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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. 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…

  3. Augmented renal clearance and therapeutic monitoring of β-lactams.

    PubMed

    Udy, Andrew A; De Waele, Jan J; Lipman, Jeffrey

    2015-04-01

    Successful application of antibacterial therapy in the critically ill requires an appreciation of the complex interaction between the host, the causative pathogen and the chosen pharmaceutical. A pathophysiological change in the intensive care unit (ICU) patient challenging the 'one dose fits all' concept includes augmented renal clearance (ARC), defined as a creatinine clearance (CL(Cr)) of ≥130 mL/min. Ideally, CL(Cr) values should be obtained by a timed measured collection of urine, with plasma and urine creatinine levels. Increased renal clearance of antibiotics also occurs in the ICU patient and therefore β-lactam antibiotic exposure in the critically ill could easily lead to trough drug concentrations below therapeutic ranges. One way to document and alter drug levels is via therapeutic drug monitoring (TDM). The interactions of ARC and β-lactam TDM are further explored in this article in specific reference to a concomitant article in this issue of the journal. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  4. [A renal function analysis using computed tomography. CT clearance versus 131I-hippuran clearance].

    PubMed

    Kaltenborn, H; Klose, K

    1992-06-01

    The CT clearance in a number of urological patients (39 patients, 25 with normal renal function) was studied by means of an "area under curve" (AUC) method, using a region of interest. 31 patients were given meglumine ioxithalamate and 8 patients Iopamidol as a contrast medium. Both for total and partial function there was highly significant correlation with isotope clearance with good reproducibility. The difference in the pharmacokinetics of the contrast media affected the absolute clearance values.

  5. 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.

  6. 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.

  7. 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.

  8. Augmented Renal Clearance in Pediatric Patients With Febrile Neutropenia Associated With Vancomycin Clearance.

    PubMed

    Hirai, Keita; Ihara, Setsuko; Kinae, Ayumi; Ikegaya, Kenichi; Suzuki, Masayuki; Hirano, Keiko; Itoh, Kunihiko

    2016-06-01

    Vancomycin (VCM) dosage optimization in the early stages of therapy is required to achieve target trough serum concentrations, particularly in critically ill patients. Augmented renal clearance (ARC), commonly characterized by an enhanced renal clearance, has been associated with subtherapeutic concentrations of antibiotics. The aim of this study was to investigate the risk factors including febrile neutropenia for both ARC and VCM clearance in Japanese pediatric patients. A total of 109 pediatric patients with normal renal function were included in this observational study. From VCM serum concentrations, individual VCM clearance was estimated by the Bayesian method using a 1-compartment model. Patients were classified on the basis of the presence of febrile neutropenia, cancer, trauma, systemic inflammatory response syndrome, and surgical operation. Risk factors for ARC, as defined by estimated glomerular filtration rate (eGFR) above median value (≥160 mL·min·1.73 m), were evaluated. Febrile neutropenia was only an independent risk factor for ARC (odds ratio, 5.86; 95% confidence interval, 1.98-21.66, P = 0.0030), which was the result of a stepwise multivariate logistic regression analysis. Although univariate analysis demonstrated a significant association of febrile neutropenia with VCM clearance, the significant independent factors of VCM clearance were age and eGFR but not febrile neutropenia, as estimated by the stepwise multivariate linear regression analysis. This observational study concluded that febrile neutropenia, a significant risk factor for ARC, indirectly influenced VCM clearance towing to an elevated eGFR. Cancer, trauma, systemic inflammatory response syndrome, and surgical operation were not significantly associated with ARC; however, more studies are needed to validate this observation. Adjustment of the initial dosage of VCM is required for achieving optimal therapeutic concentrations in pediatric patients with febrile neutropenia.

  9. Increasing Haemodialytic Clearances as Residual Renal Function Declines: An Incremental Approach.

    PubMed

    Tangvoraphonkchai, Kamonwan; Davenport, Andrew

    2017-08-16

    Many patients with chronic kidney disease start undergoing thrice-weekly haemodialysis (HD), aiming for an HD sessional dialyzer urea clearance target, irrespective of whether they have residual renal function (RRF). While increasing sessional dialyzer urea clearance above a target of 1.2 has not been shown to improve patient survival, it has been shown that the preservation of RRF improves patient self-reported outcomes and survival. Observational studies have suggested that initiating twice-weekly HD schedules leads to greater preservation of RRF. This has led to the concept of following an incremental approach to initiating HD, steadily increasing the amount of weekly dialyzer clearance as RRF decreases. Incremental dialysis practice requires the regular assessment of RRF to prevent inadequate delivery of dialysis treatment. Once RRF is lost, then the dialysis schedule and modality need to be adjusted to try to increase the middle-sized solute clearance and protein-bound toxins. © 2017 S. Karger AG, Basel.

  10. Simple sampling strategy for measuring inulin renal clearance.

    PubMed

    Horio, Masaru; Imai, Enyu; Yasuda, Yoshinari; Hishida, Akira; Matsuo, Seiichi

    2009-02-01

    In the standard method of inulin clearance (Cin), three sets of serum and urine samples are collected during a 2-hour clearance period. For a practical use of this method, sampling should be the minimal number allowable while still providing enough accuracy. The aim of this study was to evaluate the validity of inulin renal clearance with assumed single urine collection with a period such as 30, 60 or 90 minutes. Inulin clearance data collected by the standard method from 737 individuals were used. Changes of serum inulin concentrations between 45 and 105 minutes after the start of the infusion were analyzed. We used first urine collection to calculate the inulin clearance with single urine collection (Cin-30 min). We assumed single urine collection for 60 or 90 minutes by combining the urine data of the consecutive 30-minute periods. Inulin clearances (Cin-60 min, Cin-90 min) were calculated from the assumed single urine collections, respectively. Serum inulin concentration did not reach equilibrium during the clearance period. It increased in subjects with low glomerular filtration rate (GFR) and decreased in subjects with normal GFR. The amount of the change was small and -0.5 +/- 12.6% in subjects with GFR over 30 ml/min per 1.73 m(2). Cin-30 min, Cin-60 min and Cin-90 min showed high correlation coefficients against Cin-ST (0.962, 0.988 and 0.998, respectively). Systemic biases in these clearances were negligible (under 1 ml/min per 1.73 m(2)). Root mean square error (RMSE) were 10.4, 5.3 and 2.3 ml/min per 1.73 m(2) for Cin-30 min, Cin-60 min and Cin-90 min, respectively. These data indicated that accuracy of inulin clearance depends on the duration of the urine collection period. Inulin clearance with a single urine collection is a convenient method. We showed that single urine collection for 30 minutes or a longer period has reasonable accuracy in calculation of inulin clearance. We propose a method of inulin clearance with single urine collection for 60

  11. A Porphyrin-PEG Polymer with Rapid Renal Clearance

    PubMed Central

    Huang, Haoyuan; Hernandez, Reinier; Geng, Jumin; Sun, Haotian; Song, Wentao; Chen, Feng; Graves, Stephen A; Nickles, Robert J.; Cheng, Chong; Cai, Weibo; Lovell, Jonathan F.

    2015-01-01

    Tetracarboxylic porphyrins and polyethylene glycol (PEG) diamines were crosslinked in conditions that gave rise to a water-soluble porphyrin polyamide. Using PEG linkers 2 kDa or larger prevented fluorescence self-quenching. This networked porphyrin mesh was retained during dialysis with membranes with a 100 kDa pore size, yet passed through the membrane when centrifugal filtration was applied. Following intravenous administration, the porphyrin mesh, but not the free porphyrin, was rapidly cleared via renal excretion. The process could be monitored by fluorescence analysis of collected urine, with minimal background due to the large Stokes shift of the porphyrin (230 nm separating excitation and emission peaks). In a rhabdomyolysis mouse model of renal failure, porphyrin mesh urinary clearance was significantly impaired. This led to slower accumulation in the bladder, which could be visualized non-invasively via fluorescence imaging. Without further modification, the porphyrin mesh was chelated with 64Cu for dynamic whole body positron emission tomography imaging of renal clearance. Together, these data show that small porphyrin-PEG polymers can serve as effective multimodal markers of renal function. PMID:26517562

  12. 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.

  13. 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.

  14. Physiological stability and renal clearance of ultrasmall zwitterionic gold nanoparticles: Ligand length matters

    NASA Astrophysics Data System (ADS)

    Ning, Xuhui; Peng, Chuanqi; Li, Eric S.; Xu, Jing; Vinluan, Rodrigo D.; Yu, Mengxiao; Zheng, Jie

    2017-05-01

    Efficient renal clearance has been observed from ultrasmall zwitterionic glutathione-coated gold nanoparticles (GS-AuNPs), which have broad preclinical applications in cancer diagnosis and kidney functional imaging. However, origin of such efficient renal clearance is still not clear. Herein, we conducted head-to-head comparison on physiological stability and renal clearance of two zwitterionic luminescent AuNPs coated with cysteine and glycine-cysteine (Cys-AuNPs and Gly-Cys-AuNPs), respectively. While both of them exhibited similar surface charges and the same core sizes, additional glycine slightly increased the hydrodynamic diameter of the AuNPs by 0.4 nm but significantly enhanced physiological stability of the AuNPs as well as altered their clearance pathways. These studies indicate that the ligand length, in addition to surface charges and size, also plays a key role in the physiological stability and renal clearance of ultrasmall zwitterionic inorganic NPs.

  15. 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

  16. Applying Organ Clearance Concepts in a Clinical Setting

    PubMed Central

    2008-01-01

    Objective To teach doctor of pharmacy (PharmD) students how to apply organ clearance concepts in a clinical setting in order to optimize dose management, select the right drug product, and promote better patient-centered care practices. Design A student-focused 5-hour topic entitled "Organ Clearance Concepts: Modeling and Clinical Applications" was developed and delivered to second-year PharmD students. Active-learning techniques, such as reading assignments and thought-provoking questions, and collaborative learning techniques, such as small groups, were used. Student learning was assessed using application cards and a minute paper. Assessment Overall student responses to topic presentation were overwhelmingly positive. The teaching strategies here discussed allowed students to play an active role in their own learning process and provided the necessary connection to keep them motivated, as mentioned in the application cards and minute paper assessments. Students scored an average of 88% on the examination given at the end of the course. Conclusion By incorporating active-learning and collaborative-learning techniques in presenting material on organ clearance concept, students gained a more thorough knowledge of dose management and drug-drug interactions than if the concepts had been presented using a traditional lecture format. This knowledge will help students in solving critical patient situations in a real-world context. PMID:19214275

  17. The biodistribution of gold nanoparticles designed for renal clearance.

    PubMed

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

    2013-07-07

    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 ((99m)Tc, (111)In) 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.

  18. 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

  19. 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.

  20. Renal clearance of endogenous creatinine, urea, sodium, and potassium in normal cats and cats with chronic renal failure.

    PubMed

    Deguchi, E; Akuzawa, M

    1997-07-01

    The renal clearance test was carried out in 6 normal male cats and 12 male cats with chronic renal failure. The average concentrations of creatinine (Cr), urea, sodium (Na), and potassium (K) in the serum of the cats with chronic renal failure were 5.09, 136.7 (mg/100 ml), 143.9 and 3.71 (mEq/l) respectively, and the specific gravity of urine was 1.009. The renal clearances of Cr, urea, Na, and K (ml/min/kg of body weight) were 2.639 +/- 0.217, 1.034 +/- 0.110, 0.024 +/- 0.007 and 0.266 +/- 0.028, respectively in normal cats, and were 0.789 +/- 0.407, 0.358 +/- 0.211, 0.095 +/- 0.084 and 0.872 +/- 0.204 in cats with chronic renal failure. Clearance of Cr and urea was significantly lower in cats with chronic renal failure than in normal cats, while the values of Na and K were significantly higher in cats with chronic renal failure. The glomerular filtration of Cr and urea and the urinary excretion of these 4 substances were significantly higher in cats with chronic renal failure. The tubular reabsorption rates of Na and K were significantly lower in cats with chronic renal failure compared to those in normal cats, but there was no significant difference in urea and creatinine.

  1. Correlation of 2 Hours and 24 Hours Creatinine Clearance in Renal Donors After Unilateral Nephrectomy

    PubMed Central

    Devanand, Viji; Chithrapavai, S.U.

    2013-01-01

    Background: The kidney performs numerous specialised functions in an effort to maintain constancy of the internal composition of body fluids. Aim: This study was done to ascertain the feasibility of estimating creatinine clearance as an outpatient procedure over a 2 hours period instead of doing the study over a 24 hours period. Material and Methods: Eighteen renal donors, Twelve females and Six males, who were closely related to recipients, were chosen. This study was done on renal donors who attended the Nephrology Department of Rajiv Gandhi Government General Hospital, Madras Medical College, Chennai–03 India. To estimate creatinine clearance in 24 hours urine, 24 hours urine sample was collected from 9 am on the first day to 9 am on the next day, after first emptying the bladder. Then, creatinine clearance was calculated by using standard formula, CC=UV/ Pt X 1.73m2/BSA of the individual. Results: There was no significant differences in mean creatinine clearance values by collecting 2 hours and 24 hours urine samples from renal donors in different stages of post nephrectomy period. It has been shown that 2 hours collection of urine sample is as good as 24 hours urine sample for estimating creatinine clearance. Conclusion: Hence it was proved that measurement of creatinine clearance could be done as an outpatient procedure, as the patient needed only 2 hours of hospital stay. PMID:24298453

  2. 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).

  3. 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).

  4. High Phenobarbital Clearance During Continuous Renal Replacement Therapy

    PubMed Central

    Rosenborg, Staffan; Saraste, Lars; Wide, Katarina

    2014-01-01

    Abstract Phenobarbital is an old antiepileptic drug used in severe epilepsy. Despite this, little is written about the need for dose adjustments in renal replacement therapy. Most sources recommend a moderately increased dose guided by therapeutic drug monitoring. A 14 year old boy with nonketotic hyperglycinemia, a rare inborn error of metabolism, characterized by high levels of glycine, epilepsy, spasticity, and cognitive impairment, was admitted to the emergency department with respiratory failure after a few days of fever and cough. The boy was unconscious at admittance and had acute renal and hepatic failure. Due to the acute respiratory infection, hypoxic hepatic and renal failure occurred and the patient had a status epilepticus. The patient was intubated and mechanically ventilated. Continuous renal replacement therapy was initiated. Despite increased phenobarbital doses, therapeutic levels were not reached until the dose was increased to 500 mg twice daily. Therapeutic drug monitoring was performed in plasma and dialysate. Calculations revealed that phenobarbital was almost freely dialyzed. Correct dosing of drugs in patients on renal replacement therapy may need a multidisciplinary approach and guidance by therapeutic drug monitoring. PMID:25101986

  5. Importance of glycosylation for hepatic clearance of renal renin

    SciTech Connect

    Kim, Shokei; Hiruma, Masahito; Ikemoto, Fumihiko; Yamamoto, Kenjiro )

    1988-11-01

    Three differently glycosylated forms of renin (renin A, B-1, and B-2) were highly purified from rat kidneys by pepstatin-aminohexyl-Sepharose affinity chromatography and by serial lectin affinity chromatography on concanavalin A (con A) and lentil lectin-Sepharose, and the role of glycosylation of renin was investigated. Renin A and renin B-1 were loosely and tightly bound to con A, respectively, but did not bind to lentil lectin. Renin B-2 bound to both con A and lentil lectin. These three forms of renin were all similar in their physicochemical characteristics, including molecular weight, isoelectric point, specific activity, K{sub m}, optimum pH, and antigenicity. Each form of renin, labeled with {sup 125}I an given intravenously to anesthetized rats, disappeared from the circulation at different rates. Labeled renin A distributed to a similar extent in the liver and kidney, whereas renins B-1 and B-2 were distributed predominantly in the liver and to a lesser extent in the kidney. Deglycosylation of renin B-1 with endoglycosidase F resulted in no loss of its enzymatic activity or antigenicity but greatly reduced the metabolic clearance rate to 18%. Deglycosylation of renin B-1 greatly decreased its uptake by the liver and increased its uptake by the kidney. These studies indicate the importance of glycosylation of renin for its hepatic uptake and metabolic clearance rate.

  6. Clearance of iohexol, chromium-51-ethylenediaminetetraacetic acid, and creatinine for determining the glomerular filtration rate in pigs with normal renal function: comparison of different clearance techniques.

    PubMed

    Frennby, B; Sterner, G; Almén, T; Chai, C M; Jönsson, B A; Månsson, S

    1996-08-01

    We wanted to improve determination of the glomerular filtration rate (GFR) with plasma clearance techniques because the alternative-renal clearance techniques-may involve inaccurate urine sampling or risk of urinary tract infection when bladder catheterization becomes necessary. Therefore, we compared the renal and plasma clearances of iohexol and chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), as well as endogenous creatinine clearance, in 19 normal pigs using different techniques. After an intravenous bolus injection of the GFR markers, 16 plasma samples were used to plot the marker concentrations versus time for 4.5 hr. Urine was collected during nine 30-min periods. Plasma clearance was calculated by dividing the dose of marker with the area under the plasma concentration curve (AUC) from the time of injection to infinity using one-compartment (ClAUC-slope) and three-compartment (ClAUC-3comp) models. The renal clearance was calculated by dividing the amount of marker excreted in the urine in a period with the AUC in the same period. This AUC was determined by integrating the total area in the period (Clren adv)--our reference method representing the "true" GFR--or by using the arithmetic mean of the plasma concentrations of the marker at the beginning and end of the urine collection period (Clren simple). Creatinine clearance was determined according to Clren simple. Renal clearances of iohexol and 51Cr-EDTA were significantly higher than creatinine clearance (P = .0002). There was no significant difference between the renal clearances of iohexol and 51Cr-EDTA or between their plasma clearances. The two mathematical methods of calculating the renal clearance of iohexol were highly correlated (rs = .99), as were the two methods of calculating its plasma clearance (rs = .95). Because of the extrarenal clearance of the markers, the plasma clearance methods for iohexol and 51Cr-EDTA always overestimated the true GFR. ClAUC-3comp was the method closest to

  7. 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

  8. [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.

  9. Augmented renal clearance in the ICU: results of a multicenter observational study of renal function in critically ill patients with normal plasma creatinine concentrations*.

    PubMed

    Udy, Andrew A; Baptista, João P; Lim, Noelle L; Joynt, Gavin M; Jarrett, Paul; Wockner, Leesa; Boots, Robert J; Lipman, Jeffrey

    2014-03-01

    To describe the prevalence and natural history of augmented renal clearance in a cohort of recently admitted critically ill patients with normal plasma creatinine concentrations. Multicenter, prospective, observational study. Four, tertiary-level, university-affiliated, ICUs in Australia, Singapore, Hong Kong, and Portugal. Study participants had to have an expected ICU length of stay more than 24 hours, no evidence of absolute renal impairment (admission plasma creatinine < 120 µmol/L), and no history of prior renal replacement therapy or chronic kidney disease. Convenience sampling was used at each participating site. Eight-hour urinary creatinine clearances were collected daily, as the primary method of measuring renal function. Augmented renal clearance was defined by a creatinine clearance more than or equal to 130 mL/min/1.73 m. Additional demographic, physiological, therapeutic, and outcome data were recorded prospectively. Nine hundred thirty-two patients were admitted to the participating ICUs over the study period, and 281 of which were recruited into the study, contributing 1,660 individual creatinine clearance measures. The mean age (95% CI) was 54.4 years (52.5-56.4 yr), Acute Physiology and Chronic Health Evaluation II score was 16 (15.2-16.7), and ICU mortality was 8.5%. Overall, 65.1% manifested augmented renal clearance on at least one occasion during the first seven study days; the majority (74%) of whom did so on more than or equal to 50% of their creatinine clearance measures. Using a mixed-effects model, the presence of augmented renal clearance on study day 1 strongly predicted (p = 0.019) sustained elevation of creatinine clearance in these patients over the first week in ICU. Augmented renal clearance appears to be a common finding in this patient group, with sustained elevation of creatinine clearance throughout the first week in ICU. Future studies should focus on the implications for accurate dosing of renally eliminated pharmaceuticals

  10. 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.

  11. 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.

  12. Comparison of clearance and arteriovenous extraction techniques for measurements of renal hemodynamic functions

    SciTech Connect

    Katzberg, R.W.; Pabico, R.C.; Morris, T.W.; Hayakawa, K.; McKenna, B.A.; Ventura, J.A.; Fischer, H.W.

    1986-12-01

    No previous studies have directly compared timed urine collections (UV/P) vs. arteriovenous (A-V) extraction methods for determination of renal function in whole kidney preparations. We examined different markers and techniques for assessing renal plasma flow (RPF), filtration fraction (FF), and glomerular filtration rate (GFR) in both steady-state and rapidly changing conditions following 2 ml/kg bolus intravenous injections of either Renografin 76% (meglumine/sodium diatrizoate-76%) or hypertonic mannitol 25%. During steady-state conditions, excellent correlations were obtained when comparing markers and techniques. Thus, timed urinary clearances of inulin vs. 99m-technetium DTPA (Tc) had a correlation coefficient (R) of .96 (P less than .01; n = 16), and the A-V extraction technique of inulin vs. Tc as determinants of GFR showed a correlation of R = .98 (P less than .01; n = 15). The timed urinary clearance of inulin vs. the A-V extraction of inulin for glomerular filtration gave a correlation of R = .93 (P less than .01; n = 15). The clearance of para-aminohippurate (PAH) divided by the extraction of PAH vs. flow determinations using the electromagnetic flowmeter gave a correlation of R = .92 (P less than .01; n = 16). The anticipated decrease in GFR following contrast medium and hypertonic mannitol was observed using the A-V extraction technique, whereas an artifactual, exaggerated increase in GFR was observed using the timed urine collection technique. Similarly, we noted an exaggerated increase in RPF using CPAH/EPAH as the methodology. We conclude that rapid changes in renal hemodynamics may be measured accurately using the A-V extraction technique but not with clearance techniques requiring timed urine collections.

  13. A model-based analysis of the predictive performance of different renal function markers for cefepime clearance in the ICU.

    PubMed

    Jonckheere, Stijn; De Neve, Nikolaas; De Beenhouwer, Hans; Berth, Mario; Vermeulen, An; Van Bocxlaer, Jan; Colin, Pieter

    2016-09-01

    Several population pharmacokinetic models for cefepime in critically ill patients have been described, which all indicate that variability in renal clearance is the main determinant of the observed variability in exposure. The main objective of this study was to determine which renal marker best predicts cefepime clearance. A pharmacokinetic model was developed using NONMEM based on 208 plasma and 51 urine samples from 20 ICU patients during a median follow-up of 3 days. Four serum-based kidney markers (creatinine, cystatin C, urea and uromodulin) and two urinary markers [measured creatinine clearance (CLCR) and kidney injury molecule-1] were evaluated as covariates in the model. A two-compartment model incorporating a renal and non-renal clearance component along with an additional term describing haemodialysis clearance provided an adequate description of the data. The Cockcroft-Gault formula was the best predictor for renal cefepime clearance. Compared with the base model without covariates, the objective function value decreased from 1971.7 to 1948.1, the median absolute prediction error from 42.4% to 29.9% and the between-subject variability in renal cefepime clearance from 135% to 50%. Other creatinine- and cystatin C-based formulae and measured CLCR performed similarly. Monte Carlo simulations using the Sanford guide dose recommendations indicated an insufficient dose reduction in patients with a decreased kidney function, leading to potentially toxic levels. The Cockcroft-Gault formula was the best predictor for cefepime clearance in critically ill patients, although other creatinine- and cystatin C-based formulae and measured CLCR performed similarly. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. 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.

  15. Effects of enoxacin on renal and metabolic clearance of theophylline in rats.

    PubMed

    Nadai, M; Hasegawa, T; Kuzuya, T; Muraoka, I; Takagi, K; Yoshizumi, H

    1990-09-01

    The effects of enoxacin and its metabolite 4-oxoenoxacin on the disposition of theophylline were investigated in rats. Systemic clearance of theophylline was significantly decreased by approximately 40, 46, and 50% after oral coadministration of 25, 100, and 200 mg of enoxacin per kg, respectively. No significant changes in the volume of distribution of theophylline were observed. 4-Oxoenoxacin had no direct effect on theophylline disposition. Significant changes in urinary excretion of theophylline and its metabolites were observed. (i) Urinary excretion of unchanged theophylline was significantly increased in proportion to increases in enoxacin dosage. (ii) Decreases in renal clearance of theophylline and metabolic clearance of 1-methyluric acid and 1,3-dimethyluric acid were observed. (iii) The percent decreases in the metabolic clearance of 1-methyluric acid were dependent on enoxacin dosage. It is likely that enoxacin inhibits the elimination process, which depends on cytochrome P-450-mediated isozymes for N demethylation and oxidation, and that the capacity of the inhibitory effect of enoxacin is greater in the N-demethylation pathway than it is in oxidation.

  16. 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.

  17. 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.

  18. The effect of frusemide and piretanide on the renal clearance of gentamicin in man.

    PubMed Central

    Whiting, P H; Barber, H E; Petersen, J

    1981-01-01

    1 Gentamicin alone (dose 1 mg/kg) or in combination with frusemide (dose 0.25 mg/kg) or piretanide (dose 0.1 mg/kg) was administered intravenously to six healthy male volunteers. 2 Blood samples were collected at various times for 24 h and urine for up to 48 h. 3 Both diuretics increased the renal clearance of gentamicin during the period of the diuresis, without influencing either the glomerular filtration rate or the distribution of the antibiotic. 4 The results are discussed in relation to gentamicin-induced nephrotoxicity. PMID:7340881

  19. 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.

  20. TGF-beta1 immunohistochemistry and promoter methylation in chronic renal failure rats treated with Uremic Clearance Granules.

    PubMed

    Miao, Xu-Hong; Wang, Chun-Guo; Hu, Bao-Quan; Li, Ai; Chen, Cheng-Bin; Song, Wen-Qin

    2010-01-01

    The aim of the study was the explain the mechanism related to therapeutic effects of Uremic Clearance Granules (Niaoduqing Keli in Chinese) on adenine-induced Chronic Renal Failure in rats. Thirty 8-week-old male Wistar rats were selected and randomly divided in to 3 groups: Normal Control Group (NCG)consisted of 10 rats, Chronic Renal Failure Pathological Control Group (PCG) 10 rats, and Uremic Clearance Granules Treatment Group (UCG) 10 rats. Each rat in PCG and UCG was fed with adenine-enriched diets, containing 10 g adenine per kg food for 6 weeks. After fed with adenine, each rat in UCG was administered orally with 2 ml solution of Uremic Clearance Granules for 6 weeks. The concentration of Uremic Clearance Granules solution was 0.42 g/ml which was 10 times of human. On days 42 and 84, the serum levels of creatinine, Blood Urea Nitrogen and homocysteine were determined. The methylation of TGFbeta1 promoter was tested by methylation-specific PCR. TGF-beta1 mRNA and protein expression in rat renal cortex were analyzed by real-time RT-PCR and Immunohistochemistry. (1) Experimented on model of Chronic Renal Failure in rats, the preparation was proved to be able to reduce serum creatinine, Blood Urea Nitrogen, and homocysteine (p<0.05), improve renal function. (2) The expression of TGF-beta1 in mRNA and protein level were down-regulated. (3) TGF-beta1 promoter was demethylated at some loci in PCG, and was recovered in UCG. After treatment with Uremic Clearance Granules, the Chronic Renal Failure Wistar rat's kidney function was recovered. The recovery may be result of the remethylation of TGF-beta1 promoter and then lead to TGF-beta1 be transcripted and translated normally. The experimental study explain the molecular mechanism by which Uremic Clearance Granules treat Chronic Renal Failure.

  1. Enhanced renal clearance of vancomycin in rats with carcinogen-induced osteosarcoma.

    PubMed

    Shimada, Izumi; Iwata, Chieko; Taga, Shino; Teramachi, Hitomi; Nomura, Masaaki; Miyamoto, Ken-Ichi; Tsuciya, Hiroyuki; Wada, Takashi; Kimura, Kazuko; Matsushita, Ryo

    2012-03-01

    Recently, it has been reported that total clearance (CLtot) of vancomycin is significantly higher in patients with malignancies compared to those without malignancies. In the present study, to clarify the mechanism of this enhancement in malignancy, we adopted rat animal models, using chemical carcinogen-induced osteosarcoma, selected lung metastatic lesions (C-SLM), transplanted into thigh muscles. The CLtot and renal clearance (CLr) of vancomycin in the tumor-bearing rats were increased compared to the ones of the control rats without tumor. However, there was no difference in the glomerular filtration rate. The plasma concentrations of interleukin (IL)-1β and IL-6, were elevated in the tumor-bearing rats. When renal proximal tubular epithelial cells (RPTEC) were exposed to IL-1β, IL-6, and tumor necrosis factor (TNF)-α simultaneously, the excretory ratio increased significantly. These findings suggest that tubular excretion or re-absorption by cytokines might be associated with changes in the vancomycin CLtot enhancement in the tumor-bearing rats.

  2. 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

  3. 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.

  4. Usefulness of clearance parametric images in detection of regional renal parenchyma dysfunction.

    PubMed

    Kuśmierek, Jacek; Bieńkiewicz, Małgorzata; Konecki, Tomasz; Surma, Marian; Sosnowski, Marek; Płachcińska, Anna

    2017-01-01

    The aim of the study was to examine whether parametric clearance images (PAR) enhance diagnostic potential of a dynamic renal scintigraphy with detection of local dysfunction of kidneys, on a model of kidneys after treatment with extracorporeal shock wave lithotripsy (ESWL), MATERIAL AND METHODS: Kidneys after ESWL were accepted as a proper model for the implementation of this objective because of the previously proven damaging effect of a shock wave on renal parenchyma and known region of ESWL application. Forty patients (23 males and 17 females) at the age of 37 to 70 years (mean value 54) with untreated earlier single, one-sided nephrolithiasis, currently treated with ESWL, underwent a study. A dynamic renal 99mTc-EC scintigraphy was performed three times: before ESWL, a week and a month after this therapeutic intervention. PAR images generated with use of an in-house developed software were compared with summation (SUM) of images obtained from radiopharmaceutical uptake phase and quantitative global function parameters (GFP) of each kidney, like split function, MTT - mean transit time and PTT - parenchymal transit time. PAR and SUM images of all 40 kidneys before ESWL were normal. PAR images revealed local or diffused defects a week and a month after therapeutic intervention in statistically significantly larger numbers of kidneys than SUM images (19 vs. 6, p = 0.002 and 16 vs. 5, p = 0.003, respectively). A week after ESWL, when defects in PAR images were observed in about a half of all renal segments (29/57 - 51%) all GFP values were significantly worse than in kidneys without defects. A month after ESWL defects in PAR images could be observed in ab. 1/3 (17/48 - 35%) of segments and were less extensive, whereas GFP values did not differ significantly from values in kidneys without clearance function impairment in the PAR images. PAR images enhance diagnostic potential of a dynamic renal scintigraphy with detection of local function defects. These images

  5. A comparison of estimates of glomerular filtration in critically ill patients with augmented renal clearance

    PubMed Central

    2011-01-01

    Introduction Increasingly, derived estimates of glomerular filtration, such as the modification of diet in renal disease (MDRD) equation and Cockcroft-Gault (CG) formula are being employed in the intensive care unit (ICU). To date, these estimates have not been rigorously validated in those with augmented clearances, resulting in potentially inaccurate drug prescription. Methods Post-hoc analysis of prospectively collected data in two tertiary level ICU's in Australia and Portugal. Patients with normal serum creatinine concentrations manifesting augmented renal clearance (ARC) (measured creatinine clearance (CLCR) > 130 ml/min/1.73 m2) were identified by chart review. Comparison between measured values and MDRD and CG estimates were then undertaken. Spearman correlation coefficients (rs) were calculated to determine goodness of fit, and precision and bias were assessed using Bland-Altman plots. Results Eighty-six patients were included in analysis. The median [IQR] measured CLCR was 162 [145-190] ml/min/1.73 m2, as compared to 135 [116-171], 93 [83-110], 124[102-154], and 108 [87-135] ml/min/1.73 m2 estimated by CG, modified CG, 4-variable MDRD and 6-variable MDRD formulae. All of the equations significantly under-estimated the measured value, with CG displaying the smallest bias (39 ml/min/1.73 m2). Although a moderate correlation was noted between CLCR and CG (rs = 0.26, P = 0.017) and 4-variable MDRD (rs = 0.22, P = 0.047), neither had acceptable precision for clinical application in this setting. CG estimates had the highest sensitivity for correctly identifying patients with ARC (62%). Conclusions Derived estimates of GFR are inaccurate in the setting of ARC, and should be interpreted with caution by the physician. A measured CLCR should be performed to accurately guide drug dosing. PMID:21651804

  6. 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)

  7. 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

  8. 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.

  9. Renal clearance of cobalt in relation to the use of metal-on-metal bearings in hip arthroplasty.

    PubMed

    Daniel, Joseph; Ziaee, Hena; Pradhan, Chandra; Pynsent, Paul B; McMinn, Derek J W

    2010-04-01

    A concern regarding the use of metal-on-metal bearings in hip arthroplasty has been that the high levels of metal ions that are released overwhelm the renal threshold for metal excretion, leading to systemic buildup of metals. The purpose of this investigation was to determine if the physiological renal capacity for cobalt clearance and cobalt concentrating efficiency is overwhelmed by the elevation in metal ion levels seen in patients with metal-on-metal-bearing hip devices. Concurrent specimens of urine and plasma were obtained from a group of 461 patients (346 men and 115 women) at various intervals after either a unilateral (296) or a bilateral (130) metal-on-metal hip arthroplasty or preoperatively (thirty-five patients; the control specimens). Metal ion analyses were performed with high-resolution inductively coupled mass spectrometry. Renal efficiency was measured as the ratio of urine cobalt concentration to plasma cobalt concentration. Cobalt clearance was calculated by dividing the urine cobalt output in twenty-four hours by the plasma cobalt concentration. Dividing the quotient by 1440 adjusts it to clearance per minute. The median renal efficiency was found to be 0.9 in the analysis of the preoperative specimens, indicating that there was renal conservation of cobalt. In patients with metal-on-metal bearings, the median renal efficiency was 3.2, indicating that, as a result of cobalt excretion, the cobalt concentration in urine was threefold higher than the concentration in plasma. Linear regression analysis showed that renal efficiency progressively increased at a rate of 9% for every microg/24 hr increase in cobalt release. Cobalt clearance showed a similar trend, increasing from 1.3 mL/min in the preoperative group to 3.7 mL/min in the follow-up group. In the follow-up group, renal cobalt clearance progressively increased from 1.9 to 7.1 mL/min with increasing daily cobalt output, which indicates that with increasing in vivo metal ion release there

  10. [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.

  11. Ex vivo Ceftolozane/Tazobactam Clearance during Continuous Renal Replacement Therapy.

    PubMed

    Chaijamorn, Weerachai; Shaw, Alexander R; Lewis, Susan J; Mueller, Bruce A

    2017-01-01

    To determine ceftolozane/tazobactam transmembrane clearances (CLTM) in continuous hemofiltration (CHF) and continuous hemodialysis (CHD) and to determine optimal ceftolozane/tazobactam dosing regimens for patients receiving continuous renal replacement therapy (CRRT). Validated, ex vivo CHF and CHD bovine blood models using polysulfone (HF1400) and AN69 (Multiflow 150-M) hemofilters were used to evaluate adsorption and CLTM at different effluent flow rates. Monte Carlo simulations (MCS) using pharmacokinetic parameters from published studies and CLTM from this study were used to generate ceftolozane/tazobactam dosing for patients receiving CRRT. CHF and CHD CLTM did not differ at equivalent effluent rates. CLTM approximated effluent flow rates. No adsorption of ceftolozane/tazobactam occurred for either hemofilter. Effluent flow was the most important determinant of MCS-derived doses. CRRT clearances of ceftolozane/tazobactam depended on effluent flow rates but not hemofilter types. MCS-derived ceftolozane/tazobactam doses of 750 (500/250)-1,500 (1,000/500) mg every 8 h met pharmacodynamic targets for virtual patients receiving CRRT at contemporary effluent rates. © 2017 S. Karger AG, Basel.

  12. 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.

  13. 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.

  14. 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.

  15. Reduced plasma total homocysteine concentrations in Type 1 diabetes mellitus is determined by increased renal clearance.

    PubMed

    Veldman, B A J; Vervoort, G; Blom, H; Smits, P

    2005-03-01

    Elevated plasma levels of total homocysteine are related to the development of vascular complications. Patients with diabetes mellitus are particularly at risk for the development of these complications. Several factors determine plasma total homocysteine including renal function. As early Type 1 diabetes is characterized by a relative glomerular hyperfiltration, increased renal clearance could contribute to decreased levels of homocysteine as observed in Type 1 diabetes mellitus. Therefore we investigated the relationship between plasma total homocysteine and the glomerular filtration rate (GFR). In 92 Type 1 diabetes patients and 44 control subjects, we measured GFR and effective renal plasma flow (ERPF) by means of continuous infusion of inulin and p-aminohippurate. Fasting plasma total homocysteine was measured using high performance liquid chromatography. GFR (121 +/- 21 resp. 104 +/- 14 ml/min; P < 0.001) and ERPF (563 +/- 127 resp. 516 +/- 121 ml/min; P = 0.05) were significantly higher in Type 1 diabetes patients as compared with control subjects. Plasma total homocysteine was reduced in Type 1 diabetes patients as compared with control subjects (11.0 +/- 4.5 resp. 13.4 +/- 7 micromol/l; P = 0.01). Plasma total homocysteine was strongly correlated with GFR (Type 1 diabetes patients: r = -0.43, P < 0.001; control subjects: r = -0.39, P = 0.01). GFR is a major determinant of plasma total homocysteine levels in Type 1 diabetes patients as well as control subjects. The reduced plasma total homocysteine levels in diabetes patients can be explained by an increased GFR.

  16. Usefulness of parametric renal clearance images in the assessment of basic risk factors for renalnal clearance images in the assessment of basic risk factors for renal scarring in children with recurrent urinary tract infections.

    PubMed

    Pietrzak-Stelasiak, Ewa; Bieńkiewicz, Małgorzata; Woźnicki, Wojciech; Bubińska, Krystyna; Kowalewska-Pietrzak, Magdalena; Płachcińska, Anna; Kuśmierek, Jacek

    2017-01-01

    Clinically confirmed incidents of acute pyelonephritis (APN) following recurrent infections of urinary tract (UTI) form basic risk factors for renal scarring in children. Vesico-uretheral reflux (VUR) of higher grade is additional risk factor for this scarring. Opinions on diagnostic value of summed sequential images of renal uptake phase (SUM) of dynamic renal scintigraphy in detection of renal scars are diverse. However, several publications point to higher diagnostic efficacy of clearance parametric images (PAR) generated from this study. To establish a clinical value of parametric renal clearance images in detection of renal scarring. A prospective study was performed in a group of 91 children at the age of 4 to 18 years with recurrent UTI. Clinically documented incidents of APN were noted in 32 children: in 8 cases - one and in the remaining 24 - 2 to 5 (mean 3) incidents. In the remaining 59 patients only infections of the lower part of urinary tract were diagnosed. Static renal 99mTc-DMSA SPECT study and after 2-4 days dynamic renal studies (99mTc-EC) were performed in every patient not earlier than 6 months after the last documented incident of UTI. PAR images generated from a dynamic study by in-house developed software and SUM images were compared with a gold standard SPECT study. Percentages of children with detected renal scar(s) with SPECT and PAR methods amounted to 55% and 54%, respectively and were statistically significantly higher (p < 0.0001) than with SUM method - 31%. Scars in children with history of APN detected with SPECT and PAR methods were significantly more frequent than with infections of only lower part of urinary tract (72% vs. 46%; p = 0.017 and 69% vs. 46%; p = 0.036, respectively). A SUM method did not reveal statistically significant differences between frequencies of detection of scars in groups specified above - 38% vs. 27% (p = 0.31). Both SPECT and PAR methods showed also that frequencies of occurrence of renal scars in

  17. 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.

  18. Influence of amylase assay technique on renal clearance of amylase-creatinine ratio.

    PubMed

    Levitt, M D; Johnson, S G; Ellis, C J; Engel, R R

    1977-06-01

    The influence of amylase assay technique on the renal amylase/creatinine clearance measurement was determined by analysis of serum and urine specimens obtained from 10 normal subjects. CAm/CCr averaged 2.19 +/- 0.18% with a saccharogenic technique, 1.52 +/- 0.2% with an iodometric technique, and 0.80 +/- 0.08% with a chromogenic technique. Each of these values differed significantly (P less than 0.05) from the other two. Recovery studies were carried out by adding partially purified human salivary or pancreatic amylase to human newborn serum or urine (which contain minimal endogenous amylase). Equal amylase activity was recovered from serum and urine by the saccharogenic technique whereas recovery from urine was less than 50% of that from serum using the iodometric and chromogenic techniques. The accuracy of the chromogenic technique is markedly improved by the addition of albumin to the urine assay system. Although it appears that only the saccharogenic method provides an accurate estimate of CAm/CCr, each assay technique distinguished the elevated CAm/CCr of patients with pancreatitis from the normal range established for that technique. Accurate clinical interpretation of CAm/CCr measurment requires knowledge of the amylase assay technique used.

  19. Trimethoprim and sulfamethoxazole transmembrane clearance during modeled continuous renal replacement therapy.

    PubMed

    Kesner, Jacob M; Yardman-Frank, Joseph Michael; Mercier, Renee-Claude; Wong, Craig S; Walker, Scott E; Argyres, Dean P; Vilay, Aloun Mary

    2014-01-01

    There is limited data regarding trimethoprim (TMP)/sulfamethoxazole (SMX) continuous renal replacement therapy (CRRT) dosing. We aimed to estimate TMP/SMX transmembrane clearance (CLtm) during continuous hemofiltration (CH) and continuous hemodialysis (CD) to guide dosing. Using an in vitro model, TMP/SMX sieving coefficients (SC) and saturation coefficients (SA) were determined with high-flux polyarylethersulfone and polyacrylonitrile-sodium methallyl sulfonate copolymer hemodiafilters at ultrafiltration/dialysate rates of 1, 2, 3, and 6 l/h. TMP/SMX CLtm was calculated using measured SC and SA. TMP/SMX CRRT doses were modeled using CLtm and published TMP/SMX pharmacokinetic parameters. TMP SC/SA during CH/CD were significantly higher than SMX SC/SA. During modeling, TMP 10 mg/kg/day and its corresponding SMX dose, 50 mg/kg/day, resulted in steady state TMP/SMX peak concentrations associated with efficacy against Pneumocystis jirovecii. CRRT resulted in greater TMP CLtm than SMX. TMP 10 mg/kg/day divided q12h may be an appropriate initial dose to consider in patients undergoing CRRT. © 2014 S. Karger AG, Basel.

  20. [PK/PD of vancomycin in patients with severe acute pancreatitis combined with augmented renal clearance].

    PubMed

    He, Juan; Mao, Enqiang; Jing, Feng; Jiang, Huiting; Xu, Wenyun; Yang, Wanhua; Chen, Erzhen

    2017-09-01

    To evaluate the serum trough concentration and the pharmacokinetics/pharmacodynamics (PK/PD) of vancomycin in patients with severe acute pancreatitis (SAP), and analyze the effect of vancomycin continuous infusion for optimizing the characteristics of its PK/PD. The inhospital patients with SAP received vancomycin treatment and admitted to emergency intensive care unit (EICU) of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2011 to December 2016 were enrolled. Steady-state trough concentrations of vancomycin from patients were collected retrospectively. The SAP patients were divided into augmented renal clearance (ARC) and non-ARC groups, as well as systemic inflammatory response syndrome (SIRS) and non-SIRS groups according to the patients with or without symptom above. Adjustments of increased dosage or 24-hour continuous infusion or increase vancomycin dose were made for patients if the steady-state trough concentrations fell below the target level. Steady state trough concentration for vancomycin intermittent infusion or steady state concentration for vancomycin continuous infusion was determined by the fluorescence polarization immunoassay method. PK parameters of vancomycin were calculated using the Bayesian estimator and the area under the serum drug concentration-time curve (AUCc-t), the minimum inhibitory concentration (MIC) and AUCc-t/MIC was recorded and calculated. The steady state trough concentration or steady state concentration from 61 patients with SAP were collected with mean steady state trough concentration of vancomycin of (7.7±4.4) mg/L, which was significantly lower than standard concentration (15 mg/L, P < 0.001). Apparent volume of distribution (Vd) and clearance of vancomycin was (1.06±0.26) L/kg and (8.9±2.8) L/h. The serum steady state trough concentration of vancomycin in ARC group (n = 33) was significantly lower than that in non-ARC group (n = 28; mg/L: 6.7±3.5 vs. 8.2±4.1, P < 0

  1. Renal failure in cirrhosis: Emerging concepts

    PubMed Central

    Bittencourt, Paulo Lisboa; Farias, Alberto Queiroz; Terra, Carlos

    2015-01-01

    Acute renal failure, now termed acute kidney injury (AKI), is frequently found in patients with cirrhosis. The occurrence of AKI, irrespective of the underlying cause, is associated with reduced in-hospital, 3-mo and 1-year survival. Hepatorenal syndrome is associated with the worst outcome among AKI patients with cirrhosis. Several definitions for AKI that have been proposed are outlined and evaluated in this paper. Among these, the International Club for Ascites-AKI criteria substantially strengthen the quality of early diagnosis and intervention according to underlying cause of AKI. PMID:26413223

  2. 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).

  3. High serum levels of soluble Fas (sFas) in CKD patients: effects of renal clearance, reabsorption and synthesis.

    PubMed

    Dalboni, M A; Cenedeze, M A; Manfredi, S R; Cruz Andreoli, M C; Pavao Dos Santos, O; Canziani, M E; Boim, M A; Goes, M A; Draibe, S A; Balakrishnan, V; Cendoroglo, M

    2008-05-01

    Increased serum concentrations of soluble Fas (sFas) have been reported in patients with chronic kidney disease (CKD). However, little is known about the renal clearance of sFas, whether sFas is reabsorbed in the renal tubules, or the behavior of sFas synthesis in CKD. We studied 69 patients with CKD (60+/-15 years old, creatinine clearance 37+19 ml/min/1.73 m2) and 14 healthy subjects (61+/-17 years, creatinine clearance 79+/-24 ml/min/1.73 m2). ELISA was used to measure the levels of sFas (pg/mL) and retinol binding protein (RBP - mg/L). RT-PCR was used to quantify sFasmRNA of leukocytes. Serum sFas levels were significantly higher in patients with CKD (2781+/-1214 vs. 2196+/-773, p=0.02). The concentrations of sFas in 24-hour urine samples (23+/-27 vs. 40+/-17, p=0.006) and sFas Clearance (0.019+/-0.022 vs. 0.036+/-0.020, p=0.01) were significantly lower in patients with CKD. sFas clearance correlated with creatinine clearance (r=0.25, p=0.02). Urine concentrations of RBP correlated with sFas concentrations in the urine (r=0.80, p<0.001). sFasmRNA were higher in patients with CKD (3.9+/-1.8 vs. 2.5+/-0.9, p<0.001). In CKD patients, the decrease in renal function is followed by a decrease in sFas clearance and an increase in serum sFas. In patients with proximal tubule dysfunction (high urinary RBP concentrations), urinary sFas is also increased, suggesting that sFas is reabsorbed by the proximal tubule. It is possible that an increase in sFas synthesis also contributes to the increase of serum sFas concentrations in uremia.

  4. 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

  5. Influence of Pelvicaliceal Anatomy on Stone Clearance After Flexible Ureteroscopy and Holmium Laser Lithotripsy for Large Renal Stones.

    PubMed

    Inoue, Takaaki; Murota, Takashi; Okada, Shinsuke; Hamamoto, Shuzo; Muguruma, Kouei; Kinoshita, Hidefumi; Matsuda, Tadashi

    2015-09-01

    This study was performed to evaluate the impact of pelvicaliceal anatomy on stone clearance in patients with remnant fragments in the lower pole after flexible ureteroscopy and holmium laser lithotripsy (fURSL) for renal stones >15 mm. This retrospective study included 67 patients with radiopaque residual fragments (>2 mm) in the lower pole after fURSL for large renal stones (>15 mm). The preoperative infundibular length (IL), infundibular width (IW), infundibulopelvic angle (IPA), and caliceal pelvic height (CPH) were measured using intravenous urography. Multivariate analysis was performed to determine whether any of these measurements affected stone clearance. Of the 67 patients, 55 (82.1%) were stone free (SF) 3 months after fURSL. The anatomic factors significantly favorable for an SF status were a short IL, broad IW, wide IPA, and low CPH. On multivariate analysis, the IPA had a significant influence on an SF status after fURSL (p=0.010). An IPA <30° was a negative risk factor (p=0.019). Postoperative complications occurred in nine patients (13.4%), including Clavien grade I complications in two patients (2.9%), grade II in six patients (8.9%), and grade IIIa in one patient (1.8%). Almost all complications were minor. An IPA <30° is the only negative risk factor for stone clearance after fURSL for large renal stones according to our multivariate analysis. Additional studies are required to further evaluate the characteristics of the pelvicaliceal anatomy influencing stone clearance.

  6. 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.

  7. 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.

  8. 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

  9. Adjusting eptifibatide doses for renal impairment: a model of dosing agreement among various methods of estimating creatinine clearance.

    PubMed

    Healy, Martha F; Speroni, Karen Gabel; Eugenio, Kenneth R; Murphy, Patricia M

    2012-04-01

    Because of the renal elimination and increased risk for bleeding events at supratherapeutic doses of eptifibatide, the manufacturer recommends dosing adjustment in patients with renal dysfunction. Methods commonly used to estimate renal dysfunction in hospital settings may be inconsistent with those studied and recommended by the manufacturer. To compare hypothetical renal dosing adjustments of eptifibatide using both the recommended method and several other commonly used formulas for estimating kidney function. Sex, age, weight, height, serum creatinine, and estimated glomerular filtration rate (eGFR) were obtained retrospectively from the records of patients who received eptifibatide during a 12-month period. Renal dosing decisions were determined for each patient based on creatinine clearance (CrCl) estimates via the Cockcroft-Gault formula (CG) with actual body weight (ABW), ideal body weight (IBW) or adjusted weight (ADJW), and eGFR from the Modification of Diet in Renal Disease formula. Percent agreement and Cohen κ were calculated comparing dosing decisions for each formula to the standard CG-ABW. In this analysis of 179 patients, percent agreement as compared to CG-ABW varied (CG-IBW: 90.50%, CG-ADJW: 95.53%, and eGFR: 93.30%). All κ coefficients were categorized as good. In the 20% of patients receiving an adjusted dose by any of the methods, 68.6% could have received a dose different from that determined using the CG-ABW formula. In the patients with renal impairment (CrCl <50 mL/min) in this study, two thirds would have received an unnecessary 50% dose adjustment discordant from the manufacturer's recommendation. Because failure to adjust eptifibatide doses in patients with renal impairment has led to increased bleeding events, practitioners may be inclined to err on the side of caution. However, studies have shown that suboptimal doses of eptifibatide lead to suboptimal outcomes. Therefore, correct dosing of eptifibatide is important to both patient

  10. 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

  11. Determining the mechanisms underlying augmented renal drug clearance in the critically ill: use of exogenous marker compounds.

    PubMed

    Udy, Andrew A; Jarrett, Paul; Stuart, Janine; Lassig-Smith, Melissa; Starr, Therese; Dunlop, Rachel; Wallis, Steven C; Roberts, Jason A; Lipman, Jeffrey

    2014-11-29

    The aim of this study was to explore changes in glomerular filtration (GFR) and renal tubular function in critically ill patients at risk of augmented renal clearance (ARC), using exogenous marker compounds. This prospective, observational pharmacokinetic (PK) study was performed in a university-affiliated, tertiary-level, adult intensive care unit (ICU). Patients aged less than or equal to 60 years, manifesting a systemic inflammatory response, with an expected ICU length of stay more than 24 hours, no evidence of acute renal impairment (plasma creatinine concentration < 120 μmol/L) and no history of chronic kidney disease or renal replacement therapy were eligible for inclusion. The following study markers were administered concurrently: sinistrin 2,500 mg (Inutest; Laevosan, Linz, Austria), p-aminohippuric acid (PAH) 440 mg (4% p-aminohippuric acid sodium salt; CFM Oskar Tropitzsch, Marktredwitz, Germany), rac-pindolol 5 or 15 mg (Barbloc; Alphapharm, Millers Point, NSW, Australia) and fluconazole 100 mg (Diflucan; Pfizer Australia Pty Ltd, West Ryde, NSW, Australia). Plasma concentrations were then measured at 5, 10, 15, 30, 60 and 120 minutes and 4, 6, 12 and 24 hours post-administration. Non-compartmental PK analysis was used to quantify GFR, tubular secretion and tubular reabsorption. Twenty patients were included in the study. Marker administration was well tolerated, with no adverse events reported. Sinistrin clearance as a marker of GFR was significantly elevated (mean, 180 (95% confidence interval (CI), 141 to 219) ml/min) and correlated well with creatinine clearance (r = 0.70, P < 0.01). Net tubular secretion of PAH, a marker of tubular anion secretion, was also elevated (mean, 428 (95% CI, 306 to 550) ml/min), as was net tubular reabsorption of fluconazole (mean, 135 (95% CI, 100 to 169) ml/min). Net tubular secretion of (S)- and (R)-pinodolol, a marker of tubular cation secretion, was impaired. In critically ill patients at risk of ARC, significant

  12. 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.

  13. Clearance of melatonin and 6-sulfatoxymelatonin by hemodialysis in patients with end-stage renal disease.

    PubMed

    Lüdemann, P; Zwernemann, S; Lerchl, A

    2001-10-01

    Patients with end-stage renal disease (ESRD) suffer from a number of related disorders. These include endocrine abnormalities, sleep disturbances, and depression. Melatonin is involved in the synchronization of exogenous zeitgebers with the endogenous rhythms, and it has effects on various psychological factors. As the concentrations of melatonin and the effects of dialysis have only occasionally been investigated in ESRD, we performed a study involving 35 patients, measuring the serum concentrations of melatonin, and of its major metabolite 6-sulfatoxymelatonin (aMT6s), before and after hemodialysis. Serum samples taken during morning hours from a control group (n=11) with intact kidneys served as controls. Patients were dialyzed for approximately 4 hr between 07:00 and 13:00 hr (S1), between 13:00 and 20:00 hr (S2), or between 18:30 and 22:30 hr (S3). Mean melatonin concentrations before hemodialysis were highly elevated when compared with the controls (40.6 vs. 6.7 pg/mL; P<0.001). Although melatonin levels were decreased to 20.3 pg/mL after dialysis, they were still well above the control levels. Likewise, aMT6s concentrations before dialysis were highly elevated in ESRD patients before dialysis when compared with controls (39.5 vs. 2.0 pg/mL; P<0.001), and also decreased by dialysis to levels still well above control levels (25.3 pg/mL). Clearance efficacy was better for melatonin (48.9%) than for aMT6s (36.6%; P<0.05). In ESRD patients, a diurnal rhythm for melatonin was observed (S1, 45.1 pg/mL; S2, 31.5 pg/mL; S3, 48.7 pg/mL; P<0.05), indicating that the normal synthesis rhythm is maintained. None of the following secondary disorders were correlated with melatonin concentrations: insomnia, delayed sleep onset, night-time arousals, and restless-leg syndrome. The reason for this observation is probably the melatonin concentrations, which were so high that no sub-classification could be identified. It is concluded that in ESRD patients, hemodialysis is unable

  14. 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.

  15. 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

  16. 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].).

  17. Reduced Renal Clearance of Cefotaxime in Asians with a Low-Frequency Polymorphism of OAT3 (SLC22A8)

    PubMed Central

    Yee, Sook Wah; Nguyen, Anh Nguyet; Brown, Chaline; Savic, Radojka M.; Zhang, Youcai; Castro, Richard A.; Cropp, Cheryl D.; Choi, Ji Ha; Singh, Diment; Tahara, Harunobu; Stocker, Sophie L.; Huang, Yong; Brett, Claire M.; Giacomini, Kathleen M.

    2014-01-01

    Organic anion transporter 3 (OAT3, SLC22A8), a transporter expressed on the basolateral membrane of the proximal tubule, plays a critical role in the renal excretion of organic anions including many therapeutic drugs. The goal of this study was to evaluate the in vivo effects of the OAT3-Ile305Phe variant (rs11568482), present at 3.5% allele frequency in Asians, on drug disposition with a focus on cefotaxime, a cephalosporin antibiotic. In HEK293- Flp-In cells, the OAT3-Ile305Phe variant had a lower maximum cefotaxime transport activity, Vmax, [159 ± 3 nmol*(mg protein)−1/min (mean ± SD)] compared with the reference OAT3 [305 ± 28 nmol*(mg protein)−1/min, (mean ± SD), p < 0.01], whereas the Michaelis-Menten constant values (Km) did not differ. In healthy volunteers, we found volunteers that were heterozygous for the Ile305Phe variant and had a significantly lower cefotaxime renal clearance (CLR; mean ± SD: 84.8 ± 32.1 mL/min, n = 5) compared with volunteers that were homozygous for the reference allele (158 ± 44.1 mL/min, n = 10; p = 0.006). Furthermore, the net secretory component of cefotaxime renal clearance (CLsec) was reduced in volunteers heterozygous for the variant allele [33.3 ± 31.8 mL/min (mean ± SD)] compared with volunteers homozygous for the OAT3 reference allele [97.0 ± 42.2 mL/min (mean ± SD), p = 0.01]. In summary, our study suggests that a low-frequency reduced-function polymorphism of OAT3 associates with reduced cefotaxime CLR and CLsec. PMID:23649425

  18. Reduced renal clearance of cefotaxime in asians with a low-frequency polymorphism of OAT3 (SLC22A8).

    PubMed

    Yee, Sook Wah; Nguyen, Anh Nguyet; Brown, Chaline; Savic, Radojka M; Zhang, Youcai; Castro, Richard A; Cropp, Cheryl D; Choi, Ji Ha; Singh, Diment; Tahara, Harunobu; Stocker, Sophie L; Huang, Yong; Brett, Claire M; Giacomini, Kathleen M

    2013-09-01

    Organic anion transporter 3 (OAT3, SLC22A8), a transporter expressed on the basolateral membrane of the proximal tubule, plays a critical role in the renal excretion of organic anions including many therapeutic drugs. The goal of this study was to evaluate the in vivo effects of the OAT3-Ile305Phe variant (rs11568482), present at 3.5% allele frequency in Asians, on drug disposition with a focus on cefotaxime, a cephalosporin antibiotic. In HEK293-Flp-In cells, the OAT3-Ile305Phe variant had a lower maximum cefotaxime transport activity, Vmax , [159 ± 3 nmol*(mg protein)(-1) /min (mean ± SD)] compared with the reference OAT3 [305 ± 28 nmol*(mg protein)(-1) /min, (mean ± SD), p < 0.01], whereas the Michaelis-Menten constant values (Km ) did not differ. In healthy volunteers, we found volunteers that were heterozygous for the Ile305Phe variant and had a significantly lower cefotaxime renal clearance (CLR ; mean ± SD: 84.8 ± 32.1 mL/min, n = 5) compared with volunteers that were homozygous for the reference allele (158 ± 44.1 mL/min, n = 10; p = 0.006). Furthermore, the net secretory component of cefotaxime renal clearance (CLsec ) was reduced in volunteers heterozygous for the variant allele [33.3 ± 31.8 mL/min (mean ± SD)] compared with volunteers homozygous for the OAT3 reference allele [97.0 ± 42.2 mL/min (mean ± SD), p = 0.01]. In summary, our study suggests that a low-frequency reduced-function polymorphism of OAT3 associates with reduced cefotaxime CLR and CL(sec) . Copyright © 2013 Wiley Periodicals, Inc.

  19. 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.

  20. 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.

  1. Continuous renal replacement therapy amino acid, trace metal and folate clearance in critically ill children.

    PubMed

    Zappitelli, Michael; Juarez, Marisa; Castillo, L; Coss-Bu, Jorge; Goldstein, Stuart L

    2009-04-01

    We hypothesized continuous veno-venous hemodialysis (CVVHD) amino acid, trace metals and folate clearance impacts nutrient balance. Critically ill children receiving CVVHD were studied prospectively for 5 days. Blood concentrations (amino acids, copper, zinc, manganese, chromium, selenium and folate) were measured at CVVHD initiation, and Days 2 and 5. CVVHD clearance, losses and nutrient balances were calculated on Days 2 and 5. We studied 15 children aged 7.7 +/- 6.7 years. Nitrogen balance was negative on Days 2 and 5. Amino acid clearances ranged from 2.8 to 51.1 ml/min per 1.73 m(2). CVVHD losses corresponded to 20% of intake. Days 2 and 5 balances were negative for selenium, but positive for other trace metals. Folate clearance was 16 ml/min per 1.73 m(2) on Days 2 and 5 and serum concentrations decreased significantly from initiation to Day 5 (P < 0.05). Nutrient losses by CVHHD may impact adequate nutrition provision.

  2. 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.

  3. High phenobarbital clearance during continuous renal replacement therapy: a case report and pharmacokinetic analysis.

    PubMed

    Rosenborg, Staffan; Saraste, Lars; Wide, Katarina

    2014-08-01

    Phenobarbital is an old antiepileptic drug used in severe epilepsy. Despite this, little is written about the need for dose adjustments in renal replacement therapy. Most sources recommend a moderately increased dose guided by therapeutic drug monitoring.A 14 year old boy with nonketotic hyperglycinemia, a rare inborn error of metabolism, characterized by high levels of glycine, epilepsy, spasticity, and cognitive impairment, was admitted to the emergency department with respiratory failure after a few days of fever and cough. The boy was unconscious at admittance and had acute renal and hepatic failure.Due to the acute respiratory infection, hypoxic hepatic and renal failure occurred and the patient had a status epilepticus.The patient was intubated and mechanically ventilated. Continuous renal replacement therapy was initiated. Despite increased phenobarbital doses, therapeutic levels were not reached until the dose was increased to 500 mg twice daily. Therapeutic drug monitoring was performed in plasma and dialysate. Calculations revealed that phenobarbital was almost freely dialyzed.Correct dosing of drugs in patients on renal replacement therapy may need a multidisciplinary approach and guidance by therapeutic drug monitoring.

  4. Telavancin and hydroxy propyl-beta-cyclodextrin clearance during continuous renal replacement therapy: an in vitro study.

    PubMed

    Patel, Jignes H; Churchwell, Marianne D; Seroogy, Julie D; Barriere, Steven L; Grio, Maricor; Mueller, Bruce

    2009-10-01

    Telavancin is a lipoglycopeptide antimicrobial agent which has been approved in Europe and has been recently FDA approved in the United States. Telavancin's parenteral solution contains hydroxy propyl-beta -cyclodextrin (HP-beta -CD) to enhance its solubility. The disposition of telavancin and HP-beta -CD during continuous renal replacement therapies (CRRT ) has not been previously reported. The transmembrane clearances (CLtm ) of telavancin and HP-beta -CD during continuous hemofiltration and hemodialysis were assessed using an in vitro bovine blood model with AN69 and polysulfone hemodiafilters at varying ultrafiltrate and dialysate flow rates (1, 2, 3, & 6 l/hr). The mean telavancin sieving coefficient ranged from 0.25 to 0.31 during continuous hemofiltration. At all ultrafiltration rates, no differences were observed in telavancin CLtm between the two hemodiafilter types. For continuous hemodialysis, mean telavancin saturation coefficients ranged from 0.10 to 0.43 and CLtm tended to be higher for the polysulfone hemodiafilter than the AN69 hemodiafilter, especially at higher flow rates. Mean HP-beta -CD sieving coefficients ranged from 0.63 to 1.03 and saturation coefficients from 0.63 to 1.38, resulting in a CLtm that was similar to ultrafiltrate and dialysate flow rates. Telavancin CLtm is dependent on hemodiafilter type, dialysate and ultrafiltration rates. CRRT with high ultrafiltrate or dialysate rates may result in sufficient telavancin clearance to alter telavancin dosing. HP-beta -CD clearance by continuous hemodialysis or continuous hemofiltration is substantial and may be sufficient to prevent HP-beta -CD accumulation in subjects receiving CRRT . Pharmacokinetic studies conducted in patients receiving CRRT and telavancin are needed to confirm these in vitro findings.

  5. 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.

  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. 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.

  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. Impact of renal replacement modalities on the clearance of piperacillin-tazobactam administered via continuous infusion in critically ill patients.

    PubMed

    Roger, Claire; Cotta, Menino O; Muller, Laurent; Wallis, Steven C; Lipman, Jeffrey; Lefrant, Jean-Yves; Roberts, Jason A

    2017-08-01

    This prospective pharmacokinetic study aimed to compare the clearance of piperacillin-tazobactam administered as a 24-h continuous infusion between continuous venovenous haemodiafiltration (CVVHDF) and continuous venovenous haemofiltration (CVVH) applied at equal dose in critically ill patients. A loading dose of 4.5 g of piperacillin-tazobactam followed by a continuous infusion (500 mg/h) was administered to patients randomized to receive CVVHDF or CVVH. Serial pre- and postfilter blood samples were drawn during an 8-h sampling interval. Piperacillin plasma concentrations were measured using a validated chromatography method. Piperacillin pharmacokinetics were calculated using a non-compartmental approach. In total, 212 piperacillin plasma concentrations were determined. Median [interquartile range (IQR)] total piperacillin clearance was 7.5 (5.9-11.2) L/h in the CVVHDF group and 4.7 (4.5-9.6) L/h in the CVVH group (P = 0.21). Median (IQR) piperacillin clearance related to continuous renal replacement therapy (CRRT) was 3.0 (2.7-3.2) L/h in the CVVHDF group and 2.6 (1.9-3.0) L/h in the CVVH group (P = 0.29). Mean (standard deviation) steady state concentrations were 68.4 (25.8) mg/L in the CVVHDF group and 89.1 (35.6) mg/L in the CVVH group (P = 0.16). The estimated unbound concentrations resulting from piperacillin continuous infusion were above the target susceptibility breakpoint (16 mg/L) for the entire dosing interval (100% fT>MIC) in all study patients. In the present study, higher (but not significantly) piperacillin clearance and lower piperacillin exposure were observed in patients receiving CVVHDF compared with CVVH. In patients receiving CRRT, the use of piperacillin continuous infusion should be considered to ensure optimal exposure for less susceptible pathogens. Copyright © 2017. Published by Elsevier B.V.

  10. Ureic clearance granule, alleviates renal dysfunction and tubulointerstitial fibrosis by promoting extracellular matrix degradation in renal failure rats, compared with enalapril.

    PubMed

    Huang, Yan-Ru; Wei, Qing-Xue; Wan, Yi-Gang; Sun, Wei; Mao, Zhi-Min; Chen, Hao-Li; Meng, Xian-Jie; Shi, Xi-Miao; Tu, Yue; Zhu, Quan

    2014-09-29

    Chinese herbal compound prescription has a unique therapeutic action on chronic kidney disease (CKD) in China. In clinics, Uremic Clearance Granules (UCG), a compounded Chinese patent medicine, has been frequently used to treat chronic renal failure (CRF) patients for nearly 30 years, however, the deep therapeutic mechanisms involved in vivo remain a challenge. This study aims to demonstrate the effects and mechanisms of UCG on renal dysfunction and tubulointerstitial fibrosis by regulating extracellular matrix (ECM) degradation and transforming growth factor (TGF)-beta1/Smad signaling activity in vivo, compared with enalapril. Twenty-six rats were randomly divided into 4 groups, a sham-operated group (Sham group), a vehicle-intervened group (Vehicle group), a UCG-treated group (UCG group) (5g/kg/day) and an enalapril-treated group (Enalapril group) (20mg/kg/day). The rats with renal failure were induced by adenine (150 mg/kg/day) and unilateral ureteral obstruction (UUO), and killed on day 35 after the administration. Proteinuria, urinary N-acetyl-beta-D-glucosaminidase (UNAG), blood biochemical parameters, renal morphological changes, collagen type IV (CIV), matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors of metalloproteinase (TIMP)-1, as well as the key molecular protein expressions in TGF-beta1/Smad signaling pathway were observed, respectively. Adenine administration and UUO induced severe renal damages, as indicated by renal dysfunction, proteinuria and the marked histopathological injuries in the tubules and interstitium, which were associated with MMP-2/TIMP-1 imbalance and TGF-beta1/Smad signaling activity, as shown by up-regulation of the protein expressions of TGF-beta1, TGF-beta receptor type I (RI), TGF-beta receptor type II (RII), Smad2/3, phosphorylated-Smad2/3 (p-Smad2/3) and Smad4, as well as down-regulation of the protein expression of Smad7 in the kidney. UCG treatment, however, significantly not only attenuated renal dysfunction

  11. Retrograde intrarenal surgery for the treatment of renal stones in children: factors influencing stone clearance and complications.

    PubMed

    Azili, Mujdem Nur; Ozcan, Fatma; Tiryaki, Tugrul

    2014-07-01

    Retrograde intrarenal surgery (RIRS) is a known option for the treatment of upper tract calculi with an excellent success. However, the reports of RIRS in prepubertal children are limited. In this study, we evaluated the factors which affected the success rate and the complications of RIRS at renal stone treatment in childhood. We retrospectively reviewed the records of children under 14 years old who underwent RIRS for renal stone disease between January 2009 and December 2012. Patients' age, gender, body mass index (BMI), stone size, stone location, stone number, intraoperative complications, stone free status, postoperative complications were recorded. There were 80 ureterorenoscopic procedures performed in 58 renal units of 47 children (23 males and 24 females). The patients' ages ranged from 8 months to 14 years (mean age 4.7 ± 3.4 years). There was a difference in the distribution of symptoms in age groups. UTI was higher in the 1-4 years age group, abdominal pain was seen mostly in children aged 5-14 years. Multiple stones (included staghorn stone) were noted in 60.4% of patients. In 27.6% of patients, ureteral stones were accompanied by renal stones in our series. In the infancy group, cystine and staghorn stones were more frequently seen, mostly bilateral. After a single ureteroscopic procedure for intrarenal stones in children, we achieved stone free status in 50.9% of the ureters (n=26). After the repeated sessions, the stone clearance rate reached to 85.1%. Retrograde intrarenal surgery can be used as a first line therapy to treat renal stones in children. This is especially important if an associated ureteral stone is present that requires treatment; or in patients with cystinuria, which is not favorably treated with ESWL. Complications were seen more frequently in patients with cystine stones. Extravasation was noted more frequently in patients admitted with UTIs. There was a significant relationship between the conversion to open procedures and the

  12. 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

  13. Single-sample 99mTc-diethylenetriamine penta-acetate plasma clearance in advanced renal failure by the mean sojourn time approach.

    PubMed

    Gref, Margareta C; Karp, Kjell H

    2009-03-01

    The single-sample Tc-diethylenetriamine penta-acetate (DTPA) clearance method by Christensen and Groth is recommended by the Radionuclides in Nephrourology Committee on Renal Clearance for use in adults with an estimated glomerular filtration rate (GFR) > or = 30 ml/min. The purpose of this study was to test a new Tc-DTPA single-sample low clearance formula for GFR lesser than 30 ml/min. Twenty-one adult patients (29 investigations) were included. Reference clearance was calculated with both Cr-EDTA and Tc-DTPA according to Brøchner-Mortensen with samples drawn between 3 and 24 h. Single-sample clearance was calculated from a 24 h sample using the low clearance formula(Equation is included in full-text article.) C(t) is the activity of the tracer in the plasma sample t minutes after the injection and Q0 is the injected amount. ECV is the extracellular volume in ml defined as the distribution volume of the tracer. ECV is estimated from the body surface area as ECV=8116.6xbody surface area-28.2. The mean difference between reference and Tc-DTPA single-sample clearance was -0.5 ml/min (SD 1.0 ml/min) for Tc-DTPA and -0.8 ml/min (SD 1.2 ml/min) for Cr-EDTA as reference clearance. In adult patients it is possible, even with GFR lesser than 30 ml/min, to get an accurate determination of Tc-DTPA plasma clearance from a single sample using the mean sojourn time approach. The blood sample should be obtained about 24 h after injection of the GFR tracer.

  14. Clearance of glucoregulatory peptide hormones during haemodialysis and haemodiafiltration in non-diabetic end-stage renal disease patients.

    PubMed

    Jørgensen, Morten B; Idorn, Thomas; Knop, Filip K; Holst, Jens J; Hornum, Mads; Feldt-Rasmussen, Bo

    2015-03-01

    Patients with end-stage renal disease (ESRD) have increased fasting concentrations and disturbed postprandial responses of several glucoregulatory hormones. We aimed to evaluate the impact of high-flux haemodialysis (HD) and high-volume haemodiafiltration (HDF) on fasting and postprandial plasma levels of glucoregulatory pancreatic and gut peptide hormones in ESRD patients. Ten non-diabetic HD-treated ESRD patients were included to undergo a 3-h standardized liquid mixed meal test 1 h into an HD and an HDF, respectively. On a third, optional, examination day, the meal test was performed without concurrent dialysis treatment. Concentrations of glucose, C-peptide, insulin, glucagon, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide were measured in plasma and dialysate. Ten participants completed the meal test during HD, eight completed the meal test during HDF and four completed the optional meal test without dialysis. All plasma hormone concentrations declined significantly during the first fasting hour of dialysis with no differences between HD and HDF. Significant clearance of the investigated hormones was observed for both dialysis modalities with significantly higher clearance of insulin, C-peptide and GIP during HDF compared with HD. The fractional appearance of hormones entering the utilized dialysate was higher during HDF. Both dialysis modalities reduced postprandial plasma hormone concentrations in a similar manner. Our findings show that HD and HDF, respectively, significantly remove glucoregulatory peptide hormones from plasma of non-diabetic ESRD patients; a phenomenon which may affect the glucose metabolism in dialysis-treated ESRD patients. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. Evaluation of IAEA Clearance Concept for Low-level Radioactive Waste from a Radioisotope Research Institute.

    PubMed

    Yumoto, Yasuhiro; Okada, Shigeru; Kinno, Ikuo; Nagamatsu, Tomohiro; Nouso, Kazuhiro; Nakayama, Eiichi

    2016-05-01

    The clearance of solid low-level radioactive laboratory waste (LLRW) after decay-in-storage (DIS) obtained from a research institute and thoroughly separated using the separation and classification protocols presented in this study was evaluated. The radioisotope (RI) content of incinerated LLRW from the specified RI research group (group A); the RI content of LLRW obtained in fiscal year 2000, which contained radionuclides with half-lives of less than 164 d (LLRW2); and the RI content of the LLRW reported in group A's disposal records were compared. The LLRW2 and LLRW of group A were incinerated after 2 y of decay-in-storage and immediately after storage, respectively. The highest ratio of the RI of incinerated LLRW to the value in the disposal records was 2.52 for ⁵¹Cr. The radioactivities of radionuclides in both the LLRW2 and LLRW for ³⁵S, ⁴⁵Ca, ⁵¹Cr, ¹²⁵I, ³²P, ³³P, and ⁹⁹mTc and the incinerated ash after 1 y later of decay-in-storage were below the clearance level defined by the RS-G-1.7 of the International Basic Safety Standard without contamination by ³H and ¹⁴C. These remains contained very small amounts of some long-half-life radionuclides of natural origin after 7 y of decay-in-storage. This LLRW separation protocol was effective for the separation of ³H and ¹⁴C. LLRW2 after 2 years of DIS and its incinerated ash after one year later of DIS were below the clearance level for radioactivity and radioactivity concentration.

  20. 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. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  1. 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

  2. The association of clearance of middle and large molecular weight substance with arterial stiffness and left ventricular mass in children receiving renal replacement therapy.

    PubMed

    Özdemir, K; Yilmaz, E; Dincel, N; Bozabali, S; Apaydın, S; Gun, Z H; Sozeri, B; Mir, S

    2015-04-30

    The prominent cause of mortality in children receiving dialysis treatment is cardiovascular diseases. Risk factors related to chronic renal disease, are effective in the development of cardiovascular diseases. The aim of study was to investigate cardiovascular system (CVS) involvement for functional and structural alterations in children receiving dialysis, and display any association between cardiovascular morbidity and uremic toxins. 20 dialysis patients and 20 healthy controls were included to the study. Clearance of small, middle and large molecular-weight uremic toxins was evaluated in blood samples collected 30 minutes before(D0) and 2 hour after dialysis(D2), and change value was calculated as; D0--D2/ D0. Cardiovascular involvement was determined by comparing arterial stiffness, Carotid intima-media thickness (CIMT) and left ventricular mass index (LVMI) with the control group. Four patients receiving hemodialysis and two patients in continuous ambulatory peritoneal dialysis (CAPD) group who have significant differences in all functional and structural parameters were detected. 4 dialysis--patients with detected cardiovascular disease have distinctively lower beta--2 micro globulin and homocysteine clearances compared to the patients with no CVS involvement. The clearance of middle and large molecular--weight substances should be closely monitored in children receiving dialysis.

  3. Progressive decline in tacrolimus clearance after renal transplantation is partially explained by decreasing CYP3A4 activity and increasing haematocrit

    PubMed Central

    de Jonge, Hylke; Vanhove, Thomas; de Loor, Henriëtte; Verbeke, Kristin; Kuypers, Dirk R J

    2015-01-01

    Aims The long-term disposition of tacrolimus following kidney transplantation is characterized by a gradual decrease in dose requirements and increase in dose-corrected exposure. This phenomenon has been attributed to a progressive decline in cytochrome P450 3A4 (CYP3A4) activity, although this has never been demonstrated in vivo. Methods Sixty-five tacrolimus- and 10 cyclosporine-treated renal transplant recipients underwent pharmacokinetic testing at day 7 and months 1, 3, 6 and 12 after transplantation, including 8-h area under the concentration-time curve (AUC) for tacrolimus or cyclosporine and assessment of CYP3A4 activity using oral and intravenous midazolam (MDZ) drug probes. Results Tacrolimus clearance decreased gradually throughout the entire first year but only in CYP3A5*3/*3 homozygous recipients (25.6 ± 11.1 l h–1 at day 7; 17 ± 9.1 l h–1 at month 12; P < 0.001). In mixed model analysis, decreasing CYP3A4 activity, measured by apparent oral MDZ clearance (924 ± 443 ml min–1 at day 7 vs. 730 ± 344 ml min–1 at month 1; P < 0.001), explained 55.4% of the decline in tacrolimus clearance in the first month. CYP3A4 activity decreased by 18.9 ml min–1 for every milligram of methylprednisolone dose tapering within the first month; beyond this point it remained stable. A gradual rise in haematocrit throughout the entire first year explained 31.7% of the decrease in tacrolimus clearance in the first month and 23.6% of the decrease between months 1 and 12. Cyclosporine clearance did not change over time. Conclusions The maturation of tacrolimus disposition in the first year after renal transplantation observed in CYP3A5*3/*3 homozygous patients can partly be explained by a (steroid tapering-related) decline in CYP3A4 activity and a progressive increase in haematocrit. PMID:26114223

  4. Progressive decline in tacrolimus clearance after renal transplantation is partially explained by decreasing CYP3A4 activity and increasing haematocrit.

    PubMed

    de Jonge, Hylke; Vanhove, Thomas; de Loor, Henriëtte; Verbeke, Kristin; Kuypers, Dirk R J

    2015-09-01

    The long-term disposition of tacrolimus following kidney transplantation is characterized by a gradual decrease in dose requirements and increase in dose-corrected exposure. This phenomenon has been attributed to a progressive decline in cytochrome P450 3A4 (CYP3A4) activity, although this has never been demonstrated in vivo. Sixty-five tacrolimus- and 10 cyclosporine-treated renal transplant recipients underwent pharmacokinetic testing at day 7 and months 1, 3, 6 and 12 after transplantation, including 8-h area under the concentration-time curve (AUC) for tacrolimus or cyclosporine and assessment of CYP3A4 activity using oral and intravenous midazolam (MDZ) drug probes. Tacrolimus clearance decreased gradually throughout the entire first year but only in CYP3A5*3/*3 homozygous recipients (25.6 ± 11.1 l h(-1) at day 7; 17 ± 9.1 l h(-1) at month 12; P < 0.001). In mixed model analysis, decreasing CYP3A4 activity, measured by apparent oral MDZ clearance (924 ± 443 ml min(-1) at day 7 vs. 730 ± 344 ml min(-1) at month 1; P < 0.001), explained 55.4% of the decline in tacrolimus clearance in the first month. CYP3A4 activity decreased by 18.9 ml min(-1) for every milligram of methylprednisolone dose tapering within the first month; beyond this point it remained stable. A gradual rise in haematocrit throughout the entire first year explained 31.7% of the decrease in tacrolimus clearance in the first month and 23.6% of the decrease between months 1 and 12. Cyclosporine clearance did not change over time. The maturation of tacrolimus disposition in the first year after renal transplantation observed in CYP3A5*3/*3 homozygous patients can partly be explained by a (steroid tapering-related) decline in CYP3A4 activity and a progressive increase in haematocrit. © 2015 The British Pharmacological Society.

  5. 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.

  6. Effective clearance of Ara-U the major metabolite of cytosine arabinoside (Ara-C) by hemodialysis in a patient with lymphoma and end-stage renal failure.

    PubMed

    Radeski, Dejan; Cull, Gavin M; Cain, Michael; Hackett, L Peter; Ilett, Kenneth F

    2011-04-01

    We report that hemodialysis clears Ara-U from the blood after high-dose Ara-C treatment in a patient with lymphoma and end-stage renal failure. The patient received two doses of Ara-C 1 g/m(2) 24 h apart and was hemodialyzed at about 6 h after each dose and subsequently as per her usual dialysis schedule. Multiple blood samples were collected after dosing. Blood and dialyzate were also collected from the dialysis circuit during a second identical treatment cycle. Ara-C and its metabolite Ara-U in plasma and dialyzate were measured chromatographically, and the data subjected to pharmacokinetic analysis. The distribution and elimination half-lives, steady-state volume of distribution and clearance values were 0.5 h, 7 h, 181 L and 307 l/h for Ara-C and 4.1 h, 34 h, 118 L and 2.64 l/h for Ara-U, respectively. The dialysis sessions immediately after the first and second doses cleared 39 and 52% (as Ara-U) of the respective Ara-C doses. Some 63% of Ara-U in plasma was extracted by dialysis. The patient showed no signs of neurotoxicity or other drug-related adverse effects. Hemodialysis is very effective in clearing Ara-U from the plasma in renal failure, and this maneuver could easily be used routinely to prevent Ara-U accumulation and minimize adverse effects in patients with renal failure.

  7. 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

  8. 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

  9. 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.

  10. 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

  11. Challenges in Individualizing Drug Dosage for Intensive Care Unit Patients: Is Augmented Renal Clearance What We Really Want to Know? Some Suggested Management Approaches and Clinical Software Tools.

    PubMed

    Jelliffe, Roger

    2016-08-01

    Acutely ill intensive care unit (ICU) patients often have large apparent volumes of distribution of drugs and, because of this, their drug clearance (CL) is usually also increased. 'Augmented renal Cl' is a current issue in the management of drug therapy for acutely ill and unstable ICU patients; however, Cl, the product of volume and the rate constant for excretion, describes only a theoretical volume of drug cleared per unit of time. Information of the actual rate of movement of the drug itself is obscured. It is suggested that the most useful clinical information is given by describing drug volume and elimination rate constant separately. This also permits better understanding of the patient's separate issues of fluid balance and drug elimination, especially when dialysis, renal replacement therapy, or extracorporeal membrane oxygenation (ECMO) may be used, and facilitates management of these two important separate clinical issues. Optimal management of drug therapy also requires optimal methods embodied in clinical software to describe drug behavior in these highly unstable patients, and considerably more data than for ordinary patients. The interacting multiple model (IMM) clinical software facilitates management of both fluid balance and drug therapy in these unstable patients. Illustrative cases are discussed, and new monitoring and management strategies are suggested. Like other ICU skills, physicians need to learn optimal tools for managing drug therapy in the ICU. Further work should help evaluate these new approaches.

  12. 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

  13. 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.

  14. 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.

  15. [Concept to improve adherence in adolescents following renal transplantation: vision or reality?].

    PubMed

    John, U; Offner, G; Breuch, K; Oldhafer, M

    2009-12-01

    Transition to adult care is a generic issue for subspecialties dealing with chronic illness and has received little attention to date. The transition from pediatric to adult care for renal transplant recipients is recognized as a high-risk period for poor graft outcome associated with more than 20% graft loss. Non-adherence to immunosuppressive medications is one of the most important factors contributing to graft loss during this period. Transition is, therefore, a concern of both pediatric and adult providers, and medical improvements in this area will require more effective collaboration at this interface. This report explores medical and psychological risk factors and barriers during the transition process. In addition, a specially developed coaching concept for young adults is presented intended to assist adolescents with early childhood end-stage renal disease in the transition from pediatric to adult care.

  16. PGI2 synthesis and excretion in dog kidney: evidence for renal PG compartmentalization

    SciTech Connect

    Boyd, R.M.; Nasjletti, A.; Heerdt, P.M.; Baer, P.G.

    1986-01-01

    To assess the concept of compartmentalization of renal prostaglandins (PG), we compared entry of PGE2 and the PGI2 metabolite 6-keto-PGF1 alpha into the renal vascular and tubular compartments, in sodium pentobarbital-anesthetized dogs. Renal arterial 6-keto-PGF1 alpha infusion increased both renal venous and urinary 6-keto-PGF1 alpha outflow. In contrast, renal arterial infusion of arachidonic acid (AA) or bradykinin (BK) increased renal venous 6-keto-PGF1 alpha outflow but had no effect on its urinary outflow. Both urinary and renal venous PGE2 outflows increased during AA or BK infusion. Ureteral stopped-flow studies revealed no postglomerular 6-keto-PGF1 alpha entry into tubular fluid. During renal arterial infusion of (3H)PGI2 and inulin, first-pass 3H clearance was 40% of inulin clearance; 35% of urinary 3H was 6-keto-PGF1 alpha, and two other urinary metabolites were found. During renal arterial infusion of (3H)6-keto-PGF1 alpha and inulin, first-pass 3H clearance was 150% of inulin clearance; 75% of urinary 3H was 6-keto-PGF1 alpha, and only one other metabolite was found. We conclude that in the dog PGE2 synthesized in the kidney enters directly into both the renal vascular and tubular compartments, but 6-keto-PGF1 alpha of renal origin enters directly into only the renal vascular compartment.

  17. 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.

  18. MINEFIELD CLEARANCE

    DTIC Science & Technology

    ACCURACY, DETONATIONS, EMPLACEMENT, ENEMY, EXPLOSIONS, GUNFIRE, MINE CLEARANCE , MINEFIELDS, MINES(ORDNANCE), RECIPROCATING ENGINES, RELIABILITY, SYNCHRONISM, TRANSVERSE, VELOCITY, VERTICAL ORIENTATION, VULNERABILITY.

  19. The assessment of glomerular function: creatinine clearance or plasma creatinine?

    PubMed Central

    Morgan, D. B.; Dillon, S.; Payne, R. B.

    1978-01-01

    Plasma creatinine concentration is superior to creatinine clearance for the detection of abnormal glomerular function, of changes of glomerular function in patients with chronic renal disease. Creatinine clearance should be abandoned as the routine assessment of glomerular function. PMID:673986

  20. 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

  1. 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

  2. Glomerular Filtration Rate Measured by 51Cr-EDTA Clearance: Evaluation of Captopril-Induced Changes in Hypertensive Patients with and without Renal Artery Stenosis

    PubMed Central

    Chaves, Anna Alice Rolim; Buchpiguel, Carlos Alberto; Praxedes, Jose Nery; Bortolotto, Luiz Aparecido; Sapienza, Marcelo Tatit

    2010-01-01

    INTRODUCTION: Renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA) could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using 51Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. METHODS: This prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21) and without renal artery stenosis, (n=20). In vitro glomerular filtration rate analysis (51Cr-EDTA) and 99mTc-DMSA scintigraphy were performed before and after captopril administration in all patients. RESULTS: The mean baseline glomerular filtration rate was 48.6±21.8 ml/kg/1.73 m2 in the group wuth renal artery stenosis, which was significantly lower than the GFR of 65.1±28.7 ml/kg/1.73m2 in the group without renal artery stenosis (p=0.04). Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6±14.8 ml/ kg/1.73m2, p=0.001) and an insignificant change in the group without RAS (to 62.2±23.6 ml/kg/1.73m2, p=0.68). Scintigraphy with technetium-99m dimercapto-succinic acid (DMSA) did not show significant

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. Multifunctional Mesoporous Silica Nanospheres with Cleavable Gd(III) Chelates as MRI Contrast Agents: Synthesis, Characterization, Target-Specificity, and Renal Clearance

    PubMed Central

    Vivero-Escoto, Juan L.; Taylor-Pashow, Kathryn M. L.; Huxford, Rachel C.; Rocca, Joseph Della; Okoruwa, Christie; An, Hongyu; Lin, Weili

    2013-01-01

    Mesoporous silica nanospheres (MSNs) are a promising material for magnetic resonance imaging (MRI) contrast agents. In this paper multifunctional MSNs with cleavable Gd(III) chelates are synthesized and characterized, and their applicability as MRI contrast agents is demonstrated both in vitro and in vivo. The MSNs contain Gd(III) chelates that are covalently linked via a redox-responsive disulfide moiety. The MSNs are further functionalized with polyethylene glycol (PEG) and an anisamide ligand to improve their biocompatibility and target specificity. The effectiveness of MSNs as an MRI imaging contrast agent and their targeting ability are successfully demonstrated in vitro using human colon adenocarcinoma and pancreatic cancer cells. Finally, the capability of this platform as an in vivo MRI contrast agent is tested using a 3T scanner. The Gd(III) chelate was quickly cleaved by the blood pool thiols and eliminated through the renal excretion pathway. Further tuning of the Gd(III) chelate release kinetics is needed before the MSN system can be used as target-specific MRI contrast agents in vivo. PMID:22069305

  11. 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.

  12. [Dose and time dependency of "CT clearance"].

    PubMed

    Kaltenborn, H A; Klose, K J; Dexheimer, C; von Steinijans

    1989-06-01

    The contrast medium dose used in CT renal function analysis corresponds to about 1 ml/kg body weight at a measurement interval of 5 or 10 minutes. In the present study the dependence of "CT clearance" on dosage and time was examined in 12 healthy subjects. The amount of clearance was directly proportional to the employed contrast medium dose and to the length of the measurement interval. On account of the superior signal-to-noise ratio, the higher dose (1 ml/kg body weight) will continue to be preferred in future. The measurement interval can be limited to 10 minutes.

  13. Tactics for Route Clearance

    DTIC Science & Technology

    1995-04-01

    Tadics for Jtoute Clearance By William C. Schneck, Jr., and Brian M. Green I n Somalia, military police used mine detectors to sweep for command...useful lessons re- garding command-detonated mines and route clearance . It is not possible to completely eliminate losses from mines, but commanders...success, route clearance must be treated as a combined arms combat operation. Infantry, armor, engineer, artillery, aviation, intelligence, and

  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. Nonlinear kinetics of the thiamine cation in humans: saturation of nonrenal clearance and tubular reabsorption.

    PubMed

    Weber, W; Nitz, M; Looby, M

    1990-12-01

    The pharmacokinetics of thiamine in plasma and urine was investigated in 13 healthy and 3 renal-insufficient volunteers. Doses ranging from 5 to 200 mg thiamine hydrochloride were administered either as an iv bolus or a 50-min infusion. A sum of 3 exponentials was used as the unit impulse response function to characterize plasma kinetics. Drug input was mathematically described as a rectangular pulse of length 2 or 50 min. Total clearance, defined as the reciprocal of the area under the unit impulse response function, was found to depend on dose and creatinine clearance, as shown by a multiple nonlinear regression analysis. The nonrenal component of the total clearance was demonstrated to be dose-dependent, whereas its mean renal component was only dependent on creatinine clearance. At high plasma concentrations renal clearance approached renal plasma flow, and remained constant during the decline to near physiological plasma levels. With further decline under a characteristic threshold concentration, renal clearance decreased far below the glomerular filtration rate, indicating tubular reabsorption. Binding to plasma proteins was excluded by ultrafiltration experiments. The process of renal excretion can be described by a combination of glomerular filtration, flow-dependent tubular secretion, and saturable tubular reabsorption. The concentration dependency of renal clearance was reflected in its mean value, which was only 76% of its maximum value measured in the higher concentration range. In the dose range studied, most of the given dose had already been linearly excreted before tubular reabsorption became evident, and consequently the measured mean renal clearances did not differ enough from one another to exhibit the expected dose dependency. With increasing dose a shift of the cleared dose fraction from the nonrenal to the renal side was observed. Saturated nonrenal clearance alone could explain this effect.

  16. Principles of antibacterial dosing in continuous renal replacement therapy.

    PubMed

    Choi, Gordon; Gomersall, Charles D; Tian, Qi; Joynt, Gavin M; Freebairn, Ross; Lipman, Jeffrey

    2009-07-01

    To outline the concepts involved in optimizing antibacterial dosing in critically ill patients with acute renal failure undergoing continuous renal replacement therapy (CRRT), provide a strategy for optimizing dosing, and summarize the data required to implement the strategy. MEDLINE search from February 1986 to 2008. Optimal dosing of antibacterials is dependent on achieving pharmacokinetic targets associated with maximal killing of bacteria and improved outcomes. The initial dose is dependent on the volume of distribution. Maintenance doses are dependent on clearance. Both should be adjusted according to the pharmacokinetic target associated with optimal bacterial killing, when known. The volume of distribution of some antibacterials is altered by critical illness or acute renal failure or both. Clearance by CRRT is dependent on the dose and mode of CRRT and the sieving or saturation coefficient of the drug. Both sieving and saturation coefficient are related to the plasma protein binding and thus may be altered in renal failure. Appropriate dose calculation requires knowledge of the pharmacokinetic target and the usual minimum inhibitory concentration of the suspected organism in the patient's locality (or if unavailable, the break point for the organism), published pharmacokinetic data (volume of distribution, non-CRRT clearance) on critically ill patients receiving CRRT (which may differ substantially from noncritically ill patients or those without renal failure), the sieving or saturation coefficient of the relevant drug in critically ill patients, the dose and mode of CRRT being used, and the actual dose of CRRT that is delivered. This large number of variables results in considerable inter- and intrapatient heterogeneity in dose requirements. This article provides basic principles and relevant data to guide the clinician in prescribing individualized dosing regimes.

  17. 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.

  18. 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.

  19. 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.

  20. Phagocytic Clearance in Neurodegeneration

    PubMed Central

    Sokolowski, Jennifer D.; Mandell, James W.

    2011-01-01

    The cellular and molecular mechanisms of phagocytic clearance of apoptotic cells and debris have been intensely studied in invertebrate model organisms and in the mammalian immune system. This evolutionarily conserved process serves multiple purposes. Uncleared debris from dying cells or aggregated proteins can be toxic and may trigger exaggerated inflammatory responses. Even though apoptotic cell death and debris accumulation are key features of neurodegenerative diseases, relatively little attention has been paid to this important homeostatic function in the central nervous system (CNS). This review attempts to summarize our knowledge of phagocytic clearance in the CNS, with a focus on retinal degeneration, forms of which are caused by mutations in genes within known phagocytic pathways, and on Alzheimer's disease (AD). Interest in phagocytic clearance mechanisms in AD was stimulated by the discovery that immunization could promote phagocytic clearance of amyloid-β; however, much less is known about clearance of neuronal and synaptic corpses in AD and other neurodegenerative diseases. Because the regulation of phagocytic activity is intertwined with cytokine signaling, this review also addresses the relationships among CNS inflammation, glial responses, and phagocytic clearance. PMID:21435432

  1. A health record integrated clinical decision support system to support prescriptions of pharmaceutical drugs in patients with reduced renal function: design, development and proof of concept.

    PubMed

    Shemeikka, Tero; Bastholm-Rahmner, Pia; Elinder, Carl-Gustaf; Vég, Anikó; Törnqvist, Elisabeth; Cornelius, Birgitta; Korkmaz, Seher

    2015-06-01

    To develop and verify proof of concept for a clinical decision support system (CDSS) to support prescriptions of pharmaceutical drugs in patients with reduced renal function, integrated in an electronic health record system (EHR) used in both hospitals and primary care. A pilot study in one geriatric clinic, one internal medicine admission ward and two outpatient healthcare centers was evaluated with a questionnaire focusing on the usefulness of the CDSS. The usage of the system was followed in a log. The CDSS is considered to increase the attention on patients with impaired renal function, provides a better understanding of dosing and is time saving. The calculated glomerular filtration rate (eGFR) and the dosing recommendation classification were perceived useful while the recommendation texts and background had been used to a lesser extent. Few previous systems are used in primary care and cover this number of drugs. The global assessment of the CDSS scored high but some elements were used to a limited extent possibly due to accessibility or that texts were considered difficult to absorb. Choosing a formula for the calculation of eGFR in a CDSS may be problematic. A real-time CDSS to support kidney-related drug prescribing in both hospital and outpatient settings is valuable to the physicians. It has the potential to improve quality of drug prescribing by increasing the attention on patients with renal insufficiency and the knowledge of their drug dosing. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. It is time to review concepts on renal involvement in leprosy: pre- and post-treatment evaluation of 189 patients.

    PubMed

    Polito, Maria Goretti; Moreira, Sílvia R; Nishida, Sonia K; Mastroianni Kirsztajn, Gianna

    2015-08-01

    Functional and morphological renal lesions have been widely described in leprosy for decades. Nevertheless few studies have assessed renal function pre- and during treatment after the advent of multidrug therapy (MDT). This is a prospective study involving 189 consecutive patients, with all forms of leprosy (Ridley-Jopling scale). Laboratory (serum urea and creatinine, estimated GFR, urinalysis, microalbuminuria, urinary RBP) and clinical features of renal disease were evaluated previously and after onset (3 and 8 months later) of MDT. One hundred and eighty-nine patients (M 1.8: F 1; mean age 44 ± 16 years) were included just after diagnosis of leprosy and before the introduction of MDT. Mean time until manifestation of symptoms and/or signs of leprosy was 29 ± 56 months (25 days-480 months). Microhematuria and microalbuminuria were detected in 7.5% and 9.6% of the cases, respectively. Elevated serum creatinine was detected in 34% pre-MDT; this was statistically more frequent in males, hypertensive and frequent users of non-steroidal anti-inflammatory drugs (NSAID), as well as in patients with erythema nodosum lepromatosum, 45.5% by the time of diagnosis, 18% after 3 months and 9% after 8 months of MDT (p = 0.039). Our results suggest that functional renal lesions in leprosy are currently mild and predominantly of glomerular origin, in opposition to the severe involvement described in the past. This improved outcome of renal disease secondary to leprosy is possibly due to the advent of MDT and effective treatment of episodes of reaction, leading to shorter periods of active infectious disease.

  3. Single center experience with application of the ALARA concept to serial imaging studies after blunt renal trauma in children--is ultrasound enough?

    PubMed

    Eeg, Kurt R; Khoury, Antoine E; Halachmi, Sarel; Braga, Luis H P; Farhat, Walid A; Bägli, Darius J; Pippi Salle, Joao L; Lorenzo, Armando J

    2009-04-01

    After properly staged renal injury many children will undergo radiological reevaluation with computerized tomography, the modality frequently favored for its widespread availability and anatomical detail. The ALARA (as low as reasonably achievable) concept attempts to balance the potential future risk of radiation induced malignancy with the added information obtained by the study. At our institution ultrasound has been increasingly adopted as the followup imaging technique of choice. We sought to evaluate this practice in pediatric blunt renal trauma management. We retrospectively analyzed the trauma database of a pediatric referral center for patients treated between 1997 and 2007. A total of 73 children with blunt renal trauma were identified. Associated injuries, mechanism of trauma, type of management, imaging studies, complications and delayed/missed injuries were evaluated. Mean patient age was 10.5 years and the male-to-female ratio was 3:2. In all patients the mechanism was blunt trauma. Average grade of injury at hospitalization was 2.4, with high grade injury observed in 32% of patients. Repeat computerized tomography was obtained in 11 patients (9 for nonurological injuries). Three nephrectomies were done in the setting of hemodynamic instability and 1 pseudoaneurysm was embolized. Four enlarging symptomatic urinomas were suspected by ultrasound. No clinically important injuries or complications due to delayed diagnosis were detected in patients followed with ultrasound. Our experience suggests that after initial computerized tomography for accurate staging of pediatric blunt renal trauma monitoring can be performed with ultrasound in most patients (excluding those with hemodynamic instability or deemed to require computerized tomography for associated injuries). Selective reevaluation with computerized tomography can be reserved for those with serial or ambiguous abnormalities detected on ultrasound, thus decreasing exposure to radiation.

  4. A Phase II Multicentre, Open-Label, Proof-of-Concept Study of Tasquinimod in Hepatocellular, Ovarian, Renal Cell, and Gastric Cancers.

    PubMed

    Escudier, Bernard; Faivre, Sandrine; Van Cutsem, Eric; Germann, Nathalie; Pouget, Jean-Christophe; Plummer, Ruth; Vergote, Ignace; Thistlethwaite, Fiona; Bjarnason, Georg A; Jones, Robert; Mackay, Helen; Edeline, Julien; Fartoux, Laetitia; Hirte, Hal; Oza, Amit

    2017-08-10

    Tasquinimod is a small molecule with immunomodulatory, anti-angiogenic, and anti-metastatic properties that targets the tumor microenvironment. This study aimed to obtain a clinical proof of concept that tasquinimod was active and tolerable in patients with advanced solid tumors. This early stopping design, open-label, proof-of-concept clinical trial evaluated the clinical activity of tasquinimod in four independent cohorts of patients with advanced hepatocellular (n = 53), ovarian (n = 55), renal cell (n = 38), and gastric (n = 21) cancers. Tasquinimod was given orally every day (0.5 mg/day for at least 2 weeks, with dose increase to 1 mg/day) until radiological progression according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria, intolerable toxicity, or patient withdrawal. The primary efficacy endpoint was progression-free survival (PFS) rate according to RECIST 1.1 by central assessment. Interim futility analyses at 8 weeks (6 weeks for the gastric cancer cohort) found adequate clinical activity of tasquinimod only in the hepatocellular cohort and recruitment to the other three cohorts was stopped. PFS rates were 26.9% at 16 weeks, 7.3% at 24 weeks, 13.2% at 16 weeks, and 9.5% at 12 weeks, respectively, in hepatocellular, ovarian, renal cell, and gastric cancer cohorts. The pre-defined PFS threshold was not reached in the hepatocellular cancer cohort at the second stage of the trial. The most common treatment-related adverse events were fatigue (48.5%), nausea (34.1%), decreased appetite (31.7%), and vomiting (24.6%). This study failed to demonstrate clinical activity of tasquinimod in heavily pre-treated patients with advanced hepatocellular, ovarian, renal cell, and gastric cancer. NCT01743469.

  5. Antimicrobial dosing in acute renal replacement.

    PubMed

    Fissell, William H

    2013-01-01

    Acute kidney injury (AKI) is a common problem in hospitalized patients and is associated with significant morbidity and mortality. Two large trials showed no benefit from increased doses of renal replacement therapy (RRT) despite previous clinical data suggesting that increased clearance from RRT has beneficial effects. Since infection is the leading cause of death in AKI, my group and others hypothesized that increased RRT antibiotic clearance might create a competing morbidity. The data from my group, as well as those of other groups, show that many patients are underdosed when routine "1 size fits all" antibiotic dosing is used in patients with AKI receiving continuous RRT (CRRT). Here, concepts of drug distribution and clearance in AKI are briefly discussed and then 1 antibiotic (piperacillin) is discussed in depth to illustrate the challenges in applying the medical literature to clinical practice. The fact that published data on drug dosing in AKI and dialysis reflect the evolution of practice patterns and often do not apply to present prescribing habits is also discussed. A more general approach to drug dosing facilitates situation-specific prescribing by the nephrologist and critical care specialist. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  6. 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

  7. 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.

  8. Carbamazepine clearance in hemodialysis and hemoperfusion.

    PubMed

    Kandrotas, R J; Oles, K S; Gal, P; Love, J M

    1989-02-01

    A 47-year-old woman with endstage renal disease and dialysis-induced encephalopathy was being treated with carbamazepine for myoclonus. Her carbamazepine serum concentration appeared to be therapeutic at 5.1 micrograms/ml. She experienced a seizure while on hemodialysis/hemoperfusion that was possibly related to the removal of carbamazepine during dialysis. The elimination of carbamazepine on a dialysis day was compared with elimination on a nondialysis day. The half-life and apparent clearance were the same for each day, indicating that hemodialysis/hemoperfusion had little effect on the overall removal of carbamazepine from the body. The possible reasons for this lack of effect are discussed.

  9. Bumetanide kinetics in renal failure

    SciTech Connect

    Pentikaeinen, P.J.P.; Pasternack, A.; Lampainen, E.; Neuvonen, P.J.; Penttilae, A.

    1985-05-01

    To study the effects of renal failure on bumetanide kinetics, the authors administered single intravenous doses of 1.0 mg/3.08 microCi /sup 14/C-bumetanide to six healthy subjects and 22 patients with variable degrees of renal failure. The kinetics of /sup 14/C-bumetanide and total /sup 14/C were adequately described by a two-compartment open model in the control subjects and in the patients. The volume of the central compartment and the distribution t1/2 were of the same order in both groups, whereas the mean (+/- SE) volume at steady state was larger (22.1 +/- 1.6 and 16.9 +/- 1.0 L) and the elimination t1/2 was longer (1.9 +/- 0.2 and 1.4 +/- 0.1 hours) in patients with renal failure than in healthy controls. Bumetanide renal clearance was lower (10 +/- 3 and 90 +/- 13 ml/min) in patients than in subjects and correlated with creatinine clearance (r = 0.784) and log serum creatinine level (r = -0.843), whereas nonrenal clearance was significantly higher in the patients (153 +/- /sup 14/ and 99 +/- 6 ml/min). Bumetanide total plasma clearance did not significantly change. The non-protein-bound, free fraction of bumetanide was higher in patients and correlated with plasma albumin levels (r = -0.777). The kinetics of total /sup 14/C showed similar but greater changes than those of 14C-bumetanide. Thus the most important changes in bumetanide kinetics in patients with renal failure are low renal clearance and a high free fraction, with a consequent increase in nonrenal clearance, volume of distribution, and elimination t1/2.

  10. 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

  11. Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis.

    PubMed

    Heintz, Brett H; Matzke, Gary R; Dager, William E

    2009-05-01

    Infectious diseases and impaired renal function often occur in critically ill patients, and delaying the start of appropriate empiric antimicrobial therapy or starting inappropriate therapy has been associated with poor outcomes. Our primary objective was to critically review and discuss the influence of chronic kidney disease (CKD) and acute kidney injury (AKI) on the clinical pharmacokinetic and pharmacodynamic properties of antimicrobial agents. The effect of continuous renal replacement therapies (CRRTs) and intermittent hemodialysis (IHD) on drug disposition in these two populations was also evaluated. Finally, proposed dosing strategies for selected antimicrobials in critically ill adult patients as well as those receiving CRRT or IHD have been compiled. We conducted a PubMed search (January 1980-March 2008) to identify all English-language literature published in which dosing recommendations were proposed for antimicrobials commonly used in critically ill patients, including those receiving CRRT or IHD. All pertinent reviews, selected studies, and associated references were evaluated to ensure their relevance. Forty antimicrobial, antifungal, and antiviral agents commonly used in critically ill patients were included for review. Dosage recommendations were synthesized from the 42 reviewed articles and peer-reviewed, evidence-based clinical drug databases to generate initial guidance for the determination of antimicrobial dosing strategies for critically ill adults. Because of the evolving process of critical illness, whether in patients with AKI or in those with CKD, prospective adaptation of these initial dosing recommendations to meet the needs of each individual patient will often rely on prospectively collected clinical and laboratory data.

  12. 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

  13. 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.

  14. Lung fluid clearance in chronic heart failure patients.

    PubMed

    Dixon, Dani-Louise; De Pasquale, Carmine G; Lawrence, Mark D; Cavallaro, Elena; Rubino, Vito; Bersten, Andrew D

    2017-10-01

    Chronic elevation of pulmonary microvascular pressure (Pmv) consistently leads to alveolocapillary barrier thickening and reduction in the filtration coefficient. In animal models of chronic heart failure (CHF) the lung remains dry despite hydrostatic forces. As fluid flux is bi-directional, it has been postulated that an increase in alveolar fluid clearance may facilitate the dry lung when Pmv is chronically elevated. In this study we aimed to examine alveolar fluid clearance in ambulatory patients with CHF secondary to left ventricular (LV) systolic dysfunction compared against non-CHF controls. Lung clearance following aerosol delivery of (99m)technetium (Tc)-diethyl triaminepentaacetic acid (DTPA) was measured non-invasively by scintigraphy and half time of (99m)Tc-DTPA clearance (T (1/2)) was calculated by mono-exponential curve fit. Alveolar fluid clearance measured as half time DTPA clearance was significantly faster in CHF patients than controls (P=0.001). This was further defined by NYHA classification. No correlation was found between DTPA clearance and plasma epinephrine, norepinephrine or aldosterone hormone (P>0.05). Our results support an association between increasing alveolar fluid clearance and disease severity in CHF, and the concept of controlled bi-directional fluid flux in CHF associated with increasing Pmv, and represents another defence mechanism of the lung against pulmonary oedema. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  15. Clearance of Tc-99m DTPA in hemodialysis and peritoneal dialysis: concise communication

    SciTech Connect

    Wainer, E.; Boner, G.; Lubin, E.; Rosenfeld, J.B.

    1981-09-01

    The clearance of Tc-99m DTPA was studied in 14 patients undergoing hemodialysis (HD) or peritoneal dialysis (PD). Mean Tc-99m DTPA clearance during HD was 37.8% +/- 10.1 of creatinine clearance. Mean Tc-99m DTPA clearance in PD was 65.1% +/- 10.3 of creatinine clearance. Tc-99m DTPA, with a larger molecular weight than that of creatinine, is cleared relatively better during PD than during HD. Thus Tc-99m DTPA may be used in the assessment of the effectiveness of different dialytic treatments for substances of similar molecular weight. In addition, our study shows that clearance of DTPA both in HD and PD is sufficiently high to allow the removal of this chelating agent in patients with renal failure.

  16. 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.

  17. 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

  18. 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.

  19. Clearance of Apoptotic Photoreceptors

    PubMed Central

    Hisatomi, Toshio; Sakamoto, Taiji; Sonoda, Koh-hei; Tsutsumi, Chikako; Qiao, Hong; Enaida, Hiroshi; Yamanaka, Ichiro; Kubota, Toshiaki; Ishibashi, Tatsuro; Kura, Shinobu; Susin, Santos A.; Kroemer, Guido

    2003-01-01

    The effective phagocytotic clearance of apoptotic debris is fundamental to the maintenance of neural tissues during apoptosis. Retinal photoreceptors undergo apoptosis after retinal detachment. Although their induction phase of apoptosis has been well discussed, their phagocytotic process remains quite unclear. We herein demonstrate that apoptotic photoreceptors are selectively eliminated from their physiological localization, the outer nuclear layer, to the subretinal space, and then phagocytosed by monocyte-derived macrophages. This could be shown by an ultrastructural and immunophenotypic analysis. Moreover, in chimera mice expressing transgenic green fluorescent protein in bone marrow-derived cells, the local infiltration of macrophages could be detected after retinal detachment-induced photoreceptor apoptosis. The local injection of an antibody blocking the phosphatidylserine receptor (PSR) or a peptide (GRGDSP)-blocking integrin αvβ3 revealed that phagocytotic clearance involves the PSR as well as integrin αvβ3 in vivo. Importantly, the level of blockade obtained with these reagents was different. Although anti-PSR increased the frequency of apoptotic cells that fail to bind to macrophages, GRGDSP prevented the engulfment (but not the recognition) of apoptotic photoreceptor cells by macrophages. To our knowledge, this is the first report describing the mechanisms through which apoptotic photoreceptors are selectively eliminated via a directional process in the subretinal space. PMID:12759244

  20. 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.

  1. Radial Clearance of Antifriction Bearings,

    DTIC Science & Technology

    The article concerns in detail the radial clearance of different antifriction bearings which belong to important parameters which influence the...longevity of the bearing to a certain extent. The effect of the influence of assembly and the wear on the radial clearance of different bearings, the...antifriction bearings operate and their respect in clearance and assembly can contribute substantially to decreasing the daily disproportionate bearing consumption for the repair and maintenance of different machines. (Author)

  2. Spreadsheet use to calculate creatinine clearance from serum creatinine.

    PubMed

    Shrewsberry, Timothy W; Banoub, Ashraf; Fleming, Kevin; Snyder, Holly; Stehlik, James

    2007-12-01

    Spreadsheets may be created to include the Cockcroft-Gault Formula (CGF) for creatinine-based estimation of glomerular filtration rate. Creatinine clearance (CrCl) provides a more accurate method for perioperative risk assessment of renal function than serum creatinine. CrCl may be used to develop guidelines for renal protective management strategies during cardiopulmonary bypass. CGF uses serum creatinine, age, kilogram weight, sex, and "logical test" functions within the spreadsheet to calculate the CrCl. Implementation of spreadsheets has the potential for numerous other calculations and may provide an accurate and consistent method of clinical perfusion management.

  3. 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

  4. 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.

  5. 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.

  6. [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.

  7. Mobile Health Medication Adherence and Blood Pressure Control in Renal Transplant Recipients: A Proof-of-Concept Randomized Controlled Trial.

    PubMed

    McGillicuddy, John W; Gregoski, Mathew J; Weiland, Anna K; Rock, Rebecca A; Brunner-Jackson, Brenda M; Patel, Sachin K; Thomas, Beje S; Taber, David J; Chavin, Kenneth D; Baliga, Prabhakar K; Treiber, Frank A

    2013-09-04

    Mobile phone based programs for kidney transplant recipients are promising tools for improving long-term graft outcomes and better managing comorbidities (eg, hypertension, diabetes). These tools provide an easy to use self-management framework allowing optimal medication adherence that is guided by the patients' physiological data. This technology is also relatively inexpensive, has an intuitive interface, and provides the capability for real-time personalized feedback to help motivate patient self-efficacy. Automated summary reports of patients' adherence and blood pressure can easily be uploaded to providers' networks helping reduce clinical inertia by reducing regimen alteration time. The aim of this study was to assess the feasibility, acceptability, and preliminary outcomes of a prototype mobile health (mHealth) medication and blood pressure (BP) self-management system for kidney transplant patients with uncontrolled hypertension. A smartphone enabled medication adherence and BP self-management system was developed using a patient and provider centered design. The development framework utilized self-determination theory with iterative stages that were guided and refined based on patient/provider feedback. A 3-month proof-of-concept randomized controlled trial was conducted in 20 hypertensive kidney transplant patients identified as non-adherent to their current medication regimen based on a month long screening using an electronic medication tray. Participants randomized to the mHealth intervention had the reminder functions of their electronic medication tray enabled and received a bluetooth capable BP monitor and a smartphone that received and transmitted encrypted physiological data and delivered reminders to measure BP using text messaging. Controls received standard of care and their adherence continued to be monitored with the medication tray reminders turned off. Providers received weekly summary reports of patient medication adherence and BP readings

  8. [Estimation of glomerular filtration rate by inulin clearance: comparison with creatinine clearance].

    PubMed

    Orita, Yoshimasa; Gejyo, Fumitake; Sakatsume, Minoru; Shiigai, Tatsuo; Maeda, Yoshitaka; Imai, Enyu; Fujii, Takashi; Endoh, Masayuki; Jinde, Kiichiro; Haneda, Masakazu; Sugimoto, Toshiro; Hishida, Akira; Takahashi, Satoru; Hosoya, Tatsuo; Yamamoto, Hiroyasu; Hora, Kazuhiko; Okada, Yoichi; Hosaka, Shigetoshi; Oguchi, Tomomasa; Kanno, Yutaka; Nishio, Yasuhide; Yano, Shintaro; Aikawa, Kazuo; Yasui, Kiyoshi

    2005-01-01

    Inulin clearance (Cin) is widely believed to be the gold standard of the glomerular filtration rate (GFR). However, in Japan, Cin has not been officially recognized by the Ministry of Health, Labour and Welfare of Japan for clinical use. Creatinine clearance (Ccr) has been used to estimate the renal function of patients, but there have been many studies in which Ccr estimates were GFR falsely high because the metabolism and tubular excretion of creatinine widely varied according to the pathophysiological state of the patient. In the present study, we determined Cin and Ccr simultaneously in 116 adult patients with renal diseases and diabetic mellitus. The clearance study was performed by the modified Wesson's method. The inulin preparation was FFI-1010 (Fuji Yakuhin Co. Ltd.). Inulin in serum and urine was determined by the newly devised enzymatic assay (Toyobo Co. Ltd.), which is specific for inulin. The mean Cin was 35.0 +/- 14.4 ml/min/1.73 m2. The mean Ccr(the enzyme assay) was 63.6 +/- 24.1 ml/min/1.73 m2 and that of the kinetic Jaffe assay was 55.3 +/- 19.3 ml/min/1.73 m2. Mean Ccr/Cin was 1.93 +/- 0.73, 1.69 +/- 0.62, respectively. This ratio was significantly different(p < 0.05) in the degree of reduction of Cin, with values of 2.07 +/- 0.82 (Cin < 40 ml/min/1.73 m2) and 1.64 +/- 0.32(40 < Cin < 80 ml/min/1.73 m2), respectively. Only 8 patients were classified into the same degree of reduced renal function (the Guideline of Japanese Society of Nephrology). The findings of this study suggest that the GFR determined by Ccr could misjudge the renal function of patient and delay the administration of proper treatment of the patient. Introduction of Cin into the clinical field is necessary to avoid this delay.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. Renal handling of fleroxacin in rabbits, dogs, and humans.

    PubMed Central

    Shiba, K; Saito, A; Shimada, J; Hori, S; Kaji, M; Miyahara, T; Kusajima, H; Kaneko, S; Saito, S; Ooie, T

    1990-01-01

    The renal handling of fleroxacin was studied by renal clearance and stop-flow techniques in rabbits and dogs and by analyzing the pharmacokinetics with and without probenecid in humans. In rabbits the excretion ratios (fleroxacin intrinsic renal clearance/glomerular filtration rate) were greater than unity (2.01) without probenecid and were decreased to a value below unity (0.680) with probenecid. In dogs, on the other hand, the excretion ratios were less than unity (0.608 and 0.456) both without and with probenecid, and so were not affected by probenecid. This fact suggested that fleroxacin was excreted into urine by both glomerular filtration and renal tubular secretion in rabbits, but only by glomerular filtration in dogs, accompanied by partial renal tubular reabsorption in both species; these mechanisms were also supported by stop-flow experiments. In humans probenecid treatment induced increases in the elimination half-life and area under the serum concentration-time curve and decreases in apparent serum clearance, renal clearance, and urinary recovery of fleroxacin. The excretion ratio without probenecid was 1.13, which was significantly decreased to 0.750 with probenecid. These results indicated that both renal tubular secretion and reabsorption contributed to renal excretion of fleroxacin in humans. The contribution of tubular secretion was species dependent and was extensive in rabbits, minimal in dogs, and moderate in humans. Renal tubular reabsorption was commonly found in every species. The long elimination half-life of fleroxacin in humans might be explained by its small total serum clearance and small renal clearance, which are attributed to less tubular secretion and more tubular reabsorption. PMID:2109576

  16. 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. © 2011 Blackwell Publishing Ltd.

  17. Renal dysfunction in patients with thalassaemia

    PubMed Central

    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.

    2014-01-01

    Summary 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 β2-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. PMID:21332704

  18. 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.

  19. Determining vancomycin clearance in an overweight and obese population.

    PubMed

    Leong, Julie V B; Boro, Maureen S; Winter, Michaele

    2011-04-01

    Two methods of calculating vancomycin clearance were compared to determine the best body weight measure to use when dosing vancomycin for overweight and obese patients. Hospitalized veterans weighing more than 120% of their ideal body weight (IBW) with serum vancomycin concentrations (SVCs) drawn between January 1, 2003, and June 30, 2005, were eligible for study inclusion. Exclusion criteria included weight of more than 300% the IBW, unstable renal function, dialysis, uncertain vancomycin dosing or sampling times, and distribution-phase sampling. Data from January 1 through December 31, 2003 (phase 1) determined the best-fit weight for vancomycin clearance for the Leonard and Boro method. The bias and precision of the modified Leonard and Boro method using the best-fit weight for vancomycin clearance were then compared with those of the Rushing and Ambrose method for predicting SVCs from January 1, 2004, through June 30, 2005 (phase 2). Forty-eight patients were included in phase 1, with 67 SVCs for analysis. During phase 1, adjusted body weight (ABW), using the Leonard and Boro method, was superior in predicting vancomycin clearance and the resultant SVCs. A total of 96 patients were included in phase 2 of the study, with 160 SVCs for analysis. The modified Leonard and Boro method was significantly more precise than the Rushing and Ambrose method in predicting vancomycin clearance. Use of ABW proved to be superior compared with total body weight when estimating vancomycin clearance in overweight and obese patients. While there was no difference in bias between methods, the modified Leonard and Boro method was significantly more precise than the Rushing and Ambrose method in predicting SVCs when dosing vancomycin for obese patients.

  20. Strategies for Determining Correct Cytochrome P450 Contributions in Hepatic Clearance Predictions: In Vitro-In Vivo Extrapolation as Modelling Approach and Tramadol as Proof-of Concept Compound.

    PubMed

    T'jollyn, Huybrecht; Snoeys, Jan; Van Bocxlaer, Jan; De Bock, Lies; Annaert, Pieter; Van Peer, Achiel; Allegaert, Karel; Mannens, Geert; Vermeulen, An; Boussery, Koen

    2017-06-01

    Although the measurement of cytochrome P450 (CYP) contributions in metabolism assays is straightforward, determination of actual in vivo contributions might be challenging. How representative are in vitro for in vivo CYP contributions? This article proposes an improved strategy for the determination of in vivo CYP enzyme-specific metabolic contributions, based on in vitro data, using an in vitro-in vivo extrapolation (IVIVE) approach. Approaches are exemplified using tramadol as model compound, and CYP2D6 and CYP3A4 as involved enzymes. Metabolism data for tramadol and for the probe substrates midazolam (CYP3A4) and dextromethorphan (CYP2D6) were gathered in human liver microsomes (HLM) and recombinant human enzyme systems (rhCYP). From these probe substrates, an activity-adjustment factor (AAF) was calculated per CYP enzyme, for the determination of correct hepatic clearance contributions. As a reference, tramadol CYP contributions were scaled-back from in vivo data (retrograde approach) and were compared with the ones derived in vitro. In this view, the AAF is an enzyme-specific factor, calculated from reference probe activity measurements in vitro and in vivo, that allows appropriate scaling of a test drug's in vitro activity to the 'healthy volunteer' population level. Calculation of an AAF, thus accounts for any 'experimental' or 'batch-specific' activity difference between in vitro HLM and in vivo derived activity. In this specific HLM batch, for CYP3A4 and CYP2D6, an AAF of 0.91 and 1.97 was calculated, respectively. This implies that, in this batch, the in vitro CYP3A4 activity is 1.10-fold higher and the CYP2D6 activity 1.97-fold lower, compared to in vivo derived CYP activities. This study shows that, in cases where the HLM pool does not represent the typical mean population CYP activities, AAF correction of in vitro metabolism data, optimizes CYP contributions in the prediction of hepatic clearance. Therefore, in vitro parameters for any test compound

  1. 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....

  2. 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....

  3. 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....

  4. 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...

  5. 2011 Report on Security Clearance Determinations

    DTIC Science & Technology

    2012-01-01

    Clearance Determinations 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK...Report on Security Clearance Determinations TABLE OF CONTENTS Table of Contents...security clearance as of October 1, 201 1, categorized by government employees and contractors and by security clearance level

  6. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.925 Propeller clearance. Unless smaller... clearance between the blade tips and the airplane structure, plus any additional radial clearance necessary... blades or cuffs and stationary parts of the airplane; and (3) Positive clearance between other...

  7. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.925 Propeller clearance. Unless smaller... clearance between the blade tips and the airplane structure, plus any additional radial clearance necessary... blades or cuffs and stationary parts of the airplane; and (3) Positive clearance between other...

  8. 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.

  9. Influence of renal function on the pharmacokinetics of lomefloxacin compared with other fluoroquinolones.

    PubMed

    Blum, R A

    1992-04-06

    Fluoroquinolones have similar chemical structures but wide differences in their pharmacokinetic profiles. Disparity in fluoroquinolone elimination is most evident in patients with various degrees of renal insufficiency. Ofloxacin is almost exclusively eliminated by the kidney, whereas pefloxacin is predominantly cleared by the liver. The fluoroquinolones eliminated by both renal and nonrenal routes (hepatic and transintestinal) include norfloxacin, ciprofloxacin, enoxacin, fleroxacin, temafloxacin, and lomefloxacin. The primary renal mechanism of elimination for norfloxacin, ciprofloxacin, enoxacin, fleroxacin, temafloxacin, and lomefloxacin is glomerular filtration and tubular secretion. Both total clearance and renal clearance significantly correlate with creatinine clearance for these fluoroquinolones, and creatinine clearance is a useful clinical marker on which to base dosage adjustments. For some fluoroquinolones, dosage adjustments are recommended when creatinine clearances fall below 30-40 mL/min. This is especially evident for lomefloxacin, temafloxacin, norfloxacin, ciprofloxacin, enoxacin, and fleroxacin. There is very little removal of fluoroquinolones from the plasma during hemodialysis due to their extensive tissue distribution.

  10. 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.

  11. 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.

  12. 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.

  13. Renal Heme Oxygenase-1 Induction with Hemin Augments Renal Hemodynamics, Renal Autoregulation, and Excretory Function

    PubMed Central

    Botros, Fady T.; Dobrowolski, Leszek; Navar, L. Gabriel

    2012-01-01

    Heme oxygenases (HO-1; HO-2) catalyze conversion of heme to free iron, carbon monoxide, and biliverdin/bilirubin. To determine the effects of renal HO-1 induction on blood pressure and renal function, normal control rats (n = 7) and hemin-treated rats (n = 6) were studied. Renal clearance studies were performed on anesthetized rats to assess renal function; renal blood flow (RBF) was measured using a transonic flow probe placed around the left renal artery. Hemin treatment significantly induced renal HO-1. Mean arterial pressure and heart rate were not different (115 ± 5 mmHg versus 112 ± 4 mmHg and 331 ± 16 versus 346 ± 10 bpm). However, RBF was significantly higher (9.1 ± 0.8 versus 7.0 ± 0.5 mL/min/g, P < 0.05), and renal vascular resistance was significantly lower (13.0 ± 0.9 versus 16.6 ± 1.4 [mmHg/(mL/min/g)], P < 0.05). Likewise, glomerular filtration rate was significantly elevated (1.4 ± 0.2 versus 1.0 ± 0.1 mL/min/g, P < 0.05), and urine flow and sodium excretion were also higher (18.9 ± 3.9 versus 8.2 ± 1.0 μL/min/g, P < 0.05 and 1.9 ± 0.6 versus 0.2 ± 0.1 μmol/min/g, P < 0.05, resp.). The plateau of the autoregulation relationship was elevated, and renal vascular responses to acute angiotensin II infusion were attenuated in hemin-treated rats reflecting the vasodilatory effect of HO-1 induction. We conclude that renal HO-1 induction augments renal function which may contribute to the antihypertensive effects of HO-1 induction observed in hypertension models. PMID:22518281

  14. Ciprofloxacin pharmacokinetics in patients with normal and impaired renal function.

    PubMed Central

    Gasser, T C; Ebert, S C; Graversen, P H; Madsen, P O

    1987-01-01

    The pharmacokinetics of ciprofloxacin following single oral doses of 500 and 750 mg in 32 patients with various degrees of renal function impairment were investigated in an open, randomized crossover fashion. Ciprofloxacin was administered after overnight fasting; the washout time between the two doses was 1 week. Serum and urine samples were collected serially between 0 and 24 h and subjected to bioassay and high-performance liquid chromatography. Pharmacokinetic parameters were analyzed, assuming an open two-compartment model with first-order input and elimination. A distinct difference was observed in pharmacokinetic parameters between patients with impaired renal function (creatinine clearance, less than 50 ml/min per 1.73 m2) and those with normal renal function (creatinine clearance, greater than or equal to 50 ml/min per 1.73 m2). For the former group, the area under the curve of serum concentration versus time was doubled, the renal clearance of ciprofloxacin was cut to one-fourth, the total and nonrenal ciprofloxacin clearance was reduced by 50%, and the elimination half-life was prolonged by a factor of approximately 1.7. The correlation between renal drug clearance and creatinine clearance was highly significant (r = 0.890; P less than 0.001). On the basis of these findings, it appears that a 50% dose reduction of ciprofloxacin in patients with impaired renal function (creatinine clearance, less than 50 ml/min per 1.73 m2) may be indicated to achieve concentrations in serum similar to those observed in normal individuals. As the concentration of ciprofloxacin in urine after 24 h remained above the MIC for most urinary pathogens, this drug appears to be of potential benefit for the treatment of urinary tract infections in patients with impaired renal function. PMID:3300537

  15. 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.

  16. Effective water clearance and tonicity balance: the excretion of water revisited.

    PubMed

    Mallie, J P; Bichet, D G; Halperin, M L

    1997-02-01

    To demonstrate (1) that hyponatremia is usually due to an inappropriately low rate of excretion of electrolyte-free water and (2) that the measure "effective water clearance" (EWC) provides better information about renal defence of the body tonicity than does the classic measure free-water clearance, and to provide the rationale for calculating a "tonicity balance," which involves using water and sodium plus potassium intakes and their renal excretion to reveal the basis for changes in body tonicity. Prospective study. Four normal subjects with no conditions affecting excretion, 10 patients with advanced congestive heart failure (CHF) and 5 patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Normals and patients were administered a standard water load (20 mL per kg of body weight) during 45 minutes, and blood and urine samples were taken before, during and after the load was given. Urine and blood sodium and potassium concentrations, osmolar clearance, free-water clearance, electrolyte clearance and EWC. The water load was excreted rapidly by normals, more slowly by patients with CHF, and not at all by patients with SIADH. The EWC was positive in normals and those with CHF, but negative in those with SIADH. In patients with CHF, the EWC, but not the free-water clearance, helped explain why hyponatremia was corrected after the water load was given. In subjects with abnormal water excretion, the EWC provides the physiologic explanation for the renal role in variations in natremia. The authors propose a bedside evaluation of renal water and electrolyte handling that takes into consideration the role of urinary potassium in body tonicity. Changes in body tonicity can be explained by a "tonicity balance," a calculation in which the source and the net balance of sodium, potassium and water are considered.

  17. Renal elimination of perfluorocarboxylates (PFCAs).

    PubMed

    Han, Xing; Nabb, Diane L; Russell, Mark H; Kennedy, Gerald L; Rickard, Robert W

    2012-01-13

    Sex-, species-, and chain length-dependent renal elimination is the hallmark of mammalian elimination of perfluorocarboxylates (PFCAs) and has been extensively studied for almost 30 years. In this review, toxicokinetic data of PFCAs (chain lengths ranging from 4 to 10) in different species are compared with an emphasis on their relevance to renal elimination. PFCAs vary in their affinities to bind to serum albumins in plasma, which is an important factor in determining the renal clearance of PFCAs. PFCA-albumin binding has been well characterized and is summarized in this review. The mechanism of the sex-, species-, and chain length-dependent renal PFCA elimination is a research area that has gained continuous interest since the beginning of toxicological studies of PFCAs. It is now recognized that organic anion transport proteins play a key role in PFCA renal tubular reabsorption, a process that is sex-, species-, and chain length-dependent. Recent studies on the identification of PFCA renal transport proteins and characterization of their transport kinetics have greatly improved our understanding of the PFCA renal transport mechanism at the molecular level. A mathematical representation of this renal tubular reabsorption mechanism has been incorporated in physiologically based pharmacokinetic (PBPK) modeling of perfluorooctanoate (PFOA). Improvement of PBPK models in the future will require more accurate and quantitative characterization of renal transport pathways of PFCAs. To that end, a basolateral membrane efflux pathway for the reabsorption of PFCAs in the kidney is discussed in this review, which could provide a future research direction toward a better understanding of the mechanisms of PFCA renal elimination.

  18. 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.

  19. Steviol effect, a glycoside of Stevia rebaudiana, on glucose clearances in rats.

    PubMed

    Melis, M S; Rocha, S T; Augusto, A

    2009-05-01

    Stevia rebaudiana, a South American plant normally used as a natural herbal sweetener, has been suggested as exerting beneficial effects on human health, including as an antihypertensive and antihyperglycemic. The present experiment was undertaken to evaluate the renal excretion of steviol, the aglycone of several natural products extracted from the leaves of S. rebaudiana, and to clarify the actual participation of this compound on the renal excretion of glucose in rats, which has been previously suggested as the preferential action of steviol on the Na+-glucose renal tubular transport system. Steviol was obtained by enzymatic hydrolysis of stevioside with pectinase. Thirty normal male Wistar rats weighing 345 g were used. After a control period, steviol was infused iv at three doses (0.5, 1.0 and 3.0 mg.kg-1/h), according to classical clearance techniques. During all the experiments no significant changes in inulin clearance (Cin) and p-aminohipuric acid clearance (C PAH) were observed. Administration of steviol resulted in a statistically significant increase in the fractional sodium excretion (FeNa+), fractional potassium excretion (FeK+), urinary flow as percent of glomerular filtration rate (V/GFR) and glucose clearance (C G) when compared to controls, but these effects were absent with the dose of 0.5 mg.kg-1/h. The steviol clearance (C S) was higher than the Cin and lower than the C PAH at all the doses employed in this study. The data suggest that steviol is secreted by renal tubular epithelium, causing diuresis, natriuresis, kaliuresis and a fall in renal tubular reabsorption of glucose.

  20. 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.

  1. 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

  2. Shape memory alloy adaptive control of gas turbine engine compressor blade tip clearance

    NASA Astrophysics Data System (ADS)

    Schetky, Lawrence M.; Steinetz, Bruce M.

    1998-06-01

    The ambient air ingested through the inlet of a gas turbine is first compressed by an axial compressor followed by further compression in a centrifugal compressor and then fed into the combustion chamber where ignition and expansion take place to produce the engine thrust. The axial compressor typically has five or more stages which consist of revolving blades and stators and the overall performance of the turbine is strongly affected by the compressor efficiency. When the turbine is turned on, to accommodate the rapid initial increase in the compressor blade length due to centrifugal force, the cold turbine has a built in clearance between the turbine blade tip and the casing. As the turbine reached its operating temperature there is a further increase in the blade length due to thermal expansion and, at the same time, the diameter of the casing increases. The net result is that when these various components have reached their equilibrium temperatures, the initial cold build clearance is reduced, but there remains a residual clearance. The magnitude of this clearance has a direct effect on the compressor efficiency and can be stated as: Δη/Δ CLR equals 0.5 where η is efficiency and CLR is the tip clearance. The concept of adaptive tip clearance control is based on the ability of a shape memory alloy ring to shrink to a predetermined diameter when heated to the temperature of a particular stage, and thus reducing the tip clearance. The ring is fabricated from a CuAlNi shape memory alloy and is mounted in the casing so as to be coaxial with the rotating blades of the particular stage. When cold, the ring dimensions are such as to provide the required cold build clearance, but when at operating temperature the reduced diameter creates a very small tip clearance. The clearance provided by this concept is much smaller than the clearance normally obtained for a turbine of the size being studied.

  3. 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

  4. 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.

  5. Noninvasive clearance of airway secretions.

    PubMed

    Hardy, K A; Anderson, B D

    1996-06-01

    Airway clearance techniques are indicated for specific diseases that have known clearance abnormalities (Table 2). Murray and others have commented that such techniques are required only for patients with a daily sputum production of greater than 30 mL. The authors have observed that patients with diseases known to cause clearance abnormalities can have sputum clearance with some techniques, such as positive expiratory pressure, autogenic drainage, and active cycle of breathing techniques, when PDPV has not been effective. Hasani et al has shown that use of the forced exhalatory technique in patients with nonproductive cough still resulted in movement of secretions proximally from all regions of the lung in patients with airway obstruction. It is therefore reasonable to consider airway clearance techniques for any patient who has a disease known to alter mucous clearance, including CF, dyskinetic cilia syndromes, and bronchiectasis from any cause. Patients with atelectasis from mucous plugs and hypersecretory states, such as asthma and chronic bronchitis, patients with pain secondary to surgical procedures, and patients with neuromuscular disease, weak cough, and abnormal patency of the airway may also benefit from the application of airway clearance techniques. Infants and children up to 3 years of age with airway clearance problems need to be treated with PDPV. Manual percussion with hands alone or a flexible face mask or cup and small mechanical vibrator/percussors, such as the ultrasonic devices, can be used. The intrapulmonary percussive ventilator shows growing promise in this area. The high-frequency oscillator is not supplied with vests of appropriate sizes for tiny babies and has not been studied in this group. Young patients with neuromuscular disease may require assisted ventilation and airway oscillations can be applied. CPAP alone has been shown to improve achievable flow rates that will increase air-liquid interactions for patients with these diseases

  6. 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.

  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. 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

  9. 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.

  10. 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

  11. 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 conductor...

  12. 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... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical conductor...

  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. 29 CFR 1917.113 - Clearance heights.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 7 2011-07-01 2011-07-01 false Clearance heights. 1917.113 Section 1917.113 Labor... (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.113 Clearance heights. Clearance heights shall be prominently posted where the height is insufficient for vehicles and equipment. ...

  15. 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 fair...

  16. 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...

  17. 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...

  18. 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...

  19. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  20. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  1. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  2. 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...

  3. 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...

  4. 14 CFR 23.925 - Propeller clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant General § 23.925 Propeller...) 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...

  5. 14 CFR 23.925 - Propeller clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant General § 23.925 Propeller...) 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...

  6. 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

  7. Wear in ceramic on ceramic type lumbar total disc replacement: effect of radial clearance.

    PubMed

    Shankar, S; Kesavan, D

    2015-01-01

    The wear of the bearing surfaces of total disc replacement (TDR) is a key problem leads to reduction in the lifetime of the prosthesis and it mainly occurs due to the range of clearances of the articulating surface between the superior plate and core. The objective of this paper is to estimate the wear using finite element concepts considering the different radial clearances between the articulating surfaces of ceramic on ceramic type Lumbar Total Disc Replacement (LTDR). The finite element (FE) model was subjected to wear testing protocols according to loading profile of International Standards Organization (ISO) 18192 standards through 10 million cycles. The radial clearance value of 0.05 mm showed less volumetric wear when compared with other radial clearance values. Hence, low radial clearance values are suitable for LTDR to minimize the wear.

  8. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial.

    PubMed

    Townsend, Raymond R; Mahfoud, Felix; Kandzari, David E; Kario, Kazuomi; Pocock, Stuart; Weber, Michael A; Ewen, Sebastian; Tsioufis, Konstantinos; Tousoulis, Dimitrios; Sharp, Andrew S P; Watkinson, Anthony F; Schmieder, Roland E; Schmid, Axel; Choi, James W; East, Cara; Walton, Anthony; Hopper, Ingrid; Cohen, Debbie L; Wilensky, Robert; Lee, David P; Ma, Adrian; Devireddy, Chandan M; Lea, Janice P; Lurz, Philipp C; Fengler, Karl; Davies, Justin; Chapman, Neil; Cohen, Sidney A; DeBruin, Vanessa; Fahy, Martin; Jones, Denise E; Rothman, Martin; Böhm, Michael

    2017-08-25

    Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; p<0·0001), office SBP -10·0 mm Hg (-15·1 to -4·9; p=0·0004), and office DBP -5·3 mm Hg (-7·8 to -2·7; p=0·0002). No significant changes were seen in the sham-control group: 24-h SBP -0·5 mm Hg (95% CI -3·9 to 2·9; p=0

  9. Renal function and histology after acute hemorrhage in rats under dexmedetomidine action.

    PubMed

    Marangoni, Marco Aurelio; Hausch, Alex; Vianna, Pedro Thadeu Galvão; Braz, José Reinaldo Cerqueira; Viero, Rosa Marlene; Castiglia, Yara Marcondes Machado

    2007-01-01

    About 50 % of indications for dialysis in acute renal failure are related to problems originated during the perioperative period. Intraoperative hemodynamic changes lead to renal vasoconstriction and hypoperfusion. Previous studies have not defined the dexmedetomidine renal role in hemorrhage situations. This study evaluated the effect of dexmedetomidine on renal function and histology after acute hemorrhage in rats. Covered study with 20 Wistars rats, anesthetized with sodium pentobarbital, 50 mg.kg(-1), intraperitoneal, randomized into 2 groups submitted to 30% volemia bleeding: DG - iv dexmedetomidine, 3 microg.kg(-1) (10 min) and continuous infusion - 3 microg.kg(-1).h(-1); CG - pentobarbital. For renal clearance estimative, sodium p-aminohippurate and iothalamate were administered. Studied attributes: heart rate, mean arterial pressure, rectal temperature, hematocrit, iothalamate and p-aminohippurate clearance, filtration fraction, renal blood flow, renal vascular resistance, and histological evaluations of the kidneys. DG showed smaller values of heart rate, mean arterial pressure, and renal vascular resistance, but iothalamate clearance and filtration fraction values were higher. There was similarity in p-aminohippurate clearance and renal blood flow. Both groups had histological changes ischemia-like, but dexmedetomidine determined higher tubular dilatation scores. In rats, after acute hemorrhage, dexmedetomidine determined better renal function, but higher tubular dilation scores.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. Renal function tests for windows--a model for the development and distribution of medical software on the Internet.

    PubMed

    Fong, B C; Doyle, D J

    1995-09-01

    A computer application (Renal Function Tests for Windows) was developed to calculate and sort data for quantitative renal function testing using the Microsoft Visual Basic for Windows programming language. The following diagnostic indices are computed: Measured creatinine clearance--The rate at which serum is cleared of creatinine. Standardized clearance--Creatinine clearance scaled by body surface area. Estimated creatinine clearance--Renal creatinine clearance estimated from serum creatinine Renal failure index--To distinguish prerenal azotemia from oliguric acute renal failure. Renal free water clearance--Net volume per min of free water excreted by the kidneys. Fractional excretion of filtered sodium--To distinguish prerenal azotemia from acute renal failure. Renal Function Tests for Windows (RFT) allows the user to choose to enter only the data that is available. The program will then calculate all the possible results from the given data. Upon request, the program will also inform the user of data that is missing for those results that cannot be calculated. The flexibility of this program allows the user to perform 'what if' analysis through the manipulation of input data. Distribution of this program was accomplished using the Internet File Transfer Protocol (FTP) service. The effectiveness of mode of distributing medical software awaits feedback from users on the Internet.

  19. 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.

  20. Replicative senescence in kidney aging, renal disease, and renal transplantation.

    PubMed

    Naesens, Maarten

    2011-01-01

    Cellular or replicative senescence is classically seen as the key element of aging. In renal disease and after kidney transplantation, there is increasing evidence that replicative senescence pathways (p53 and p16) play a central role in disease progression and graft outcome, independent of chronological age. In this review, we summarize the current concepts in the molecular mechanisms of cellular senescence, and correlate these theories with the available literature on aging of native kidneys, kidney diseases, and outcome of renal allografts. Recent data illustrate the complex biology of senescence in vivo, and disprove the concept that senescence is an intrinsic injury process with immanent deleterious consequences. Senescence acts as a homeostatic mechanism that can even limit renal fibrosis, at least in animal studies. In a human setting, it remains to be investigated whether cellular senescence plays an active or a bystander role in fibrogenesis and atrophy of renal tissue.

  1. 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.

  2. Application of a Physiologically Based Pharmacokinetic Model to Assess Propofol Hepatic and Renal Glucuronidation in Isolation: Utility of In Vitro and In Vivo Data

    PubMed Central

    Gill, Katherine L.; Gertz, Michael; Houston, J. Brian

    2013-01-01

    A physiologically based pharmacokinetic (PBPK) modeling approach was used to assess the prediction accuracy of propofol hepatic and extrahepatic metabolic clearance and to address previously reported underprediction of in vivo clearance based on static in vitro–in vivo extrapolation methods. The predictive capacity of propofol intrinsic clearance data (CLint) obtained in human hepatocytes and liver and kidney microsomes was assessed using the PBPK model developed in MATLAB software. Microsomal data obtained by both substrate depletion and metabolite formation methods and in the presence of 2% bovine serum albumin were considered in the analysis. Incorporation of hepatic and renal in vitro metabolic clearance in the PBPK model resulted in underprediction of propofol clearance regardless of the source of in vitro data; the predicted value did not exceed 35% of the observed clearance. Subsequently, propofol clinical data from three dose levels in intact patients and anhepatic subjects were used for the optimization of hepatic and renal CLint in a simultaneous fitting routine. Optimization process highlighted that renal glucuronidation clearance was underpredicted to a greater extent than liver clearance, requiring empirical scaling factors of 17 and 9, respectively. The use of optimized clearance parameters predicted hepatic and renal extraction ratios within 20% of the observed values, reported in an additional independent clinical study. This study highlights the complexity involved in assessing the contribution of extrahepatic clearance mechanisms and illustrates the application of PBPK modeling, in conjunction with clinical data, to assess prediction of clearance from in vitro data for each tissue individually. PMID:23303442

  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. 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.

  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. 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

  7. Role of the renal sympathetic nervous system in mediating renal ischaemic injury-induced reductions in renal haemodynamic and excretory functions.

    PubMed

    Salman, Ibrahim M; Ameer, Omar Z; Sattar, Munavvar A; Abdullah, Nor A; Yam, Mun F; Najim, Hafsa S; Khan, Abdul Hye; Johns, Edward J

    2010-04-01

    We investigated the role of renal sympathetic innervation in the deterioration of renal haemodynamic and excretory functions during the early post-ischaemic phase of renal ischaemia/reperfusion injury. Anaesthetised male Sprague-Dawley rats were subjected to unilateral renal ischaemia by clamping the left renal artery for 30 min followed by reperfusion. Following acute renal denervation clearance experiments were performed. In a different set of experiments, the renal nerves were electrically stimulated at increasing frequencies and responses in renal blood flow and renal vascular resistance were recorded. Denervated post-ischaemic acute renal failure (ARF) rats showed higher urine flow rate, absolute and fractional sodium excretions, urinary sodium to urinary potassium, glomerular filtration rate and basal renal blood flow but lower basal renal vascular resistance (all p < 0.05 vs innervated ARF rats). Potassium excretion was significantly lower in denervated group as per fractional (p < 0.05 vs innervated ARF rats) but not absolute potassium excretion (p > 0.05 vs innervated ARF rats). The rise in mean arterial pressure and renal vasoconstrictor response to renal nerve stimulation were blunted in denervated ischaemic ARF rats (all p < 0.05 vs innervated ARF rats). Renal histopathology in denervated ARF rats manifested a significantly lower medullary congestion, inflammation and tubular injury compared to innervated counterparts (p < 0.05 vs innervated ARF rats). The findings strongly suggest the involvement of renal sympathetic tone in the post-ischaemic events of ischaemic ARF, as the removal of its action to a degree ameliorated the post-ischaemic renal dysfunctions.

  8. 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.

  9. 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

  10. 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.

  11. Renal denervation for hypertension refractory to renal artery stenting.

    PubMed

    Bausback, Yvonne; Friedenberger, Josef; Hertting, Klaus; Werner, Martin; Branzan, Daniela; Freitas, Bruno; Piorkowski, Michael; Schmidt, Andrej; Scheinert, Dierk

    2014-04-01

    To investigate the effect of renal denervation (RDN) on blood pressure and renal function in refractory hypertension after renal artery recanalization and optimal medical therapy. Ten patients (6 women; mean age 70.0±5.1 years) with an office systolic blood pressure >160 mmHg despite taking ≥3 antihypertensive drugs and uni- or bilateral renal artery stenting were treated with RDN. Radiofrequency (RF) energy was delivered to the native segment of the artery keeping a 5-mm safe distance from the stented segments. Standardized office (OBP) and ambulatory (ABP) blood pressure measurements, medication, and renal assessment, including renal duplex ultrasound and renal function, were determined at baseline and on follow-up to 12 months. OBP (systolic/diastolic) at baseline was 190.0±20.4 / 84.2±10.1 mmHg. It decreased to 171.1±28.7* / 82.2±8.7, 165.5±28.4(†) / 76.1±7.4, and 158.3±14.2(†) / 75.5±9.5(†) mmHg (*p<0.001; (†)p<0.01) at 3, 6, and 12 months after RDN, respectively. Average ABP (systolic/diastolic) after 6 and 12 months decreased by -7.6(‡) / -3.1 and -11.3(‡) / -5.1(‡) mmHg ((‡)p<0.05). There was no renal artery (re)stenosis, dissection, or aneurysm within 12 months. Creatinine, cystatin C, and glomerular filtration rate remained unchanged. Urine albumin excretion decreased in 4/10 patients. Renal resistive indices improved in native, but not in stented renal arteries within the follow-up period. This proof-of-concept study demonstrates that RF-based RDN can be safely and effectively delivered in patients with resistant hypertension and previous renal artery stenting.

  12. Creatinine clearance versus serum creatinine as a risk factor in cardiac surgery.

    PubMed

    Walter, Jörg; Mortasawi, Amir; Arnrich, Bert; Albert, Alexander; Frerichs, Inez; Rosendahl, Ulrich; Ennker, Jürgen

    2003-06-17

    Renal impairment is one of the predictors of mortality in cardiac surgery. Usually a binarized value of serum creatinine is used to assess the renal function in risk models. Creatinine clearance can be easily estimated by the Cockcroft and Gault equation from serum creatinine, gender, age and body weight. In this work we examine whether this estimation of the glomerular filtration rate can advantageously replace the serum creatinine in the EuroSCORE preoperative risk assessment. In a group of 8138 patients out of a total of 11878 patients, who underwent cardiac surgery in our hospital between January 1996 and July 2002, the 18 standard EuroSCORE parameters could retrospectively be determined and logistic regression analysis performed. In all patients scored, creatinine clearance was calculated according to Cockcroft and Gault. The relationship between the predicted and observed 30-days mortality was evaluated in systematically selected intervals of creatinine clearance and significance values computed by employing Monte Carlo methods. Afterwards, risk scoring was performed using a continuous or a categorical value of creatinine clearance instead of serum creatinine. The predictive ability of several risk score models and the individual contribution of their predictor variables were studied using ROC curve analysis. The comparison between the expected and observed 30-days mortalities, which were determined in different intervals of creatinine clearance, revealed the best threshold value of 55 ml/min. A significantly higher 30-days mortality was observed below this threshold and vice versa (both with p < 0.001). The local adaptation of the EuroSCORE is better than the standard EuroSCORE and was further improved by replacing serum creatinine (SC) by creatinine clearance (CC). Differential ROC analysis revealed that CC is superior to SC in providing predictive power within the logistic regression. Variable rank comparison identified CC as the best single variable

  13. 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.

  14. Techniques and Procedures for Route Clearance

    DTIC Science & Technology

    1996-03-01

    In response to the mme threal. in Bosnia, we haue included two articles with information on route- clearance techniques. The first article expands...Techniques and Procedures for Route Clearance By William C. Schneck, Jr. and Brian M. Green L and mines are the major threat to U.S. forces...learned many lessons about route clearance during the Vietnam War and had to relearn them a few years ago in Mogadishu, Somalia. While the U.S

  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. 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.

  17. Effect of hydrochlorothiazide and indomethacin treatment on renal function in nephrogenic diabetes insipidus.

    PubMed

    Jakobsson, B; Berg, U

    1994-05-01

    The purpose of this study was to investigate the effects of treatment with hydrochlorothiazide and hydrochlorothiazide and indomethacin combined on renal function in four boys, two with nephrogenic diabetes insipidus and two with partial nephrogenic diabetes insipidus using the clearances of inulin and para-aminohippuric acid under water diuresis and lithium clearance. Hydrochlorothiazide reduced urine flow and lithium clearance. These effects were further potentiated by addition of indomethacin. No consistent effects on renal plasma flow or glomerular filtration rate were found. It is concluded that treatment with hydrochlorothiazide alone and hydrochlorothiazide and indomethacin combined reduces urine flow in nephrogenic diabetes insipidus by increasing proximal tubular reabsorption of sodium.

  18. The prevalence of radiological markers of renal osteodystrophy in patients with chronic renal failure in Enugu.

    PubMed

    Odenigbo, U C; Ijoma, C K; Ulasi, I; Udeh, A C; Ibeh, C C

    2006-12-01

    To study the prevalence of renal osteodystrophy in Chronic renal failure patients in Enugu, using radiological methods. Ninety adult patients (56 male and 34 female) were recruited from the renal clinics of the University of Nigeria Teaching Hospital, Enugu over a period of twelve consecutive months. A structured questionnaire was administered and a physical examination carried out at the initial interview. This was followed by other investigations including renal ultrasonography, plain radiographs and laboratory investigations including serum electrolytes, urea and creatinine, calcium and phosphate, total alkaline phosphate and creatinine clearance estimation. There was no obvious relationship between bone pain (a symptom of renal osteodystrophy) and the presence ofradiological features of renal osteodystrophy. The findings of the study showed that renal osteodystrophy, demonstrable by radiography is relatively uncommon, existing in only 3 subjects (3.35%). Among the 3 subjects, 2 showed radiological features of osteitis fibrosa cystica (one male and one female), while the other subject (one female) had radiological features of osteoporosis. All these subjects belonged to group 3 and had been on maintainance haemodialysis for more than 6 months. Other forms of renal osteodystrophy were not demonstrated. Renal osteodystrophy is probably not as common in Nigerian patients as in Caucasians and there may be reasons for this.

  19. To increase or decrease dosage of antimicrobials in septic patients during continuous renal replacement therapy: the eternal doubt.

    PubMed

    Wong, Wai-Tat; Choi, Gordon; Gomersall, Charles D; Lipman, Jeffrey

    2015-10-01

    Critical illness, acute renal failure and continuous renal replacement therapy (CRRT) are associated with changes in pharmacokinetics. Initial antibiotic dose should be based on published volume of distribution and generally be at least the standard dose, as volume of distribution is usually unchanged or increased. Subsequent doses should be based on total clearance. Total clearance varies with the CRRT clearance which mainly depends on effluent flow rate, sieving coefficient/saturation coefficient. As antibiotic clearance by healthy kidneys is usually higher than clearance by CRRT, except for colistin, subsequent doses should generally be lower than given to patients without renal dysfunction. In the future therapeutic drug monitoring, together with sophisticated pharmacokinetic models taking into account the pharmacokinetic variability, may enable more appropriate individualized dosing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. The pharmacokinetics of remoxipride and metabolites in patients with various degrees of renal function.

    PubMed Central

    Movin-Osswald, G; Boelaert, J; Hammarlund-Udenaes, M; Nilsson, L B

    1993-01-01

    1. The pharmacokinetics of remoxipride, a new neuroleptic, were investigated in an open study with three parallel groups. Twenty-one patients with severely impaired (ClCr < 25 ml min-1), moderately impaired (ClCr 25-50 ml min-1) and normal (ClCr > 65 ml min-1) renal function were evaluated. A single oral dose of remoxipride hydrochloride 100 mg was administered, and blood and urine were collected over 48 h. Concentrations of remoxipride and metabolites were measured by h.p.l.c. 2. In patients with severely decreased renal function, the AUC and Cmax of remoxipride were increased significantly, and t1/2 was prolonged, as compared with the control patients. The renal clearance and urinary recovery of the unchanged drug were significantly diminished. 3. The unbound fraction of remoxipride in plasma was decreased in patients with renal failure, in association with a disease-related increase in alpha 1-acid glycoprotein. In spite of a 25% recovery of unchanged drug in the urine in patients with normal renal function, the AUC of unbound drug was twice as high in patients with severely impaired renal function. 4. A strong correlation between creatinine clearance and renal drug clearance was observed indicating a direct relationship between kidney function and the renal clearance of remoxipride. 5. Remoxipride was the predominant compound in plasma as well as in urine in patients with severely decreased as well as normal renal function. In patients with severely decrease renal function, remoxipride and all five pharmacologically inactive metabolites showed increased peak plasma concentrations, delayed tmax, increased AUC, prolonged half-lives and decreased renal clearance. PMID:8329289

  1. 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

  2. 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.

  3. RENAL EFFECTS OF HEMOGLOBIN INFUSIONS IN DOGS IN HEMORRHAGIC SHOCK

    PubMed Central

    Hamilton, Paul B.; Hiller, Alma; Van Slyke, Donald D.

    1947-01-01

    The immediate effects of treating hemorrhagic shock in dogs by replacing lost blood with 7 per cent hemoglobin solution were favorable, both on renal function and on general condition. However, subsequent transitory depression of the urea clearance for several days, shown by some of the treated animals, but not by untreated bled controls, indicates sufficient possibility of renal damage by the hemoglobin solution to prevent its recommendation at present as a blood substitute. PMID:19871692

  4. 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

  5. Renal sodium reabsorption after acute renal denervation in the rabbit

    PubMed Central

    Blake, William D.; Jurf, Amin N.

    1968-01-01

    1. Separate effects on the functions of left and right kidneys were examined after left-sided renal handling and acute denervation. Studies were done on pentobarbital-anaesthetized rabbits using clearance techniques to evaluate renal haemodynamics and water and electrolyte excretion. 2. When compared with its counterpart, the handled kidney exhibited some decrease in function for at least 20 min. Recovery of most functions occurred in 40-60 min. 3. The effects of denervation on renal functions were observed when the effects of handling had subsided. Renal plasma flow (R.P.F.) and glomerular filtration rate (G.F.R.) were not significantly changed, whereas the decrease in Na, K and water excretion, which was usually observed for no ascertained reason in the innervated kidney, was prevented. 4. The magnitude of the denervation natriuresis was greater in these rabbits than in dogs studied previously; other functions studied were comparable in the two species. 5. The results from thirty-five experiments are interpreted to indicate that denervation decreases Na reabsorption independently of G.F.R., perhaps by a direct effect on tubular transport, but more probably by a redistribution of filtration to nephrons of lesser reabsorptive capacity. PMID:5653887

  6. Renal denervation and hypertension.

    PubMed

    Schlaich, Markus P; Krum, Henry; Sobotka, Paul A; Esler, Murray D

    2011-06-01

    Essential hypertension remains one of the biggest challenges in medicine with an enormous impact on both individual and society levels. With the exception of relatively rare monogenetic forms of hypertension, there is now general agreement that the condition is multifactorial in nature and hence requires therapeutic approaches targeting several aspects of the underlying pathophysiology. Accordingly, all major guidelines promote a combination of lifestyle interventions and combination pharmacotherapy to reach target blood pressure (BP) levels in order to reduce overall cardiovascular risk in affected patients. Although this approach works for many, it fails in a considerable number of patients for various reasons including drug-intolerance, noncompliance, physician inertia, and others, leaving them at unacceptably high cardiovascular risk. The quest for additional therapeutic approaches to safely and effectively manage hypertension continues and expands to the reappraisal of older concepts such as renal denervation. Based on the robust preclinical and clinical data surrounding the role of renal sympathetic nerves in various aspects of BP control very recent efforts have led to the development of a novel catheter-based approach using radiofrequency (RF) energy to selectively target and disrupt the renal nerves. The available evidence from the limited number of uncontrolled hypertensive patients in whom renal denervation has been performed are auspicious and indicate that the procedure has a favorable safety profile and is associated with a substantial and presumably sustained BP reduction. Although promising, a myriad of questions are far from being conclusively answered and require our concerted research efforts to explore the full potential and possible risks of this approach. Here we briefly review the science surrounding renal denervation, summarize the current data on safety and efficacy of renal nerve ablation, and discuss some of the open questions that need

  7. 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... Agreement § 205.20 What is a clearance pattern? States use clearance patterns to project when funds are paid... patterns meet the following standards: (a) A clearance pattern must be auditable. (b) A clearance pattern...

  8. 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; Electronic...

  9. 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;...

  10. 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...

  11. Cardiopulmonary fitness and respirator clearance: an update.

    PubMed

    Belafsky, Sheri; Vlach, Justin; McCurdy, Stephen A

    2013-01-01

    This review addresses five key questions regarding respirator clearance: What is the efficacy of different methods of respirator clearance? Which diagnostic test is most predictive of cardiac event during respirator use? Is spirometry accurate in predicting respiratory distress/insufficiency during respirator use? Is exercise tolerance testing accurate in predicting cardiac injury during respirator use? Which periodicity of clearance evaluations is most protective against cardiac event during respirator use? The medical literature was searched using PubMed, the Cochrane Library, and Web of Science. Relevant articles were reviewed to assess current recommendations and practices in respirator clearance. Between the years 1970 and 2011, 144 articles were identified, and 21 were included in this review. Current recommendations for respirator clearance are based on consensus rather than outcome studies, and opinions differed between expert sources. Many authors observed the need for cost-effective respirator clearance, but none proposed evidence-based strategies. Prospective studies on respirator clearance that evaluate cardiac and pulmonary outcomes are necessary to establish an evidence base for improving the validity, efficiency, and consistency of respirator clearance testing.

  12. 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;...

  13. 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;...

  14. 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;...

  15. 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 Export...

  16. 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...

  17. AHERA CLEARANCE AT TWENTY ABATEMENT SITES

    EPA Science Inventory

    A study was conducted during the summer of 1988 to document Asbestos Hazard Emergency Response Act (AHERA) clearance air-sampling practices and clearance concentrations of airborne asbestos at 20 asbestos-abatement sites in New Jersey. Each abatement took place in a school buildi...

  18. 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 or...

  19. 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 or...

  20. 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 ...

  1. 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. ...

  2. 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 ...

  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 57.7028 - 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 or...

  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 or...

  6. 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. ...

  7. 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 ...

  8. 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. ...

  9. 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. ...

  10. 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....

  11. 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....

  12. 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.

  13. 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

  14. 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 ...

  15. 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.

  16. Clearance of materials from accelerator facilities

    NASA Astrophysics Data System (ADS)

    Rokni, Sayed H.; Davis, Scott L.; Ford, Ryan; Liu, James C.; Marshall, Elaine; Schwahn, Scott O.; Welch, Keith

    2017-09-01

    A new Technical Standard that supports the clearance of materials and equipment (personal property) from U.S. Department of Energy (DOE) accelerator facilities has been developed. The Standard focuses on personal property that has the potential to be radiologically impacted by accelerator operations. It addresses material clearance programs and protocols for off-site releases without restriction on use. Common metals with potential volumetric activation are of main interest with technical bases provided in Appendices of the Standard. The clearance protocols in the Standard include three elements: 1) clearance criteria, 2) process knowledge, and 3) measurement methods. This paper presents the technical aspects of the new Standard, discusses operational experience gained in clearance of materials and equipment from several accelerator facilities at SLAC and examples as to how this Standard can be applied to benefit the entirety of the DOE Accelerator Complex.

  17. 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.

  18. Concomitant Administration of High-dose Methotrexate and Low-dose Aspirin Without Any Delay in Methotrexate Clearance in a Patient With Osteosarcoma: A Case Report and Review of the Literature.

    PubMed

    Renzi, Samuele; Tsimerman, Ekaterina; Taylor, Tracey; Hopyan, Sevan; Koo, Alicia; Gupta, Abha

    2017-09-08

    Methotrexate (MTX) is a commonly used agent in the treatment of oncology patients whose clearance depends on renal health maintaining glomerular filtration and tubular secretion. Thus concomitant use of other drugs that utilize the same mechanism of clearance are generally avoided as this may contribute to increased MTX-associated toxicity. Herein, we describe the use of low-dose aspirin with high-dose MTX in a patient with osteosarcoma. Concomitant aspirin use did not affect the clearance of high-dose MTX and the patient did not experience any MTX-related toxicity including mucositis or renal impairment.

  19. DOD Personnel Clearances. DOD Faces Multiple Challenges in Its Efforts to Improve Clearance Processes for Industry Personnel

    DTIC Science & Technology

    2008-02-13

    Services, House of Representatives DOD PERSONNEL CLEARANCES DOD Faces Multiple Challenges in Its Efforts to Improve Clearance Processes for Industry...Personnel Clearances . DOD Faces Multiple Challenges in Its Efforts to Improve Clearance Processes for Industry Personnel 5a. CONTRACT NUMBER 5b...Accountability Office Why GAO Did This Study Highlights Accountability Integrity Reliability February 13, 2008 DOD PERSONNEL CLEARANCES DOD Faces Multiple

  20. Renal tubular secretion of pramipexole.

    PubMed

    Knop, Jana; Hoier, Eva; Ebner, Thomas; Fromm, Martin F; Müller, Fabian

    2015-11-15

    The dopamine agonist pramipexole is cleared predominantly by the kidney with a major contribution of active renal secretion. Previously the organic cation transporter 2 (OCT2) was shown to be involved in the uptake of pramipexole by renal tubular cells, while the mechanism underlying efflux into tubular lumen remains unclear. Cimetidine, a potent inhibitor of multidrug and toxin extrusion proteins 1 (MATE1) and 2-K (MATE2-K), decreases renal pramipexole clearance in humans. We hypothesized that, in addition to OCT2, pramipexole may be a substrate of MATE-mediated transport. Pramipexole uptake was investigated using MDCK or HEK cells overexpressing OCT2, MATE1 or MATE2-K and the respective vector controls (Co). Transcellular pramipexole transport was investigated in MDCK cells single- or double-transfected with OCT2 and/or MATE1 and in Co cells, separating a basal from an apical compartment in a model for renal tubular secretion. Pramipexole uptake was 1.6-, 1.1-, or 1.6-folds in cells overexpressing OCT2, MATE1 or MATE2-K, respectively as compared to Co cells (p<0.05). In transcellular transport experiments, intracellular pramipexole accumulation was 1.7-folds in MDCK-OCT2 (p<0.001), and transcellular pramipexole transport was 2.2- and 4.0-folds in MDCK-MATE1 and MDCK-OCT2-MATE1 cells as compared to Co cells (p<0.001). Transcellular pramipexole transport was pH dependent and inhibited by cimetidine with IC50 values of 12μM and 5.5μM in MATE1 and OCT2-MATE1 cells, respectively. Taken together, coordinate activity of OCT2-mediated uptake and MATE-mediated efflux determines pramipexole renal secretion. Reduced OCT2 or MATE transport activity due to genetic variation or drug-drug interactions may affect pramipexole renal secretion. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. 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

  2. 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.

  3. 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

  4. The measurement of dog gastric mucosal blood flow by radioactive aniline clearance compared with amidopyrine clearance

    PubMed Central

    Curwain, B. P.; Holton, Pamela

    1973-01-01

    1. Methods for the estimation of radioactive aniline in body fluids are described. The recovery of aniline added to blood, plasma and gastric juice was over 90% of the recovery from saline. 2. In the doses used aniline caused methaemoglobinaemia of 5-11% of total haemoglobin. No other effect was detected. Gastric secretion was also unaffected. 3. Aniline clearance increased in parallel with acid secretion from Heidenhain pouches in conscious dogs and in anaesthetized dogs. In conscious dogs the ratio of aniline clearance to acid secretion was significantly higher for histamine stimulation than for pentagastrin stimulation. 4. Aniline and amidopyrine clearances were compared simultaneously in the same dogs. Aniline clearance was about 80% of amidopyrine clearance. 5. The proportion of aniline bound to plasma proteins was measured by two methods and found to be 25%. When aniline clearance was corrected for plasma binding, aniline and amidopyrine clearances were equal. PMID:4689959

  5. 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.

  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. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  13. A semi-mechanistic model to predict the effects of liver cirrhosis on drug clearance.

    PubMed

    Johnson, Trevor N; Boussery, Koen; Rowland-Yeo, Karen; Tucker, Geoffrey T; Rostami-Hodjegan, Amin

    2010-03-01

    Liver cirrhosis is characterized by a decrease in functional hepatocytes, lowered circulating levels of plasma proteins and alterations in blood flow due to the development of portacaval shunts. Depending on the interplay between these parameters and the characteristics of an administered drug, varying degrees of impaired systemic clearance and first-pass metabolism are anticipated. The Simcyp Population-based ADME Simulator has already been used successfully to incorporate genetic, physiological and demographic attributes of certain subgroups within healthy populations into in vitro-in vivo extrapolation (IVIVE) of xenobiotic clearance. The objective of this study was to extend population models to predict systemic and oral drug clearance in relation to the severity of liver cirrhosis. Information on demographics, changes in hepatic blood flow, cytochrome P450 enzymes, liver size, plasma protein binding and renal function was incorporated into three separate population libraries. The latter corresponded to Child-Pugh scores A (mild), B (moderate) and C (severe) liver cirrhosis. These libraries, together with mechanistic IVIVE within the Simcyp Simulator, were used to predict the clearance of intravenous and oral midazolam, oral caffeine, intravenous and oral theophylline, intravenous and oral metoprolol, oral nifedipine, oral quinidine, oral diclofenac, oral sildenafil, and intravenous and oral omeprazole. The simulated patients matched the clinical studies as closely as possible with regard to demographics and Child-Pugh scores. Predicted clearance values in both healthy control and liver cirrhosis populations were compared with observed values, as were the fold increases in clearance values between these populations. There was good agreement (lack of statistically significant difference, two-tailed paired t-test) between observed and predicted clearance ratios, with the exception of those for two studies of intravenous omeprazole. Predicted clearance ratios were

  14. 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.

  15. Airway clearance therapy in cystic fibrosis patients.

    PubMed

    Pisi, Giovanna; Chetta, Alfredo

    2009-08-01

    Cystic fibrosis (CF) is the most common life-shortening inherited disease affecting Caucasian people. In CF, the major feature of lung disease is the retention of mucus due to impaired clearance of abnormally viscous airway secretions. Airway clearance techniques (ACTs) may significantly improve mucociliary clearance and gas exchange, thereby being of clinical benefit in reducing pulmonary complications in CF patients. ACTs include conventional chest physiotherapy, active cycle of breathing techniques, autogenic drainage, positive expiratory pressure and high-frequency chest compression. In order to suit the needs of patients, families and care-givers, ACTs need to be individually and continuously adapted.

  16. Physiologically-based pharmacokinetic modeling of renally excreted antiretroviral drugs in pregnant women.

    PubMed

    De Sousa Mendes, Maïlys; Hirt, Deborah; Urien, Saik; Valade, Elodie; Bouazza, Naïm; Foissac, Frantz; Blanche, Stephane; Treluyer, Jean-Marc; Benaboud, Sihem

    2015-11-01

    Physiological changes during pregnancy can affect drug disposition. Anticipating these changes will help to maximize drug efficacy and safety in pregnant women. Our objective was to determine if physiologically-based pharmacokinetics (PBPK) can accurately predict changes in the disposition of renally excreted antiretroviral drugs during pregnancy. Whole body PBPK models were developed for three renally excreted antiretroviral drugs, tenofovir (TFV), emtricitabine (FTC) and lamivudine (3TC). To assess the impact of pregnancy on PK, time-varying pregnancy-related physiological parameters available within the p-PBPK Simcyp software package were used. Renal clearance during pregnancy followed glomerular filtration changes with or without alterations in secretion. PK profiles were simulated and compared with observed data, i.e. area under the curves (AUC), peak plasma concentrations (Cmax ) and oral clearances (CL/F). PBPK models successfully predicted TFV, FTC and 3TC disposition for non-pregnant and pregnant populations. Both renal secretion and filtration changed during pregnancy. Changes in renal clearance secretion were related to changes in renal plasma flow. The maximum clearance increases were approximately 30% (TFV 33%, FTC 31%, 3TC 29%). Pregnancy PBPK models are useful tools to quantify a priori the drug exposure changes during pregnancy for renally excreted drugs. These models can be applied to evaluate alternative dosing regimens to optimize drug therapy during pregnancy. © 2015 The British Pharmacological Society.

  17. 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

  18. [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.

  19. 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.

  20. Utility of radioisotopic filtration markers in chronic renal insufficiency: Simultaneous comparison of sup 125 I-iothalamate, sup 169 Yb-DTPA, sup 99m Tc-DTPA, and inulin. The Modification of Diet in Renal Disease Study

    SciTech Connect

    Perrone, R.D.; Steinman, T.I.; Beck, G.J.; Skibinski, C.I.; Royal, H.D.; Lawlor, M.; Hunsicker, L.G. )

    1990-09-01

    Assessment of glomerular filtration rate (GFR) with inulin is cumbersome and time-consuming. Radioisotopic filtration markers have been studied as filtration markers because they can be used without continuous intravenous (IV) infusion and because analysis is relatively simple. Although the clearances of 99mTc-DTPA, 169Yb-DTPA, and 125I-iothalamate have each been compared with inulin, rarely has the comparability of radioisotopic filtration markers been directly evaluated in the same subject. To this purpose, we determined the renal clearance of inulin administered by continuous infusion and the above radioisotopic filtration markers administered as bolus injections, simultaneously in four subjects with normal renal function and 16 subjects with renal insufficiency. Subjects were studied twice in order to assess within-study and between-study variability. Unlabeled iothalamate was infused during the second half of each study to assess its effect on clearances. We found that renal clearance of 125I-iothalamate and 169Yb-DTPA significantly exceeded clearance of inulin in patients with renal insufficiency, but only by several mL.min-1.1.73m-2. Overestimation of inulin clearance by radioisotopic filtration markers was found in all normal subjects. No differences between markers were found in the coefficient of variation of clearances either between periods on a given study day (within-day variability) or between the two study days (between-day variability). The true test variability between days did not correlate with within-test variability. We conclude that the renal clearance of 99mTc-DTPA, 169Yb-DTPA, or 125I-iothalamate administered as a single IV or subcutaneous injection can be used to accurately measure GFR in subjects with renal insufficiency; use of the single injection technique may overestimate GFR in normal subjects.

  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. 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.

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. Airway-clearance therapy guidelines and implementation.

    PubMed

    Lester, Mary K; Flume, Patrick A

    2009-06-01

    The clearance of secretions from the lungs of patients with cystic fibrosis (CF) is an important component in the fight to preserve their lung function. There is excessive inflammation in the airways of these patients, which is thought to be exaggerated by ineffective mucociliary clearance and bacterial infection. In 2005 the Cystic Fibrosis Foundation formed the Pulmonary Therapies Committee to review all of the medical literature on the various airway-clearance therapies used in treating CF lung disease. The recommendations were: an airway-clearance therapy should be performed by all patients with CF, no form of airway-clearance therapy stood out as being superior to another, and that patients may express a preference of one therapy over another. They also concluded that aerobic exercise is beneficial to patients with CF, as it is to everyone, and that exercise should be a component to the overall health routine of patients with CF. The challenge for respiratory and physical therapists together with the patient/family is to develop a plan of attack through the use of various airway-clearance therapies. The respiratory and physical therapists are integral in helping patients and families develop airway-clearance routines that aid in the removal of the secretions that cause airway obstruction. There is a wide range of airway-clearance therapies that therapists can choose from when they are teaching the patients and family members the strategies of secretion removal. The questions are: What therapy is best for what age or stage of lung disease? What therapies will the patient do? And which therapies will be covered by medical insurance? These are all fundamental questions that must be answered when guiding families in finding therapies that are effective and appropriate for each CF patient's unique situation.

  8. Effects of flurbiprofen on renal function in patients with moderate renal insufficiency.

    PubMed Central

    Murray, M D; Greene, P K; Brater, D C; Manatunga, A K; Hall, S D

    1992-01-01

    1. Renal function was assessed in eight patients with chronic renal insufficiency following the administration of flurbiprofen 50 mg as a single dose and after chronic administration of 50 mg four times daily for 8 and 27 days. Diet and fluid intake were controlled. 2. Inulin and creatinine clearances and urinary excretion of sodium were measured at baseline and every 20 min for at least 3 h after dosing. The time of the mean peak concentration of (S)-flurbiprofen was used to guide the analysis of the clearances. Creatinine clearance, urinary excretion of sodium, and serum sodium and potassium were also assessed for 24 h after the dose and on a daily basis. Body weight and blood pressure were measured on a daily basis. 3. Decrements in inulin and creatinine clearances were small and reversible within 3 h of an oral dose of flurbiprofen. Comparison of baseline clearances for the three study periods (first dose and at 8 and 27 days of chronic dosing) revealed a lack of chronic effect on glomerular filtration rate. 4. In contrast, flurbiprofen caused a substantial (73 to 86%) and progressive decrease in the urinary excretion of sodium that reached a nadir within 4-5 h after drug administration. However, comparison of baseline values did not differ, indicating that balance conditions had been re-established. 5. Results of 24 h assessments were in agreement with the clearance study results. Reduced urinary excretion of sodium appeared to be limited to the first few days of flurbiprofen administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1576067

  9. 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.

  10. The evidence for secretion clearance techniques.

    PubMed

    Hess, D R

    2001-11-01

    Many acute and chronic respiratory diseases are associated with increased respiratory secretions in the airways. Narrative reviews and a few systematic reviews of secretion clearance techniques have been published. These reviews raise concerns regarding the lack of evidence to support the various secretion clearance techniques. I conducted a comprehensive MEDLINE search of the following subjects: chest physical therapy, chest physiotherapy, postural drainage, forced expiratory technique, autogenic drainage, high-frequency chest wall compression, flutter device and secretions, positive expiratory pressure and secretions, intrapulmonary percussion, mechanical in-exsufflation and secretions. This was followed by a comprehensive search of cross-references to identify additional studies. The results of this review are reported herein. There are a number of methodological limitations of the literature reporting studies of the use of secretion clearance techniques. Most of the studies were small, most used crossover designs, and few used sham therapy. Many studies were limited to short-term outcomes such as sputum clearance with a single treatment session. Despite the clinical observation that retained secretions are detrimental to respiratory function and despite anecdotal associations between secretion clearance and improvements in respiratory function, there is a dearth of high-level evidence to support any secretion clearance technique.

  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. Accurate determination of renal function in patients with intestinal urinary diversions

    SciTech Connect

    McDougal, W.S.; Koch, M.O.

    1986-06-01

    The regular determination of renal function is a critical part of the management of patients who have had the urinary tract reconstructed with intestinal segments. These intestinal segments reabsorb urinary solutes and, thereby, complicate the determination of renal function by conventional methods. Urinary clearances of urea, creatinine and inulin were performed in patients with intestinal segments in the urinary tract and controls under varying diuretic conditions. Patients with intestinal diversions also underwent radioisotopic determination of renal function. The urinary clearances of urea, creatinine and inulin are highly dependent on the rate of urine flow in patients with intestinal segments in the urinary tract. Diuresis maximizes the urinary clearances of these solutes by minimizing intestinal reabsorption. Creatinine clearance prediction from the serum creatinine underestimates true glomerular filtration rate. Radioisotopic determination of renal function correlates poorly with true glomerular filtration rate. Only creatinine clearance measured under diuretic conditions correlates well with true renal function. Urine concentrating ability cannot be assessed accurately in patients with intestinal segments in the urinary tract, since osmolality rapidly equilibrates across the segments.

  13. Serum gastrin in patients with chronic renal failure.

    PubMed

    Taylor, I L; Sells, R A; McConnell, R B; Dockray, G J

    1980-12-01

    The realisation that circulating gastrin is heterogeneous necessitates a reappraisal of gastrin's role in the increased incidence of duodenal ulcer disease that occurs in chronic renal failure. Radioimmunoassays employing region-specific antisera have been used to examine renal and extrarenal factors controlling serum gastrin concentration in patients with chronic renal failure. The present study has shown that basal serum gastrin concentrations measured with a carboxyl-terminal specific antibody were significantly higher in eight patients with chronic renal failure treated by dietary restriction (388+/-196 pM) than in 14 patients with chronic renal failure treated by haemodialysis (28.7+/-4.6 pM). However, basal gastrin concentrations in both groups of patients were significantly higher than in 25 normal subjects (12.3+/-1.8 pM) and showed significant negative correlations with maximal gastric acid secretion (p < 0.01). Markedly raised basal gastrin concentrations were observed only in chronic renal failure patients who were also achlorhydric. Although the peak postprandial increment in big gastrin concentration in 11 chronic renal failure patients (34.0+/-7.5 pM) was significantly greater (p < 0.05) than in 25 normal subjects (19.5+/-4.6 pM), the little gastrin responses were not significantly different. In addition, clearance of exogenous little gastrin was similar in four chronic failure patients (clearance half time: 8.1+/-0.7 min) and four normal subjects (clearance half time: 6.5+/-1.2 min). These studies suggest that the human kidney is unimportant in the metabolism of little gastrin. As circulating little gastrin is six times more potent than big gastrin in stimulating acid secretion, these studies suggest that the raised gastrin concentrations observed in patients with chronic renal failure have little significance in terms of their increased incidence of duodenal ulcer disease.

  14. 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.

  15. 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.

  16. 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...

  17. 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...

  18. 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...

  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, 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...

  1. 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....

  2. 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...

  3. 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...

  4. 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 officer...

  5. 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 blanket...

  6. 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 blanket...

  7. 48 CFR 801.602-76 - Business clearance review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 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 blanket...

  8. The description of a method for accurately estimating creatinine clearance in acute kidney injury.

    PubMed

    Mellas, John

    2016-05-01

    Acute kidney injury (AKI) is a common and serious condition encountered in hospitalized patients. The severity of kidney injury is defined by the RIFLE, AKIN, and KDIGO criteria which attempt to establish the degree of renal impairment. The KDIGO guidelines state that the creatinine clearance should be measured whenever possible in AKI and that the serum creatinine concentration and creatinine clearance remain the best clinical indicators of renal function. Neither the RIFLE, AKIN, nor KDIGO criteria estimate actual creatinine clearance. Furthermore there are no accepted methods for accurately estimating creatinine clearance (K) in AKI. The present study describes a unique method for estimating K in AKI using urine creatinine excretion over an established time interval (E), an estimate of creatinine production over the same time interval (P), and the estimated static glomerular filtration rate (sGFR), at time zero, utilizing the CKD-EPI formula. Using these variables estimated creatinine clearance (Ke)=E/P * sGFR. The method was tested for validity using simulated patients where actual creatinine clearance (Ka) was compared to Ke in several patients, both male and female, and of various ages, body weights, and degrees of renal impairment. These measurements were made at several serum creatinine concentrations in an attempt to determine the accuracy of this method in the non-steady state. In addition E/P and Ke was calculated in hospitalized patients, with AKI, and seen in nephrology consultation by the author. In these patients the accuracy of the method was determined by looking at the following metrics; E/P>1, E/P<1, E=P in an attempt to predict progressive azotemia, recovering azotemia, or stabilization in the level of azotemia respectively. In addition it was determined whether Ke<10 ml/min agreed with Ka and whether patients with AKI on renal replacement therapy could safely terminate dialysis if Ke was greater than 5 ml/min. In the simulated patients there

  9. 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.

  10. Factors determining renal impairment in unilateral ureteral colic secondary to calcular disease: a prospective study.

    PubMed

    Al-Ani, Ammar; Al-Jalham, Khaled; Ibrahim, Tarek; Majzoub, Ahmad; Al-Rayashi, Maged; Hayati, Ahmed; Mubarak, Walid; Al-Rayahi, Jehan; Khairy, Ahmed T

    2015-07-01

    To evaluate all possible risk factors that can cause impairment of overall renal function in patients with unilateral ureteral calculus and a normal contralateral kidney. This is a prospective study of 90 patients who presented to our institute complaining of renal colic secondary to unilateral ureteral calculus. All patients were evaluated with a thorough history, physical examination, and laboratory and radiological investigations including renal function testing, urine analysis, non-contrast computed topography, and radionucleotide scan. Patients were divided into two groups according to their calculated creatinine clearance using the Modification of Diet in Renal Disease (MDRD) formula. Group I (favorable group) had a creatinine clearance >60 ml/min, while group II (unfavorable group) had a creatinine clearance <60 ml/min. The patients' mean age ± SD was 38.8 ± 11.4 years. Group I included 54 patients (60 %), while group II included 36 patients (40 %). On univariate analysis, factors that were associated with overall renal function impairment were patients' age, urea-to-creatinine ratio (UCR), use of nonsteroidal anti-inflammatory drugs, stone location, and presence of obstruction. However, using binary logistic regression analysis, only patients' age, UCR, and presence of obstruction sustained statistical significance in association with renal function impairment. The study of factors that help explain the presence of renal impairment in patients with unilateral ureteral calculus is important in the clinical setting. Patients' age, urea-to-creatinine ratio, and degree of obstruction seem to be significantly associated with overall renal function impairment.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. Prediction of glucuronidated drug clearance in pediatrics (≤5 years): An allometric approach.

    PubMed

    Mahmood, Iftekhar

    2015-03-01

    Children are not small adults. The differences between children of different age groups and adults are not merely due to body weight, but also due to physiological and biochemical differences resulting in different rates of drug metabolism or renal clearance. Glucuronidation is an important pathway of drug metabolism. Therefore, the objective of this study is to evaluate the predictive performance of several allometric exponents in children of ≤5 years for the total clearance of drugs which are mainly metabolized by glucuronidation. Four exponents (0.75, 1.0, 1.2, or 1.4) on the body weights and an allometric model developed from adults were evaluated. The four exponents and the allometric model were examined to determine the suitability of the method(s) to predict the clearances of drugs which are glucuronidated in children ≤5 years of age. Based on the analysis of ten drugs, it was noted that the combination of two allometric exponents 1.2 (for children ≤3 months) and 1.0 (for children ≥3 months ≤5 years) can be used to predict mean clearances of drugs which are mainly metabolized by glucuronidation. The suggested approach may be used to estimate a first-in-pediatric dose to initiate a pediatric clinical trial.

  16. Dopamine-Induced Changes in Serum Erythropoietin and Creatinine Clearance Reflect Risk Factors for Progression of IgA Nephropathy.

    PubMed

    Sulikowska, Beata; Johnson, Richard J; Wiechecka-Korenkiewicz, Joanna; Korenkiewicz, Jadwiga; Marszalek, Andrzej; Odrowaz-Sypniewska, Grazyna; Manitius, Jacek

    2015-08-01

    The infusion of low-dose dopamine is normally associated with an increase in creatinine clearance, thereby allowing one to assess renal functional reserve. Increased renal blood flow is also associated with a reduction in erythropoietin (EPO) levels. We evaluated the use of dopamine infusion in subjects with IgA nephropathy to determine if these functional changes correlate with risk factors for progression and compared this to the renal biopsy findings. Changes in creatinine clearance and EPO levels were determined in 46 non-nephrotic IgA patients with relative preserved renal function after the infusion of low dose dopamine. Control subjects (n = 15) were evaluated using similar protocols. Subjects with IgA nephropathy could be separated into those who showed a fall in EPO levels (n = 24) and those who showed no change or a rise in EPO levels (n = 22). Subjects showing the expected fall in EPO demonstrated a higher increase in creatinine clearance, similar to that observed in control subjects. Most importantly, subjects who showed a fall in EPO had less proteinuria, less N-acetyl-β-D-glucosaminidase excretion, lower serum uric acid, blood pressure, and less features of metabolic syndrome despite similar inflammation and fibrosis on biopsy as compared to the others. A decrease in EPO in response to dopamine is associated with a clinical phenotype that is less likely to develop progressive renal disease. These studies suggest that a fall in EPO in response to dopamine likely reflects preserved tubulointerstitial function that cannot be assessed by renal biopsy alone.

  17. Cystic fibrosis pulmonary guidelines: airway clearance therapies.

    PubMed

    Flume, Patrick A; Robinson, Karen A; O'Sullivan, Brian P; Finder, Jonathan D; Vender, Robert L; Willey-Courand, Donna-Beth; White, Terry B; Marshall, Bruce C

    2009-04-01

    Cystic fibrosis (CF) is a genetic disease characterized by dehydration of airway surface liquid and impaired mucociliary clearance. As a result, there is difficulty clearing pathogens from the lung, and patients experience chronic pulmonary infections and inflammation. Clearance of airway secretions has been a primary therapy for those with CF, and a variety of airway clearance therapies (ACTs) have been developed. Because ACTs are intrusive and require considerable time and effort, it is important that appropriate techniques are recommended on the basis of available evidence of efficacy and safety. Therefore, the Cystic Fibrosis Foundation established a committee to examine the clinical evidence for each therapy and provide guidance for their use. A systematic review was commissioned, which identified 7 unique reviews and 13 additional controlled trials that addressed one or more of the comparisons of interest and were deemed eligible for inclusion. Recommendations for use of the ACTs were made, balancing the quality of evidence and the potential harms and benefits. The committee determined that, although there is a paucity of controlled trials that assess the long-term effects of ACTs, the evidence quality overall for their use in CF is fair and the benefit is moderate. The committee recommends airway clearance be performed on a regular basis in all patients. There are no ACTs demonstrated to be superior to others, so the prescription of ACTs should be individualized. Aerobic exercise is recommended as an adjunctive therapy for airway clearance and for its additional benefits to overall health.

  18. Functional characteristics of the renal tubular secretion of amprolium, a quaternary organic base.

    PubMed

    Beyer, K H; Gelarden, R T

    1975-11-01

    Amprolium [1-(4-amino-2-propyl-5-pyrimidinemethyl)-2-methyl-pyridinium chloride hydrochloridel is a basic (quaternary) organic compound. At very low plasma concentration, it is cleared by the kidney at a rate approximating renal plasma flow in the dog. Its renal clearance is not depressed by organic acids (p-aminohippurate or probenecid) but is reduced by the quaternary base, mepiperphenidol. Acetate and pantothenate may influence the clearance of amprolium but, if this is the case, the effect is less than for p-aminohippurate. Its clearance is depressed as urinary pH is increased. The clearance of amprolium was not altered over a substantial range in urine flow at either high or low urinary pH.

  19. 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.

  20. Renal Calculi

    PubMed Central

    Yendt, E. R.

    1970-01-01

    The pathogenesis of renal calculi is reviewed in general terms followed by the results of investigation of 439 patients with renal calculi studied by the author at Toronto General Hospital over a 13-year period. Abnormalities of probable pathogenetic significance were encountered in 76% of patients. Idiopathic hypercalciuria was encountered in 42% of patients, primary hyperparathyroidism in 11%, urinary infection in 8% and miscellaneous disorders in 8%. The incidence of uric acid stones and cystinuria was 5% and 2% respectively. In the remaining 24% of patients in whom no definite abnormalities were encountered the mean urinary magnesium excretion was less than normal. Of 180 patients with idiopathic hypercalciuria, only 24 were females. In the diagnosis of hyperparathyroidism, the importance of detecting minimal degrees of hypercalcemia is stressed; attention is also drawn to the new observation that the upper limit of normal for serum calcium is slightly lower in females than in males. The efficacy of various measures advocated for the prevention of renal calculi is also reviewed. In the author's experience the administration of thiazides has been particularly effective in the prevention of calcium stones. Thiazides cause a sustained reduction in urinary calcium excretion and increase in urinary magnesium excretion. These agents also appear to affect the skeleton by diminishing bone resorption and slowing down bone turnover. PMID:5438766

  1. The Role of the Kidney in Drug Elimination: Transport, Metabolism, and the Impact of Kidney Disease on Drug Clearance.

    PubMed

    Miners, J O; Yang, X; Knights, K M; Zhang, L

    2017-09-01

    Recent advances in the identification and characterization of renal drug transporters and drug-metabolizing enzymes has led to greater understanding of their roles in drug and chemical elimination and in modulation of the intrarenal exposure and response to drugs, nephrotoxic compounds, and physiological mediators. Furthermore, there is increasing awareness of the potential importance of drug-drug interactions (DDIs) arising from inhibition of renal transporters, and regulatory agencies now provide recommendations for the evaluation of transporter-mediated DDIs. Apart from the well-recognized effects of kidney disease on renal drug clearance, there is a growing body of evidence demonstrating that the nonrenal clearances of drugs eliminated by certain transporters and drug-metabolizing enzymes are decreased in patients with chronic kidney disease (CKD). Based on these observations, renal impairment guidance documents of regulatory agencies recommend pharmacokinetic characterization of both renally cleared and nonrenally cleared drugs in CKD patients to inform possible dosage adjustment. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  2. 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

  3. Temafloxacin pharmacokinetics in subjects with normal and impaired renal function.

    PubMed Central

    Granneman, G R; Braeckman, R; Kraut, J; Shupien, S; Craft, J C

    1991-01-01

    The pharmacokinetics of temafloxacin were investigated following oral administration of single 400-mg doses to 6 normal subjects and 18 subjects with various degrees of impaired renal function. Renal impairment did not significantly affect the peak concentration, time to peak concentration, or the nonrenal clearance of temafloxacin. Both renal clearance (CLR) and total apparent clearance (CLT/F, where F represents the fraction of dose absorbed) of temafloxacin were highly correlated with creatinine clearance (CLCR). The regression equations were as follows: CLR = 0.85.CLCR, with R2 = 0.907, and CLT/F = 56.0 + 0.92.CLCR, with R2 = 0.656. The half-life (mean +/- standard deviation) increased from 10.6 +/- 2.4 h in the normal volunteers to 24.6 +/- 7.3 h in the subjects with a CLCR of less than 10 ml/min; the respective CLT/F decreased from 169 +/- 58 to 70 +/- 27 ml/min. Compared with the CLT/F in the subjects with normal renal function, CLT/F was reduced 60% in subjects with a CLCR of less than 40 ml/min, indicating that the dosage should be reduced by at least one-half for patients with comparable impairment. For the subjects on chronic hemodialysis, most of the variability in the nonrenal clearance and the terminal-phase rate constant of temafloxacin was associated with the quantity of calcium carbonate and related medication taken for the treatment of hyperphosphatemia. Supplemental dosage is not required for patients undergoing hemodialysis, since the distribution of temafloxacin in tissue is extensive and the recoveries from 4-h dialysis sessions accounted for less than 10% of the drug present at the start of the dialysis. PMID:1666497

  4. The use of biocompatible dialysis membranes in acute renal failure.

    PubMed

    Himmelfarb, J; Hakim, R M

    1997-04-01

    The interactions between blood and the dialysis membrane, aside from solute clearance, can be referred to as biocompatibility. It has increasingly been recognized that significant side effects may occur as a result of interactions of blood with the dialysis membrane itself. The use of unmodified cellulosic hemodialysis membranes results in potent activation of the alternative pathway of complement, and numerous investigators have now carefully defined the membrane characteristics that contribute to complement activation, adsorption, and clearance. Complement-dependent granulocyte activation during hemodialysis causes neutrophil degranulation and protease release, the production of reactive oxygen species, and modulation of granulocyte cell adhesion molecules. Recently, a number of experimental studies in animal models suggest that complement and granulocyte activation during hemodialysis could contribute to the prolongation of acute renal failure. Based on the hypothesis that hemodialysis with complement and granulocyte-activating membranes could contribute to the prolongation of acute renal failure and increased mortality, several recent prospective randomized clinical trials examining the role of membrane biocompatibility in the treatment of acute renal failure have been reported. Although not unanimous in their conclusions, most studies suggest that hemodialysis with more biocompatible membranes in patients with acute renal failure leads to a more rapid return of renal function and a lower morbidity and mortality. Thus, hemodialysis membrane biocompatibility may be an important contributor to the outcome of patients with acute renal failure who require dialysis.

  5. Acute renal toxic effect of amiodarone in rats.

    PubMed

    Morales, Ana Isabel; Barata, Jose Diogo; Bruges, Margarida; Arévalo, Miguel Angel; González de Buitrago, José Manuel; Palma, Patricia; Branco, Patricia; Pérez-Barriocanal, Fernando

    2003-01-01

    Amiodarone is an antiarrhythmic drug now more frequently used after a number of years in which the use had been on the decline due to a number of studies which reported side effects such as chronic toxicity, primarily in the lungs, liver and thyroid glands. Additionally, in some patients an increase in serum creatinine was noted, however the effect of amiodarone on renal function had never been closely examined. Thus, the aim of our study was to analyse the effects of amiodarone on renal function in rats. Experiments were carried out in male Wistar rats divided in two experimental groups: 1) a control group, (n=8), 2) a group that received a daily intraperitoneal injection of amiodarone (50 mg/kg body weight) for 6 days (n=5). At the end of the treatment, renal function was measured by clearance creatinine and acute clearance studies. Renal toxicity was evaluated by urinary N-acetyl-glucosamine and alkaline phosphatase. At the end of the experiment, histology studies were done. Rats treated with amiodarone had a higher serum creatinine (182%) and a lower glomerular filtration rate (53%), renal plasma flow (68%) and filtration fraction (62%) than controls. Rats treated with amiodarone also showed an increase in urinary N-acetyl-glucosamine (221%) and alkaline phosphatase (4.151%) excretion which corresponds with tubular alterations showed on electron microscopy. In conclusion our data confirm that amiodarone induces acute renal damage in the rat.

  6. 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.

  7. 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

  8. Complete stone clearance using a modified supine position: initial experience and comparison with prone percutaneous nephrolithotomy.

    PubMed

    McCahy, Philip; Rzetelski-West, Kathryn; Gleeson, Jacob

    2013-06-01

    The recently described Galdakao-modified supine Valdivia position for percutaneous nephrolithotomy (PCNL) has become increasingly popular. We have made further modifications to this and describe our recent experience compared with our previous prone cases. From April 2011, all patients undergoing PCNL have been placed in the modified supine position. A suction beanbag is used to secure the patient and improve renal access. Data on patient age, comorbidities, stone size, operative time, radiation exposure, complications, stone clearance, and length of stay was collected, analyzed, and compared with data from our previous year's prone surgery. Thirty-six patients in each group underwent 41 PCNLs. The groups were well matched for age, sex, and comorbidity. The supine patients tended to have a higher body mass index. Stones in the supine group were larger (32.6 vs 25.7 mm, P=0.0402), and the operative time was shorter (86.2 vs 116.6 min, P=0.003). Radiation time was similar in the two groups, but the dose was higher in the supine group. Stone clearance rates, length of stay (2.5 days), and complications were similar. Nineteen (46%) patients underwent simultaneous lower urinary tract procedures including 4 (10%) with complete staghorn calculi for which ureterorenoscopy was used to fragment ureteral and upper renal pole stones. The modified supine position for PCNL has a number of advantages for the patient and staff compared with the prone position. Despite a more obese study group with larger stones, we have maintained stone clearance rates and significantly reduced operative time with no increase in complications. The technique has been easy to learn and teach. A major advantage has been simultaneous access to the lower urinary tract for ureteroscopy and stent placement, and this has helped with complete stone clearance.

  9. Potential Effect of Substituting Estimated Glomerular Filtration Rate for Estimated Creatinine Clearance for Dosing of Direct Oral Anticoagulants.

    PubMed

    Schwartz, Janice B

    2016-10-01

    To determine the potential effect of substituting glomerular filtration rate (GFR) estimates for renal clearance estimated using the Cockcroft-Gault method (CrCL-CG) to calculate direct oral anticoagulant (DOAC) dosing. Simulation and retrospective data analysis. Community, academic institution, nursing home. Noninstitutionalized individuals aged 19 to 80 from the National Health and Nutrition Examination Survey (NHANES) (2011/12) (n = 4,687) and medically stable research participants aged 25 to 105 (n = 208). Age, height, weight, sex, race, serum creatinine, CrCL-CG, and GFR (according to the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations). Outcome measures were dosing errors if GFR were to be substituted for CrCL-CG. Renal clearance estimates according to all methods were highly correlated (P < .001), although at lower clearances, substitution of GFR estimates for CrCL-CG resulted in failure to recognize needs for dose reductions of rivaroxaban or edoxaban in 28% of NHANES subjects and 47% to 56% of research subjects. At a CrCL-CG of less than 30 mL/min, GFR estimates missed indicated dosage reductions for dabigatran in 18% to 21% of NHANES subjects and 57% to 86% of research subjects. Age and weight contributed to differences between renal clearance estimates (P < .001), but correction of GFR for body surface area (BSA) did not reduce dosing errors. At a CrCL-CG greater than 95 mL/min, edoxaban is not recommended, and GFR esimates misclassified 24% of NHANES and 39% of research subjects. Correction for BSA reduced misclassification to 7% for NHANES and 14% in research subjects. Substitution of GFR estimates for estimated CrCl can lead to failure to recognize indications for reducing DOAC dose and potentially higher bleeding rates than in randomized trials. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  10. 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.

  11. 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.

  12. 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.

  13. Airway clearance techniques for bronchiectasis.

    PubMed

    Lee, Annemarie L; Burge, Angela; Holland, Anne E

    2013-05-31

    People with non-cystic fibrosis bronchiectasis commonly experience chronic cough and sputum production and these features may be associated with progressive decline in clinical status. Airway clearance techniques (ACTs) are often prescribed to facilitate expectoration of sputum from the lungs, but the efficacy of these techniques in a stable clinical state or during an acute exacerbation of bronchiectasis is unclear. Primary: to determine the effects of ACTs on the rate of acute exacerbations, incidence of hospitalisation and health-related quality of life in individuals with acute and stable bronchiectasis.Secondary: to determine whether a) ACTs are safe for individuals with acute and stable bronchiectasis and b) ACTs have beneficial effects on physiology and symptoms in individuals with acute and stable bronchiectasis. We searched the Cochrane Airways Group Specialised Register of trials from inception to October 2012, PEDro in October 2012 and handsearched relevant journals. Randomised controlled parallel and cross-over trials that compared an ACT to no treatment, sham ACT or directed coughing in participants with bronchiectasis. We used standard methodological procedures expected by The Cochrane Collaboration. Five studies involving 51 participants met the inclusion criteria of the review, all of which were cross-over design. Four studies were on adults with stable bronchiectasis, and the other study was on clinically stable children with bronchiectasis. Three studies were single treatment sessions, two were longer-term studies. The interventions varied and some control groups received a sham intervention while others were inactive. The methodological quality of the studies was variable and the studies were not able to blind participants and personal. Heterogeneity between studies precluded these data from meta-analysis and the review was therefore narrative.One study on 20 adults comparing an airway oscillatory device with no treatment found no significant

  14. Airway clearance techniques for bronchiectasis.

    PubMed

    Lee, Annemarie L; Burge, Angela T; Holland, Anne E

    2015-11-23

    People with non-cystic fibrosis bronchiectasis commonly experience chronic cough and sputum production, features that may be associated with progressive decline in clinical and functional status. Airway clearance techniques (ACTs) are often prescribed to facilitate expectoration of sputum from the lungs, but the efficacy of these techniques in a stable clinical state or during an acute exacerbation of bronchiectasis is unclear. Primary: to determine effects of ACTs on rates of acute exacerbation, incidence of hospitalisation and health-related quality of life (HRQoL) in individuals with acute and stable bronchiectasis. Secondary: to determine whether:• ACTs are safe for individuals with acute and stable bronchiectasis; and• ACTs have beneficial effects on physiology and symptoms in individuals with acute and stable bronchiectasis. We searched the Cochrane Airways Group Specialised Register of trials from inception to November 2015 and PEDro in March 2015, and we handsearched relevant journals. Randomised controlled parallel and cross-over trials that compared an ACT versus no treatment, sham ACT or directed coughing in participants with bronchiectasis. We used standard methodological procedures as expected by The Cochrane Collaboration. Seven studies involving 105 participants met the inclusion criteria of this review, six of which were cross-over in design. Six studies included adults with stable bronchiectasis; the other study examined clinically stable children with bronchiectasis. Three studies provided single treatment sessions, two lasted 15 to 21 days and two were longer-term studies. Interventions varied; some control groups received a sham intervention and others were inactive. The methodological quality of these studies was variable, with most studies failing to use concealed allocation for group assignment and with absence of blinding of participants and personnel for outcome measure assessment. Heterogeneity between studies precluded inclusion of

  15. 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. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. 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

  17. Chronic renal failure, cachexia, and ghrelin.

    PubMed

    Laviano, A; Krznaric, Z; Sanchez-Lara, K; Preziosa, I; Cascino, A; Rossi Fanelli, F

    2010-01-01

    Protein energy wasting is frequently observed in patients with advanced chronic renal failure and end-stage renal disease. Anorexia and reduced food intake are critical contributing factors and negatively impact on patients' survival. Ghrelin is a prophagic peptide produced by the stomach and acting at the hypothalamic level to increase the activity of orexigenic neurons. In patients with chronic renal disease, plasma levels are increased as a likely effect of reduced renal clearance. Nevertheless, patients' food intake is significantly reduced, suggesting inflammation-mediated resistance of hypothalamic nuclei to peripheral signals. A number of forms of evidence show that ghrelin resistance could be overcome by the administration of exogenous ghrelin. Therefore, ghrelin has been proposed as a potential strategy to improve food intake in chronic renal failure patients with protein energy wasting. Preliminary data are encouraging although larger prospective clinical trials are needed to confirm the results and to identify those patients who are likely to benefit most from the administration of exogenous ghrelin.

  18. [Pharmacokinetic principles and drug-dosing adjustments during continuous renal replacement therapies (CRRT)].

    PubMed

    Morabito, S; Guzzo, I; Vitaliano, E; Muzi, L; Solazzo, A; Pistolesi, V; Pierucci, A

    2006-01-01

    In the critically ill, acute renal failure (ARF) and "Multiple Organ Dysfunction Syndrome" (MODS) can be associated with significant modifications of many pharmacokinetic parameters, such as protein binding, volume of distribution and total body clearance. The start of renal replacement therapy (RRT) represents an additional variable to take in consideration for drug-dosing adjustments. Drugs significantly eliminated by the kidney are likely to be removed during RRT and a supplemental dose or further dosing adjustments are required if extracorporeal clearance is more than 25-30% of total body clearance. The impact of RRT on plasma drug concentrations can be substantially different in relation to the type of treatment (diffusive, convective or both), membrane characteristics (low-flux or high-flux), filter surface area and prescribed dialysis dose. The molecular weight cut-offs of high-flux membrane are much higher than the molecular weight of most drugs. Therefore, molecular size will not be a limitation for the removal of the unbound fraction of the drugs most commonly used in the critically ill undergoing continuous renal replacement therapy (CRRT). However, diffusive clearance could be significantly lower than convective clearance for drugs in the middle molecular weight range. In any case, the extracorporeal clearances report-ed with the use of high-volume CRRT (>50-60 L/2 h) are often surprisingly elevated and can lead to drug underdosing in clinical conditions where adequate antibiotic treatment is essential.

  19. 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

  20. 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.

  1. Posterior urethral valves: relationship between vesicoureteral reflux and renal function.

    PubMed

    Cozzi, Denis A; Morgante, Debora; Frediani, Simone; Iaconelli, Romina; Ceccanti, Silvia; Mele, Ermelinda; Cozzi, Francesco

    2011-05-01

    To investigate the relationship between renal function and vesicoureteral reflux before and after valve ablation in patients with posterior urethral valves. In these patients, back pressure may not be the only cause of renal damage. We conducted a retrospective review of 37 patients with valves consecutively treated between 1970 and 2002. Data were available for 31 patients, 19 of whom presented reflux at presentation. Grade of reflux was ascertained by voiding cystourethrography. Overall renal function was measured by serum creatinine, and split renal function was estimated by dimercaptosuccinic acid scan available for all patients but two. Before relief of obstruction, there was no correlation between split renal function and grade of reflux into 25 kidneys of the 17 patients (r = -.13; 95% CI, -.50 to .27; P = .51). High-grade reflux (grade IV-V) affected 6 of the 11 renal units, with split renal function >40% vs 11 of the 14 units with split renal function <40% (P = .38). After successful valve ablation, reflux resolved in all the 11 units with split renal function >40% vs 4 of the 14 units with split renal function <40% (P = .0005). The good renal function of more than half of the renal units with high-grade reflux at presentation, and the persistence of reflux mainly in nonfunctioning or poorly functioning kidneys after valve ablation, support the concept that in some patients with valves, reflux and renal damage are associated anomalies. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. 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

  3. Renal functional recovery of the hydronephrotic kidney predicted before relief of the obstruction

    SciTech Connect

    McDougal, W.S.; Flanigan, R.C.

    1981-05-01

    Employing technetium labeled dimercaptosuccinic acid, we predicted the inulin and p-aminohippuric acid (PAH) clearances after recovery of an obstructed kidney before relief of the obstruction. Sixteen rabbits had one renal unit obstructed for varying period of time. The animals were scanned immediately before relief of the obstruction. After 4 to 6 months recovery, inulin and PAH clearances were measured in all animals. The scans were mathematically analyzed, and accurately predicted the inulin and PAH clearances obtained after complete recovery (P less than 0.001 and P less than 0.001, respectively). Six rabbits were scanned at the time of the clearance measurements. By a different mathematical analysis, inulin and PAH clearance measured concurrently correlated with the scan (P less than 0.001 and P less than 0.01 respectively).

  4. 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

  5. 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

  6. Understanding renal replacement therapy and dosing of drugs in pediatric patients with kidney disease.

    PubMed

    Zuppa, Athena F

    2012-01-01

    Multifaceted factors need to be considered when prescribing renal replacement therapy (RRT) and dosing of drugs in pediatric patients with kidney disease. RRTs in pediatrics such as intermittent hemodialysis, continuous venovenous hemofiltration, continuous venovenous hemodialysis, and continuous venovenous hemodiafiltration affect solute and drug clearance. Drug properties such as molecular weight, molecular charge, volume of distribution, and protein binding affect drug clearance. RRT prescription parameters such as blood flow rate, ultrafiltration rate, membrane size, and pore size can also influence drug clearance. Furthermore, the pediatric patient presents additional concerns because of developmental factors in children that affect both pharmacokinetics of drugs.

  7. Serum albumin and creatinine clearance rate among smear positive pulmonary tuberculosis patients in Bangladesh.

    PubMed

    Hoque, M R; Chakraborty, P K; Paul, U K; Sarkar, S; Akhter, S; Shahidullah, S M; Gautam, B; Sultana, S; Ferdous, N; Samsunnahar, M

    2014-07-01

    This case control study was carried out in the Department of Biochemistry, Mymensingh Medical College in cooperation with the Outpatient Department and Medicine Units of Mymensingh Medical College Hospital, Fulbaria Upazilla Health Complex, Mymensingh and some DOTS centers of BRAC, a non-government organization during the period of July 2006 to June 2007. The aim of the study was to explore the status of serum albumin & creatinine clearance levels in smear positive Bangladeshi pulmonary tuberculosis patients as a means to monitor the possibility of management of these patients as these levels decrease significantly. Serum albumin level was investigated in TB patients for monitoring the nutritional status of TB patients and also for the adjustment of serum calcium level. Creatinine clearance rate was investigated in TB patients for monitoring the impairment of renal function and nutritional depletion in tuberculosis patients. A total of 120 people of different age groups were included in this study. Subjects were divided into two groups- Group I (Control; n=60) - apparently healthy people selected matching by age, sex and socioeconomic status with the cases and Group II (Case; n=60) - people with smear positive pulmonary tuberculosis. Serum albumin was estimated by colorimetric principle. Serum creatinine was also estimated by colorimetric principle & creatinine clearance rate was estimated from serum creatinine by Cockcroft- Gault equation. Statistical analysis was done by using SPSS windows package. Among the groups, mean±SD of serum albumin in Group II (3.74±0.44gm/dl) was significantly lower (p<0.001) than that in Group I (4.85±0.31gm/dl). Mean±SD of creatinine clearance rate in Group II (35.36±8.29ml/min) was also significantly lower than that in Group I (84.16±20.20ml/min). It is evident from the study that serum albumin & creatinine clearance rate levels significantly decrease in smear positive Bangladeshi pulmonary tuberculosis patients.

  8. In silico classification of major clearance pathways of drugs with their physiochemical parameters.

    PubMed

    Kusama, Makiko; Toshimoto, Kouta; Maeda, Kazuya; Hirai, Yuka; Imai, Satoki; Chiba, Koji; Akiyama, Yutaka; Sugiyama, Yuichi

    2010-08-01

    Predicting major clearance pathways of drugs is important in understanding their pharmacokinetic properties in clinical use, such as drug-drug interactions and genetic polymorphisms, and their subsequent pharmacological/toxicological effects. In this study, we established an in silico classification method to predict the major clearance pathways of drugs by identifying the boundaries of physicochemical parameters in empirical decisions for each clearance pathway. It requires only four physicochemical parameters [charge, molecular weight (MW), lipophilicity (log D), and protein unbound fraction in plasma (f(up))] that were predicted from their molecular structures without performing any benchwork experiments. The training dataset consisted of 141 approved drugs whose major clearance pathways were determined to be metabolism by CYP3A4, CYP2C9, and CYP2D6, hepatic uptake by OATPs, or renal excretion in an unchanged form. After grouping by charge, each drug was plotted in a three-dimensional space according to three axes of MW, log D, and f(up). Then, rectangular boxes for each clearance pathway were drawn mathematically under the criterion of "maximizing F value (harmonic mean of precision and recall) with minimum volume," yielding to a precision of 88%, which was confirmed through two types of validation: leave-one-out method and validation using a new dataset. With further modification toward multiple pathways and/or other pathways, not only would this in silico classification system be useful for industrial scientists at the early stage of drug development, which can lead to the selection of candidate compounds with optimal pharmacokinetic properties, but also for regulators in evaluating new drugs and giving regulatory requirements that are pharmacokinetically reasonable.

  9. 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.

  10. 2015 Annual Report on Security Clearance Determinations

    DTIC Science & Technology

    2016-06-28

    Element of the Intelligence Community .................... 7 i. The time in days to process the shortest and longest security clearance determination...EXECUTIVE SUMMARY The Intelligence Authorization Act (IAA) for Fiscal Year (FY) 20101 requires the President to submit an annual Report on Security

  11. 29 CFR 1918.41 - Coaming clearances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... hatch beams and hatch covers are not protected by a coaming at least 24-inch (.61 m) high, a taut... athwartship hatch beams, and at both ends of those hatches with fore and aft hatch beams, before intermediate deck hatch covers and hatch beams are removed or replaced. Exception: The three-foot (.91 m) clearance...

  12. 30 CFR 56.7018 - Hand clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or...

  13. 30 CFR 57.7018 - Hand clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while...

  14. 30 CFR 57.7028 - Hand clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  15. 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...

  16. 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...

  17. 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.

  18. 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

  19. 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...

  20. 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...

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. Possible removal of topiramate by continuous renal replacement therapy.

    PubMed

    Browning, Linda; Parker, Dennis; Liu-DeRyke, Xi; Shah, Aashit; Coplin, William M; Rhoney, Denise H

    2010-01-15

    Topiramate is primarily renally eliminated and requires dosage adjustment based upon renal function. While there is data to suggest drug removal during intermittent hemodialysis (IHD), little is known regarding its clearance and dosing during continuous renal replacement therapy (CRRT). We describe a 59-year-old man with refractory status epilepticus who was started on continuous venovenous hemodiafiltration (CVVHDF) for acute renal failure while receiving topiramate with a series of serum concentrations to assess for removal during CVVHDF. Our data suggest clinically important amounts of topiramate are removed by CRRT, and higher topiramate dosage may be needed for these patients instead of the current recommended 50% of normal dosage. Unfortunately, there is no antiepileptic drug dosing recommendation when used during CRRT due to the paucity of data. This case highlights a need for research evaluating the effect of CRRT on AED elimination in order to optimize therapy for seizure control.

  8. 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. ...

  9. 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... Programs Directorate (NPPD), Office of Infrastructure Protection (IP) will submit the following Information... information provided. SUPPLEMENTARY INFORMATION: The Critical Infrastructure Private Sector Clearance Program...

  10. 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.

  11. 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.

  12. Adjustable Bearing System with Selectively Optimized Installational Clearances

    DTIC Science & Technology

    1997-06-30

    ÄÖQ¥ÄL1HE mssx^. Navy Case No. 78,325 PATENTS ADJUSTABLE BEARING SYSTEM WITH SELECTIVELY OPTIMIZED INSTALLATIONAL CLEARANCES BACKGROUND OF THE... clearance 7 conditions. 8 9 10 .. small range of clearances within which to accommodate various operational conditions. Thus, a 12 very tight... clearance is extremely difficult to achieve for certain installations or conditions such as 13 quiet submarine control surface operation and

  13. Impaired renal functional reserve and albuminuria in essential hypertension

    PubMed Central

    Losito, Attilio; Fortunati, Federico; Zampi, Ivano; Del Favero, Albano

    1988-01-01

    The stimulatory effects of an infusion of amino acids on glomerular filtration rate has previously been used to measure renal functional reserve and detect glomerular hyperfiltration. Thirty four patients with mild to moderate essential hypertension and seemingly normal renal function and 22 healthy controls were given infusions of amino acids to investigate whether renal functional reserve is reduced in essential hypertension and to detect patients at risk of renal damage. Although basal creatinine clearance increased after the infusion of amino acids in the controls (mean 27·9 ml/min; 95% confidence interval 18·2 to 37·6), the overall change was lower in the patients (mean 13·4 ml/min; 8·3 to 18·5), 11 of the 34 showing no increase at all. In these 11 non-responders the mean systolic blood pressure was higher than that in the 23 others (178·5 mm Hg v 157 mm Hg, respectively). Mean urinary albumin excretion was abnormal in the patients (93·3 mg/24 h; 44·2 to 142·4); eight of the 11 non-responders had an albumin excretion above the normal range (>20 mg/24 h). In the 11 patients without renal functional reserve a positive correlation was found between basal creatinine clearance and albumin excretion (r=0·695). As consumed renal reserve and albuminuria are markers of glomerular hyperfiltration studying renal function before and after infusion of amino acids can detect hypertensive patients at risk of progressive renal damage. PMID:3135009

  14. 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.

  15. 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.

  16. Pharmacokinetics of pefloxacin in renal insufficiency.

    PubMed

    Montay, G; Jacquot, C; Bariety, J; Cunci, R

    1985-01-01

    The kinetics of pefloxacin has been studied after a single intravenous infusion of 8 mg X kg-1 in 15 male patients with various degrees of renal failure. No difference in distribution or elimination of the drug was observed between patients with mild or severe renal impairment. The mean volume of distribution (Vd area) and the mean plasma clearance were 2.03 l X kg-1 and 121.3 ml X min-1, respectively. The mean apparent elimination half-life was 13.5 h. These values are close to those observed in healthy subjects. No accumulation of the active N-desmethylmetabolite was observed in cases of severe failure as compared to mild impairment; its apparent elimination half-life was about twice that of the parent drug. The efficacy of a 4 haemodialysis in 6 additional anuric subjects done to remove pefloxacin from the body was poor.

  17. 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.

  18. Assessment of Acute Kidney Injury and Renal Fibrosis after Renal Ischemia Protocols in Cats

    PubMed Central

    Dickerson, Vanna M; Rissi, Daniel R; Brown, Cathy A; Brown, Scott A; Schmiedt, Chad W

    2017-01-01

    In an attempt to identify a feline model of acute or chronic kidney disease, this study was designed to evaluate the effects of 15 or 30 min of bilateral renal ischemia (RI) and 60 min of unilateral RI with delayed contralateral nephrectomy as models of acute kidney injury and chronic interstitial fibrosis in cats. Adult, purpose-bred, USDA Class A cats (n = 14) were randomly assigned to receive bilateral RI for 15 min (n = 3) or 30 min (n = 3), unilateral RI for 60 min with a delayed (2 wk) contralateral nephrectomy (n = 5), or sham unilateral RI with a delayed contralateral nephrectomy (n = 3). Serum creatinine concentration, urine specific gravity, and plasma clearance of iohexol were assessed at several time points throughout the study. Renal interstitial inflammatory cell counts and descriptive histopathology were acquired in all cats. Histomorphometry was used to quantify renal interstitial fibrosis and collagen at 120 d after RI in cats undergoing unilateral RI. Renal histopathology was evaluated at 21 and 120 d after bilateral and unilateral RI, respectively. Neither duration of bilateral RI resulted in appreciable histologic renal damage at 21 d after ischemia. At 120 d after ischemia, variable amounts of renal fibrosis were noted after 60 min of unilateral RI with delayed contralateral nephrectomy. Neither of the tested methods is a suitable model of consistent renal interstitial fibrosis in cats. Healthy cats appear able to sustain bilateral RI for as long as 30 min with no apparent effects on renal morphology or function at 21 d after ischemia. PMID:28222840

  19. Serum leptin level has a positive correlation with BMI and creatinine clearance in CAPD patients.

    PubMed

    Seirafian, S; Momeni, A; Taheri, S; Mortazavi, M; Paknahad, Z

    2012-01-01

    In a cross sectional study, 75 patients (42 males and 33 females) on continuous ambulatory peritoneal dialysis (CAPD) were enrolled from October 2007 to February 2008. Serum levels of leptin, albumin, triglyceride, dialysis adequacy (total KT/V), renal creatinine clearance (Cr Cl), mid arm circumference and demographic findings were measured in all patients. The mean age of patients was 53±14.76. The history of hemodialysis was seen in 23 patients. Mean serum leptin level in women and men were 27±23µg/l and 16±13µg/l, respectively. A significant correlation of serum leptin level with body mass index (BMI) (p<0.001) and renal Cr Cl (p<0.001) was found. There was no significant correlation of serum leptin level with KT/V, duration of renal failure, serum triglycerides (TG), serum low density lipoprotein (LDL) cholesterol and mid arm circumference (p>0.05). To our knowledge, this is probably the first study to report that serum leptin level has a direct positive correlation with renal Cr Cl in CAPD patients. This may explain the increase in mortality in patients with lower serum leptin levels (Tab. 2, Fig. 2, Ref. 25).

  20. Vancomycin clearance during continuous venovenous haemofiltration in critically ill patients.

    PubMed

    Boereboom, F T; Ververs, F F; Blankestijn, P J; Savelkoul, T J; van Dijk, A

    1999-10-01

    To study the pharmacokinetics of vancoymcin in critically ill patients with acute renal failure treated with continuous venovenous haemofiltration (CVVHF). Open-label study. Hospital pharmacy centre and medical intensive care unit of the University Medical Centre Utrecht. In a laboratory setting, the sieving coefficient (s) of vancomycin by polyacrilonitrile (PAN) haemofilters of different surface areas was studied. In one patient, the pharmacokinetics of vancomycin were studied following a single dose of vancomycin. Another patient was treated with a vancomycin dosing regimen based on data from the literature, but high trough concentrations made dose reduction necessary after 24 h of withholding therapy. After two doses of 250 mg, serum and ultrafiltrate samples were collected for pharmacokinetic evaluation. INTERVENTIONS++: CVVHF with the following operational characteristics: blood flow 200 ml/min, ultrafiltrate flow 25 ml/min, postdilution, PAN 06 hollow fibre haemofilter. The average sieving coefficient in vitro was 0.73 +/- 0.06, 0.86 +/- 0.11, and 0.80 +/- 0.06 for the PAN 03, 06, and 10 haemofilters, respectively. Changes in the sieving coefficient by increasing the ultrafiltration rate were not clinically significant. The first patient was given a single dose of vancomycin, 1000 mg by intravenous infusion. The following pharmacokinetic data were obtained: apparent volume of distribution (Vd) 55.8 l, terminal half-life time (t(1/2 term)) 15.4 h, total clearance (Cl(tot)) 2.5 l/h, CVVHF clearance (CL(CVVHF, form 1)) 1.4 l/h, and body clearance (Cl(body)) 1.1 l/h. The average sieving coefficient during the study period was 0.89 +/- 0.03. In the second patient, the pharmacokinetics of vancomycin were studied following dose reduction: Vd 41.7 l, (1/2 term) 20.3 h, Cl(tot) 1.4 l/h, Cl(CVVHF, form 1) 1.4 l/h, and Cl(body) < 0.1 l/h. The average sieving coefficient during the study period was 0.88 +/- 0. 03. The cumulative amount of vancomycin removed by means of

  1. 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....

  2. 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....

  3. 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....

  4. 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,...

  5. 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,...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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,...

  14. 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...

  15. 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...

  16. 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),...

  17. 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....

  18. 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...

  19. 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...

  20. 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,...

  1. 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....

  2. 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....

  3. 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),...

  4. 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...

  5. 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....

  6. 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. ...

  7. 30 CFR 56.9330 - Clearance for surface equipment.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 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 from...

  8. 30 CFR 56.9330 - Clearance for surface equipment.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 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 from...

  9. 30 CFR 56.9330 - Clearance for surface equipment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 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 from...

  10. 30 CFR 56.9330 - Clearance for surface equipment.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 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 from...

  11. 24 CFR 3285.305 - Clearance under homes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 5 2011-04-01 2011-04-01 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 frame...

  12. 14 CFR 27.661 - Rotor blade clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Rotor blade clearance. 27.661 Section 27... 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...

  13. 14 CFR 27.661 - Rotor blade clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Rotor blade clearance. 27.661 Section 27... 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...

  14. 14 CFR 29.661 - Rotor blade clearance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Rotor blade clearance. 29.661 Section 29... 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...

  15. 14 CFR 27.661 - Rotor blade clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Rotor blade clearance. 27.661 Section 27... 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...

  16. 14 CFR 29.661 - Rotor blade clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Rotor blade clearance. 29.661 Section 29... 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...

  17. 14 CFR 27.661 - Rotor blade clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Rotor blade clearance. 27.661 Section 27... 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...

  18. 14 CFR 27.661 - Rotor blade clearance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Rotor blade clearance. 27.661 Section 27... 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...

  19. 14 CFR 29.661 - Rotor blade clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Rotor blade clearance. 29.661 Section 29... 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...

  20. 14 CFR 29.661 - Rotor blade clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Rotor blade clearance. 29.661 Section 29... 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...

  1. 14 CFR 29.661 - Rotor blade clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Rotor blade clearance. 29.661 Section 29... 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...

  2. 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...

  3. 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 no...

  4. 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 no...

  5. 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 no...

  6. 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

  7. 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.

  8. 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

  9. 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,…

  10. 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,…

  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. Gas turbine engine active clearance control

    NASA Technical Reports Server (NTRS)

    Deveau, Paul J. (Inventor); Greenberg, Paul B. (Inventor); Paolillo, Roger E. (Inventor)

    1985-01-01

    Method for controlling the clearance between rotating and stationary components of a gas turbine engine are disclosed. Techniques for achieving close correspondence between the radial position of rotor blade tips and the circumscribing outer air seals are disclosed. In one embodiment turbine case temperature modifying air is provided in flow rate, pressure and temperature varied as a function of engine operating condition. The modifying air is scheduled from a modulating and mixing valve supplied with dual source compressor air. One source supplies relatively low pressure, low temperature air and the other source supplies relatively high pressure, high temperature air. After the air has been used for the active clearance control (cooling the high pressure turbine case) it is then used for cooling the structure that supports the outer air seal and other high pressure turbine component parts.

  13. 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

  14. Microbiota-derived uremic retention solutes: perpetrators of altered nonrenal drug clearance in kidney disease.

    PubMed

    Prokopienko, Alexander J; Nolin, Thomas D

    2017-09-20

    Scientific interest in the gut microbiota is increasing due to improved understanding of its implications in human health and disease. In patients with kidney disease, gut microbiota-derived uremic toxins directly contribute to altered nonrenal drug clearance. Microbial imbalances, known as dysbiosis, potentially increase formation of microbiota-derived toxins, and diminished renal clearance leads to toxin accumulation. High concentrations of microbiota-derived toxins such as indoxyl sulfate and p-cresol sulfate perpetrate interactions with drug metabolizing enzymes and transporters, which provides a mechanistic link between increases in drug-related adverse events and dysbiosis in kidney disease. Areas covered: This review summarizes the effects of microbiota-derived uremic toxins on hepatic phase I and phase II drug metabolizing enzymes and drug transporters. Research articles that tested individual toxins were included. Therapeutic strategies to target microbial toxins are also discussed. Expert commentary: Large interindividual variability in toxin concentrations may explain some differences in nonrenal clearance of medications. Advances in human microbiome research provide unique opportunities to systematically evaluate the impact of individual and combined microbial toxins on drug metabolism and transport, and to explore microbiota-derived uremic toxins as potential therapeutic targets.

  15. 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

  16. Renal hemodynamic effects of the HMG-CoA reductase inhibitors in autosomal dominant polycystic kidney disease.

    PubMed

    Zand, Ladan; Torres, Vicente E; Larson, Timothy S; King, Bernard F; Sethi, Sanjeev; Bergstralh, Eric J; Angioi, Andrea; Fervenza, Fernando C

    2016-08-01

    To determine the effect of statins on renal hemodynamics in normal volunteers and those with autosomal dominant polycystic kidney disease either with mild or moderate renal dysfunction. Thirty-two study subjects were enrolled in this study: 11 normal volunteers, 11 study subjects with autosomal dominant polycystic kidney disease (ADPKD) and mild kidney disease and 10 study subjects with ADPKD and moderate kidney disease. Subjects in each group received simvastatin 40 mg once daily for a period of 4 weeks. Renal blood flow was measured based on para-amino-hippurate (PAH) clearance and with the use of a magnetic resonance (MR) scanner at the beginning and following 4 weeks of therapy with statins. At the end of the study, except for the lipid profile, which was significantly lower in all groups, other laboratory results showed no change. Four weeks of therapy with simvastatin resulted in no change in serum creatinine, 24-h urinary protein, sodium, iothalamate clearance, PAH clearance or renal blood flow as measured by MRI or based on PAH clearance. Four weeks of therapy with simvastatin did not change renal blood flow in the study subjects with ADPKD with mild-to-moderate renal dysfunction or in healthy volunteers. NCT02511418. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  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. 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

  19. 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.

  20. 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

  1. Evaluation of lung clearance of inhaled pertechnegas.

    PubMed

    Fanti, S; Compagnone, G; Pancaldi, D; Franchi, R; Corbelli, C; Marengo, M; Onofri, C; Galassi, R; Levorato, M; Monetti, N

    1996-02-01

    Pertechnegas is a new ventilation agent produced by modifying the atmosphere of combustion of Technegas. Due to its rapid disappearance from the lungs, Pertechnegas has been suggested as useful in measuring pulmonary epithelial permeability. This study aimed to assess the reliability of ventilation scans with Pertechnegas to evaluate alveolar-capillary permeability. Six non-smokers with no evidence of pulmonary disease were investigated. Scintigraphic data were used to evaluate the site of Pertechnegas deposition (by assessing the Penetration Index [PI] of the gas), its clearance rate (by calculating the time to half-clearance [T1/2]) and its lung distribution (by means of a pixel-by-pixel analysis. PI measurements produced a mean value of 88.8 +/- 13.3% (range 69-117%). Time activity curves showed a fast clearance in all cases (mean T1/2 = 10.7 +/- 2.1 min, range 8.1-14.3 min). Comparison of statistical indices of uniform deposition (skewness and kurtosis) indicated satisfactory homogeneity of Pertechnegas distribution throughout the lungs. These data show that after inhalation Pertechnegas has a peripheral deposition and a homogeneous distribution in the lungs and is rapidly cleared through the alveolar-capillary barrier. In conclusion Pertechnegas can be recommended as a potential radiopharmaceutical for studying the pulmonary epithelial barrier.

  2. Antipyrine clearance during occupational exposure to styrene.

    PubMed Central

    Døssing, M

    1983-01-01

    Animal experiments have indicated that styrene, which is a widely used organic solvent, may induce the microsomal enzyme function of the liver. Thirteen workers with long-term exposure to styrene in a polyester plant were investigated. They worked at air concentrations about the maximal allowed time-weighted average concentration of styrene in most Western countries (50 ppm). The clearance of antipyrine was determined from saliva concentrations before and after three weeks free of exposure and then again three weeks after returning to work. Thirteen matched controls were investigated with similar intervals and methods. No significant differences were found between the half life, apparent volume of distribution, or clearance of antipyrine either within the groups or between the groups. The data exclude (95% confidence limit) the possibility that occupational exposure to styrene at concentrations about 50 ppm stimulates the microsomal enzyme function of the liver to a degree compatible with an increase in antipyrine clearance of more than 2 ml x min-1 (3%). While the first antipyrine estimation was carried out under medical supervision, the workers themselves managed to perform the antipyrine test correctly after verbal and written instructions. This has broadened the application of the antipyrine test. PMID:6131688

  3. Airway clearance strategies for the pediatric patient.

    PubMed

    Davidson, Kathryn L

    2002-07-01

    Clinicians who care for cystic fibrosis (CF) patients have many techniques to choose from to facilitate mucus clearance. Little has been published about when to introduce the various techniques and in what order to teach them. Debates have occurred over these issues in the CF community, and there is now consensus on some topics. It is very important to teach adherence to therapy at an early age. Adherence to an airway clearing regimen assists in maintaining good pulmonary function in CF patients. Knowing when and how to introduce airway clearance techniques beyond chest physiotherapy (CPT) is clinically relevant and useful. A 5-position modified CPT routine can be used with infants and children, and it takes less time and may improve adherence. Infants and toddlers can be taught breathing games that eventually lead them to perform diaphragmatic breathing and huffing. Once they have mastered diaphragmatic breathing and huffing, children can be taught the active cycle of breathing technique. Modified CPT can be phased out at that point. Positive expiratory pressure therapy can usually be introduced around 6-7 years of age. High-frequency chest wall oscillation, oscillating positive expiratory pressure, and autogenic drainage all follow. CF patients should be given every opportunity to learn and master various techniques to promote mucus clearance.

  4. 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.

  5. Influence of clearance between piston and cylinder on piston friction

    SciTech Connect

    Takiguchi, M.; Kikuchi, H.; Furuhama, S

    1988-01-01

    It is desired to minimize clearance between the piston and the cylinder to reduce noise and suppress vibration. Although significant effort has been made for this purpose, increased piston friction force and the occurrence of seizure still prevent the ideal clearance from being realized. In order to determine the lower limit of the piston clearance, it is crucial to clarify the following unknowns; which part of piston contributes to friction increase as the piston clearance is decreased, during which phase of the piston motion the friction increase occurs, and how the piston clearance affects lubrication phenomena.

  6. 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.

  7. 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.

  8. 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

  9. Drug dosing during continuous renal replacement therapies.

    PubMed

    Thompson, A Jill

    2008-04-01

    Continuous renal replacement therapies (CRRT) are used to manage fluid overload and/or renal failure. The continuous nature of the fluid and solute removal has less impact on hemodynamic variables in critically ill patients, making CRRT preferred over intermittent hemodialysis for some patients in the intensive care arena. The impact of CRRT on drug removal is variable depending on the CRRT modality, the ultrafiltrate and dialysate flow rates, the filter, and the patient's residual renal function; all of these may change from patient to patient or even in the same patient depending on the clinical status. However, CRRT modalities are generally more efficient than intermittent hemodialysis at drug removal, in some cases approximating or even exceeding normal renal function, resulting in a significant risk of subtherapeutic dosing if conventional hemodialysis dosing recommendations are followed. This annotated bibliography provides a summary of publications analyzing drug removal during CRRT, including CRRT settings and drug clearance values found in each study. Caution is warranted as findings from one study may not be generalizable to all patients due to the many factors that influence drug removal. Serum drug concentrations should be monitored when available, and patient clinical status is exceedingly important for following expected and unexpected responses to drug therapies. Reviews on general drug dosing calculations in CRRT are available elsewhere.

  10. 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.

  11. 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.

  12. A study of nephron function in normal tropical residents using the creatinine and lithium clearances

    NASA Astrophysics Data System (ADS)

    Arthur, S. K.; Nyarko, A. K.; Asaku, J. Y.; Akyeampong, A. Y.

    The kidney bears the brunt of the demands of a tropical climate for water and electrolyte homeostasis. We hypothesised that a tropical climate may cause adaptive changes in the entire organism leading to altered renal function in our subjects. Hence renal function data for residents of a temperate climate may not be applic- able to tropical residents. We therefore sought to elucidate renal function in subjects residing in a tropical climate. We used lithium clearance, CLi, a non-invasive tool for assessing proximal tubular function in humans, and endogenous creatinine clearance, CCr, to estimate proximal tubular function and glomerular function, respectively, in our subjects. We did this in order to establish whether or not nephron function in our subjects differs from that for residents of a temperate climate. Nineteen male and 12 female Ghanaian subjects aged between 15 and 48 years were studied. The estimated GCr was 117.3+/-6.6 ml/min for male subjects and 97+/-6.4 ml/min for female subjects. CLi was 20.3+/-1.6 ml/min for male and 19.1+/-0.4 ml/min for female subjects, respectively. The estimated absolute reabsorption rate of fluid of proximal tubules was 97.0+/-6.0 ml/min for males and 78.1+/-6.0 ml/min for females. The percentage proximal fluid reabsorption for male and female subjects was 81.2+/-1.4 and 79.5+/-1.6, respectively. The differences between male and female values (mean+/-SEM) were not statistically significant. The data suggest that the proximal tubule in residents of a tropical climate may reabsorb more fluid compared to that in residents of a temperate climate. Our values for proximal tubular reabsorption are higher than those reported for residents of a temperature climate. Our estimate of glomerular filtration, however, is similar to published data for Caucasians. The difference in proximal tubular function may reflect possible renal adaptation to a hot, humid climate. We conclude that renal function of tropical residents differs from that of

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. High serum apolipoprotein AIV levels in renal transplant recipients.

    PubMed

    Massy, Z A; Kandoussi, A M; Mamzer-Bruneel, M F; Kreis, H; Drüeke, T; Lacour, B

    2001-02-01

    Human apolipoprotein (apo) AIV might play a role in post-transplant reverse cholesterol transport, which appears to be comparable to that seen in healthy subjects. However, there may be subtle differences between healthy individuals and renal transplant recipients, given the other abnormalities of lipoprotein metabolism in the latter. Therefore, the aim of the present study was to investigate possible changes of serum apo AIV levels in renal transplant recipients, and to evaluate potential factors influencing these levels. Total and free serum apo AIV was determined in 36 clinically stable renal transplant recipients and in 20 sex- and age-matched healthy control subjects. Mean total serum apo IV concentrations (+/- SD) were significantly higher in renal transplant recipients than in control subjects (202 +/- 102 vs 79 +/- 45 mg/l, p < 0.01). The percentage of lipoprotein-free fractions of apo AIV was comparable in both groups. The elevated total serum concentrations of apo AIV were mainly related to creatinine clearance and partially to serum triglyceride levels in renal transplant recipients. Our data suggest that the observed elevation of serum apo AIV concentrations in renal transplant recipients is essentially related to the presence of impaired renal function.

  20. 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.