP2D activity. After oral administration of 1.5 mg/kg metoprolol to DMIS rats, gastrointestinal absorption was >99% of the oral dose for both groups, while the area under the curve (AUC) was 27.9% smaller, which could be caused by the greater hepatic metabolism seen in the i.v. study. These findings have potential therapeutic implications, assuming that the DMIS rats qualitatively reflect similar changes in patients with diabetes.

  3. Plasma Creatinine Clearance in the Dog

    ERIC Educational Resources Information Center

    Frazier, Loy W.

    1977-01-01

    Lists materials and methods for an experiment that demonstrates the concept of glomerular filtration rate (GFR) using anesthesized dogs. In the dog, GFR is equivalent to the renal plasma clearance of exogenous creatinine. (CS)

  4. Postnatal development of renal function: micropuncture and clearance studies in the dog

    PubMed Central

    Horster, Michael; Valtin, Heinz

    1971-01-01

    Postnatal renal development was studied in dogs between 2 and 77 days. Single, superficial nephrons were evaluated by micropuncture, concurrently with measurements of total renal function and morphometric analyses in the same animals. Glomerular filtration rate for the entire kidney increased linearly from 0.13 ml/min per g kidney weight at 2 days to 0.91 at 77 days. Extraction of p-aminohippurate increased from about 20 to 80%, and renal plasma flow per g kidney weight, measured as Cpah/Epah, increased threefold during the same period. Filtration fraction increased to the mature value during the first half of the postnatal period studied. The clearance of urea per unit of renal mass increased with age, whereas the fraction of filtered urea reabsorbed declined during the early part of the postnatal period. The pattern of fractional urea reabsorption may be due mainly to increased medullary recycling of urea and to a rise in the reabsorption of water from the medullary collecting duct. Urine osmolality was higher than plasma from birth onward and rose with age. Osmolal equality of collecting duct fluid and medullary interstitium reflected mature vasopressin (ADH)-induced water permeability. The rise in urinary concentration was predominantly due to increasing medullary sequestration of urea. Glomerular filtration rate of the superficial nephron increased from 3.2 nl/min at 21 days, when subcapsular nephrons were uniformly patent, to 23.1 at 77 days. Despite this rise in filtered load, fractional reabsorption of sodium and water in superficial proximal tubules was constant and at the mature level from the onset of intratubular perfusion. Changes in arterial plasma protein concentration, in filtration fraction, and in the hydrostatic pressure gradient between proximal tubule and peritubular capillary may interact to maintain glomerulotubular balance. The data, together with results of an accompanying morphological study, demonstrate a sequence of coordinated changes

  5. Quantitative Prediction of Human Renal Clearance and Drug-Drug Interactions of Organic Anion Transporter Substrates Using In Vitro Transport Data: A Relative Activity Factor Approach.

    PubMed

    Mathialagan, Sumathy; Piotrowski, Mary A; Tess, David A; Feng, Bo; Litchfield, John; Varma, Manthena V

    2017-04-01

    Organic anion transporters (OATs) are important in the renal secretion, and thus, the clearance, of many drugs; and their functional change can result in pharmacokinetic variability. In this study, we applied transport rates measured in vitro using OAT-transfected human embryonic kidney cells to predict human renal secretory and total renal clearance of 31 diverse drugs. Selective substrates to OAT1 (tenofovir), OAT2 (acyclovir and ganciclovir), and OAT3 (benzylpenicillin, oseltamivir acid) were used to obtain relative activity factors (RAFs) for these individual transporters by relating in vitro transport clearance (after physiologic scaling) to in vivo secretory clearance. Using the estimated RAFs (0.64, 7.3, and 4.1, respectively, for OAT1, OAT2, and OAT3, respectively) and the in vitro active clearances, renal secretory clearance and total renal clearance were predicted with average fold errors (AFEs) of 1.89 and 1.40, respectively. The results show that OAT3-mediated transport play a predominant role in renal secretion for 22 of the 31 drugs evaluated. This mechanistic static approach was further applied to quantitatively predict renal drug-drug interactions (AFE ∼1.6) of the substrate drugs with probenecid, a clinical probe OAT inhibitor. In conclusion, the proposed in vitro-in vivo extrapolation approach is the first comprehensive attempt toward mechanistic modeling of renal secretory clearance based on routinely employed in vitro cell models.

  6. Augmented renal clearance in critically ill patients: etiology, definition and implications for beta-lactam dose optimization.

    PubMed

    Sime, Fekade Bruck; Udy, Andrew A; Roberts, Jason A

    2015-10-01

    The renal clearance of antibiotics may be elevated in some critically ill patients. This paper reviews this recently described phenomenon, referred to as augmented renal clearance (ARC). ARC is considered to be driven by pathophysiological elevation of glomerular filtration, and is defined as a creatinine clearance >130mL/min/173m(2). This in turn promotes very low antibiotic concentrations. This effect may lead to adverse clinical outcomes, particularly with beta-lactam antibiotics, as they require prolonged exposure for optimal antibacterial activity. The use of extended or continuous infusions is an effective strategy to improve exposure. However, because the effect of ARC is potentially quite variable, regular therapeutic drug monitoring (TDM) may be necessary to ensure all patients achieve effective concentrations.

  7. [The equivalent renal urea clearance. Its relationship with mortality in chronic hemodialysed patients].

    PubMed

    Barreneche, M; Carreras, R; Leanza, H J; Najún Zarazaga, C J

    1999-01-01

    The Equivalent Renal Urea Clearance (EKR) integrates the residual renal function (KR) and the dialysis dose (Kt/V). The present study was performed with these objectives: to calculate EKR in our hemodialysis (HD) patients during a three year follow up, to define its relationship with mortality and to compare its importance as a risk factor among others and to calculate actuarial survival. We analyzed 267 chronic HD patients. We measured Kt/V single pool, TACu, albumin, creatinine, hemoglobin and HD time and we calculated KR, EKR, KRc and EKRc (the last two corrected for V* 401--to compare clearances of different size patients). The EKRc median was 14.20 ml/min and it was taken as cut off point. The mortality OR was 2.17. The multivariated analysis showed, as independent mortality predictors, the albumin (the most significant), the EKRc and the HD time. The actuarial survival of EKRc, Kt/V and albumin showed marked similarity of their curves. The significant differences between the predictor curves began on the 2nd year of HD, for albumin they began in levels lesser than 3.5 g/dl and higher than 3.4 g/dl. Therefore, we consider that the best advantage of EKRc, compared to other parameters derived from the urea kinetics model, was the possibility to valuate the weekly HD adequation (once, twice or three times a week) and this, depending on the KR and the Kt/V of each HD treatment. Besides, the EKRc could also be used as adequacy criterion in CAPD considering daily Kt/V so that we could employ EKRc as adequacy parameter for both replacement therapies.

  8. Augmented renal clearance in septic patients and implications for vancomycin optimisation.

    PubMed

    Baptista, João Pedro; Sousa, Eduardo; Martins, Paulo J; Pimentel, Jorge M

    2012-05-01

    The aim of this study was to evaluate the effect of augmented renal clearance (ARC) on vancomycin serum concentrations in critically ill patients. This prospective, single-centre, observational, cohort study included 93 consecutive, critically ill septic patients who started treatment that included vancomycin by continuous infusion, admitted over a 2-year period (March 2006 to February 2008). ARC was defined as 24-h creatinine clearance (CL(Cr))>130 mL/min/1.73 m(2). Two groups were analysed: Group A, 56 patients with a CL(Cr)≤130 mL/min/1.73 m(2); and Group B, 37 patients with a CL(Cr)>130 mL/min/1.73 m(2). Vancomycin therapeutic levels were assessed on the first 3 days of treatment (D(1), D(2) and D(3)). Serum vancomycin levels on D(1), D(2) and D(3), respectively, were 13.1, 16.6 and 18.6 μmol/L for Group A and 9.7, 11.7 and 13.8 μmol/L for Group B (P<0.05 per day). The correlation between CL(Cr) and serum vancomycin on D(1) was -0.57 (P<0.001). ARC was strongly associated with subtherapeutic vancomycin serum concentrations on the first 3 days of treatment.

  9. PAH clearance after renal ischemia and reperfusion is a function of impaired expression of basolateral Oat1 and Oat3.

    PubMed

    Bischoff, Ariane; Bucher, Michael; Gekle, Michael; Sauvant, Christoph

    2014-02-01

    Determination of renal plasma flow (RPF) by para-aminohippurate (PAH) clearance leads to gross underestimation of this respective parameter due to impaired renal extraction of PAH after renal ischemia and reperfusion injury. However, no mechanistic explanation for this phenomenon is available. Based on our own previous studies we hypothesized that this may be due to impairment of expression of the basolateral rate limiting organic anion transporters Oat1 and Oat3. Thus, we investigated this phenomenon in a rat model of renal ischemia and reperfusion by determining PAH clearance, PAH extraction, PAH net secretion, and the expression of rOat1 and rOat3. PAH extraction was seriously impaired after ischemia and reperfusion which led to a threefold underestimation of RPF when PAH extraction ratio was not considered. PAH extraction directly correlated with the expression of basolateral Oat1 and Oat3. Tubular PAH secretion directly correlated with PAH extraction. Consequently, our data offer an explanation for impaired renal PAH extraction by reduced expression of the rate limiting basolateral organic anion transporters Oat1 and Oat3. Moreover, we show that determination of PAH net secretion is suitable to correct PAH clearance for impaired extraction after ischemia and reperfusion in order to get valid results for RPF.

  10. Reproducibility of the measurements of creatinine clearance in patients with a stable renal function.

    PubMed

    Wieczorowska-Tobis, Katarzyna; Guzik, Przemyslaw; Niemir, Zofia; Breborowicz, Andrzej; Oreopoulos, Dimitrios G

    2004-01-01

    In everyday practice the measurement of creatinine clearance (CCr) is used for the evaluation of the renal function. Since large body of evidence points to the inaccuracy of this test, we decided to check whether a repeated measurement of CCr might improve the assessment of the glomerular filtration rate. The study comprised 233 subjects, 105 females and 128 males, aged 22-80 years (mean age: 50.8 +/- 12.8 years) with the history of renal stones and a stable renal function, e.g. without changes in plasma creatinine. In every patient CCr was measured twice. Thereafter, all studied subjects were sorted by the increasing absolute values of the difference between two measurements of CCr e.g. as the difference between two measurements of CCr with omitted sign (absDCCr). Then, they were divided into 3 groups corresponding to the tertiles of absDCCr (tertile = 1/3). When the two values of CCr were compared among all patients, the mean difference between them (DCCr) was only 1.51 +/- 26.86 ml/min. The values of the individual DCCr varied, however, from -122.2. ml/min to 69.3 ml/min. As far as sex, age and height were concerned, there were no differences between the groups. However, weight was lower in group A (first tertile) vs. group B (second tertile) (p < 0.05). Also, BMI was lower in the group A vs. both group B and C (p < 0.05 and p < 0.01; respectively). In conclusion, our study points out to a poor reproducibility of the measurements of CCr in non-hospitalized subjects, especially in those with the high BMI.

  11. Prednisone lowers serum uric acid levels in patients with decompensated heart failure by increasing renal uric acid clearance.

    PubMed

    Liu, Chao; Zhen, Yuzhi; Zhao, Qingzhen; Zhai, Jian-Long; Liu, Kunshen; Zhang, Jian-Xin

    2016-07-01

    Clinical studies have shown that large doses of prednisone could lower serum uric acid (SUA) in patients with decompensated heart failure (HF); however, the optimal dose of prednisone and underlying mechanisms are unknown. Thirty-eight patients with decompensated HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/day, n = 8), medium-dose (30 mg/day, n = 10), or high-dose prednisone (60 mg/day, n = 10), for 10 days. At the end of the study, only high-dose prednisone significantly reduced SUA, whereas low- and medium-dose prednisone and standard HF care had no effect on SUA. The reduction in SUA in high-dose prednisone groups was associated with a significant increase in renal uric acid clearance. In conclusion, prednisone can reduce SUA levels by increasing renal uric acid clearance in patients with decompensated HF.

  12. The use of specific radioimmunoassays to determine the renal clearance rates of estrone and 17 beta-estradiol during the menstrual cycle.

    PubMed

    Wright, K; Collins, D C; Preedy, J R

    1978-11-01

    Specific RIAs requiring ether extraction only were established for estrone and 17 beta-estradiol both in plasma and in urine from the nonpregnant female. These assays were used to measure the renal clearance rates of estrone and of 17 beta-estradiol in eight ambulatory women in the follicular and in the luteal phases of the menstrual cycle. The mean (+/-SE) for the renal clearance rate of estrone was 0.71 +/- 0.058 ml/min in the follicular phase and 1.26 +/- 0.35 ml/min in the luteal phase. The mean (+/-SE) renal clearance rate of 17 beta-estradiol was 0.44 +/- 0.055 ml/min in the follicular phase and 0.29 +/- 0.043 ml/min in the luteal phase. There was no significant difference in the renal clearance rates of either estrone or of 17 beta-estradiol between the follicular and luteal phases of the cycle. The renal clearances of estrone and 17 beta-estradiol were highly correlated (r = 0.84; P less than 0.01). The renal clearance rate of estrone was significantly greater than that of 17 beta-estradiol in both phases of the cycle (P less than 0.01).

  13. Cancer Theranostic Nanoparticles Self-Assembled from Amphiphilic Small Molecules with Equilibrium Shift-Induced Renal Clearance

    PubMed Central

    Ma, Yuan; Mou, Quanbing; Sun, Mo; Yu, Chunyang; Li, Jianqi; Huang, Xiaohua; Zhu, Xinyuan; Yan, Deyue; Shen, Jian

    2016-01-01

    Nano drug delivery systems have emerged as promising candidates for cancer therapy, whereas their uncertainly complete elimination from the body within specific timescales restricts their clinical translation. Compared with hepatic clearance of nanoparticles, renal excretion of small molecules is preferred to minimize the agent-induced toxicity. Herein, we construct in vivo renal-clearable nanoparticles, which are self-assembled from amphiphilic small molecules holding the capabilities of magnetic resonance imaging (MRI) and chemotherapy. The assembled nanoparticles can accumulate in tumor tissues for their nano-characteristics, while the small molecules dismantled from the nanoparticles can be efficiently cleared by kidneys. The renal-clearable nanoparticles exhibit excellent tumor-inhibition performance as well as low side effects and negligible chronic toxicity. These results demonstrate a potential strategy for small molecular nano drug delivery systems with obvious anticancer effect and low-toxic metabolism pathway for clinical applications. PMID:27446502

  14. The clearance concept with special reference to determination of glomerular filtration rate in patients with fluid retention.

    PubMed

    Henriksen, Ulrik L; Henriksen, Jens H

    2015-01-01

    In subjects without fluid retention, the total plasma clearance of a renal filtration indicator (inulin, (99m) Tc-DTPA, (51) Cr-EDTA) is close to the urinary plasma clearance. Conversely, in patients with fluid retention (oedema, pleural effusions, ascites), there is a substantial discrepancy between the total plasma clearance and the urinary plasma clearance. This is owing to delayed indicator distribution to smaller or larger parts of the interstitial space, which in patients with ascites may simulate a peritoneal dialysator. In patients with fluid retention, urinary plasma clearance should be assessed to obtain a correct measurement of the glomerular filtration rate (GFR). In theory, total plasma clearance with late samples (24-h, 48-h) may be applied in patients with fluid retention, but validation hereof has not been performed. Until such studies are completed, it is recommended that patients with fluid retention have their GFR measured by a urinary plasma clearance technique with controlled quantitative urinary sampling within a few hours after indicator injection.

  15. Test Rig for Evaluating Active Turbine Blade Tip Clearance Control Concepts

    NASA Technical Reports Server (NTRS)

    Lattime, Scott B.; Steinetz, Bruce M.; Robbie, Malcolm G.; Erker, Arthur H.

    2004-01-01

    The objectives of the research presented in this viewgraph presentation are to 1) Design a mechanical ACC system for HPT tip seal clearance management; 2) Design a test rig to evaluate ACC system concepts. We have focused our efforts on designing mechanical ACC systems that articulate the seal shroud via mechanical linkages connected to actuators that reside outside the extreme environment of the HPT. We opted for this style of design due to a lack of high temperature/low profile actuators that are presently available. We have also selected multiple hydraulic actuators for this first generation ACC system. Fuel-draulic actuators are already a well established technology.

  16. Clearance (née Rowland) concepts: a downdate and an update.

    PubMed

    Benet, Leslie Z

    2010-12-01

    A number of experimental observations in the late 1960s, early 1970s could not be explained by the pharmacokinetic theory available at that time. For example rats receiving phenobarbital as an enzyme inducing agent exhibited increased elimination of phenylbutazone in vitro in liver microsomes and in vivo in whole animals compared to that observed in non-induced animals. However, for desipramine, although phenobarbital increased elimination in microsomes, no change in plasma disappearance was noted in vivo for this drug between rats induced with phenobarbital and control rats. Similar in vitro-in vivo discordancies were seen with changes in protein binding. The introduction of clearance concepts in the early 1970s by Professor Rowland and others provided the scientific rationale for these apparently contradictory findings and the recognition that clearance, not half-life, was the measure of the body's ability to eliminate drugs and most importantly that changes in pathology and physiology could be correlated with measures of clearance. Up to that time half-life was well recognized in terms of basic chemical principles as an appropriate measure of the rate of elimination and reflective of changes in the rate of elimination. The difference between chemistry and pharmacokinetics, however, is that in chemistry the volume in which the reaction occurs does not change. In contrast, in pharmacokinetics, disease states and differences in physiology can change the space available in which the drug may distribute in the body. Thus, it was necessary to develop a pharmacokinetic measure of volume that was independent of elimination, i.e., V(ss). Now, the relationship between V(ss) and clearance led to a unique measure of time of drug in the body, the mean residence time. Although this parameter is calculated in all PK programs, very few pharmaceutical scientists know how it can be useful. Very recently, we have shown that the concepts of accumulation, prediction of which is the

  17. Lactate clearance is associated with mortality in septic patients with acute kidney injury requiring continuous renal replacement therapy

    PubMed Central

    Passos, Rogério da Hora; Ramos, Joao Gabriel Rosa; Gobatto, André; Mendonça, Evandro José Bulhões; Miranda, Eva Alves; Dutra, Fábio Ricardo Dantas; Coelho, Maria Fernanda R; Pedroza, Andrea C; Batista, Paulo Benigno Pena; Dutra, Margarida Maria Dantas

    2016-01-01

    Abstract The aim of the study was to assess the clinical utility of lactate measured at different time points to predict mortality at 48 hours and 28 days in septic patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). Consecutive critically ill patients with septic AKI requiring CRRT were prospectively studied. Variables were collected at initiation of CRRT and 24 hours later. In total, 186 patients were analyzed. Overall mortality at 48 hours was 28% and at 28 days was 69%. Initial lactate, lactate at 24 hours and the proportion of patients with a lactate clearance superior to 10% were different between survivors at 28 days [2.0 mmol/L, 1.95 mmol/L and 18/45 (40%)] and nonsurvivors [3.46 mmol, 4.66 mmol, and 18/94 (19%)]. Multivariate analysis demonstrated that lactate at 24 hours and lactate clearance, but not initial lactate, were independently associated to mortality. Area under the ROC curves for 28-day mortality was 0.635 for initial lactate; 0.828 for lactate at 24 hours and 0.701 for lactate clearance. Lactate clearance and lactate after 24 hours of CRRT, but not initial lactate, were independently associated with mortality in septic AKI patients undergoing CRRT. Serial lactate measurements may be useful prognostic markers than initial lactate in these patients. PMID:27749594

  18. Filterable plasma concentration, glomerular filtration, tubular balance, and renal clearance of heavy metals and organic substances in metal workers

    SciTech Connect

    Araki, S.; Aono, H.; Yokoyama, K.; Murata, K.

    1986-07-01

    To estimate filterable plasma concentration (FPx), glomerular filtration, tubular balance, and renal clearance of heavy metals and organic substances, the authors examined the regressions of the 24-hr urinary excretion on glomerular filtration rate (GFR, 24-hr endogenous creatinine (Cn) clearance) in 19 gun-metal foundry workers with blood lead (Pb) concentrations of 25-59 micrograms/dl. It was estimated that the proportion of FPx to total plasma concentration was on average 15, 7, 3, 0.6, 0.06, and 0.008% for Pb, cadmium (Cd), manganese (Mn), zinc (Zn), chromium (Cr), and copper (Cu), respectively. The estimated FPx value was 2.8 X 10(2), 4, 0.08, and 2.8 X 10(4) micrograms/dl for hippuric acid (HA), delta-aminolevulinic acid (ALA), coproporphyrin (CP), and total urinary solutes (TUS), respectively. The estimated glomerular filtration was significantly greater than the zero level for all substances but inorganic mercury (Hg). Similarly, the estimated net tubular secretion was significantly greater than the zero level for Cr, Cu, and TUS; the net tubular reabsorption was significantly greater than the zero level for Pb, ALA, and CP. The renal clearance of ''filterable'' plasma substance was significantly greater than GFR for Cr, Cu, and TUS and was significantly smaller for Pb, ALA, and CP. Thus the renal excretory mechanisms of substances were classified into four major categories: glomerular filtration for Cd, Mn, Zn, HA, and Cn; glomerular filtration and net tubular secretion for Cr, Cu, and TUS; glomerular filtration and net tubular reabsorption for Pb, ALA, and CP; and no glomerular filtration, i.e., suspected tubular secretion, for Hg.

  19. Measurement of glomerular filtration rate, renal plasma flow, and endogenous creatinine clearance in cheetahs (Acinonyx jubatus jubatus).

    PubMed

    Holder, Erin Hall; Citino, Scott B; Businga, Nancy; Cartier, Leslie; Brown, Scott A

    2004-06-01

    Glomerular filtration rate (GFR), renal plasma flow (RPF), and the endogenous creatinine clearance (CCr) rate were determined in 13 captive cheetahs, Acinonyx jubatus jubatus (seven females and six males, 1.5-7.5 yr of age, x = 5.02 yr), during general anesthesia with Telazol and isoflurane by measuring the urinary clearances of inulin, para-aminohipppuric acid, and endogenous creatinine, respectively. Methods to determine GFR, RPF, and endogenous CCr in captive cheetahs were evaluated, and the relationship between GFR and CCr for this species was determined. The GFR and the RPF were stable during the procedure, with mean values of 1.59+/-0.17 ml/min/kg body weight and 5.12+/-1.15 ml/min/kg body weight, respectively. Although the mean value for CCr (1.47+/-0.20 ml/min/kg body weight) was significantly less than the corresponding value for GFR, the mean difference (0.11+/-0.02 ml/min/kg weight) between the two measurements was slight, and the values were highly correlated (R2 = 0.928; P < 0.0001). The measurement of CCr in cheetahs should provide a reliable estimate of GFR, facilitating the early detection of renal disease in this species.

  20. Augmented renal clearance implies a need for increased amoxicillin-clavulanic acid dosing in critically ill children.

    PubMed

    De Cock, Pieter A J G; Standing, Joseph F; Barker, Charlotte I S; de Jaeger, Annick; Dhont, Evelyn; Carlier, Mieke; Verstraete, Alain G; Delanghe, Joris R; Robays, Hugo; De Paepe, Peter

    2015-11-01

    There is little data available to guide amoxicillin-clavulanic acid dosing in critically ill children. The primary objective of this study was to investigate the pharmacokinetics of both compounds in this pediatric subpopulation. Patients admitted to the pediatric intensive care unit (ICU) in whom intravenous amoxicillin-clavulanic acid was indicated (25 to 35 mg/kg of body weight every 6 h) were enrolled. Population pharmacokinetic analysis was conducted, and the clinical outcome was documented. A total of 325 and 151 blood samples were collected from 50 patients (median age, 2.58 years; age range, 1 month to 15 years) treated with amoxicillin and clavulanic acid, respectively. A three-compartment model for amoxicillin and a two-compartment model for clavulanic acid best described the data, in which allometric weight scaling and maturation functions were added a priori to scale for size and age. In addition, plasma cystatin C and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanic acid were 17.97 liters/h/70 kg and 12.20 liters/h/70 kg, respectively. In 32% of the treated patients, amoxicillin-clavulanic acid therapy was stopped prematurely due to clinical failure, and the patient was switched to broader-spectrum antibiotic treatment. Monte Carlo simulations demonstrated that four-hourly dosing of 25 mg/kg was required to achieve the therapeutic target for both amoxicillin and clavulanic acid. For patients with augmented renal function, a 1-h infusion was preferable to bolus dosing. Current published dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks clinical failure in critically ill children, and therefore need to be updated. (This study has been registered at Clinicaltrials.gov as an observational study [NCT02456974].).

  1. Augmented Renal Clearance Implies a Need for Increased Amoxicillin-Clavulanic Acid Dosing in Critically Ill Children

    PubMed Central

    Standing, Joseph F.; Barker, Charlotte I. S.; de Jaeger, Annick; Dhont, Evelyn; Carlier, Mieke; Verstraete, Alain G.; Delanghe, Joris R.; Robays, Hugo; De Paepe, Peter

    2015-01-01

    There is little data available to guide amoxicillin-clavulanic acid dosing in critically ill children. The primary objective of this study was to investigate the pharmacokinetics of both compounds in this pediatric subpopulation. Patients admitted to the pediatric intensive care unit (ICU) in whom intravenous amoxicillin-clavulanic acid was indicated (25 to 35 mg/kg of body weight every 6 h) were enrolled. Population pharmacokinetic analysis was conducted, and the clinical outcome was documented. A total of 325 and 151 blood samples were collected from 50 patients (median age, 2.58 years; age range, 1 month to 15 years) treated with amoxicillin and clavulanic acid, respectively. A three-compartment model for amoxicillin and a two-compartment model for clavulanic acid best described the data, in which allometric weight scaling and maturation functions were added a priori to scale for size and age. In addition, plasma cystatin C and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanic acid were 17.97 liters/h/70 kg and 12.20 liters/h/70 kg, respectively. In 32% of the treated patients, amoxicillin-clavulanic acid therapy was stopped prematurely due to clinical failure, and the patient was switched to broader-spectrum antibiotic treatment. Monte Carlo simulations demonstrated that four-hourly dosing of 25 mg/kg was required to achieve the therapeutic target for both amoxicillin and clavulanic acid. For patients with augmented renal function, a 1-h infusion was preferable to bolus dosing. Current published dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks clinical failure in critically ill children, and therefore need to be updated. (This study has been registered at Clinicaltrials.gov as an observational study [NCT02456974].) PMID:26349821

  2. A comparative study of renal scintigraphy and clearance with technetium-99m-MAG3 and iodine-123-hippurate in patients with renal disorders

    SciTech Connect

    Mueller-Suur, R.B.; Bois-Svensson, I.; Mesko, L. )

    1990-11-01

    The aim of this study was to compare kit prepared technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3) with our routine radiopharmaceutical, iodine-123-hippurate our routine radiopharmaceutical, iodine-123-hippurate ((123I)OIH) for renal dynamic scintigraphy. Seventeen patients with different nephrologic disorders or hypertension were first studied with OIH and then reinvestigated with MAG3 2-8 days later. Renal MAG3 gamma camera images were almost identical with those of OIH except for higher (p less than 0.01) liver-to-background ratios at 20 min postinjection, irrespective of kidney function. Urinary peristalsis was visible longer and more clearly in the MAG3 studies. MAG3 and OIH renograms showed identical relative kidney uptake (r = 0.99), but elimination of MAG3 from the kidneys was slower (p less than 0.01). The plasma clearance of MAG3 was lower than that of OIH, but correlated (r = 0.92) significantly. The plasma distribution volume and content in blood cells was lower (p less than 0.01), but the binding of MAG3 to plasma proteins was higher, 90%, as compared with 74% for OIH, p less than 0.01. Urinary excretion expressed as a percent of the given dose 60 min after injection was the same for the two substances. Thus, there are some significant differences in the renal handling, plasma distribution, and cell penetration between MAG3 and (123I)OIH. MAG3, however, seems to have particular qualifications as a radionuclide for dynamic renal scintigraphy, especially in patients who require acute investigations or in those with low renal function.

  3. Test Rig for Evaluating Active Turbine Blade Tip Clearance Control Concepts

    NASA Technical Reports Server (NTRS)

    Lattime, Scott B.; Steinetz, Bruce M.; Robbie, Malcolm G.

    2003-01-01

    Improved blade tip sealing in the high pressure compressor and high pressure turbine can provide dramatic improvements in specific fuel consumption, time-on-wing, compressor stall margin and engine efficiency as well as increased payload and mission range capabilities of both military and commercial gas turbine engines. The preliminary design of a mechanically actuated active clearance control (ACC) system for turbine blade tip clearance management is presented along with the design of a bench top test rig in which the system is to be evaluated. The ACC system utilizes mechanically actuated seal carrier segments and clearance measurement feedback to provide fast and precise active clearance control throughout engine operation. The purpose of this active clearance control system is to improve upon current case cooling methods. These systems have relatively slow response and do not use clearance measurement, thereby forcing cold build clearances to set the minimum clearances at extreme operating conditions (e.g., takeoff, re-burst) and not allowing cruise clearances to be minimized due to the possibility of throttle transients (e.g., step change in altitude). The active turbine blade tip clearance control system design presented herein will be evaluated to ensure that proper response and positional accuracy is achievable under simulated high-pressure turbine conditions. The test rig will simulate proper seal carrier pressure and temperature loading as well as the magnitudes and rates of blade tip clearance changes of an actual gas turbine engine. The results of these evaluations will be presented in future works.

  4. Test Rig for Active Turbine Blade Tip Clearance Control Concepts: An Update

    NASA Technical Reports Server (NTRS)

    Taylor, Shawn; Steinetz, Bruce; Oswald, Jay; DeCastro, Jonathan; Melcher, Kevin

    2006-01-01

    The objective is to develop and demonstrate a fast-acting active clearance control system to improve turbine engine performance, reduce emissions, and increase service life. System studies have shown the benefits of reducing blade tip clearances in modern turbine engines. Minimizing blade tip clearances throughout the engine will contribute materially to meeting NASA's Ultra-Efficient Engine Technology (UEET) turbine engine project goals. NASA GRC is examining two candidate approaches including rub-avoidance and regeneration which are explained in subsequent slides.

  5. Atherosclerotic renal artery stenosis in the post-CORAL era part 1: the renal penumbra concept and next-generation functional diagnostic imaging.

    PubMed

    Sag, Alan Alper; Inal, Ibrahim; Okcuoglu, John; Rossignol, Patrick; Ortiz, Alberto; Afsar, Baris; Sos, Thomas A; Kanbay, Mehmet

    2016-04-01

    After three neutral trials in which renal artery stenting failed to improve renal function or reduce cardiovascular and renal events, the controversy surrounding diagnosis and treatment of atherosclerotic renal artery stenosis and renovascular hypertension has led to paradigm shifts in the diagnostic algorithm. Noninvasive determination of earlier events (cortex hypoxia and renal artery hemodynamic changes) will supersede late sequelae (calcific stenosis, renal cortical thinning). Therefore, this review proposes the concept of renal penumbra in defining at-risk ischemic renal parenchyma. The complex field of functional renal magnetic resonance imaging will be reviewed succinctly in a clinician-directed fashion.

  6. High Temperature Investigations into an Active Turbine Blade Tip Clearance Control Concept

    NASA Technical Reports Server (NTRS)

    Taylor, Shawn C.; Steinetz, Bruce; Oswald, Jay J.

    2008-01-01

    System studies have shown the benefits of reducing blade tip clearances in modern turbine engines. Minimizing blade tip clearances throughout the engine will contribute materially to meeting NASA s Ultra-Efficient Engine Technology (UEET) turbine engine project goals. NASA GRC is examining two candidate approaches including rub-avoidance and regeneration which are explained in subsequent slides.

  7. High Temperature Investigations into an Active Turbine Blade Tip Clearance Control Concept

    NASA Technical Reports Server (NTRS)

    Taylor, Shawn; Steinetz, Bruce M.; Oswald, Jay J.

    2007-01-01

    System studies have shown the benefits of reducing blade tip clearances in modern turbine engines. Minimizing blade tip clearances throughout the engine will contribute materially to meeting NASA s Ultra-Efficient Engine Technology (UEET) turbine engine project goals. NASA GRC is examining two candidate approaches including rub-avoidance and regeneration which are explained in subsequent slides.

  8. Renal clearance studies of effect of left atrial distension in the dog.

    NASA Technical Reports Server (NTRS)

    Kinney, M. J.; Discala, V. A.

    1972-01-01

    Investigation of the water diuresis of left atrial distension in 16 dogs on the basis of clearance studies employing hydration, chronic and acute salt loading, deoxycorticosterone (DOCA) in excess, and distal tubular nephron blockade with diuretics. The diuresis was found in hydrated and salt-loaded dogs and was independent of DOCA and presumed renin depletion. It was not found in five dogs after distal tubular blockade. No significant reproducible saluresis was ever documented. The water diuresis was always stopped by exogenous vasopressin (seven dogs). Antidiuretic hormone inhibition with distal tubular nephron water permeability changes appears to be the sole mechanism of the diuresis of left atrial distension in the dog.

  9. Clearance concepts applied to the metabolism of inhaled vapors in tissues lining the nasal cavity.

    PubMed

    Andersen, M E; Sarangapani, R

    1999-10-01

    Some inhaled vapors are metabolized by tissues in the nasal cavity or carried away in nasal venous blood after diffusing from the lumen through the nasal epithelial tissues. These processes remove chemical from the airstream. Clearance (volume/time) is the volumetric airflow from which chemical would have to be completely removed to account for the net loss. We present here a steady-state analysis of a series of physiologically based clearance-extraction (PBCE) models for nasal clearance of inhaled vapors, consisting of one, two, three, or four subcompartments. A two-compartment model is the simplest representation of tissues in the nasal cavity, with an air and a tissue compartment. The three-compartment model had air, mucus, and tissue phases. The four-compartment model included both epithelial and submucosal tissues in addition to the air and mucus compartments. For the two-, three-, and four-compartment models, the airstream clearance (Cl(sys)) equation has a common form. Cl(sys) = Cl(tot)H(m:a)PA(gas)Q divided by Cl(tot)H(m:a)(Q + PA(gas)) + PA(gas)Q. In this equation, Cl(tot) is the total tissue clearance, PA(gas) is the gas-phase diffusional clearance, Q is the airflow, and H(muc:a) is the mucus air partition coefficient. Cl(tot) varies in complexity for the different models since it encompasses tissue diffusion, tissue clearance due to metabolism, and blood flow. A physiologically based clearance-extraction (PBCE) model for the whole nose with three nasal tissue regions, each containing a four-compartment tissue stack, was used to simulate nasal uptake of three vapors-acetone, methyl methacrylate (MMA), and vinyl acetate (VA)-to show the dependence of clearance on different parameters for specific compounds. Acetone is not metabolized in the nose, MMA is metabolized at a moderate rate by nasal tissues, and VA is metabolized at a high rate in mucus and tissues. Equations derived from steady-state analyses show the importance of the specific biochemical and

  10. Increased Renal Clearance of Rocuronium Compensates for Chronic Loss of Bile Excretion, via upregulation of Oatp2

    PubMed Central

    Wang, Long; Zhou, Mai-Tao; Chen, Cai-Yang; Yin, Wen; Wen, Da-Xiang; Cheung, Chi-Wai; Yang, Li-Qun; Yu, Wei-Feng

    2017-01-01

    Requirement for rocuronium upon surgery changes only minimally in patients with end-stage liver diseases. Our study consisted of both human and rat studies to explore the reason. The reduction rate of rocuronium infusion required to maintain neuromuscular blockade during the anhepatic phase (relative to paleohepatic phase) was examined in 16 children with congenital biliary atresia receiving orthotopic liver transplantation. Pharmacodynamics and pharmacokinetics of rocuronium were studied based on BDL rats. The role of increased Oatp2 and decrease Oatp1 expressions in renal compensation were explored. The reduction of rocuronium requirements significantly decreased in obstructively jaundiced children (24 ± 9 vs. 39 ± 11%). TOF50 in BDL rats was increased by functional removal of the kidneys but not the liver, and the percentage of rocuronium excretion through urine increased (20.3 ± 6.9 vs. 8.6 ± 1.8%), while that decreased through bile in 28d-BDL compared with control group. However, this enhanced renal secretion for rocuronium was eliminated by Oatp2 knock-down, rather than Oatp1 overexpression (28-d BDL vs. Oatp1-ShRNA or Oatp2-ShRNA, 20.3 ± 6.9 vs. 17.0 ± 6.6 or 9.3 ± 3.2%). Upon chronic/sub-chronic loss of bile excretion, rocuronium clearance via the kidneys is enhanced, by Oatp2 up-regulation. PMID:28084414

  11. Biodistribution and Renal Clearance of Biocompatible Lung Targeted Poly(ethylene glycol) (PEG) Nanogel Aggregates

    PubMed Central

    Deshmukh, Manjeet; Kutscher, Hilliard L.; Gao, Dayuan; Sunil, Vasanthi R.; Malaviya, Rama; Vayas, Kinal; Stein, Stanley; Laskin, Jeffrey D.; Laskin, Debra L.; Sinko, Patrick J.

    2013-01-01

    A novel stabilized aggregated nanogel particle (SANP) drug delivery system was prepared for injectable passive lung targeting. Gel nanoparticles (GNPs) were synthesized by irreversibly cross-linking 8 Arm PEG thiol with 1,6-Hexane-bis-vinylsulfone (HBVS) in phosphate buffer (PB, pH 7.4) containing 0.1% v/v Tween™ 80. Aggregated nanogel particles (ANPs) were generated by aggregating GNPs to micron-size, which were then stabilized (i.e., SANPs) using a PEG thiol polymer to prevent further growth-aggregation. The size of SANPs, ANPs and GNPs was analyzed using a Coulter counter and transmission electron microscopy (TEM). Stability studies of SANPs were performed at 37 °C in rat plasma, phosphate buffered saline (PBS, pH 7.4) and PB (pH 7.4). SANPs were stable in rat plasma, PBS and PB over 7 days. SANPs were covalently labeled with HiLyteFluor™750 (DYE-SANPs) to facilitate ex vivo imaging. Biodistribution of intravenous DYE-SANPs (30 μm, 4 mg in 500 μL PBS) in male Sprague-Dawley rats was compared to free HiLyteFluor™750 DYE alone (1 mg in 500 μL PBS) and determined using a Xenogen IVIS®100 Imaging System. Biodistribution studies demonstrated that free DYE was rapidly eliminated from the body by renal filtration, whereas DYE-SANPs accumulated in the lung within 30 minutes and persisted for 48 h. DYE-SANPs were enzymatically degraded to their original principle components (i.e., DYE-PEG-thiol and PEG-VS polymer) and were then eliminated from the body by renal filtration. Histological evaluation using H & E staining and broncho alveolar lavage (BAL) confirmed that these flexible SANPs were not toxic. This suggests that because of their flexible and non-toxic nature, SANPs may be a useful alternative for treating pulmonary diseases such as asthma, pneumonia, tuberculosis and disseminated lung cancer. PMID:23041417

  12. Garlic Attenuates Plasma and Kidney ACE-1 and AngII Modulations in Early Streptozotocin-Induced Diabetic Rats: Renal Clearance and Blood Pressure Implications

    PubMed Central

    Al-Qattan, Khaled K.; Jayasree, Divya; Ali, Muslim

    2016-01-01

    Raw garlic aqueous extract (GE) has ameliorative actions on the renin-angiotensin system in type-1 diabetes mellitus (DM); however its effects on plasma and kidney angiotensin I converting enzyme type-1 (ACE-1) and angiotensin II (AngII) require further elucidation. This study investigated the effect of GE on plasma and kidney ACE-1 and AngII concentrations and in relation to systemic and renal clearance indicators significant to blood pressure (BP) homeostasis in early streptozotocin- (STZ-) induced type-1 DM. Normal rats (n = 10) received 0.5 mL normal saline (NR/NS), diabetic rats (n = 10) received 0.5 mL NS (DR/NS), and treated diabetic rats (n = 10) received 50 mg/0.1 mL/100 g body weight GE (DR/GE) as daily intraperitoneal injections for 8 weeks. Compared to NR/NS, DR/NS showed a significant increase in plasma ACE-1 and AngII and conversely a decrease in kidney ACE-1 and AngII. These changes were associated with an increase in BP and clearance functions. Alternatively and compared to DR/NS, DR/GE showed normalization or attenuation in plasma and kidney ACE-1 and AngII. These GE induced rectifications were associated with moderation in BP elevation and renal clearance functions. Garlic attenuates modulations in plasma and kidney ACE-1 and AngII, in addition to BP and renal clearance function in type-1 DM. PMID:27293465

  13. Prediction of the overall renal tubular secretion and hepatic clearance of anionic drugs and a renal drug-drug interaction involving organic anion transporter 3 in humans by in vitro uptake experiments.

    PubMed

    Watanabe, Takao; Kusuhara, Hiroyuki; Watanabe, Tomoko; Debori, Yasuyuki; Maeda, Kazuya; Kondo, Tsunenori; Nakayama, Hideki; Horita, Shigeru; Ogilvie, Brian W; Parkinson, Andrew; Hu, Zhuohan; Sugiyama, Yuichi

    2011-06-01

    The present study investigated prediction of the overall renal tubular secretion and hepatic clearances of anionic drugs based on in vitro transport studies. The saturable uptake of eight drugs, most of which were OAT3 substrates (rosuvastatin, pravastatin, pitavastatin, valsartan, olmesartan, trichlormethiazide, p-aminohippurate, and benzylpenicillin) by freshly prepared human kidney slices underestimated the overall intrinsic clearance of the tubular secretion; therefore, a scaling factor of 10 was required for in vitro-in vivo extrapolation. We examined the effect of gemfibrozil and its metabolites, gemfibrozil glucuronide and the carboxylic metabolite, gemfibrozil M3, on pravastatin uptake by human kidney slices. The inhibition study using human kidney slices suggests that OAT3 plays a predominant role in the renal uptake of pravastatin. Comparison of unbound concentrations and K(i) values (1.5, 9.1, and 4.0 μM, for gemfibrozil, gemfibrozil glucuronide, and gemfibrozil M3, respectively) suggests that the mechanism of the interaction is due mainly to inhibition by gemfibrozil and gemfibrozil glucuronide. Furthermore, extrapolation of saturable uptake by cryopreserved human hepatocytes predicts clearance comparable with the observed hepatic clearance although fluvastatin and rosuvastatin required a scaling factor of 11 and 6.9, respectively. This study suggests that in vitro uptake assays using human kidney slices and hepatocytes provide a good prediction of the overall tubular secretion and hepatic clearances of anionic drugs and renal drug-drug interactions. It is also recommended that in vitro-in vivo extrapolation be performed in animals to obtain more reliable prediction.

  14. Renal Transport of Uric Acid: Evolving Concepts and Uncertainties

    PubMed Central

    Bobulescu, Ion Alexandru; Moe, Orson W.

    2013-01-01

    In addition to its role as a metabolic waste product, uric acid has been proposed to be an important molecule with multiple functions in human physiology and pathophysiology and may be linked to human diseases beyond nephrolithiasis and gout. Uric acid homeostasis is determined by the balance between production, intestinal secretion, and renal excretion. The kidney is an important regulator of circulating uric acid levels, by reabsorbing around 90% of filtered urate, while being responsible for 60–70% of total body uric acid excretion. Defective renal handling of urate is a frequent pathophysiologic factor underpinning hyperuricemia and gout. In spite of tremendous advances over the past decade, the molecular mechanisms of renal urate transport are still incompletely understood. Many transport proteins are candidate participants in urate handling, with URAT1 and GLUT9 being the best characterized to date. Understanding these transporters is increasingly important for the practicing clinician as new research unveils their physiology, importance in drug action, and genetic association with uric acid levels in human populations. The future may see the introduction of new drugs that specifically act on individual renal urate transporters for the treatment of hyperuricemia and gout. PMID:23089270

  15. Exaggerated natriuretic response to isotonic volume expansion in hypertensive renal transplant recipients: evaluation of proximal and distal tubular reabsorption by simultaneous determination of renal plasma clearance of lithium and 51Cr-EDTA.

    PubMed

    Nielsen, A H; Knudsen, F; Danielsen, H; Pedersen, E B; Fjeldborg, P; Madsen, M; Brøchner-Mortensen, J; Kornerup, H J

    1987-02-01

    In fourteen hypertensive and fourteen normotensive renal transplant recipients, and in a group of thirteen healthy controls, changes in natriuresis, glomerular filtration rate (GFR), and tubular reabsorption of sodium were determined in relation to intravenous infusion of 2 mmol isotonic sodium chloride per kg body weight. An exaggerated natriuresis was demonstrated in the hypertensive renal transplant recipients. This new finding indicates that the augmented natriuresis following plasma volume expansion, which is a characteristic finding in subjects with arterial hypertension, is not mediated by the renal nerves. Investigation of the tubular reabsorption rates of sodium by simultaneous determination of the renal clearance of 51Cr-EDTA and lithium showed that in the hypertensives the changes in tubular handling of sodium were different from those registered in the normotensive subjects. The increased sodium excretion in the hypertensive renal transplant recipients was caused by an increased output of sodium from the proximal tubules which was not fully compensated for by an increased distal reabsorption. Whether this increased delivery of sodium to the distal segments was caused by changes in GFR or in the proximal tubular reabsorption of sodium could not be clarified in the present study and warrants further investigations.

  16. High-performance liquid chromatography of the renal blood flow marker p-aminohippuric acid (PAH) and its metabolite N-acetyl PAH improves PAH clearance measurements.

    PubMed

    Decosterd, L A; Karagiannis, A; Roulet, J M; Bélaz, N; Appenzeller, M; Buclin, T; Vogel, P; Biollaz, J

    1997-12-05

    PAH (N-(4-aminobenzoyl)glycin) clearance measurements have been used for 50 years in clinical research for the determination of renal plasma flow. The quantitation of PAH in plasma or urine is generally performed by colorimetric method after diazotation reaction but the measurements must be corrected for the unspecific residual response observed in blank plasma. We have developed a HPLC method to specifically determine PAH and its metabolite NAc-PAH using a gradient elution ion-pair reversed-phase chromatography with UV detection at 273 and 265 nm, respectively. The separations were performed at room temperature on a ChromCart (125 mmx4 mm I.D.) Nucleosil 100-5 microm C18AB cartridge column, using a gradient elution of MeOH-buffer pH 3.9 1:99-->15:85 over 15 min. The pH 3.9 buffered aqueous solution consisted in a mixture of 375 ml sodium citrate-citric acid solution (21.01 g citric acid and 8.0 g NaOH per liter), added up with 2.7 ml H3PO4 85%, 1.0 g of sodium heptanesulfonate and completed ad 1000 ml with ultrapure water. The N-acetyltransferase activity does not seem to notably affect PAH clearances, although NAc-PAH represents 10.2+/-2.7% of PAH excreted unchanged in 12 healthy subjects. The performance of the HPLC and the colorimetric method have been compared using urine and plasma samples collected from healthy volunteers. Good correlations (r=0.94 and 0.97, for plasma and urine, respectively) are found between the results obtained with both techniques. However, the colorimetric method gives higher concentrations of PAH in urine and lower concentrations in plasma than those determined by HPLC. Hence, both renal (ClR) and systemic (Cls) clearances are systematically higher (35.1 and 17.8%, respectively) with the colorimetric method. The fraction of PAH excreted by the kidney ClR/ClS calculated from HPLC data (n=143) is, as expected, always <1 (mean=0.73+/-0.11), whereas the colorimetric method gives a mean extraction ratio of 0.87+/-0.13 implying some

  17. Renal

    MedlinePlus

    ... term "renal" refers to the kidney. For example, renal failure means kidney failure. Related topics: Kidney disease Kidney disease - diet Kidney failure Kidney function tests Renal scan Kidney transplant

  18. Impaired maraviroc and raltegravir clearance in a human immunodeficiency virus-infected patient with end-stage liver disease and renal impairment: a management dilemma.

    PubMed

    Pau, Alice K; Penzak, Scott R; Boyd, Sarita D; McLaughlin, Mary; Morse, Caryn G

    2012-01-01

    Current product labels for maraviroc and raltegravir provide no dosing guidance for patients with end-stage liver disease and worsening renal function. We describe a 41-year-old man with human immunodeficiency virus (HIV) infection and rapidly progressive liver failure and vanishing bile duct syndrome at presentation. Despite discontinuation of all potential offending drugs, the patient's liver function continued to deteriorate. To achieve and maintain HIV suppression while awaiting liver transplantation, a regimen consisting of maraviroc, raltegravir, and enfuvirtide was started. These agents were chosen because the patient was not exposed to them before the onset of liver failure. While receiving product label-recommended twice-daily dosing of these drugs, he achieved and maintained HIV suppression. During a complicated and prolonged hospitalization, the patient also developed renal dysfunction. As hepatic metabolism is the primary route of clearance of maraviroc and raltegravir, we predicted that using approved doses of these drugs could result in significant drug accumulation. Since the safety profiles of supratherapeutic concentrations of these agents are not well defined, we chose to use therapeutic drug monitoring to guide further dosing. The reported concentrations showed severely impaired metabolic clearance of both drugs, with markedly prolonged elimination half-lives of 189 hours for maraviroc and 61 hours for raltegravir. Previously reported half-lives for maraviroc and raltegravir in HIV-infected patients with normal hepatic and renal function are 14-18 hours and 9-12 hours, respectively. Based on these results, the dosing intervals were extended from twice/day to twice/week for maraviroc and every 48 hours for raltegravir. Unfortunately, the patient's clinical condition continued to deteriorate, and he eventually died of complications related to end-stage liver disease. This case illustrates the difficulties in managing antiretroviral therapy in

  19. PEGylation of the peptide Bac7(1-35) reduces renal clearance while retaining antibacterial activity and bacterial cell penetration capacity.

    PubMed

    Benincasa, Monica; Zahariev, Sotir; Pelillo, Chiara; Milan, Annalisa; Gennaro, Renato; Scocchi, Marco

    2015-05-05

    The proline-rich antibacterial peptide Bac7(1-35) protects mice against Salmonella typhimurium infection, despite its rapid clearance. To overcome this problem the peptide was linked to a polyethylene glycol (PEG) molecule either via a cleavable ester bond or via a non-hydrolysable amide bond. Both the PEGylated conjugates retained most of the in vitro activity against S. typhimurium. In addition, the ester bond was cleaved in human serum or plasma, releasing a carboxymethyl derivative of Bac7(1-35) which accounts for a higher activity of this peptide with relative to the other, non-hydrolysable form. Both PEGylated peptides maintained the capacity of the unconjugated form to kill bacteria without permeabilizing the bacterial membranes, by penetrating into cells. They exploited the same transporter as unmodified Bac7(1-35), suggesting it has the capacity to internalize quite sizeable cargo if this is linked to Bac7 fragment. PEGylation allows the peptide to have a wide distribution in mice, and a slow renal clearance, indicating that this strategy would improve the bioavailability of Bac7, and in principle of other antimicrobial peptides. This can be an equally important issue to reducing cytotoxicity for therapeutic use of these antibacterials.

  20. Mass transfer, clearance and plasma concentration of procalcitonin during continuous venovenous hemofiltration in patients with septic shock and acute oliguric renal failure

    PubMed Central

    Level, Claude; Chauveau, Philippe; Guisset, Olivier; Cazin, Marie Cécile; Lasseur, Catherine; Gabinsky, Claude; Winnock, Stéphane; Montaudon, Danièle; Bedry, Régis; Nouts, Caroline; Pillet, Odile; Benissan, Georges Gbikpi; Favarel-Guarrigues, Jean Claude; Castaing, Yves

    2003-01-01

    Objectives To measure the mass transfer and clearance of procalcitonin (PCT) in patients with septic shock during continuous venovenous hemofiltration (CVVH), and to assess the mechanisms of elimination of PCT. Setting The medical department of intensive care. Design A prospective, observational study. Patients Thirteen critically ill patients with septic shock and oliguric acute renal failure requiring continuous venovenous postdilution hemofiltration with a high-flux membrane (AN69 or polyamide) and a 'conventional' substitution volume (< 2.5 l/hour). Measurements and main results PCT was measured with the Lumitest PCT Brahms® in the prefilter and postfilter plasma, in the ultrafiltrate at the beginning of CVVH (T0) and 15 min (T15'), 60 min (T60') and 6 hours (T6h) after setup of CVVH, and in the prefilter every 24 hours during 4 days. Mass transfer was determined and the clearance and the sieving coefficient were calculated according to the mass conservation principle. Plasma and ultrafiltrate clearances, respectively, at T15', T60' and T6h were 37 ± 8.6 ml/min (not significant) and 1.8 ± 1.7 ml/min (P < 0.01), 34.7 ± 4.1 ml/min (not significant) and 2.3 ± 1.8 ml/min (P < 0.01), and 31.5 ± 7 ml/min (not significant) and 5 ± 2.3 ml/min (P < 0.01). The sieving coefficient significantly increased from 0.07 at T15' to 0.19 at T6h, with no difference according to the nature of the membrane. PCT plasma levels were not significantly modified during the course of CCVH. Conclusions We conclude that PCT is removed from the plasma of patients with septic shock during CCVH. Most of the mass is eliminated by convective flow, but adsorption also contributes to elimination during the first hours of CVVH. The effect of PCT removal with a conventional CVVH substitution fluid rate (<2.5 l/hour) on PCT plasma concentration seems to be limited, and PCT remains a useful diagnostic marker in these septic patients. The impact of high-volume hemofiltration on the PCT clearance

  1. Post-renal-transplant hypertension. Urine volume, free water clearance and plasma concentrations of arginine vasopressin, angiotensin II and aldosterone before and after oral water loading in hypertensive and normotensive renal transplant recipients.

    PubMed

    Pedersen, E B; Danielsen, H; Knudsen, F; Nielsen, A H; Jensen, T; Kornerup, H J; Madsen, M

    1986-09-01

    Urine volume (V), free water clearance (CH2O) and plasma concentrations of arginine vasopressin (AVP), angiotensin II (A II) and aldosterone (Aldo) were determined before and three times during the first 5 h after an oral water load of 20 ml/kg body wt in 19 patients with post-renal-transplant hypertension (group I), in 13 normotensive renal transplant recipients (group II) and in 20 control subjects (group III). Both V and CH2O increased significantly in all groups, but considerably less in groups I and II than in group III. When CH2O was related to glomerular filtration rate no differences existed between patients and control subjects. Basal AVP was the same in groups I (3.3 pmol/l, median) and II (3.0 pmol/l), but significantly (p less than 0.01) higher than in group III (1.9 pmol/l). Basal A II was significantly (p less than 0.01) elevated in group I (18 pmol/l) when compared to both groups II (10 pmol/l) and III (11 pmol/l), and the level was independent of the presence of native kidneys. Basal Aldo was the same in all groups. During loading, AVP was reduced in all groups, A II was almost unchanged, and Aldo was increased in groups I and II and reduced in group III depending on alterations in serum potassium. Thus urinary diluting ability is reduced in renal transplant recipients due to a reduced glomerular filtration rate. The enhanced A II in hypertensive renal transplant recipients gives further evidence for the point of view that hypertension is angiotensin-dependent in most of these patients.

  2. Microsomal and cytosolic scaling factors in dog and human kidney cortex and application for in vitro-in vivo extrapolation of renal metabolic clearance.

    PubMed

    Scotcher, Daniel; Billington, Sarah; Brown, Jay; Jones, Christopher; Brown, Colin D A; Rostami-Hodjegan, Amin; Galetin, Aleksandra

    2017-03-07

    In vitro-in vivo extrapolation of drug metabolism data obtained in enriched preparations of sub-cellular fractions rely upon robust estimates of physiologically relevant scaling factors for prediction of clearance in vivo. The purpose of the current study was to measure the microsomal and cytosolic protein per gram of kidney (MPPGK and CPPGK) in dog and human kidney cortex using appropriate protein recovery markers, and evaluate functional activity of human cortex microsomes. Cytochrome P450 (CYP) content and glucose-6-phosphatase activity were used as microsomal protein markers, whereas glutathione-S-transferase activity was a cytosolic marker. Functional activity of human microsomal samples was assessed by measuring mycophenolic acid glucuronidation. MPPGK was 33.9 and 44.0 mg/g dog kidney cortex, and 41.1 and 63.6 mg/g dog liver (n=17), using CYP content and glucose-6-phosphatase activity, respectively. There were no trends between kidney, liver and intestinal scalars from the same animals. Species differences were evident, as human MPPGK and CPPGK were 26.2 and 53.3 mg/g kidney cortex (n=38), respectively. MPPGK was 2-fold higher than the commonly used in vitro-in vivo extrapolation scalar; difference was mainly attributed to tissue source (mixed kidney regions vs cortex). Robust human MPPGK and CPPGK scalars were measured for the first time. The work emphasized the importance of regional differences (cortex vs. whole kidney specific MPPGK, tissue weight and blood flow) and a need to account for these to improve assessment of renal metabolic clearance and its extrapolation to in vivo.

  3. Lower metabolic clearance of tizanidine in Japanese subjects.

    PubMed

    Momo, Kenji; Homma, Masato; Kohda, Yukinao

    2013-12-01

    Our aim was to determine whether metabolic clearance, renal clearance, or both elimination pathways contribute to ethnic differences in tizanidine clearance, which is ~ 2-fold higher in Caucasians than in Asians. The pharmacokinetic parameters of tizanidine in 9 healthy male Japanese subjects were compared with those of Caucasians in previous studies. Metabolic clearance of tizanidine was lower in Japanese than in Caucasian subjects (5.9 vs. 8.1 - 10.9 l/h/kg), although renal clearances were similar (0.040 vs. 0.047 - 0.055 l/h/kg). The results suggest that ethnic differences in tizanidine clearance are due to differences in metabolic clearance.

  4. Association of Alternative Approaches to Normalizing Peritoneal Dialysis Clearance with Mortality and Technique Failure: A Retrospective Analysis Using the United States Renal Data System-Dialysis Morbidity and Mortality Study, Wave 2.

    PubMed

    Boyle, Suzanne M; Li, Yimei; Wilson, F Perry; Glickman, Joel D; Feldman, Harold I

    ♦ BACKGROUND: Total body water (V) is an imprecise metric for normalization of dialytic urea clearance (Kt). This poses a risk of early mortality/technique failure (TF). We examined differences in the distribution of peritoneal Kt/V when V was calculated with actual weight (AW), ideal weight (IW), and adjusted weight (ADW). We also examined the associations of these Kt/V measurements, Kt/body surface area (BSA), and non-normalized Kt with mortality and TF. ♦ METHODS: This is a retrospective cohort study of 534 incident peritoneal dialysis (PD) patients from the Dialysis Morbidity and Mortality Study Wave 2 linked with United States Renal Data System through 2010. Using Cox-proportional hazard models, we examined the relationship of several normalization strategies for peritoneal urea clearance, including Kt/VAW, Kt/VIW, Kt/VADW, Kt/BSA, and non-normalized Kt, with the outcomes of mortality and TF. Harrell's c-statistics were used to assess the relative predictive ability of clearance metrics for mortality and TF. The distributions of Kt/VAW, KT/VIW, and KT/VADW were compared within and between body mass index (BMI) strata. ♦ RESULTS: Median patient age: 59 (54% male; 72% white; 91% continuous ambulatory PD [CAPD]). Median 24-hour urine volume: 700 mL; median estimated glomerular filtration rate (eGFR) at initiation: 7.15 mL/min/1.73 m(2). Technique failure and transplant-censored mortality at 5 years: 37%. Death and transplant-censored TF at 5 years: 60%. There were no significant differences in initial eGFR and 24-hour urine volume across BMI strata. There were statistically significant differences in each Kt/V calculation within the underweight, overweight, and obese strata. After adjustment, there were no significant differences in the hazard ratios (HRs) for TF/mortality for each clearance calculation. Harrell's c-statistics for mortality for each clearance calculation were 0.78, and for TF, 0.60 - 0.61. ♦ CONCLUSIONS: Peritoneal urea clearances are

  5. Establishment and use of surgical rat models for assessment of organ specific in vivo clearance.

    PubMed

    Vestergaard, Bill

    2016-06-01

    Knowledge of clearance plays a key role in the development of new drug entities, especially in the development of improved analogues for treatment of chronic conditions. Improved pharmacokinetic properties can be used to increase dosing interval and thereby improve patient compliance. This will lead to improved treatment outcome or decreased risk of treatment failure when treating chronic conditions. Therefore, animal models for assessment of organ-specific clearance are of great value in preclinical drug development. These models can be used to obtain insights into the relative importance of a clearance organ and thereby guide drug design of new analogues in early drug discovery. The current PhD project was undertaken to explore surgical in vivo models, which could be used in the assessment of the relative importance of major clearance organs. It was the aim of the PhD project to establish and validate both a nephrectomy model and a hepatectomy model as tools to investigate relative importance of renal and hepatic clearance. Furthermore, the project aim was to investigate renal clearance of rFVIIa and rhGH using a nephrectomy model in rats. The thesis is composed of a short theoretical background, a literature review, two papers based on experimental work as well as experimental work not included in the papers. Chapter one is an introduction with the specific aims and hypotheses. The chapters from two to five contain theoretical background of the clearance concept, anatomical and physiological description of clearance organs and a brief overview of potential clearance models including in vivo models. Chapters six through nine highlight the experimental work with the results obtained during the PhD project. Lastly, the chapters from ten to twelve contain a general discussion, conclusion and perspectives of the current thesis. Paper I "Nephrectomized and hepatectomized animal models as tools in preclinical pharmacokinetics" provides a literature review of animal

  6. Association between augmented renal clearance and clinical outcomes in patients receiving β-lactam antibiotic therapy by continuous or intermittent infusion: a nested cohort study of the BLING-II randomised, placebo-controlled, clinical trial.

    PubMed

    Udy, Andrew A; Dulhunty, Joel M; Roberts, Jason A; Davis, Joshua S; Webb, Steven A R; Bellomo, Rinaldo; Gomersall, Charles; Shirwadkar, Charudatt; Eastwood, Glenn M; Myburgh, John; Paterson, David L; Starr, Therese; Paul, Sanjoy K; Lipman, Jeffrey

    2017-03-09

    Augmented renal clearance (ARC) is known to influence β-lactam antibiotic pharmacokinetics. This substudy of the BLING-II trial aimed to explore the association between ARC and patient outcomes in a large randomised clinical trial. BLING-II enrolled 432 participants with severe sepsis randomised to receive β-lactam therapy by continuous or intermittent infusion. An 8-h creatinine clearance (CLCr) measured on Day 1 was used to identify ARC, defined as CLCr ≥ 130 mL/min. Patients receiving any form of renal replacement therapy were excluded. Primary outcome was alive ICU-free days at Day 28. Secondary outcomes included 90-day mortality and clinical cure at 14 days following antibiotic cessation. A total of 254 patients were included, among which 45 (17.7%) manifested ARC [median (IQR) CLCr 165 (144-198) mL/min]. ARC patients were younger (P <0.001), more commonly male (P = 0.04) and had less organ dysfunction (P <0.001). There was no difference in ICU-free days at Day 28 [ARC, 21 (12-24) days; no ARC, 21 (11-25) days; P = 0.89], although clinical cure was significantly greater in the unadjusted analysis in those manifesting ARC [33/45 (73.3%) vs. 115/209 (55.0%) P = 0.02]. This was attenuated in the multivariable analysis. No difference was noted in 90-day mortality. There were no statistically significant differences in clinical outcomes in ARC patients according to the dosing strategy employed. In this substudy of a large clinical trial of β-lactam antibiotics in severe sepsis, ARC was not associated with any differences in outcomes, regardless of dosing strategy.

  7. Psychosocial impact of illness intrusiveness moderated by self-concept and age in end-stage renal disease.

    PubMed

    Devins, G M; Beanlands, H; Mandin, H; Paul, L C

    1997-11-01

    This study assesses whether a person's self-concept as a "chronic kidney patient" differentially moderates the psychosocial impact of illness intrusiveness--illness-induced lifestyle disruptions--across the life span. Renal transplant (n = 52) and maintenance dialysis patients (n = 49) completed the illness Intrusiveness Ratings Scale, a semantic-differential self-concept measure, and structured interviews measuring psychosocial well-being and emotional distress. Across ages, distress rose with increasing illness intrusiveness when self-concept was similar, but not dissimilar, to the chronic kidney patient stereotype. The relation between illness intrusiveness and psychosocial well-being differed significantly between younger and older respondents depending on whether they construed themselves as similar versus dissimilar to the chronic kidney patient. Although self-definition moderates the psychosocial impact of chronic disease, this varies across the life span and across affect states.

  8. Comparison of glomerular filtration rate estimated by plasma clearance method with modification of diet in renal disease prediction equation and Gates method.

    PubMed

    Prasad, N; Barai, S; Gambhir, S; Parasar, D S; Ora, M; Gupta, A; Sharma, R K

    2012-03-01

    Glomerular filtration rate (GFR) prediction equations are widely used in clinical practice for quick assessment of kidney function. Gates method using radionuclide technique is an alternative to prediction equations for quick assessment of GFR. Aim of the study was to compare Gates method and modification of diet in renal disease (MDRD) equation in a sizeable patient population with wide range of renal function to evaluate their clinical utility. GFR was estimated in 897 subjects with wide range of renal function by gates method, and MDRD equation and results were compared against measured GFR. Subjects were divided in to 4 groups (0-30 ml, 31-60 ml, 61-90 ml, >90 ml) on the basis of measured GFR and comparison between two methods done through linear regression analysis. Analysis of R(2) indicated that 56% of the interindividual variability for Gates GFR was in accordance to variation in measured GFR, in the GFR range of (0-30 ml), this value dropped to 39% in the GFR range of 31-60 ml, 40% in the GFR range of 61-90 ml, 26.4% in the GFR range of >90 ml, the corresponding figure for MDRD GFR were 47.9%, 31.1%, 17.6% and 16.1%, respectively. Gates method is more precise for GFR estimation at all levels of renal function.

  9. New IVIVE method for the prediction of total human clearance and relative elimination pathway contributions from in vitro hepatocyte and microsome data.

    PubMed

    Riede, Julia; Poller, Birk; Umehara, Ken-ichi; Huwyler, Jörg; Camenisch, Gian

    2016-04-30

    Total human clearance is a key determinant for the pharmacokinetic behavior of drug candidates. Our group recently introduced the Extended Clearance Model (ECM) as an accurate in vitro-in vivo extrapolation (IVIVE) method for the prediction of hepatic clearance. Yet, knowledge about relative elimination pathway contributions is needed in order to predict the total human clearance of drug candidates. In the present work, a training set of 18 drug compounds was used to describe the affiliations between in vitro sinusoidal uptake clearance and the fractional contributions of hepatic (metabolic and biliary) or renal clearance to overall in vivo elimination. By means of these quantitative relationships and using a validation set of 10 diverse drug molecules covering different (sub)classes of the Extended Clearance Concept Classification System (ECCCS), the relative contributions of elimination pathways were calculated and demonstrated to well correlate with human reference data. Likewise, ECM- and pathway-based predictions of total clearances from both data sets demonstrated a strong correlation with the observed clinical values with 26 out of 28 compounds within a three-fold deviation. Hence, total human clearance and relative contributions of elimination pathways were successfully predicted by the presented method using solely hepatocyte and microsome in vitro data.

  10. Current concepts and perspectives of renal volume regulation in relationship to hypertension.

    PubMed

    Guyton, A C; Manning, R D; Norman, R A; Montani, J P; Lohmeier, T E; Hall, J E

    1986-10-01

    The renal-body fluid mechanism for arterial pressure control is almost certainly the most primitive of all the pressure-regulating mechanisms in animals. Through the stages of evolution, the system has been greatly improved. Nervous controls provide rapid pressure-control mechanisms that function almost instantaneously, many hours or days before the renal-body fluid mechanism can act fully. The renin-angiotensin-aldosterone system plays another important role: this system ensures that very large changes in salt intake, from as little as one-tenth normal up to as high as 10 times normal, have very little effect on the regulated level of the arterial pressure. Finally, the long-term autoregulatory mechanism helps to dissociate the long-term control of cardiac output from long-term control of arterial pressure; it also makes it possible for extremely slight increases in body fluid volume to cause chronic volume-loading hypertension.

  11. Diabetes and end-stage renal disease; a review article on new concepts.

    PubMed

    Ghaderian, Seyed Bahman; Hayati, Fatemeh; Shayanpour, Shokouh; Beladi Mousavi, Seyed Seifollah

    2015-01-01

    It is well established that diabetic nephropathy is the most common cause or in combination with hypertensive nephropathy are the most common causes of end-stage renal disease (ESRD) in developed and developing countries. For this review, we used a variety of sources by searching through PubMed, Embase, Scopus, Current Content and Iran Medex from January 1990 up to December 2014. Manuscripts published in English and Persian languages, as full-text articles, and or as abstract were included in the study. Patient survival in diabetics on maintenance renal replacement therapy including hemodialysis (HD), peritoneal dialysis (PD) and kidney transplantation is significantly lower than that seen in nondiabetics with ESRD. The poor prognosis of diabetic patients with ESRD is partly due to presence of significant cardiovascular disease, problems with vascular access, more susceptible to infections, foot ulcer, and hemodynamic instability during HD. Although, many complications related to kidney transplantation may occur in diabetic ESRD patients, multiple studies have found that the kidney transplantation is the preferred renal replacement therapy for diabetic patients with ESRD and it is associated with a much better survival and quality of life than dialysis among these patients.

  12. Predicting Clearance Mechanism in Drug Discovery: Extended Clearance Classification System (ECCS).

    PubMed

    Varma, Manthena V; Steyn, Stefanus J; Allerton, Charlotte; El-Kattan, Ayman F

    2015-12-01

    Early prediction of clearance mechanisms allows for the rapid progression of drug discovery and development programs, and facilitates risk assessment of the pharmacokinetic variability associated with drug interactions and pharmacogenomics. Here we propose a scientific framework--Extended Clearance Classification System (ECCS)--which can be used to predict the predominant clearance mechanism (rate-determining process) based on physicochemical properties and passive membrane permeability. Compounds are classified as: Class 1A--metabolism as primary systemic clearance mechanism (high permeability acids/zwitterions with molecular weight (MW) ≤400 Da), Class 1B--transporter-mediated hepatic uptake as primary systemic clearance mechanism (high permeability acids/zwitterions with MW >400 Da), Class 2--metabolism as primary clearance mechanism (high permeability bases/neutrals), Class 3A--renal clearance (low permeability acids/zwitterions with MW ≤400 Da), Class 3B--transporter mediated hepatic uptake or renal clearance (low permeability acids/zwitterions with MW >400 Da), and Class 4--renal clearance (low permeability bases/neutrals). The performance of the ECCS framework was validated using 307 compounds with single clearance mechanism contributing to ≥70% of systemic clearance. The apparent permeability across clonal cell line of Madin - Darby canine kidney cells, selected for low endogenous efflux transporter expression, with a cut-off of 5 × 10(-6) cm/s was used for permeability classification, and the ionization (at pH7) was assigned based on calculated pKa. The proposed scheme correctly predicted the rate-determining clearance mechanism to be either metabolism, hepatic uptake or renal for ~92% of total compounds. We discuss the general characteristics of each ECCS class, as well as compare and contrast the framework with the biopharmaceutics classification system (BCS) and the biopharmaceutics drug disposition classification system (BDDCS

  13. Assessment of renal response with urinary exosomes in patients with AL amyloidosis: A proof of concept.

    PubMed

    Ramirez-Alvarado, Marina; Barnidge, David R; Murray, David L; Dispenzieri, Angela; Marin-Argany, Marta; Dick, Christopher J; Cooper, Shawna A; Nasr, Samih H; Ward, Christopher J; Dasari, Surendra; Jiménez-Zepeda, Víctor H; Leung, Nelson

    2017-03-10

    Immunoglobulin light chain (AL) amyloidosis is a fatal complication of B-cell proliferation secondary to deposition of amyloid fibrils in various organs. Urinary exosomes (UEX) are the smallest of the microvesicles excreted in the urine. Previously, we found UEX of patients with AL amyloidosis contained immunoglobulin light chain (LC) oligomers that patients with multiple myeloma did not have. To further explore the role of the LC oligomers, UEX was isolated from an AL amyloidosis patient with progressive renal disease despite achieving a complete response. LC oligomers were identified. Mass spectrometry (MS) of the UEX and serum identified two monoclonal lambda LCs. Proteomics of the trypsin digested amyloid fragments in the kidney by laser microdissection and MS analysis identified a λ6 LC. The cDNA from plasma cell clone was from the IGLV- 6-57 family and it matched the amino acid sequences of the amyloid peptides. The predicted mass of the peptide product of the cDNA matched the mass of one of the two LCs identified in the UEX and serum. UEX combined with MS were able to identify 2 monoclonal lambda LCs that current clinical methods could not. It also identified the amyloidogenic LC which holds potential for response assessment in the future. This article is protected by copyright. All rights reserved.

  14. Renal arteriography

    MedlinePlus

    Renal angiogram; Angiography - kidney; Renal angiography; Renal artery stenosis - arteriography ... an artery by a blood clot Renal artery stenosis Renal cell cancer Angiomyolipomas (noncancerous tumors of the ...

  15. Controls Considerations for Turbine Active Clearance Control

    NASA Technical Reports Server (NTRS)

    Melcher, Kevin J.

    2004-01-01

    This presentation discusses active control of turbine tip clearance from a control systems perspective. It is a subset of charts that were presented at the 2003 meeting of the International Society of Air Breathing Engines which was held August 31 through September 5 in Cleveland, Ohio. The associated reference paper is cited at the end of the presentation. The presentation describes active tip clearance control research being conducted by NASA to improve turbine engine systems. The target application for this effort is commercial aircraft engines. However, it is believed that the technologies developed as part of this research will benefit a broad spectrum of current and future turbomachinery. The first part of the presentation discusses the concept of tip clearance, problems associated with it, and the benefits of controlling it. It lays out a framework for implementing tip clearance controls that enables the implementation to progress from purely analytical to hardware-in-the-loop to fully experimental. And it briefly discusses how the technologies developed will be married to the previously described ACC Test Rig for hardware-in-the-loop demonstrations. The final portion of the presentation, describes one of the key technologies in some detail by presenting equations and results for a functional dynamic model of the tip clearance phenomena. As shown, the model exhibits many of the clearance dynamics found in commercial gas turbine engines. However, initial attempts to validate the model identified limitations that are being addressed to make the model more realistic.

  16. Fuel conservation through active control of rotor clearances

    NASA Technical Reports Server (NTRS)

    Beitler, R. S.; Saunders, A. A.; Wanger, R. P.

    1980-01-01

    Under the NASA-sponsored Energy Efficient Engine (EEE) Project, technology is being developed which will significantly reduce the fuel consumption of turbofan engines for subsonic transport aircraft. One technology concept being pursued is active control of rotor tip clearances. Attention is given to rotor tip clearance considerations and an overview of preliminary study results as well as the General Electric EEE clearance control approach is presented. Finally, potential fuel savings with active control of rotor clearances for a typical EEE mission are predicted.

  17. Malaria parasite clearance.

    PubMed

    White, Nicholas J

    2017-02-23

    Following anti-malarial drug treatment asexual malaria parasite killing and clearance appear to be first order processes. Damaged malaria parasites in circulating erythrocytes are removed from the circulation mainly by the spleen. Splenic clearance functions increase markedly in acute malaria. Either the entire infected erythrocytes are removed because of their reduced deformability or increased antibody binding or, for the artemisinins which act on young ring stage parasites, splenic pitting of drug-damaged parasites is an important mechanism of clearance. The once-infected erythrocytes returned to the circulation have shortened survival. This contributes to post-artesunate haemolysis that may follow recovery in non-immune hyperparasitaemic patients. As the parasites mature Plasmodium vivax-infected erythrocytes become more deformable, whereas Plasmodium falciparum-infected erythrocytes become less deformable, but they escape splenic filtration by sequestering in venules and capillaries. Sequestered parasites are killed in situ by anti-malarial drugs and then disintegrate to be cleared by phagocytic leukocytes. After treatment with artemisinin derivatives some asexual parasites become temporarily dormant within their infected erythrocytes, and these may regrow after anti-malarial drug concentrations decline. Artemisinin resistance in P. falciparum reflects reduced ring stage susceptibility and manifests as slow parasite clearance. This is best assessed from the slope of the log-linear phase of parasitaemia reduction and is commonly measured as a parasite clearance half-life. Pharmacokinetic-pharmacodynamic modelling of anti-malarial drug effects on parasite clearance has proved useful in predicting therapeutic responses and in dose-optimization.

  18. Clinical review: Drug metabolism and nonrenal clearance in acute kidney injury

    PubMed Central

    Vilay, A Mary; Churchwell, Mariann D; Mueller, Bruce A

    2008-01-01

    Decreased renal drug clearance is an obvious consequence of acute kidney injury (AKI). However, there is growing evidence to suggest that nonrenal drug clearance is also affected. Data derived from human and animal studies suggest that hepatic drug metabolism and transporter function are components of nonrenal clearance affected by AKI. Acute kidney injury may also impair the clearance of formed metabolites. The fact that AKI does not solely influence kidney function may have important implications for drug dosing, not only of renally eliminated drugs but also of those that are hepatically cleared. A review of the literature addressing the topic of drug metabolism and clearance alterations in AKI reveals that changes in nonrenal clearance are highly complicated and poorly studied, but they may be quite common. At present, our understanding of how AKI affects drug metabolism and nonrenal clearance is limited. However, based on the available evidence, clinicians should be cognizant that even hepatically eliminated drugs and formed drug metabolites may accumulate during AKI, and renal replacement therapy may affect nonrenal clearance as well as drug metabolite clearance. PMID:19040780

  19. Analysis and design of a uniform-clearance, pumping-ring rod seal for the Stirling engine

    NASA Technical Reports Server (NTRS)

    Etsion, I.

    1980-01-01

    A uniform clearance pumping ring, as opposed to the conventional taper clearance one, is described. The uniform clearance concept eliminates complex elastohydrodynamic problems and enables a simple analytical treatment to be made. An analytical expression is derived for the pumping rate showing the effect of various design parameters on the pumping ring's performance. An optimum clearance is found by which the pumping rate is maximized and a numerical example is presented to demonstrate the potential of the uniform clearance design.

  20. Cimetidine impairs nitrazepam clearance.

    PubMed

    Ochs, H R; Greenblatt, D J; Gugler, R; Müntefering, G; Locniskar, A; Abernethy, D R

    1983-08-01

    The effect of cimetidine on hepatic clearance of the benzodiazepine derivative nitrazepam was evaluated in healthy subjects. Six received a single 5- or 10-mg oral nitrazepam dose in the drug-free state and again with therapeutic cimetidine doses. Nitrazepam kinetics were determined from multiple serum concentrations measured during the 72 hr after each dose. Cimetidine had no effect on nitrazepam absorption kinetics, since peak serum nitrazepam concentration and time of peak concentration were not altered. Cimetidine did not alter nitrazepam volume of distribution, but cimetidine consistently reduced nitrazepam clearance, from a mean of 1.41 ml/min/kg in the control state to 1.17 ml/min/kg during cimetidine treatment. This resulted in prolongation of nitrazepam elimination t1/2 from 22.2 to 27.8 hr. Thus the ability of cimetidine to impair drug oxidation in man extends to the capacity for clearance of nitrazepam, a compound biotransformed mainly by nitroreduction.

  1. Alternative Terrain Following System Concepts,

    DTIC Science & Technology

    1977-11-01

    inertial altitude rate command in response to errors in terrain clearance altitude. This command is limited and summed with the actual rate of change of...altitude rate command in response to errors in the clearance altitude. This command is limited and summed with the rate of change of clearance...altitude. The normal acceleration command is generated in response to errors in the rate of change of terrain clearance. System Concept B describes a

  2. Optical Detection of Hepatic and Renal Function.

    NASA Astrophysics Data System (ADS)

    Dorshow, Richard B.; Bugaj, Joseph E.; Burleigh, B. Daniel; Johnson, Michael A.; Jones, William B.; Duncan, James R.

    1997-03-01

    The feasibility of a new methodology for organ function determination, based on optical detection, is investigated. Differentiation between normal and abnormal organ function is demonstrated in an animal model for both the liver and the kidney. Two commercial dyes were employed in this initial study. Characteristic blood clearance curves associated with normal hepatic function and normal renal function are obtained. Upon ablation of a portion of the liver, the clearance curve ascribed to hepatic function is greatly extended as expected. Upon ligation of both kidneys, the clearance curve ascribed to renal function remains elevated and constant, indicating little if any clearance. The clearance curves are fit to standard physiological compartment models to yield quantitative information on decay times.

  3. Advanced Thermal HPT Clearance Control

    NASA Technical Reports Server (NTRS)

    WojciechVoytek, Sak

    2006-01-01

    OBJECTIVE: Develop a fast acting HPT Active Clearance Control System to improve engine efficiency and reduce emissions CHALLENGE: Reduction of HPT blade clearance throughout engine operation System complexity, reliability and cost must remain comparable or surpass today s engines Reduced clearance may increase possibility of rubs

  4. Renal functional reserve is impaired in patients with systemic sclerosis without clinical signs of kidney involvement

    PubMed Central

    Livi, R; Teghini, L; Pignone, A; Generini, S; Matucci-Cerinic, M; Cagnoni, M

    2002-01-01

    Objective: To evaluate the functional response of the kidney to an amino acid challenge (the so called renal functional reserve (RFR)) in patients with systemic sclerosis (SSc) with no clinical sign of renal involvement. Methods: Before and after an intravenous amino acid load (Freamine III Baxter, 8.5% solution, 4.16 ml/min for two hours), glomerular filtration rate (GFR, as creatinine clearance), effective renal plasma flow (ERPF, as para-aminohyppurate clearance), and calculated total renal vascular resistance (TRVR) were measured in 21 patients with SSc with apparently normal renal function and 10 normal controls. Results: In basal conditions, patients had lower ERPF (403.5 (SD 43.8) v 496.4 (SD 71.3) ml/min, p<0.0002) and higher TRVR (10 822 (SD 2044) v 8874 (SD 1639) dyne/sxcm-5, p<0.014) than controls. The RFR, evaluated as the percentage increase of GFR after the amino acid load, was significantly reduced in patients with SSc (SSc +1.9 (SD18.6)%, controls +34.8 (SD 13.9)%; p<0.0002). However, the response of patients was not uniform. Multiple regression analysis showed that the RFR was inversely dependent on the patients' mean arterial pressure at admission and basal GFR (R2=65%, p<0.0001). Conclusions: Most patients with SSc cannot increase renal filtration under the challenge of a protein overload. This defective renal response to the amino acid load test sustains the concept of the prevalence of vasoconstrictor over vasodilating factors in the kidney of these patients. PMID:12117672

  5. Effect of renal function on risedronate pharmacokinetics after a single oral dose

    PubMed Central

    Mitchell, D Y; St Peter, J V; Eusebio, R A; Pallone, K A; Kelly, S C; Russell, D A; Nesbitt, J D; Thompson, G A; Powell, J H

    2000-01-01

    Aims To determine the relationship between risedronate pharmacokinetics and renal function. Methods Risedronate was administered to adult men and women (n = 21) with various degrees of renal function (creatinine clearance 15–126 ml min−1) as a single oral dose of 30 mg. Serum samples were obtained for 72 h after dosing, and urine samples were collected for 72 h after dosing and then periodically for 6 weeks. Risedronate concentrations were determined using an enzyme-linked immunosorbent assay (ELISA). Risedronate serum concentration-time and urinary excretion rate-time profiles were analysed simultaneously using nonlinear regression. Results Renal clearance and volume of distribution were linearly related to creatinine clearance (r2 = 0.854, P < 0.001; and r2 = 0.317, P < 0.01, respectively). Decreases in predicted renal clearance and volume of distribution of 82 and 69%, respectively, were observed when creatinine clearance decreased from 120 to 20 ml min−1. A 64% decrease in predicted oral clearance was observed when creatinine clearance decreased from 120 to 20 ml min−1 (P = 0.064). Iohexol clearance, a predictor of renal function, produced similar results to those observed with creatinine clearance. Risedronate was well tolerated by the study population. Conclusions Risedronate renal clearance was significantly related to a decrease in renal function. There was a consistent reduction in oral clearance with a decrease in creatinine clearance. However, based on the regression analysis, generally no dosage adjustment appears to be necessary for most patients with mild or moderate renal impairment (creatinine clearance > 20 ml min−1). PMID:10718776

  6. Effects of radiofrequency ablation on individual renal function: assessment by technetium-99m mercaptoacetyltriglycine renal scintigraphy.

    PubMed

    Mukai, Takashi; Sato, Shuhei; Iguchi, Toshihiro; Mimura, Hidefumi; Yasui, Kotaro; Gobara, Hideo; Saika, Takashi; Nasu, Yasutomo; Kumon, Hiromi; Kanazawa, Susumu

    2006-04-01

    We quantitatively evaluated total and individual renal function by technetium-99m mercaptoacetyltriglycine (Tc-99m MAG3) renal scintigraphy before and after radiofrequency ablation (RFA) of renal tumors. Eleven patients who underwent Tc-99m MAG3 renal scintigraphy 1 week before and after RFA were evaluated (7 men and 4 women; age range: 23-83 years; mean age: 60.6 years). Five patients had solitary kidneys, and five had normally or minimally functioning contralateral kidneys. One patient had a renal cell carcinoma in the contralateral kidney. One patient with a solitary kidney underwent RFA a second time for a residual tumor. In patients with a solitary kidney, MAG3 clearance decreased after 5 of 6 RFAs, and in patients with a normally functioning contralateral kidney, MAG3 clearance decreased after 4 of 5 RFAs, but no significant differences were observed between before and after treatments. In addition to the total MAG3 clearance, the split MAG3 clearance was evaluated in patients with a normally functioning contralateral kidney. MAG3 clearance decreased in 4 of 5 treated kidneys, while it adversely increased in the contralateral kidneys after 4 of 5 RFAs. No significant differences, however, were observed between before and after treatments. The results of our study revealed no significant differences in sCr, BUN, CCr, or MAG3 clearance between pre- and post-RFA values. These results support data regarding the functional impact and safety of renal RFA in published reports. We evaluated total and individual renal function quantitatively using Tc-99m MAG3 renal scintigraphy before and after treatment. This scintigraphy was very useful in assessing the effects of RFA on renal function.

  7. Changes in renal function in early pregnancy in women with one kidney.

    PubMed

    Davison, J M

    1978-01-01

    In healthy women the 24-hour endogenous creatinine clearance is elevated by some 50 percent within 6 weeks of conception and an analogous increase of the 24-hour glucose excretion occurs. 24-hour glucose excretion later reverts to normal, reflecting a delayed onset of increased tubular reabsorption.Following unilateral nephrectomy there are marked increases in RPF and GFR in the contralateral kidney. Single hypertrophied kidneys apparently can adapt still further as in normal pregnancy. We have studied 5 women, in satisfactory general health prior to the pregnancy, each with only one kidney, before conception and during early pregnancy. Three had had unilateral nephrectomy for renal trauma 6-9 years earlier. two had received renal allografts 3 years earlier. In all cases the endogenous creatinine clearance began to rise in the second half of the menstrual cycle and when pregnancy supervened it rose rapidly to a peak value of 30-40 percent above the midcycle level within 7-10 weeks of the last menstrual period. That early peak was not always sustained and GFR subsequently fell to a level of 25-30 percent above the midcycle level. These changes in renal function were slower and smaller than in healthy women with 2 kidneys but were compatible with a successful outcome of pregnancy in these five cases.

  8. Site clearance working group

    SciTech Connect

    1997-03-01

    The Gulf of Mexico and Louisiana continue to be areas with a high level of facility removal, and the pace of removal is projected to increase. Regulations were promulgated for the Gulf of Mexico and Louisiana requiring that abandoned sites be cleared of debris that could interfere with fishing and shrimping activities. The site clearance regulations also required verification that the sites were clear. Additionally, government programs were established to compensate fishermen for losses associated with snagging their equipment on oil and gas related objects that remained on the water bottoms in areas other than active producing sites and sites that had been verified as clear of obstructions and snags. The oil and gas industry funds the compensation programs. This paper reviews the regulations and evolving operating practices in the Gulf of Mexico and Louisiana where site clearance and fisherman`s gear compensation regulations have been in place for a number of years. Although regulations and guidelines may be in place elsewhere in the world, this paper focuses on the Gulf of Mexico and Louisiana. Workshop participants are encouraged to bring up international issues during the course of the workshop. Additionally, this paper raises questions and focuses on issues that are of concern to the various Gulf of Mexico and Louisiana water surface and water bottom stakeholders. This paper does not have answers to the questions or issues. During the workshop participants will debate the questions and issues in an attempt to develop consensus opinions and/or make suggestions that can be provided to the appropriate organizations, both private and government, for possible future research or policy adjustments. Site clearance and facility removal are different activities. Facility removal deals with removal of the structures used to produce oil and gas including platforms, wells, casing, piles, pipelines, well protection structures, etc.

  9. Carbamazepine clearance and seizure stability during pregnancy.

    PubMed

    Johnson, Emily L; Stowe, Zachary N; Ritchie, James C; Newport, D Jeffrey; Newman, Melanee L; Knight, Bettina; Pennell, Page B

    2014-04-01

    The aims of this study were to characterize the alterations in total and free carbamazepine (CBZ) and in total and free carbamazepine-epoxide (CBZ-EPO) clearances during pregnancy, to calculate the change in free fractions of CBZ and CBZ-EPO during pregnancy, and to determine whether seizure worsening is associated with a low ratio to nonpregnant baseline concentration of total or free CBZ or CBZ-EPO. Women on CBZ were enrolled before conception or during pregnancy in this prospective, observational study. Concomitant medications and seizure frequency were recorded. Serum total and free CBZ and CBZ-EPO were collected at each visit. Changes in the clearance of all four compounds and free fractions of CBZ and CBZ-EPO were compared with nonpregnant baseline. During pregnancy, the ratios to baseline concentrations of total and free CBZ and CBZ-EPO were compared for months with and without increased seizure frequency. Total and free CBZ and CBZ-EPO clearances were calculated in 15 pregnancies in 12 women. Clearances did not change for any of these compounds during pregnancy. The free fraction of CBZ increased from 0.23 at baseline to a maximum of 0.32 in the third trimester (p=0.008). In the six women on CBZ monotherapy with adequate seizure diaries and blood sampling, seizure worsening did not correspond to a ratio to baseline concentration of less than 0.65 for total or free CBZ or CBZ-EPO. In conclusion, total and free CBZ and CBZ-EPO clearances did not change substantially during pregnancy, and seizure frequency worsening was not associated with decreased concentrations of total or free CBZ; therefore, therapeutic drug monitoring may not be necessary for all women on CBZ during pregnancy. Further studies with larger sample sizes are needed before definitive recommendations can be made. Carbamazepine monotherapy may be a relatively safe and cost effective treatment option for women with focal epilepsy syndromes during pregnancy.

  10. [Creatinine clearance and contrast nephropathy in patients with normal creatinine levels].

    PubMed

    de Agustín, José A; Carda, Rocío; Manzano, María del C; Ruiz-Mateos, Borja; García-Rubira, Juan C; Fernández-Ortiz, Antonio; Vilacosta, Isidre; Macaya, Carlos

    2007-07-01

    The main risk factor for contrast nephropathy is the presence of poor renal function. Plasma creatinine level is not a reliable measure of renal function as its value could lie within the normal range despite the presence of significant nephropathy. The purpose of this study was to evaluate the creatinine clearance rate as a predictor of contrast nephropathy in patients with a normal plasma creatinine level. The study included 273 consecutive patients with non-ST elevation acute coronary syndrome (NSTEACS) and a normal plasma creatinine level at admission who underwent coronary angiography. Patients who developed contrast nephropathy had a lower creatinine clearance rate at admission (66.3 mL/min vs. 83.4 mL/min; P<.001). A creatinine clearance rate < 80 mL/min had a sensitivity of 81% for predicting contrast nephropathy. Creatinine clearance should be measured routinely in patients with NSTEACS who are scheduled for coronary angiography.

  11. Renal angiography with iohexol and metrizoate

    SciTech Connect

    Toernquist, C.; Holtaes, S.

    1984-02-01

    The nephrotoxicity of the ionic contrast medium metrizoate was compared with that of nonionic iohexol when used for renal angiography. Fifteen patients who underwent renal angiography with metrizoate and 15 with iohexol were studied. Serum creatinine level, Cr-51-EDTA clearance, and urine albumin level were recorded before and after angiography. Metrizoate affected renal function, as indicated both by a transient decrease in glomerular filtration rate and by a transient albuminuria. Renal function was unaffected by iohexol. Furthermore, iohexol produced less subjective discomfort than metrizoate. There appeared to be no difference in the quality of the angiograms obtained with the two media.

  12. Renal replacement therapy for acute renal failure.

    PubMed

    Macedo, E; Bouchard, J; Mehta, R L

    2009-09-01

    Renal replacement therapy became a common clinical tool to treat patients with severe acute kidney injury (AKI) since the 1960s. During this time dialytic options have expanded considerably; biocompatible membranes, bicarbonate dialysate and dialysis machines with volumetric ultrafiltration control have improved the treatment for acute kidney injury. Along with advances in methods of intermittent hemodialysis, continuous renal replacement therapies have gained widespread acceptance in the treatment of dialysis-requiring AKI. However, many of the fundamental aspects of the renal replacement treatment such as indication, timing of dialytic intervention, and choice of dialysis modality are still controversial and may influence AKI patient's outcomes. This review outlines current concepts in the use of dialysis techniques for AKI and suggests an approach for selecting the optimal method of renal replacement therapy.

  13. Turbomachinery Clearance Control

    NASA Technical Reports Server (NTRS)

    Chupp, Raymond E.; Hendricks, Robert C.; Lattime, Scott B.; Steinetz, Bruce M.; Aksit, Mahmut F.

    2007-01-01

    Controlling interface clearances is the most cost effective method of enhancing turbomachinery performance. Seals control turbomachinery leakages, coolant flows and contribute to overall system rotordynamic stability. In many instances, sealing interfaces and coatings are sacrificial, like lubricants, giving up their integrity for the benefit of the component. They are subjected to abrasion, erosion, oxidation, incursive rubs, foreign object damage (FOD) and deposits as well as extremes in thermal, mechanical, aerodynamic and impact loadings. Tribological pairing of materials control how well and how long these interfaces will be effective in controlling flow. A variety of seal types and materials are required to satisfy turbomachinery sealing demands. These seals must be properly designed to maintain the interface clearances. In some cases, this will mean machining adjacent surfaces, yet in many other applications, coatings are employed for optimum performance. Many seals are coating composites fabricated on superstructures or substrates that are coated with sacrificial materials which can be refurbished either in situ or by removal, stripping, recoating and replacing until substrate life is exceeded. For blade and knife tip sealing an important class of materials known as abradables permit blade or knife rubbing without significant damage or wear to the rotating element while maintaining an effective sealing interface. Most such tip interfaces are passive, yet some, as for the high-pressure turbine (HPT) case or shroud, are actively controlled. This work presents an overview of turbomachinery sealing. Areas covered include: characteristics of gas and steam turbine sealing applications and environments, benefits of sealing, types of standard static and dynamics seals, advanced seal designs, as well as life and limitations issues.

  14. Renal dysfunction in patients with thalassaemia.

    PubMed

    Quinn, Charles T; Johnson, Valerie L; Kim, Hae-Young; Trachtenberg, Felicia; Vogiatzi, Maria G; Kwiatkowski, Janet L; Neufeld, Ellis J; Fung, Ellen; Oliveri, Nancy; Kirby, Melanie; Giardina, Patricia J

    2011-04-01

    Little is known about the effects of thalassaemia on the kidney. Characterization of underlying renal function abnormalities in thalassaemia is timely because the newer iron chelator, deferasirox, can be nephrotoxic. We aimed to determine the prevalence and correlates of renal abnormalities in thalassaemia patients, treated before deferasirox was widely available, using 24-h collections of urine. We calculated creatinine clearance and urine calcium-to-creatinine ratio and measured urinary β(2) -microglobulin, albumin, and protein. We used multivariate modelling to identify clinical, therapeutic, and laboratory predictors of renal dysfunction. One-third of thalassaemia patients who were not regularly transfused had abnormally high creatinine clearance. Regular transfusions were associated with a decrease in clearance (P = 0·004). Almost one-third of patients with thalassaemia had hypercalciuria, and regular transfusions were associated with an increase in the frequency and degree of hypercalciuria (P < 0·0001). Albuminuria was found in over half of patients, but was not consistently associated with transfusion therapy. In summary, renal hyperfiltration, hypercalciuria, and albuminuria are common in thalassaemia. Higher transfusion intensity is associated with lower creatinine clearance but more frequent hypercalciuria. The transfusion effect needs to be better understood. Awareness of underlying renal dysfunction in thalassaemia can inform decisions now about the use and monitoring of iron chelation.

  15. Predictive value of the efficacy of tolvaptan in liver cirrhosis patients using free water clearance

    PubMed Central

    MIYAAKI, HISAMITSU; NAKAMURA, YUTAKA; ICHIKAWA, TATSUKI; TAURA, NAOTA; MIUMA, SATOSHI; SHIBATA, HIDETAKA; HONDA, TAKUYA; NAKAO, KAZUHIKO

    2015-01-01

    Tolvaptan, an arginine vasopressin V2 antagonist, is available for patients with refractory ascites. Free water clearance was evaluated as a predictor of tolvaptan efficacy. Twenty-one patients with refractory ascites were enrolled in the present study. Liver function test, renal function test, urine volume, free water clearance and osmotic pressure were measured at baseline (day 0) and for each dose of tolvaptan (1.875, 3.75 and 7.5 mg), and compared for efficacy. Tolvaptan increased urine volume and free water clearance decreased osmotic pressure at each dose of tolvaptan, compared to pretreatment levels. Compared to baseline, an increased volume of free water clearance at 1.875 mg of tolvaptan showed a significant correlation with body weight reduction (r=0.480 and P=0.028). Any factors (age, liver function test and renal function test) at pretreatment showed no significant correlation with body weight reduction. An increased volume of urine and osmotic pressure at each dose was not significantly correlated with the tolvaptan effect. Compared to baseline, an increased volume of free water clearance at 1.875 mg of tolvaptan in responders was significantly increased, compared to non-responders (270±241 ml/day: 27±257 ml/day; P=0.042). In conclusion, an increased volume of free water clearance on day 1 was significantly associated with body weight reduction. Free water clearance could be a simple and useful marker for the prediction of tolvaptan efficacy. PMID:26623035

  16. The kidneys play a central role in the clearance of rhGH in rats.

    PubMed

    Vestergaard, Bill; Thygesen, Peter; Kreilgaard, Mads; Fels, Johannes Josef; Lykkesfeldt, Jens; Agersø, Henrik

    2016-04-30

    The kidneys are thought to play an important role in the clearance of recombinant human growth hormone (rhGH), but the relative importance is not clear. Obtaining knowledge of clearance pathway is an important prerequisite for the development of new long acting growth hormone analogues targeted at treatment of patients with growth hormone disorders. The purpose of this study was to investigate the relative importance of the kidneys in the clearance of rhGH. The study employed a newly validated nephrectomy rat model and a population based pharmacokinetic approach to assess renal clearance of rhGH in non-anesthetized rats, anesthetized rats and in nephrectomized anesthetized rats. Clearance in non-anesthetized rats was 290 ml/h/kg. This was reduced to 185 ml/h/kg by anesthesia and further reduced to 18 ml/h/kg by nephrectomy. As nephrectomy was able to reduce clearance with 90%, we conclude that renal clearance plays a pivotal role in the elimination of rhGH in rats.

  17. Predictive value of the efficacy of tolvaptan in liver cirrhosis patients using free water clearance.

    PubMed

    Miyaaki, Hisamitsu; Nakamura, Yutaka; Ichikawa, Tatsuki; Taura, Naota; Miuma, Satoshi; Shibata, Hidetaka; Honda, Takuya; Nakao, Kazuhiko

    2015-11-01

    Tolvaptan, an arginine vasopressin V2 antagonist, is available for patients with refractory ascites. Free water clearance was evaluated as a predictor of tolvaptan efficacy. Twenty-one patients with refractory ascites were enrolled in the present study. Liver function test, renal function test, urine volume, free water clearance and osmotic pressure were measured at baseline (day 0) and for each dose of tolvaptan (1.875, 3.75 and 7.5 mg), and compared for efficacy. Tolvaptan increased urine volume and free water clearance decreased osmotic pressure at each dose of tolvaptan, compared to pretreatment levels. Compared to baseline, an increased volume of free water clearance at 1.875 mg of tolvaptan showed a significant correlation with body weight reduction (r=0.480 and P=0.028). Any factors (age, liver function test and renal function test) at pretreatment showed no significant correlation with body weight reduction. An increased volume of urine and osmotic pressure at each dose was not significantly correlated with the tolvaptan effect. Compared to baseline, an increased volume of free water clearance at 1.875 mg of tolvaptan in responders was significantly increased, compared to non-responders (270±241 ml/day: 27±257 ml/day; P=0.042). In conclusion, an increased volume of free water clearance on day 1 was significantly associated with body weight reduction. Free water clearance could be a simple and useful marker for the prediction of tolvaptan efficacy.

  18. Contrast media and glomerular filtration: dose dependence of clearance for three agents

    SciTech Connect

    Baeck, S.E.K.; Krutzen, E.; Nilsson-Ehle, P.

    1988-09-01

    Determination of plasma clearance of contrast agents has been advocated as a means to assess glomerular filtration rate. To evaluate the feasibility of different agents for this purpose, we have compared, in healthy volunteers, the dose dependence of plasma clearance for three contrast media (iohexol, a nonionic agent, and iothalamate and metrizoate, which are ionic substances), with special emphasis on the lower dose range (2-20 mL corresponding to 0.9-12.9 g, depending on dose and agent). Iohexol and iothalamate were cleared at constant rates, irrespective of given dose, whereas metrizoate clearance increased significantly at lower doses. In general, the clearances or iothalamate and metrizoate were, respectively, moderately and markedly higher than that of iohexol. The clearance of different doses of metrizoate (2 mL versus a radiographic dose of 40 mL or more) was also compared with the clearance of (/sup 51/Cr)EDTA in two groups of patients with reduced renal function. When compared with (/sup 51/Cr)EDTA in patients with renal dysfunction, metrizoate was cleared significantly faster after a 2-mL dose, whereas clearances were identical when the metrizoate dose was 40 mL or more. These findings indicate that tubular secretion plays an active role in the elimination of metrizoate. The pharmacokinetic properties of iohexol, in combination with its low toxicity, make it a suitable agent for determination of glomerular filtration rate in clinical practice.

  19. Hypogonadism and renal failure: An update.

    PubMed

    Thirumavalavan, Nannan; Wilken, Nathan A; Ramasamy, Ranjith

    2015-01-01

    The prevalence of both hypogonadism and renal failure is increasing. Hypogonadism in men with renal failure carries with it significant morbidity, including anemia and premature cardiovascular disease. It remains unclear whether testosterone therapy can affect the morbidity and mortality associated with renal failure. As such, in this review, we sought to evaluate the current literature addressing hypogonadism and testosterone replacement, specifically in men with renal failure. The articles chosen for this review were selected by performing a broad search using Pubmed, Embase and Scopus including the terms hypogonadism and renal failure from 1990 to the present. This review is based on both primary sources as well as review articles. Hypogonadism in renal failure has a multifactorial etiology, including co-morbid conditions such as diabetes, hypertension, old age and obesity. Renal failure can lead to decreased luteinizing hormone production and decreased prolactin clearance that could impair testosterone production. Given the increasing prevalence of hypogonadism and the potential morbidity associated with hypogonadism in men with renal failure, careful evaluation of serum testosterone would be valuable. Testosterone replacement therapy should be considered in men with symptomatic hypogonadism and renal failure, and may ameliorate some of the morbidity associated with renal failure. Patients with all stages of renal disease are at an increased risk of hypogonadism that could be associated with significant morbidity. Testosterone replacement therapy may reduce some of the morbidity of renal failure, although it carries risk.

  20. The rebirth of interest in renal tubular function.

    PubMed

    Lowenstein, Jerome; Grantham, Jared J

    2016-06-01

    The measurement of glomerular filtration rate by the clearance of inulin or creatinine has evolved over the past 50 years into an estimated value based solely on plasma creatinine concentration. We have examined some of the misconceptions and misunderstandings of the classification of renal disease and its course, which have followed this evolution. Furthermore, renal plasma flow and tubular function, which in the past were estimated by the clearance of the exogenous aryl amine, para-aminohippurate, are no longer measured. Over the past decade, studies in experimental animals with reduced nephron mass and in patients with reduced renal function have identified small gut-derived, protein-bound uremic retention solutes ("uremic toxins") that are poorly filtered but are secreted into the lumen by organic anion transporters (OATs) in the proximal renal tubule. These are not effectively removed by conventional hemodialysis or peritoneal dialysis. Residual renal function, urine produced in patients with advanced renal failure or undergoing dialysis treatment, may represent, at least in part, secretion of fluid and uremic toxins, such as indoxyl sulfate, mediated by proximal tubule OATs and might serve as a useful survival function. In light of this new evidence of the physiological role of proximal tubule OATs, we suggest that measurement of renal tubular function and renal plasma flow may be of considerable value in understanding and managing chronic kidney disease. Data obtained in normal subjects indicate that renal plasma flow and renal tubular function might be measured by the clearance of the endogenous aryl amine, hippurate.

  1. The renal quantitative scintillation camera study for determination of renal function

    SciTech Connect

    Thompson, I.M. Jr.; Boineau, F.G.; Evans, B.B.; Schlegel, J.U.

    1983-03-01

    The renal quantitative scintillation camera study assesses glomerular filtration rate and effective renal plasma flow based upon renal uptake of 99mtechnetium-iron ascorbate and 131iodine-hippuran, respectively. The method was compared to inulin, para-aminohippuric acid and creatinine clearance studies in 7 normal subjects and 9 patients with various degrees of reduced renal function. The reproducibility of the technique was determined in 15 randomly selected pediatric patients. The values of glomerular filtration rate and effective renal plasma flow were not significantly different from those of inulin and para-aminohippuric acid studies. The reproducibility of the technique was comparable to that of inulin and para-aminohippuric acid studies. Patient acceptance of the technique is excellent and the cost is minimal. Renal morphology and excretory dynamics also are demonstrated. The technique is advocated as a clinical measure of renal function.

  2. Renal handling of matrix Gla-protein in humans with moderate to severe hypertension.

    PubMed

    Rennenberg, Roger J M W; Schurgers, Leon J; Vermeer, Cees; Scholte, Jan B J; Houben, Alphons J H M; de Leeuw, Peter W; Kroon, Abraham A

    2008-09-01

    Vascular calcifications are common among patients with hypertension. The vitamin K-dependent protein matrix Gla-protein plays an important role in preventing arterial calcification. Since a decrease in renal clearance is a prevalent clinical problem in patients with hypertension, we aimed to study the renal clearance of matrix Gla-protein from the circulation in these patients having a wide range of creatinine clearances. Ninety moderate to severe hypertensive patients who were scheduled for renal angiography were enrolled in the study. In these patients, renal arterial and renal venous blood was sampled prior to the administration of contrast material in order to determine the total renal and single kidney clearance of matrix Gla-protein. The average renal fractional extraction of matrix Gla-protein was 12.8%. There was no significant correlation between creatinine clearance (range 26-154) and renal fractional extraction of matrix Gla-protein in this population. The extraction of matrix Gla-protein was not influenced by the presence of a renal artery stenosis. In conclusion, we demonstrate that the kidney is able to extract matrix Gla-protein from the plasma at a constant level of 12.8%, independent of renal function in hypertensive subjects.

  3. Clearance Prediction of Targeted Covalent Inhibitors by In Vitro-In Vivo Extrapolation of Hepatic and Extrahepatic Clearance Mechanisms.

    PubMed

    Leung, Louis; Yang, Xin; Strelevitz, Timothy J; Montgomery, Justin; Brown, Matthew F; Zientek, Michael A; Banfield, Christopher; Gilbert, Adam M; Thorarensen, Atli; Dowty, Martin E

    2017-01-01

    The concept of target-specific covalent enzyme inhibitors appears attractive from both an efficacy and a selectivity viewpoint considering the potential for enhanced biochemical efficiency associated with an irreversible mechanism. Aside from potential safety concerns, clearance prediction of covalent inhibitors represents a unique challenge due to the inclusion of nontraditional metabolic pathways of direct conjugation with glutathione (GSH) or via GSH S-transferase-mediated processes. In this article, a novel pharmacokinetic algorithm was developed using a series of Pfizer kinase selective acrylamide covalent inhibitors based on their in vitro-in vivo extrapolation of systemic clearance in rats. The algorithm encompasses the use of hepatocytes as an in vitro model for hepatic clearance due to oxidative metabolism and GSH conjugation, and the use of whole blood as an in vitro surrogate for GSH conjugation in extrahepatic tissues. Initial evaluations with clinical covalent inhibitors suggested that the scaling algorithm developed from rats may also be useful for human clearance prediction when species-specific parameters, such as hepatocyte and blood stability and blood binding, were considered. With careful consideration of clearance mechanisms, the described in vitro-in vivo extrapolation approach may be useful to facilitate candidate optimization, selection, and prediction of human pharmacokinetic clearance during the discovery and development of targeted covalent inhibitors.

  4. Indapamide is superior to thiazide in the preservation of renal function in patients with renal insufficiency and systemic hypertension.

    PubMed

    Madkour, H; Gadallah, M; Riveline, B; Plante, G E; Massry, S G

    1996-02-22

    The long-term effects of indapamide or hydrochlorothiazide on blood presssure and renal function were examined in patents with impaired renal function and moderate hypertension. Both drugs controlled hypertension and blood pressure remained normal during the 2 years of the study. Despite this comparable control of hypertension, indapamide therapy was associated with a 28.5 +/- 4.4% increase in creatinine clearance, whereas treatment with hydrochlorothiazide was associated with a 17.4 +/- 3.0% decrease in creatinine clearance. The results of the study indicate that indapamide is superior to hydrochlorothiazide in the treatment of patients with impaired renal function and moderate hypertension.

  5. 30 CFR 57.11010 - Stairstep clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Stairstep clearance. 57.11010 Section 57.11010... Escapeways Travelways-Surface and Underground § 57.11010 Stairstep clearance. Vertical clearance above stair... to indicate an impaired clearance....

  6. 30 CFR 57.11008 - Restricted clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Restricted clearance. 57.11008 Section 57.11008... Escapeways Travelways-Surface and Underground § 57.11008 Restricted clearance. Where restricted clearance creates a hazard to persons, the restricted clearance shall be conspicuously marked....

  7. 30 CFR 56.11010 - Stairstep clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Stairstep clearance. 56.11010 Section 56.11010... Stairstep clearance. Vertical clearance above stair steps shall be a minimum of seven feet, or suitable warning signs or similar devices shall be provided to indicate an impaired clearance....

  8. 28 CFR 524.74 - Activities clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Activities clearance. 524.74 Section 524... clearance. (a) Except as provided for in paragraph (b) of this section, the Warden is the clearance... Security cases. Central Office Inmate Monitoring Section staff shall be the clearance authority on...

  9. 30 CFR 56.11008 - Restricted clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Restricted clearance. 56.11008 Section 56.11008 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Restricted clearance. Where restricted clearance creates a hazard to persons, the restricted clearance...

  10. Renal perfusion scintiscan

    MedlinePlus

    Renal perfusion scintigraphy; Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion ... supply the kidneys. This is a condition called renal artery stenosis. Significant renal artery stenosis may be ...

  11. Renal amyloidosis in a drug abuser.

    PubMed

    Tan, A U; Cohen, A H; Levine, B S

    1995-03-01

    Drug abusers, particularly those who inject drugs s.c. ("skin popping"), may develop amyloidosis. Chronic infections are thought to play a pathogenetic role in this setting. A patient is presented who had a history of "skin popping" cocaine and heroin and developed nephrotic syndrome, with an elevated serum creatinine and a creatinine clearance of 61 mL/min. Renal biopsy demonstrated amyloidosis. Treatment with colchicine was initiated, and proteinuria decreased to near normal levels after 12 months. Concomitant with the decrease in proteinuria, creatinine clearance improved, although a repeat renal biopsy failed to show any significant improvement in amyloid burden. These observations suggest that colchicine may be a useful treatment in reversing the proteinuria of renal amyloidosis associated with drug abuse. Furthermore, clinical improvement may occur before any demonstrable regression in the amyloidosis.

  12. Effect of renal impairment on the pharmacokinetics of grepafloxacin.

    PubMed

    Efthymiopoulos, C; Bramer, S L; Maroli, A; Gambertoglio, J G

    1997-01-01

    Grepafloxacin is mainly (approximately 90%) excreted by nonrenal mechanisms. The effect of renal impairment on the pharmacokinetics of grepafloxacin was evaluated in an open-label study involving 20 adults, 15 of whom had some degree of renal impairment (creatinine clearance 7.5 to 64.0 ml/min). Of these 15, 3 had mild renal impairment, 6 had moderate renal impairment, and 6 had severe renal impairment. Grepafloxacin 400 mg was administered orally once daily for 7 days, and pharmacokinetic parameters were measured on days 1 and 7. The results show that both renal clearance and the amount of grepafloxacin excreted unchanged in urine, on day 1 and day 7, were significantly lower in individuals with severe renal impairment compared with those who were healthy. Renal clearance was 0.50 +/- 0.05 ml/min/kg in healthy individuals vs 0.15 +/- 0.05 ml/min/kg in patients with severe renal impairment on day 1, while the corresponding values on day 7 were 0.46 +/- 0.04 ml/min/kg vs 0.14 +/- 0.08 ml/min/kg, respectively. The percentage of grepafloxacin excreted unchanged in urine on day 1 was 5.1 +/- 3.0 in the healthy individuals and 1.5 +/- 0.7 in those with severe renal impairment. On day 7, the corresponding values were 7.9 +/- 1.9 and 2.9 +/- 2.2. No other significant pharmacokinetic differences occurred between the 2 groups. Accumulation during multiple dose administration did not vary with the degree of renal impairment. We conclude that the pharmacokinetics of grepafloxacin are not significantly different in individuals with varying degrees of renal impairment. Hence, dose adjustment is not necessary during treatment of patients with renal dysfunction.

  13. Interspecies scaling and prediction of human clearance: comparison of small- and macro-molecule drugs

    PubMed Central

    Huh, Yeamin; Smith, David E.; Feng, Meihau Rose

    2014-01-01

    Human clearance prediction for small- and macro-molecule drugs was evaluated and compared using various scaling methods and statistical analysis.Human clearance is generally well predicted using single or multiple species simple allometry for macro- and small-molecule drugs excreted renally.The prediction error is higher for hepatically eliminated small-molecules using single or multiple species simple allometry scaling, and it appears that the prediction error is mainly associated with drugs with low hepatic extraction ratio (Eh). The error in human clearance prediction for hepatically eliminated small-molecules was reduced using scaling methods with a correction of maximum life span (MLP) or brain weight (BRW).Human clearance of both small- and macro-molecule drugs is well predicted using the monkey liver blood flow method. Predictions using liver blood flow from other species did not work as well, especially for the small-molecule drugs. PMID:21892879

  14. Interspecies scaling and prediction of human clearance: comparison of small- and macro-molecule drugs.

    PubMed

    Huh, Yeamin; Smith, David E; Feng, Meihau Rose

    2011-11-01

    Human clearance prediction for small- and macro-molecule drugs was evaluated and compared using various scaling methods and statistical analysis. Human clearance is generally well predicted using single or multiple species simple allometry for macro- and small-molecule drugs excreted renally. The prediction error is higher for hepatically eliminated small-molecules using single or multiple species simple allometry scaling, and it appears that the prediction error is mainly associated with drugs with low hepatic extraction ratio (Eh). The error in human clearance prediction for hepatically eliminated small-molecules was reduced using scaling methods with a correction of maximum life span (MLP) or brain weight (BRW). Human clearance of both small- and macro-molecule drugs is well predicted using the monkey liver blood flow method. Predictions using liver blood flow from other species did not work as well, especially for the small-molecule drugs.

  15. Pharmacokinetics of brotizolam in renal failure

    PubMed Central

    Evers, J.; Renner, E.; Bechtel, W. D.

    1983-01-01

    1 Kinetics of brotizolam (0.25 mg) were studied in patients with different degrees of renal failure after single and repeated oral ingestion. Serum levels were analysed by radio-immunoassay. 2 Patients were divided into three groups according to their renal function, i.e. creatinine clearance values of 45-80, 15-45, or less than 15 ml/min. 3 The mean elimination half-life was 6.9-8.15 h, with a considerable variation of the peak concentration and elimination half-life in slight to moderate renal failure. There was no delay in elimination in severe renal failure and there was no drug accumulation. 4 No dose adjustment is necessary for brotizolam in renal failure. PMID:6661376

  16. Mannitol clearance for the determination of glomerular filtration rate-a validation against clearance of (51) Cr-EDTA.

    PubMed

    Kiss, Katalin; Molnár, Miklós; Söndergaard, Sören; Molnár, Gyula; Ricksten, Sven-Erik

    2016-06-03

    We studied the agreement between plasma clearance of mannitol and the reference method, plasma clearance of (51) Cr-EDTA in outpatients with normal to moderately impaired renal function. Forty-one patients with a serum creatinine <200 μmol l(-1) entered the study. (51) Cr-EDTA clearance was measured with the standard bolus injection technique and glomerular filtration rate (GFR) was calculated by the single-sample method described by Jacobsson. Mannitol, 0·25 g kg(-1) body weight (150 mg ml(-1) ), was infused for 4-14 min and blood samples taken at 1-, 2-, 3- and 4-h (n = 24) or 2-, 3-, 3·5- and 4-h after infusion (n = 17). Mannitol in serum was measured by an enzymatic method. Plasma clearance for mannitol and its apparent volume of distribution (Vd) were calculated according to Brøchner-Mortensen. Mean plasma clearance (±SD) for (51) Cr-EDTA was 59·7 ± 18·8 ml min(-1) . The mean plasma clearance for mannitol ranged between 57·0 ± 20·1 and 61·1 ± 16·7 ml min(-1) and Vd was 21·3 ± 6·2% per kg b.w. The between-method bias ranged between -0·23 and 2·73 ml min(-1) , the percentage error between 26·7 and 39·5% and the limits of agreement between -14·3/17·2 and -25·3/19·9 ml min(-1) . The best agreement was seen when three- or four-sample measurements of plasma mannitol were obtained and when sampling started 60 min after injection. Furthermore, accuracy of plasma clearance determinations was 88-96% (P30) and 41-63% (P10) and was highest when three- or four-sample measurements of plasma mannitol were obtained, including the first hour after the bolus dose. We conclude that there is a good agreement between plasma clearances of mannitol and (51) Cr-EDTA for the assessment of GFR.

  17. Pharmacokinetics of renally excreted drug dexpramipexole in subjects with impaired renal function

    PubMed Central

    He, Ping; Kerr, Doug; Marbury, Thomas; Ries, Daniel; Farwell, Wildon; Stecher, Scott; Dong, Yingwen; Wei, Dong; Rogge, Mark

    2014-01-01

    This phase I, open-label, single-dose study evaluated the pharmacokinetics, safety, and tolerability of renally excreted drug dexpramipexole in subjects with normal and impaired renal function, i.e. mild, moderate, severe renal impairment, or end-stage renal disease (ESRD) requiring hemodialysis when matched by age and sex. Dexpramipexole area under the curves (AUCs), but not Cmax, were significantly increased with the severity of renal impairment after a single dose administration. The geometric mean ratio of dose-normalized AUC(0–72) was 1.4, 1.7, 2.7, and 4.5, respectively, in mild, moderate, severe renal impairment, and ESRD subjects when compared to healthy subjects. There was a strong association between renal function (eGFR) and dexpramipexole CLr. The slope (90% confidence interval(CI)) of eGFR and renal clearance (CLr) in the regression model was 3.1 (2.4, 3.7). Dexpramipexole elimination in ESRD subjects during both dialysis and non-dialysis (i.e., interval between dialysis) was insignificant. Single 75 mg and 150 mg doses of dexpramipexole were well tolerated, and the safety profile was comparable across renal function groups. Extensive drug accumulation may occur with repeated dosing in patients with significant renal impairment. It is recommended that dexpramipexole not to be given to patients with severe renal impairment or in those with ESRD. PMID:24965504

  18. Continuous intragastric delivery of fenoldopam: relationship between plasma concentration and effects on renal function.

    PubMed Central

    Ziemniak, J A; Boppana, V K; Cyronak, M J; Beck, T R; Familiar, R G; Dubb, J W; Allison, N L; Stote, R M

    1988-01-01

    1. The pharmacodynamics of the dopamine DA1 agonist fenoldopam were examined in six healthy male volunteers after constant intragastric infusions of fenoldopam at dosages of 0, 10, 25, 50 and 75 mg h-1 for 6 h. 2. Hourly p-aminohippurate (PAH) clearance was used to assess fenoldopam induced renal plasma flow changes. Marked dose-related increases in renal plasma flow were noted with a maximal increase of 65% over baseline values of 711 ml min-1 being seen at the 75 mg h-1 rate. No changes in sodium excretion and glomerular filtration rate were observed. 3. Mean steady-state fenoldopam plasma concentrations were related to mean PAH clearance based on an Emax model (r = 0.996) with an Emax of 1350 ml min-1 and an EC50 of 6.2 ng ml-1. 4. Mean steady-state plasma concentrations of fenoldopam-7-sulphate and fenoldopam-8-sulphate failed to increase with dose but were linearly correlated to mean PAH changes (r = 0.998, r = 0.981 respectively). 5. These results support the concept of extending fenoldopam's duration of action through the development of an oral sustained delivery system. PMID:2896014

  19. Clearance of von Willebrand factor.

    PubMed

    Denis, Cécile V; Christophe, Olivier D; Oortwijn, Beatrijs D; Lenting, Peter J

    2008-02-01

    The life cycle of von Willebrand factor (VWF) comprises a number of distinct steps, ranging from the controlled expression of the VWF gene in endothelial cells and megakaryocytes to the removal of VWF from the circulation. The various aspects of VWF clearance have been the objects of intense research in the last few years, stimulated by observations that VWF clearance is a relatively common component of the pathogenesis of type 1 von Willebrand disease (VWD). Moreover, improving the survival of VWF is now considered as a viable therapeutic strategy to prolong the half-life of factor VIII in order to optimise treatment of haemophilia A. The present review aims to provide an overview of recent findings with regard to the molecular basis of VWF clearance. A number of parameters have been identified that influence VWF clearance, including its glycosylation profile and a number of VWF missense mutations. In addition, in-vivo studies have been used to identify cells that contribute to the catabolism of VWF, providing a starting point for the identification of receptors that mediate the cellular uptake of VWF. Finally, we discuss recent data describing chemically modification of VWF as an approach to prolong the half-life of the VWF/FVIII complex.

  20. Aerial Refueling Clearance Initiation Request

    DTIC Science & Technology

    2016-07-14

    and receiver agencies. The AR Clearance Initiation Request document recognizes the requirement for definitive aerial refueling agreements between...include directions for the development or content of these contractual agreements. 15. –SUBJECT TERMS See Document Terms and Definitions , Page 8 16...7 Terms and Definitions

  1. Myeloid cell turnover and clearance

    PubMed Central

    Janssen, William J.; Bratton, Donna L.; Jakubzick, Claudia V.; Henson, Peter M.

    2016-01-01

    Given the dual and intrinsically contradictory roles for myeloid cells in both protective and yet also damaging effects of inflammatory and immunological processes we suggest that it is important to consider the mechanisms and circumstances by which these cells are removed, either in the normal unchallenged state or during inflammation or disease. In this essay we address these subjects from a conceptual perspective, focusing as examples on four main myeloid cell types (neutrophils, monocytes, macrophages and myeloid dendritic cells) and their clearance from the circulation or from naïve and inflamed tissues. While the primary clearance process appears to involve endocytic uptake into macrophages, various tissue cell types can also recognize and remove dying cells though their overall quantitative contribution is unclear. In fact, surprisingly, given the wealth of study in this area over the last 30 years, our conclusion is that we are still challenged with substantial lack of mechanistic and regulatory understanding of when, how and by what mechanisms migratory myeloid cells come to die, are recognized as needing to be removed and indeed the precise processes of uptake of either the intact or fragmented cells. This reflects the extreme complexity and inherent redundancy of the clearance processes and argues for substantial investigative effort in this arena. In addition, it leads us to a sense that approaches to significant therapeutic modulation of selective myeloid clearance is still a long way off. PMID:27837740

  2. Impact of pregnancy on underlying renal disease.

    PubMed

    Baylis, Chris

    2003-01-01

    Normal pregnancy involves marked renal vasodilation and large increases in glomerular filtration rate (GFR). Studies in rats reveal that the gestational renal vasodilation is achieved by parallel reductions in tone in afferent and efferent arterioles so GFR rises without a change in glomerular blood pressure. There is some evidence from animal studies that increased renal generation of nitric oxide (NO) may be involved. Although chronic renal vasodilation has been implicated in causing progression of renal disease in nonpregnant states by glomerular hypertension, there are no long-term deleterious effects of pregnancies on the kidney when maternal renal function is normal because glomerular blood pressure remains normal. When maternal renal function is compromised before conception, there are no long-term adverse effects on renal function in most types of renal disease, providing that the GFR is well maintained before conception. When serum creatinine exceeds approximately 1.4 mg/dL, pregnancy may accelerate the renal disease increases and when serum creatinine >2 mg/dL, the chances are greater than 1 in 3 that pregnancy will hasten the progression of the renal disease. The available animal studies suggest that glomerular hypertension does not occur despite diverse injuries. Thus, the mechanisms of the adverse interaction between pregnancy and underlying renal disease remain unknown.

  3. Renal Stones

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Renal stones are never convenient, but they are a particular concern for astronauts who have limited access to treatment during flight. Researchers are examining how earthbound preventions for renal stone formation work in flight, ensuring missions are not ended prematurely due to this medical condition. The micrograph shows calcium oxalate crystals in urine. These small crystals can develop to form renal stones. Principal Investigator: Dr. Peggy Whitson, NASA Johnson Space Center, Houston, TX.

  4. Renal and extrarenal regulation of potassium.

    PubMed

    Giebisch, G; Krapf, R; Wagner, C

    2007-08-01

    The ISN Forefronts in Nephrology Symposium took place 8-11 September 2005 in Kartause Ittingen, Switzerland. It was dedicated to the memory of Robert W. Berliner, who died at age 86 on 5 February 2002. Dr Berliner contributed in a major way to our understanding of potassium transport in the kidney. Starting in the late 1940s, without knowledge of how potassium was transported across specific nephron segments and depending only on renal clearance methods, he and his able associates provided a still-valid blueprint of the basic transport properties of potassium handling by the kidney. They firmly established that potassium was simultaneously reabsorbed and secreted along the nephron; that variations in secretion in the distal nephron segments play a major role in regulating potassium excretion; and that such secretion is modulated by sodium, acid-base factors, hormones, and diuretics. These conclusions were presented in a memorable Harvey Lecture some forty years ago, and they have remained valid ever since. The concepts have also provided the foundation and stimulation for later work on single nephrons, tubule cells, and transport proteins involved in potassium transport.

  5. Interactions Among Drinking and Ground Water Contaminants on Renal and Hepatic Function

    DTIC Science & Technology

    1988-07-25

    inulin . The change was more pronounced in the saline group, because the MCA + oil group had a somewhat diminished GFR. There were no significant effects...flow rate were not affected by MCA, VDC or the combined treatment. ftEMALES VDC decreased GFR, assessed as clearance of inulin , in both saline and MCA...apparently disparate, they are in agreement with the known relationship between renal function assessed by inulin clearance and lack of clearance of

  6. Effects of water immersion on renal hemodynamics in normal man

    NASA Technical Reports Server (NTRS)

    Epstein, M.; Levinson, R.; Loutzenhiser, R.

    1976-01-01

    The present study was undertaken to delineate the effects of water immersion to the neck (NI) on renal plasma flow and glomerular filtration rate as assessed by the clearance of p-aminohippuric acid (PAH) and inulin, respectively. Nine normal male subjects were studied on two occasions, control and NI. The conditions of seated posture and time of day were identical. Immersion did not alter either clearance at a time when sodium excretion was increasing markedly. The constancy of PAH clearance during NI suggests that renal blood flow is unaltered and that the natriuresis of NI is mediated independently of alterations in overall renal perfusion. The sluggish decline of a natriuresis during recovery is consistent with the presence of a humoral factor contributing to the encountered natriuresis.

  7. Microwave Blade Tip Clearance System: An Update

    NASA Technical Reports Server (NTRS)

    Geisheimer, Jon

    2006-01-01

    Newer engines use compressor bleed air and a model to close clearances open loop. Measuring clearances and closing the control loop can add additional efficiencies. Tip clearance control has been identified as a key technology for future engines Additional benefits in prognostics, NSMS, and condition-based maintenance. In the HPT for every 1 mil improvement in clearance: a) SFC decreases 0.1%; and b) EGT margin increases 1 C.

  8. Physiologically Based Pharmacokinetic Predictions of Tramadol Exposure Throughout Pediatric Life: an Analysis of the Different Clearance Contributors with Emphasis on CYP2D6 Maturation.

    PubMed

    T'jollyn, Huybrecht; Snoeys, Jan; Vermeulen, An; Michelet, Robin; Cuyckens, Filip; Mannens, Geert; Van Peer, Achiel; Annaert, Pieter; Allegaert, Karel; Van Bocxlaer, Jan; Boussery, Koen

    2015-11-01

    This paper focuses on the retrospective evaluation of physiologically based pharmacokinetic (PBPK) techniques used to mechanistically predict clearance throughout pediatric life. An intravenous tramadol retrograde PBPK model was set up in Simcyp® using adult clearance values, qualified for CYP2D6, CYP3A4, CYP2B6, and renal contributions. Subsequently, the model was evaluated for mechanistic prediction of total, CYP2D6-related, and renal clearance predictions in very early life. In two in vitro pediatric human liver microsomal (HLM) batches (1 and 3 months), O-desmethyltramadol and N-desmethyltramadol formation rates were compared with CYP2D6 and CYP3A4 activity, respectively. O-desmethyltramadol formation was mediated only by CYP2D6, while N-desmethyltramadol was mediated in part by CYP3A4. Additionally, the clearance maturation of the PBPK model predictions was compared to two in vivo maturation models (Hill and exponential) based on plasma concentration data, and to clearance estimations from a WinNonlin® fit of plasma concentration and urinary excretion data. Maturation of renal and CYP2D6 clearance is captured well in the PBPK model predictions, but total tramadol clearance is underpredicted. The most pronounced underprediction of total and CYP2D6-mediated clearance was observed in the age range of 2-13 years. In conclusion, the PBPK technique showed to be a powerful mechanistic tool capable of predicting maturation of CYP2D6 and renal tramadol clearance in early infancy, although some underprediction occurs between 2 and 13 years for total and CYP2D6-mediated tramadol clearance.

  9. 14 CFR 23.925 - Propeller clearance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., an airplane with an aft mounted propeller must be designed such that the propeller will not contact...) Structural clearance. There must be— (1) At least one inch radial clearance between the blade tips and the... least one-half inch longitudinal clearance between the propeller blades or cuffs and stationary parts...

  10. 14 CFR 23.925 - Propeller clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., an airplane with an aft mounted propeller must be designed such that the propeller will not contact...) Structural clearance. There must be— (1) At least one inch radial clearance between the blade tips and the... least one-half inch longitudinal clearance between the propeller blades or cuffs and stationary parts...

  11. 14 CFR 23.925 - Propeller clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., an airplane with an aft mounted propeller must be designed such that the propeller will not contact...) Structural clearance. There must be— (1) At least one inch radial clearance between the blade tips and the... least one-half inch longitudinal clearance between the propeller blades or cuffs and stationary parts...

  12. 14 CFR 23.925 - Propeller clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., an airplane with an aft mounted propeller must be designed such that the propeller will not contact...) Structural clearance. There must be— (1) At least one inch radial clearance between the blade tips and the... least one-half inch longitudinal clearance between the propeller blades or cuffs and stationary parts...

  13. 29 CFR 1917.113 - Clearance heights.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Clearance heights. 1917.113 Section 1917.113 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.113 Clearance heights. Clearance heights shall...

  14. 22 CFR 16.6 - Security clearances.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a...

  15. 22 CFR 16.6 - Security clearances.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a...

  16. 22 CFR 16.6 - Security clearances.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a...

  17. 22 CFR 16.6 - Security clearances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a...

  18. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical...

  19. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical...

  20. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical...

  1. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical...

  2. Security Clearances: Consideration of Sexual Orientation in the Clearance Process.

    DTIC Science & Technology

    1995-03-01

    Until about 1991, when agencies began to change their security policies and practices regarding sexual orientation , there were a number of documented...cases where defense civilian or contractor employees’ security clearances were denied or revoked because of their sexual orientation . However our...forward and discuss their cases. Notwithstanding these limitations, our work disclosed no evidence that sexual orientation has been used as a criterion

  3. Effects of exercise on renal function in patients with moderate impairment of renal function compared to normal men.

    PubMed

    Taverner, D; Craig, K; Mackay, I; Watson, M L

    1991-01-01

    The renal excretory and haemodynamic responses to sustained moderate exertion were investigated in normotensive humans with impaired renal function and normal volunteers. The heart rate increase with exercise was similar in each group. Subjects with impaired renal function showed a significant fall in glomerular filtration rate on exertion, while normals did not. In the presence of renal disease, urine osmolality did not rise with exertion, although it rose markedly in the normal group. Free water clearance became negative after exercise in the normal group only. The diseased kidney is unable to maintain glomerular filtration rate or conserve water under the stress of exertion as well as the normal kidney.

  4. Removal - An alternative to clearance

    SciTech Connect

    Feinhals, J.; Kelch, A.; Kunze, V.

    2007-07-01

    This presentation shows the differences between the application of clearance and removal, both being procedures for materials leaving radiation protection areas permanently. The differentiation will be done on the basis of the German legislation but may be also applicable for other national legislation. For clearance in Germany two basic requirements must be given, i.e. that the materials are activated or contaminated and that they result from the licensed use or can be assigned to the scope of the license. Clearance needs not to be applied to objects in Germany which are to be removed only temporarily from controlled areas with the purpose of repair or reuse in other controlled areas. In these cases only the requirements of contamination control apply. In the case of removal it must either be proved by measurements that the relevant materials are neither activated nor contaminated or that the materials result from areas where activation or contamination is impossible due to the operational history considering operational procedures and events. If the material is considered neither activated nor contaminated there is no need for a clearance procedure. Therefore, these materials can be removed from radiation protection areas and the removal is in the responsibility of the licensee. Nevertheless, the removal procedure and the measuring techniques to be applied for the different types of materials need an agreement from the competent authority. In Germany a maximum value of 10% of the clearance values has been established in different licenses as a criterion for the application of removal. As approximately 2/3 of the total mass of a nuclear power plant is not expected to be contaminated or activated there is a need for such a procedure of removal for this non contaminated material without any regulatory control especially in the case of decommissioning. A remarkable example is NPP Stade where in the last three years more than 8600 Mg were disposed of by removal and

  5. Treatment of severe hypothyroidism in a patient with progressive renal failure leads to significant improvement of renal function.

    PubMed

    van Welsem, M E; Lobatto, S

    2007-06-01

    The case of a 41-year-old patient with end-stage renal failure and diabetes mellitus Type 1 who was being prepared for renal replacement therapy is described. After severe hypothyroidism was diagnosed, thyroid hormone substitution therapy was started. Subsequently, a substantial decline in serum creatinine was observed. Creatinine clearance rose from 19 to 40 ml/min and renal replacement therapy was no longer imminent. Several studies have described the pathophysiology of diminished renal function in hypothyroidism. Few studies or case reports have shown amelioration of end-stage renal failure as seen in our patient. The etiology is presumed to be multifactorial, in which hemodynamic effects and a direct effect of thyroid hormone on the kidney play an important role. Diagnosing signs of hypothyroidism and therapy with thyroid hormone in progressive renal failure could be very important in delaying the need for renal replacement therapy.

  6. Renal denervation and heart failure.

    PubMed

    Böhm, Michael; Ewen, Sebastian; Kindermann, Ingrid; Linz, Dominik; Ukena, Christian; Mahfoud, Felix

    2014-06-01

    Renal denervation has been developed in order to lower systolic blood pressure in resistant hypertension by a reduction in renal afferent and efferent sympathetic nerve activity. In heart failure sympathetic activation, in particular, renal norepinephrine release is closely associated with morbidity and mortality. Initial studies have shown that renal denervation is able to reduce not only blood pressure but also heart rate, and is associated with a reduction in myocardial hypertrophy, improved glucose tolerance, and ameliorated microalbuminuria. Since some experimental and observational data suggest an antiarrhythmic effect, it is possible that renal denervation might also play a therapeutic role in arrhythmias often occurring in chronic heart failure. The first proof-of-concept studies are planned to evaluate the clinical effect of this pathophysiologically plausible method, which might be able to change clinical practice.

  7. Longitudinal Hemodiafilter Performance in Modeled Continuous Renal Replacement Therapy

    PubMed Central

    Pasko, Deborah A.; Churchwell, Mariann D.; Salama, Noha N.; Mueller, Bruce A.

    2011-01-01

    Background/Aims With advanced anticoagulation, many institutions operate continuous renal replacement therapy (CRRT) circuits longer than manufacturers’ recommendations. This extended use may change hemodiafilter performance and clearance properties. However, hemodiafilter performance over time has not been assessed. We investigated solute clearance over time in modeled CRRT. Methods In vitro continuous hemofiltration (CH) and continuous hemodialysis (CD) were operated for 48 h using AN69 polyacrylonitrile, cellulose triacetate, F70 polysulfone, and Optiflux F160NR polysulfone hemodiafilters with citrated bovine blood. Urea, creatinine, gentamicin, vancomycin, and albumin clearances were assessed in CH (ultrafiltration rates = 1 and 3 l/h). Clearances of urea, creatinine, gentamicin, and albumin, were assessed in CD with dialysate flow rate of 2 l/h. Results Solute CH clearances were significantly higher at 3 l/h. Only creatinine and gentamicin clearances were affected by time. Creatinine CD clearance significantly declined at 48 h for all hemodiafilters, especially polysulfone hemodiafilters. Conclusions CRRT duration affects solute transmembrane clearance. Clinicians should consider hemodiafilter age when assessing hemodialysis dose or drug clearance. PMID:21372565

  8. Aerial Refueling Clearance Process Guide

    DTIC Science & Technology

    2014-08-21

    08-2014 2. REPORT TYPE Guidance Document 3. DATES COVERED 2008-2014 4. TITLE AND SUBTITLE Aerial Refueling Clearance Process Guide Attachment: Aerial...ATP-3.3.4.2 covers general operational procedures for AR and national/organizational SRDs cover data and procedures specific to their AR platforms...Receptacle, Probe/Drogue, and BDA Kit. 3.1.3 The items for assessment consideration cover several areas of interface for both the tanker and the

  9. A novel rodent model of severe renal ischemia reperfusion injury.

    PubMed

    Whalen, Henry; Shiels, Paul; Littlejohn, Marc; Clancy, Marc

    2016-11-01

    Renal ischemia reperfusion injury (IRI) is a major problem, currently without treatments in clinical use. This reflects the failure of animal models to mimic the severity of IRI observed in clinical practice. Most described models lack both the ability to inflict a permanent reduction in renal function and the sensitivity to demonstrate the protective efficacy of different therapies in vivo. To test novel cell-based therapies, we have developed a model of renal IRI in Fisher 344 rats. Animals were subjected to 120 min of unilateral warm ischemia, during which they underwent an intra-renal artery infusion of therapeutic agents or vehicle. At either 2 or 6 weeks post-surgery, animals underwent terminal glomerular filtration rate (GFR) studies by inulin clearance to most accurately quantify renal function. Harvested kidneys underwent histological analysis. Compared to sham operations, saline treated animals suffered a long-term reduction in GFR of ≈50%. Histology revealed short- and long-term disruption of renal architecture. Despite the injury severity, post-operative animal losses are <5%. This model produces a severe, consistent renal injury that closely replicates the pathological processes encountered in clinical medicine. Renal artery infusion mimics the route likely employed in clinical transplantation, where the renal artery is accessible. Inulin clearance characterizes GFR, allowing full assessment of therapeutic intervention. This model is useful for screening therapeutic agents prior to testing in a transplant model. This reduces animal numbers needed to test drugs for clinical transplantation and allows for refinement of dosing schedules.

  10. Reification of abstract concepts to improve comprehension using interactive virtual environments and a knowledge-based design: a renal physiology model.

    PubMed

    Alverson, Dale C; Saiki, Stanley M; Caudell, Thomas P; Goldsmith, Timothy; Stevens, Susan; Saland, Linda; Colleran, Kathleen; Brandt, John; Danielson, Lee; Cerilli, Lisa; Harris, Alexis; Gregory, Martin C; Stewart, Randall; Norenberg, Jeffery; Shuster, George; Panaoitis; Holten, James; Vergera, Victor M; Sherstyuk, Andrei; Kihmm, Kathleen; Lui, Jack; Wang, Kin Lik

    2006-01-01

    Several abstract concepts in medical education are difficult to teach and comprehend. In order to address this challenge, we have been applying the approach of reification of abstract concepts using interactive virtual environments and a knowledge-based design. Reification is the process of making abstract concepts and events, beyond the realm of direct human experience, concrete and accessible to teachers and learners. Entering virtual worlds and simulations not otherwise easily accessible provides an opportunity to create, study, and evaluate the emergence of knowledge and comprehension from the direct interaction of learners with otherwise complex abstract ideas and principles by bringing them to life. Using a knowledge-based design process and appropriate subject matter experts, knowledge structure methods are applied in order to prioritize, characterize important relationships, and create a concept map that can be integrated into the reified models that are subsequently developed. Applying these principles, our interdisciplinary team has been developing a reified model of the nephron into which important physiologic functions can be integrated and rendered into a three dimensional virtual environment called Flatland, a virtual environments development software tool, within which a learners can interact using off-the-shelf hardware. The nephron model can be driven dynamically by a rules-based artificial intelligence engine, applying the rules and concepts developed in conjunction with the subject matter experts. In the future, the nephron model can be used to interactively demonstrate a number of physiologic principles or a variety of pathological processes that may be difficult to teach and understand. In addition, this approach to reification can be applied to a host of other physiologic and pathological concepts in other systems. These methods will require further evaluation to determine their impact and role in learning.

  11. Prediction of human drug clearance by multiple metabolic pathways: integration of hepatic and intestinal microsomal and cytosolic data.

    PubMed

    Cubitt, Helen E; Houston, J Brian; Galetin, Aleksandra

    2011-05-01

    The current study assesses hepatic and intestinal glucuronidation, sulfation, and cytochrome P450 (P450) metabolism of raloxifene, quercetin, salbutamol, and troglitazone using different in vitro systems. The fraction metabolized by conjugation and P450 metabolism was estimated in liver and intestine, and the importance of multiple metabolic pathways on accuracy of clearance prediction was assessed. In vitro intrinsic sulfation clearance (CL(int, SULT)) was determined in human intestinal and hepatic cytosol and compared with hepatic and intestinal microsomal glucuronidation (CL(int, UGT)) and P450 clearance (CL(int, CYP)) expressed per gram of tissue. Hepatic and intestinal cytosolic scaling factors of 80.7 mg/g liver and 18 mg/g intestine were estimated from published data. Scaled CL(int, SULT) ranged between 0.7 and 11.4 ml · min(-1) · g(-1) liver and 0.1 and 3.3 ml · min(-1) · g(-1) intestine (salbutamol and quercetin were the extremes). Salbutamol was the only compound with a high extent of sulfation (51 and 28% of total CL(int) for liver and intestine, respectively) and also significant renal clearance (26-57% of observed plasma clearance). In contrast, the clearance of quercetin was largely accounted for by glucuronidation. Drugs metabolized by multiple pathways (raloxifene and troglitazone) demonstrated improved prediction of intravenous clearance using data from all hepatic pathways (44-86% of observed clearance) compared with predictions based only on the primary pathway (22-36%). The assumption of no intestinal first pass resulted in underprediction of oral clearance for raloxifene, troglitazone, and quercetin (3-22% of observed, respectively). Accounting for the intestinal contribution to oral clearance via estimated intestinal availability improved prediction accuracy for raloxifene and troglitazone (within 2.5-fold of observed). Current findings emphasize the importance of both hepatic and intestinal conjugation for in vitro-in vivo extrapolation

  12. Prediction of drug clearance in children.

    PubMed

    Foissac, Frantz; Bouazza, Naïm; Valade, Elodie; De Sousa Mendes, Mailys; Fauchet, Floris; Benaboud, Sihem; Hirt, Déborah; Tréluyer, Jean-Marc; Urien, Saïk

    2015-07-01

    The pediatric population is often exposed to drugs without sufficient knowledge about pharmacokinetics. The prediction of accurate clearance values in children, especially in neonates and infants, will improve the rational in dosing decisions. Drug clearances from birth to adulthood were compiled after a systematic review of pharmacokinetic reports. The analysis was performed using NONMEM. Clearance predictions were then evaluated by external validation. Prediction errors were also compared with those obtained from weight-based allometric scaling and physiologically based clearance (PBCL) models. For the analysis, 17 and 15 drugs were used for model building and external validation, respectively. A model based on the adult drug clearance value and taking into account both weight and age was retained. Age-related maturation of clearance reached 90% of the adult value within 1.5 years of life. For children less than 2 years old, allometric scaling alone systematically overestimated clearances. Accounting for age improved the clearance prediction in the 6 months-2 years age group (prediction error < 25%). Predictions obtained from the PBCL approach were close to our results. This analysis established a single equation using the adult clearance value as well as individual age and weight to predict drug clearance in children older than 6 months.

  13. Effects of Probenecid and Cimetidine on Renal Disposition of Ofloxacin in Rats

    PubMed Central

    Foote, Edward F.; Halstenson, Charles E.

    1998-01-01

    The renal handling of ofloxacin in rats which were given ofloxacin either alone or in combination with probenecid or cimetidine was studied. In the presence of cimetidine or probenecid, ofloxacin’s total and renal clearances were reduced and its half-life was prolonged. This suggests that ofloxacin is secreted by both the anionic and cationic transport systems. PMID:9527807

  14. Technetium-99m MAG-3 clearances after captopril in experimental renovascular hypertension

    SciTech Connect

    Lee, H.B.; Blaufox, M.D.

    1989-05-01

    Rats with one kidney clamped (2K1C), both kidneys clamped (2K2C), unilaterally nephrectomized with remaining kidney clamped (1K1C), and normals, were studied using /sup 99m/Tc mercaptoacetyltriglycine ((/sup 99m/Tc)MAG-3) and /sup 131/I orthoiodohippurate ((/sup 131/I)OIH). Clearances of (/sup 99m/Tc)MAG-3 and (/sup 131/I)OIH were performed after constricted rats became hypertensive. Clearances were repeated after i.v. Captopril. Clearances of (/sup 99m/Tc)MAG-3 and (/sup 131/I)OIH in normals didn't change significantly after Captopril. Clearances of (/sup 99m/Tc)MAG-3 and (/sup 131/I)OIH decreased insignificantly after Captopril in the 2K2C model. in the 2K1C group, normal kidney clearance increased ((/sup 99m/Tc)MAG-3 p less than 0.01 and (/sup 131/I)OIH p less than 0.025) and clamped kidney clearance decreased after inhibition ((/sup 99m/Tc)MAG-3, p less than 0.01, (/sup 131/I)OIH p less than 0.02). Clearances increased in the 1K1C group after Captopril ((/sup 99m/Tc)MAG-3 p less than 0.0025 and (/sup 131/I)OIH, p less than 0.001). The ratio of (/sup 99m/Tc)MAG-3 to (/sup 131/I)OIH before Captopril was 0.81 and 0.84 after Captopril. Changes in renal function after Captopril depend on the model of renovascular hypertension and possibly the dose administered. Technetium-99m MAG-3 clearance parallels (/sup 131/I)orthoiodohippurate in renovascular hypertension.

  15. Mechanism of ritonavir changes in methadone pharmacokinetics and pharmacodynamics: I. Evidence against CYP3A mediation of methadone clearance.

    PubMed

    Kharasch, E D; Bedynek, P S; Park, S; Whittington, D; Walker, A; Hoffer, C

    2008-10-01

    Ritonavir diminishes methadone plasma concentrations, an effect attributed to CYP3A induction, but the actual mechanisms are unknown. We determined ritonavir effects on stereoselective methadone pharmacokinetics and clinical effects (pupillary miosis) in healthy human immunodeficiency virus-negative volunteers. Subjects received intravenous plus oral (deuterium-labeled) racemic methadone after no ritonavir, short-term (3-day) ritonavir, and steady-state ritonavir. Acute and steady-state ritonavir, respectively, caused 1.5- and 2-fold induction of systemic and apparent oral R- and S-methadone clearances. Ritonavir increased renal clearance 40-50%, and stereoselectively (S > R) increased hepatic methadone N-demethylation 50-80%, extraction twofold, and clearance twofold. Bioavailability was unchanged despite significant inhibition of intestinal P-glycoprotein. Intestinal and hepatic CYP3A was inhibited > 70%. Ritonavir shifted methadone plasma concentration-miosis curves leftward and upward. Rapid ritonavir induction of methadone clearance results from increased renal clearance and induced hepatic metabolism. Induction of methadone metabolism occurred despite profound CYP3A inhibition, suggesting no role for CYP3A in clinical methadone metabolism and clearance. Ritonavir may alter methadone pharmacodynamics.

  16. Intradialytic clearance of opioids: methadone versus hydromorphone.

    PubMed

    Perlman, Ryan; Giladi, Hili; Brecht, Krista; Ware, Mark A; Hebert, Terence E; Joseph, Lawrence; Shir, Yoram

    2013-12-01

    Opioids are commonly prescribed to patients with chronic pain associated with end-stage renal disease requiring hemodialysis. The stability of opioid analgesia during dialysis may vary among different opioids. No studies to date have corroborated this clinical observation by directly comparing plasma concentrations of different opioids during dialysis. We compared changes in peridialysis plasma concentrations of 2 pharmacokinetically distinct opioids, methadone and hydromorphone (HM). Fourteen dialysis patients with chronic pain received either methadone or HM for at least 2 weeks before beginning the study. Blood samples were obtained immediately before, during, and after hemodialysis in 2 separate dialysis sessions, 1 week apart, and were analyzed for opioid concentrations. Methadone plasma concentrations were more stable during hemodialysis compared to HM: the mean percent change of methadone plasma levels was 14.9% ± 8.2% (± SD) compared with 55.1% ± 8.1% in the HM treatment group, a difference of 40.2% (95% confidence interval 17.14 to 63.14). The mean plasma clearance of methadone was 19.9 ± 8.5 mL/min (± SD) compared with 105.7 ± 8.3 mL/min for HM, a difference of 85.7 mL/min (95% confidence interval 61.9 to 109.1). There were no differences between the 2 opioid groups in pain scores, side effect profile, and quality of life. Methadone therapy was not associated with an increased rate of adverse events. If confirmed by larger clinical studies, methadone could be considered as one of the opioids of choice in dialysis patients.

  17. Renal Scintigraphy

    MedlinePlus

    ... size with caption Related Articles and Media General Nuclear Medicine Radiation Dose in X-Ray and CT Exams X-ray, Interventional Radiology and Nuclear Medicine Radiation Safety Images related to Renal Scintigraphy Sponsored by ...

  18. Associations between Tumor Vascularity, Vascular Endothelial Growth Factor Expression and PET/MRI Radiomic Signatures in Primary Clear-Cell-Renal-Cell-Carcinoma: Proof-of-Concept Study.

    PubMed

    Yin, Qingbo; Hung, Sheng-Che; Wang, Li; Lin, Weili; Fielding, Julia R; Rathmell, W Kimryn; Khandani, Amir H; Woods, Michael E; Milowsky, Matthew I; Brooks, Samira A; Wallen, Eric M; Shen, Dinggang

    2017-03-03

    Studies have shown that tumor angiogenesis is an essential process for tumor growth, proliferation and metastasis. Also, tumor angiogenesis is an important prognostic factor of clear cell renal cell carcinoma (ccRCC), as well as a factor in guiding treatment with antiangiogenic agents. Here, we attempted to find the associations between tumor angiogenesis and radiomic imaging features from PET/MRI. Specifically, sparse canonical correlation analysis was conducted on 3 feature datasets (i.e., radiomic imaging features, tumor microvascular density (MVD), and vascular endothelial growth factor (VEGF) expression) from 9 patients with primary ccRCC. In order to overcome the potential bias of intratumoral heterogeneity of angiogenesis, this study investigated the relationship between regional expressions of angiogenesis and VEGF, and localized radiomic features from different parts within the tumors. Our study highlighted the significant strong correlations between radiomic features and MVD, and also demonstrated that the spatiotemporal features extracted from DCE-MRI provided stronger radiomic correlation to MVD than the textural features extracted from Dixon sequences and FDG PET. Furthermore, PET/MRI, which takes advantage of the combined functional and structural information, had higher radiomics correlation to MVD than solely utilizing PET or MRI alone.

  19. Associations between Tumor Vascularity, Vascular Endothelial Growth Factor Expression and PET/MRI Radiomic Signatures in Primary Clear-Cell–Renal-Cell-Carcinoma: Proof-of-Concept Study

    PubMed Central

    Yin, Qingbo; Hung, Sheng-Che; Wang, Li; Lin, Weili; Fielding, Julia R.; Rathmell, W. Kimryn; Khandani, Amir H.; Woods, Michael E.; Milowsky, Matthew I.; Brooks, Samira A.; Wallen, Eric. M.; Shen, Dinggang

    2017-01-01

    Studies have shown that tumor angiogenesis is an essential process for tumor growth, proliferation and metastasis. Also, tumor angiogenesis is an important prognostic factor of clear cell renal cell carcinoma (ccRCC), as well as a factor in guiding treatment with antiangiogenic agents. Here, we attempted to find the associations between tumor angiogenesis and radiomic imaging features from PET/MRI. Specifically, sparse canonical correlation analysis was conducted on 3 feature datasets (i.e., radiomic imaging features, tumor microvascular density (MVD), and vascular endothelial growth factor (VEGF) expression) from 9 patients with primary ccRCC. In order to overcome the potential bias of intratumoral heterogeneity of angiogenesis, this study investigated the relationship between regional expressions of angiogenesis and VEGF, and localized radiomic features from different parts within the tumors. Our study highlighted the significant strong correlations between radiomic features and MVD, and also demonstrated that the spatiotemporal features extracted from DCE-MRI provided stronger radiomic correlation to MVD than the textural features extracted from Dixon sequences and FDG PET. Furthermore, PET/MRI, which takes advantage of the combined functional and structural information, had higher radiomics correlation to MVD than solely utilizing PET or MRI alone. PMID:28256615

  20. Elastic clearance change in axisymmetric shearing process

    NASA Astrophysics Data System (ADS)

    Yoshida, Yoshinori

    2016-10-01

    An axisymmetric shearing experiment is conducted for a sheet of low carbon steel and stainless steel. Elastic change in the clearance between punch and die is measured. The increase of the clearance in shearing is confirmed and the influence of sheared material's flow stress on the clearance change is shown. Finite element analysis (FEA) of shearing with Gurson-Tvergaard-Needlman model (GTN model) is conducted for shearing of the carbon steels with rigid tools as a numerical experiment. Burr height is predicted in the FEA and the result is compared with the experimental result. In addition, the influence of the clearance on stress state in the material is investigated.

  1. Exercise acutely increases renal transit time of Tc-99m mercaptoacetyltriglycine (MAG3) in a post-liver transplant patient.

    PubMed

    Murthy, Rajan; Chahal, Manisha; Appel, Gerald; Bergmann, Steven; Tikofsky, Ronald; Fawwaz, Rashid; Van Heertum, Ronald

    2006-12-01

    This case demonstrates the effect of exercise on the clearance of Tc-99m MAG3 in a patient with renal insufficiency status post-liver transplant. Even after furosemide administration, the tracer was retained in the kidneys after exercise. This is in contrast to normal clearance demonstrated on a baseline study performed 3 days previously.

  2. Challenges and future of renal replacement therapy.

    PubMed

    de Francisco, Angel L M; Piñera, Celestino

    2006-01-01

    Renal community increasingly recognizes the challenges of very high mortality, morbidity and low quality of life among dialysis patients. Current hemodialysis (HD) schedule provides less than 10% of the clearance power of the natural kidneys and therefore current standard HD treatment is still a long way from providing adequate renal replacement. In the future it would be expected to improve dialysis control with the development of new technology: membranes, dialysate buffer, electrolyte concentration, system interface, arteriovenous access monitoring. Online technology must be adapted to routine HD for new prescription monitoring such as creatinine online sensing technology, sodium-specific electrode or hydrogen ion concentration. Online convective therapies offer the opportunity for a more biological renal replacement therapy increasing convective transport in order to "reproduce" glomerular function and improving small and middle molecular clearance in an economically feasible and safe way. The paradigm of thrice-weekly dialysis is faced with diminishing returns, with the possible exception of long dialysis sessions. More frequent (daily) dialysis represents a very promising tool for improving dialysis outcomes and quality of life. Future technologies for renal replacement include bioartificial kidneys based in continuous hemofiltration and bioartificial tubules. Although Phase I/II clinical trial on 10 patients with acute renal failure has been reported the procedure requires further evaluation. Organogenesis, therapeutic cloning, or cloning and organogenesis combined might in the future produce a functional and histocompatible kidney. The continuous increase in incidence and prevalence of renal-replacement therapy is a world-wide phenomenon, although the rates in Europe are still much lower than in the U.S. The increase in rates applies especially to older patients, patients with diabetes mellitus and renal vascular disease and the consequences of this

  3. Drugs in pregnancy. Renal disease.

    PubMed

    Marsh, J E; Maclean, D; Pattison, J M

    2001-12-01

    The management of pregnant women with renal impairment presents a major challenge to obstetricians, nephrologists, and ultimately paediatricians. As renal failure progresses there is an increase in both maternal and fetal complications. Often these women have intercurrent medical conditions and, prior to conception, are receiving a broad range of prescribed medications. A successful obstetric outcome relies upon careful pre-pregnancy counselling and planning, obsessive monitoring during pregnancy, and close liaison between different specialist teams. Experience is mounting in the management of pregnant transplant recipients, but the introduction of newer immunosuppressive agents which have great promise in prolonging graft survival present new problems for those recipients of a kidney transplant who are planning to conceive. We review drug prescription for pregnant patients with renal impairment, end-stage renal failure, or a kidney transplant.

  4. Creatinine clearance as a substitute for the glomerular filtration rate in the assessment of glomerular hemodynamics.

    PubMed

    Okada, N; Imanishi, M; Yoshioka, K; Konishi, Y; Okumura, M; Tanaka, S; Fujii, S

    1999-11-01

    A method for the clinical assessment of glomerular hemodynamics has been published previously. We here examined whether, when using this method, renal creatinine clearance (Ccr) can be substituted for the glomerular filtration rate (GFR). The study subjects comprised 57 inpatients from Osaka City General Hospital: 30 with type 2 diabetes mellitus and 27 with chronic glomerulonephritis. During the 2-wk study, patients received a high-salt diet for 1 wk and a low-salt diet for 1 wk. Urinary sodium excretion and systemic blood pressure were measured daily. The renal plasma flow, Ccr, and plasma total protein concentration were also evaluated simultaneously on the last day of the high-salt diet. The GFR was also calculated from the fractional renal accumulation of 99mTc-diethylenetriaminepentaacetic acid (DTPA). Glomerular hemodynamics, represented by the glomerular capillary hydraulic pressure and the resistance of afferent and efferent arterioles, were calculated using the renal clearance, the plasma total protein concentration, and the pressure-natriuresis relationship. Values for renal hemodynamics with the Ccr-derived GFR were compared with those from the 99mTc-DTPA-derived GFR. Ccr values of 53 to 169 ml/min correlated with the 99mTc-DTPA-derived clearance of 39 to 179 ml/min (n=57, r=.71, p<.001). Values for the glomerular pressure and the resistances of afferent and efferent arterioles calculated using the Ccr-derived GFR correlated significantly with those calculated using the 99mTc-DTPA-derived GFR (r=.99, p<.001 and r=.99, p<.001, respectively). These results indicate that the Ccr is an accurate representation of the GFR for use in glomerular hemodynamic analysis of the pressure-natriuresis relationship.

  5. Radiomics Analysis on FLT-PET/MRI for Characterization of Early Treatment Response in Renal Cell Carcinoma: A Proof-of-Concept Study1

    PubMed Central

    Antunes, Jacob; Viswanath, Satish; Rusu, Mirabela; Valls, Laia; Hoimes, Christopher; Avril, Norbert; Madabhushi, Anant

    2016-01-01

    Studying early response to cancer treatment is significant for patient treatment stratification and follow-up. Although recent advances in positron emission tomography (PET) and magnetic resonance imaging (MRI) allow for evaluation of tumor response, a quantitative objective assessment of treatment-related effects offers localization and quantification of structural and functional changes in the tumor region. Radiomics, the process of computerized extraction of features from radiographic images, is a new strategy for capturing subtle changes in the tumor region that works by quantifying subvisual patterns which might escape human identification. The goal of this study was to demonstrate feasibility for performing radiomics analysis on integrated PET/MRI to characterize early treatment response in metastatic renal cell carcinoma (RCC) undergoing sunitinib therapy. Two patients with advanced RCC were imaged using an integrated PET/MRI scanner. [18 F] fluorothymidine (FLT) was used as the PET radiotracer, which can measure the degree of cell proliferation. Image acquisitions included test/retest scans before sunitinib treatment and one scan 3 weeks into treatment using [18 F] FLT-PET, T2-weighted (T2w), and diffusion-weighted imaging (DWI) protocols, where DWI yielded an apparent diffusion coefficient (ADC) map. Our framework to quantitatively characterize treatment-related changes involved the following analytic steps: 1) intraacquisition and interacquisition registration of protocols to allow voxel-wise comparison of changes in radiomic features, 2) correction and pseudoquantification of T2w images to remove acquisition artifacts and examine tissue-specific response, 3) characterization of information captured by T2w MRI, FLT-PET, and ADC via radiomics, and 4) combining multiparametric information to create a map of integrated changes from PET/MRI radiomic features. Standardized uptake value (from FLT-PET) and ADC textures ranked highest for reproducibility in a

  6. Ciclosporin to Protect Renal function In Cardiac Surgery (CiPRICS): a study protocol for a double-blind, randomised, placebo-controlled, proof-of-concept study

    PubMed Central

    Grins, Edgars; Dardashti, Alain; Brondén, Björn; Metzsch, Carsten; Erdling, André; Nozohoor, Shahab; Mokhtari, Arash; Hansson, Magnus J; Elmér, Eskil; Algotsson, Lars; Jovinge, Stefan; Bjursten, Henrik

    2016-01-01

    Introduction Acute kidney injury (AKI) after cardiac surgery is common and results in increased morbidity and mortality. One possible mechanism for AKI is ischaemia–reperfusion injury caused by the extracorporeal circulation (ECC), resulting in an opening of the mitochondrial permeability transition pore (mPTP) in the kidneys, which can lead to cell injury or cell death. Ciclosporin may block the opening of mPTP if administered before the ischaemia–reperfusion injury. We hypothesised that ciclosporin given before the start of ECC in cardiac surgery can decrease the degree of AKI. Methods and analysis Ciclosporin to Protect Renal function In Cardiac Surgery (CiPRICS) study is an investigator-initiated double-blind, randomised, placebo-controlled, parallel design, single-centre study performed at a tertiary university hospital. The primary objective is to assess the safety and efficacy of ciclosporin to limit the degree of AKI in patients undergoing coronary artery bypass grafting surgery. We aim to evaluate 150 patients with a preoperative estimated glomerular filtration rate of 15–90 mL/min/1.73 m2. Study patients are randomised in a 1:1 ratio to receive study drug 2.5 mg/kg ciclosporin or placebo as an intravenous injection after anaesthesia induction but before start of surgery. The primary end point consists of relative P-cystatin C changes from the preoperative day to postoperative day 3. The primary variable will be tested using an analysis of covariance method. Secondary end points include evaluation of P-creatinine and biomarkers of kidney, heart and brain injury. Ethics and dissemination The trial is conducted in compliance with the current version of the Declaration of Helsinki and the International Council for Harmonisation (ICH) Good Clinical Practice guidelines E6 (R1) and was approved by the Regional Ethical Review Board, Lund and the Swedish Medical Products Agency (MPA). Written and oral informed consent is obtained before enrolment into

  7. Radiomics Analysis on FLT-PET/MRI for Characterization of Early Treatment Response in Renal Cell Carcinoma: A Proof-of-Concept Study.

    PubMed

    Antunes, Jacob; Viswanath, Satish; Rusu, Mirabela; Valls, Laia; Hoimes, Christopher; Avril, Norbert; Madabhushi, Anant

    2016-04-01

    Studying early response to cancer treatment is significant for patient treatment stratification and follow-up. Although recent advances in positron emission tomography (PET) and magnetic resonance imaging (MRI) allow for evaluation of tumor response, a quantitative objective assessment of treatment-related effects offers localization and quantification of structural and functional changes in the tumor region. Radiomics, the process of computerized extraction of features from radiographic images, is a new strategy for capturing subtle changes in the tumor region that works by quantifying subvisual patterns which might escape human identification. The goal of this study was to demonstrate feasibility for performing radiomics analysis on integrated PET/MRI to characterize early treatment response in metastatic renal cell carcinoma (RCC) undergoing sunitinib therapy. Two patients with advanced RCC were imaged using an integrated PET/MRI scanner. [18 F] fluorothymidine (FLT) was used as the PET radiotracer, which can measure the degree of cell proliferation. Image acquisitions included test/retest scans before sunitinib treatment and one scan 3 weeks into treatment using [18 F] FLT-PET, T2-weighted (T2w), and diffusion-weighted imaging (DWI) protocols, where DWI yielded an apparent diffusion coefficient (ADC) map. Our framework to quantitatively characterize treatment-related changes involved the following analytic steps: 1) intraacquisition and interacquisition registration of protocols to allow voxel-wise comparison of changes in radiomic features, 2) correction and pseudoquantification of T2w images to remove acquisition artifacts and examine tissue-specific response, 3) characterization of information captured by T2w MRI, FLT-PET, and ADC via radiomics, and 4) combining multiparametric information to create a map of integrated changes from PET/MRI radiomic features. Standardized uptake value (from FLT-PET) and ADC textures ranked highest for reproducibility in a

  8. Bioaerosols in the lungs of subjects with different ages—Part 2: clearance modeling

    PubMed Central

    2017-01-01

    Background The present contribution deals with theoretical aspects regarding biogenic particle clearance from various lung structures of probands with different ages (1, 5, 15, 20 y). With reference to part 1 of the study, particles varying in size and shape are subject to a detailed analysis. The main goal of the investigation consists in an increase of our knowledge concerning the clearance behaviour of bioparticles and its dependence upon various physiological and anatomical factors. Methods Theoretical clearance of biogenic particles was subdivided into four main phases, namely fast bronchial clearance, slow bronchial clearance, fast alveolar clearance, and slow alveolar clearance. All of these phases were simulated by using a well validated stochastic modeling approach, where the main focus is set on the randomly varied particle mass transfer between main compartments of the human respiratory tract. Whilst effects of particle geometry on clearance were approximated by application of the projective-diameter concept, age dependence of the particle removal process was expressed by the experimentally proven relationship between bronchial mucus velocities and morphometry of the airway tree. Results According to the results of the theoretical simulations efficiency of fast bronchial clearance, expressed by the 24-h-retention value, exhibits a negative correlation with proband's age, whereas the other clearance phases are characterized by a rather conservative behaviour among the different age categories. Highest clearance rates may be observed for very fine (<0.01 µm) and very coarse particles (>5 µm) preferentially deposited in the upper bronchial airways, whilst large particles accumulated in the alveoli may be stored there for several months to years. Conclusions The study comes to the conclusion that infants and children dispose of an enhanced bronchial clearance efficiency with respect to adolescents and adults, which results in a faster removal of

  9. Intelligent Engine Systems: HPT Clearance Control

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The Advanced Thermally Actuated Clearance Control System underwent several studies. Improved flow path isolation quantified what can be gained by making the HPT case nearly adiabatic. The best method of heat transfer was established, and finally two different borrowed air cooling circuits were evaluated to be used for the HPT Active Clearance Control System.

  10. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... following: (a) Ground clearance. There must be a clearance of at least seven inches (for each airplane with nose wheel landing gear) or nine inches (for each airplane with tail wheel landing gear) between each propeller and the ground with the landing gear statically deflected and in the level takeoff, or...

  11. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... following: (a) Ground clearance. There must be a clearance of at least seven inches (for each airplane with nose wheel landing gear) or nine inches (for each airplane with tail wheel landing gear) between each propeller and the ground with the landing gear statically deflected and in the level takeoff, or...

  12. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... following: (a) Ground clearance. There must be a clearance of at least seven inches (for each airplane with nose wheel landing gear) or nine inches (for each airplane with tail wheel landing gear) between each propeller and the ground with the landing gear statically deflected and in the level takeoff, or...

  13. 19 CFR 122.77 - Clearance certificate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Clearance certificate. 122.77 Section 122.77 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Documents Required for Clearance and Permission To Depart;...

  14. 19 CFR 122.77 - Clearance certificate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Clearance certificate. 122.77 Section 122.77 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Documents Required for Clearance and Permission To Depart;...

  15. 19 CFR 122.77 - Clearance certificate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Clearance certificate. 122.77 Section 122.77 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Documents Required for Clearance and Permission To Depart;...

  16. 19 CFR 122.77 - Clearance certificate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Clearance certificate. 122.77 Section 122.77 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Documents Required for Clearance and Permission To Depart;...

  17. 19 CFR 122.77 - Clearance certificate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Clearance certificate. 122.77 Section 122.77 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Documents Required for Clearance and Permission To Depart;...

  18. 15 CFR 752.15 - Export clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Export clearance. 752.15 Section 752... OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS SPECIAL COMPREHENSIVE LICENSE § 752.15 Export clearance. (a) Shipper's Export Declaration (SED) or Automated...

  19. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... nose wheel landing gear) or nine inches (for each airplane with tail wheel landing gear) between each propeller and the ground with the landing gear statically deflected and in the level takeoff, or taxiing... the corresponding landing gear strut bottomed. (b) Water clearance. There must be a clearance of...

  20. 30 CFR 56.7018 - Hand clearance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Hand clearance. 56.7018 Section 56.7018 Mineral... Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling....

  1. 30 CFR 56.7018 - Hand clearance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Hand clearance. 56.7018 Section 56.7018 Mineral... Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling....

  2. 30 CFR 57.7028 - Hand clearance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Hand clearance. 57.7028 Section 57.7028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  3. 30 CFR 57.7018 - Hand clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Hand clearance. 57.7018 Section 57.7018 Mineral... Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling. Drilling—Underground Only...

  4. 30 CFR 57.7018 - Hand clearance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Hand clearance. 57.7018 Section 57.7018 Mineral... Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling. Drilling—Underground Only...

  5. 30 CFR 57.7028 - Hand clearance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Hand clearance. 57.7028 Section 57.7028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  6. 30 CFR 57.7018 - Hand clearance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Hand clearance. 57.7018 Section 57.7018 Mineral... Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling. Drilling—Underground Only...

  7. 30 CFR 57.7028 - Hand clearance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Hand clearance. 57.7028 Section 57.7028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  8. 30 CFR 57.7018 - Hand clearance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Hand clearance. 57.7018 Section 57.7018 Mineral... Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling. Drilling—Underground Only...

  9. 30 CFR 57.7028 - Hand clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Hand clearance. 57.7028 Section 57.7028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  10. 30 CFR 57.7018 - Hand clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Hand clearance. 57.7018 Section 57.7018 Mineral... Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling. Drilling—Underground Only...

  11. 30 CFR 57.7028 - Hand clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Hand clearance. 57.7028 Section 57.7028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  12. 30 CFR 56.7018 - Hand clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Hand clearance. 56.7018 Section 56.7018 Mineral... Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling....

  13. 30 CFR 56.7018 - Hand clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Hand clearance. 56.7018 Section 56.7018 Mineral... Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling....

  14. 30 CFR 56.7018 - Hand clearance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Hand clearance. 56.7018 Section 56.7018 Mineral... Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling....

  15. 30 CFR 56.11010 - Stairstep clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Stairstep clearance. 56.11010 Section 56.11010 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... warning signs or similar devices shall be provided to indicate an impaired clearance....

  16. 30 CFR 56.11010 - Stairstep clearance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Stairstep clearance. 56.11010 Section 56.11010 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... warning signs or similar devices shall be provided to indicate an impaired clearance....

  17. [Pregnancy in patients with underlying renal disease].

    PubMed

    Golshayan, D; Mathieu, C; Burnier, M

    2007-03-07

    Pregnancy has generally been regarded as very high risk in women with chronic renal insufficiency. In this review, we describe the physiologic changes in systemic and renal haemodynamics during pregnancy, as well as the nature and severity of possible maternal and foetal complications in the setting of underlying renal disease. The risks are proportional to the degree of functional renal impairment, the presence or not of proteinuria and/or arterial hypertension at the time of conception, and are related to the type of underlying nephropathy or systemic disease in the mother. Furthermore, if the renal disease has been diagnosed before pregnancy, a better planning of the moment of conception, as well as a tight follow-up, allow for a better maternal and obstetrical outcome.

  18. Clearance Pathways and Tumor Targeting of Imaging Nanoparticles

    PubMed Central

    Yu, Mengxiao; Zheng, Jie

    2016-01-01

    A basic understanding of how imaging nanoparticles are removed from the normal organs/tissues but retained in the tumors is important for their future clinical applications in early cancer diagnosis and therapy. In this review, we discuss current understandings of clearance pathways and tumor targeting of small-molecule- and inorganic-nanoparticle-based imaging probes with an emphasis on molecular nanoprobes, a class of inorganic nanoprobes that can escape reticuloendothelial system (RES) uptake and be rapidly eliminated from the normal tissues/organs via kidneys but can still passively target the tumor with high efficiency through the enhanced permeability permeability and retention (EPR) effect. The impact of nanoparticle design (size, shape, and surface chemistry) on their excretion, pharmacokinetics, and passive tumor targeting were quantitatively discussed. Synergetic integration of effective renal clearance and EPR effect offers a promising pathway to design low-toxicity and high-contrast-enhancement imaging nanoparticles that could meet with the clinical translational requirements of regulatory agencies. PMID:26149184

  19. Major contribution of tubular secretion to creatinine clearance in mice

    PubMed Central

    Eisner, Christoph; Faulhaber-Walter, Robert; Wang, Yaohui; Leelahavanichkul, Asada; Yuen, Peter S.T.; Mizel, Diane; Star, Robert A.; Briggs, Josephine P.; Levine, Mark; Schnermann, Jurgen

    2011-01-01

    This study was performed to quantify the fraction of excreted creatinine not attributable to creatinine filtration for accurately determining the glomerular filtration rate in mice. To measure this we compared creatinine filtration with the simultaneous measurement of inulin clearance using both single-bolus fluorescein isothiocyanate (FITC)-inulin elimination kinetics and standard FITC-inulin infusion. During anesthesia, creatinine filtration was found to be systematically higher than inulin clearance in both male and female C57BL/6J mice. The secretion fraction was significantly less in female mice. Administration of either cimetidine or para-aminohippuric acid, competitors of organic cation and anion transport respectively, significantly reduced the secretion fraction in male and female mice and both significantly increased the plasma creatinine level. Creatinine secretion in both genders was not mediated by the organic cation transporters OCT1 or OCT 2 since secretion fraction levels were identical in FVB wild-type and OCT1/2 knockout mice. Thus, secretion accounts for about 50 and 35% of excreted creatinine in male and female mice, respectively. Increasing plasma creatinine threefold by infusion further increased the secretion fraction. Renal organic anion transporter 1 mRNA expression was higher in male than in female mice, reflecting the gender difference in creatinine secretion. Hence we show that there is a major secretory contribution to creatinine excretion mediated through the organic anion transport system. This feature adds to problems associated with measuring endogenous creatinine filtration in mice. PMID:20032962

  20. Bacterial clearance in the intact and regenerating liver

    SciTech Connect

    Gross, K.; Katz, S.; Dunn, S.P.; Cikrit, D.; Rosenthal, R.; Grosfeld, J.L.

    1985-08-01

    The Kupffer cells in the liver play an important role in reticuloendothelial system (RES) function by clearing particulate matter and bacteria from the blood stream. While hepatocyte regeneration and function have been extensively studied following partial hepatectomy, little information is available concerning RES function in the regenerating liver. This study investigates hepatic RES function by evaluating bacterial clearance (live E. coli) in the intact and regenerating liver. Thirty-four young male Sprague Dawley rats were studied. Twenty-two animals underwent a standard 70% partial hepatectomy using ligature technique and 12 had a sham operation. Both groups of rats received 10(9) organism of TVS labeled E coli, intravenously at 24 hours, 72 hours, 2 1/2 weeks, and 6 weeks postoperatively. Rats were killed 10 minutes following injection and liver, lung, spleen, and kidney harvested, fixed, and radioactivity was determined using a scintillation spectrometer interfaced with a micro-computer counting the TVS radiolabel. The total organ count of trapped bacteria in liver in partially hepatectomized rats was lower than intact controls at 24 hours, but was similar at 72 hours, 2 1/2 weeks, and 6 weeks. Partial hepatectomy increased the amount of bacterial trapping in the lung at 24 hours and 72 hours and returned to normal at 2 1/2 weeks and 6 weeks. Splenic activity was increased following hepatectomy at 2 1/2 weeks. Renal clearance was increased at 72 hours and 2 1/2 weeks.

  1. Efficacy of the lithotripsy in treating lower pole renal stones.

    PubMed

    Cui, Helen; Thomee, Eeke; Noble, Jeremy G; Reynard, John M; Turney, Benjamin W

    2013-06-01

    Use of extracorporeal lithotripsy is declining in North America and many European countries despite international guidelines advocating it as a first-line therapy. Traditionally, lithotripsy is thought to have poor efficacy at treating lower pole renal stones. We evaluated the success rates of lithotripsy for lower pole renal stones in our unit. 50 patients with lower pole kidney stones ≤15 mm treated between 3/5/11 and 19/4/12 were included in the study. Patients received lithotripsy on a fixed-site Storz Modulith SLX F2 lithotripter according to a standard protocol. Clinical success was defined as stone-free status or asymptomatic clinically insignificant residual fragments (CIRFs) ≤3 mm at radiological follow-up. The mean stone size was 7.8 mm. The majority of stones (66 %) were between 5 and 10 mm. 28 % of stones were between 10 and 15 mm. For solitary lower pole stones complete stone clearance was achieved in 63 %. Total stone clearance including those with CIRFs was achieved in 81 % of patients. As expected, for those with multiple lower pole stones the success rates were lower: complete clearance was observed in 39 % and combined clearance including those with CIRFs was 56 %. Overall, complete stone clearance was observed in 54 % of patients and clearance with CIRFs was achieved in 72 % of patients. Success rate could not be attributed to age, stone size or gender. Our outcome data for the treatment of lower pole renal stones (≤15 mm) compare favourably with the literature. With this level of stone clearance, a non-invasive, outpatient-based treatment like lithotripsy should remain the first-line treatment option for lower pole stones. Ureteroscopy must prove that it is significantly better either in terms of clinical outcome or patient satisfaction to justify replacing lithotripsy.

  2. Nasal mucociliary clearance after radiation therapy.

    PubMed

    Stringer, S P; Stiles, W; Slattery, W H; Krumerman, J; Parsons, J T; Mendenhall, W M; Cassisi, N J

    1995-04-01

    Irradiation has been demonstrated to cause decreased mucociliary clearance in animal models. We sought to verify this effect clinically by using the saccharin transport test to evaluate nasal mucociliary clearance in 9 patients previously treated with radiation therapy to the nasal cavity. The patients also completed a questionnaire examining the prevalence of nasal symptoms before and after radiation therapy. Patients who received radiation therapy had no clearance of saccharin from the nasal cavity at a minimum of 20 minutes. The controls had a median clearance time of 5 minutes. The patients noted a higher prevalence of nasal congestion, drainage, and facial pain after radiation therapy. This study demonstrates that radiation therapy to the nasal cavity causes a decrease in nasal mucociliary clearance. This alteration should be considered when selecting therapy for malignancies in the nasal area.

  3. Use of a Microsoft Excel based add-in program to calculate plasma sinistrin clearance by a two-compartment model analysis in dogs.

    PubMed

    Steinbach, Sarah M L; Sturgess, Christopher P; Dunning, Mark D; Neiger, Reto

    2015-06-01

    Assessment of renal function by means of plasma clearance of a suitable marker has become standard procedure for estimation of glomerular filtration rate (GFR). Sinistrin, a polyfructan solely cleared by the kidney, is often used for this purpose. Pharmacokinetic modeling using adequate software is necessary to calculate disappearance rate and half-life of sinistrin. The purpose of this study was to describe the use of a Microsoft excel based add-in program to calculate plasma sinistrin clearance, as well as additional pharmacokinetic parameters such as transfer rates (k), half-life (t1/2) and volume of distribution (Vss) for sinistrin in dogs with varying degrees of renal function.

  4. Clearance of vancomycin during continuous infusion in Intensive Care Unit patients: correlation with measured and estimated creatinine clearance and serum cystatin C.

    PubMed

    Kees, Martin G; Hilpert, Justus W; Gnewuch, Carsten; Kees, Frieder; Voegeler, Stephan

    2010-12-01

    Vancomycin (VAN) dosing requires adjustment to renal function, which is often estimated using the Cockcroft-Gault formula; however, its precision is poor in Intensive Care Unit (ICU) patients. VAN clearance (CL(Van)) during continuous infusion was prospectively determined in 25 ICU patients [14 male, 11 female; age range 31-82 years; body mass index (BMI) 16.5-41.5 kg/m²; Acute Physiology and Chronic Health Evaluation (APACHE) II score at admission 8-36; creatinine clearance 25-195 mL/min] and its correlation with measured creatinine clearance (CL(Crea)), estimated creatinine clearance using the Cockcroft-Gault formula (CL(CG)) and estimated glomerular filtration rate according to Hoek's formula based on serum cystatin C (GFR(Hoek)) was investigated. The correlation between CL(Van) and CL(Crea) was very good (r²=0.88), but it was rather poor with CL(CG) (r² = 0.37) and was acceptable with GFR(Hoek) (r² = 0.70). For VAN dose adjustments in ICU patients, determination of cystatin C may be an interesting and practical alternative to measured CL(Crea), whereas the Cockcroft-Gault formula should be used with caution.

  5. Multiphoton imaging of renal regulatory mechanisms.

    PubMed

    Peti-Peterdi, János; Toma, Ildikó; Sipos, Arnold; Vargas, Sarah L

    2009-04-01

    Most physiological functions of the kidneys, including the clearance of metabolic waste products, maintenance of body fluid, electrolyte homeostasis, and blood pressure, are achieved by complex interactions between multiple renal cell types and previously inaccessible structures in many organ parts that have been difficult to study. Multiphoton fluorescence microscopy offers a state-of-the-art imaging technique for deep optical sectioning of living tissues and organs with minimal deleterious effects. Dynamic regulatory processes and multiple functions in the intact kidney can be quantitatively visualized in real time, noninvasively, and with submicron resolution. This article reviews innovative multiphoton imaging technologies and their applications that provided the most complex, immediate, and dynamic portrayal of renal function-clearly depicting as well as analyzing the components and mechanisms involved in renal (patho)physiology.

  6. Alveolar edema fluid clearance and acute lung injury.

    PubMed

    Berthiaume, Yves; Matthay, Michael A

    2007-12-15

    Although lung-protective ventilation strategies have substantially reduced mortality of acute lung injury patients there is still a need for new therapies that can further decrease mortality in patients with acute lung injury. Studies of epithelial ion and fluid transport across the distal pulmonary epithelia have provided important new concepts regarding potential new therapies for acute lung injury. Overall, there is convincing evidence that the alveolar epithelium is not only a tight epithelial barrier that resists the movement of edema fluid into the alveoli, but it is also actively involved in the transport of ions and solutes, a process that is essential for edema fluid clearance and the resolution of acute lung injury. The objective of this article is to consider some areas of recent progress in the field of alveolar fluid transport under normal and pathologic conditions. Vectorial ion transport across the alveolar and distal airway epithelia is the primary determinant of alveolar fluid clearance. The general paradigm is that active Na(+) and Cl(-) transport drives net alveolar fluid clearance, as demonstrated in several different species, including the human lung. Although these transport processes can be impaired in severe lung injury, multiple experimental studies suggest that upregulation of Na(+) and Cl(-) transport might be an effective therapy in acute lung injury. We will review mechanisms involved in pharmacological modulation of ion transport in lung injury with a special focus on the use of beta-adrenergic agonists which has generated considerable interest and is a promising therapy for clinical acute lung injury.

  7. Active Piezoelectric Structures for Tip Clearance Management Assessed

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Managing blade tip clearance in turbomachinery stages is critical to developing advanced subsonic propulsion systems. Active casing structures with embedded piezoelectric actuators appear to be a promising solution. They can control static and dynamic tip clearance, compensate for uneven deflections, and accomplish electromechanical coupling at the material level. In addition, they have a compact design. To assess the feasibility of this concept and assist the development of these novel structures, the NASA Lewis Research Center developed in-house computational capabilities for composite structures with piezoelectric actuators and sensors, and subsequently used them to simulate candidate active casing structures. The simulations indicated the potential of active casings to modify the blade tip clearance enough to improve stage efficiency. They also provided valuable design information, such as preliminary actuator configurations (number and location) and the corresponding voltage patterns required to compensate for uneven casing deformations. An active ovalization of a casing with four discrete piezoceramic actuators attached on the outer surface is shown. The center figure shows the predicted radial displacements along the hoop direction that are induced when electrostatic voltage is applied at the piezoceramic actuators. This work, which has demonstrated the capabilities of in-house computational models to analyze and design active casing structures, is expected to contribute toward the development of advanced subsonic engines.

  8. Residual renal function: a paradigm shift.

    PubMed

    Lowenstein, Jerome; Grantham, Jared J

    2017-03-01

    Residual renal function (RRF) in patients undergoing dialysis treatments is currently viewed as glomerular filtrate that has escaped tubular reabsorption. RRF has been quantified as a clearance of urea or creatinine, or urea + creatinine. A major paradigm shift has followed the recognition that a substantial number of organic anion retention solutes (possible "uremic toxins") are protein-bound and therefore are not readily filtered. These protein-bound aryl compounds are secreted by renal tubular organic anion transporters (OATs). This has led to the recognition that RRF in dialysis patients probably represents not only unreabsorbed glomerular filtrate but also a contribution of renal tubular transporters that secrete organic anions. Tubular secretion of hippurate, indoxyl sulfate, and p-cresol sulfate, protein-bound organic anions retained in the plasma of end-stage renal disease patients, can be quantified and used to evaluate the integrity of a function dependent on active solute transport. Here we propose a shift away from the exclusive "glomerulocentric" view of RRF as unreabsorbed glomerular filtrate and of the progression of renal disease as progressive glomerular loss. We expand the definition of RRF to include the combined renal and tubule functions remaining after a disease begins to destroy nephrons and proceeds to anuria. We propose renewed application of the first principles of renal physiology, articulated in the last century by Homer Smith, to the understanding and monitoring of RRF and progression of renal injury in patients during the sometimes long course of and at the end stage of chronic renal disease.

  9. 19 CFR 4.61 - Requirements for clearance.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... optional clearance locations. (b) When clearance required. Under certain circumstances, American vessels.... While American vessels transporting unentered foreign merchandise must fully comply with usual clearance procedures, American vessels carrying no unentered foreign merchandise but that have in-bond...

  10. 77 FR 21989 - Critical Infrastructure Private Sector Clearance Program Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-12

    ... SECURITY Critical Infrastructure Private Sector Clearance Program Request AGENCY: National Protection and... information provided. SUPPLEMENTARY INFORMATION: The Critical Infrastructure Private Sector Clearance Program (PSCP) sponsors clearances for private sector partners who are responsible for critical...

  11. Renal Cysts

    MedlinePlus

    ... as “simple” cysts, meaning they have a thin wall and contain water-like fluid. Renal cysts are fairly common in ... simple kidney cysts, meaning they have a thin wall and only water-like fluid inside. They are fairly common in ...

  12. Renal hemodynamic effects of relaxin in humans.

    PubMed

    Smith, Marie; Davison, John; Conrad, Kirk; Danielson, Lee

    2005-05-01

    Rat studies have convincingly demonstrated the essential role of the ovarian hormone relaxin in mediating gestational renal hemodynamic and osmoregulatory changes in that species. We describe a model in nonpregnant volunteers using exogenous hCG to stimulate the production and release of ovarian relaxin in order to assess renal hemodynamic responses. Women (n = 10) were serially studied +/- hCG stimulation during menstrual cycles with measurement of inulin, PAH, and neutral dextran clearances (to determine glomerular filtration rate [GFR], renal plasma flow [RPF], and glomerular porosity, respectively). Controls were women without ovarian function (n = 6) and men (n = 10). GFR and RPF were increased in the luteal phase compared to the follicular phase (15.3% increase in GFR, P < 0.005; 17.8% increase in RPF, P < 0.05). In controls, GFR and RPF were not significantly different between study occasions. Although exogenous hCG did not stimulate relaxin secretion in women without ovarian function or in men, it did so in normal women, but not into the pregnancy range. In no group were renal hemodynamics augmented by administered hCG. In naturally occurring cycles, increased serum relaxin is associated with augmented renal hemodynamics. As luteal stimulation with hCG failed to yield pregnancy relaxin levels, the use of exogenous relaxin for human administration is needed to further elucidate the renal vasodilatory properties of relaxin.

  13. Plasma clearance, tissue distribution and metabolism of hyaluronic acid injected intravenously in the rabbit.

    PubMed Central

    Fraser, J R; Laurent, T C; Pertoft, H; Baxter, E

    1981-01-01

    The plasma clearance, tissue distribution and metabolism of hyaluronic acid were studied with a high average molecular weight [3H]acetyl-labelled hyaluronic acid synthesized in synovial cell cultures. After intravenous injection in the rabbit the label disappeared from the plasma with a half-life of 2.5--4.5 min, which corresponds to a normal hyaluronic acid clearance of approx. 10 mg/day per kg body weight. Injection of unlabelled hyaluronic acid 15 min after the tracer failed to reverse its absorption. Clearance of labelled polymer was retarded by prior injection of excess unlabelled hyaluronic acid. The maximum clearance capacity was estimated in these circumstances to be about 30 mg/day per kg body wt. The injected material was concentrated in the liver and spleen. As much as 88% of the label was absorbed by the liver, where it was found almost entirely in non-parenchymal cells. Degradation was rapid and complete, since volatile material, presumably 3H2O, appeared in the plasma within 20 min. Undegraded [3H]hyaluronic acid, small labelled residues and 3H2O were detected in the liver, but there was little evidence of intermediate oligosaccharides. No metabolite except 3H2O was recognized in plasma or urine. Two-thirds of the radioactivity was retained in the body water 24 h later, and small amounts were found in liver lipids. Radioactivity did not decline in the spleen as rapidly as in the liver. The upper molecular weight limit for renal excretion was about 25 000. Renal excretion played a negligible part in clearance. It is concluded that hyaluronic acid is removed from the plasma and degraded quickly by an efficient extrarenal system with a high reserve capacity, sited mainly in the liver. PMID:7340841

  14. The effects of renal impairment on the pharmacokinetics, safety, and tolerability of naloxegol.

    PubMed

    Bui, Khanh; She, Fahua; Sostek, Mark

    2014-12-01

    The impact of renal impairment on the pharmacokinetics of a 25-mg oral dose of naloxegol was examined in patients with renal impairment classified as moderate, severe, or end-stage renal disease (ESRD) and compared with healthy subjects (n = 8/group). Geometric mean area under the plasma concentration-time curve (AUC) was increased in patients with moderate (1.7-fold) or severe (2.2-fold) impairment, and maximum plasma concentrations (Cmax ) were elevated in patients with moderate (1.1-fold) or severe (1.8-fold) impairment. These findings were driven by higher exposures in two patients in each of the moderate and severe impairment groups; exposures in all other patients were similar to the control group. Overall exposures in ESRD patients were similar and Cmax was 29% lower versus normal subjects. Renal impairment minimally affected other plasma pharmacokinetic parameters. As renal clearance was a minor component of total clearance, exposure to naloxegol was unaffected by the degree of renal impairment, with no correlation between either AUC or Cmax and estimated glomerular filtration rate (eGFR). Hemodialysis was an ineffective means to remove naloxegol. Naloxegol was generally well tolerated in all groups. Renal impairment could adversely affect clearance by hepatic and gut metabolism, resulting in the increased exposures observed in outliers of the moderate and severe renal impairment groups.

  15. Advanced optical blade tip clearance measurement system

    NASA Technical Reports Server (NTRS)

    Ford, M. J.; Honeycutt, R. E.; Nordlund, R. E.; Robinson, W. W.

    1978-01-01

    An advanced electro-optical system was developed to measure single blade tip clearances and average blade tip clearances between a rotor and its gas path seal in an operating gas turbine engine. This system is applicable to fan, compressor, and turbine blade tip clearance measurement requirements, and the system probe is particularly suitable for operation in the extreme turbine environment. A study of optical properties of blade tips was conducted to establish measurement system application limitations. A series of laboratory tests was conducted to determine the measurement system's operational performance characteristics and to demonstrate system capability under simulated operating gas turbine environmental conditions. Operational and environmental performance test data are presented.

  16. Development of a computerised decisions support system for renal risk drugs targeting primary healthcare

    PubMed Central

    Helldén, Anders; Al-Aieshy, Fadiea; Bastholm-Rahmner, Pia; Bergman, Ulf; Gustafsson, Lars L; Höök, Hans; Sjöviker, Susanne; Söderström, Anders; Odar-Cederlöf, Ingegerd

    2015-01-01

    Objectives To assess general practitioners (GPs) experience from the implementation and use of a renal computerised decision support system (CDSS) for drug dosing, developed for primary healthcare, integrated into the patient’s electronic health record (EHR), and building on estimation of the patient's creatinine clearance (ClCG). Design Qualitative research design by a questionnaire and a focus group discussion. Setting and participants Eight GPs at two primary healthcare centres (PHCs). Interventions The GP at PHC 1, and the project group, developed and tested the technical solution of the CDSS. Proof-of-concept was tested by seven GPs at PHC 2. They also participated in a group discussion and answered a questionnaire. A web window in the EHR gave drug and dosage in relation to ClCG. Each advice was according to three principles: If? Why? Because. Outcome measures (1) The GPs’ experience of ‘easiness to use’ and ‘perceived usefulness’ at PHC 2, based on loggings of use, answers from a questionnaire using a 5-point Likert scale, and answers from a focus group discussion. (2) The number of patients aged 65 years and older with an estimation of ClCG before and after the implementation of the CDSS. Results The GPs found the CDSS fast, simple and easy to use. They appreciated the automatic presentation of the CICG status on opening the medication list, and the ability to actively look up specific drug recommendations in two steps. The CDSS scored high on the Likert scale. All GPs wanted to continue the use of the CDSS and to recommend it to others. The number of patients with an estimated ClCG increased 1.6-fold. Conclusions Acceptance of the simple graphical interface of this push and pull renal CDSS was high among the primary care physicians evaluating this proof of concept. The graphical model should be useful for further development of renal decision support systems. PMID:26150141

  17. Single-dose pharmacokinetics and safety of pegylated interferon-alpha2b in patients with chronic renal dysfunction.

    PubMed

    Gupta, Samir K; Pittenger, Amy L; Swan, Suzanne K; Marbury, Thomas C; Tobillo, Emlyn; Batra, Vijay; Sack, Marshall; Glue, Paul; Jacobs, Sheila; Affrime, Melton

    2002-10-01

    This study evaluates the pharmacokinetics and safety of pegylated interferon-alpha2b (PEG-Intron) following a single-dose subcutaneous injection into subjects with normal renal function, subjects with chronic renal impairment, and patients on hemodialysis. In this open-label, single-dose, parallel group study, subjects were divided into five groups according to their degree of renal function: four groups as defined by measured creatinine clearance and a fifth hemodialysis dependent group. They received 1 microg/kg PEG-Intron subcutaneously after a 10-hour fast. Pharmacokinetic and safety assessments were performed up to 168 hours postdose. Hemodialysis patients had a second PEG-Intron dose 12 hours prior to a hemodialysis session. PEG-Intron pharmacokinetic parameters (AUCtf, Cmax, and t1/2) increased progressively as CL(CR) declined. All subjects reported at least one adverse event, which were typical of those reported after alpha-interferon administration (e.g., flu-like symptoms, headache). Single-dose PEG-Intron administration to volunteers with normal renal function and chronic renal impairment was safe and well tolerated. In patients with CL(CR) < 30 ml/min, AUCand Cmax values were increased 90% compared with controls, while half-life was increased by up to 40% over controls. Based on the relationship between PEG-Intron apparent clearance and CL(CR), renal clearance accountsfor less than half of its total clearance. Hemodialysis did not affect PEG-Intron apparent clearance.

  18. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... attitude, whichever is most critical. In addition, there must be positive clearance between the propeller and the ground when in the level takeoff attitude with the critical tire(s) completely deflated...

  19. Shear-Joint Capability Versus Bolt Clearance

    NASA Technical Reports Server (NTRS)

    Lee, H. M.

    1994-01-01

    NASA Technical Memorandum presents theoretical study of relationships between load-bearing capabilities of shear joints that comprise plates clamped together by multiple bolts and clearances between bolts and boltholes in those joints.

  20. Shear joint capability versus bolt clearance

    NASA Technical Reports Server (NTRS)

    Lee, H. M.

    1992-01-01

    The results of a conservative analysis approach into the determination of shear joint strength capability for typical space-flight hardware as a function of the bolt-hole clearance specified in the design are presented. These joints are comprised of high-strength steel fasteners and abutments constructed of aluminum alloys familiar to the aerospace industry. A general analytical expression was first arrived at which relates bolt-hole clearance to the bolt shear load required to place all joint fasteners into a shear transferring position. Extension of this work allowed the analytical development of joint load capability as a function of the number of fasteners, shear strength of the bolt, bolt-hole clearance, and the desired factor of safety. Analysis results clearly indicate that a typical space-flight hardware joint can withstand significant loading when less than ideal bolt hole clearances are used in the design.

  1. Compressor airfoil tip clearance optimization system

    DOEpatents

    Little, David A.; Pu, Zhengxiang

    2015-08-18

    A compressor airfoil tip clearance optimization system for reducing a gap between a tip of a compressor airfoil and a radially adjacent component of a turbine engine is disclosed. The turbine engine may include ID and OD flowpath boundaries configured to minimize compressor airfoil tip clearances during turbine engine operation in cooperation with one or more clearance reduction systems that are configured to move the rotor assembly axially to reduce tip clearance. The configurations of the ID and OD flowpath boundaries enhance the effectiveness of the axial movement of the rotor assembly, which includes movement of the ID flowpath boundary. During operation of the turbine engine, the rotor assembly may be moved axially to increase the efficiency of the turbine engine.

  2. Voltage-clearance recommendations for printed boards

    SciTech Connect

    Jennings, C W; Cave, G; Evans, A; Harrington, D J; Kirchenbaum, J; Martz, R E; Mierendorf, R C; Smith, G A

    1980-01-01

    Present and future trends in printed board designs point to higher circuit densities with narrower lines and closer spacings. Some designers are now laying out boards with 0.13 mm lines and spacings. The reduction of nominal spacing between conductive elements has raised questions concerning the adequacy of present voltage-clearance recommendations. The present recommendations are considered too conservative in that they are weighted with large safety factors, especially for small clearances, and are frequently disregarded by many designers. Published voltage breakdown measurements made on printed boards with comb patterns with their enhanced conductor test lengths show breakdowns occurring at much higher voltages than those specified for the clearances in existing documents. A Task Group was set up to review published breakdown measurements and to make any additional measurements necessary to provide voltage-clearance recommendations. These recommendations are reported.

  3. Lipoprotein lipase activity and chylomicron clearance in rats fed a high fat diet

    SciTech Connect

    Brown, C.M.; Layman, D.K.

    1988-11-01

    The relationships of tissue and plasma lipoprotein lipase (LPL) activities to tissue uptake and plasma clearance of UC-labeled chylomicron-triglyceride ( UC-CM-TG) were studied in female rats fed isoenergetic and isonitrogenous control (12% kJ from fat) or high fat diets (72% kJ from fat) for 8 wk. Animals fed the high-fat diet had higher levels of fasting plasma triglycerides and lower LPL activities in heart, renal adipose tissue and post-heparin plasma. Changes in LPL activities of skeletal muscles varied among muscles with higher values in the soleus and plantaris (32-61%) and no differences in the gastrocnemius. The lower LPL activity in renal adipose tissue was associated with lower uptake of fatty acids from UC-CM-TG by adipose. Fatty-acid uptake from labeled TG was not associated with tissue LPL activity in other tissues. Clearance of UC-CM-TG from plasma and the half-lives of UC-CM-TG were similar in both dietary groups. These data indicate that tissue and plasma LPL activities are not a direct index of uptake of fatty acids by tissues or clearance of chylomicron triglycerides.

  4. 2015 Annual Report on Security Clearance Determinations

    DTIC Science & Technology

    2016-06-28

    preceding fiscal year that resulted in a denial or revocation of a security clearance...and o more than 1 year. iii. Percentage of reviews during the preceding fiscal year that resulted in a denial or revocation of a security clearance...1,322 in FY 2014 to 2,526 in FY 20154. iii. The percentage of reviews during the preceding fiscal year that resulted in a denial or revocation of a

  5. Plasma Polyunsaturated Fatty Acids and the Decline of Renal Function

    PubMed Central

    Lauretani, Fulvio; Semba, Richard D.; Bandinelli, Stefania; Miller, Edgar R.; Ruggiero, Carmelinda; Cherubini, Antonio; Guralnik, Jack M.; Ferrucci, Luigi

    2009-01-01

    Background Recent studies suggest an association between polyunsaturated fatty acids (PUFAs) and the development of chronic kidney disease. The aim of this study was to examine the relationship between PUFAs and renal function in older adults. Methods We performed a cross-sectional and prospective analysis of 931 adults, ≥65 years old, enrolled in the InCHIANTI study, a population-based cohort in Tuscany, Italy. Plasma PUFAs were measured at enrollment, and creatinine clearance was estimated by the Cockcroft-Gault equation at baseline and after 3-year follow-up. Results At enrollment, participants with higher creatinine clearance had higher concentrations of HDL cholesterol, total plasma PUFAs, plasma n-3 fatty acid (FA), and plasma n-6 FA and lower triglycerides. From enrollment to the 3-year follow-up visit, creatinine clearance declined by 7.8 (12.2) mL/min (P <0.0001). Baseline total plasma PUFAs, n-3 FA, n-6 FA, and linoleic, linolenic, and arachidonic acids were strong independent predictors of less steep decline in creatinine clearance from baseline to follow-up (P <0.0001, after adjusting for baseline creatinine clearance). After adjusting for baseline creatinine, baseline total plasma PUFAs, n-3 FA, and linoleic, linolenic, and arachidonic acids were negatively associated with creatinine at 3-year follow-up. Participants with higher plasma PUFAs at enrollment had a lower risk of developing renal insufficiency, defined by a creatinine clearance <60 mL/min, during 3-year follow-up. Conclusion High PUFA concentrations, both n-3 FA and n-6 FA, may attenuate the age-associated decline in renal function among older community-dwelling women and men. PMID:18202159

  6. ADAPTIVE CLEARANCE CONTROL SYSTEMS FOR TURBINE ENGINES

    NASA Technical Reports Server (NTRS)

    Blackwell, Keith M.

    2004-01-01

    The Controls and Dynamics Technology Branch at NASA Glenn Research Center primarily deals in developing controls, dynamic models, and health management technologies for air and space propulsion systems. During the summer of 2004 I was granted the privilege of working alongside professionals who were developing an active clearance control system for commercial jet engines. Clearance, the gap between the turbine blade tip and the encompassing shroud, increases as a result of wear mechanisms and rubbing of the turbine blades on shroud. Increases in clearance cause larger specific fuel consumption (SFC) and loss of efficient air flow. This occurs because, as clearances increase, the engine must run hotter and bum more fuel to achieve the same thrust. In order to maintain efficiency, reduce fuel bum, and reduce exhaust gas temperature (EGT), the clearance must be accurately controlled to gap sizes no greater than a few hundredths of an inch. To address this problem, NASA Glenn researchers have developed a basic control system with actuators and sensors on each section of the shroud. Instead of having a large uniform metal casing, there would be sections of the shroud with individual sensors attached internally that would move slightly to reform and maintain clearance. The proposed method would ultimately save the airline industry millions of dollars.

  7. Renal handling and acute urinary electrolyte effects of aminoglycoside antibiotics: use of a solitary renal autotransplant in the conscious sheep.

    PubMed

    Bennett, W M; McDougall, J; Potocnik, S; Wright, R D; Whitworth, J A

    1983-01-17

    Renal handling of the aminoglycoside antibiotics gentamicin and tobramycin were studied before and after one hour of constant intravenous infusions adjusted to maintain a concentration of 15 micrograms/mL. A solitary renal autotransplant model in four conscious volume replete 40 Kg sheep was used. This unique surgical preparation allows sampling of renal arterial and renal venous blood as well as urine drained through an exteriorized parotid-ureteral fistula. This surgical preparation has considerable potential in renal pharmacology since it uses a conscious, large animal. Baseline studies in this preparation demonstrated normal, 51CrEDTA and 125 I PAH, clearances which were unaffected by the drugs. Aminoglycoside binding to pooled sheep sera was 11% at physiologic PH, calcium and magnesium concentrations. A-V difference was 1.3 +/- .3 micrograms/mL and extraction by the kidney was 9 +/- 3.2% with no differences between gentamicin and tobramycin. Clearance of gentamicin was 84% and tobramycin 86% of GFR. There was no evidence of tubular injury as evidenced by unchanged urinary beta-2 microglobulin excretion. Serum Na, K, Ca and Mg did not change over the course of the study. Both drugs caused a prompt decrease in absolute and fractional sodium excretion while only gentamicin produced a kaliuresis. Early aminoglycoside effects on electrolyte balance may be an eventual determinant of nephrotoxic potential rather than differences in renal drug handling.

  8. Renal conservation of ketone bodies during starvation.

    PubMed

    Sapir, D G; Owen, O E

    1975-01-01

    Renal handling of acetoacetate and beta-hydroxybutyrate was studied in 12 obese subjects undergoing total starvation. Simultaneously, the acetoacetate, beta-hydroxybutyrate, and inulin clearance rates were measured, and acetoacetate and beta-hydroxybutyrate reabsorption rates were calculated. Renal clearance of blood acetoacetate and beta-hydroxybutyrate remained constant. In contrast, acetoacetate reabsorption rate increased significantly from 47 plus or minus 10 mumoles/min on day 3 to 106 plus or minus 15, 89 plus or minus 10, and 96 plus or minus 10 mumoles/min on days 10, 17, and 24, respectively. Similarly, beta-hydroxybutyrate reabsorption rate increased significantly from 154 plus or minus 27 mumoles/min on day 3 to 419 plus or minus 53, 399 plus or minus 25, and 436 plus or minus 53 mumoles/min on days 10, 17, and 24, respectively. Both acetoacetate and beta-hydroxybutyrate reabsorption rates increased linearly when plotted against their filtered loads. Thus, no tubular maximal transport rate exists for acetoacetate or beta-hydroxybutyrate during physiologic ketonemia. Conservation 450-500 mmoles of ketone bodies/day prevents large urinary losses of cations during prolonged starvation. Since ammonium becomes the major cation excreted during prolonged fasting, the increased renal reabsorption of ketone bodies minimizes body protein loss and aids in maintaining high circulating acetoacetate and beta-hydroxybutyrate concentrations.

  9. Mechanisms of hypertension in renal radiation

    SciTech Connect

    Juncos, L.; Cornejo, J.C.; Cejas, H.; Broglia, C. )

    1990-02-01

    This study was undertaken to investigate the role played by renal functional and structural changes in the development of radiation-induced hypertension. Four groups of rats were studied: (1) left kidney radiated, (2) sham procedure, (3) uninephrectomy followed 3 weeks later by radiation of the contralateral kidney, and (4) uninephrectomy followed by sham procedure 3 weeks later. All radiated rats became hypertensive at 12 weeks (p less than 0.05) and had higher protein excretion (p less than 0.05). In the presence of an intact contralateral kidney, radiation causes mild-to-moderate histological abnormalities, and therefore, creatinine clearance and water and sodium handling do not change. Plasma renin activity increased in this group (p less than 0.05). Radiated uninephrectomized rats showed decreased creatinine clearance (p less than 0.05), but renin activity remained unchanged. These rats developed severe histological abnormalities in glomeruli, interstitia, tubuli, and vessels resulting in increased sodium and water output. The average of individual tubular and interstitial scores correlated significantly with both water intake and output but not with sodium excretion. These studies suggest that in the presence of an intact kidney, renin is an important determinant in the development or maintenance of radiation hypertension, whereas in the absence of the contralateral kidney, severe histological changes and renal failure are prominent despite increased water intake and output. The more severe glomerular sclerosis and proteinuria in the latter model could be related to diminished renal mass.

  10. 48 CFR 945.603-70 - Plant clearance function.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Plant clearance function... Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the contracting officer shall assume all responsibilities of the plant clearance...

  11. 48 CFR 245.7203 - Assigning plant clearance case numbers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Assigning plant clearance....7203 Assigning plant clearance case numbers. (a) Use a three-part, 11-character number constructed as... clearance number on DD Form 1635, Plant Clearance Case Register, or mechanized equivalent....

  12. 48 CFR 245.7202 - Establishing a plant clearance case.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... clearance case. 245.7202 Section 245.7202 Federal Acquisition Regulations System DEFENSE ACQUISITION....7202 Establishing a plant clearance case. (a) Upon receipt of an acceptable inventory schedule or a DD Form 1342, DoD Property Record, the plant clearance officer shall establish a plant clearance case...

  13. 7 CFR 1927.55 - Title clearance services.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Title clearance services. 1927.55 Section 1927.55... REGULATIONS TITLE CLEARANCE AND LOAN CLOSING Real Estate Title Clearance and Loan Closing § 1927.55 Title clearance services. (a) Responsibilities of closing agents. Services to be provided to the agency and...

  14. 48 CFR 945.603-70 - Plant clearance function.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Plant clearance function... Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the contracting officer shall assume all responsibilities of the plant clearance...

  15. 48 CFR 945.603-70 - Plant clearance function.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Plant clearance function... Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the contracting officer shall assume all responsibilities of the plant clearance...

  16. 48 CFR 801.602-76 - Business clearance review.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is a... obtain a business clearance review prior to award of any contract, task or delivery order, or...

  17. 48 CFR 801.602-76 - Business clearance review.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is a... obtain a business clearance review prior to award of any contract, task or delivery order, or...

  18. 32 CFR 644.517 - Clearance of Army lands.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 4 2013-07-01 2013-07-01 false Clearance of Army lands. 644.517 Section 644.517... ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from Proposed Excess Land and Improvements § 644.517 Clearance of Army lands. The responsibility for performing clearance...

  19. 32 CFR 644.517 - Clearance of Army lands.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 4 2012-07-01 2011-07-01 true Clearance of Army lands. 644.517 Section 644.517... ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from Proposed Excess Land and Improvements § 644.517 Clearance of Army lands. The responsibility for performing clearance...

  20. 32 CFR 644.517 - Clearance of Army lands.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 4 2014-07-01 2013-07-01 true Clearance of Army lands. 644.517 Section 644.517... ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from Proposed Excess Land and Improvements § 644.517 Clearance of Army lands. The responsibility for performing clearance...

  1. 32 CFR 644.517 - Clearance of Army lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of Army lands. 644.517 Section 644.517... ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from Proposed Excess Land and Improvements § 644.517 Clearance of Army lands. The responsibility for performing clearance...

  2. Targeted Fcγ Receptor (FcγR)-mediated Clearance by a Biparatopic Bispecific Antibody.

    PubMed

    Kasturirangan, Srinath; Rainey, G Jonah; Xu, Linda; Wang, Xinwei; Portnoff, Alyse; Chen, Tracy; Fazenbaker, Christine; Zhong, Helen; Bee, Jared; Zeng, Zhutian; Jenne, Craig; Wu, Herren; Gao, Changshou

    2017-03-10

    Soluble ligands have commonly been targeted by antibody therapeutics for cancers and other diseases. Although monoclonal antibodies targeting such ligands can block their interactions with their cognate receptors, they can also significantly increase the half-life of their ligands by FcRn-mediated antibody recycling, thereby evading ligand renal clearance and requiring increasingly high antibody doses to neutralize the increasing pool of target. To overcome this issue, we generated a bispecific/biparatopic antibody (BiSAb) that targets two different epitopes on IL-6 to block IL-6-mediated signaling. The BiSAb formed large immune complexes with IL-6 that can bind Fcγ receptors on phagocytic cells and are rapidly internalized. In addition, rapid clearance of the BiSAb·IL-6 complex was observed in mice while the parental antibodies prolonged the serum half-life of IL-6. Intravital imaging of the liver in mice confirmed that the rapid clearance of these large immune complexes was associated with Fcγ receptor-dependent binding to Kupffer cells in the liver. The approach described here provides a general strategy for therapeutic antibodies with the ability to not only neutralize but also actively drive clearance of their soluble antigens.

  3. A case of delayed methotrexate clearance following administration of a complementary medication containing chlorophyll.

    PubMed

    Brooks, Sally L; Sanders, Julie; Seymour, John F; Mellor, James D

    2014-06-01

    A 54-year-old male with relapsed primary cerebral lymphoma and normal renal function was treated with methotrexate (MTX) 3 g/m(2) monthly by intravenous infusion. Throughout treatment the patient self-administered a complementary medicine (Jason Winter's chlorophyll®), which he was advised to cease during methotrexate treatment due to the potential for unknown interactions. For the first four cycles, chlorophyll was ceased two days prior to commencement of methotrexate and withheld until clearance. These cycles were administered without complication, and the methotrexate level reduced to <0.05 µmol/L within three days of each dose. Prior to cycle 5, chlorophyll was not ceased and there were no changes to concomitant medications. A literature search found no documented interactions between methotrexate and chlorophyll and the chemotherapy was administered without a delay in treatment. The methotrexate level three days post-administration was 0.36 µmol/L and did not reduce to <0.05 µmol/L until day 10. Consequently, from cycles 6 to 12, the methotrexate dose was halved, and the patient ceased chlorophyll 48 h prior to methotrexate administration until clearance. There were no further episodes of delayed methotrexate clearance. No impurities were detected in a sample of Jason Winter's chlorophyll®. It is therefore likely that the patient's delayed methotrexate clearance was due to an interaction with chlorophyll. It is recommended that such chlorophyll containing preparations be avoided in patients treated with methotrexate.

  4. Targeted Fcγ Receptor (FcγR)-mediated Clearance by a Biparatopic Bispecific Antibody*

    PubMed Central

    Kasturirangan, Srinath; Rainey, G. Jonah; Xu, Linda; Wang, Xinwei; Portnoff, Alyse; Chen, Tracy; Fazenbaker, Christine; Zhong, Helen; Bee, Jared; Zeng, Zhutian; Jenne, Craig; Wu, Herren; Gao, Changshou

    2017-01-01

    Soluble ligands have commonly been targeted by antibody therapeutics for cancers and other diseases. Although monoclonal antibodies targeting such ligands can block their interactions with their cognate receptors, they can also significantly increase the half-life of their ligands by FcRn-mediated antibody recycling, thereby evading ligand renal clearance and requiring increasingly high antibody doses to neutralize the increasing pool of target. To overcome this issue, we generated a bispecific/biparatopic antibody (BiSAb) that targets two different epitopes on IL-6 to block IL-6-mediated signaling. The BiSAb formed large immune complexes with IL-6 that can bind Fcγ receptors on phagocytic cells and are rapidly internalized. In addition, rapid clearance of the BiSAb·IL-6 complex was observed in mice while the parental antibodies prolonged the serum half-life of IL-6. Intravital imaging of the liver in mice confirmed that the rapid clearance of these large immune complexes was associated with Fcγ receptor-dependent binding to Kupffer cells in the liver. The approach described here provides a general strategy for therapeutic antibodies with the ability to not only neutralize but also actively drive clearance of their soluble antigens. PMID:28100773

  5. Renal disease in pregnancy.

    PubMed

    Thorsen, Martha S; Poole, Judith H

    2002-03-01

    Anatomic and physiologic adaptations within the renal system during pregnancy are significant. Alterations are seen in renal blood flow and glomerular filtration, resulting in changes in normal renal laboratory values. When these normal renal adaptations are coupled with pregnancy-induced complications or preexisting renal dysfunction, the woman may demonstrate a reduction of renal function leading to an increased risk of perinatal morbidity and mortality. This article will review normal pregnancy adaptations of the renal system and discuss common pregnancy-related renal complications.

  6. Renal Denervation

    PubMed Central

    Persu, Alexandre; Renkin, Jean; Thijs, Lutgarde; Staessen, Jan A.

    2013-01-01

    The term “ultima ratio” has multiple, though related, meanings. The motto “ultima ratio regum,” cast on the cannons of the French army of King Louis XIV, meant that war is the last argument of kings, that is, the one to be used after all diplomatic arguments have failed. Along similar lines, we propose that, given the current evidence, renal denervation should be used as a last resort, after state-of-the-art drug treatment optimized at expert centers failed to control blood pressure. PMID:22851728

  7. Drug Dosage in Patients with Renal Failure Optimized by Immediate Concurrent Feedback

    PubMed Central

    Falconnier, Ariane D; Haefeli, Walter E; Schoenenberger, Ronald A; Surber, Christian; Martin-Facklam, Meret

    2001-01-01

    OBJECTIVE To examine the impact of immediate concurrent feedback on dose adjustment in patients with renal failure. DESIGN Prospective 12-month study in patients with various degrees of renal failure, with comparison to a retrospective control group. SETTING A 39-bed unit of a university hospital providing primary and tertiary care. PATIENTS Patients with renal failure (estimated creatinine clearance ≤50 mL/min) receiving at least 1 pharmacologically active drug. INTERVENTIONS Education of physicians and immediate concurrent feedback on the ward giving estimated creatinine clearance and dose recommendations for renally eliminated drugs adjusted to individual renal function. MEASUREMENTS AND MAIN RESULTS The percentage of dosage regimens adjusted to renal function and cost assessment of drug therapy were calculated. Overall, 17% of the patients had at least 1 estimated creatinine clearance ≤50 mL/min. In the intervention group, the dose of 81% of renally eliminated drugs was adjusted to renal function, compared with 33% in the control group ( P < .001). The mean difference in cost between standard and adjusted dose of renally eliminated drugs in the intervention and control groups was 5.3 ± 12.3 and 0.75 ± 2.8 Swiss francs (approximately US$3.5 and US$0.5), respectively ( P < .001), accounting for 16.5% and 2.8%, respectively, of daily medication costs of all drugs. CONCLUSIONS The proportion of doses of renally eliminated drugs adjusted to renal function can be substantially increased by immediate concurrent feedback. This saves drug costs and has the potential to prevent adverse drug reactions. PMID:11422633

  8. Creatinine, urea, uric acid, water and electrolytes renal handling in the healthy oldest old

    PubMed Central

    Musso, Carlos Guido; Álvarez Gregori, Joaquín; Jauregui, José Ricardo; Macías Núñez, Juan Florencio

    2012-01-01

    Renal physiology in the healthy oldest old has the following characteristics, in comparison with the renal physiology in the young: a reduced creatinine clearance, tubular pattern of creatinine back-filtration, preserved proximal tubule sodium reabsorption and uric acid secretion, reduced sodium reabsorption in the thick ascending loop of Henle, reduced free water clearance, increased urea excretion, presence of medulla hypotonicity, reduced urinary dilution and concentration capabilities, and finally a reduced collecting tubules response to furosemide which expresses a reduced potassium excretion in this segment due to a sort of aldosterone resistance. All physiological changes of the aged kidney are the same in both genders. PMID:24175249

  9. A Pharmacokinetic and Safety Study of Trebananib, a Fc-Fusion Peptibody, in Patients with Advanced Solid Tumors and Varying Degrees of Renal Dysfunction.

    PubMed

    Wu, Benjamin; Lewis, Lionel D; Harvey, R Donald; Rasmussen, Erik; Gamelin, Erick; Sun, Yu-Nien; Friberg, Gregory; Koyner, Jay L; Dowlati, Afshin; Maitland, Michael L

    2017-01-11

    Clearance of trebananib (AMG 386), a 64 kD anti-angiogenic peptibody, has been associated with estimated glomerular filtration rate (eGFR). We prospectively evaluated trebananib pharmacokinetics and safety/tolerability in advanced solid tumor patients with varying degrees of renal function. Patients were assigned to normal renal function, mild, moderate, or severe renal dysfunction cohorts based on eGFR, received trebananib 15 mg/kg IV weekly, and underwent week 1 and week 5 pharmacokinetic and weekly safety assessments. For 28 patients, trebananib clearance decreased from normal renal function (1.52 mL/hr/kg), to mild (1.20 mL/hr/kg), moderate (0.79 mL/hr/kg), and severe (0.53 mL/hr/kg) renal dysfunction (P ≤ 0.001). Treatment-related adverse events showed no association with clearance. Trebananib clearance was proportional to eGFR and unrelated to pretreatment protein excretion. These data confirm a role for renal clearance of a recombinant peptibody with molecular weight < 69 kD and support a longer dosing interval for patients with severe renal dysfunction. This article is protected by copyright. All rights reserved.

  10. A re-appraisal of volume status and renal function impairment in chronic heart failure: combined effects of pre-renal failure and venous congestion on renal function.

    PubMed

    Sinkeler, Steef J; Damman, Kevin; van Veldhuisen, Dirk J; Hillege, Hans; Navis, Gerjan

    2012-03-01

    The association between cardiac failure and renal function impairment has gained wide recognition over the last decade. Both structural damage in the form of systemic atherosclerosis and (patho) physiological hemodynamic changes may explain this association. As regards hemodynamic factors, renal impairment in chronic heart failure is traditionally assumed to be mainly due to a decrease in cardiac output and a subsequent decrease in renal perfusion. This will lead to a decrease in glomerular filtration rate and a compensatory increase in tubular sodium retention. The latter is a physiological renal response aimed at retaining fluids in order to increase cardiac filling pressure and thus renal perfusion. In heart failure, however, larger increases in cardiac filling pressure are needed to restore renal perfusion and thus more volume retention. In this concept, in chronic heart failure, an equilibrium exists where a certain degree of congestion is the price to be paid to maintain adequate renal perfusion and function. Recently, this hypothesis was challenged by new studies, wherein it was found that the association between right-sided cardiac filling pressures and renal function is bimodal, with worse renal function at the highest filling pressures, reflecting a severely congested state. Renal hemodynamic studies suggest that congestion negatively affects renal function in particular in patients in whom renal perfusion is also compromised. Thus, an interplay between cardiac forward failure and backward failure is involved in the renal function impairment in the congestive state, presumably along with other factors. Only few data are available on the impact of intervention in volume status on the cardio-renal interaction. Sparse data in cardiac patients as well as evidence from cohorts with primary renal disease suggest that specific targeting of volume overload may be beneficial for long-term outcome, in spite of a certain further decrease in renal function, at least

  11. Lupus nephritis and renal disease in pregnancy.

    PubMed

    Germain, S; Nelson-Piercy, C

    2006-01-01

    Management of pregnant women with renal disease involves awareness of, and allowance for, physiological changes including decreased serum creatinine and increased proteinuria. For women with systemic lupus erythematosus (SLE), pregnancy increases likelihood of flare. These can occur at any stage, and are more difficult to diagnose, as symptoms overlap those of normal pregnancy. Renal involvement is no more common in pregnancy. Worsening proteinuria may be lupus flare but differential includes pre-eclampsia. In women with chronic renal disease, pregnancy may accelerate decline in renal function and worsen hypertension and proteinuria, with increased risk of maternal (eg, pre-eclampsia) and fetal (eg, IUGR, IUD) complications, strongly correlating with degree of renal impairment peri-conception. Pregnancy success rate varies from 20% to 95% depending on base-line creatinine. Best outcome is obtained if disease was quiescent for >6 months pre-conception. Women on dialysis or with renal transplants can achieve successful pregnancy but have higher maternal and fetal complication rates. Acute on chronic renal failure can develop secondary to complications such as HELLP and AFLP. Management needs to be by a multidisciplinary team involving physicians and obstetricians, ideally beginning with pre-pregnancy counselling. Treatment of flares includes corticosteroids, hydroxychloroquine, azothioprine, NSAIDs and MME Blood pressure is controlled with methyldopa, nifedipine or hydralazine.

  12. Noninvasive fluorescence detection of hepatic and renal function

    NASA Astrophysics Data System (ADS)

    Dorshow, Richard B.; Bugaj, Joseph E.; Burleigh, B. D.; Duncan, James R.; Johnson, Michael A.; Jones, William B.

    1998-07-01

    A noninvasive in vivo fluorescence detection scheme was employed to continuously monitor exogenous dye clearance from the vasculature. Differentiation between normal and impaired physiological function in a rat model was demonstrated for both liver and kidney. A fiber optic transmitted light from source to ear; a second fiber optic positioned near the ear transmitted the fluorescent light to a detector system. Two model dye systems were employed in this initial study. Indocyanine green, known to be exclusively cleared from the blood stream by the liver, was excited in vivo with laser light at 780 nm. The fluorescence signal was detected at 830 nm. A characteristic clearance curve of normal hepatic function was obtained. After a partial hepatectomy of the liver, the clearance curve was extended in time, as would be expected from reduced hepatic function. In addition, fluorescein labeled poly-D-lysine, a small polymer predominantly cleared from the blood stream by the kidney, was excited in vivo with laser light at 488 nm. The fluorescence signal was detected at 518 nm. A characteristic clearance curve of normal renal function was obtained. After a bilateral ligation of the kidneys, the clearance curve remained elevated and constant, indicating little if any clearance. Thus, the feasibility of a new noninvasive method for physiological function assessment was established.

  13. Technetium-99m dimercaptosuccinic acid uptake in long-term catheterized kidney. Comparison with renal function

    SciTech Connect

    Higashihara, E.; Tokuda, H.; Kishi, H.; Niijima, T.; Okada, Y.; Nishikawa, J.; Iio, M.

    1988-04-01

    We studied 23 long-term catheterized kidneys in 14 patients. The uptake of /sup 99m/Tc acid (/sup 99m/Tc-DMSA) was measured at one- and two-hour intervals after injection, and the uptake was corrected for variations in renal depth. These values were compared with inulin, creatinine, and para-amino hippurate (PAH) clearances which were measured in each kidney by collecting urine through long-term catheterization. Correlation coefficient was obtained between PAH clearance corrected for the body surface area and the two-hour uptake of /sup 99m/Tc-DMSA. The correlation coefficients between the two-hour uptake of /sup 99m/Tc-DMSA and the clearance values are not significantly different from those between the one-hour uptake and the clearance values. Corrections of the uptake for variations in renal depth did not improve the correlation coefficients. The results show that /sup 99m/Tc-DMSA is an excellent method to estimate the renal plasma flow and the one-hour uptake without correction for renal depth is clinically sufficient to evaluate the split renal function.

  14. Assessment of glomerular filtration rate and effective renal plasma flow in cystic fibrosis

    SciTech Connect

    Spino, M.; Chai, R.P.; Isles, A.F.; Balfe, J.W.; Brown, R.G.; Thiessen, J.J.; MacLeod, S.M.

    1985-07-01

    A study was conducted to examine renal function in 10 healthy control subjects and eight patients with cystic fibrosis in stable condition. Sequential bolus injections of /sup 99m/Tc-DTPA and /sup 125/I-OIH were administered to assess glomerular filtration rate and effective renal plasma flow, respectively. Blood was subsequently collected for 3 hours, and urine for 24 hours. Renal clearances of both radioisotope markers were virtually identical in patients and controls. Inasmuch as neither glomerular filtration rate nor effective renal plasma flow was enhanced in patients with cystic fibrosis, increased clearance of drugs in these patients is unlikely to be the result of enhanced glomerular filtration or tubular secretion.

  15. Effects of airborne pollutants on mucociliary clearance.

    PubMed Central

    Wolff, R K

    1986-01-01

    The mucociliary clearance system is a first line of defense against inhaled agents, and so its compromise can adversely affect health. The purpose of this paper is to provide a review of data on the effect of in vivo air pollutant exposures on the clearance of test particles from airways. Data from both animals and humans are compared whenever possible, so that estimates of human health effects may be made. Mechanisms of action are also discussed, presenting the view that for low level exposures, changes in secretions are probably responsible for most observed changes in clearance. The pollutants pertinent to this review are those that are common in the environment and most likely to have impacts on large numbers of people: sulfur oxides, sulfuric acid mist, O3, NO2, particulates, diesel exhaust, and cigarette smoke. Images FIGURE 1. FIGURE 2. a FIGURE 2. b FIGURE 4. PMID:3519203

  16. Effects of airborne pollutants on mucociliary clearance

    SciTech Connect

    Wolff, R.K.

    1986-04-01

    The mucociliary clearance system is a first line of defense against inhaled agents, and so its compromise can adversely affect health. The purpose of this paper is to provide a review of data on the effect of in vivo air pollutant exposures on the clearance of test particles from airways. Data from both animals and humans are compared whenever possible, so that estimates of human health effects may be made. Mechanisms of action are also discussed, presenting the view that for low level exposures, changes in secretions are probably responsible for most observed changes in clearance. The pollutants pertinent to this review are those that are common in the environment and most likely to have impacts on large numbers of people: sulfur oxides, sulfuric acid mist, O/sub 3/, NO/sub 2/, particulates, diesel exhaust, and cigarette smoke.149 references.

  17. Renal effects of continuous negative pressure breathing

    NASA Technical Reports Server (NTRS)

    Kinney, M. J.; Discala, V. A.

    1975-01-01

    Continuous negative pressure breathing (CNPB) was utilized to simulate the thoracic vascular distension of zero g or space, in 11 anesthetized rats. The animals underwent renal clearance and micropuncture renal nephron studies before, during, and after CNPB. Rats were pretreated with a high salt diet and I-M desoxycorticosterone (DOCA) in excess. None of these rats diuresed with CNPB. In contrast 5 of the 7 remaining rats increased the fraction of the filtered sodium excreted (C sub Na/GFR, p .05) and their urinary flow rate (V, p .05). Potassium excretion increased (U sub k V, p .05). End proximal tubular fluid specimen's TF/P inulin ratios were unchanged. Whole kidney and single nephron glomerular filtration rates fell 10%. CNPB, a mechanism for atrial distension, appears to cause, in rats, a decrease in distal tubular sodium, water and potassium reabsorption. Exogenous mineral-corticoid prevents the diuresis, saluresis, and kaluresis.

  18. Use of radionuclide renal imaging for clinical followup after extracorporeal shock wave lithotripsy of renal stones.

    PubMed

    Michaels, E K; Pavel, D G; Orellana, P; Montes, A; Olea, E

    1992-09-01

    Patients treated by extracorporeal shock wave lithotripsy (ESWL) are usually evaluated by excretory urography within 1 month after treatment to determine the clearance of stone debris and rule out asymptomatic obstruction. In an attempt to obtain more precise functional information, we used 99mtechnetium-diethylenetriaminepentaacetic acid and 131iodine-hippurate radionuclide renal imaging studies, and a plain abdominal radiograph as the initial followup study after ESWL of 64 kidneys in 55 patients. Of 53 kidneys studied within 60 days after ESWL 42 had abnormal radionuclide renal imaging studies demonstrating pelviocaliceal stasis, excretory delay or poor function, 8 of which required subsequent interventions for obstructing stone debris. Five patients had excretory delay after ESWL that was unexpected based on a pre-ESWL excretory urogram showing normal function without dilation. A subset of 23 patients with large stone burden or anatomical deformity from a prior operation had baseline radionuclide renal imaging studies before ESWL; function improved in 4 and worsened in 5 by radionuclide renal imaging studies after completion of treatment. A total of 19 patients had radionuclide renal imaging studies earlier (within 17 days) after ESWL because of poor function and/or large stone burden, and as expected they had evidence of obstruction from stone debris, which necessitated further followup. Our experience suggests that followup of ESWL by radionuclide renal imaging studies provides specific functional information that is of particular value in the management of patients with obstructing stone debris and/or diminished renal function. Radionuclide renal imaging studies may also reveal unsuspected obstruction or functional impairment after ESWL of uncomplicated stones, and is recommended as routine followup after ESWL.

  19. Pharmacologic agents for mucus clearance in bronchiectasis.

    PubMed

    Nair, Girish B; Ilowite, Jonathan S

    2012-06-01

    There are no approved pharmacologic agents to enhance mucus clearance in non-cystic fibrosis (CF) bronchiectasis. Evidence supports the use of hyperosmolar agents in CF, and studies with inhaled mannitol and hypertonic saline are ongoing in bronchiectasis. N-acetylcysteine may act more as an antioxidant than a mucolytic in other lung diseases. Dornase α is beneficial to patients with CF, but is not useful in patients with non-CF bronchiectasis. Mucokinetic agents such as β-agonists have the potential to improve mucociliary clearance in normals and many disease states, but have not been adequately studied in patients with bronchiectasis.

  20. Mucociliary clearance from the calf lung.

    PubMed Central

    Jones, C D

    1983-01-01

    Mucociliary clearance rate constants for ten calves were obtained using Technetium 99m-sulphur colloid complex. The mean rate constant measured at the lung for all calves was 0.012 (+/- 0.009) min-1 (half-life 58 minutes). The clearance rate constants obtained from measurements made at the larynx were higher (0.02 +/- 0.007 min-1), although not significantly higher, than those determined from measurements taken at the lung. The constants can be used to predict the particle burden on the lungs of calves kept under husbandry systems of varying air hygiene. Images Fig. 1. PMID:6640409

  1. Functions of the Renal Nerves.

    ERIC Educational Resources Information Center

    Koepke, John P.; DiBona, Gerald F.

    1985-01-01

    Discusses renal neuroanatomy, renal vasculature, renal tubules, renin secretion, renorenal reflexes, and hypertension as related to renal nerve functions. Indicates that high intensitites of renal nerve stimulation have produced alterations in several renal functions. (A chart with various stimulations and resultant renal functions and 10-item,…

  2. Epigenetic Regulation of MicroRNAs Controlling CLDN14 Expression as a Mechanism for Renal Calcium Handling

    PubMed Central

    Gong, Yongfeng; Himmerkus, Nina; Plain, Allein; Bleich, Markus

    2015-01-01

    The kidney has a major role in extracellular calcium homeostasis. Multiple genetic linkage and association studies identified three tight junction genes from the kidney—claudin-14, -16, and -19—as critical for calcium imbalance diseases. Despite the compelling biologic evidence that the claudin-14/16/19 proteins form a regulated paracellular pathway for calcium reabsorption, approaches to regulate this transport pathway are largely unavailable, hindering the development of therapies to correct calcium transport abnormalities. Here, we report that treatment with histone deacetylase (HDAC) inhibitors downregulates renal CLDN14 mRNA and dramatically reduces urinary calcium excretion in mice. Furthermore, treatment of mice with HDAC inhibitors stimulated the transcription of renal microRNA-9 (miR-9) and miR-374 genes, which have been shown to repress the expression of claudin-14, the negative regulator of the paracellular pathway. With renal clearance and tubule perfusion techniques, we showed that HDAC inhibitors transiently increase the paracellular cation conductance in the thick ascending limb. Genetic ablation of claudin-14 or the use of a loop diuretic in mice abrogated HDAC inhibitor-induced hypocalciuria. The genetic mutations in the calcium-sensing receptor from patients with autosomal dominant hypocalcemia (ADH) repressed the transcription of miR-9 and miR-374 genes, and treatment with an HDAC inhibitor rescued the phenotypes of cell and animal models of ADH. Furthermore, systemic treatment of mice with antagomiRs against these miRs relieved claudin-14 gene silencing and caused an ADH-like phenotype. Together, our findings provide proof of concept for a novel therapeutic principle on the basis of epigenetic regulation of renal miRs to treat hypercalciuric diseases. PMID:25071082

  3. Modified Augmented Renal Clearance Score Predicts Rapid Piperacillin and Tazobactam Clearance in Critically Ill Surgery and Trauma Patients

    DTIC Science & Technology

    2014-04-24

    unit (ICU) patients re-mains high despite numerous clinical and technologic advances supporting the care of critically ill patients. Sepsis continues...From 83 subjects in both studies, 13 met the criteria for inclusion. The subjects varied in their mechanisms of injury/ illness, indication for...Characteristics of Study Subjects Receiving Piperacillin/Tazobactam Included in This Study Subject Age, y Sex Mechanism Indication Dose* eGFR** SOFA† APACHE II

  4. Pharmacokinetics of netivudine, a potent anti-varicella zoster virus drug, in patients with renal impairment.

    PubMed

    Fillastre, J P; Godin, M; Legallicier, B; Chretien, P; Bidault, R; Gillotin, C; Wooton, R; Posner, J; Peck, R W

    1996-05-01

    The pharmacokinetics of a single oral 200 mg dose of netivudine (1-(beta-D-arabinofuranosyl)-5-(1-propynyl)uracil), a nucleoside analogue under development for use in varicella zoster virus infections, were studied in 12 renal failure (RF) subjects (creatinine clearance 15 +/- 7 mL/min) and 12 age-matched healthy subjects with normal creatinine clearance. Blood and urine samples were collected up to nine days after drug administration. Concentrations of netivudine and of its main metabolite, the pyrimidine base 5-(1-propynyl)uracil (5 PU), were determined by a specific high performance liquid chromatography assay. The mean peak plasma concentrations of netivudine, Tmax, and volume of distribution were not significantly affected by RF. The elimination half-life of netivudine was approximately 15 h in subjects with normal renal function and 60 h in RF patients. Plasma and renal clearances of netivudine were significantly reduced in RF patients and AUC was three to four times higher in these patients. Cmax and AUC of 5 PU were higher in RF patients, and the half-life was also significantly longer. However, the half-life of this metabolite was much lower than that of the parent compound. Tmax and the lag time were similar in the two groups. There were highly significant correlations for netivudine and 5 PU between half-life and creatinine clearance and between renal clearance and creatinine clearance. These findings suggest that netivudine dosage may need to be reduced in patients with severe renal failure, and confirm that formation of the 5 PU is independent of the elimination of netivudine from plasma.

  5. Radial Clearance Found To Play a Key Role in the Performance of Compliant Foil Air Bearings

    NASA Technical Reports Server (NTRS)

    Radil, Kevin C.

    2003-01-01

    Compliant foil air bearings are at the forefront of the Oil-Free turbomachinery revolution, which supports gas turbine engines with hydrodynamic bearings that use air instead of oil as the working fluid. These types of bearings have been around for almost 50 years and have found a home in several commercial applications, such as in air cycle machines, turbocompressors, and microturbines, but are now being aggressively pursued for use in small and midrange aircraft gas turbine engines. Benefits include higher operating speeds and temperatures, lower maintenance costs, and greater reliability. The Oil-Free Turbomachinery team at the NASA Glenn Research Center is working to foster the transition of Oil-Free technology into gas turbine engines by performing in-house experiments on foil air bearings in order to gain a greater insight into their complex operating principles. A research program recently undertaken at Glenn focused on the concept of radial clearance and its influence on bearing performance. The tests were conducted on foil bearings with different radial clearances. As defined for a foil bearing, radial clearance is a measure of the small amount of shaft radial motion that is present from play that exists in the elastic support structure, such as between the top and bump foils and the bump foils and bearing shell (see the drawing). With an insufficient amount of radial clearance, the bearing imparts a high preload on the shaft, which when excessive, can reduce the loadcarrying capability of the bearing. On the other hand, systems using foil bearings with excessive radial clearance may experience rotordynamic instabilities because of low bearing preload. Therefore, without a more thorough understanding of radial clearance, it is difficult to accurately predict the performance of a given bearing design. The test program demonstrated that there is a direct correlation between radial clearance and the performance of foil air bearings. As shown in the graph, an

  6. Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

    PubMed

    Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

    2011-01-01

    The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

  7. Bioartificial Renal Epithelial Cell System (BRECS): A Compact, Cryopreservable Extracorporeal Renal Replacement Device

    PubMed Central

    Buffington, Deborah A.; Pino, Christopher J.; Chen, Lijun; Westover, Angela J.; Hageman, Gretchen; Humes, H. David

    2012-01-01

    Renal cell therapy has shown clinical efficacy in the treatment of acute renal failure (ARF) and promise for treatment of end-stage renal disease (ESRD) by supplementing conventional small solute clearance (hemodialysis or hemofiltration) with endocrine and metabolic function provided by cells maintained in an extracorporeal circuit. A major obstacle in the widespread adoption of this therapeutic approach is the lack of a cryopreservable system to enable distribution, storage, and therapeutic use at point of care facilities. This report details the design, fabrication, and assessment of a Bioartificial Renal Epithelial Cell System (BRECS), the first all-in-one culture vessel, cryostorage device, and cell therapy delivery system. The BRECS was loaded with up to 20 cell-seeded porous disks, which were maintained by perfusion culture. Once cells reached over 5×106 cells/disk for a total therapeutic dose of approximately 108 cells, the BRECS was cryopreserved for storage at −80°C or −140°C. The BRECS was rapidly thawed, and perfusion culture was resumed. Near precryopreservation values of cell viability, metabolic activity, and differentiated phenotype of functional renal cells were confirmed postreconstitution. This technology could be extended to administer other cell-based therapies where metabolic, regulatory, or secretion functions can be leveraged in an immunoisolated extracorporeal circuit. PMID:24575327

  8. Renal effects of continuous negative pressure breathing

    NASA Technical Reports Server (NTRS)

    Kinney, M. J.

    1975-01-01

    Continuous negative pressure breathing (CNPB) was utilized to simulate the thoracic vascular distension of zero G in 11 anesthetized rats. The animals underwent renal clearance and micropuncture renal nephron studies before, during, and after CNPB. Four rats were pretreated with a high salt diet and I-M desoxycorticosterone (DOCA) in excess. None of these rats diuresed with CNPB. In contrast, five of the seven remaining rats increased the fraction of the filtered sodium excreted and their urinary flow rate. Potassium excretion increased. End proximal tubular fluid specimen's TF/P inulin ratios were unchanged. Whole kidney and single nephron glomerular filtration rates fell 10%. CNPB, a mechanism for atrial distension, appears to cause in the rat a decrease in distal tubular sodium and water reabsorption. Exogenous mineral-corticoid prevents the diuresis, saluresis, and kaluresis. The adequacy of other nonatrial volume control mechanisms in regulating renal salt and water conservation in opposition to the studied atrial-renal (Henry-Gauer) reflex of thoracic vascular distension is confirmed.

  9. Effects of Bearing Clearance on Turbopump Stability

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Effects of bearing clearances, or "dead bands," on bearing loads and rotor stability in turbopumps examined in a 194-page report. Relatively simple mathematical force model for analyzing effects highlighted. Report shows nonlinear characteristics resulting from bearing dead bands have significant effect on dynamics of turbomachinery and not ignored as in the past.

  10. 32 CFR 154.16 - Security clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Security clearance. 154.16 Section 154.16 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE SECURITY DEPARTMENT OF DEFENSE PERSONNEL SECURITY PROGRAM REGULATION Personnel Security Investigative Requirements § 154.16...

  11. 32 CFR 154.16 - Security clearance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 1 2014-07-01 2014-07-01 false Security clearance. 154.16 Section 154.16 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE SECURITY DEPARTMENT OF DEFENSE PERSONNEL SECURITY PROGRAM REGULATION Personnel Security Investigative Requirements § 154.16...

  12. 32 CFR 154.16 - Security clearance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false Security clearance. 154.16 Section 154.16 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE SECURITY DEPARTMENT OF DEFENSE PERSONNEL SECURITY PROGRAM REGULATION Personnel Security Investigative Requirements § 154.16...

  13. 32 CFR 154.16 - Security clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false Security clearance. 154.16 Section 154.16 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE SECURITY DEPARTMENT OF DEFENSE PERSONNEL SECURITY PROGRAM REGULATION Personnel Security Investigative Requirements § 154.16...

  14. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electrical clearances. 18.24 Section 18.24 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and...

  15. 30 CFR 57.11010 - Stairstep clearance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Stairstep clearance. 57.11010 Section 57.11010 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... steps shall be a minimum of seven feet, or suitable warning signs or similar devices shall be...

  16. 30 CFR 57.11010 - Stairstep clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Stairstep clearance. 57.11010 Section 57.11010 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... steps shall be a minimum of seven feet, or suitable warning signs or similar devices shall be...

  17. Clearance of seborrhoeic keratoses with topical dobesilate

    PubMed Central

    Cuevas, Pedro; Angulo, Javier; Salgüero, Irene; Giménez-Gallego, Guillermo

    2012-01-01

    A patient with two seborrhoeic keratoses in the face received a single daily application of dobesilate cream during 6 months. Dobesilate achieved complete clearance of the seborrhoeic keratosis lesions with good cosmoses, suggesting that this compound is a safe and efficient candidate in the treatment of seborrhoeic keratoses. PMID:22729328

  18. Decreased renal uptake of (99m)Tc-DMSA in patients with tubular proteinuria.

    PubMed

    Lee, Beom Hee; Lee, So Hee; Choi, Hyun Jin; Kang, Hee Gyung; Oh, So Won; Lee, Dong Soo; Ha, Il Soo; Choi, Yong; Cheong, Hae Il

    2009-11-01

    Although technetium-99m-dimercaptosuccinic acid ((99m)Tc-DMSA) renal scans are widely used to evaluate renal tubular mass function, the mechanism by which renal uptake of DMSA occurs is still the subject of debate. Patients with various proximal tubular disorders show markedly decreased renal DMSA uptake, even when there is normal creatinine clearance. We measured the renal uptake of (99m)Tc-DMSA 3 h after its injection in 13 patients with Dent disease or Lowe syndrome, both of which are typical proximal tubular disorders with defective megalin and cubilin-mediated endocytosis. Serial images of three patients were also obtained at 0.5, 1, 2 and 3 h post-injection. The correlations between renal uptake of (99m)Tc-DMSA and creatinine clearance and the degrees of acidemia and tubular proteinuria were then evaluated. The renal uptake of (99m)Tc-DMSA was markedly decreased in all patients, and the decreased uptake was detected in all serial images. In contrast, bladder radioactivity was higher than normal in all of the serial images when compared to renal radioactivity. Additionally, the uptake of (99m)Tc-DMSA was inversely proportional to the amount of urine beta(2)-microglobulin. These results strongly suggest that DMSA is filtered in the glomeruli and subsequently undergoes megalin- and cubilin-mediated endocytosis in the proximal tubules.

  19. A comparison of toxicities in acute myeloid leukemia patients with and without renal impairment treated with decitabine.

    PubMed

    Levine, Lauren B; Roddy, Julianna Vf; Kim, Miryoung; Li, Junan; Phillips, Gary; Walker, Alison R

    2017-01-01

    Purpose There are limited data regarding the clinical use of decitabine for the treatment of acute myeloid leukemia in patients with a serum creatinine of 2 mg/dL or greater. Methods We retrospectively evaluated 111 patients with acute myeloid leukemia who had been treated with decitabine and compared the development of toxicities during cycle 1 in those with normal renal function (creatinine clearance greater than or equal to 60 mL/min) to those with renal dysfunction (creatinine clearance less than 60 mL/min). Results Notable differences in the incidence of grade ≥3 cardiotoxicity (33% of renal dysfunction patients vs. 16% of normal renal function patients, p = 0.042) and respiratory toxicity (40% of renal dysfunction patients vs. 14% of normal renal function patients, p = 0.0037) were observed. The majority of heart failure, myocardial infarction, and atrial fibrillation cases occurred in the renal dysfunction group. The odds of developing grade ≥3 cardiotoxicity did not differ significantly between patients with and without baseline cardiac comorbidities (OR 1.43, p = 0.43). Conclusions This study noted a higher incidence of grade ≥3 cardiac and respiratory toxicities in decitabine-treated acute myeloid leukemia patients with renal dysfunction compared to normal renal function. This may prompt closer monitoring, regardless of baseline cardiac comorbidities. Further evaluation of decitabine in patients with renal dysfunction is needed.

  20. Mechanism of renal concentration of technetium-99m glucoheptonate

    SciTech Connect

    Lee, H.B.; Blaufox, M.D.

    1985-11-01

    Seventy female Sprague-Dawley rats were studied to determine the mechanism of tubular localization and the effects of commonly encountered changes in hydration and acid-base balance on renal uptake and urinary excretion of technetium-99m glucoheptonate ((/sup 99m/Tc)GHA). The in-vivo protein binding and protein-free plasma clearance of (/sup 99m/Tc)GHA also were quantitated. Kidney uptake of (/sup 99m/Tc)GHA averaged 11% of the injected dose in control animals. This varied slightly among groups but was significantly reduced by probenecid blockade and para-aminohippuric acid (PAH) competition to 4 and 2, respectively. Technetium-99m DMSA was not affected in its renal accumulation by these maneuvers. The total plasma clearance of (/sup 99m/Tc)GHA was lower than iodine-125( SVI)iothalamate but the clearance of the protein free supernate was higher, raising a possibility of some tubular secretion. Hepatic uptake was minimal in all groups averaging less than 1% injected dose. These data demonstrate that renal accumulation of (/sup 99m/Tc)GHA is blocked by probenecid and PAH suggesting that it is actively concentrated in the proximal tubule by enzyme systems similar to those involved in PAH and hippuran transport. It appears that (/sup 99m/Tc)GHA uptake measures a different aspect of kidney function than (/sup 99m/Tc)DMSA.

  1. Effects of renal function on pharmacokinetics and pharmacodynamics of lesinurad in adult volunteers

    PubMed Central

    Gillen, Michael; Valdez, Shakti; Zhou, Dongmei; Kerr, Bradley; Lee, Caroline A; Shen, Zancong

    2016-01-01

    Introduction Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of gout in combination with a xanthine oxidase inhibitor (XOI) in patients who have not achieved target serum uric acid (sUA) levels with an XOI alone. Most people with gout have chronic kidney disease. The pharmacokinetics, pharmacodynamics, and safety of lesinurad were assessed in subjects with impaired renal function. Methods Two Phase I, multicenter, open-label, single-dose studies enrolled subjects with normal renal function (estimated creatinine clearance [eCrCl] >90 mL/min; N=12) or mild (eCrCl 60–89 mL/min; N=8), moderate (eCrCl 30–59 mL/min; N=16), or severe (eCrCl <30 mL/min; N=6) renal impairment. Subjects were given a single oral lesinurad dose of 200 mg (N=24) or 400 mg (N=18). Blood and urine samples were analyzed for plasma lesinurad concentrations and serum and urine uric acid concentrations. Safety was assessed by adverse events and laboratory data. Results Mild, moderate, and severe renal impairment increased lesinurad plasma area under the plasma concentration–time curve by 34%, 54%–65%, and 102%, respectively. Lesinurad plasma Cmax was unaffected by renal function status. Lower renal clearance and urinary excretion of lesinurad were associated with the degree of renal impairment. The sUA-lowering effect of a single dose of lesinurad was similar between mild renal impairment and normal function, reduced in moderate impairment, and greatly diminished in severe impairment. Lesinurad increased urinary urate excretion in normal function and mild renal impairment; the increase was less with moderate or severe renal impairment. Lesinurad was well tolerated by all subjects. Conclusion Lesinurad exposure increased with decreasing renal function; however, the effects of lesinurad on sUA were attenuated in moderate to severe renal impairment. PMID:27843295

  2. Pitfalls and Limitations of Radionuclide Renal Imaging in Adults.

    PubMed

    Keramida, Georgia; James, Jacqueline M; Prescott, Mary C; Peters, Adrien Michael

    2015-09-01

    To understand pitfalls and limitations in adult renography, it is necessary to understand firstly the physiology of the kidney, especially the magnitude and control of renal blood flow, glomerular filtration rate and tubular fluid flow rate, and secondly the pharmacokinetics and renal handling of the three most often used tracers, Tc-99m-mercaptoacetyltriglycine (MAG3), Tc-99m-diethylene triamine pentaacetic acid (DTPA) and Tc-99m-dimercaptosuccinic acid (DMSA). The kidneys may be imaged dynamically with Tc-99m-MAG3 or Tc-99m-DTPA, with or without diuretic challenge, or by static imaging with Tc-99m-DMSA. Protocols are different according to whether the kidney is native or transplanted. Quantitative analysis of dynamic data includes measurement of renal vascularity (important for the transplanted kidney), absolute tracer clearance rates, differential renal function (DRF) and response to diuretic challenge. Static image reveals functional renal parenchymal damage, both focal and global, is useful in the clinical management of obstructive uropathy, renal stone disease and hypertension (under angiotensin converting enzyme inhibition), and is the preferred technique for determining DRF. Diagnosis based on morphological appearances is important in transplant management. Even though nuclear medicine is now in the era of hybrid imaging, renal imaging remains an important subspecialty in nuclear medicine and requires a sound basing in applied physiology, the classical supporting discipline of nuclear medicine.

  3. 19 CFR 122.26 - Entry and clearance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... AIR COMMERCE REGULATIONS Private Aircraft § 122.26 Entry and clearance. Private aircraft, as defined... information as set forth in § 122.22(c), and grants electronic clearance via electronic mail or telephone....

  4. Effect of chronic accumulation of aluminum on renal function, cortical renal oxidative stress and cortical renal organic anion transport in rats.

    PubMed

    Mahieu, Stella T; Gionotti, Marisa; Millen, Néstor; Elías, María Mónica

    2003-11-01

    The aim of the present work was to study the nephrotoxicity of aluminum lactate administered for 3 months (0.57 mg/100 g bodyweight aluminum, i.p., three times per week) to male Wistar rats. Renal function was studied after 6 weeks of treatment (urine was obtained from rats in metabolic cages) and at the end of the treatment using clearance techniques. Another group of rats was used as kidneys donors at the end of treatment. The renal cortex was separated and homogenized to determine glutathione (GSH) level, glutathione S-transferase (GST) activity and lipid peroxidation (LPO) level. Renal cortex slices were also used to study the p-aminohippuric acid (PAH) accumulation during steady-state conditions and the kinetics of uptake process. Clearance results, at the end of the treatment, indicated that renal functions in treated-rats were not different from those measured in control rats, although the renal concentration parameters differ when they were measured in treated rats after 24 h of food and water deprivation. Balances of water and sodium were also modified at both 1.5 and 3 months of treatment. The activity of alkaline phosphatase (AP) relative to inulin excreted in urine was significantly impaired: controls 2.2+/-0.6 IUI/mg, Al-treated 5.1+/-0.5 IU/mg, P<0.05. These data indicated that proximal tubular cells were loosing apical brush border membranes. Data obtained in cortex homogenates indicated that both GSH and GST activity were significantly decreased, and a significant increase of LPO was noted simultaneously in Al-treated rats. Renal accumulation of PAH, estimated as slice-to-medium ratio, decreased significantly in the Al-treated rats: control rats 3.06+/-0.02 ( n=12), Al-treated rats 2.26+/-0.04 ( n=12), P<0.0001. The maximal rate of uptake was also diminished in treated rats, while the apparent affinity remained unchanged. All these results indicate that aluminum accumulation in renal tissue affects cellular metabolism, promotes oxidative stress and

  5. The effect of radiopharmaceutical choice on the determination of relative renal function in rats with unilateral renal obstruction

    SciTech Connect

    Taylor, A.; Lallone, R.

    1984-01-01

    A significant divergence of GFR and ERPF within a single kidney could lead to different estimates of relative renal function depending on which radiopharmaceutical is administered. To address this question, the authors studied adult male Sprague-Dawley rats with unilateral ureteral obstruction by giving each animal an intravenous injection of 10 ..mu..Ci of I-125 iothalamate (GFR), I-131 hippurate (ERPF), and TC-99m DMSA and measuring the 30 minute clearance (renal uptake and urine excretion) of each agent. Normal control animals were sham operated; 25 experimental animals were subjected to permanent unilateral ureteral occlusion and studied at 6 hours, 1, 3, 7 and 14 days. Acute ureteral obstruction impaired the clearance of iothalamate to a much greater degree than OIH or DMSA at 6 hours and 1 day (rho<.005) and 3 days (rho<.05). The decline in DMSA clearance reflected ERPF more closely than GFR. In evaluating renal disease, one should consider the functional parameter reflected by the radiopharmaceutical as well as the underlying disease state.

  6. WWW-based data entry for document clearance requests

    SciTech Connect

    Stasiak, D.M.

    1997-10-08

    All documents created at Argonne must be cleared before being published. The clearance process is coordinated by the Publications and Record Services. The Electronic Document Review and Clearance System (EDRC) consists of a Web-based system for submission of clearance requests, an electronic staging area for document awaiting review, and Web-based review and clearance of documents. This report covers the document clearing process, the EDRC system, expected benefits/costs, and a demonstration.

  7. Human-in-the-Loop Assessment of Alternative Clearances in Interval Management Arrival Operations

    NASA Technical Reports Server (NTRS)

    Baxley, Brian T.; Wilson, Sara R.; Swieringa, Kurt A.; Johnson, William C.; Roper, Roy D.; Hubbs, Clay E.; Goess, Paul A.; Shay, Richard F.

    2016-01-01

    Interval Management Alternative Clearances (IMAC) was a human-in-the-loop simulation experiment conducted to explore the Air Traffic Management (ATM) Technology Demonstration (ATD-1) Concept of Operations (ConOps), which combines advanced arrival scheduling, controller decision support tools, and aircraft avionics to enable multiple time deconflicted, efficient arrival streams into a high-density terminal airspace. Interval Management (IM) is designed to support the ATD-1 concept by having an "Ownship" (IM-capable) aircraft achieve or maintain a specific time or distance behind a "Target" (preceding) aircraft. The IM software uses IM clearance information and the Ownship data (route of flight, current location, and wind) entered by the flight crew, and the Target aircraft's Automatic Dependent Surveillance-Broadcast state data, to calculate the airspeed necessary for the IM-equipped aircraft to achieve or maintain the assigned spacing goal.

  8. 48 CFR 245.602-70 - Plant clearance procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case....

  9. 14 CFR 29.661 - Rotor blade clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Rotors § 29.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure to... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Rotor blade clearance. 29.661 Section...

  10. 14 CFR 27.661 - Rotor blade clearance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Rotors § 27.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure to... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Rotor blade clearance. 27.661 Section...

  11. 14 CFR 29.661 - Rotor blade clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Rotors § 29.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure to... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Rotor blade clearance. 29.661 Section...

  12. 14 CFR 29.661 - Rotor blade clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Rotors § 29.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure to... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Rotor blade clearance. 29.661 Section...

  13. 14 CFR 27.661 - Rotor blade clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Rotors § 27.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure to... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Rotor blade clearance. 27.661 Section...

  14. 14 CFR 27.661 - Rotor blade clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Rotors § 27.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure to... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Rotor blade clearance. 27.661 Section...

  15. 14 CFR 27.661 - Rotor blade clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Rotors § 27.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure to... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Rotor blade clearance. 27.661 Section...

  16. 14 CFR 29.661 - Rotor blade clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Rotors § 29.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure to... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Rotor blade clearance. 29.661 Section...

  17. 14 CFR 29.661 - Rotor blade clearance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Rotors § 29.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure to... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Rotor blade clearance. 29.661 Section...

  18. 14 CFR 27.661 - Rotor blade clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Rotors § 27.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure to... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Rotor blade clearance. 27.661 Section...

  19. 48 CFR 2452.237-75 - Clearance of contractor personnel.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Clearance of contractor... Clauses 2452.237-75 Clearance of contractor personnel. As prescribed in 2437.110(e), insert the following clause in solicitations and contracts. Clearance of Contractor Personnel (OCT 1999) (a) General....

  20. 32 CFR 644.69 - Title Clearance-Easements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Title Clearance-Easements. 644.69 Section 644.69... ESTATE HANDBOOK Acquisition Procurement of Title Evidence, Title Clearance, and Closings § 644.69 Title Clearance—Easements. (a) Easements Costing in Excess of $1,000. Curative action and clearance of title...

  1. 10 CFR 706.31 - Clearance of conciliators and arbitrators.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Clearance of conciliators and arbitrators. 706.31 Section... RELATIONS Contract Negotiation and Administration § 706.31 Clearance of conciliators and arbitrators. Conciliators and arbitrators who are regularly assigned to DOE cases may be processed for “Q” clearance at...

  2. 30 CFR 56.19104 - Clearance at shaft stations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Clearance at shaft stations. 56.19104 Section 56.19104 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Hoisting Shafts § 56.19104 Clearance at shaft stations. Suitable clearance at shaft stations shall...

  3. 14 CFR 375.24 - Entry and clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Entry and clearance. 375.24 Section 375.24 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) SPECIAL... Entry and clearance. All U.S. entry and clearance requirements for aircraft, passengers, crews,...

  4. 24 CFR 3285.305 - Clearance under homes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main...

  5. 30 CFR 57.19104 - Clearance at shaft stations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Clearance at shaft stations. 57.19104 Section 57.19104 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Hoisting Shafts § 57.19104 Clearance at shaft stations. Suitable clearance at shaft stations shall...

  6. 75 FR 70341 - Agency Information Collection Activities: Emergency Clearance Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-17

    ... ADMINISTRATION Agency Information Collection Activities: Emergency Clearance Request The Social Security Administration (SSA) publishes a list of information collection packages requiring clearance by the Office of... Desk Officer and SSA Reports Clearance Officer to the following addresses or fax numbers. (OMB),...

  7. 19 CFR 122.158 - Other entry and clearance requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Other entry and clearance requirements. 122.158 Section 122.158 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... clearance requirements. All other provisions of this part relating to entry and clearance of aircraft...

  8. 30 CFR 56.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Clearance on adjacent tracks. 56.9103 Section..., Hauling, and Dumping Traffic Safety § 56.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  9. 76 FR 17615 - Highway-Rail Grade Crossing; Safe Clearance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-30

    ... Parts 177 and 392 RIN 2137-AE69 & 2126-AB04 Highway-Rail Grade Crossing; Safe Clearance AGENCY: Pipeline... that PHMSA and FMCSA extend the comment period for the Highway-Rail Grade Crossing; Safe Clearance... Crossing; Safe Clearance Notice of Proposed Rulemaking, which was published on January 28, 2011 (76 FR...

  10. 10 CFR 706.13 - Clearance of counsel.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Clearance of counsel. 706.13 Section 706.13 Energy... and Procedures in National Labor Relations Board Proceedings § 706.13 Clearance of counsel. It is recognized that clearance of counsel for the parties is sometimes desirable for proper preparation of a...

  11. 8 CFR 1280.6 - Bond to obtain clearance; form.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Bond to obtain clearance; form. 1280.6... IMMIGRATION REGULATIONS IMPOSITION AND COLLECTION OF FINES § 1280.6 Bond to obtain clearance; form. A bond to obtain clearance of a vessel or aircraft under section 231, 237, 239, 243, 251, 253, 254, 255, 256,...

  12. 10 CFR 95.17 - Processing facility clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Processing facility clearance. 95.17 Section 95.17 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Physical Security § 95.17 Processing facility clearance....

  13. 10 CFR 95.23 - Termination of facility clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Termination of facility clearance. 95.23 Section 95.23 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Physical Security § 95.23 Termination of facility clearance....

  14. 19 CFR 122.157 - Documents required for clearance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Documents required for clearance. 122.157 Section 122.157 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... clearance. As a condition precedent to clearance, the aircraft commander shall present to Customs: (a)...

  15. 75 FR 37518 - Agency Information Collection Activities: Emergency Clearance Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-29

    ... ADMINISTRATION Agency Information Collection Activities: Emergency Clearance Request The Social Security Administration (SSA) publishes a list of information collection packages requiring clearance by the Office of... Desk Officer and SSA Reports Clearance Officer to the following addresses or fax numbers. (OMB),...

  16. 8 CFR 280.6 - Bond to obtain clearance; form.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Bond to obtain clearance; form. 280.6 Section 280.6 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS IMPOSITION AND COLLECTION OF FINES § 280.6 Bond to obtain clearance; form. A bond to obtain clearance of a...

  17. 30 CFR 57.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Clearance on adjacent tracks. 57.9103 Section..., Hauling, and Dumping Traffic Safety § 57.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  18. 14 CFR 1260.63 - Customs clearance and visas.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas...

  19. 30 CFR 56.9330 - Clearance for surface equipment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Clearance for surface equipment. 56.9330... NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Loading... Dumping Sites § 56.9330 Clearance for surface equipment. Continuous clearance of at least 30 inches...

  20. 30 CFR 57.9330 - Clearance for surface equipment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Clearance for surface equipment. 57.9330 Section 57.9330 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Dumping Sites § 57.9330 Clearance for surface equipment. Continuous clearance of at least 30 inches...

  1. 31 CFR 205.20 - What is a clearance pattern?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What is a clearance pattern? 205.20 Section 205.20 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL... Agreement § 205.20 What is a clearance pattern? States use clearance patterns to project when funds are...

  2. 30 CFR 56.9306 - Warning devices for restricted clearances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Warning devices for restricted clearances. 56... Loading and Dumping Sites § 56.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of...

  3. 30 CFR 56.9306 - Warning devices for restricted clearances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Warning devices for restricted clearances. 56... Loading and Dumping Sites § 56.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of...

  4. 30 CFR 56.9306 - Warning devices for restricted clearances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Warning devices for restricted clearances. 56... Loading and Dumping Sites § 56.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of...

  5. 30 CFR 56.9306 - Warning devices for restricted clearances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Warning devices for restricted clearances. 56... Loading and Dumping Sites § 56.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of...

  6. 48 CFR 245.602-70 - Plant clearance procedures.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case....

  7. 48 CFR 245.602-70 - Plant clearance procedures.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case....

  8. 48 CFR 245.602-70 - Plant clearance procedures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case....

  9. 48 CFR 945.670-1 - Plant clearance function.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Plant clearance function... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal 945.670-1 Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency,...

  10. 48 CFR 945.670-1 - Plant clearance function.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Plant clearance function... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal 945.670-1 Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency,...

  11. 46 CFR 56.75-10 - Joint clearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be...

  12. 46 CFR 56.75-10 - Joint clearance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be...

  13. 46 CFR 56.75-10 - Joint clearance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be...

  14. 46 CFR 56.75-10 - Joint clearance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be...

  15. 46 CFR 56.75-10 - Joint clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be...

  16. 10 CFR 706.13 - Clearance of counsel.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Clearance of counsel. 706.13 Section 706.13 Energy DEPARTMENT OF ENERGY SECURITY POLICIES AND PRACTICES RELATING TO LABOR-MANAGEMENT RELATIONS Security Policies... responsible for requesting clearance of its counsel well in advance so that clearance requirements will...

  17. Renal handling of technetium-99m DMSA: Evidence for glomerular filtration and peritubular uptake

    SciTech Connect

    de Lange, M.J.; Piers, D.A.; Kosterink, J.G.; van Luijk, W.H.; Meijer, S.; de Zeeuw, D.; van der Hem, G.K.

    1989-07-01

    The finding of an enhanced excretion of (/sup 99m/Tc)dimercaptosuccinic acid (DMSA) in patients with tubular reabsorption disorders prompted us to investigate the role of filtration in the renal handling of (/sup 99m/Tc)DMSA. Our studies in human serum indicated that binding to serum proteins was approximately 90%. Chromatography of human urine and studies in rats showed that the complex was excreted unaltered into the urine. Renal extraction of (/sup 99m/Tc)DMSA in a human volunteer was 5.8%. Continuous infusion of (/sup 99m/Tc)DMSA in 13 individuals with normal renal function gave the following results (mean +/- s.d.): plasma clearance of (/sup 99m/Tc)DMSA 34 +/- 4 ml/min, urinary clearance of (/sup 99m/Tc)DMSA 12 +/- 3 ml/min. The calculated filtered load of (/sup 99m/Tc)DMSA closely resembled the urinary clearance, whereas the plasma clearance was about three times faster. This indicates that peritubular uptake accounts for approximately 65% and filtration for approximately 35% of the renal handling of (/sup 99m/Tc)DMSA.

  18. Simultaneous technetium-99 MAG(3), iodine-131-orthoiodohippurate and iodine-125 iothalamate clearance and biodistribution after bolus injection in rats.

    PubMed

    Casadevall, G; Turull, A; Piera, C; Queralt, J

    2000-07-01

    A bolus injection multiple blood sampling method was developed for the simultaneous measurement of blood and plasma clearance of three radiopharmaceuticals in rats. Technetium-99m mercaptoacetyltriglycine ([(99m)Tc]MAG(3)) and iodine-131-orthoiodohippurate ([(131)I]OIH) were used as makers of effective renal blood flow (ERBF), and iodine-125 iothalamate ([(125)I]IOT) was used as a marker of glomerular filtration rate (GFR). These methods can be easily performed in rats without arterial catheterization. Tissue biodistribution was studied in four groups of rats subjected to the following: group A, renal pedicle isolation (sham-operated); group B, ligature of one kidney pedicle; group C, ligature of both renal pedicles; and group D, ligature of both kidney pedicles and the bile duct. Renal clearance of [(99m)Tc]MAG(3) was greater than [(131)I]OIH and both agents were cleared faster than ([(125)I]-IOT). Either of the two markers of ERBF may be used in experimental studies, but it should be borne in mind that these are relative measurements of kidney performance. [(99m)Tc]MAG(3) and [(125)I]-IOT showed bile excretion in healthy rats, so they cannot completely fulfill the requirements for use as markers of ERBF. When renal function was impaired experimentally, [(99m)Tc]MAG(3) and [(125)I]-IOT were excreted in bile and [(131)I]OIH was secreted in the intestine. Thus, while the markers of ERBF and GFR may be reliable under normal physiological conditions, they may give progressively more erroneous values as renal function deteriorates.

  19. Renal functional reserve and renal recovery after acute kidney injury.

    PubMed

    Sharma, Aashish; Mucino, Marìa Jimena; Ronco, Claudio

    2014-01-01

    Renal functional reserve (RFR) represents the capacity of the kidney to increase glomerular filtration rate (GFR) in response to certain physiological or pathological stimuli or conditions. Once baseline GFR is determined, RFR can be assessed clinically after an oral protein load or intravenous amino acid infusion. In clinical practice, baseline GFR displays variable levels due to diet or other factors. RFR is the difference between peak 'stress' GFR induced by the test (p.o. or i.v.) and the baseline GFR. In clinical scenarios where hyperfiltration is present (high baseline GFR due to pregnancy, hypertension or diabetic nephropathy, in solitary kidney or kidney donors), RFR may be fully or partially used to achieve normal or supranormal renal function. Since commonly used renal function markers, such as GFR, may remain within normal ranges until 50% of nephrons are lost or in patients with a single remnant kidney, the RFR test may represent a sensitive and early way to assess the functional decline in the kidney. RFR assessment may become an important tool to evaluate the ability of the kidney to recover completely or partially after a kidney attack. In case of healing with a defect and progressive fibrosis, recovery may appear complete clinically, but a reduced RFR may be a sign of a maladaptive repair or subclinical loss of renal mass. Thus, a reduction in RFR may represent the equivalent of renal frailty or susceptibility to insults. The main aim of this article is to review the concept of RFR, its utility in different clinical scenarios, and future perspective for its use.

  20. Effects of tenoxicam on renal function and the disposition of inulin and p-aminohippurate in healthy volunteers and patients with chronic renal failure.

    PubMed Central

    Freestone, S; McAuslane, J A; Prescott, L F

    1991-01-01

    1. The effects of tenoxicam on renal function were studied in 10 patients with chronic renal failure (creatinine clearance 46.7 +/- 11.9 ml min-1 1.73 m-2) and eight healthy volunteers. A parallel treatment control group of eight healthy volunteers received placebo. Tenoxicam was given orally in a dose of 40 mg daily for 2 days followed by 20 mg daily for a further 8 days. Renal function was assessed by measurement of the renal clearances of inulin and p-aminohippurate (PAH) using the single injection technique before and during administration of tenoxicam. 2. In the healthy volunteers there were no changes in glomerular filtration rate, effective renal plasma flow, or the urinary excretion of N-acetylglucosaminidase and beta 2-microglobulin on the 3rd and 10th days of treatment with tenoxicam. The mean urinary excretion of prostaglandins E2 and 6-keto F1 alpha decreased during treatment but there was great individual variation and the differences were not statistically significant. Tenoxicam had no effect on the half-life, clearance, volume of distribution or urinary recovery of inulin and PAH. 3. There was no significant change in the clearance of inulin and creatinine after treatment with tenoxicam for 10 days in the patients with chronic renal failure. However, in this group there was a significant increase in plasma creatinine on the 3rd and 6th days with a return to pretreatment levels by the 10th day. The administration of tenoxicam for 10 days was associated with a small but significant increase in the plasma half-life and volume of distribution of inulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1958445

  1. [Assessment of renal function in elderly after eighty years: Cockroft and Gault or Modification of diet in renal disease equation?].

    PubMed

    Andro, M; Estivin, S; Comps, E; Gentric, A

    2011-11-01

    Assessment of renal function is essential in the management of hospitalised patients, particularly in geriatric practice. Impairment of renal function is common in the elderly, aged of 80 years and over, and should be taken into account before prescribing drugs eliminated through the kidneys or performing investigations requiring iodine injection. Renal failure is also a predictor of mortality. In clinical practice, creatinine-based equations are recommended to assess kidney function. The most widely used equations are the Cockroft and Gault (CG) and the simplified Modification of diet in renal disease (MDRD) formulas. The former estimates the clearance of creatinine in millilitres per minute, the latter estimates the glomerular filtration rate in millilitres per minute per 1.73 m(2). In 2002, the French high authority for health recommended the use of the CG formula, but no recommendation was given for the elderly. In the literature, no study has compared CG and MDRD formulas with a reference method in this very old population. In the octogenarians, two studies have compared these formulas with the creatinine clearance calculated on the basis of a 24-hour urine collection and four studies have compared the formulas head to head. All these studies showed that the results obtained with the MDRD formula are higher from 10 to 30 mL/min/1.73 m(2) than the results obtained with the CG formula. Studies simulating drug prescription showed that the use of the MDRD formula would lead to a risk of drug over dosage in 20 to 36% of the elderly. Also, two studies have suggested that only creatinine clearance measured by the CG formula is a predictor of mortality in the very old population. In conclusion, in the octogenarian, none of these two formulas is ideal. However, based on the results of studies targeted to this elderly population, the best solution seems to be the use of the CG formula expecting new methods of evaluation of renal function.

  2. Evaluation of vascular clearance as a marker for virulence of alphaviruses: disassociation of rapid clearance with low virulence of venezuelan encephalitis virus strains in guinea pigs.

    PubMed Central

    Jahrling, P B; Heisey, G B; Hesse, R A

    1977-01-01

    The concept that relates low virulence of certain alphaviruses to low viremia and efficient vascular clearance of virus was tested in guinea pigs. Previously published studies with hamsters suggested that virulent strains maintain high viremias primarily because they are cleared inefficiently from the blood. In the present study, with guinea pigs, six of six virulent strains of Venezuelan encephalitis virus were cleared inefficiently, whereas three of six nonlethal or benign virus strains were cleared rapidly. However, three other guinea pig-benign Venezuelan encephalitis virus strains cleared slowly, to produce a high viremia was correlated with inefficient growth in primary viral replication sites. Thus, the potential of some alphaviruses to produce destructive lesions may be restricted by efficient clearance of virus from the blood, whereas the growth of other benign alphavirus strains may be restricted after the virus is presented to target cells. PMID:892910

  3. Predictive Performance of Physiologically Based Pharmacokinetic and Population Pharmacokinetic Modeling of Renally Cleared Drugs in Children

    PubMed Central

    Zhou, W; Johnson, TN; Xu, H; Cheung, SYA; Bui, KH; Li, J; Al‐Huniti, N

    2016-01-01

    Predictive performance of physiologically based pharmacokinetic (PBPK) and population pharmacokinetic (PopPK) models of drugs predominantly eliminated through kidney in the pediatric population was evaluated. After optimization using adult clinical data, the verified PBPK models can predict 33 of 34 drug clearance within twofold of the observed values in children 1 month and older. More specifically, 10 of 11 of predicted clearance values were within 1.5‐fold of those observed in children between 1 month and 2 years old. The PopPK approach also predicted 19 of 21 drug clearance within twofold of the observed values in children. In summary, our analysis demonstrated both PBPK and PopPK adult models, after verification with additional adult pharmacokinetic (PK) studies and incorporation of known ontogeny of renal filtration, could be applied for dosing regimen recommendation in children 1 month and older for renally eliminated drugs in a first‐in‐pediatric study. PMID:27566992

  4. Acute Bilateral Renal and Splenic Infarctions Occurring during Chemotherapy for Lung Cancer

    PubMed Central

    Koyama, Noriko; Tomoda, Koichi; Matsuda, Masayuki; Fujita, Yukio; Yamamoto, Yoshifumi; Hontsu, Shigeto; Tasaki, Masato; Yoshikawa, Masanori; Kimura, Hiroshi

    2016-01-01

    We herein report a rare case of acute bilateral renal and splenic infarctions occurring during chemotherapy for lung cancer. A 60-year-old man presented with acute and intensive upper abdominal and back pain during chemotherapy with cisplatin and etoposide for lung cancer. Contrast-enhanced computed tomography (CT) revealed bilateral renal and splenic infarctions. After the administration of unfractionated heparin his pain was relieved with a clearance of the infarctions in the CT findings and a recovery of renal dysfunction. Enhanced coagulation by lung cancer and arterial ischemia by chemotherapy may therefore contribute to the development of these infarctions. PMID:27980265

  5. Effects of acute hepatic and renal failure on pharmacokinetics of flunixin meglumine in rats.

    PubMed

    Hwang, Youn-Hwan; Yun, Hyo-In

    2011-01-01

    The aim of this study was to investigate the effects of hepatic and renal failure on the pharmacokinetics of flunixin in carbon tetrachloride (CCl(4))- and glycerol-treated rats. After intravenous administration of flunixin (2 mg/kg), the plasma concentration of flunixin was measured by high-performance liquid chromatography. Both acute hepatic and renal failure resulted in significantly increased area under the curve (AUC), prolonged elimination half-life (t(1/2β)), and reduced total body clearance (Cl(tot)) compared with respective controls (P<0.05). In conclusion, hepatic failure as well as renal failure modified the pharmacokinetics of flunixin.

  6. Lower bound of optimization in radiological protection system taking account of practical implementation of clearance

    SciTech Connect

    Hattori, Takatoshi

    2007-07-01

    The dose criterion used to derive clearance and exemption levels is of the order of 0.01 mSv/y based on the Basic Safety Standard (BSS) of the International Atomic Energy Agency (IAEA), the use of which has been agreed upon by many countries. It is important for human beings, who are facing the fact that global resources for risk reduction are limited, to carefully consider the practical implementation of radiological protection systems, particularly for low-radiation-dose regions. For example, in direct gamma ray monitoring, to achieve clearance level compliance, difficult issues on how the uncertainty (error) of gamma measurement should be handled and also how the uncertainty (scattering) of the estimation of non-gamma emitters should be treated in clearance must be resolved. To resolve these issues, a new probabilistic approach has been proposed to establish an appropriate safety factor for compliance with the clearance level in Japan. This approach is based on the fundamental concept that 0.1 mSv/y should be complied with the 97.5. percentile of the probability distribution for the uncertainties of both the measurement and estimation of non-gamma emitters. The International Commission on Radiological Protection, ICRP published a new concept of the representative person in Publication 101 Part I. The representative person is a hypothetical person exposed to a dose that is representative of those of highly exposed persons in a population. In a probabilistic dose assessment, the ICRP recommends that the representative person should be defined such that the probability of exposure occurrence is lower than about 5% that of a person randomly selected from the population receiving a high dose. From the new concept of the ICRP, it is reasonable to consider that the 95. percentile of the dose distribution for the representative person is theoretically always lower than the dose constraint. Using this established relationship, it can be concluded that the minimum dose

  7. Renal arteries (image)

    MedlinePlus

    A renal angiogram is a test used to examine the blood vessels of the kidneys. The test is performed ... main vessel of the pelvis, up to the renal artery that leads into the kidney. Contrast medium ...

  8. Primary renal carcinoid tumor.

    PubMed

    Kanodia, K V; Vanikar, A V; Patel, R D; Suthar, K S; Kute, V B; Modi, P R; Trivedi, H L

    2013-09-01

    Primary renal carcinoid tumor is extremely rare and, therefore, its pathogenesis and prognosis is not well known. We report a primary renal carcinoid in a 26-year-old man treated by radical nephrectomy.

  9. Kidney (Renal) Failure

    MedlinePlus

    ... News Physician Resources Professions Site Index A-Z Kidney Failure Kidney failure, also known as renal failure, ... evaluated? How is kidney failure treated? What is kidney (renal) failure? The kidneys are designed to maintain ...

  10. Renal vein thrombosis

    MedlinePlus

    ... the kidneys. Possible Complications Complications may include: Acute renal failure (especially if thrombosis occurs in a dehydrated child) ... Saunders; 2012:chap 34. Read More Acute kidney failure Arteriogram Blood ... embolus Renal Tumor Review Date 5/19/2015 Updated by: ...

  11. Market Mechanism for Line Congestion Clearance

    NASA Astrophysics Data System (ADS)

    Ruiz Monroy, José Joaquín; Kita, Hiroyuki; Tanaka, Eiichi; Hasegawa, Jun

    This paper proposes a mechanism for clearance of line congestion and power flow control in a deregulated market environment. The mechanism applies penalties to the bilateral transactions that cause line congestion by increasing the prices of such transactions. The market regulates itself by redefining the transactions and checking again for violations, applying penalties if necessary and repeating the process until all the demand is satisfied without causing line congestion to the system. A bilateral transaction matrix (BTM) creation algorithm developed by the authors and a DC power flow program are integrated as parts of the market mechanism proposed in this paper. The congestion is cleared by the market participants when they reschedule their transactions. This mechanism is useful to study the effects of bilateral transactions on a power system and helps the Independent System Operator (ISO) to create rules and market mechanisms for line congestion clearance and power flow control.

  12. Clearance Kinetics and Clearance Routes of Molecules From the Suprachoroidal Space After Microneedle Injection

    PubMed Central

    Chiang, Bryce; Wang, Ke; Ethier, C. Ross; Prausnitz, Mark R.

    2017-01-01

    Purpose To determine clearance kinetics and routes of clearance of molecules from the suprachoroidal space (SCS) of live New Zealand White rabbits. Methods Suprachoroidal space collapse rate and pressure changes after microneedle injection into SCS were determined. Fluorescent fundus images were acquired to determine clearance rates of molecules ranging in size from 332 Da to 2 MDa. Microneedle injections of fluorescein were performed, and samples were taken from various sites over time to determine amount of fluorescein exiting the eye. Clearance transport was modeled theoretically and compared with experimental data. Results After injection, pressures in SCS and vitreous humor spiked and returned to baseline within 20 minutes; there was no difference between these two pressures. Suprachoroidal space collapse occurred within 40 minutes. One hour after fluorescein injection, 46% of fluorescein was still present in the eye, 15% had transported across sclera, 6% had been cleared by choroidal vasculature, and 4% had exited via leakage pathways. Characteristic clearance time increased in proportion with molecular radius, but total clearance of 2 MDa FITC-dextran was significantly slower (21 days) than smaller molecules. These data generally agreed with predictions from a theoretical model of molecular transport. Conclusions Guided by experimental data in the context of model predictions, molecular clearance from SCS occurred in three regimes: (1) on a time scale of approximately 10 minutes, fluid and molecules exited SCS by diffusion into sclera and choroid, and by pressure-driven reflux via transscleral leakage sites; (2) in approximately 1 hour, molecules cleared from choroid by blood flow; and (3) in 1 to 10 hours, molecules cleared from sclera by diffusion and convection. PMID:28125841

  13. Renal disease in pregnancy.

    PubMed

    Sanders, C L; Lucas, M J

    2001-09-01

    Women with renal disease who conceive and continue a pregnancy are at significant risk for adverse maternal and fetal outcomes. Risk is inversely related to the degree of renal insufficiency. Pregnancy-induced changes in the urinary tract can temporarily increase renal function compromise, such as nephrosis, but most often results in no net increase in dysfunction. Common complications of pregnancy--such as hypertension and hypovolemia--can be associated with acute renal injury or aggravation of pre-existing disease.

  14. Effect of ultrafiltration on peritoneal dialysis drug clearances.

    PubMed

    Lau, A H; Chow-Tung, E; Assadi, F K; Fornell, L; John, E

    1985-01-01

    To determine the effect of dialysate osmolarity on peritoneal dialysis drug transfer, peritoneal dialysis clearances of theophylline, phenobarbital, and tobramycin were determined in 10 rabbits using dialysate containing 1.5 and 4.25% glucose. Urea and creatinine clearances were also obtained for comparison. Under similar dialysis conditions, the peritoneal clearances of the three drugs remained unchanged for the two types of dialysate. In contrast, the peritoneal clearances of urea and creatinine were significantly higher with the use of 4.25% glucose dialysate (p less than 0.001). Thus, peritoneal dialysis clearances of theophylline, phenobarbital and tobramycin are not significantly affected by hypertonicity-induced ultrafiltration during acute peritoneal dialysis.

  15. Deposition and clearance of inhaled particles.

    PubMed Central

    Stuart, B O

    1976-01-01

    Theoretical models of respiratory tract deposition of inhaled particles are compared to experimental studies of deposition patterns in humans and animals, as determined principally by particle size, density, respiratory rate and flow parameters. Various models of inhaled particle deposition make use of convenient approximations of the respiratory tract to predict tractional deposition according to fundamental physical processes of impaction, sedimentation, and diffusion. These theoretical models for both total deposition and regional (nasopharyngeal, tracheobronchial, and pulmonary) deposition are compared with experimental studies of inhaled dusts in humans or experimental animals that have been performed in many laboratories over several decades. Reasonable correlation has been obtained between theoretical and experimental studies, but the behavior of very fine (less than 0.01 mum) particles requires further refinement.Properties of particle shape, charge, and hygroscopicity as well as the degree of respiratory tract pathology also influence deposition patterns and further experimental work is urgently needed in these areas. The influence upon deposition patterns of dynamic alterations in inspiratory flow profiles caused by a variety of breathing patterns also requires further study, and the use of such techniques with selected inhaled particle size holds promise in possible diagnostic aid in diagnosis of normal versus disease conditions. Mechanisms of conducting airway and alveolar clearance processes involving mucociliary clearance, dissolution, transport to systemic circulation, and translocation via regional lymphatic clearance are discussed. The roles of the pulmonary macrophage in airway and alveolar clearance are described, and the applicability of recent solubility models for translocation or deposited materials to liver, skeleton, or other systemic organs is discussed. PMID:797567

  16. Activating the 42d Clearance Company

    DTIC Science & Technology

    2011-12-01

    System– Enhanced. ■ Establishing supply and maintenance accounts. ■ Procuring the unit guidon . Other documents created to expedite and track the...SUBTITLE Activating the 42d Clearance Company 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) 5d. PROJECT NUMBER 5e. TASK...NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) Army Engineer School,Engineer Professional Bulletin,464 MANSCEN

  17. Army Delivers Route Clearance Vehicle Capabilities

    DTIC Science & Technology

    2010-08-01

    the Husky Vehicle-Mount- ed Mine-Detection (VMMD) System, the Buffalo® Mine- Protected Clearance Vehicle (MPCV), the Panther Medium Mine-Protected...cord (POR) RCVs—the Husky, the Buf- falo, and the Panther . POR-configured Huskys, Buffalos, and Panthers have already been fielded in-theater—albeit...IED vehicle equipped with a distinctive hydraulic arm that inter- rogates suspected explosive hazards and clears them when necessary. The Panther

  18. Reduced methadone clearance during aromatase inhibition.

    PubMed

    Lu, Wenjie Jessie; Thong, Nancy; Flockhart, David A

    2012-08-01

    Methadone is increasingly used in pain management and is a cornerstone in the treatment of opiate withdrawal. It is subject to highly variable clearance among patients. The complete metabolic disposition of methadone is likely to involve a number of enzymes, including specifically CYP2B6. Previous studies in vitro suggest that metabolism by aromatase may also contribute. Single-dose methadone pharmacokinetics (2 mg, intravenous) were studied in 15 healthy postmenopausal women in the presence and absence of a potent aromatase inhibitor, letrozole. A sequential design was used, involving a control period followed by treatment with letrozole (2.5 mg/d, 11 days), in which each subject served as her own control. On average, letrozole treatment reduced methadone systemic clearance by 22% (P = 0.001), increased methadone AUC by 23% (P = 0.007), and increased elimination half-life by 21% (P = 0.042). The plasma parent-to-metabolite ratio also increased (P = 0.009), and there was a linear relationship (R2 = 0.74) between change in this plasma ratio and change in methadone AUC0-∞. In contrast, there was no such association with change in apparent urinary methadone clearance. Letrozole did not change methadone distribution half-life or its volume of distribution. Overall, these data demonstrate a significant decrease in methadone clearance during coadministration of letrozole, consistent with decreased metabolism brought about by aromatase inhibition. An involvement of aromatase in the disposition of methadone may help explain the difficulty in methadone dosing and suggests a broader role for this catalyst of endogenous steroid metabolism in xenobiotic drug disposition.

  19. Renal Denervation

    PubMed Central

    Pan, Tao; Guo, Jin-he; Teng, Gao-jun

    2015-01-01

    Abstract Type 2 diabetes mellitus (T2DM) is a group of metabolic diseases of multiple etiologies. Although great progress has been made, researchers are still working on the pathogenesis of T2DM and how to best use the treatments available. Aside from several novel pharmacological approaches, catheter-based sympathetic renal denervation (RDN) has gained a significant role in resistant hypertension, as well as improvements in glycemic control in T2DM. In this article, we will summarize herein the role sympathetic activation plays in the progression of T2DM and review the recent clinical RDN experience in glucose metabolism. We performed systematic review in online databases, including PubMed, EmBase, and Web of Science, from inception until 2015. Studies were included if a statistical relationship was investigated between RDN and T2DM. The quality of each included study was assessed by Newcastle–Ottawa scale score. To synthesize these studies, a random-effects model or a fixed-effects model was applied as appropriate. Then, we calculated heterogeneity, performed sensitivity analysis, tested publication bias, and did meta-regression analysis. Finally, we identified 4 eligible articles. In most studies, RDN achieved via novel catheter-based approach using radiofrequency energy has gained a significant role in resistant hypertension, as well as improvements in glycemic control in T2DM. But the DREAMS-Study showed that RDN did not change median insulin sensitivity nor systemic sympathetic activity. Firstly, the current published studies lacked a proper control group, along with the sample capacity was small. Also, data obtained in the subgroups of diabetic patients were not separately analyzed and the follow-up period was very short. In addition, a reduction in blood pressure accounts for the improvements in glucose metabolism and insulin resistance cannot be excluded. If the favorable result of better glucose metabolism is confirmed in large-scale, randomized studies

  20. Effect of 2'-phosphophloretin on renal function in chronic renal failure rats.

    PubMed

    Peerce, B E; Weaver, L; Clarke, R D

    2004-07-01

    Hyperhosphatemia and secondary hyperparathyroidism are common and severe complications of chronic renal failure. Therapies to reduce serum phosphate have been shown to reduce serum parathyroid hormone (PTH) and slow the progression of renal failure. The effect of the inhibitor of intestinal phosphate absorption, 2'-phosphophloretin (2'-PP), on serum and urine chemistry, renal histology, and cardiac structure in the uremic rat model of renal failure, 5/6 nephrectomy (5/6 NX), was examined. The effect of 2'-PP on serum phosphate, serum PTH, serum total Ca(2+), and ionized Ca(2+), Ca(2+) x P(i) product, urine protein, urine osmolality, and creatinine clearance in 5/6 NX rats was examined. Uremic rats in chronic renal failure were gavaged daily with 25 microM 2'-PP. Over the course of a 5-wk experiment, serum chemistry in untreated uremic rats, 2'-PP-treated uremic rats, and age-matched control rats with normal renal function was determined twice a week. Urine creatinine, urine osmolality, urine phosphate, and urine protein were determined once a week from 24-h collections. 2'-PP reduced serum phosphate 40 +/- 3% compared with a 17% increase in untreated uremic control rats. 2'-PP did not alter total serum Ca(2+). During 5-wk experiments, serum PTH increased 65 +/- 25% in untreated uremic rats and decreased 70 +/- 7% in uremic rats treated with 25 microM 2'-PP. Creatinine clearance decreased 20% in untreated uremic rats compared with a 100% increase in 2'-PP-treated uremic rats. Urine protein decreased and urine osmolality increased in uremic rats treated with 2'-PP. The mechanism of the effect of 2'-PP on serum phosphate was inhibition of intestinal phosphate absorption. 2-PP inhibited intestinal phosphate absorption 50% without altering dietary protein absorption or intestinal Ca(2+) absorption. Over the course of the 5-wk treatment with 2'-PP, uremic animals treated with 2'-PP had a 2-4% weight gain/wk, similar to the weight gain seen in age-matched control rats

  1. Renal Tubular Acidosis

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Renal Tubular Acidosis KidsHealth > For Parents > Renal Tubular Acidosis Print A A A What's in ... Causes Symptoms Diagnosis Treatment en español Acidosis tubular renal Each time our internal organs do something, such ...

  2. [Idiopathic renal arteriovenous fistula].

    PubMed

    Bennani, S; Ait Bolbarod, A; el Mrini, M; Kadiri, R; Benjelloun, S

    1996-06-01

    The authors report a case of idiopathic renal arteriovenous fistula. The diagnosis was established angiographically in a 24 year old man presenting gross hematuria. Embolization of the fistula was performed. Efficiency of this treatment was appreciated clinically and by duplex renal ultrasonography. The characteristics of renal arteriovenous fistulas are reviewed.

  3. Cardio-renal syndrome

    PubMed Central

    Gnanaraj, Joseph; Radhakrishnan, Jai

    2016-01-01

    Cardio-renal syndrome is a commonly encountered problem in clinical practice. Its pathogenesis is not fully understood. The purpose of this article is to highlight the interaction between the cardiovascular system and the renal system and how their interaction results in the complex syndrome of cardio-renal dysfunction. Additionally, we outline the available therapeutic strategies to manage this complex syndrome. PMID:27635229

  4. Similarity analysis of compressor tip clearance flow structure

    NASA Technical Reports Server (NTRS)

    Chen, G. T.; Greitzer, E. M.; Tan, C. S.; Marble, F. E.

    1991-01-01

    A new approach is presented for analyzing compressor tip clearance flow. The basic idea is that the clearance velocity field can be (approximately) decomposed into independent throughflow and crossflow, since chordwise pressure gradients are much smaller than normal pressure gradients in the clearance region. As in the slender body approximation in external aerodynamics, this description implies that the three-dimensional steady clearance flow can be viewed as a two-dimensional, unsteady flow. Using this approach, a similarity scaling for the crossflow in the clearance region is developed and a generalized description of the clearance vortex is derived. Calculations based on the similarity scaling agree well with a wide range of experimental data in regard to flow features such as crossflow velocity field, static pressure field, and tip clearance vortex trajectory.

  5. Effect of reduced renal mass on renal ammonia transporter family, Rh C glycoprotein and Rh B glycoprotein, expression.

    PubMed

    Kim, Hye-Young; Baylis, Chris; Verlander, Jill W; Han, Ki-Hwan; Reungjui, Sirirat; Handlogten, Mary E; Weiner, I David

    2007-10-01

    Kidneys can maintain acid-base homeostasis, despite reduced renal mass, through adaptive changes in net acid excretion, of which ammonia excretion is the predominant component. The present study examines whether these adaptations are associated with changes in the ammonia transporter family members, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg). We used normal Sprague-Dawley rats and a 5/6 ablation-infarction model of reduced renal mass; control rats underwent sham operation. After 1 wk, glomerular filtration rate, assessed as creatinine clearance, was decreased, serum bicarbonate was slightly increased, and Na(+) and K(+) were unchanged. Total urinary ammonia excretion was unchanged, but urinary ammonia adjusted for creatinine clearance, an index of per nephron ammonia metabolism, increased significantly. Although reduced renal mass did not alter total Rhcg protein expression, both light microscopy and immunohistochemistry with quantitative morphometric analysis demonstrated hypertrophy of both intercalated cells and principal cells in the cortical and outer medullary collecting duct that was associated with increased apical and basolateral Rhcg polarization. Rhbg expression, analyzed using immunoblot analysis, immunohistochemistry, and measurement of cell-specific expression, was unchanged. We conclude that altered subcellular localization of Rhcg contributes to adaptive changes in single-nephron ammonia metabolism and maintenance of acid-base homeostasis in response to reduced renal mass.

  6. Anemia in pediatric renal transplant recipients.

    PubMed

    Kausman, Joshua Yehuda; Powell, Harley Robert; Jones, Colin Lindsay

    2004-05-01

    The aim of this study was to establish the prevalence of anemia in stable pediatric renal transplant recipients and to examine the association of anemia with renal function, immunosuppressants, angiotensin converting enzyme inhibitors, and growth, as well as iron, vitamin B(12), and folate stores. This is a cross-sectional study of the 50 renal transplant recipients currently followed at our center. Patient data were collected regarding hematological parameters, growth, medications, renal function, underlying renal disease, delayed graft function, episodes of rejection, and iron or erythropoietin therapy post transplantation. The mean hemoglobin level (Hb) was 110 g/l and the overall prevalence of anemia was 60%, including 30% who were severely anemic (Hb<100 g/l). There was a high rate of iron deficiency (34%) and serum iron was the parameter of iron metabolism most closely associated with anemia. Hb in patients with low serum iron was 90.7 g/l versus 114.4 g/l in those with normal serum iron ( P<0.01). Both univariate and multiple linear regression determined tacrolimus dose and creatinine clearance to be significant factors associated with anemia. Tacrolimus dose correlated with a 10 g/l reduction in Hb for every increase of tacrolimus dose of 0.054 mg/kg per day ( P=0.001). The dose of mycophenolate was positively correlated with Hb, but this was likely to be confounded by our practice of dose reduction in the setting of anemia. Angiotensin converting enzyme inhibitor use was not associated with anemia. Severely anemic patients tended to be shorter, with a mean Z-score for height of -1.8 compared with -0.9 for those with normal Hb ( P=0.02). Anemia is a significant and common problem in pediatric renal transplant patients. Deteriorating renal function is an important cause, but other factors like iron deficiency and immunosuppression are involved. Definition of iron deficiency is difficult and serum iron may be a valuable indicator. Medication doses

  7. Effects of renal impairment on aluminum (Al) kinetics and Al-induced toxicity

    SciTech Connect

    Yokel, R.A.; McNamara, P.J.

    1986-03-01

    Al-induced toxicity most commonly occurs in the renally impaired. To study the influence of renal impairment on Al kinetics and toxicity, renally impaired rabbits were prepared by the remnant kidney procedure. Six weeks after partial nephrectomy creatinine clearance was 21% of controls and serum creatinine, BUN, Ca, and PO/sub 4/ were 222, 248, 122, and 50% of presurgery levels respectively. Serum Al kinetics after i.v. Al were: Al clearance 27%, initial and steady state volumes of distribution 50 and 80%, half life 362% and mean residence time 300% of controls (renally intact rabbits). Beginning 9 weeks after partial nephrectomy, rabbits received 145 to 160 ..mu..mole Al/kg s.c. daily, 5 x weekly x 4 weeks. Acquisition of a classically conditioned reflex (nictitating membrane extension) was impaired comparable to that produced by 100-200 ..mu..mole Al in controls but retention and extinction deficits were greater than those seen after 400 ..mu..mole Al in controls. Tissue Al concentrations were less than those seen after 200 ..mu..mole Al in controls. Body weight was comparable to that produced by 400 ..mu..mole Al in controls. These results suggest that renal impairment alters Al serum distribution, impairs its clearance, and increases the Al-induced impairment of memory and body weight gain.

  8. Progress on Shape Memory Alloy Actuator Development for Active Clearance Control

    NASA Technical Reports Server (NTRS)

    DeCastro, Jonathan; Melcher, Kevin; Noebe, Ronald

    2006-01-01

    Results of a numerical analysis evaluating the feasibility of high-temperature shape memory alloys (HTSMA) for active clearance control actuation in the high-pressure turbine section of a modern turbofan engine has been conducted. The prototype actuator concept considered here consists of parallel HTSMA wires attached to the shroud that is located on the exterior of the turbine case. A transient model of an HTSMA actuator was used to evaluate active clearance control at various operating points in a test bed aircraft engine simulation. For the engine under consideration, each actuator must be designed to counteract loads from 380 to 2000 lbf and displace at least 0.033 in. Design results show that an actuator comprised of 10 wires 2 in. in length is adequate for control at critical engine operating points and still exhibit acceptable failsafe operability and cycle life. A proportional-integral-derivative (PID) controller with integrator windup protection was implemented to control clearance amidst engine transients during a normal mission. Simulation results show that the control system exhibits minimal variability in clearance control performance across the operating envelope. The final actuator design is sufficiently small to fit within the limited space outside the high-pressure turbine case and is shown to consume only small amounts of bleed air to adequately regulate temperature.

  9. Using human recombinant UDP-glucuronosyltransferase isoforms and a relative activity factor approach to model total body clearance of laropiprant (MK-0524) in humans.

    PubMed

    Gibson, Christopher R; Lu, Ping; Maciolek, Cheri; Wudarski, Christen; Barter, Zoe; Rowland-Yeo, Karen; Stroh, Mark; Lai, Eseng; Nicoll-Griffith, Deborah A

    2013-12-01

    A major pathway of elimination of the prostaglandin D2 receptor 1 antagonist laropiprant in humans is by uridine diphosphate-glucuronosyltransferase (UGT)-mediated biotransformation. In this study, liver and kidney relative activity factors were developed for UGT1A1, 1A9 and 2B7 to allow for in vitro-in vivo extrapolation of intrinsic clearance data to whole organ clearance using recombinant human UGT isoforms applying this to laropiprant as a model substrate. The total body metabolic clearance of laropiprant determined using this approach (5.0 L/hr) agreed well with the value determined in vivo following intravenous administration to healthy human volunteers (5.1 L/hr). The results suggest that approximately 36%, 36% and 28% of the hepatic metabolic clearance of laropiprant was mediated by UGT1A1, 1A9 and 2B7, respectively. Likewise, 80% and 20% of the renal metabolic clearance was mediated by UGT1A9 and 2B7, respectively. Furthermore, the data suggested that the contribution of the kidney to the overall total metabolic clearance was minor relative to the liver (≈ 12%).

  10. Deposition, retention, and clearance of inhaled particles.

    PubMed Central

    Lippmann, M; Yeates, D B; Albert, R E

    1980-01-01

    The relation between the concentrations and characteristics of air contaminants in the work place and the resultant toxic doses and potential hazards after their inhalation depends greatly on their patterns of deposition and the rates and pathways for their clearance from the deposition sites. The distribution of the deposition sites of inhaled particles is strongly dependent on their aerodynamic diameters. For normal man, inhaled non-hygroscopic particles greater than or equal to 2 micrometers that deposit in the conducting airways by impaction are concentrated on to a small fraction of the surface. Cigarette smoking and bronchitis produce a proximal shift in the deposition pattern. The major factor affecting the deposition of smaller particles is their transfer from tidal to reserve air. For particles soluble in respiratory tract fluid, systemic uptake may be relatively complete for all deposition patterns, and there may be local toxic or irritant effects or both. On the other hand, slowly soluble particles depositing in the conducting airways are carried on the surface to the glottis and are swallowed within one day. Mucociliary transport rates are highly variable, both along the ciliated airways of a given individual and between individuals. The changes in clearance rates produced by drugs, cigarette smoke, and other environmental pollutants can greatly increase or decrease these rates. Particles deposited in non-ciliated airways have large surface-to-volume ratios, and clearance by dissolution can occur for materials generally considered insoluble. They may also be cleared as free particles either by passive transport along surface liquids or, after phagocytosis, by transport within alveolar macrophages. If the particles penetrate the epithelium, either bare or within macrophages, they may be sequestered within cells or enter the lymphatic circulation and be carried to pleural, hilar, and more distant lymph nodes. Non-toxic insoluble particles are cleared from

  11. Renal function and glomerular hemodynamics in male endotoxemic rats.

    PubMed

    Lugon, J R; Boim, M A; Ramos, O L; Ajzen, H; Schor, N

    1989-10-01

    The renal effects of a single intravenous dose of two different E. coli lipopolysaccharides (LPS 0111:B4 and LPS 0127:B8), at the same dose of 100 micrograms/kg, were evaluated in euvolemic Munich-Wistar (MW) rats by whole kidney clearance techniques and micropuncture studies. Following LPS infusion, a significant decrease (8%) in mean BP was observed only in the LPS 0127:B8 treated group. Inulin clearance fell 57% (LPS 0111:B4), P less than 0.01, and 38% (LPS 0127:B8), P less than 0.01. Para-aminohippuric (PAH) clearance decreased 31% (P less than 0.01) and total effective renal vascular resistance rose 70% (P less than 0.03) in response to LPS 0111:B4. No significant change in PAH clearance was noted in the LPS 0127:B8 group. Superficial single nephron glomerular filtration rate (SNGFR) was reduced 69% (LPS 0111:B4), P less than 0.03, and 33% (LPS 0127:B8), P less than 0.02. Superficial glomerular plasma flow fell 48% (LPS 0111:B4), P less than 0.03, and 24% (LPS 0127:B8), P less than 0.03. Both lipopolysaccharides were associated with an increase in afferent arteriolar resistance (RA) which accounted for a reduction in the glomerular capillary hydraulic pressure (PGC). There was no change in the proximal tubular pressure in either group and, therefore, the net transcapillary hydraulic pressures were reduced. No measurable change in the ultrafiltration coefficient. Kf, was observed in either group. In a second set of protocols, the effect of prior administration of indomethacin or captopril on LPS 0111:B4 action was investigated. A significant decrease in BP occurred when animals were pretreated with captopril. Both indomethacin and captopril prevented the renal effects of LPS 0111:B4.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Effects of positive acceleration /+Gz/ on renal function and plasma renin in normal man

    NASA Technical Reports Server (NTRS)

    Epstein, M.; Shubrooks, S. J., Jr.; Fishman, L. M.; Duncan, D. C.

    1974-01-01

    The effects of positive radial centrifugation (+Gz) on plasma resin activity (PRA) and renal function were assessed in 15 normal male subjects under carefully controlled conditions of Na, K, and water intake. Twenty minutes of +2.0 Gz resulted in significant decreases in the mean rate of sodium excretion and creatine clearance and in a doubling of PRA in seven sodium-depleted subjects (10 meq Na intake). In eight sodium-replete subjects (200 mq Na intake), 30 min of +2.0 Gz was also associated with a decrease in the mean rate of sodium excretion. As a consequence of a concurrent decrease in creatine clearance, the fractional excretion of sodium during centrifugation did not differ from control, suggesting that the changes in Na excretion were mediated primarily by renal hemodynamic factors, although enhanced renal tubular sodium reabsorption may also have played a role.

  13. Rapid hepatic clearance of full length CCN-2/CTGF: a putative role for LRP1-mediated endocytosis.

    PubMed

    Gerritsen, K G F; Bovenschen, N; Nguyen, T Q; Sprengers, D; Koeners, M P; van Koppen, A N; Joles, J A; Goldschmeding, R; Kok, R J

    2016-12-01

    CCN-2 (connective tissue growth factor; CTGF) is a key factor in fibrosis. Plasma CCN-2 has biomarker potential in numerous fibrotic disorders, but it is unknown which pathophysiological factors determine plasma CCN-2 levels. The proteolytic amino-terminal fragment of CCN-2 is primarily eliminated by the kidney. Here, we investigated elimination and distribution profiles of full length CCN-2 by intravenous administration of recombinant CCN-2 to rodents. After bolus injection in mice, we observed a large initial distribution volume (454 mL/kg) and a fast initial clearance (120 mL/kg/min). Immunosorbent assay and immunostaining showed that CCN-2 distributed mainly to the liver and was taken up by hepatocytes. Steady state clearance in rats, determined by continuous infusion of CCN-2, was fast (45 mL/kg/min). Renal CCN-2 clearance, determined by arterial and renal vein sampling, accounted for only 12 % of total clearance. Co-infusion of CCN-2 with receptor-associated protein (RAP), an antagonist of LDL-receptor family proteins, showed that RAP prolonged CCN-2 half-life and completely prevented CCN-2 internalization by hepatocytes. This suggests that hepatic uptake of CCN-2 is mediated by a RAP-sensitive mechanism most likely involving LRP1, a member of the LDL-receptor family involved in hepatic clearance of various plasma proteins. Surface plasmon resonance binding studies confirmed that CCN-2 is an LRP1 ligand. Co-infusion of CCN-2 with an excess of the heparan sulphate-binding protamine lowered the large initial distribution volume of CCN-2 by 88 % and reduced interstitial staining of CCN-2, suggesting binding of CCN-2 to heparan sulphate proteoglycans (HSPGs). Protamine did not affect clearance rate, indicating that RAP-sensitive clearance of CCN-2 is HSPG independent. In conclusion, unlike its amino-terminal fragment which is cleared by the kidney, full length CCN-2 is primarily eliminated by the liver via a fast RAP-sensitive, probably LRP1-dependent

  14. Renal artery aneurysms.

    PubMed

    González, J; Esteban, M; Andrés, G; Linares, E; Martínez-Salamanca, J I

    2014-01-01

    A renal artery aneurysm is defined as a dilated segment of renal artery that exceeds twice the diameter of a normal renal artery. Although rare, the diagnosis and incidence of this entity have been steadily increasing due to the routine use of cross-sectional imaging. In certain cases, renal artery aneurysms may be clinically important and potentially lethal. However, knowledge of their occurrence, their natural history, and their prognosis with or without treatment is still limited. This article aims to review the recent literature concerning renal artery aneurysms, with special consideration given to physiopathology, indications for treatment, different technical options, post-procedure complications and treatment outcomes.

  15. QTc interval in children with chronic renal failure and with renal transplants.

    PubMed

    Butani, Lavjay; Berg, Gerre; Makker, Sudesh P

    2002-01-01

    Prolongation of the QTc interval, a risk factor for cardiac arrhythmias, has been observed in adult hemodialysis patients; there are few data on the QTc interval in children with chronic renal failure (CRF) and following renal transplantation (Tx). The purpose of our study was to determine the QTc interval in children with CRF and post renal Tx. Twenty children with CRF and 16 children with renal Tx who were followed at the University of California, Davis, underwent prospective EKG monitoring. The mean QTc interval in the CRF and post-Tx cohorts was normal at 407.9 ms and 408.2 ms, respectively. None of the children with CRF had QTc prolongation. Two Tx recipients had QTc prolongation; both had cardiac dilatation on echocardiography (ECHO). There was no correlation between the QTc interval and the creatinine clearance in either group. However, a significant correlation was noted between QTc prolongation and cardiac dilatation on ECHO in the Tx group (P=0.02, Fisher's exact test). In conclusion, QTc prolongation is uncommon in children with CRF and following Tx, in the absence of cardiac dilatation. However, caution is still needed before prescribing medications known to cause QTc prolongation.

  16. [Dose estimation for renal-excretion drugs in neonates and infants based on physiological development of renal function].

    PubMed

    Suzuki, Shinya; Murayama, Yuka; Sugiyama, Erika; Sekiyama, Masao; Sato, Hitoshi

    2009-07-01

    We established dose estimation formulae for renal-excretion drugs using the glomerular filtration rate (GFR), tubular secretion clearance (Sc), and unbound fraction of drug in plasma (fp) as a renal function index of physiological development in neonates and infants not more than 2 years of age. A dose ratio of (DC/DA)=clearance ratio of (CLC/CLA) congruent with(fpC.GFRC)/(fpA.GFRA) for neonates and infants/adults was applied to drugs with fp.GFR>Sc, while DC/DA=CLC/CLA congruent with(beta.BSAC+fpC.GFRC)/(beta.BSAA+fpA.GFRA) was applied to drugs with Sc>fp.GFR using the coefficient of each drug (beta) and body surface area (BSA). Validity of the estimation formulae was investigated in drugs with fp.GFR>Sc such as vancomycin (VCM), arbekacin (ABK), fosfomycin (FOM) and norfloxacin (NFLX), and in drugs with Sc>fp.GFR such as digoxin (DGX) and amoxicillin (AMPC). First, we compared the clearance ratio (CLC/ CLA) of VCM, ABK, and DGX estimated by our method with those calculated using the Japanese population clearance values and those estimated allometrically (BSAC/BSAA). Next, we compared the established doses of all drugs investigated with the doses for neonates and infants calculated from the conventional dose estimation methods for children and our estimation formulae, and evaluated our method. As a result, favorable consistency was observed in the CL ratio for all drugs, and the doses of VCM, FOM, NFLX and AMPC calculated from our estimation formulae approximated the established doses. In conclusion, the validity of the dose estimation method using pharmacokinetic factors related to physiological development (i.e., GFR, fp, Sc) for renal-excretion drugs in neonates and infants was demonstrated.

  17. Plasma exogenous creatinine clearance in clinically healthy cats: comparison with urinary exogenous creatinine clearance, tentative reference intervals and indexation to bodyweight.

    PubMed

    Reynolds, B S; Massal, M R; Nguyen, P; Grégoire, L L; Périgaud, A E; Concordet, D; Biourge, V; Lefebvre, H P

    2014-10-01

    Glomerular filtration rate (GFR) is considered to be the best indicator of overall kidney function. The major objectives of this study were to compare plasma exogenous creatinine clearance (PECC) with a reference method, to establish reference intervals (RIs) for PECC and to assess the effects of indexation of GFR to bodyweight (BW) in cats. PECC was compared with urinary clearance of exogenous creatinine (UECC) in six clinically healthy domestic shorthair cats (experiment 1). Tentative RIs were determined according to current guidelines and the effects of indexation to BW and of covariables on GFR were assessed in 43 clinically healthy cats of various breeds (experiment 2). PECC was 15% higher than UECC (P <0.01), but the two estimates were strongly correlated (r(2)=0.97, P = 0.001). RIs for PECC were 6.4-21.3 mL/min or 1.2-4.9 mL/min/kg. The absolute (i.e. non-indexed) GFR value was not dependent on BW. Thus, indexation of GFR to BW in cats would not standardize the GFR value, but could introduce bias in clinical interpretation. Significant effects of breed, plasma protein concentration and plasma albumin concentration on GFR were demonstrated. Plasma concentrations of urea and creatinine, when assessed separately, were also weakly correlated with GFR in healthy cats. These combined findings contribute to a better understanding of renal function assessment in cats.

  18. Role of No in the Regulation of Systemic and Renal Hemodynamics Following Hemorrhagic Shock in the Rate

    DTIC Science & Technology

    2007-11-02

    suprapubic incision for urine sampling. The right internal jugular vein was cannulated with two PE-50 catheters. Inulin , PAH and pentobarbital sodium...aortic arch (10). Glomerular filtration rate (GFR) and effective renal plasma flow were determined by the renal clearance of inulin -carboxyl...Carboxyl-14C] and aminohippuric acid P-[glycyl-2-3H] respectively (New England Nuclear, Boston, MA). The 14C- inulin was infused at a rate of 0.06uCi/min

  19. Influence of renal insufficiency on the pharmacokinetics of cicletanine and its effects on the urinary excretion of electrolytes and prostanoids.

    PubMed Central

    Ferry, N; Geoffroy, J; Pozet, N; Cuisinaud, G; Benzoni, D; Zech, P Y; Sassard, J

    1988-01-01

    1. The kinetics of a single oral dose (300 mg) of cicletanine a new antihypertensive drug with diuretic properties, and its effects on the urinary excretion of electrolytes and of the major stable metabolites of prostacyclin and thromboxane A2 were studied in patients with normal renal function (n = 6), mild (n = 9) and severe (n = 10) renal insufficiency. 2. In normotensive subjects with normal renal function, cicletanine was rapidly and regularly absorbed, its apparent elimination half-life established around 7 h, and both its renal clearance (0.4 ml min-1) and its cumulative renal excretion (0.85% of the administered dose), were low. Mild renal insufficiency did not significantly alter these parameters, while severe renal impairment reduced the renal clearance and the cumulative urinary excretion of cicletanine and increased its apparent elimination half-life (31 h). However the area under the plasma curve was not changed due to reduced plasma concentrations in these patients. 3. Cicletanine induced a rapid and marked (four fold as a mean) increase in the urinary excretion of water, sodium and potassium which lasted for 6 to 10 h, in subjects with normal renal function. Renal insufficiency did not alter the slope of the calculated plasma concentration-effects curves but reduced the maximum effect observed for water, sodium and potassium. 4. A single oral dose of cicletanine did not change the urinary excretion of 6-keto-prostaglandin F1 alpha and thromboxane B2 in the three groups of patients studied, the basal values of which being found to be closely related to the creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3358898

  20. Apoptosis inhibitor of macrophage protein enhances intraluminal debris clearance and ameliorates acute kidney injury in mice.

    PubMed

    Arai, Satoko; Kitada, Kento; Yamazaki, Tomoko; Takai, Ryosuke; Zhang, Xizhong; Tsugawa, Yoji; Sugisawa, Ryoichi; Matsumoto, Ayaka; Mori, Mayumi; Yoshihara, Yasunori; Doi, Kent; Maehara, Natsumi; Kusunoki, Shunsuke; Takahata, Akiko; Noiri, Eisei; Suzuki, Yusuke; Yahagi, Naoki; Nishiyama, Akira; Gunaratnam, Lakshman; Takano, Tomoko; Miyazaki, Toru

    2016-02-01

    Acute kidney injury (AKI) is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been established. Here we show that the apoptosis inhibitor of macrophage (AIM) protein on intraluminal debris interacts with kidney injury molecule (KIM)-1 and promotes recovery from AKI. During AKI, the concentration of AIM increases in the urine, and AIM accumulates on necrotic cell debris within the kidney proximal tubules. The AIM present in this cellular debris binds to KIM-1, which is expressed on injured tubular epithelial cells, and enhances the phagocytic removal of the debris by the epithelial cells, thus contributing to kidney tissue repair. When subjected to ischemia-reperfusion (IR)-induced AKI, AIM-deficient mice exhibited abrogated debris clearance and persistent renal inflammation, resulting in higher mortality than wild-type (WT) mice due to progressive renal dysfunction. Treatment of mice with IR-induced AKI using recombinant AIM resulted in the removal of the debris, thereby ameliorating renal pathology. We observed this effect in both AIM-deficient and WT mice, but not in KIM-1-deficient mice. Our findings provide a basis for the development of potentially novel therapies for AKI.

  1. Facile synthesis, pharmacokinetic and systemic clearance evaluation, and positron emission tomography cancer imaging of ⁶⁴Cu-Au alloy nanoclusters.

    PubMed

    Zhao, Yongfeng; Sultan, Deborah; Detering, Lisa; Luehmann, Hannah; Liu, Yongjian

    2014-11-21

    Gold nanoparticles have been widely used for oncological applications including diagnosis and therapy. However, the non-specific mononuclear phagocyte system accumulation and potential long-term toxicity have significantly limited clinical translation. One strategy to overcome these shortcomings is to reduce the size of gold nanoparticles to allow renal clearance. Herein, we report the preparation of (64)Cu alloyed gold nanoclusters ((64)CuAuNCs) for in vivo evaluation of pharmacokinetics, systemic clearance, and positron emission tomography (PET) imaging in a mouse prostate cancer model. The facile synthesis in acqueous solution allowed precisely controlled (64)Cu incorporation for high radiolabeling specific activity and stability for sensitive and accurate detection. Through surface pegylation with 350 Da polyethylene glycol (PEG), the (64)CuAuNCs-PEG350 afforded optimal biodistribution and significant renal and hepatobiliary excretion. PET imaging showed low non-specific tumor uptake, indicating its potential for active targeting of clinically relevant biomarkers in tumor and metastatic organs.

  2. Renal disease and hypertension in pregnancy.

    PubMed

    Palma-Reis, Ines; Vais, Alina; Nelson-Piercy, Catherine; Banerjee, Anita

    2013-02-01

    Because women are becoming pregnant at a later age, hypertension is more commonly encountered in pregnancy. In addition, with increasing numbers of young women living with renal transplants and kidney disease, it is important for physicians to be aware of the effects of pregnancy on these diseases. A multidisciplinary approach is essential to assess and care for pregnant women with kidney disease. Pre-pregnancy counselling should be offered to all women with chronic kidney disease. A review of medication to avoid teratogenicity and optimise the disease prior to conception is the ideal. Pregnancy may be the first medical review for a young woman, who may present with a previously undiagnosed renal problem.

  3. Tip Clearance Control Using Plasma Actuators

    DTIC Science & Technology

    2007-03-01

    Clearance Control Using Plasma Actuators 4 posed by Denton (1993). A number of investigators have used partial shrouds, or " winglet " designs to...main molded blade with a span of 3.42 in., a removable molded blade segment with a span of 0.1875 in., and removable blade tip winglets made of glass...segment and the main blade to vary the distance between the blade end and the front wall of the cascade section. The winglets were machined using a

  4. Statistical Tolerance and Clearance Analysis for Assembly

    NASA Technical Reports Server (NTRS)

    Lee, S.; Yi, C.

    1996-01-01

    Tolerance is inevitable because manufacturing exactly equal parts is known to be impossible. Furthermore, the specification of tolerances is an integral part of product design since tolerances directly affect the assemblability, functionality, manufacturability, and cost effectiveness of a product. In this paper, we present statistical tolerance and clearance analysis for the assembly. Our proposed work is expected to make the following contributions: (i) to help the designers to evaluate products for assemblability, (ii) to provide a new perspective to tolerance problems, and (iii) to provide a tolerance analysis tool which can be incorporated into a CAD or solid modeling system.

  5. Metabolism in immunoreactive parathyroid hormone in the dog. The role of the kidney and the effects of chronic renal disease.

    PubMed Central

    Hruska, K A; Kopelman, R; Rutherford, W E; Klahr, S; Slatopolsky, E; Greenwalt, A; Bascom, T; Markham, J

    1975-01-01

    The role of the kidney in the metabolism of parathyroid hormone (PTH) was examined in the dog. Studies were performed in awake normal and uremic dogs after administration of bovine parathyroid hormone (b-PTH) or synthetic amino terminal tetratricontapeptide of b-PTH (syn b-PTH 1-34). The renal clearance of immunoreactive PTH was determined from the product of renal plasma flow and the percent extraction of PTH immunoreactivity by the kidney. Blood levels of circulating immunoreactive PTH were determined by radioimmunoassay. The normal dog kidney extracted 20 plus or minus 1% of the immunoreactive b-PTH delivered to it, and renal clearance (RC) of immunoreactivity was 60 ml/min. When RC was compared to an estimate of total metabolic clearance (MCR) of immunoreactivity, it accounted for 61% of the total. Both MCR and RC were markedly decreased in dogs with chronic renal disease. However, the percent extraction of immunoreactive PTH was unchanged in chronic renal disease, and the observed decrease in RC was due to changes in renal plasma flow. The largest portion of the reduction in total MCR was accounted for by the decrease in RC, and there was no compensation for the decrease in RC by extrarenal sites of PTH metabolism. PMID:1141439

  6. Renal scintiscanning. A review

    PubMed Central

    Davies, E. Rhys

    1970-01-01

    Renal scintiscanning is a simple investigation that does not require special preparation and is well tolerated by patients. Radiopharmaceuticals used in linear scanning are accumulated in the renal cortex. This accumulation is diminished: (a) when the cortex is destroyed, e.g. by pyelonephritis, injury, etc.; and (b) when the amount available to the cortex is reduced, e.g. by ischaemia. The scintigram depicts the kidneys unimpeded by bowel contents, gives a qualitative assessment of renal function and shows the distribution of zones of normal function. Recent technical improvements show great promise in deriving a quantitative measure of renal function in some circumstances. The location of normally functioning cortex is often important in the management of renal diseases and the value of scintiscanning is then considerable. It is occasionally useful in planning surgery. The anatomy of the renal collecting system can be shown only by urography. High dose techniques achieve this even in the face of renal failure, and scintiscanning has few indications in investigating lesions that distort the renal anatomy, e.g. tumours and cysts. Renal scintiscanning is a very valuable additional method to urography, arteriography and renography in investigation of renal disorders. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8 PMID:4905447

  7. Testing of a Microwave Blade Tip Clearance Sensor at the NASA Glenn Research Center

    NASA Technical Reports Server (NTRS)

    Woike, Mark R.; Roeder, James W.; Hughes, Christopher E.; Bencic, Timothy J.

    2009-01-01

    The development of new active tip clearance control and structural health monitoring schemes in turbine engines and other types of rotating machinery requires sensors that are highly accurate and can operate in a high temperature environment. The use of a microwave sensor to acquire blade tip clearance and tip timing measurements is being explored at the NASA Glenn Research Center. The microwave blade tip clearance sensor works on principles that are very similar to a short range radar system. The sensor sends a continuous microwave signal towards a target and measures the reflected signal. The phase difference of the reflected signal is directly proportional to the distance between the sensor and the target being measured. This type of sensor is beneficial in that it has the ability to operate at extremely high temperatures and is unaffected by contaminants that may be present in turbine engines. The use of microwave sensors for this application is a new concept. Techniques on calibrating the sensors along with installation effects are not well quantified as they are for other sensor technologies. Developing calibration techniques and evaluating installation effects are essential in using these sensors to make tip clearance and tip timing measurements. As a means of better understanding these issues, the microwave sensors were used on a bench top calibration rig, a large axial vane fan, and a turbofan. Background on the microwave tip clearance sensor, an overview of their calibration, and the results from their use on the axial vane fan and the turbofan will be presented in this paper.

  8. Testing of a Microwave Blade Tip Clearance Sensor at the NASA Glenn Research Center

    NASA Technical Reports Server (NTRS)

    Woike, Mark R.; Roeder, James W.; Hughes, Christopher E.; Bencic, Timothy J.

    2009-01-01

    The development of new active tip clearance control and structural health monitoring schemes in turbine engines and other types of rotating machinery requires sensors that are highly accurate and can operate in a high-temperature environment. The use of a microwave sensor to acquire blade tip clearance and tip timing measurements is being explored at the NASA Glenn Research Center. The microwave blade tip clearance sensor works on principles that are very similar to a short-range radar system. The sensor sends a continuous microwave signal towards a target and measures the reflected signal. The phase difference of the reflected signal is directly proportional to the distance between the sensor and the target being measured. This type of sensor is beneficial in that it has the ability to operate at extremely high temperatures and is unaffected by contaminants that may be present in turbine engines. The use of microwave sensors for this application is a new concept. Techniques on calibrating the sensors along with installation effects are not well quantified as they are for other sensor technologies. Developing calibration techniques and evaluating installation effects are essential in using these sensors to make tip clearance and tip timing measurements. As a means of better understanding these issues, the microwave sensors were used on a benchtop calibration rig, a large axial vane fan, and a turbofan. Background on the microwave tip clearance sensor, an overview of their calibration, and the results from their use on the axial vane fan and the turbofan will be presented in this paper.

  9. Alteration of renal function of rats following spaceflight.

    PubMed

    Wade, C E; Morey-Holton, E

    1998-10-01

    Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.

  10. Alteration of renal function of rats following spaceflight

    NASA Technical Reports Server (NTRS)

    Wade, C. E.; Morey-Holton, E.

    1998-01-01

    Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.

  11. Dynamics analysis of space robot manipulator with joint clearance

    NASA Astrophysics Data System (ADS)

    Zhao, Yang; Bai, Zheng Feng

    2011-04-01

    A computational methodology for analysis of space robot manipulator systems, considering the effects of the clearances in the joint, is presented. The contact dynamics model in joint clearance is established using the nonlinear equivalent spring-damp model and the friction effect is considered using the Coulomb friction model. The space robot system dynamic equation of manipulator with clearance is established. Then the dynamics simulation is presented and the dynamics characteristics of robot manipulator with clearance are analyzed. This work provides a practical method to analyze the dynamics characteristics of space robot manipulator with joint clearance and improves the engineering application. The computational methodology can predict the effects of clearance on space robot manipulator preferably, which is the basis of space robot manipulator design, precision analysis and ground test.

  12. Study of blade clearance effects on centrifugal pumps

    NASA Technical Reports Server (NTRS)

    Hoshide, R. K.; Nielson, C. E.

    1972-01-01

    A program of analysis, design, fabrication, and testing has been conducted to develop and experimentally verify analytical models to predict the effects of impeller blade clearance on centrifugal pumps. The effect of tip clearance on pump efficiency, and the relationship between the head coefficient and torque loss with tip clearance was established. Analysis were performed to determine the cost variation in design, manufacture, and test that would occur between unshrouded and shrouded impellers. An impeller, representative of typical rocket engine impellers, was modified by removing its front shroud to permit variation of its blade clearances. It was tested in water with special instrumentation to provide measurements of blade surface pressures during operation. Pump performance data were obtained from tests at various impeller tip clearances. Blade pressure data were obtained at the nominal tip clearance. Comparisons of predicted and measured data are given.

  13. Numerical investigation of hub clearance flow in a Kaplan turbine

    NASA Astrophysics Data System (ADS)

    Wu, H.; Feng, J. J.; Wu, G. K.; Luo, X. Q.

    2012-11-01

    In this paper, the flow field considering the hub clearance flow in a Kaplan turbine has been investigated through using the commercial CFD code ANSYS CFX based on high-quality structured grids generated by ANSYS ICEM CFD. The turbulence is simulated by k-ω based shear stress transport (SST) turbulence model together with automatic near wall treatments. Four kinds of simulations have been conducted for the runner geometry without hub clearance, with only the hub front clearance, with only the rear hub clearance, and with both front and rear clearance. The analysis of the obtained results is focused on the flow structure of the hub clearance flow, the effect on the turbine performance including hydraulic efficiency and cavitation performance, which can improve the understanding on the flow field in a Kaplan turbine.

  14. Is the gravity effect of radiographic anatomic features enough to justify stone clearance or fragments retention following extracorporeal shock wave lithotripsy (SWL).

    PubMed

    Mustafa, Mahmoud

    2012-08-01

    We determined whether the gravity effect of radiographic anatomic features on the preoperative urography (IVP) are enough to predict fragments clearance after shock wave lithotripsy (SWL). A Total of 282 patients with mean age 45.8 ± 13.2 years (189 male, 93 female), who underwent SWL due to renal calculi between October 2005 and August 2009 were enrolled. The mean calculi load was 155.72 ± 127.66 mm². The patients were stratified into three groups: patients with pelvis calculi (group 1); patients with upper or middle pole calculi (group 2) and patients with lower pole calculi (group 3). Three angles on the pretreatment IVP were measured: the inner angle between the axis of the lower pole infundibular and ureteropelvic axis (angle I); the inner angle between the lower pole infundibular axis and main axis of pelvis-ureteropelvic (UP) junction point (angle II) and the inner angle between the lower pole infundibular axis and perpendicular line (angle III). Multivariate analysis was used to define the significant predictors of stone clearance. The overall success rate was 85.81%. All angles, sessions number, shock waves number and stone burden were significant predictors of success in patients in group 1. However, in group 2 only angle II and in group 3 angles I and II had significant effect on stone clearance. Radiographic anatomic features have significant role in determining the stone-free rate following satisfactory fragmentation of renal stones with SWL. The measurement of infundibulopelvic angle in different manner helps to predict the stone-free status in patients with renal calculi located not only in lower pole, but also in renal pelvis and upper or middle pole. Gravity effect is not enough to justify the significant influence of the radiographic anatomic features on the stone clearance and fragments retention after SWL.

  15. Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease.

    PubMed

    Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

    2016-01-01

    Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI.

  16. Measuring foot placement and clearance during stair descent.

    PubMed

    Muhaidat, Jennifer; Kerr, Andrew; Rafferty, Danny; Skelton, Dawn A; Evans, Jonathan J

    2011-03-01

    Falls during stair descent are a serious problem and can lead to accidental death. Inappropriate foot placement on, and clearance over, steps have been identified as causes for falls on stairs. This study investigated a new method for measuring placement and clearance during stair descent in 10 healthy young subjects. The effect of foot length was accounted for during the measurement of foot placement by calculating the percentage length of the foot overhanging the step. Foot clearance was measured as the resultant of the minimum vertical and horizontal distances from the heel of the foot to the edge of the step. Clearance was divided into landing and passing clearance depending on the planned placement of the foot in relation to the step edge being cleared. Each subject performed seven trials of stairs descent. Mean (SD) and CV (SD) were 16% (6), 0.28 (0.15) for placement; 45.88 (10.05), 0.21 (0.07) for landing clearance; 107.25 (5.59), 0.25 (0.08) for passing clearance. There was no statistically significant effect of trial on placement and clearance (p>0.05). There was a significant effect of step number on landing and passing clearance (p=0.01, p<0.001 respectively). Landing and passing clearances were greater for the third step compared to the second step. Passing clearance was also significantly greater than landing clearance (p<0.001). The repeatable methods and findings from this study might be useful in providing a technical background and normal values for the design of future gait studies on stairs.

  17. Deposition and clearance of inhaled particles.

    PubMed Central

    Stuart, B O

    1984-01-01

    Theoretical models of respiratory tract deposition of inhaled particles are compared to experimental studies of deposition patterns in humans and animals, as governed principally by particle size, density, respiratory rate and flow parameters. Various models of inhaled particle deposition make use of approximations of the respiratory tract to predict fractional deposition caused by fundamental physical processes of particle impaction, sedimentation, and diffusion. These models for both total deposition and regional (nasopharyngeal, tracheobronchial, and pulmonary) deposition are compared with early and recent experimental studies. Reasonable correlation has been obtained between theoretical and experimental studies, but the behavior in the respiratory tract of very fine (less than 0.1 micron) particles requires further investigation. Properties of particle shape, charge and hygroscopicity as well as the degree of respiratory tract pathology also influence deposition patterns; definitive experimental work is needed in these areas. The influence upon deposition patterns of dynamic alterations in inspiratory flow profiles caused by a variety of breathing patterns also requires further study, and the use of differing ventilation techniques with selected inhaled particle sizes holds promise in diagnosis of respiratory tract diseases. Mechanisms of conducting airway and alveolar clearance processes involving the pulmonary macrophage, mucociliary clearance, dissolution, transport to systemic circulation, and translocation via regional lymphatic vessels are discussed. PMID:6376108

  18. Renal Artery Embolization

    PubMed Central

    Sauk, Steven; Zuckerman, Darryl A.

    2011-01-01

    Renal artery embolization (RAE) is an effective minimally invasive alternative procedure for the treatment of a variety of conditions. Since the 1970s when RAE was first developed, technical advances and growing experience have expanded the indications to not only include treatment of conditions such as symptomatic hematuria and palliation for metastatic renal cancer, but also preoperative infarction of renal tumors, treatment of angiomyolipomas, vascular malformations, medical renal disease, and complications following renal transplantation. With the drastically improved morbidity associated with this technique in part due to the introduction of more precise embolic agents and smaller delivery catheters, RAE continues to gain popularity for various urologic conditions. The indications and techniques for renal artery embolization are reviewed in the following sections. PMID:23204638

  19. Application of clearance automatic laser inspection system to clearance measurement of concrete waste

    SciTech Connect

    Sasaki, Michiya; Ogino, Haruyuki; Hattori, Takatoshi

    2007-07-01

    Recently, the Clearance Automatic Laser Inspection System (CLALIS) has been developed for the clearance measurement of metal scraps. It utilizes three-dimensional (3D) laser scanning, y-ray measurement and Monte Carlo calculation, and has outstanding detection ability. For the clearance measurement of concrete segments, the effect of background (BG) gamma rays from natural radionuclides in the measurement target, such as K-40 and the radioactive decay products of Th-232 and U-238, should be compensated for to ensure adequate waste management. Since NE102A plastic scintillation detectors are used for y-ray measurement in CLALIS, it is impossible to distinguish between count rates of natural radionuclides and contaminants on the basis of gamma-ray energy information. To apply CLALIS to the clearance measurement of concrete segments, the original activity evaluation method was improved by adding a new compensation procedure. In this procedure, BG count rate due to natural radionuclides is estimated by a Monte Carlo calculation with pre-analyzed data of a representative sample of the measurement target. The activity concentration of natural radionuclides in concrete differs markedly depending on the production location of its components, such as cement and aggregates. In this study, using six mock concrete waste samples, which were composed of cement and fine aggregate from various production locations, the accuracy of BG compensation was experimentally estimated. In addition, the accuracy of calibration for concrete waste was also estimated using a number of mock concrete segments of small and large triangular prisms. By considering the uncertainties of BG compensation and calibration, the detection limit of CLALIS for concrete waste was estimated. As a result, it was revealed that CLALIS could be applied to the clearance measurement of concrete segments when the mass of the measurement target is greater than approximately 1.1 kg and the key radionuclide is Co-60

  20. ESR measurement of radical clearance in lung of whole mouse

    SciTech Connect

    Takeshita, K.; Utsumi, H.; Hamada, A. )

    1991-06-14

    Clearance of the nitroxide radicals, hydroxy-TEMPO and carboxy-PROxYL, in whole-mouse lung was directly measured by in vivo ESR. After injecting a nitroxide radical, distribution of the nitroxide radical all over the lung was confirmed by ESR imaging. The ESR signal of hydroxy-TEMPO was reduced in the lung and the clearance obeyed first-order kinetics, whereas the signal of carboxy-PROxYL remained constant. Comparison of the clearance rates of live and dead mice indicated the presence of 2 different clearance systems in the lung: loss of its paramagnetism in the lung, and transfer from alveolar to the blood circulation system.

  1. Amino acid infusion blocks renal tubular uptake of an indium-labelled somatostatin analogue.

    PubMed Central

    Hammond, P. J.; Wade, A. F.; Gwilliam, M. E.; Peters, A. M.; Myers, M. J.; Gilbey, S. G.; Bloom, S. R.; Calam, J.

    1993-01-01

    The Indium-labelled somatostatin analogue pentetreotide has been successfully developed for imaging of somatostatin receptor positive tumours. However there is significant renal tubular uptake of the radiolabelled peptide, which can obscure upper abdominal tumours and would preclude its use for targeted radiotherapy. The aim of this study was to determine whether amino acid infusion, which has been shown to block renal tubular peptide reabsorption, diminishes renal parenchymal uptake of this radiolabelled analogue. Eight patients being scanned with the 111In-labelled somatostatin analogue, pentetreotide, for localisation of gastroenteropancreatic tumours received an infusion of synthetic amino acids. The ratio of isotope uptake in kidney to that in spleen was assessed, and compared to the ratio for matched control patients, to determine if amino acid infusion reduced renal parenchymal uptake of the radiopharmaceutical. The amount of isotope in the urine was determined to ensure that any effect of the amino acid infusion was unrelated to changes in clearance. Infusion of amino acids significantly reduced renal parenchymal uptake of isotope at 4 h. There was a non-significant increase in urinary clearance of isotope over the 4 h, consistent with reduced reuptake and a lack of effect on glomerular filtration rate. This technique, by preventing renal damage, may allow the use of this somatostatin analogue for local radiotherapy, and could be of wider value in blocking tubular re-uptake of potentially nephrotoxic agents, such as radiolabelled Fab fragments. Images Figure 1 PMID:8099808

  2. Influence of different degrees of reduced renal mass on the renal and hepatic disposition of administered cadmium

    SciTech Connect

    Zalups, R.K.

    1997-06-27

    The present study was designed to evaluate, in rats, the effect of varying degrees of reduced renal mass on the disposition of administered cadmium. As part of this evaluation, the intrarenal, hepatic, and hematological disposition of cadmium and the urinary and fecal excretion of cadmium were studied and characterized in control, uninephrectomized (NPX), and 75% nephrectomized (75% NPX) rats 1 d, 2 d, and 7 d after the intravenous injection of a nonnephrotoxic 8.9 {mu}mol/kg dose of cadmium chloride. Renal accumulation of cadmium was reduced significantly in the 75% NPX rats, but not in the NPX rats, between d 2 and 7 after the injection of cadmium. This diminution in cadmium accumulation was most likely due to diminished glomerular filtration rate and renal clearance of cadmium induced by 75% nephrectomy. Despite reduced glomerular filtration rate, the cumulative urinary excretion of cadmium in the 75% NPX rats was significantly greater than that in either the NPX rats or the control rats. However, that very little of the administered dose of cadmium was excreted in the urine by any of the three groups of rats. Interestingly, the content of cadmium in the liver was significantly greater in 75% NPX rats than in NPX or control rats between d 1 and 7 after the injection of cadmium. Moreover, the 75% NPX rats excreted significantly less cadmium in the feces over the 7 d of study than did the other 2 groups of rats, indicating that 75% nephrectomy causes a significant alteration in one or more of the mechanisms involved in the fecal excretion of cadmium. in summary, the findings from the present study indicate that the renal and hepatic handling of administered cadmium in rats changes significantly when renal mass is reduced by 75%. Further studies are needed to better characterize the effects of reductions of renal mass, which impair renal function significantly, on both the disposition and toxicity of cadmium in renal and hepatic tissues. 25 refs., 5 figs., 1 tab.

  3. Maintenance of residual renal function 10 years after the start of hemodialysis: the advantage of tailored schedules?

    PubMed

    Piccoli, G B; Burdese, M; Mezza, E; Consiglio, V; Mangiarotti, G; Thea, A; Bermond, F; Gai, M; Lanfranco, G; Jeantet, A; Segoloni, G P

    2004-03-01

    Maintenance of residual renal clearance is a clinical advantage, protecting against the long-term effects of uremia: although demonstrated in peritoneal dialysis, the strategies in hemodialysis are less clear. This case suggests that dialysis schedules individualized on the basis of renal clearances may help preserve residual function. SB is a 58 year-old male who started dialysis in emergency (creatinine 30.7 mg/dL) in 1993. He had a history of gout, small shrunken kidneys and moderate hypertension. The clinical diagnosis was vasculointerstitial nephropathy. Eighteen months after starting hemodialysis on a conventional thrice weekly schedule, the patient was switched to 2 sessions/week (creatinine clearance increased to 6 ml/min). Thereafter, clearances were checked in alternate months and treatment was tailored to an equivalent renal clearance > or =12 ml/min (1-2 sessions, 2-3.30 hours/week). Ten years after beginning dialysis, he is on a twice weekly schedule (3.30 hours), is normotensive, works full-time and does not want to go on a transplant waiting list.

  4. Facile synthesis, pharmacokinetic and systemic clearance evaluation, and positron emission tomography cancer imaging of 64Cu-Au alloy nanoclusters

    NASA Astrophysics Data System (ADS)

    Zhao, Yongfeng; Sultan, Deborah; Detering, Lisa; Luehmann, Hannah; Liu, Yongjian

    2014-10-01

    Gold nanoparticles have been widely used for oncological applications including diagnosis and therapy. However, the non-specific mononuclear phagocyte system accumulation and potential long-term toxicity have significantly limited clinical translation. One strategy to overcome these shortcomings is to reduce the size of gold nanoparticles to allow renal clearance. Herein, we report the preparation of 64Cu alloyed gold nanoclusters (64CuAuNCs) for in vivo evaluation of pharmacokinetics, systemic clearance, and positron emission tomography (PET) imaging in a mouse prostate cancer model. The facile synthesis in acqueous solution allowed precisely controlled 64Cu incorporation for high radiolabeling specific activity and stability for sensitive and accurate detection. Through surface pegylation with 350 Da polyethylene glycol (PEG), the 64CuAuNCs-PEG350 afforded optimal biodistribution and significant renal and hepatobiliary excretion. PET imaging showed low non-specific tumor uptake, indicating its potential for active targeting of clinically relevant biomarkers in tumor and metastatic organs.Gold nanoparticles have been widely used for oncological applications including diagnosis and therapy. However, the non-specific mononuclear phagocyte system accumulation and potential long-term toxicity have significantly limited clinical translation. One strategy to overcome these shortcomings is to reduce the size of gold nanoparticles to allow renal clearance. Herein, we report the preparation of 64Cu alloyed gold nanoclusters (64CuAuNCs) for in vivo evaluation of pharmacokinetics, systemic clearance, and positron emission tomography (PET) imaging in a mouse prostate cancer model. The facile synthesis in acqueous solution allowed precisely controlled 64Cu incorporation for high radiolabeling specific activity and stability for sensitive and accurate detection. Through surface pegylation with 350 Da polyethylene glycol (PEG), the 64CuAuNCs-PEG350 afforded optimal

  5. The Changing Landscape of Renal Inflammation.

    PubMed

    Ernandez, Thomas; Mayadas, Tanya Norton

    2016-02-01

    Kidney inflammation is a major contributor to progressive renal injury, leading to glomerulonephritis (GN) and chronic kidney disease. We review recent advances in our understanding of leukocyte accumulation in the kidney, emphasizing key chemokines involved in GN. We discuss features of renal inflammation such as the evolving concept of immune cell plasticity. We also describe certain aspects of organ-specific tissue microenvironments in shaping immune cell responses, as well as the current knowledge of how regulatory T lymphocytes impact on other immune effector cell populations to control inflammation. It is clear that present and future research in these areas may contribute to the development of novel targeted therapeutics, with the hope of alleviating the burden of end-stage renal disease (ESRD).

  6. Comparative evaluation of Tc-99m cystine and Tc-99m MAG3 in normals and patients with renal functional impairment.

    PubMed

    Misra, Mridula; Pradhan, Prasanta K; De, Kakali; Chandra, Susmita; Das, Birendra K

    2009-03-01

    Tc-99m cystine has been proved to be a good renal agent in animals for morphologic as well as the functional status of the kidney. In this study, we compared Tc-99m cystine with Tc-99m mercaptoacetyltriglycine, which is used for evaluation of renal function in normal patients, and those with various degrees of renal functional impairment. The clearance values and static images are compared with Tc-99m mercaptoacetyltriglycine. The results show that Tc-99m cystine has good radiopharmaceutical characteristics suitable for evaluation of both renal function as well as morphology.

  7. Renal pelvis or ureter cancer

    MedlinePlus

    Transitional cell cancer of the renal pelvis or ureter; Kidney cancer - renal pelvis; Ureter cancer ... Cancer can grow in the urine collection system, but it is uncommon. Renal pelvis and ureter cancers ...

  8. Renal function and endocrine responses to arm exercise in euhydrated individuals with spinal cord injury.

    PubMed

    Kawasaki, Takashi; Nakamura, Takeshi; Sasaki, Yusuke; Sakamoto, Keiko; Ito, Tomoyuki; Goto, Masaki; Shimomatsu, Tomoya; Tajima, Fumihiro

    2012-04-01

    This study investigated the renal and endocrine responses to arm exercise in persons with spinal cord injury (SCI) under euhydration conditions (ad libitum drinking of water) and determined the physiological effects of exercise on renal function in these subjects. Eleven SCI (spinal lesions between T6 and L1, American Spinal Injury Association impairment scale A) and 14 able-bodied (AB) persons first rested for 1 h in a sitting position, before undergoing 2-h arm-crank ergometer exercise at 60% of maximum oxygen consumption followed by a 2-h recovery period. On another day, all subjects participated in a time control study (5 h of rest condition in sitting position). Urine and blood samples were collected hourly. There were no differences in mean blood pressure between the two groups. SCI patients showed attenuated increase in plasma adrenaline and increase in plasma aldosterone compared with AB controls, but similar changes in human atrial natriuretic polypeptide, plasma renin activity and plasma antidiuretic hormone following the exercise. Creatinine clearance, osmolal clearance, free water clearance and fractional excretion of Na(+) did not change during exercise in any of the subjects. These findings suggested that activated aldosterone and attenuated adrenaline responses during exercise in SCI could be due to adaptation to disordered sympathetic nervous system triggered to maintain renal function. The results showed no exercise-related adverse effects on renal function in hydrated subjects with SCI.

  9. CSF clearance in Alzheimer Disease measured with dynamic PET.

    PubMed

    de Leon, Mony J; Li, Yi; Okamura, Nobuyuki; Tsui, Wai H; Saint Louis, Les A; Glodzik, Lidia; Osorio, Ricardo S; Fortea, Juan; Butler, Tracy; Pirraglia, Elizabeth; Fossati, Silvia; Kim, Hee-Jin; Carare, Roxana O; Nedergaard, Maiken; Benveniste, Helene; Rusinek, Henry

    2017-03-16

    Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer's disease (AD) comes from primarily from rodent models. However, unlike rodents where predominant extra-cranial CSF egress is via olfactory nerves traversing the cribriform plate, human CSF clearance pathways are not well characterized. Using dynamic Positron Emission Tomography (PET) with (18)F-THK5117 a tracer for tau pathology, the ventricular CSF time activity was used as a biomarker for CSF clearance. We tested three hypotheses: 1. Extra-cranial CSF is detected at the superior turbinates; 2. CSF clearance is reduced in AD; and 3. CSF clearance is inversely associated with amyloid deposition. Methods: 15 subjects, 8 with AD and 7 normal control volunteers were examined with (18)F-THK5117. 10 subjects additionally received (11)C-PiB PET scans and 8 were PiB positive. Ventricular time activity curves (TAC) of (18)F-THK5117 were used to identify highly correlated TAC from extra-cranial voxels. Results: For all subjects, the greatest density of CSF positive extra-cranial voxels was in the nasal turbinates. Tracer concentration analyses validated the superior nasal turbinate CSF signal intensity. AD patients showed ventricular tracer clearance reduced by 23% and 66% fewer superior turbinate CSF egress sites. Ventricular CSF clearance was inversely associated with amyloid deposition. Conclusion: The human nasal turbinate is part of the CSF clearance system. Lateral ventricle and superior nasal turbinates CSF clearance abnormalities are found in AD. Ventricular CSF clearance reductions are associated with increased brain amyloid depositions. These data suggest that PET measured CSF clearance is a biomarker of potential interest in AD and other neurodegenerative diseases.

  10. Complex Disease–, Gene–, and Drug–Drug Interactions: Impacts of Renal Function, CYP2D6 Phenotype, and OCT2 Activity on Veliparib Pharmacokinetics

    PubMed Central

    Li, Jing; Kim, Seongho; Sha, Xianyi; Wiegand, Richard; Wu, Jianmei; LoRusso, Patricia

    2014-01-01

    Purpose Veliparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, undergoes renal excretion and liver metabolism. This study quantitatively assessed the interactions of veliparib with metabolizing enzyme (CYP2D6) and transporter (OCT2) in disease settings (renal impairment). Experimental Design Veliparib in vitro metabolism was examined in human liver microsomes and recombinant enzymes carrying wild-type CYP2D6 or functional defect variants (CYP2D6*10 and *4). Plasma pharmacokinetics were evaluated in 27 patients with cancer. A parent–metabolite joint population model was developed to characterize veliparib and metabolite (M8) pharmacokinetics and to identify patient factors influencing veliparib disposition. A physiologically based pharmacokinetic model integrated with a mechanistic kidney module was developed to quantitatively predict the individual and combined effects of renal function, CYP2D6 phenotype, and OCT2 activity on veliparib pharmacokinetics. Results In vitro intrinsic clearance of CYP2D6.1 and CYP2D6.10 for veliparib metabolism were 0.055 and 0.017 μL/min/pmol CYP, respectively. Population mean values for veliparib oral clearance and M8 clearance were 13.3 and 8.6 L/h, respectively. Creatinine clearance was identified as the significant covariate on veliparib oral clearance. Moderate renal impairment, CYP2D6 poor metabolizer, and co-administration of OCT2 inhibitor (cimetidine) increased veliparib steady-state exposure by 80%, 20%, and 30%, respectively. These factors collectively led to >2-fold increase in veliparib exposure. Conclusions Renal function (creatinine clearance) is a significant predictor for veliparib exposure in patients with cancer. Although a single factor (i.e., renal impairment, CYP2D6 deficiency, and reduced OCT2 activity) shows a moderate impact, they collectively could result in a significant and potentially clinically relevant increase in veliparib exposure. PMID:24947923

  11. [Biochemical evaluation of renal lesions produced by electrohydraulic shock waves].

    PubMed

    Rodriguez Vela, L; Abadia Bayona, T; Lazaro Castillo, J; Guallar Labrador, A; Rioja Sanz, C; Rioja Sanz, L A

    1995-01-01

    The authors present a biochemical study of the renal lesions produced during extracorporeal electrohydraulic shock wave lithotripsy (ESWL). The sequential variation (before and after ESWL) of various biochemical parameters of the blood and 24-hour urine was analysed in 50 patients. A significant increase of urinary N-Acetyl-Glucosaminidase (NAG), urinary NAG/urinary creatinine quotient, proteinuria, serum creatinine and potassium was detected during the 24 hours following ESWL. A significant fall in creatinine clearance, urinary osmolarity and uric acid clearance was also detected. A positive correlation was observed between these alterations, the number of shocks and the kilovoltage used. On the 7th and 15th days, no significant difference was observed compared to the baseline values before ESWL. This can be explained by the fact that the lesions caused by shock waves are already in the repair phase.

  12. Renal Response to Chronic Centrifugation in Rats

    NASA Technical Reports Server (NTRS)

    Ortiz, Rudy M.; Wang, T. J.; Corbin, B. J.; Wade, C. E.; Hargens, Alan R. (Technical Monitor)

    1996-01-01

    Previously reported effects of chronic centrifugation on renal function in mammals are contradictory. The present study was conducted as an effort to provide a comprehensive analysis of renal response to chronic centrifugation (12 days at +2 Gz). Sixteen male Sprague-Dawley rats (210-230 g) were used: eight centrifuged (EC) and eight off centrifuge controls (OCC). During centrifugation EC had lower body weight and food consumption. EC showed a decrease (72%) in water intake for the first two days (T1 and T2) followed by significant increases from T4-T6. EC urine output increased two-fold over the first four days, returning to baseline by T9. EC urea excretion was elevated on T3 through T5. Creatinine, Na(+), K(+), and osmolar excretion were lower than OCC over the last four days of the study. Assuming constant plasma osmolarity and creatinine levels, EC free water clearance (C(sub H2O)) was elevated significantly on T4 when the peak urine output was exhibited. EC also had a greater C(sub H2O) over the last four days, associated with a significantly lower osmolar clearance and GFR. The initial diuresis exhibited during centrifugation can be attributed to a reduced water resorption and increased urea excretion. This diuresis was mediated independent of changes in GFR over the first eight days. However, differences in excretion seen after eight days of centrifugation are probably GFR mediated which would imply animals established a new homeostatic setpoint by that time. Centrifugation elicites an acute alteration in fluid homeostasis followed by adaptation within a week.

  13. A Microwave Blade Tip Clearance Sensor for Propulsion Health Monitoring

    NASA Technical Reports Server (NTRS)

    Woike, Mark R.; Abdul-Aziz, Ali; Bencic, Timothy J.

    2010-01-01

    Microwave sensor technology is being investigated by the NASA Glenn Research Center as a means of making non-contact structural health measurements in the hot sections of gas turbine engines. This type of sensor technology is beneficial in that it is accurate, it has the ability to operate at extremely high temperatures, and is unaffected by contaminants that are present in turbine engines. It is specifically being targeted for use in the High Pressure Turbine (HPT) and High Pressure Compressor (HPC) sections to monitor the structural health of the rotating components. It is intended to use blade tip clearance to monitor blade growth and wear and blade tip timing to monitor blade vibration and deflection. The use of microwave sensors for this application is an emerging concept. Techniques on their use and calibration needed to be developed. As a means of better understanding the issues associated with the microwave sensors, a series of experiments have been conducted to evaluate their performance for aero engine applications. This paper presents the results of these experiments.

  14. Specific autoantibody slows the rapid plasma clearance of 125I-SS-B (La) in mice.

    PubMed Central

    Schrieber, L; Melsom, R D; Venables, P J; McCarthy, D A; Maini, R N

    1984-01-01

    In BALB/c mice the plasma clearance of intravenously (i.v.) injected 125I-SS-B (La) (T 1/2 = 3 min) is markedly delayed when complexed in vitro to specific autoantibody (T 1/2 = 60 min) and is associated with diminished hepatic and renal uptake. The in vivo behaviour of 11S 125I-SS-B-IgG-anti-SS-B complexes was similar to that of 20-30S 125I-heat-aggregated IgG. The presence of anti-SS-B antibodies in systemic lupus erythematosus and Sjögren's syndrome could similarly result in persistence of SS-B containing immune complexes and provide a mechanism which may perpetuate autoimmunity. PMID:6611229

  15. Pharmacokinetics of iothalamate in endstage renal disease

    SciTech Connect

    Evans, J.R.; Cutler, R.E.; Forland, S.C.

    1988-09-01

    Some nephrologists make alterations in routine peritoneal and hemodialysis schedules after diagnostic studies that use radiographic contrast agents. A study to determine the pharmacokinetics of one contrast agent, iothalamate, is reported. The plasma (total body) clearance of iothalamate was measured in seven patients who had endstage renal disease (ESRD) and who received maintenance hemodialysis. During an interdialytic period, plasma clearance of iothalamate varied from 0.7 to 5.2 mL/min (3.1 +/- 1.8 mL/min, mean +/- SD) with an elimination rate constant (beta) of 0.0164 +/- 0.01 hr-1, a terminal half-life of 61 +/- 42 hours, and an estimated distribution volume of 11 +/- 3.9 L. Hemodialysis clearance of iothalamate was 104 +/- 54 mL/min. With the assumption that iothalamate is mainly distributed in the extracellular fluid (ECF) compartment, the theoretical fluid shift from the intracellular fluid (ICF) compartment to the ECF compartment was 323 mL after administration of the largest dose (2.1 mL/kg or 1.6 mmol/kg of body weight) of 60% meglumine iothalamate solution. The average maximum serum osmolarity change was less than expected, suggesting some type of internal buffering of meglumine iothalamate. In the first few hours after radiocontrast administration in four patients, the average change in serum osmolarity was 5 mmol/L; the average change in serum sodium concentration during this same time was a decrease of 0.5 mmol/L. The minor increase in ECF volume induced by hyperosmolar contrast agents does not require immediate dialysis in most patients. When needed, however, for contrast-related adverse effects, hemodialysis is efficient in rapidly removing iothalamate.

  16. Validation of Dose Calculation Codes for Clearance

    SciTech Connect

    Menon, S.; Wirendal, B.; Bjerler, J.; Studsvik; Teunckens, L.

    2003-02-27

    Various international and national bodies such as the International Atomic Energy Agency, the European Commission, the US Nuclear Regulatory Commission have put forward proposals or guidance documents to regulate the ''clearance'' from regulatory control of very low level radioactive material, in order to allow its recycling as a material management practice. All these proposals are based on predicted scenarios for subsequent utilization of the released materials. The calculation models used in these scenarios tend to utilize conservative data regarding exposure times and dose uptake as well as other assumptions as a safeguard against uncertainties. None of these models has ever been validated by comparison with the actual real life practice of recycling. An international project was organized in order to validate some of the assumptions made in these calculation models, and, thereby, better assess the radiological consequences of recycling on a practical large scale.

  17. Improved Flight Test Procedures for Flutter Clearance

    NASA Technical Reports Server (NTRS)

    Lind, Rick C.; Brenner, Martin J.; Freudinger, Lawrence C.

    1997-01-01

    Flight flutter testing is an integral part of flight envelope clearance. This paper discusses advancements in several areas that are being investigated to improve efficiency and safety of flight test programs. Results are presented from recent flight testing of the F/A-18 Systems Research Aircraft. A wingtip excitation system was used to generate aeroelastic response data. This system worked well for many flight conditions but still displayed some anomalies. Wavelet processing is used to analyze the flight data. Filtered transfer functions are generated that greatly improve system identification. A flutter margin is formulated that accounts for errors between a model and flight data. Worst-case flutter margins are computed to demonstrate the flutter boundary may lie closer to the flight envelope than previously estimated. This paper concludes with developments for a distributed flight analysis environment and on-line health monitoring.

  18. [Mucociliary clearance function and medicamentous modification].

    PubMed

    Konrad, F

    1996-09-01

    Mucociliary clearance represents a complex self-cleaning mechanism of the lung and is based on the functional unity of ciliated columnar cells and the special viscoelastic properties of the secretion produced in the tracheobronchial system. It has been known for a long time that intubation and mechanical ventilation can impair mucous transport and lead to morphological damage to the tracheobronchial mucosa. Recent studies made it clear, however, that mechanical ventilation during anaesthesia using an appropriate anaesthesiological technique has no deleterious effect on mucus transport in patients with healthy lungs. Ventilated patients in the intensive-care unit frequently have impaired mucus transport, which is associated with the development of retention of secretion and nosocomial pneumonia. In these patients a number of factors combine to form a formidable potential insult to the mucociliary transport mechanism. Numerous drugs can affect mucociliary transport. Beta-mimetics and theophylline, in particular, have a favourable effect on mucociliary transport, whereas the effect of mucolytic agents is controversial.

  19. Anthrax edema toxin impairs clearance in mice.

    PubMed

    Sastalla, Inka; Tang, Shixing; Crown, Devorah; Liu, Shihui; Eckhaus, Michael A; Hewlett, Indira K; Leppla, Stephen H; Moayeri, Mahtab

    2012-02-01

    The anthrax edema toxin (ET) of Bacillus anthracis is composed of the receptor-binding component protective antigen (PA) and of the adenylyl cyclase catalytic moiety, edema factor (EF). Uptake of ET into cells raises intracellular concentrations of the secondary messenger cyclic AMP, thereby impairing or activating host cell functions. We report here on a new consequence of ET action in vivo. We show that in mouse models of toxemia and infection, serum PA concentrations were significantly higher in the presence of enzymatically active EF. These higher concentrations were not caused by ET-induced inhibition of PA endocytosis; on the contrary, ET induced increased PA binding and uptake of the PA oligomer in vitro and in vivo through upregulation of the PA receptors TEM8 and CMG2 in both myeloid and nonmyeloid cells. ET effects on protein clearance from circulation appeared to be global and were not limited to PA. ET also impaired the clearance of ovalbumin, green fluorescent protein, and EF itself, as well as the small molecule biotin when these molecules were coinjected with the toxin. Effects on injected protein levels were not a result of general increase in protein concentrations due to fluid loss. Functional markers for liver and kidney were altered in response to ET. Concomitantly, ET caused phosphorylation and activation of the aquaporin-2 water channel present in the principal cells of the collecting ducts of the kidneys that are responsible for fluid homeostasis. Our data suggest that in vivo, ET alters circulatory protein and small molecule pharmacokinetics by an as-yet-undefined mechanism, thereby potentially allowing a prolonged circulation of anthrax virulence factors such as EF during infection.

  20. 14 CFR 29.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Ground clearance: tail rotor guard. 29.411 Section 29.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 29.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor...

  1. 14 CFR 29.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Ground clearance: tail rotor guard. 29.411 Section 29.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 29.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor...

  2. 14 CFR 29.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Ground clearance: tail rotor guard. 29.411 Section 29.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 29.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor...

  3. 14 CFR 27.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Ground clearance: tail rotor guard. 27.411 Section 27.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 27.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor...

  4. 14 CFR 27.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Ground clearance: tail rotor guard. 27.411 Section 27.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 27.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor...

  5. 14 CFR 27.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Ground clearance: tail rotor guard. 27.411 Section 27.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 27.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor...

  6. 14 CFR 29.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Ground clearance: tail rotor guard. 29.411 Section 29.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 29.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor...

  7. 14 CFR 27.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Ground clearance: tail rotor guard. 27.411 Section 27.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 27.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor...

  8. 76 FR 17978 - Agency Information Collection Activities: Emergency Clearance Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-31

    ... From the Federal Register Online via the Government Publishing Office SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Emergency Clearance Request The Social Security Administration (SSA) publishes a list of information collection packages requiring clearance by the Office of Management and Budget (OMB) in compliance...

  9. 20 CFR 655.150 - Interstate clearance of job order.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated...

  10. 20 CFR 655.150 - Interstate clearance of job order.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated...

  11. 20 CFR 655.150 - Interstate clearance of job order.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated...

  12. 20 CFR 655.150 - Interstate clearance of job order.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated...

  13. 20 CFR 655.150 - Interstate clearance of job order.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated...

  14. Mechanistic evaluation of virus clearance by depth filtration.

    PubMed

    Venkiteshwaran, Adith; Fogle, Jace; Patnaik, Purbasa; Kowle, Ron; Chen, Dayue

    2015-01-01

    Virus clearance by depth filtration has not been well-understood mechanistically due to lack of quantitative data on filter charge characteristics and absence of systematic studies. It is generally believed that both electrostatic interactions and sized based mechanical entrapment contribute to virus clearance by depth filtration. In order to establish whether the effectiveness of virus clearance correlates with the charge characteristics of a given depth filter, a counter-ion displacement technique was employed to determine the ionic capacity for several depth filters. Two depth filters (Millipore B1HC and X0HC) with significant differences in ionic capacities were selected and evaluated for their ability to eliminate viruses. The high ionic capacity X0HC filter showed complete porcine parvovirus (PPV) clearance (eliminating the spiked viruses to below the limit of detection) under low conductivity conditions (≤2.5 mS/cm), achieving a log10 reduction factor (LRF) of > 4.8. On the other hand, the low ionic capacity B1HC filter achieved only ∼2.1-3.0 LRF of PPV clearance under the same conditions. These results indicate that parvovirus clearance by these two depth filters are mainly achieved via electrostatic interactions between the filters and PPV. When much larger xenotropic murine leukemia virus (XMuLV) was used as the model virus, complete retrovirus clearance was obtained under all conditions evaluated for both depth filters, suggesting the involvement of mechanisms other than just electrostatic interactions in XMuLV clearance.

  15. 49 CFR 229.71 - Clearance above top of rail.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Clearance above top of rail. 229.71 Section 229.71....71 Clearance above top of rail. No part or appliance of a locomotive except the wheels, flexible nonmetallic sand pipe extension tips, and trip cock arms may be less than 21/2 inches above the top of rail....

  16. 49 CFR 229.71 - Clearance above top of rail.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Clearance above top of rail. 229.71 Section 229.71....71 Clearance above top of rail. No part or appliance of a locomotive except the wheels, flexible nonmetallic sand pipe extension tips, and trip cock arms may be less than 21/2 inches above the top of rail....

  17. 19 CFR 122.26 - Entry and clearance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Entry and clearance. 122.26 Section 122.26 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY... information as set forth in § 122.22(c), and grants electronic clearance via electronic mail or telephone....

  18. 14 CFR 29.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Ground clearance: tail rotor guard. 29.411 Section 29.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 29.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor...

  19. 5 CFR 720.307 - Interagency report clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Interagency report clearance. 720.307 Section 720.307 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... Interagency report clearance. The reports contained in this regulation have been cleared in accordance...

  20. 10 CFR 95.53 - Termination of facility clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Termination of facility clearance. 95.53 Section 95.53 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Control of Information § 95.53 Termination of facility...

  1. Benefits of Improved HP Turbine Active Clearance Control

    NASA Technical Reports Server (NTRS)

    Ruiz, Rafael; Albers, Bob; Sak, Wojciech; Seitzer, Ken; Steinetz, Bruce M.

    2007-01-01

    As part of the NASA Propulsion 21 program, GE Aircraft Engines was contracted to develop an improved high pressure turbine(HPT) active clearance control (ACC) system. The system is envisioned to minimize blade tip clearances to improve HPT efficiency throughout the engine operation range simultaneously reducing fuel consumption and emissions.

  2. 48 CFR 245.7310-8 - Antitrust clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Antitrust clearance. 245.7310-8 Section 245.7310-8 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... Antitrust clearance. When property with an acquisition cost of $3 million or more is to be sold, include...

  3. 30 CFR 77.514 - Switchboards; passageways and clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Switchboards; passageways and clearance. 77.514 Section 77.514 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE... COAL MINES Electrical Equipment-General § 77.514 Switchboards; passageways and clearance....

  4. 14 CFR 93.311 - Minimum terrain clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Minimum terrain clearance. 93.311 Section 93.311 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... of Grand Canyon National Park, AZ § 93.311 Minimum terrain clearance. Except in an emergency,...

  5. 33 CFR 160.115 - Withholding of clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Withholding of clearance. 160.115... § 160.115 Withholding of clearance. Each District Commander or Captain of the Port may request the Secretary of the Treasury, or the authorized representative thereof, to withhold or revoke the...

  6. 7 CFR 1927.55 - Title clearance services.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 12 2012-01-01 2012-01-01 false Title clearance services. 1927.55 Section 1927.55 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE SERVICE, RURAL UTILITIES SERVICE, AND FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE PROGRAM REGULATIONS TITLE CLEARANCE AND...

  7. 32 CFR 644.69 - Title Clearance-Easements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 4 2014-07-01 2013-07-01 true Title Clearance-Easements. 644.69 Section 644.69 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Acquisition Procurement of Title Evidence, Title Clearance, and Closings § 644.69 Title Clearance—Easements. (a)...

  8. 32 CFR 644.69 - Title Clearance-Easements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 4 2012-07-01 2011-07-01 true Title Clearance-Easements. 644.69 Section 644.69 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Acquisition Procurement of Title Evidence, Title Clearance, and Closings § 644.69 Title Clearance—Easements. (a)...

  9. 32 CFR 644.69 - Title Clearance-Easements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 4 2013-07-01 2013-07-01 false Title Clearance-Easements. 644.69 Section 644.69 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Acquisition Procurement of Title Evidence, Title Clearance, and Closings § 644.69 Title Clearance—Easements. (a)...

  10. 7 CFR 1927.55 - Title clearance services.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 12 2014-01-01 2013-01-01 true Title clearance services. 1927.55 Section 1927.55 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE SERVICE, RURAL UTILITIES SERVICE, AND FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE PROGRAM REGULATIONS TITLE CLEARANCE AND...

  11. 32 CFR 644.521 - Limitations on clearance cost.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Limitations on clearance cost. 644.521 Section 644.521 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from...

  12. 32 CFR 644.522 - Clearance of military scrap.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of military scrap. 644.522 Section 644.522 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from...

  13. 32 CFR 644.521 - Limitations on clearance cost.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 4 2011-07-01 2011-07-01 false Limitations on clearance cost. 644.521 Section 644.521 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from...

  14. 32 CFR 644.522 - Clearance of military scrap.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 4 2011-07-01 2011-07-01 false Clearance of military scrap. 644.522 Section 644.522 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from...

  15. 32 CFR 644.527 - Recording Statements of Clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Recording Statements of Clearance. 644.527 Section 644.527 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from...

  16. 32 CFR 644.527 - Recording Statements of Clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 4 2011-07-01 2011-07-01 false Recording Statements of Clearance. 644.527 Section 644.527 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from...

  17. Allometric scaling for predicting human clearance of bisphenol A

    SciTech Connect

    Collet, Séverine H. Picard-Hagen, Nicole Lacroix, Marlène Z. Puel, Sylvie Viguié, Catherine Bousquet-Melou, Alain Toutain, Pierre-Louis Gayrard, Véronique

    2015-05-01

    The investigation of interspecies differences in bisphenol A (BPA) pharmacokinetics (PK) may be useful for translating findings from animal studies to humans, identifying major processes involved in BPA clearance mechanisms, and predicting BPA PK parameters in man. For the first time, a large range of species in terms of body weight, from 0.02 kg (mice) to 495 kg (horses) was used to predict BPA clearance in man by an allometric approach. BPA PK was evaluated after intravenous administration of BPA in horses, sheep, pigs, dogs, rats and mice. A non-compartmental analysis was used to estimate plasma clearance and steady state volume of distribution and predict BPA PK parameters in humans from allometric scaling. In all the species investigated, BPA plasma clearance was high and of the same order of magnitude as their respective hepatic blood flow. By an allometric scaling, the human clearance was estimated to be 1.79 L/min (equivalent to 25.6 mL/kg.min) with a 95% prediction interval of 0.36 to 8.83 L/min. Our results support the hypothesis that there are highly efficient and hepatic mechanisms of BPA clearance in man. - Highlights: • Allometric scaling was used to predict BPA pharmacokinetic parameters in humans. • In all species, BPA plasma clearance approached hepatic blood flow. • Human BPA clearance was estimated to be 1.79 L/min.

  18. 33 CFR 151.1508 - Revocation of clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Revocation of clearance. 151.1508 Section 151.1508 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... River § 151.1508 Revocation of clearance. A COTP may request the District Director of Customs...

  19. 32 CFR 644.516 - Clearance of Air Force lands.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 4 2012-07-01 2011-07-01 true Clearance of Air Force lands. 644.516 Section 644... Excess Land and Improvements § 644.516 Clearance of Air Force lands. The Chief of Engineers has no responsibility for inspecting or clearing excess Air Force land of explosives or chemical/biological...

  20. 32 CFR 644.516 - Clearance of Air Force lands.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 4 2014-07-01 2013-07-01 true Clearance of Air Force lands. 644.516 Section 644... Excess Land and Improvements § 644.516 Clearance of Air Force lands. The Chief of Engineers has no responsibility for inspecting or clearing excess Air Force land of explosives or chemical/biological...

  1. 32 CFR 644.516 - Clearance of Air Force lands.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 4 2013-07-01 2013-07-01 false Clearance of Air Force lands. 644.516 Section... Excess Land and Improvements § 644.516 Clearance of Air Force lands. The Chief of Engineers has no responsibility for inspecting or clearing excess Air Force land of explosives or chemical/biological...

  2. 32 CFR 644.516 - Clearance of Air Force lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 4 2011-07-01 2011-07-01 false Clearance of Air Force lands. 644.516 Section... Excess Land and Improvements § 644.516 Clearance of Air Force lands. The Chief of Engineers has no responsibility for inspecting or clearing excess Air Force land of explosives or chemical/biological...

  3. 32 CFR 644.522 - Clearance of military scrap.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 4 2013-07-01 2013-07-01 false Clearance of military scrap. 644.522 Section 644... Excess Land and Improvements § 644.522 Clearance of military scrap. Military scrap can contain or be... destruction, by using command, of all military scrap and scrap metal from lands suitable for cultivation...

  4. 32 CFR 644.522 - Clearance of military scrap.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 4 2012-07-01 2011-07-01 true Clearance of military scrap. 644.522 Section 644... Excess Land and Improvements § 644.522 Clearance of military scrap. Military scrap can contain or be... destruction, by using command, of all military scrap and scrap metal from lands suitable for cultivation...

  5. 32 CFR 644.522 - Clearance of military scrap.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 4 2014-07-01 2013-07-01 true Clearance of military scrap. 644.522 Section 644... Excess Land and Improvements § 644.522 Clearance of military scrap. Military scrap can contain or be... destruction, by using command, of all military scrap and scrap metal from lands suitable for cultivation...

  6. 48 CFR 952.204-73 - Facility clearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ....204-73 Section 952.204-73 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... granted by the Secretary of Energy. In addition, a Facility Clearance and foreign ownership, control and... Department of Energy Facility Clearance generally need not resubmit the following foreign...

  7. 32 CFR 644.516 - Clearance of Air Force lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of Air Force lands. 644.516 Section 644... Excess Land and Improvements § 644.516 Clearance of Air Force lands. The Chief of Engineers has no responsibility for inspecting or clearing excess Air Force land of explosives or chemical/biological...

  8. 48 CFR 32.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance...

  9. 48 CFR 32.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance...

  10. 48 CFR 1432.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to...

  11. 48 CFR 1432.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to...

  12. 48 CFR 832.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking...

  13. 48 CFR 832.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking...

  14. 48 CFR 1432.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to...

  15. 48 CFR 832.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking...

  16. 48 CFR 32.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance...

  17. 48 CFR 32.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance...

  18. 48 CFR 832.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking...

  19. 48 CFR 1432.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to...

  20. 48 CFR 32.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance...

  1. 48 CFR 832.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking...

  2. 48 CFR 1432.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to...

  3. Is the new GFR equation using inulin clearance a more accurate method for Asian patients?

    PubMed

    Kim, Beom Seok; Lee, Yong Kyu; Choi, Hoon Young; Choi, Seung Ok; Shin, Sug Kyun; Ha, Sung Kyu; Lee, Kang Wook; Kim, Yang Wook; Kim, Yong Lim; Yasuda, Yoshinari; Imai, Enyu; Horio, Masaru; Tomino, Yasuhiko; Matsuo, Seiichi; Lee, Ho Yung

    2015-12-01

    Recently, a new glomerular filtration rate (GFR) equation for the Japanese population was proposed using measured inulin clearance. To expand its applicability to other Asian populations, we performed a comparative study in the Korean population. Inulin clearance was measured in 166 patients from seven participating medical centers in Korea. Patient's sera and urine were collected, and baseline clinical characteristics were measured to provide an estimated GFR (eGFR) by the Japanese GFR equation using inulin clearance (Japanese-GFR equation), the Modification of Diet in Renal Disease (MDRD) study equation, and the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) equation. We compared the results to determine which equation best estimated the measured GFR (mGFR). Accuracy (95% CI) within 30% of mGFR by the Japanese-GFR equation, the CKD-EPI equation and the MDRD study equation were 66 (58 - 72), 51 (43 - 58), and 55 (47 - 62)%, respectively. Bias (mGFR minus eGFR) were 3.4 ± 22.4, -12.0 ± 22.1, and -9.7 ± 23.8 mL/min/1.73 m2, respectively. The accuracy of the Japanese-GFR equation was significantly better than MDRD study equation in subjects with mGFR < 60 mL/min/1.73 m2 and in total subjects. The bias of the Japanese-GFR equation was significantly smaller compared with other two equations in total subjects. The Japanese-GFR equation has a higher accuracy with less bias than the other equations in estimating GFR in Korean populations. Further studies are required to determine if the current Japanese-GFR equation could represent the standard eGFR for other Asian populations.

  4. Loss of Lrp2 in zebrafish disrupts pronephric tubular clearance but not forebrain development

    PubMed Central

    Kur, Esther; Christa, Anna; Veth, Kerry N.; Gajera, Chandresh R.; Andrade-Navarro, Miguel A.; Zhang, Jingjing; Willer, Jason R.; Gregg, Ronald G.; Abdelilah-Seyfried, Salim; Bachmann, Sebastian; Link, Brian A.; Hammes, Annette; Willnow, Thomas E.

    2012-01-01

    Low-density lipoprotein receptor-related protein 2 (LRP2) is a multifunctional cell surface receptor conserved from nematodes to humans. In mammals, it acts as regulator of sonic hedgehog and bone morphogenetic protein pathways in patterning of the embryonic forebrain and as a clearance receptor in the adult kidney. Little is known about activities of this LRP in other phyla. Here, we extend the functional elucidation of LRP2 to zebrafish as model organism of receptor (dys)function. We demonstrate that expression of Lrp2 in embryonic and larval fish recapitulates the patterns seen in mammalian brain and kidney. Furthermore, we studied the consequence of receptor deficiencies in lrp2 and in lrp2b, a homologue unique to fish, using ENU mutagenesis or morpholino knockdown. While receptor-deficient zebrafish suffer from overt renal resorption deficiency, their brain development proceeds normally, suggesting evolutionary conservation of receptor functions in pronephric duct clearance but not in patterning of the teleost forebrain. PMID:21455927

  5. Atheroembolic renal disease.

    PubMed

    Scolari, Francesco; Ravani, Pietro

    2010-05-08

    Atheroembolic renal disease develops when atheromatous aortic plaques rupture, releasing cholesterol crystals into the small renal arteries. Embolisation often affects other organs, such as the skin, gastrointestinal system, and brain. Although the disease can develop spontaneously, it usually develops after vascular surgery, catheterisation, or anticoagulation. The systemic nature of atheroembolism makes diagnosis difficult. The classic triad of a precipitating event, acute or subacute renal failure, and skin lesions, are strongly suggestive of the disorder. Eosinophilia further supports the diagnosis, usually confirmed by biopsy of an affected organ or by the fundoscopic finding of cholesterol crystals in the retinal circulation. Renal and patient prognosis are poor. Treatment is mostly preventive, based on avoidance of further precipitating factors, and symptomatic, aimed to the optimum treatment of hypertension and cardiac and renal failure. Statins, which stabilise atherosclerotic plaques, should be offered to all patients. Steroids might have a role in acute or subacute progressive forms with systemic inflammation.

  6. [Sarcoidosis : Renal manifestations].

    PubMed

    Löffler, C; Bergner, R

    2017-04-12

    Renal involvement in sarcoidosis is much more common than generally assumed from old epidemiological studies and is often only detected when actively searched for. Many patients with renal sarcoidosis present with no or only few symptoms. The diagnostic work-up of sarcoidosis should always include a possible renal involvement. In cases of impaired renal function, proteinuria or a pathological urine sediment, a renal biopsy specimen should be obtained to assess the type, severity and prognosis of the kidney disease. Treatment is primarily based on the use of corticosteroids. Steroid-sparing agents, such as disease-modifying antirheumatic drugs and infliximab can be applied; however, the evidence for efficacy of these therapies is mostly based on case series and expert opinions. Discontinuation of immunosuppression therapy bears a high risk of relapse.

  7. Comparison of serum iohexol clearance and plasma creatinine clearance in clinically normal horses.

    PubMed

    Wilson, Katherine E; Wilcke, Jeff R; Crisman, Mark V; Ward, Daniel L; McKenzie, Harold C; Scarratt, W Kent

    2009-12-01

    Objective-To determine whether a limited sampling time method based on serum iohexol clearance (Cl(iohexol)) would yield estimates of glomerular filtration rate (GFR) in clinically normal horses similar to those for plasma creatinine clearance (Cl(creatinine)). Animals-10 clinically normal adult horses. Procedures-A bolus of iohexol (150 mg/kg) was administered IV, and serum samples were obtained 5, 20, 40, 60, 120, 240, and 360 minutes after injection. Urinary clearance of exogenous creatinine was measured during three 20-minute periods. The GFR determined by use of serum Cl(iohexol) and plasma Cl(creatinine) was compared with limits of agreement plots. Results-Values obtained for plasma Cl(creatinine) ranged from 1.68 to 2.69 mL/min/kg (mean, 2.11 mL/min/kg). Mean serum Cl(iohexol) was 2.38 mL/min/kg (range, 1.95 to 3.33 mL/min/kg). Limits of agreement plots indicated good agreement between the methods. Conclusions and Clinical Relevance-Use of serum Cl(iohexol) yielded estimates of GFR in clinically normal adult horses similar to those for plasma Cl(creatinine). This study was the first step in the evaluation of the use of serum Cl(iohexol) for estimating GFR in adult horses.

  8. sup 99m Tc renal tubular function agents: Current status

    SciTech Connect

    Eshima, D.; Fritzberg, A.R.; Taylor, A. Jr. )

    1990-01-01

    Orthoiodohippuric (OIH) acid labeled with 131I is a widely used renal radiopharmaceutical agent and has been the standard radiopharmaceutical agent for the measurement of effective renal plasma flow (EPRF). Limitations to the routine clinical use of 131I OIH are related to the suboptimal imaging properties of the 131I radionuclide and its relatively high radiation dose. 123I has been substituted for 131I; however, its high cost and short shelf-life have limited its widespread use. Recent work has centered on the development of a new 99mTc renal tubular function agent, which would use the optimal radionuclidic properties and availability of 99mTc and combine the clinical information provided by OIH. The search for a suitable 99mTc renal tubular function agent has focused on the diamide dithiolate (N2S2), the paraaminohippuric iminodiacetic acid (PAHIDA), and the triamide mercaptide (N3S) donor ligand systems. To date, the most promising 99mTc tubular function agent is the N3S complex: 99mTc mercaptoacetyltriglycine (99mTc MAG3). Studies in animal models in diuresis, dehydration, acid or base imbalance, ischemia, and renal artery stenosis demonstrate that 99mTc MAG3 behaves similarly to 131I OIH. A simple kit formulation is available that yields the 99mTc MAG3 complex in high radiochemical purity. Studies in normal subjects and patients indicate that 99mTc MAG3 is an excellent 99mTc renal tubular agent, but its plasma clearance is only 50% to 60% that of OIH. In an effort to develop an improved 99mTc renal tubular function agent, changes have been made in the core N3S donor ligand system, but to date no agent has been synthesized that is clinically superior to 99mTc MAG3. 61 references.

  9. A model of clearance rate regulation in mussels

    NASA Astrophysics Data System (ADS)

    Fréchette, Marcel

    2012-10-01

    Clearance rate regulation has been modelled as an instantaneous response to food availability, independent of the internal state of the animals. This view is incompatible with latent effects during ontogeny and phenotypic flexibility in clearance rate. Internal-state regulation of clearance rate is required to account for these patterns. Here I develop a model of internal-state based regulation of clearance rate. External factors such as suspended sediments are included in the model. To assess the relative merits of instantaneous regulation and internal-state regulation, I modelled blue mussel clearance rate and growth using a DEB model. In the usual standard feeding module, feeding is governed by a Holling's Type II response to food concentration. In the internal-state feeding module, gill ciliary activity and thus clearance rate are driven by internal reserve level. Factors such as suspended sediments were not included in the simulations. The two feeding modules were compared on the basis of their ability to capture the impact of latent effects, of environmental heterogeneity in food abundance and of physiological flexibility on clearance rate and individual growth. The Holling feeding module was unable to capture the effect of any of these sources of variability. In contrast, the internal-state feeding module did so without any modification or ad hoc calibration. Latent effects, however, appeared transient. With simple annual variability in temperature and food concentration, the relationship between clearance rate and food availability predicted by the internal-state feeding module was quite similar to that observed in Norwegian fjords. I conclude that in contrast with the usual Holling feeding module, internal-state regulation of clearance rate is consistent with well-documented growth and clearance rate patterns.

  10. Pharmacokinetics of serelaxin in patients with severe renal impairment or end-stage renal disease requiring hemodialysis: A single-dose, open-label, parallel-group study.

    PubMed

    Dahlke, Marion; Halabi, Atef; Canadi, Jasna; Tsubouchi, Chiaki; Machineni, Surendra; Pang, Yinuo

    2016-04-01

    Serelaxin, a recombinant human relaxin-2 hormone, is in clinical development for treating acute heart failure. This open-label, parallel-group study investigated serelaxin pharmacokinetics (PK) after a single 4-hour intravenous infusion (10 µg/kg) in patients with severe renal impairment (n = 6) or end-stage renal disease (ESRD) requiring hemodialysis (PK on the day of dialysis [n = 6] or during dialysis-free interval [n = 6]), compared with matched healthy subjects (n = 18). In all participants, serum serelaxin concentration peaked at the end of infusion and subsequently declined with mean terminal elimination half-life of 6.5-8.8 hours. Compared with healthy subjects, a moderate decrease in serelaxin systemic clearance (37%-52%) and increase in its exposure (30%-115%) were observed in all patients. During the 4-hour hemodialysis in ESRD patients, 30% serelaxin was removed, with hemodialysis clearance constituting approximately 52% of total systemic clearance. Serelaxin was well tolerated with no deaths, serious adverse events (AE), or AE-related discontinuations. Antiserelaxin antibodies were not detected in any participant. Given the shallow dose-response relationship observed with serelaxin in clinical studies and its wide therapeutic window, the observed PK differences in patients with severe renal impairment compared with healthy subjects are unlikely to pose a safety risk and do not warrant a predefined dosage adjustment in such patients.

  11. Relationships between Serum Levels of Atazanavir and Renal Toxicity or Lithiasis.

    PubMed

    Marinescu, C I; Leyes, M; Ribas, M A; Peñaranda, M; Murillas, J; Campins, A A; Martin-Pena, L; Barcelo, B; Barceló-Campomar, C; Grases, F; Frontera, G; Riera Jaume, Melchor

    2015-01-01

    The main aim of this study is to describe the relationship between serum levels of atazanavir, renal toxicity, and lithiasis. This is a prospective observational study of patients being treated with atazanavir (ATV) at Son Espases Teaching Hospital, Palma de Mallorca, between 2011 and 2013. The study includes 98 patients. Sixteen were found to have a history of urolithiasis. During a median monitoring period of 23 months, nine patients suffered renal colic, in three of whom ATV crystals were evidenced in urine. Cumulative incidence of renal colic was 9.2 per 100 patients. The variables related to having renal colic were the presence of alkaline urine pH and lower basal creatinine clearance. The mean serum level of ATV was slightly higher in patients with renal colic-1,303 μg/L versus 1,161 μg/L-but did not reach statistical significance. Neither were any significant differences detected by analysing the levels according to the timetable for ATV dosage. Cumulative incidence of renal colic was high in patients being treated with ATV, in 33% of whom the presence of ATV crystals was evidenced in urine. We were unable to demonstrate a relationship between ATV serum levels and renal colic or progression towards renal failure.

  12. Relationships between Serum Levels of Atazanavir and Renal Toxicity or Lithiasis

    PubMed Central

    Marinescu, C. I.; Leyes, M.; Ribas, M. A.; Peñaranda, M.; Murillas, J.; Campins, A. A.; Martin-Pena, L.; Barcelo, B.; Barceló-Campomar, C.; Grases, F.; Frontera, G.; Riera Jaume, Melchor

    2015-01-01

    The main aim of this study is to describe the relationship between serum levels of atazanavir, renal toxicity, and lithiasis. This is a prospective observational study of patients being treated with atazanavir (ATV) at Son Espases Teaching Hospital, Palma de Mallorca, between 2011 and 2013. The study includes 98 patients. Sixteen were found to have a history of urolithiasis. During a median monitoring period of 23 months, nine patients suffered renal colic, in three of whom ATV crystals were evidenced in urine. Cumulative incidence of renal colic was 9.2 per 100 patients. The variables related to having renal colic were the presence of alkaline urine pH and lower basal creatinine clearance. The mean serum level of ATV was slightly higher in patients with renal colic—1,303 μg/L versus 1,161 μg/L—but did not reach statistical significance. Neither were any significant differences detected by analysing the levels according to the timetable for ATV dosage. Cumulative incidence of renal colic was high in patients being treated with ATV, in 33% of whom the presence of ATV crystals was evidenced in urine. We were unable to demonstrate a relationship between ATV serum levels and renal colic or progression towards renal failure. PMID:26064679

  13. Effect of carotid occlusion and of perfusion pressure on renal function in conscious dogs.

    PubMed

    Gross, R; Kirchheim, H; Ruffmann, K

    1981-06-01

    We studied the effect of bilateral common carotid occlusion (implanted pneumatic cuffs) on renal blood flow (electromagnetic flowmeter) and renal function (implanted ureteral catheter) in nine chronically instrumented, conscious dogs on a high sodium diet (14 mmol/kg body weight per day). By means of suprarenal aortic constriction (pneumatic cuff) the influence of renal perfusion pressure was investigated. There was no change in renal blood flow or glomerular filtration rate (inulin clearance) with either reflexly increasing (+49.6%) or constant renal perfusion pressure. Carotid occlusion caused an increase of urine output by 80.5% and of sodium excretion by 85.3% due to a fall in fractional sodium reabsorption (-0.9%) when renal perfusion pressure was allowed to rise. Neither an increase of diuresis or sodium excretion nor an antinatriuresis was observed when renal perfusion pressure was kept constant during carotid occlusion. We conclude that, in conscious dogs at rest, the moderate sympathetic activation associated with carotid occlusion is too small to induce renal sympathetic vasoconstriction or antinatriuresis. The "carotid sinus polyuria" is a pressure-diuresis.

  14. Obesity triggers enhanced MDSC accumulation in murine renal tumors via elevated local production of CCL2.

    PubMed

    Hale, Malika; Itani, Farah; Buchta, Claire M; Wald, Gal; Bing, Megan; Norian, Lyse A

    2015-01-01

    Obesity is one of the leading risk factors for developing renal cell carcinoma, an immunogenic tumor that is treated clinically with immunostimulatory therapies. Currently, however, the mechanisms linking obesity with renal cancer incidence are unclear. Using a model of diet-induced obesity, we found that obese BALB/c mice with orthotopic renal tumors had increased total frequencies of myeloid-derived suppressor cells (MDSC) in renal tumors and spleens by d14 post-tumor challenge, relative to lean counterparts. Renal tumors from obese mice had elevated concentrations of the known myeloid cell chemoattractant CCL2, which was produced locally by increased percentages of dendritic cells, macrophages, B cells, and CD45- cells in tumors. MDSC expression of the CCL2 receptor, CCR2, was unaltered by obesity but greater percentages of CCR2+ MDSCs were present in renal tumors from obese mice. Of note, the intracellular arginase levels and per-cell suppressive capacities of tumor-infiltrating and splenic MDSCs were unchanged in obese mice relative to lean controls. Thus, our findings suggest that obesity promotes renal tumor progression via development of a robust immunosuppressive environment that is characterized by heightened local and systemic MDSC prevalence. Targeted intervention of the CCL2/CCR2 pathway may facilitate immune-mediated renal tumor clearance in the obese.

  15. Elevated systemic elimination of cimetidine in rats with acute biliary obstruction: the role of renal organic cation transporter OCT2.

    PubMed

    Kurata, Tomohiko; Muraki, Yuichi; Mizutani, Hideki; Iwamoto, Takuya; Okuda, Masahiro

    2010-01-01

    Renal tubular secretion of cationic drugs is dominated by two classes of organic cation transporters, OCT2/SLC22A2 and MATE1/SLC47A1, localized to the basolateral and brush-border membranes of the renal tubular epithelial cells, respectively. However, little is known about the expression and function of these transporters in acute cholestasis. Systemic clearance of cimetidine was significantly higher in rats with bile duct ligation (BDL) for 24 hours than in sham-operated rats, with no significant changes in the volume of distribution between the groups. In addition, net tubular secretory clearance of cimetidine was significantly higher in the BDL rats compared with the sham rats, with no significant changes in the glomerular filtration rate. Moreover, the renal tissue-to-plasma concentration ratio of cimetidine was elevated in BDL rats, although the renal tissue-to-urine clearance ratio of cimetidine was not different between the two groups. The expression level of basolateral organic cation transporter rOCT2 protein in the kidney cortex was markedly higher in BDL rats than that in the sham rats, but that of H+/organic cation antiporter rMATE1 protein in the brush-border membranes was not significantly different between the two groups. These results demonstrate that the renal tubular secretion of cimetidine was increased by acute cholestasis, and this increase was attributable to elevated expression levels of rOCT2 but not of rMATE1 in the rat.

  16. An Overview of Advanced Concepts for Launch

    DTIC Science & Technology

    2012-02-09

    public release; distribution unlimited. PA Clearance Number XXXXX 22 Ideal Process LCA LMS Practical Process LTF None Net? Clear nCA nMS nTF...Advanced Propellants Concept Description Pros Eval. Cons Lithium-Fluorine-Hydrogen LCA LMS LTF nCA nMS nTF m TIsp ∝ •Low m usually low ρ...Air Breathing Concepts Concept Description Pros Eval. Cons X-51 WaveRider LCA LMS LTF nCA nMS nTF mox >> mpay •Multiple modes required

  17. Urinary neutrophil gelatinase-associated lipocalin is a potential biomarker for renal damage in patients with systemic lupus erythematosus.

    PubMed

    Yang, Chun-Chen; Hsieh, Song-Chou; Li, Ko-Jen; Wu, Cheng-Han; Lu, Ming-Chi; Tsai, Chang-Youh; Yu, Chia-Li

    2012-01-01

    Neutrophil gelatinase-associated lipocalin (NGAL) has been demonstrated to be a novel biomarker in acute and chronic kidney disease. We hypothesized that 24-hour urinary NGAL excretion may be a predictor for renal damage in patients with systemic lupus erythematosus (SLE). Thirty-four SLE patients with renal involvement (SLE-renal group), 8 SLE patients without renal involvement (SLE-nonrenal group), 14 patients with non-SLE autoimmune diseases (disease control or DC group), and 12 healthy volunteers (normal control or NC group) were compared for 24-hour urinary excretion of NGAL and different cytokines. We found that the 24-hour urinary NGAL excretion in the SLE-renal group was higher than that in the SLE-non-renal, DC, and NC groups. However, the excretion of interleukin-10, transforming growth factor-β1, and tumor necrosis factor-α was not different between the SLE-renal and SLE-non-renal groups. Furthermore, NGAL excretion in the SLE-renal group was correlated with serum creatinine levels and creatinine clearance, but not with the SLE Disease Activity Index score. Multivariate logistic regression analysis and receiver operating characteristic curve analysis revealed that 24-hour urinary NGAL excretion is a potential biomarker for renal damage in SLE patients, with higher sensitivity and specificity than anti-dsDNA antibody titers.

  18. Endotoxaemia and renal failure in cirrhosis and obstructive jaundice.

    PubMed Central

    Wilkinson, S P; Moodie, H; Stamatakis, J D; Kakkar, V V; Williams, R

    1976-01-01

    An investigation into the possible role of endotoxins in the pathogenesis of renal failure in cirrhosis and obstructive jaundice showed the two to be closely related. None of the patients with cirrhosis who had endotoxaemia had other evidence of Gram-negative infection at the time of the study, and the endotoxaemia was therefore probably due to impaired hepatic clearance of toxins normally absorbed from the gastrointestinal tract. In contrast, bacteriological evidence of Gram-negative infection was found in most of the patients with obstructive jaundice and endotoxaemia. PMID:795499

  19. Role of megalin and cubilin in renal physiology and pathophysiology.

    PubMed

    Christensen, E I; Nielsen, R

    2007-01-01

    Megalin and cubilin are endocytic receptors highly expressed in the endocytic apparatus of the renal proximal tubule. These receptors appear to be responsible for the tubular clearance of most proteins filtered in the glomeruli. Cubilin is a peripheral membrane protein, and therefore it does not have an endocytosis signaling sequence. It appears that megalin is responsible for internalization of cubilin and its ligands in addition to internalizing its own ligands. The proteinuria observed in megalin-deficient mice, in dogs lacking functional cubilin, and in patients with distinct mutations of the cubilin gene illustrates the importance of the receptors.

  20. Predictive factors for renal failure and a control and treatment algorithm

    PubMed Central

    Cerqueira, Denise de Paula; Tavares, José Roberto; Machado, Regimar Carla

    2014-01-01

    Objectives to evaluate the renal function of patients in an intensive care unit, to identify the predisposing factors for the development of renal failure, and to develop an algorithm to help in the control of the disease. Method exploratory, descriptive, prospective study with a quantitative approach. Results a total of 30 patients (75.0%) were diagnosed with kidney failure and the main factors associated with this disease were: advanced age, systemic arterial hypertension, diabetes mellitus, lung diseases, and antibiotic use. Of these, 23 patients (76.6%) showed a reduction in creatinine clearance in the first 24 hours of hospitalization. Conclusion a decline in renal function was observed in a significant number of subjects, therefore, an algorithm was developed with the aim of helping in the control of renal failure in a practical and functional way. PMID:26107827