Nordholm, Anders; Mace, Maria L; Gravesen, Eva; Hofman-Bang, Jacob; Morevati, Marya; Olgaard, Klaus; Lewin, Ewa
2018-05-01
In a new paradigm of etiology related to chronic kidney disease-mineral and bone disorder (CKD-MBD), kidney injury may cause induction of factors in the injured kidney that are released into the circulation and thereby initiate and maintain renal fibrosis and CKD-MBD. Klotho is believed to ameliorate renal fibrosis and CKD-MBD, while activin A might have detrimental effects. The unilateral ureter obstruction (UUO) model is used here to examine this concept by investigating early changes related to renal fibrosis in the obstructed kidney, untouched contralateral kidney, and vasculature which might be affected by secreted factors from the obstructed kidney, and comparing with unilateral nephrectomized controls (UNX). Obstructed kidneys showed early Klotho gene and protein depletion, whereas plasma Klotho increased in both UUO and UNX rats, indicating an altered metabolism of Klotho. Contralateral kidneys had no compensatory upregulation of Klotho and maintained normal expression of the examined fibrosis-related genes, as did remnant UNX kidneys. UUO caused upregulation of transforming growth factor-β and induction of periostin and activin A in obstructed kidneys without changes in the contralateral kidneys. Plasma activin A doubled in UUO rats after 10 days while no changes were seen in UNX rats, suggesting secretion of activin A from the obstructed kidney with potentially systemic effects on CKD-MBD. As such, increased aortic sclerostin was observed in UUO rats compared with UNX and normal controls. The present results are in line with the new paradigm and show very early vascular effects of unilateral kidney fibrosis, supporting the existence of a new kidney-vasculature axis.
El-Merhi, Fadi; Mohamad, May; Haydar, Ali; Naffaa, Lena; Nasr, Rami; Deeb, Ibrahim Al-Sheikh; Hamieh, Nadine; Tayara, Ziad; Saade, Charbel
2018-04-01
To evaluate the performance of non-contrast computed tomography (CT) by reporting the difference in attenuation between normal and inflamed renal parenchyma in patients clinically diagnosed with acute pyelonephritis (APN). This is a retrospective study concerned with non-contrast CT evaluation of 74 patients, admitted with a clinical diagnosis of APN and failed to respond to 48h antibiotics treatment. Mean attenuation values in Hounsfield units (HU) were measured in the upper, middle and lower segments of the inflamed and the normal kidney of the same patient. Independent t-test was performed for statistical analysis. Image evaluation included receiver operating characteristic (ROC), visual grading characteristic (VGC) and kappa analyses. The mean attenuation in the upper, middle and lower segments of the inflamed renal cortex was 32%, 25%, and 29% lower than the mean attenuation of the corresponding cortical segments of the contralateral normal kidney, respectively (p<0.01). The mean attenuation in the upper, middle, and lower segments of the inflamed renal medulla was 48%, 21%, and 30%, lower than the mean attenuation of the corresponding medullary segments of the contralateral normal kidney (p<0.02). The mean attenuation between the inflamed and non-inflamed renal cortex and medulla was 29% and 30% lower respectively (p<0.001). The AUCROC (p<0.001) analysis demonstrated significantly higher scores for pathology detection, irrespective of image quality, compared to clinical and laboratory results with an increased inter-reader agreement from poor to substantial. Non-contrast CT showed a significant decrease in the parenchymal density of the kidney affected with APN in comparison to the contralateral normal kidney of the same patient. This can be incorporated in the diagnostic criteria of APN in NCCT in the emergency setting. Copyright © 2017 Elsevier Inc. All rights reserved.
Senyucel, M F; Boybeyi, O; Ayva, S; Aslan, M K; Soyer, T; Demet, A I; Kısa, U; Basar, M; Cakmak, M A
2013-10-01
An experimental study was carried out to evaluate the effects of extracorporeal shock wave lithotripsy (ESWL) on contralateral kidney, liver and lung by histopathological and biochemical methods. Twelve New Zealand rabbits were allocated to two groups (n = 6). Tissues of control group (CG, n = 6) were harvested without any intervention. In ESWL group (EG), right kidneys were exposed to 3,000 shock waves at 14 kV energy using electro-hydraulic type ESWL device three times every other day. Both kidneys, liver, and right lobe of lung tissues in EG were harvested on seventh day. Kidneys were examined histopathologically for presence of glomerular and tubular injury, interstitial edema, congestion, inflammation and fibrosis. Livers were examined for hepatocyte vacuolization, congestion, portal inflammation and fibrosis. Lung tissues were examined for loss of normal structure, emphysema, interstitial congestion-edema, prominent alveolar septal vessels, interstitial inflammation, intra-alveolar hemorrhage, intraluminal hemorrhage, peribronchial edema, congestion, inflammation in bronchial wall and epithelial desquamation. Biochemical analysis of tissue samples was performed for oxidative injury markers. Histopathological evaluations revealed that tubular injury was found in both shocked and contralateral kidneys (p < 0.05). EG showed higher grades of portal fibrosis in liver and higher grades of peribronchial congestion in lung when compared to CG (p < 0.05). Biochemical evaluations of both kidneys showed that malondialdehyde levels were higher in EG than in CG (p < 0.05). ESWL causes histopathologic alterations both in shocked and contralateral kidneys. Extrarenal tissues such as liver and lung can be affected by shock waves histopathologically and oxidative injury of contralateral kidney may occur acutely after ESWL.
Adaptive functional change of the contralateral kidney after partial nephrectomy.
Choi, Se Young; Yoo, Sangjun; You, Dalsan; Jeong, In Gab; Song, Cheryn; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong; Kim, Choung-Soo
2017-08-01
Partial nephrectomy aims to maintain renal function by nephron sparing; however, functional changes in the contralateral kidney remain unknown. We evaluate the functional change in the contralateral kidney using a diethylene triamine penta-acetic acid (DTPA) renal scan and determine factors predicting contralateral kidney function after partial nephrectomy. A total of 699 patients underwent partial nephrectomy, with a DTPA scan before and after surgery to assess the separate function of each kidney. Patients were divided into three groups according to initial contralateral glomerular filtration rate (GFR; group 1 : <30 ml·min -1 ·1.73 m -2 , group 2 : 30-45 ml·min -1 ·1.73 m -2 , and group 3 : ≥45 ml·min -1 ·1.73 m -2 ). Multiple-regression analysis was used to identify the factors associated with increased GFR of the contralateral kidney over a 4-yr postoperative period. Patients in group 1 had a higher mean age and hypertension history, worse American Society of Anesthesiologists score, and larger tumor size than in the other two groups. The ipsilateral GFR changes at 4 yr after partial nephrectomy were -18.9, -3.6, and 3.9% in groups 1 , 2 , and 3 , respectively, whereas the contralateral GFR changes were 10.8, 25.7, and 38.8%. Age [β: -0.105, 95% confidence interval (CI): -0.213; -0.011, P < 0.05] and preoperative contralateral GFR (β: -0.256, 95% CI: -0.332; -0.050, P < 0.01) were significant predictive factors for increased GFR of the contralateral kidney after 4 yr. The contralateral kidney compensated for the functional loss of the ipsilateral kidney. The increase of GFR in contralateral kidney is more prominent in younger patients with decreased contralateral renal function. Copyright © 2017 the American Physiological Society.
Kim, Hee Youn; Lee, Seung-Ju; Yoo, Je Mo; Lee, Joon Ho
2017-01-01
Purpose To determine whether kidney sizes were changed after ureteral stents were instilled, and if so, what parameters were significant. Methods Parenchymal width (PW) of 98 patients with unilateral ureteral stents was measured from the coronal view of CT scans for both stented and unstented contralateral kidney. The mean PW and % change of mean PW were calculated before stenting and at the time of last stent change. Estimated glomerular filtrate rate (eGFR) was recorded as well. Results The mean duration of ureteral stent indwelled was 15.6 ± 10.2 (mean ± SD) months. The change of mean PW of stented kidneys and unstented contralateral kidneys was −16.9 ± 16.4 (mean ± SD)% and 3.6 ± 10.7%, respectively. eGFR before and at the time of the last stent change did not show significant difference (p = 0.294). Duration of ureteral stent indwelled was found to be inversely related to the % change of mean PW (Spearman's correlation coefficient = −0.291, p < 0.001). Conclusions For unilateral ureteral obstruction, kidney size was decreased over time in spite of indwelling ureteral stent. This finding can be overlooked by clinicians due to compensatory growth of contralateral kidney and resultant normal eGFR. PMID:28656136
Kazama, Itsuro; Nakajima, Toshiyuki
2017-10-01
In patients with bilateral ureteral obstruction, the serum creatinine levels are often elevated, sometimes causing postrenal acute kidney injury (AKI). In contrast, those with unilateral ureteral obstruction present normal serum creatinine levels, as long as their contralateral kidneys are preserved intact. However, the unilateral obstruction of the ureter could affect the renal function, as it humorally influences the renal hemodynamics. A 66-year-old man with a past medical history of hypertension and diabetes mellitus came to our outpatient clinic because of right abdominal dullness. Unilateral ureteral obstruction caused by a radio-opaque calculus in the right upper ureter and a secondary renal dysfunction. As oral hydration and the use of calcium antagonists failed to allow the spontaneous stone passage, extracorporeal shock wave lithotripsy (ESWL) was performed. Immediately after the passage of the stone, the number of red blood cells in the urine was dramatically decreased and the serum creatinine level almost returned to the normal range with the significant increase in glomerular filtration rate. Unilateral ureteral obstruction by the calculus, which caused reflex vascular constriction and ureteral spasm in the contralateral kidney, was thought to be responsible for the deteriorating renal function.
Park, Bong Hee; Cho, Kang Jun; Kim, Jung Im; Bae, Sang Rak; Lee, Yong Seok; Kang, Sung Hak; Kim, Joon Chul; Han, Chang Hee
2018-02-01
To investigate the usefulness of the ellipsoid formula for assessing compensatory hypertrophy of the contralateral kidney on pre-operative and post-operative CT in renal cell carcinoma (RCC) patients. We retrospectively identified 389 patients who had radical nephrectomy for RCC between 2011 and 2015. Contrast-enhanced CT was performed within 3 months pre-operative and at 1 year post-operative. The kidney volumes were calculated from CT using the ellipsoid formula. We subdivided patients into three groups based on tumour size (I: ≤4 cm, II: 4-7 cm, III: >7 cm). Volumetric renal parameters were compared and multivariate analyses were performed to determine predictors associated with pre-operative and post-operative compensatory hypertrophy. Kidney volume calculation using the ellipsoid method took a median of 51 s. Group III had a significantly larger median pre-operative contralateral renal volume than Groups I and II (I: 140.4, II: 141.6, III: 166.7 ml, p < 0.05). However, the median ratio of post-operative contralateral renal volume change was significantly higher in Groups I and II than Group III (I: 0.36, II: 0.23, III: 0.12, p < 0.001). On multivariate analysis, tumour size revealed the strongest positive association with pre-operative contralateral kidney volume (partial regression coefficient: β = 30.8, >7 cm) and ratio of post-operative contralateral kidney volume change (β = 0.214, I vs III; β = 0.168, II vs III). Kidney volume calculation for assessing pre- and post-operative compensatory hypertrophy of the contralateral kidney in RCC patients can be easily and rapidly performed from CT images using the ellipsoid formula. Advances in knowledge: The ellipsoid formula allows reliable method for assessing pre-operative and post-operative compensatory hypertrophy of the contralateral kidney in RCC.
Bagheri, Fariborz; Pusztai, Csaba; Farkas, László; Kallidonis, Panagiotis; Buzogány, István; Szabó, Zsuzsanna; Lantos, János; Imre, Marianna; Farkas, Nelli; Szántó, Árpád
2016-12-01
To elucidate the impact of renal parenchymal loss and the ischemic reperfusion injury (RI) on the renal function after laparoscopic partial nephrectomy (LPN) under warm ischemia (WI). Thirty-five patients with a single polar renal mass ≤4 cm and normal contralateral kidney underwent LPN. Transperitoneal LPN with WI using en bloc hilar occlusion was performed. The total differential renal function (T-DRF) using 99m Tc-dimercaptosuccinic acid was evaluated preoperatively and postoperatively over a period of 1 year. A special region of interest (ROI) was selected on the non-tumorous pole of the involved kidney, and was compared with the same ROI in the contralateral kidney. The latter comparison was defined as partial differential renal function (P-DRF). Any postoperative decline in the P-DRF of the operated kidney was attributed to the RI. Subtraction of the P-DRF decline from the T-DRF decline was attributed to the parenchymal loss caused by the resection of the tumor and suturing of the normal parenchyma. The mean WI time was 22 min, and the mean weight of resected specimen was 18 g. The mean postoperative eGFR declined to 87 ml/min/1.73 m 2 from its baseline mean value of 97 ml/min/1.73 m 2 (p value = 0.075). Mean postoperative T-DRF and P-DRF of the operated kidney declined by 7 and 3 %, respectively. After LPN of small renal mass, decline in renal function is primarily attributed to parenchymal loss caused by tumor resection and suturing of the normal parenchyma rather than the RI.
Renal expression of aminopeptidase A in rats with two-kidney, one-clip hypertension.
Wolf, G; Wenzel, U; Assmann, K J; Stahl, R A
2000-12-01
Angiotensin II (ANG II) is a major factor involved in the progression of chronic renal disease. Although the generation of this vasoactive peptide has been investigated in great detail, only a few studies have hitherto addressed the metabolism of ANG II into fragments such as angiotensin III and IV (ANG III, IV) which may exert physiological effects independent of ANG II. Aminopeptidase A (APA) is the major enzyme degrading ANG II. The aim of the current study was to evaluate glomerular APA expression in rats with two-kidney, one-clip hypertension. The left renal artery was restricted with a 0.2-mm silver clip. Kidneys were harvested 1 and 4 weeks after surgery. APA enzyme and protein expression was evaluated in kidney sections. Total APA enzyme activity and mRNA expression was assessed in isolated glomeruli. Degradation of exogenous ANG II by isolated glomeruli was measured with reverse-phase high-performance liquid chromatography. APA enzyme activity, protein, and mRNA expression were stimulated in the clipped kidney 1 week after surgery compared with the contralateral kidney or normal controls. In contrast, 4 weeks after clipping APA activity and expression was higher in the contralateral kidney. In parallel to these findings, degradation of ANG II was greatest in isolated glomeruli obtained from the clipped kidney after 1 week. However, preparations from the contralateral kidney 4 weeks after surgery were more active in the metabolism of exogenous ANG II. The present study provides evidence that APA is complexly regulated in in vivo situations with an activated local renin-ANG II system. ANG II appears to play a direct role in this regulation. However, since conversion of ANG II to ANG III by APA is the initial step leading to the formation of ANG IV which may exert detrimental effects not mediated through classical ANG II receptors, a local increase in APA activity may contribute to the progression of chronic renal disease even during complete AT(1)-receptor blockade.
Zhang, Xin; Zhu, Xiangyang; Ferguson, Christopher M.; Jiang, Kai; Burningham, Tyson; Lerman, Amir; Lerman, Lilach O.
2018-01-01
Object Low-energy shockwave (SW) therapy attenuates damage in the stenotic kidney (STK) caused by atherosclerotic renal artery stenosis (ARAS). We hypothesized that magnetic resonance elastography (MRE) would detect attenuation of fibrosis following SW in unilateral ARAS kidneys. Materials and Methods Domestic pigs were randomized to control, unilateral ARAS, and ARAS treated with 6 sessions of SW over 3 consecutive weeks (n=7 each) starting after 3 weeks of ARAS or sham. Four weeks after SW treatment, renal fibrosis was evaluated with MRE in-vivo or trichrome staining ex-vivo. Blood pressure, single-kidney renal-blood-flow (RBF) and glomerular-filtration-rate (GFR) were assessed. Results MRE detected increased stiffness in the STK medulla (15.3±2.1 vs. 10.1±0.8 kPa, p<0.05) that moderately correlated with severity of fibrosis (R2=0.501, p<0.01), but did not identify mild STK cortical or contralateral kidney fibrosis. Trichrome staining showed that medullary fibrosis was increased in ARAS and alleviated by SW (10.4±1.8% vs. 2.9±0.2%, p<0.01). SW slightly decreased blood pressure and normalized STK RBF and GFR in ARAS. In the contralateral kidney, SW reversed the increase in RBF and GFR. Conclusion MRE might be a tool for noninvasive monitoring of medullary fibrosis in response to treatment in kidney disease. PMID:29289980
Peptide-induced prostaglandin biosynthesis in the renal-vein-constricted kidney
Myers, Stuart I.; Zipser, Robert; Needleman, Philip
1981-01-01
The ipsilateral kidney was removed from a rabbit 48h after unilateral partial renal-vein-constriction and was perfused with Krebs–Henseleit media at 37°C. Hourly administration of a fixed dose of bradykinin to the renal-vein-constricted kidney demonstrated a marked time-dependent increase in the release of bioassayable prostaglandin E2 and thromboxane A2 into the venous effluent as compared with the response of the contralateral control kidney. The renal-vein-constricted kidney produced up to 60 times more prostaglandin E2 in response to bradykinin after 6h of perfusion as compared with the contralateral kidney; thromboxane A2 was not demonstratable in the contralateral kidney. Inhibition of protein synthesis de novo in the perfused renal-vein-constricted kidney with cycloheximide lessened the hormone-stimulated increase in prostaglandin E2 by 94% and in thromboxane A2 by 90% at 6h of perfusion. Covalent acetylation of the renal cyclo-oxygenase by prior oral administration of aspirin to the rabbit inhibited initial bradykinin-stimulated prostaglandin E2 biosynthesis 71% at 1h of perfusion. However, there was total recovery from aspirin in the renal-vein-constricted kidney by 2h of perfusion after bradykinin stimulation. Total cyclo-oxygenase activity as measured by [14C]arachidonate metabolism to labelled prostaglandins by renal cortical and renal medullary microsomal fractions prepared from 6h-perfused kidneys demonstrated that renal-vein-constricted kidney-cortical cyclo-oxygenase activity was significantly greater than the contralateral-kidney-cortical conversion, whereas medullary arachidonate metabolism was comparable in both the renal-vein-constricted kidney and contralateral kidney. These data suggest that perfusion of a renal-vein-constricted kidney initiates a time-dependent induction of synthesis of prostaglandin-producing enzymes, which appear to be primarily localized in the renal cortex. The presence of the synthetic capacity to generate very potent vasodilator and vasoconstrictor prostaglandins in the renal cortex suggests that these substances could mediate or modulate changes in renal vascular resistance in pathological states. PMID:6798974
Infundibulopelvic stenosis in children
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lucaya, J.; Enriquez, G.; Delgado, R.
1984-03-01
Of 11,500 children who underwent excretory urography during a 17-year period, three were found to have the rare renal malformation infundibulopelvic stenosis, characterized by caliceal dilatation, infundibular stenosis, and hypoplasia or stenosis of the renal pelvis. The contralateral kidney was absent in two cases and normal in the other. Voiding cystourethrograms were normal in all three. Renal sonography showed a variable degree of caliceal dilatation without associated pelvic dilatation. The diagnosis was confirmed by retrograde ureteropyelography in one case. Two patients were followed for 12 and 18 months, respectively; both remained asymptomatic with normal renal function, and sequential sonographic examinationsmore » of their kidneys have shown no significant changes. The third patient died of an unrelated condition. Infundibulopelvic stenosis has highly characteristic radiographic features, and prognosis is good for most affected patients.« less
Zhang, Xin; Zhu, Xiangyang; Ferguson, Christopher Martyn; Jiang, Kai; Burningham, Tyson; Lerman, Amir; Lerman, Lilach Orly
2018-06-01
Low-energy shockwave (SW) therapy attenuates damage in the stenotic kidney (STK) caused by atherosclerotic renal artery stenosis (ARAS). We hypothesized that magnetic resonance elastography (MRE) would detect attenuation of fibrosis following SW in unilateral ARAS kidneys. Domestic pigs were randomized to control, unilateral ARAS, and ARAS treated with 6 sessions of SW over 3 consecutive weeks (n = 7 each) starting after 3 weeks of ARAS or sham. Four weeks after SW treatment, renal fibrosis was evaluated with MRE in vivo or trichrome staining ex vivo. Blood pressure, single-kidney renal-blood-flow (RBF) and glomerular-filtration-rate (GFR) were assessed. MRE detected increased stiffness in the STK medulla (15.3 ± 2.1 vs. 10.1 ± 0.8 kPa, p < 0.05) that moderately correlated with severity of fibrosis (R 2 = 0.501, p < 0.01), but did not identify mild STK cortical or contralateral kidney fibrosis. Trichrome staining showed that medullary fibrosis was increased in ARAS and alleviated by SW (10.4 ± 1.8% vs. 2.9 ± 0.2%, p < 0.01). SW slightly decreased blood pressure and normalized STK RBF and GFR in ARAS. In the contralateral kidney, SW reversed the increase in RBF and GFR. MRE might be a tool for noninvasive monitoring of medullary fibrosis in response to treatment in kidney disease.
The Role of Procurement Biopsies in Acceptance Decisions for Kidneys Retrieved for Transplant
Stewart, Darren E.; Bista, Bipin R.; Salkowski, Nicholas; Snyder, Jon J.; Israni, Ajay K.; Crary, Gretchen S.; Rosendale, John D.; Matas, Arthur J.; Delmonico, Francis L.
2014-01-01
Background and objectives There is a shortage of kidneys for transplant, and many patients on the deceased donor kidney transplant waiting list would likely benefit from kidneys that are currently being discarded. In the United States, the most common reason given for discarding kidneys retrieved for transplant is procurement biopsy results. This study aimed to compare biopsy results from discarded kidneys with discard attributed to biopsy findings, with biopsy results from comparable kidneys that were successfully transplanted. Design, setting, participants, & measurements In this retrospective, observational, case-control study, biopsy reports were examined from 83 kidneys discarded in 2010 due to biopsy findings (cases), 83 contralateral transplanted kidneys from the same donor (contralateral controls), and 83 deceased donors randomly matched to cases by donor risk profile (randomly matched controls). A second procurement biopsy was obtained in 64 of 332 kidneys (19.3%). Results The quality of biopsy reports was low, with amounts of tubular atrophy, interstitial inflammation, arteriolar hyalinosis, and acute tubular necrosis often not indicated; 69% were wedge biopsies and 94% used frozen tissue. The correlation between first and second procurement biopsies was poor; only 25% of the variability (R2) in glomerulosclerosis was explained by biopsies being from the same kidney. The percentages of glomerulosclerosis overlapped substantially between cases, contralateral controls, and randomly matched controls: 17.1%±15.3%, 9.0%±6.6%, and 5.0%±5.9%, respectively. Of all biopsy findings, only glomerulosclerosis>20% was independently correlated with discard (cases versus contralateral controls; odds ratio, 15.09; 95% confidence interval, 2.47 to 92.41; P=0.003), suggesting that only this biopsy result was used in acceptance decisions. One-year graft survival was 79.5% and 90.7% in contralateral and randomly matched controls, respectively, versus 91.6% among all deceased donor transplants in the Scientific Registry of Transplant Recipients. Conclusions Routine use of biopsies could lead to unnecessary kidney discards. PMID:24558053
Ureteric entrapment in sacroiliac joint causing hydroureter and ipsilateral kidney hypertrophy.
Otsuru, Yurie; Kondo, Chuichi; Hara, Shohei; Takahashi, Hideo; Matsuno, Kenjiro
2018-06-01
A unilateral megaureter was found in an elderly female cadaver during routine dissection. The left proximal ureter, which was thick and convolute, descended and entered into the pelvic cavity, where the distal ureter was attached to the posterior pelvic wall at the inlet level. Removal of connective tissue surrounding the attached region revealed ureteric entrapment in the sacroiliac joint. The ipsilateral kidney, from which the megaureter originated, showed no pelvicalyceal dilatation. In contrast, the left kidney was enlarged, weighing 24% more than the right kidney. Differences in the upper urinary system between the obstructed and normal sides were examined in terms of gross anatomy, measurements, and histology. Although ureteric obstruction frequently causes hydroureter and hydronephrosis, the present case is very rare as the incomplete obstruction may have stimulated ipsilateral kidney growth, instead of contralateral compensatory augmentation.
Mulder, Jan; Hökfelt, Tomas; Knuepfer, Mark M.
2013-01-01
Efferent renal sympathetic nerves reinnervate the kidney after renal denervation in animals and humans. Therefore, the long-term reduction in arterial pressure following renal denervation in drug-resistant hypertensive patients has been attributed to lack of afferent renal sensory reinnervation. However, afferent sensory reinnervation of any organ, including the kidney, is an understudied question. Therefore, we analyzed the time course of sympathetic and sensory reinnervation at multiple time points (1, 4, and 5 days and 1, 2, 3, 4, 6, 9, and 12 wk) after renal denervation in normal Sprague-Dawley rats. Sympathetic and sensory innervation in the innervated and contralateral denervated kidney was determined as optical density (ImageJ) of the sympathetic and sensory nerves identified by immunohistochemistry using antibodies against markers for sympathetic nerves [neuropeptide Y (NPY) and tyrosine hydroxylase (TH)] and sensory nerves [substance P and calcitonin gene-related peptide (CGRP)]. In denervated kidneys, the optical density of NPY-immunoreactive (ir) fibers in the renal cortex and substance P-ir fibers in the pelvic wall was 6, 39, and 100% and 8, 47, and 100%, respectively, of that in the contralateral innervated kidney at 4 days, 4 wk, and 12 wk after denervation. Linear regression analysis of the optical density of the ratio of the denervated/innervated kidney versus time yielded similar intercept and slope values for NPY-ir, TH-ir, substance P-ir, and CGRP-ir fibers (all R2 > 0.76). In conclusion, in normotensive rats, reinnervation of the renal sensory nerves occurs over the same time course as reinnervation of the renal sympathetic nerves, both being complete at 9 to 12 wk following renal denervation. PMID:23408032
Choline pathways during normal and stimulated renal growth in rats.
Bean, G H; Lowenstein, L M
1978-01-01
Cellular membrane synthesis occurs during normal and stimulated renal growth. Choline in the kidney is utilized as a precursor for membrane synthesis via the choline kinase reaction. We investigated choline phosphorylation during normal and stimulated renal growth. Rapidly growing neonatal rat kidneys contained relatively high levels of choline kinase activity (61 pmol phosphorylcholine/min per mg protein). Choline kinase activity and phosphorylcholine production then fell gradually over the 1st mo of life; by 1 mo phosphorylcholine production was 34 pmol phosphorylcholine/min per mg protein. Choline kinase activity increased by 27% (P less than 0.001) in 28-day-old rats when renal growth was stimulated by contralateral nephrectomy; the increase occurred within 2 h after surgery. Thus, changes in the activity of this important enzyme in the initiation of membrane synthesis is associated both with normal renal development and with adaptation to nephron loss. The findings further suggest that the cell membrane may be involved in the initiation of compensatory renal growth. PMID:659614
[Glomerular changes in the contralateral kidney in the rat with experimental hydronephrosis].
Castillo Bernabéu, R; Gázquez Ortiz, A; Bonillo Morales, A; Sierra Planas, M A; Ocaña Losa, J M; Romanos Lezcano, A
1985-10-31
We have studied under optic and electronmicroscopes the alterations of glomeruli in contralateral kidneys of rats with experimental hydronephrosis. Forty-eight Wistar rats, divided into two groups (control and experimental) were used. They were sacrificed 3, 6, 9 and 12 days after ureteral obstruction. There was a slight hypertrophy of glomeruli and hiperplasia of other components accompanied by a increased development of podocytes.
Mohseni, Mohammad Ghasem; H Khazaeli, Mahziar; Aghamir, Seyed Mohammad Kazem; Biniaz, Farzad
2007-01-01
Our aim was to study the changes in resistive index (RI) of the ipsilateral and contralateral kidneys following electromagnetic extracorporeal shock wave lithotripsy (SWL) of the kidney calculi. Using color Doppler ultrasonography, the RI was determined in 21 patients with unilateral caliceal and pelvic kidney calculi. The RI of the interlobar renal arteries were measured for the regions near and far from the calculi (distance, less and more than 2 cm), before, 30 minutes after, and 1 week after SWL. The same measurements were carried out for the contralateral kidney. Changes in the RI values and their relation with age were evaluated. The RI near the calculi increased 30 minutes after SWL from 0.594 +/- 0.062 to 0.620 +/- 0.048 (P = .003; 95% confidence interval, 0.020 to 0.073), but returned to the pre-SWL values 1 week later. The RI values of the region remote from the calculus and in the contralateral kidney did not change significantly. There was a weak correlation between age and the RI far from the calculus before and 1 week after SWL. There were no relationships between the RI and age, sex, weight, blood pressure, and smoking. The results suggest that SWL of the kidney calculi changes the RI only near the calculus which is immediate, transient, and not age-related.
Kim, Dae Keun; Jang, Yujin; Lee, Jaeseon; Hong, Helen; Kim, Ki Hong; Shin, Tae Young; Jung, Dae Chul; Choi, Young Deuk; Rha, Koon Ho
2015-12-01
To analyze long-term changes in both kidneys, and to predict renal function and contralateral hypertrophy after robot-assisted partial nephrectomy. A total of 62 patients underwent robot-assisted partial nephrectomy, and renal parenchymal volume was calculated using three-dimensional semi-automatic segmentation technology. Patients were evaluated within 1 month preoperatively, and postoperatively at 6 months, 1 year and continued up to 2-year follow up. Linear regression models were used to identify the factors predicting variables that correlated with estimated glomerular filtration rate changes and contralateral hypertrophy 2 years after robot-assisted partial nephrectomy. The median global estimated glomerular filtration rate changes were -10.4%, -11.9%, and -2.4% at 6 months, 1 and 2 years post-robot-assisted partial nephrectomy, respectively. The ipsilateral kidney median parenchymal volume changes were -24%, -24.4%, and -21% at 6 months, 1 and 2 years post-robot-assisted partial nephrectomy, respectively. The contralateral renal volume changes were 2.3%, 9.6% and 12.9%, respectively. On multivariable linear analysis, preoperative estimated glomerular filtration rate was the best predictive factor for global estimated glomerular filtration rate change on 2 years post-robot-assisted partial nephrectomy (B -0.452; 95% confidence interval -0.84 to -0.14; P = 0.021), whereas the parenchymal volume loss rate (B -0.43; 95% confidence interval -0.89 to -0.15; P = 0.017) and tumor size (B 5.154; 95% confidence interval -0.11 to 9.98; P = 0.041) were the significant predictive factors for the degree of contralateral renal hypertrophy on 2 years post-robot-assisted partial nephrectomy. Preoperative estimated glomerular filtration rate significantly affects post-robot-assisted partial nephrectomy renal function. Renal mass size and renal parenchyma volume loss correlates with compensatory hypertrophy of the contralateral kidney. Contralateral hypertrophy of the renal parenchyma compensates for the functional loss of the ipsilateral kidney. © 2015 The Japanese Urological Association.
Captopril inhibits tumour growth in a xenograft model of human renal cell carcinoma.
Hii, S. I.; Nicol, D. L.; Gotley, D. C.; Thompson, L. C.; Green, M. K.; Jonsson, J. R.
1998-01-01
The effect of captopril on tumour growth was examined in a xenograft model of human renal cell carcinoma (RCC). Inoculation of the human RCC cell line SN12K-1 (10(6) cells) under the left kidney capsule of severe combined immunodeficient (SCID) mice resulted in the growth of large tumours, with an increase in weight of the inoculated kidney of 3.69+/-1.63-fold (mean+/-s.d.) when compared with the contralateral normal kidney. In mice treated with captopril (19 mg kg(-1) day(-1) or 94 mg kg(-1) day(-1) administered in the drinking water), there was a significant dose-related reduction in tumour development; the tumour bearing kidneys weighed 1.9+/-0.42 and 1.55+/-0.42 times the normal kidneys, respectively (P< 0.05 compared with untreated animals). In vitro, captopril at clinically achievable doses (0.1-10 microM) had no significant effect on the incorporation of [3H]thymidine into SN12K-1 cells. Thus, this highly significant attenuation by captopril of in vivo tumour growth does not appear to be due to a direct effect on the proliferation of the tumour cells. Further studies are required to determine the mechanism of inhibition of tumour growth by captopril, in particular to evaluate the role of angiotensin II in this process. Images Figure 1 PMID:9528828
Hillman, Gilda Gali; Singh-Gupta, Vinita; Al-Bashir, Areen K; Yunker, Christopher K; Joiner, Michael C; Sarkar, Fazlul H; Abrams, Judith; Haacke, E Mark
2011-01-01
Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to monitor vascular changes induced by sunitinib within a murine xenograft kidney tumor, we previously determined a dose that caused only partial destruction of blood vessels leading to “normalization” of tumor vasculature and improved blood flow. In the current study, kidney tumors were treated with this dose of sunitinib to modify the tumor microenvironment and enhance the effect of kidney tumor irradiation. The addition of soy isoflavones to this combined antiangiogenic and radiotherapy approach was investigated based on our studies demonstrating that soy isoflavones can potentiate the radiation effect on the tumors and act as antioxidants to protect normal tissues from treatment-induced toxicity. DCE-MRI was used to monitor vascular changes induced by sunitinib and schedule radiation when the uptake and washout of the contrast agent indicated regularization of blood flow. The combination of sunitinib with tumor irradiation and soy isoflavones significantly inhibited the growth and invasion of established kidney tumors and caused marked aberrations in the morphology of residual tumor cells. DCE-MRI studies demonstrated that the three modalities, sunitinib, radiation, and soy isoflavones, also exerted antiangiogenic effects resulting in increased uptake and clearance of the contrast agent. Interestingly, DCE-MRI and histologic observations of the normal contralateral kidneys suggest that soy could protect the vasculature of normal tissue from the adverse effects of sunitinib. An antiangiogenic approach that only partially destroys inefficient vessels could potentially increase the efficacy and delivery of cytotoxic therapies and radiotherapy for unresectable primary renal cell carcinoma tumors and metastatic disease. PMID:21461174
DOE Office of Scientific and Technical Information (OSTI.GOV)
Poelstra, K.; Baller, J.F.; Hardonk, M.J.
1991-04-01
It has been proposed, predominantly from ex vivo studies, that glomerular ADPase may function as an antithrombotic principle within the rat kidney. Therefore, intraglomerular platelet aggregation was studied in vivo in rats after impairment of glomerular ADPase activity using local X-irradiation (20 Gy). Biochemical assays in suspensions of glomeruli obtained from rats 24 hours after local X-irradiation (group I) demonstrated a significant reduction in ADPase activity as compared to sham treated rats (group II; p less than 0.01). Cytochemical observations at the ultrastructural level showed that this reduction in glomerular enzyme activity represents in particular ADPase activity detectable in themore » basement membrane. Following X-irradiation, intraglomerular platelet aggregation was quantitatively studied in two groups of rats. Both groups received X-irradiation of the left kidney (20 Gy). Twenty-four hours after X-irradiation, animals received an intravenous injection of either 0.5 ml of saline (group III; N = 6) or 0.5 ml of heterologous nephrotoxic serum (NTS; group IV; N = 6). Subsequently, 24 hours after this injection, platelet aggregation in left kidneys was compared with aggregation in contralateral non-X-irradiated kidneys. The results showed that while X-irradiation per se did not induce intraglomerular platelet aggregation as compared with the contralateral kidney (0.20 +/- 0.08% versus 0.17 +/- 0.06% platelet aggregation/glomerulus), a significant increase in platelet aggregation could be demonstrated in X-irradiated kidneys in the early phase of nephrotoxic serum nephritis as compared with the contralateral nephritic kidney. A potential effect of altered influx of inflammatory cells after X-irradiation could be excluded since no difference in H2O2 producing cells was observed between left and right kidneys.« less
Yin, Hang; Arpali, Emre; Leverson, Glen E; Sollinger, Hans W; Kaufman, Dixon B; Odorico, Jon S
2018-06-28
In a diabetic, uremic kidney transplant recipient that may receive a future pancreas after kidney (PAK) transplant, the kidney is typically implanted on the left side in anticipation of the subsequent pancreas transplant on the right side. In this study, we sought to determine if ipsilateral PAK (iPAK) is as safe as contralateral PAK (cPAK). 115 PAK transplants (iPAK n=57, cPAK n=58) were performed from 1997-2010 and results were compared between the groups. Kidney graft survival and pancreas graft survival was similar between the two groups. Kidney graft function according to serum creatinine and eGFR was not different between the cPAK and iPAK groups and there were no episodes of kidney graft thrombosis in either group. Subgroup analyses focusing on donor source, also did not show worse outcomes for graft survivals in iPAK group when compared to cPAK group. Pancreas and kidney graft survival in PAK transplants is unaffected by the surgical procedure and iPAK is safe. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Assessment of Renal Ischemia By Optical Spectroscopy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fitzgerald, J T; Demos, S; Michalopoulou, A
2004-01-07
Introduction: No reliable method currently exists for quantifying the degree of warm ischemia in kidney grafts prior to transplantation. We describe a method for evaluating pretransplant warm ischemia time using optical spectroscopic methods. Methods: Lewis rat kidney vascular pedicles were clamped unilaterally in vivo for 0, 5, 10, 20, 30, 60, 90 or 120 minutes; 8 animals were studied at each time point. Injured and contra-lateral control kidneys were then flushed with Euro-Collins solution, resected and placed on ice. 335 nm excitation autofluorescence as well as cross polarized light scattering images were taken of each injured and control kidney usingmore » filters of various wavelengths. The intensity ratio of the injured to normal kidneys was compared to ischemia time. Results: Autofluorescence intensity ratios through a 450 nm filter and light scattering intensity ratios through an 800 nm filter both decreased significantly with increasing ischemia time (p < 0.0001 for each method, one-way ANOVA). All adjacent and non-adjacent time points between 0 and 90 minutes were distinguishable using one of these two modalities by Fisher's PLSD. Conclusions: Optical spectroscopic methods can accurately quantify warm ischemia time in kidneys that have been subsequently hypothermically preserved. Further studies are needed to correlate results with physiological damage and posttransplant performance.« less
Pabst, R; Kamran, D
1983-06-01
In minipigs 1 ureter was replaced by a loop of the terminal ileum and the contralateral kidney removed. After 2.5 to 3 years the morphology of the replaced ureter was compared with the normal ileum. Independent of the 3 different operative techniques used, in about half of the pigs there was loss or flattening of the villi. In the other pigs the morphometrically determined number of intraepithelial lymphocytes, the cell density in the lamina propria and the length of the villi did not differ significantly compared with the normal ileum. There was no increase in goblet cells in the crypts. The transitional epithelium covered only a short distance at the anastomotic junctions. Peyer's patches of normal age-related size were found in the replaced ureter. Despite the long-term contact with urine instead of gut contents, in many pigs a normal amount of lymphocytes remained in the "ileal ureter".
Bricker, N S; Morrin, P A; Kime, S W
1997-09-01
Clinical and experimental data relating to the functional capacity of the surviving nephrons of the chronically diseased kidney for the most part support the thesis that these nephrons retain their essential functional integrity regardless of the nature of the underlying form of chronic Bright's disease. There are instances in which specific alterations of function correlate with pathologic involvement of a particular site of the nephron but these appear to represent the exceptions, and in general the more advanced the disease becomes, the less evident are the differentiating features. Studies on dogs with unilateral renal disease indicate that the functional capacity of the nephrons of the diseased kidney parallels that of the nephrons of the contralateral normal kidney. These data tend to exclude widespread intrinsic damage to the functioning nephrons by the underlying pathologic processes. From these observations, as well as from certain supporting clinical and experimental observations, it is suggested that the majority of surviving nephrons in the patient with bilateral renal disease similarly are functionally intact. Concepts of the pathologic physiology of the kidney, based on the "intact nephron hypothesis", are presented. Within the framework of this hypothesis it is concluded that (1) the diseased kidney consists of a diminished number of nephrons, most of which retain essentially normal functional abilities; (2) certain of the apparent abnormalities in function in bilateral renal disease may relate to adaptive changes imposed by the decreased nephron population and the attendant derangements in body fluids rather than to structural distortion of nephrons; (3) the over-all flexibility of the diseased kidney decreases as the number of constituent nephrons decreases; but (4) there is an orderly and predictable pattern of excretion for all substances.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Geyskes, G.G.; Oei, H.Y.; Puylaert, C.B.
Radioisotope renography was performed in 21 patients with hypertension and unilateral renal artery stenosis with and without premedication with 25 mg of captopril, and the results were compared with the effect of percutaneous transluminal angioplasty on the blood pressure, assessed 6 weeks after angioplasty. Angioplasty caused a considerable decrease in blood pressure in 15 of the 21 patients. In 12 of these 15 patients, captopril induced changes in the time-activity curves of the affected kidney only, suggesting deterioration of the excretory function of that kidney, while the function of the contralateral kidney remained normal. After angioplasty the asymmetry in themore » time-activity curves diminished despite identical pretreatment with captopril. Such captopril-induced unilateral impairment of the renal function was not seen in the six patients with unilateral renal artery stenosis whose blood pressure did not change after percutaneous transluminal angioplasty or in 13 patients with hypertension and normal renal arteries. The functional impairment of the affected kidneys was characterized by a decrease of /sup 99m/Tc-diethylenetriamine pentaacetic acid uptake and a delay of /sup 131/I-hippurate excretion, while the /sup 131/I-hippurate uptake remained unaffected. These data are in agreement with a reduced glomerular filtration rate and diuresis during preservation of the renal blood flow, changes that can be expected after converting enzyme inhibition in a kidney with low perfusion and an active, renin-mediated autoregulation of the glomerular filtration rate. These data suggest that functional captopril-induced unilateral changes, shown by split renal function studies with noninvasive gamma camera scintigraphy, can be used as a diagnostic test for renovascular hypertension caused by unilateral renal artery stenosis.« less
Schlotmann, Andreas; Clorius, John H; Clorius, Sandra N
2009-10-01
The recognition of those hydronephrotic kidneys which require therapy to preserve renal function remains difficult. We retrospectively compared the 'tissue tracer transit' (TTT) of (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG(3)) with 'response to furosemide stimulation' (RFS) and with 'single kidney function < 40%' (SKF < 40%) to predict functional course and thereby need for surgery. Fifty patients with suspected unilateral obstruction and normal contralateral kidney had 115 paired (baseline/follow-up) (99m)Tc-MAG(3) scintirenographies. Three predictions of the functional development were derived from each baseline examination: the first based on TTT (visually assessed), the second on RFS and the third on SKF < 40%. Each prediction also considered whether the patient had surgery. Possible predictions were 'better', 'worse' or 'stable' function. A comparison of SKF at baseline and follow-up verified the predictions. The frequency of correct predictions for functional improvement following surgery was 8 of 10 kidneys with delayed TTT, 9 of 22 kidneys with obstructive RFS and 9 of 21 kidneys with SKF < 40%; for functional deterioration without surgery it was 2 of 3 kidneys with delayed TTT, 3 of 20 kidneys with obstructive RFS and 3 of 23 kidneys with SKF < 40%. Without surgery 67 of 70 kidneys with timely TTT maintained function. Without surgery 0 of 9 kidneys with timely TTT but obstructive RFS and only 1 of 16 kidneys with timely TTT but SKF < 40% lost function. Delayed TTT appears to identify the need for therapy to preserve function of hydronephrotic kidneys, while timely TTT may exclude risk even in the presence of an obstructive RFS or SKF < 40%.
Jandaghi, Ali Babaei; Falahatkar, Siavash; Alizadeh, Ahmad; Kanafi, Alireza Rajabzadeh; Pourghorban, Ramin; Shekarchi, Babak; Zirak, Amin Keshavarz; Esmaeili, Samaneh
2013-04-01
This study was designed to evaluate ureterovesical jet dynamics in obstructed ureter and to compare it with those of contralateral unobstructed side. Forty-six patients with diagnosis of ureteral stone, based on imaging findings in computed tomography were enrolled in this study. The gray-scale ultrasound exam from both kidneys and urinary bladder was performed. Then, ureterovesical jet characteristics including ureteral jet frequency, duration and peak velocity were assessed by color Doppler and duplex Doppler studies in both obstructed and unobstructed ureters by a radiologist, 15-30 min after oral hydration with 750-1,000 mL of water. When compared with contralateral normal side, the ureterovesical jet in obstructed ureter showed less frequency (0.59 vs. 3.04 jets/min; P < 0.05), shorter duration (1.24 vs. 5.26 s; P < 0.05) and lower peak velocity (5.41 vs. 32.09 cm/s; P < 0.05). The cut-off points of 1.5 jets/min, 2.5 s and 19.5 cm/s for difference of ureteral jet frequency, duration and peak velocity between obstructed and contralateral normal ureters yielded sensitivities of 97.8, 95.6 and 100 % and specificities of 87, 87.9 and 97.8 %, respectively for diagnosis of ureteral obstruction. Given the safety of Doppler study and significant differences in flow dynamics of obstructed versus unobstructed ureters, our findings demonstrated the utility of Doppler ultrasound examination as a useful adjunct to gray-scale ultrasound by improving the accuracy of ultrasound exam in diagnosis of ureteral obstruction.
Aronoff, Justin M.; Padilla, Monica; Fu, Qian-Jie; Landsberger, David M.
2015-01-01
Contralateral masking is the phenomenon where a masker presented to one ear affects the ability to detect a signal in the opposite ear. For normal hearing listeners, contralateral masking results in masking patterns that are both sharper and dramatically smaller in magnitude than ipsilateral masking. The goal of this study was to investigate whether medial olivocochlear (MOC) efferents are needed for the sharpness and relatively small magnitude of the contralateral masking function. To do this, bilateral cochlear implant patients were tested because, by directly stimulating the auditory nerve, cochlear implants circumvent the effects of the MOC efferents. The results indicated that, as with normal hearing listeners, the contralateral masking function was sharper than the ipsilateral masking function. However, although there was a reduction in the magnitude of the contralateral masking function compared to the ipsilateral masking function, it was relatively modest. This is in sharp contrast to the results of normal hearing listeners where the magnitude of the contralateral masking function is greatly reduced. These results suggest that MOC function may not play a large role in the sharpness of the contralateral masking function but may play a considerable role in the magnitude of the contralateral masking function. PMID:25798581
Atar, Murat; Bozkurt, Yasar; Soylemez, Haluk; Penbegul, Necmettin; Sancaktutar, Ahmet Ali; Bodakci, Mehmet Nuri; Hatipoglu, Namik Kemal; Hamidi, Cihad; Ozler, Ali
2012-01-01
The aim of this study was to evaluate the use of Doppler ultrasonography (DUS) and semi-rigid ureteroscopy (URS) for managing symptomatic persistent hydronephrosis during pregnancy. The study included 19 pregnant patients with unilateral symptomatic persistent hydronephrosis. All pregnant patients were assessed with conventional ultrasonography (US) followed by DUS for both kidneys. The mean patient age was 26 years (range 19-40), and the gestational period was 24 weeks (range 16-33). There was a significantly higher mean resistive index in the kidneys with ureteral obstruction than in the contralateral normal kidneys. Spinal anesthesia was performed on 18 patients, while general anesthesia was performed on 1 patient. Endoscopically stones were found in 17 patients (89.5%), while no stone was found in 2 patients (10.5%). The stones were fragmented by holmium laser and retracted with forceps. After lithotripsy, a ureteral JJ stent was inserted in 8 of 17 (47%) patients with ureteral stones. Intraoperatively, there were no obstetric complications, while ureteral perforation was seen in one patient. Two patients are still pregnant at the time of this writing, and 17 babies were born normally. Both RI and ΔRI increase in unilateral symptomatic persistent hydronephrosis during pregnancy. Semi-rigid URS can be used successfully for diagnosis and treatment in these patients. Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
Hu, Lingzhi; Chen, Junjie; Yang, Xiaoxia; Senpan, Angana; Allen, John S.; Yanaba, Noriko; Caruthers, Shelton D.; Lanza, Gregory M.; Hammerman, Marc R.; Wickline, Samuel A.
2014-01-01
Purpose We sought to develop a unique sensor-reporter approach for functional kidney imaging that employs circulating perfluorocarbon nanoparticles (PFC NPs) and 19F MRI. Methods Because the detected 19F signal intensity directly reflects local blood volume, and the 19F R1 is linearly proportional to local blood oxygen content (pO2), 19F spin density weighted and T1 weighted images were utilized to generate quantitative functional mapping in both healthy and ischemia-reperfusion (acute kidney injury, AKI) injured mouse kidneys. 1H Blood-Oxygenation-Level-Dependant (BOLD) MRI was also employed as a supplementary approach to facilitate the compressive analysis of renal circulation and its pathological changes in AKI. Results Heterogeneous blood volume distribution and intrarenal oxygenation gradient were confirmed in healthy kidneys by 19F MRI. In a mouse model of AKI, 19F MRI, in conjunction with BOLR MRI, sensitively delineated renal vascular damage and recovery. In the cortico-medullary (CM) junction region, we observed 25% lower 19F signal (p<0.05) and 70% longer 1H T2* (p<0.01) in injured kidneys compared to contralateral kidneys at 24 hours after initial ischemia-reperfusion injury. We also detected 71% higher 19F signal (p<0.01) and 40% lower 1H T2* (p<0.05) in the renal medulla region of injured kidneys compared to contralateral kidneys. Conclusion With demonstrated superior diagnostic capability, functional kidney 19F MRI using PFC NPs could serve as a new diagnostic measures for comprehensive evaluation of renal function and pathology. PMID:23929727
Peripapillary Pachychoroid in Nonarteritic Anterior Ischemic Optic Neuropathy
Nagia, Lina; Huisingh, Carrie; Johnstone, John; Kline, Lanning B.; Clark, Mark; Girard, Michael J. A.; Mari, Jean Martial; Girkin, Christopher A.
2016-01-01
Purpose This study examined the peripapillary choroidal thickness (PCT) in nonarteritic ischemic optic neuropathy (NAION) in comparison to contralateral eyes and normal eyes. Methods We used enhanced depth imaging spectral-domain optical coherence tomography to image the optic nerve head of 20 NAION, 10 contralateral eyes, and 102 normal eyes. Following compensation, the scans were manually delineated to identify relevant surfaces including Bruch's membrane opening (BMO), Bruch's membrane, and anterior sclera. The PCT was defined as the measurement between Bruch's membrane and the anterior sclera and was measured at increasing distance from BMO. Models adjusted for age, BMO area, and axial length were used to compare the mean PCT between NAION and normal eyes, and contralateral eyes and normal eyes. Paired t-tests were used to compare the PCT between NAION and contralateral eyes. Results The mean PCT was thicker in NAION and contralateral eyes when compared with normal eyes at all distances from BMO (P < 0.001). The PCT was not significantly thicker in contralateral eyes when compared with affected NAION eyes. Choroidal thickness was thinnest in the inferior quadrant in all eyes regardless of the group. Conclusions Increased peripapillary choroidal thickness was noted in both NAION and contralateral eyes. The thicker choroid may be an associated feature or a result of the disorder. Although further longitudinal study is required to determine causation, these findings may suggest that a thickened peripapillary choroid may be a component of the disk-at-risk clinical phenotype. PMID:27583829
Shacklock, Michael; Yee, Brian; Van Hoof, Tom; Foley, Russ; Boddie, Keith; Lacey, Erin; Poley, J Bryan; Rade, Marinko; Kankaanpää, Markku; Kröger, Heikki; Airaksinen, Olavi
2016-02-01
Part 1: A randomized, single-blind study on the effect of contralateral knee extension on sensations produced by the slump test (ST) in asymptomatic subjects. Part 2: A cadaver study simulating the nerve root behavior of part 1. Part 1: Test if contralateral knee extension consistently reduces normal stretch sensations with the ST.Part 2: Ascertain in cadavers an explanation for the results. In asymptomatic subjects, contralateral knee extension reduces stretch sensations with the ST. In sciatica patients, contralateral SLR also can temporarily reduce sciatica. We studied this methodically in asymptomatic subjects before considering a clinical population. Part 1: Sixty-one asymptomatic subjects were tested in control (ST), sham, or intervention (contralateral ST) groups and their sensation response intensity compared.Part 2: Caudal tension was applied to the L5 nerve root of 3 cadavers and tension behavior of the contralateral neural tissue recorded visually. Part 1: Reduction of stretch sensations occurred in the intervention group but not in control and sham groups (P ≤ 0.001).Part 2: Tension in the contralateral lumbar nerve roots and dura reduced in a manner consistent with the responses in the intervention (contralateral ST) group. Part 1: In asymptomatic subjects, normal thigh stretch sensations with the ST reduced consistently with the contralateral ST, showing that this is normal and may now be compared with patients with sciatica.Part 2: Contralateral reduction in lumbar neural tension with unilateral application of tension-producing movements also occurred in cadavers, supporting the proposed explanatory hypothesis.
Incidental Detection of Urinary Leakage on FDG PET/CT Imaging for Staging of Gastric Cancer.
Kim, Dae-Weung; Kim, Myoung Hyoun; Kim, Chang Guhn
2016-03-01
A 71-year-old woman presented to the emergency department with right flank pain and dysuria. An abdominal CT scan detected a gastric malignancy and hydronephrosis with urinary leakage of the right kidney. Percutaneous nephrostomy was performed on the right kidney. F-FDG PET/CT for staging the gastric malignancy revealed additional urinary leakage of the contralateral kidney. The interest in this case is the incidental detection of unexpected urinary leakage during an oncologic assessment with FDG PET/CT.
MMP-2 as an early synovial biomarker for cranial cruciate ligament disease in dogs.
Boland, L; Danger, R; Cabon, Q; Rabillard, M; Brouard, S; Bouvy, B; Gauthier, O
2014-01-01
To measure the activity of matrix metalloproteinases (MMP)-2 and -9 in synovial fluid from the stifle joints of dogs with cranial cruciate ligament (CrCL) rupture and to compare that to values from contralateral stifle joints and dogs with clinically normal stifle joints. Additionally, the C-reactive protein (CRP) levels were also measured. Fourteen large breed dogs with unilateral CrCL rupture and 11 large breed normal dogs were included in this prospective clinical study. Synovial fluid was collected from CrCL-ruptured stifle joints, contralateral clinically normal stifle joints of the same dogs, and stifle joints of normal dogs. Serum was also collected. Synovial fluid activities of MMP-2 and MMP-9 and serum CRP level were measured. The MMP-2 activity in synovial fluid was significantly higher in CrCL-ruptured joints compared to contralateral joints and to stifles from normal dogs. There was no significant difference in activity of MMP-2 in contralateral joints of CrCL-ruptured dogs compared to normal dogs. Both serum CRP level and MMP-9 activity did not differ significantly between the studied conditions. It was confirmed that MMP-2 activity is significantly related to CrCL rupture, but there was a failure to demonstrate any significant increase in the contralateral joints compared to the stifle joints of normal dogs. The MMP-2 involvement in progressing CrCL disease still has to be defined.
Jouglar, Emmanuel; Wagner, Antoine; Delpon, Grégory; Campion, Loïc; Meingan, Philippe; Bernier, Valérie; Demoor-Goldschmidt, Charlotte; Mahé, Marc-André; Lacornerie, Thomas; Supiot, Stéphane
2016-01-01
Late abdominal irradiation toxicity during childhood included renal damage, hepatic toxicity and secondary diabetes mellitus. We compared the potential of conformal radiotherapy (CRT), helical tomotherapy (HT) and proton beam therapy (PBT) to spare the abdominal organs at risk (pancreas, kidneys and liver- OAR) in children undergoing abdominal irradiation. We selected children with abdominal tumors who received more than 10 Gy to the abdomen. Treatment plans were calculated in order to keep the dose to abdominal OAR as low as possible while maintaining the same planned target volume (PTV) coverage. Dosimetric values were compared using the Wilcoxon signed-rank test. The dose distribution of 20 clinical cases with a median age of 8 years (range 1-14) were calculated with different doses to the PTV: 5 medulloblastomas (36 Gy), 3 left-sided and 2 right-sided nephroblastomas (14.4 Gy to the tumor + 10.8 Gy boost to para-aortic lymphnodes), 1 left-sided and 4 right-sided or midline neuroblastomas (21 Gy) and 5 Hodgkin lymphomas (19.8 Gy to the para-aortic lymphnodes and spleen). HT significantly reduced the mean dose to the whole pancreas (WP), the pancreatic tail (PT) and to the ipsilateral kidney compared to CRT. PBT reduced the mean dose to the WP and PT compared to both CRT and HT especially in midline and right-sided tumors. PBT decreased the mean dose to the ispilateral kidney but also to the contralateral kidney and the liver compared to CRT. Low dose to normal tissue was similar or increased with HT whereas integral dose and the volume of normal tissue receiving at least 5 and 10 Gy were reduced with PBT compared to CRT and HT. In children undergoing abdominal irradiation therapy, proton beam therapy reduces the dose to abdominal OAR while sparing normal tissue by limiting low dose irradiation.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Silva, Suresh de, E-mail: suresh.desilva@unsw.edu.au; Mackie, Simon; Aslan, Peter
BackgroundIntra-arterial brachytherapy with yttrium-90 ({sup 90}Y) resin microspheres (radioembolization) is a procedure to selectively deliver high-dose radiation to tumors. The purpose of this research was to compare the radioembolic effect of {sup 90}Y-radioembolization versus the embolic effect of bland microspheres in the porcine kidney model.MethodsIn each of six pigs, ~25–33 % of the kidney volume was embolized with {sup 90}Y resin microspheres and an equivalent number of bland microspheres in the contralateral kidney. Kidney volume was estimated visually from contrast-enhanced fluoroscopy imaging. Morphologic and histologic analysis was performed 8–9 weeks after the procedure to assess the locations of the microspheres and extentmore » of tissue necrosis from {sup 90}Y-radioembolization and bland embolization. A semi-quantified evaluation of the non-acute peri-particle and perivascular tissue reaction was conducted. All guidelines for the care and use of animals were followed.ResultsKidneys embolized with {sup 90}Y-radioembolization decreased in mass by 30–70 % versus the contralateral kidney embolized with bland microspheres. These kidneys showed significant necrosis/fibrosis, avascularization, and glomerular atrophy in the immediate vicinity of the {sup 90}Y resin microspheres. By contrast, glomerular changes were not observed, even with clusters of bland microspheres in afferent arterioles. Evidence of a foreign body reaction was recorded in some kidneys with bland microspheres, and subcapsular scarring/infarction only with the highest load (4.96 × 10{sup 6}) of bland microspheres.ConclusionThis study showed that radioembolization with {sup 90}Y resin microspheres produces localized necrosis/fibrosis and loss of kidney mass in a porcine kidney model. This result supports the study of {sup 90}Y resin microspheres for the localized treatment of kidney tumors.« less
Marcus, Sonya; Whitlow, Christopher T; Koonce, James; Zapadka, Michael E; Chen, Michael Y; Williams, Daniel W; Lewis, Meagan; Evans, Adele K
2014-02-01
Prior studies have associated gross inner ear abnormalities with pediatric sensorineural hearing loss (SNHL) using computed tomography (CT). No studies to date have specifically investigated morphologic inner ear abnormalities involving the contralateral unaffected ear in patients with unilateral SNHL. The purpose of this study is to evaluate contralateral inner ear structures of subjects with unilateral SNHL but no grossly abnormal findings on CT. IRB-approved retrospective analysis of pediatric temporal bone CT scans. 97 temporal bone CT scans, previously interpreted as "normal" based upon previously accepted guidelines by board certified neuroradiologists, were assessed using 12 measurements of the semicircular canals, cochlea and vestibule. The control-group consisted of 72 "normal" temporal bone CTs with underlying SNHL in the subject excluded. The study-group consisted of 25 normal-hearing contralateral temporal bones in subjects with unilateral SNHL. Multivariate analysis of covariance (MANCOVA) was then conducted to evaluate for differences between the study and control group. Cochlea basal turn lumen width was significantly greater in magnitude and central lucency of the lateral semicircular canal bony island was significantly lower in density for audiometrically normal ears of subjects with unilateral SNHL compared to controls. Abnormalities of the inner ear were present in the contralateral audiometrically normal ears of subjects with unilateral SNHL. These data suggest that patients with unilateral SNHL may have a more pervasive disease process that results in abnormalities of both ears. The findings of a cochlea basal turn lumen width disparity >5% from "normal" and/or a lateral semicircular canal bony island central lucency disparity of >5% from "normal" may indicate inherent risk to the contralateral unaffected ear in pediatric patients with unilateral sensorineural hearing loss. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Ziadloo, Ali; Burks, Scott R.; Gold, Eric M.; Lewis, Bobbi K.; Chaudhry, Aneeka; Merino, Maria J.; Frenkel, Victor; Frank, Joseph A.
2012-01-01
Bone marrow stromal cells (BMSC) have shown significant promise in the treatment of disease, but their therapeutic efficacy is often limited by inefficient homing of systemically-administered cells, which results in low numbers of cells accumulating at sites of pathology. BMSC home to areas of inflammation where local expression of integrins and chemokine gradients are present. We demonstrated that non-destructive pulsed focused ultrasound (pFUS) exposures that emphasize the mechanical effects of ultrasound-tissue interactions induced local and transient elevations of chemoattractants (i.e., cytokines, integrins, and growth factors) in the murine kidney. pFUS-induced upregulation of cytokines occurred through approximately 1 day post-treatment and returned to contralateral kidney levels by day 3. This window of significant increases in cytokine expression was accompanied by local increases of other trophic factors and integrins that have been shown to promote BMSC homing. When BMSC were administered intravenously following pFUS treatment to a single kidney, enhanced homing, permeability, and retention of BMSC was observed in the treated kidney versus the contralateral kidney. Histological analysis revealed up to 8 times more BMSC in the peritubular regions of the treated kidneys on days 1 and 3 post-treatment. Furthermore, cytokine levels in pFUS-treated kidneys following BMSC administration were found to be similar to controls, suggesting modulation of cytokine levels by BMSC. pFUS could potentially improve cell-based therapies as a noninvasive modality to target BMSC homing by establishing local chemoattractant gradients and increasing expression of integrins to enhance tropism of BMSC toward treated tissues. PMID:22593018
Ko, Seung-Nam
2017-01-01
Posterior cruciate ligament (PCL) reconstruction for patients with PCL insufficiency has been associated with postoperative improvements in proprioceptive function due to mechanoreceptor regeneration. However, it is unclear whether reconstructed PCL or contralateral normal knees have better proprioceptive function outcomes. This meta-analysis was designed to compare the proprioceptive function of reconstructed PCL or contralateral normal knees in patients with PCL insufficiency. All studies that compared proprioceptive function, as assessed with threshold to detect passive movement (TTDPM) or joint position sense (JPS) in PCL reconstructed or contralateral normal knees were included. JPS was calculated by reproducing passive positioning (RPP). Five studies met the inclusion/exclusion criteria for the meta-analysis. The proprioceptive function, defined as TTDPM (95% CI: 0.25 to 0.51°; P<0.00001) and RPP (95% CI: 0.19 to 0.45°; P<0.00001), was significantly different between the reconstructed PCL and contralateral normal knees. The mean difference in angle of error between the reconstructed PCL and contralateral normal knees was 0.06° greater in TTDPM than by RPP. In addition, results from subgroup analyses, based on the starting angles and the moving directions of the knee, that evaluated TTDPM at 15° flexion to 45° extension, TTDPM at 45° flexion to 110° flexion, RPP in flexion, and RPP in extension demonstrated that mean angles of error were significantly greater, by 0.38° (P = 0.0001), 0.36° (P = 0.02), 0.36° (P<0.00001), and 0.23° (P = 0.04), respectively, in reconstructed PCL than in contralateral normal knees. The proprioceptive function of PCL reconstructed knees was decreased, compared with contralateral normal knees, as determined by both TTDPM and RPP. In addition, the amount of loss of proprioception was greater in TTDPM than in RPP, even with minute differences. Results from subgroup analysis, that evaluated the mean angles of error in moving directions through RPP, suggested that the moving direction of flexion has a significantly greater mean for angles of error than the moving direction of extension. Although the level of differences between various parameters were statistically significant, further studies are needed to determine whether the small differences (>1°) of the loss of proprioception are clinically relevant. PMID:28922423
Repair after nephron ablation reveals limitations of neonatal neonephrogenesis
Tögel, Florian; Freedman, Benjamin S.; Iatrino, Rossella; Grinstein, Mor; Bonventre, Joseph V.
2017-01-01
The neonatal mouse kidney retains nephron progenitor cells in a nephrogenic zone for 3 days after birth. We evaluated whether de novo nephrogenesis can be induced postnatally beyond 3 days. Given the long-term implications of nephron number for kidney health, it would be useful to enhance nephrogenesis in the neonate. We induced nephron reduction by cryoinjury with or without contralateral nephrectomy during the neonatal period or after 1 week of age. There was no detectable compensatory de novo nephrogenesis, as determined by glomerular counting and lineage tracing. Contralateral nephrectomy resulted in additional adaptive healing, with little or no fibrosis, but did not also stimulate de novo nephrogenesis. In contrast, injury initiated at 1 week of age led to healing with fibrosis. Thus, despite the presence of progenitor cells and ongoing nephron maturation in the newborn mouse kidney, de novo nephrogenesis is not inducible by acute nephron reduction. This indicates that additional nephron progenitors cannot be recruited after birth despite partial renal ablation providing a reparative stimulus and suggests that nephron number in the mouse is predetermined at birth. PMID:28138555
Zhu, Wan-Jun; Nakayama, Masaaki; Mori, Takefumi; Nakayama, Keisuke; Katoh, Junichiro; Murata, Yaeko; Sato, Toshinobu; Kabayama, Shigeru; Ito, Sadayoshi
2011-07-01
Hydrogen (H(2)) reportedly produces an antioxidative effect by quenching cytotoxic oxygen radicals. We studied the biological effects of water with dissolved H(2) on ischemia-induced cardio-renal injury in a rat model of chronic kidney disease (CKD). Dahl salt-sensitive rats (7 weeks old) were allowed ad libitum drinking of filtered water (FW: dissolved H(2), 0.00 ± 0.00 mg/L) or water with dissolved H(2) produced by electrolysis (EW: dissolved H(2), 0.35 ± 0.03 mg/L) for up to 6 weeks on a 0.5% salt diet. The rats then underwent ischemic reperfusion (I/R) of one kidney and were killed a week later for investigation of the contralateral kidney and the heart. In the rats given FW, unilateral kidney I/R induced significant increases in plasma monocyte chemoattractant protein-1, methylglyoxal and blood urea nitrogen. Histologically, significant increases were found in glomerular adhesion, cardiac fibrosis, number of ED-1 (CD68)-positive cells and nitrotyrosine staining in the contralateral kidney and the heart. In rats given EW, those findings were significantly ameliorated and there were significant histological differences between rats given FW and those given EW. Consumption of EW by ad libitum drinking has the potential to ameliorate ischemia-induced cardio-renal injury in CKD model rats. This indicates a novel strategy of applying H(2) produced by water electrolysis technology for the prevention of CKD cardio-renal syndrome.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nally, J.V. Jr.; Clarke, H.S. Jr.; Grecos, G.P.
In an effort to improve on the noninvasive detection of renal artery stenosis, we investigated the effect of angiotensin converting enzyme inhibition on computer-assisted /sup 99m/Tc-diethylenetriaminepentaacetic acid (DTPA) renal flow studies in a canine model of two-kidney, one clip hypertension and compared these findings with clearances of inulin and p-aminohippuric acid in the stenotic and contralateral kidney before and after converting enzyme inhibition. The /sup 99m/Tc-DTPA renal flow study with the converting enzyme inhibitor captopril (1.5 mg/kg bolus with 1.5 mg/min infusion) showed an increased sensitivity in the detection of unilateral renal artery stenosis over the use of the /supmore » 99m/Tc-DTPA study alone. Captopril induced striking alterations that were most evident in the 15-minute /sup 99m/Tc-DTPA renal flow study, in which all nine curves exhibited severely blunted uptake and excretion of the radionuclide. These changes were reversed during a recovery study without converting enzyme inhibition and were not seen when blood pressure was lowered with nitroprusside to a level similar to that observed during converting enzyme inhibition. The changes shown by the /sup 99m/Tc-DTPA study during converting enzyme inhibition correlated with a decrease in the glomerular filtration rate of the stenotic kidney. Captopril infusion significantly decreased the glomerular filtration rate of the stenotic kidney (16.0 +/- 3.1 vs 11.0 +/- 2.5 mg/min, p less than 0.03) but not of the contralateral kidney (32.4 +/- 2.6 vs 28.4 +/- 2.8 mg/min).« less
Klinghoffer, Zachary; Tarride, Jean-Eric; Novara, Giacomo; Ficarra, Vincenzo; Kapoor, Anil; Shayegan, Bobby; Braga, Luis H.
2013-01-01
Objectives: We compare the cost-utility of laparoscopic radical nephrectomy (LRN), laparoscopic partial nephrectomy (LPN) and open partial nephrectomy (OPN) in the management of small renal masses (SRMs) when the impact of ensuing chronic kidney disease (CKD) disease is considered. Methods: We designed a Markov decision analysis model with a 10-year time horizon. Estimates of costs, utilities, complication rates and probabilities of developing CKD were derived from the literature. The base case patient was assumed to be a 65-year-old patient with a <4-cm unilateral renal mass, a normal contralateral kidney and a normal preoperative serum creatinine. Univariate and probabilistic sensitivity analyses were conducted to address the uncertainty associated with the study parameters. Results: OPN was the least costly strategy at $25 941 USD and generated 7.161 quality-adjusted life years (QALYs) over 10 years. LPN yielded 0.098 additional QALYs at an additional cost of $888 for an incremental cost-effectiveness ratio of $9057 per QALY, well below a commonly cited willingness-to-pay threshold of $50 000 per QALY. LRN was more costly and yielded fewer QALYs than OPN and LPN. Sensitivity analyses demonstrated our model to be robust to changes to key parameters. Age had no effect on preferred strategy. Conclusions: Partial nephrectomy (PN) is the preferred treatment strategy for SRMs. In centres where LPN is not available, OPN remains considerably more cost-effective than LRN. Furthermore, our study demonstrates that there is no age at which PN is not preferred to LRN. Our study provides additional evidence to advocate PN for the management of all amenable SRMs. PMID:23671525
Multicystic dysplastic kidney: a retrospective study.
Sharada, Sathish; Vijayakumar, Mahalingam; Nageswaran, Prahlad; Ekambaram, Sudha; Udani, Amish
2014-08-01
To report the renal structural and functional anomalies in children with multicystic dysplastic kidneys. Retrospective descriptive analysis of 47 children with multicystic dysplastic kidney seen in a pediatric nephrology unit over a period of 6 years. Antenatal diagnosis of multicystic dysplastic kidney was made in 34 (72.3%) patients. On follow up of 31 children for more than 12 months, 21 (68%) had involution, 4 [13%] had non-regression, and 4 (13%) were nephrectomized. Vesico-ureteric reflux (n=13; 28%) was the commonest renal abnormality. The serum creatinine values were higher (P=0.006) in children with contralateral reflux. Sub-nephrotic proteinuria was noted in 9 (29%) and was significantly associated with complete involution (P=<0.023). None of the patients developed hypertension and 2 (6.4%) had renal failure. Close nephrological follow-up is needed in children with multicystic dysplasia of kidneys.
Zhu, Jundong; Jiang, Fan; Li, Pu; Shao, Pengfei; Liang, Chao; Xu, Aiming; Miao, Chenkui; Qin, Chao; Wang, Zengjun; Yin, Changjun
2017-09-11
To explore the feasibility and safety of retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping for the patients with multiple renal tumor of who have solitary kidney or contralateral kidney insufficiency. Nine patients who have undergone retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping between October 2010 and January 2017 were retrospectively analyzed. Clinical materials and parameters during and after the operation were summarized. Nineteen tumors were resected in nine patients and the operations were all successful. The operation time ranged from 100 to 180 min (125 min); clamping time of segmental renal artery was 10 ~ 30 min (23 min); the amount of blood loss during the operation was 120 ~ 330 ml (190 ml); hospital stay after the operation is 3 ~ 6d (5d). There was no complication during the perioperative period, and the pathology diagnosis after the surgery showed that there were 13 renal clear cell carcinomas, two papillary carcinoma and four perivascular epithelioid cell tumors with negative margins from the 19 tumors. All patients were followed up for 3 ~ 60 months, and no local recurrence or metastasis was detected. At 3-month post-operation follow-up, the mean serum creatinine was 148.6 ± 28.1 μmol/L (p = 0.107), an increase of 3.0 μmol/L from preoperative baseline. For the patients with multiple renal tumors and solitary kidney or contralateral kidney insufficiency, retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping was feasible and safe, which minimized the warm ischemia injury to the kidney and preserved the renal function effectively.
Abu Aboud, Omran; Habib, Samy L.; Trott, Josephine; ...
2017-10-11
Many cancers appear to activate intrinsic antioxidant systems as a means to counteract oxidative stress. Some cancers, such as clear cell renal cell carcinoma (ccRCC), require exogenous glutamine for growth and exhibit reprogrammed glutamine metabolism, at least in part due to the glutathione pathway, an efficient cellular buffering system that counteracts reactive oxygen species (ROS) and other oxidants. We show here that ccRCC xenograft tumors under the renal capsule exhibit enhanced oxidative stress compared to adjacent normal tissue and the contralateral kidney. Upon glutaminase inhibition with CB-839 or BPTES, the RCC cell lines SN12PM-6-1 (SN12) and 786-O exhibited decreased survivalmore » and pronounced apoptosis associated with a decreased GSH/GSSG ratio, augmented nuclear factor erythroid related factor 2 (NRF2), and increased 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a marker of DNA damage. SN12 tumor xenografts showed decreased growth when treated with CB-839. Furthermore, PET imaging confirmed that ccRCC tumors exhibited increased tumoral uptake of 18F-(2S,4R)4- fluoroglutamine (18F-FGln) compared to the kidney in the orthotopic mouse model. This technique can be utilized to follow changes in ccRCC metabolism in vivo. Further development of these paradigms will lead to new treatment options with glutaminase inhibitors and the utility of PET to identify and manage ccRCC patients who are likely to respond to glutaminase inhibitors in the clinic.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Abu Aboud, Omran; Habib, Samy L.; Trott, Josephine
Many cancers appear to activate intrinsic antioxidant systems as a means to counteract oxidative stress. Some cancers, such as clear cell renal cell carcinoma (ccRCC), require exogenous glutamine for growth and exhibit reprogrammed glutamine metabolism, at least in part due to the glutathione pathway, an efficient cellular buffering system that counteracts reactive oxygen species (ROS) and other oxidants. We show here that ccRCC xenograft tumors under the renal capsule exhibit enhanced oxidative stress compared to adjacent normal tissue and the contralateral kidney. Upon glutaminase inhibition with CB-839 or BPTES, the RCC cell lines SN12PM-6-1 (SN12) and 786-O exhibited decreased survivalmore » and pronounced apoptosis associated with a decreased GSH/GSSG ratio, augmented nuclear factor erythroid related factor 2 (NRF2), and increased 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a marker of DNA damage. SN12 tumor xenografts showed decreased growth when treated with CB-839. Furthermore, PET imaging confirmed that ccRCC tumors exhibited increased tumoral uptake of 18F-(2S,4R)4- fluoroglutamine (18F-FGln) compared to the kidney in the orthotopic mouse model. This technique can be utilized to follow changes in ccRCC metabolism in vivo. Further development of these paradigms will lead to new treatment options with glutaminase inhibitors and the utility of PET to identify and manage ccRCC patients who are likely to respond to glutaminase inhibitors in the clinic.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Streitparth, F., E-mail: florian.streitparth@charite.de; Walter, A.; Stolzenburg, N.
Purpose. To evaluate the feasibility and efficacy of image-guided periarterial ethanol injection as an alternative to transluminal radiofrequency ablation. Methods. Unilateral renal periarterial ethanol injection was performed under general anesthesia in 6 pigs with the contralateral kidney serving as control. All interventions were performed in an open 1.0 T MRI system under real-time multiplanar guidance. The injected volume was 5 ml (95 % ethanol labelled marked MR contrast medium) in 2 pigs and 10 ml in 4 pigs. Four weeks after treatment, the pigs underwent MRI including MRA and were killed. Norepinephrine (NE) concentration in the renal parenchyma served asmore » a surrogate parameter to analyze the efficacy of sympathetic denervation. In addition, the renal artery and sympathetic nerves were examined histologically to identify evidence of vascular and neural injury. Results. In pigs treated with 10 ml ethanol, treatment resulted in neural degeneration. We found a significant reduction of NE concentration in the kidney parenchyma of 53 % (p < 0.02) compared with the untreated contralateral kidney. In pigs treated with 5 ml ethanol, no significant changes in histology or NE were observed. There was no evidence of renal arterial stenosis in MRI, macroscopy or histology in any pig. Conclusion. MR-guided periarterial ethanol injection was feasible and efficient for renal sympathetic denervation in a swine model. This technique may be a promising alternative to the catheter-based approach in the treatment of resistant arterial hypertension.« less
Rey, Jorge; Golpanian, Samuel; Yang, Jane K; Moreno, Enrique; Velazquez, Omaida C; Goldstein, Lee J; Chahwala, Veer
2015-07-01
Abdominal aortic aneurysm complicated by a horseshoe kidney (HSK, fused kidney) represents a unique challenge for repair. Renal arteries arising from the aneurysmal aorta can further complicate intervention. Reports exist describing the repair of these complex anatomies using fenestrated endografts, hybrid open repairs (debranching), and open aneurysmorrhaphy with preservation of renal circulation. We describe an extra-anatomic, fully endovascular repair of an abdominal aortic aneurysm with a HSK partially supplied by a renal artery arising from the aneurysm. We successfully applied aortouni-iliac endografting, femorofemoral bypass, and retrograde renal artery perfusion via the contralateral femoral artery to exclude the abdominal aortic aneurysm and preserve circulation to the HSK. Copyright © 2015 Elsevier Inc. All rights reserved.
Stuart, Andrew; Preast, June L
2012-01-01
In previous studies, otoacoustic emissions (OAEs) have been found to be larger in normal-hearing children with sickle cell disease (SCD). It was hypothesized that some dysfunction or reduction in the medial olivocochlear efferent suppression of outer hair cell activity was responsible for this phenomenon. To test this hypothesis, contralateral suppression of transient-evoked otoacoustic emissions (TEOAEs) was examined in children with and without SCD. Thirteen African American school-aged normal-hearing children with homozygous SCD and 13 age- and gender-matched control children participated. TEOAEs were obtained bilaterally with 80 dB peSPL nonlinear click stimuli. To examine contralateral suppression, TEOAEs were obtained with 60 dB peSPL linear click stimuli with and without a contralateral 65 dB SPL white noise suppressor. Overall and half-octave band TEOAE levels were found to be larger in children with SCD relative to the normal control children (p < 0.05), consistent with previous reports of increased OAE levels. There was no significant difference (p > 0.05) in the absolute or proportional amount of TEOAE suppression as a function of group and ear. There were also no significant correlations or linear predictive relationships between TEOAE suppression and TEOAE level for either ear or group (p > 0.05). These findings do not support the notion that increased OAE levels in children with SCD are a consequence of abnormal medial olivocochlear system function as assessed with contralateral suppression of TEOAEs.
Pluto, Charles P; Chiaia, Nicolas L; Rhoades, Robert W; Lane, Richard D
2005-09-01
In adult rats that sustained forelimb amputation on the day of birth, >30% of multiunit recording sites in the forelimb-stump representation of primary somatosensory cortex (SI) also respond to cutaneous hindlimb stimulation when cortical GABA(A+B) receptors are blocked (GRB). This study examined whether hindlimb receptive fields could also be revealed in forelimb-stump sites by reducing one known source of excitatory input to SI GABAergic neurons, the contralateral SI cortex. Corpus callosum projection neurons connect homotopic SI regions, making excitatory contacts onto pyramidal cells and interneurons. Thus in addition to providing monosynaptic excitation in SI, callosal fibers can produce disynaptic inhibition through excitatory synapses with inhibitory interneurons. Based on the latter of these connections, we hypothesized that inactivating the contralateral (intact) SI forelimb region would "unmask" normally suppressed hindlimb responses by reducing the activity of SI GABAergic neurons. The SI forelimb-stump representation was first mapped under normal conditions and then during GRB to identify stump/hindlimb responsive sites. After GRB had dissipated, the contralateral (intact) SI forelimb region was mapped and reversibly inactivated with injections of 4% lidocaine, and selected forelimb-stump sites were retested. Contralateral SI inactivation revealed hindlimb responses in approximately 60% of sites that were stump/hindlimb responsive during GRB. These findings indicate that activity in the contralateral SI contributes to the suppression of reorganized hindlimb receptive fields in neonatally amputated rats.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mann, S.J.; Pickering, T.G.; Sos, T.A.
The purpose of this study was to determine the sensitivity, specificity, and clinical usefulness of renography performed in combination with captopril administration (captopril renography) in diagnosing renal artery stenosis. Fifty-five patients with suspected renal artery stenosis underwent renography prior to performance of renal angiography. Renography was performed on two consecutive days using technetium-99m-diethylenetiamine pentaacetic acid (DTPA) as an index of glomerular filtration rate and iodine-131-orthoiodohippurate (OIH) as an index of renal blood flow. Captopril (25 mg orally, crushed) was administered 1 hour before the second study. Renal artery stenosis was defined as a stenosis exceeding 70%. Renographic criteria were thenmore » established, retrospectively, to differentiate renal artery stenosis from essential hypertension based on (1) asymmetry of function and (2) the presence of captopril-induced changes. Renal artery stenosis was detected in 35 of 55 patients (21 with unilateral and 14 with bilateral stenosis). Three criteria were established for diagnosing renal artery stenosis: (1) a percent uptake of DTPA by the affected kidney of less than 40% of the combined bilateral uptake, (2) a delayed time to peak uptake of DTPA, which was more than 5 minutes longer in the affected kidney than in the contralateral kidney, (3) a delayed excretion of DTPA, with retention at 15 minutes, as a fraction of peak activity, more than 20% greater than in the contralateral kidney. The presence of one or more of these criteria was diagnostic of renal artery stenosis, with a sensitivity and specificity of 71% and 75%, respectively before captopril administration, and 94% and 95% after captopril administration. Lesser degrees of asymmetry (i.e., uptake of 40% to 50%) had very poor diagnostic specificity.« less
Difference of motor overflow depending on the impaired or unimpaired hand in stroke patients.
Kim, Yushin; Kim, Woo-Sub; Shim, Jae Kun; Suh, Dong Won; Kim, TaeYeong; Yoon, BumChul
2015-02-01
The aim of this study was to investigate the patterns of contralateral motor overflow (i.e. mirror movement) between the homologous body parts on the right and left side, in stroke patients during single-finger and multi-finger maximum force production tasks. Forty subjects, including stroke (n=20) and normal subjects (n=20), participated in this study. The stroke subjects maximally pressed force sensors with their fingers in a flexed position using a single (index, middle, ring, or little) or all fingers (all 4 fingers) using the impaired (IH) or unimpaired (UIH) hand, while the non-patient subjects used their right hands for the same tasks. The maximal voluntary forces in the ipsilateral and unintended pressing forces of each contralateral finger were recorded during the tasks. The magnitude of motor overflow to the contralateral side was calculated using the index of contralateral independence (CI). During the single finger tasks, the finger CI was significantly decreased in the UIH (91%) compared with that in the IH (99%) or normal hands (99%). Likewise, the multiple finger tasks showed that the CI was significantly lower in the UIH (84%) compared with that in the IH (96%) or normal hands (99%). However, the maximal forces were significantly lower in the IH relative to those in the UIH and normal hands. These data demonstrate that stroke patients have greater motor overflow from the UIH to the IH. Copyright © 2014 Elsevier B.V. All rights reserved.
Contralateral Noise Stimulation Delays P300 Latency in School-Aged Children.
Ubiali, Thalita; Sanfins, Milaine Dominici; Borges, Leticia Reis; Colella-Santos, Maria Francisca
2016-01-01
The auditory cortex modulates auditory afferents through the olivocochlear system, which innervates the outer hair cells and the afferent neurons under the inner hair cells in the cochlea. Most of the studies that investigated the efferent activity in humans focused on evaluating the suppression of the otoacoustic emissions by stimulating the contralateral ear with noise, which assesses the activation of the medial olivocochlear bundle. The neurophysiology and the mechanisms involving efferent activity on higher regions of the auditory pathway, however, are still unknown. Also, the lack of studies investigating the effects of noise on human auditory cortex, especially in peadiatric population, points to the need for recording the late auditory potentials in noise conditions. Assessing the auditory efferents in schoolaged children is highly important due to some of its attributed functions such as selective attention and signal detection in noise, which are important abilities related to the development of language and academic skills. For this reason, the aim of the present study was to evaluate the effects of noise on P300 responses of children with normal hearing. P300 was recorded in 27 children aged from 8 to 14 years with normal hearing in two conditions: with and whitout contralateral white noise stimulation. P300 latencies were significantly longer at the presence of contralateral noise. No significant changes were observed for the amplitude values. Contralateral white noise stimulation delayed P300 latency in a group of school-aged children with normal hearing. These results suggest a possible influence of the medial olivocochlear activation on P300 responses under noise condition.
Renal autotransplantation for vascular disease: late outcome according to etiology.
Chiche, Laurent; Kieffer, Edouard; Sabatier, Jean; Colau, Alexandre; Koskas, Fabien; Bahnini, Amine
2003-02-01
The purpose of this study was to evaluate the early and late outcomes of renal autotransplantation (RAT) according to the etiology of the underlying renal artery disease. Between January 1985 and April 2001, we performed 68 RAT procedures in 57 patients. The surgical indications were fibromuscular dysplasia (FMD) for 34 RAT procedures in 30 patients (11 men, 19 women; mean age, 41.3 +/- 14.6 years), Takayasu's disease (TD) for 26 RAT procedures in 19 patients (five men, 14 women; mean age, 33.0 +/- 12.3 years), and atherosclerosis for eight RAT procedures in eight patients (seven men, one woman; mean age, 66.5 +/- 7.9 years). The incidence rate of hypertension was 87% in patients with FMD and 100% in patients with TD and atherosclerosis. The incidence rate of renal dysfunction was 75% in patients with atherosclerosis, 27% in patients with FMD, and 16% in patients with TD. Autotransplantation was isolated in 31 cases and was associated with another vascular procedure in 37 cases, including 22 thoracoabdominal aorta repairs and 11 abdominal aorta or iliac artery repairs. The technique used to achieve renal revascularization was direct reimplantation in 17 cases and indirect reimplantation in 51 cases. The conduit used for indirect reimplantation was an arterial autograft in 42 cases, a vein autograft in seven cases, and a prosthetic graft in two cases. Simultaneous revascularization of the contralateral kidney was performed in 21 patients and included nine RAT procedures. Contralateral nephrectomy was performed in five patients. In the FMD group, early segmental infarction was observed in four cases. Secondary nephrectomy was necessary in one case (at 88 months). Actuarial survival rates were 96.2% +/- 0.03% at 5 years and 84.1% +/- 0.11% at 10 years. Secondary patency rates were 100% at 5 years and 92% +/- 0.07% at 10 years. Hypertension normalized or improved in 96% of patients. Renal function improved in 50% of patients. In the TD group, one patient died of multiple organ failure 4 days after the procedure. Nephrectomy was necessary in one case. The actuarial survival rate was 94.7% +/- 0.05% and the secondary patency rate was 91.3% +/- 0.05% at both 5 and 10 years. Hypertension normalized or improved in 89% of the cases, and kidney function improved in all cases. In the atherosclerosis group, nephrectomy was necessary during the early postoperative period in three cases and during late follow-up in two cases (at 9 months and at 68 months, respectively). Actuarial survival rates were 54.7% +/- 0.2% at 5 years and 18.2% +/- 0.16% at 10 years. The secondary patency rates were 50.0% +/- 0.17% at 5 years and 33.3% +/- 0.18% at 10 years. Hypertension normalized or improved in 50% of cases, and kidney function improved in 33% of cases. RAT is highly effective for treatment of complex renovascular lesions related to FMD and TD. Although RAT is less effective for atherosclerosis, it may be the only alternative in cases involving extensive renovascular disease.
Mazzuca, Steven A; Brandt, Kenneth D; Lane, Kathleen A; Chakr, Rafael
2011-11-01
To explore whether the risk of incident tibiofemoral (TF) osteoarthritis (OA) in the radiographically normal contralateral knee of overweight/obese women with unilateral knee OA is mediated by malalignment and/or preceded by increased turnover of subchondral bone. We used data of post hoc analyses from a randomized controlled trial. Cross-sectional analyses evaluated the baseline association between frontal plane alignment and bone turnover in the medial TF compartment in 78 radiographically normal contralateral knees. Longitudinal analyses ascertained whether incident radiographic OA (TF osteophyte formation within 30 months) was associated with malalignment and/or increased bone turnover at baseline. Alignment subcategories (varus/neutral/valgus) were based on the anatomic axis angle. (99m)Tc-methylene diphosphonate uptake in a late-phase bone scan was quantified in regions of interest in the medial tibia (MT) and medial femur (MF) and adjusted for uptake in a reference segment of the ipsilateral tibial shaft (TS). MF and MT uptake in varus contralateral knees was 50-55% greater than in the TS. Adjusted MT uptake in varus contralateral knees was significantly greater than that in neutral and valgus contralateral knees (mean 1.55 versus 1.38 and 1.43, respectively; P < 0.05). Among 69 contralateral knees followed longitudinally, 22 (32%) developed TF OA. Varus angulation was associated with a marginally significant increase in the odds of incident OA (adjusted odds ratio 3.98, P = 0.067). While the small sample size limited our ability to detect statistically significant risk factors, these data suggest that the risk of developing bilateral TF OA in overweight/obese women may be mediated by varus malalignment. Copyright © 2011 by the American College of Rheumatology.
Effects of Platelet-Rich Plasma (PRP) on a Model of Renal Ischemia-Reperfusion in Rats.
Martín-Solé, Oriol; Rodó, Joan; García-Aparicio, Lluís; Blanch, Josep; Cusí, Victoria; Albert, Asteria
2016-01-01
Renal ischemia-reperfusion injury is a major cause of acute renal failure, causing renal cell death, a permanent decrease of renal blood flow, organ dysfunction and chronic kidney disease. Platelet-rich plasma (PRP) is an autologous product rich in growth factors, and therefore able to promote tissue regeneration and angiogenesis. This product has proven its efficacy in multiple studies, but has not yet been tested on kidney tissue. The aim of this work is to evaluate whether the application of PRP to rat kidneys undergoing ischemia-reperfusion reduces mid-term kidney damage. A total of 30 monorrenal Sprague-Dawley male rats underwent renal ischemia-reperfusion for 45 minutes. During ischemia, PRP (PRP Group, n = 15) or saline solution (SALINE Group, n = 15) was administered by subcapsular renal injection. Control kidneys were the contralateral organs removed immediately before the start of ischemia in the remaining kidneys. Survival, body weight, renal blood flow on Doppler ultrasound, kidney weight, kidney volume, blood biochemistry and histopathology were determined for all subjects and kidneys, as applicable. Correlations between these variables were searched for. The PRP Group showed significantly worse kidney blood flow (p = 0.045) and more histopathological damage (p<0.0001). Correlations were found between body weight, kidney volume, kidney weight, renal blood flow, histology, and serum levels of creatinine and urea. Our study provides the first evidence that treatment with PRP results in the deterioration of the kidney's response to ischemia-reperfusion injury.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zurl, Brigitte, E-mail: brigitte.zurl@klinikum-graz.at; Stranzl, Heidi; Winkler, Peter
2013-02-01
Purpose: Whole breast irradiation with deep-inspiration breath-hold (DIBH) technique among left-sided breast cancer patients significantly reduces cardiac irradiation; however, a potential disadvantage is increased incidental irradiation of the contralateral breast. Methods and Materials: Contralateral breast dose (CBD) was calculated by comparing 400 treatment plans of 200 left-sided breast cancer patients whose tangential fields had been planned on gated and nongated CT data sets. Various anatomic and field parameters were analyzed for their impact on CBD. For a subgroup of patients (aged {<=}45 years) second cancer risk in the contralateral breast (CB) was modeled by applying the linear quadratic model, compoundmore » models, and compound models considering dose-volume information (DVH). Results: The mean CBD was significantly higher in DIBH with 0.69 Gy compared with 0.65 Gy in normal breathing (P=.01). The greatest impact on CBD was due to a shift of the inner field margin toward the CB in DIBH (mean 0.4 cm; range, 0-2), followed by field size in magnitude. Calculation with different risk models for CBC revealed values of excess relative risk/Gy ranging from 0.48-0.65 vs 0.46-0.61 for DIBH vs normal breathing, respectively. Conclusion: Contralateral breast dose, although within a low dose range, was mildly but significantly increased in 200 treatment plans generated under gated conditions, predominately due to a shift in the medial field margin. Risk modeling for CBC among women aged {<=}45 years also pointed to a higher risk when comparing DIBH with normal breathing. This risk, however, was substantially lower in the model considering DVH information. We think that clinical decisions should not be affected by this small increase in CBD with DIBH because DIBH is effective in reducing the dose to the heart in all patients.« less
Ladrón De Guevara Hernández, D; Ham, H; Franken, P; Piepsz, A; Lobo Sotomayor, G
2002-01-01
The aim of the study was to evaluate three different methods for calculating the split renal function in patients with only one functioning kidney, keeping in mind that the split function should be zero on the side of the non-functioning kidney. We retrospectively selected 28 99mTc MAG3 renograms performed in children, 12 with unilateral nephrectomy, 4 with unilateral agenesis and 12 with a non-functioning kidney. A renal and perirenal region of interest (ROI) were delineated around the functioning kidney. The ROIs around the empty kidney were drawn symmetrically to the contralateral side. The split renal function was calculated using three different methods, the integral method, the slope method and the Patlak-Rutland algorithm. For the whole group of 28 kidneys as well as for the three categories of patients, the three methods provided a split function on the side of the non-functioning kidney close to the zero value, regardless of whether the empty kidney was the left or the right one. We recommend the use of the integral method for the whole range of split renal function with 99mTc MAG3. No significant improvement was obtained by means of the more sophisticated Patlak-Rutland method.
Four-Dimensional CT of the Diaphragm in Children: Initial Experience
2018-01-01
Objective To evaluate the technical feasibility of four-dimensional (4D) CT for the functional evaluation of the pediatric diaphragm. Materials and Methods In 22 consecutive children (median age 3.5 months, age range 3 days–3 years), 4D CT was performed to assess diaphragm motion. Diaphragm abnormalities were qualitatively evaluated and diaphragm motion was quantitatively measured on 4D CT. Lung density changes between peak inspiration and expiration were measured in the basal lung parenchyma. The diaphragm motions and lung density changes measured on 4D CT were compared between various diaphragm conditions. In 11 of the 22 children, chest sonography was available for comparison. Results Four-dimensional CT demonstrated normal diaphragm (n = 8), paralysis (n = 10), eventration (n = 3), and diffusely decreased motion (n = 1). Chest sonography demonstrated normal diaphragm (n = 2), paralysis (n = 6), eventration (n = 2), and right pleural effusion (n = 1). The sonographic findings were concordant with the 4D CT findings in 90.9% (10/11) of the patients. In diaphragm paralysis, the affected diaphragm motion was significantly decreased compared with the contralateral normal diaphragm motion (−1.1 ± 2.2 mm vs. 7.6 ± 3.8 mm, p = 0.005). The normal diaphragms showed significantly greater motion than the paralyzed diaphragms (4.5 ± 2.1 mm vs. −1.1 ± 2.2 mm, p < 0.0001), while the normal diaphragm motion was significantly smaller than the motion of the contralateral normal diaphragm in paralysis (4.5 ± 2.1 mm vs. 7.6 ± 3.8 mm, p = 0.01). Basal lung density change of the affected side was significantly smaller than that of the contralateral side in diaphragm paralysis (89 ± 73 Hounsfield units [HU] vs. 180 ± 71 HU, p = 0.03), while no significant differences were found between the normal diaphragms and the paralyzed diaphragms (136 ± 66 HU vs. 89 ± 73 HU, p = 0.1) or between the normal diaphragms and the contralateral normal diaphragms in paralysis (136 ± 66 HU vs. 180 ± 71 HU, p = 0.1). Conclusion The functional evaluation of the pediatric diaphragm is feasible with 4D CT in select children. PMID:29354007
Effects of Platelet-Rich Plasma (PRP) on a Model of Renal Ischemia-Reperfusion in Rats
Martín-Solé, Oriol; Rodó, Joan; García-Aparicio, Lluís; Blanch, Josep; Cusí, Victoria; Albert, Asteria
2016-01-01
Renal ischemia-reperfusion injury is a major cause of acute renal failure, causing renal cell death, a permanent decrease of renal blood flow, organ dysfunction and chronic kidney disease. Platelet-rich plasma (PRP) is an autologous product rich in growth factors, and therefore able to promote tissue regeneration and angiogenesis. This product has proven its efficacy in multiple studies, but has not yet been tested on kidney tissue. The aim of this work is to evaluate whether the application of PRP to rat kidneys undergoing ischemia-reperfusion reduces mid-term kidney damage. A total of 30 monorrenal Sprague-Dawley male rats underwent renal ischemia-reperfusion for 45 minutes. During ischemia, PRP (PRP Group, n = 15) or saline solution (SALINE Group, n = 15) was administered by subcapsular renal injection. Control kidneys were the contralateral organs removed immediately before the start of ischemia in the remaining kidneys. Survival, body weight, renal blood flow on Doppler ultrasound, kidney weight, kidney volume, blood biochemistry and histopathology were determined for all subjects and kidneys, as applicable. Correlations between these variables were searched for. The PRP Group showed significantly worse kidney blood flow (p = 0.045) and more histopathological damage (p<0.0001). Correlations were found between body weight, kidney volume, kidney weight, renal blood flow, histology, and serum levels of creatinine and urea. Our study provides the first evidence that treatment with PRP results in the deterioration of the kidney’s response to ischemia-reperfusion injury. PMID:27551718
Walker, P M; Ben Salem, D; Giroud, M; Brunotte, F
2006-05-01
This retrospective study investigated the dependence of N-acetyl aspartate (NAA) ratios on risk factors for cerebral vasculopathy such as sex, age, hypertension, diabetes mellitus, carotid stenosis, and dyslipidaemia, which may have affected brain vessels and induced metabolic brain abnormalities prior to stroke. We hypothesise that in stroke patients metabolic alterations in the apparently normal contralateral brain are dependent on the presence or not of such risk factors. Fifty nine patients (31 male, 28 female: 58.8+/-16.1 years old) with cortical middle cerebral artery (MCA) territory infarction were included. Long echo time chemical shift imaging spectroscopy was carried out on a Siemens 1.5 T Magnetom Vision scanner using a multi-voxel PRESS technique. Metabolite ratios (NAA/choline, NAA/creatine, lactate/choline, etc) were studied using uni- and multivariate analyses with respect to common risk factors. The influence of age, stroke lesion size, and time since stroke was studied using a linear regression approach. Age, sex, and hypertension all appeared to individually influence metabolite ratios, although only hypertension was significant after multivariate analysis. In both basal ganglia and periventricular white matter regions in apparently normal contralateral brain, the NAA/choline ratio was significantly lower in hypertensive (1.37+/-0.16 and 1.50+/-0.19, respectively) than in normotensive patients (1.72+/-0.19 and 1.85+/-0.15, respectively). Regarding MCA infarction, contralateral tissue remote from the lesion behaves abnormally in the presence of hypertension, the NAA ratios in hypertensive patients being significantly lower. These data suggest that hypertension may compromise the use of contralateral tissue data as a reference for comparison with ischaemic tissue.
de Bruin, Tanya; de Rooster, Hilde; van Bree, Henri; Duchateau, Luc; Cox, Eric
2007-09-01
To examine mRNA expression of cytokines in synovial fluid (SF) cells from dogs with cranial cruciate ligament (CrCL) rupture and medial patellar luxation (MPL) and determine mRNA expression for 3 joints (affected stifle, unaffected contralateral stifle, and left shoulder joints) in dogs with unilateral CrCL rupture. 29 stifle joints with CrCL rupture (29 dogs), 8 stifle joints with MPL (7 dogs), and 24 normal stifle joints (16 clinically normal dogs). Immediately before reconstructive surgery, SF was aspirated from the cruciate-deficient stifle joint or stifle joint with MPL. Fourteen of 29 dogs had unilateral CrCL rupture; SF was also aspirated from the unaffected contralateral stifle joint and left shoulder joint. Those 14 dogs were examined 6 and 12 months after reconstructive surgery. Total RNA was extracted from SF cells and reverse transcription-PCR assay was performed to obtain cDNA. Canine-specific cytokine mRNA expression was determined by use of a real-time PCR assay. Interleukin (IL)-8 and -10 and interferon-gamma expression differed significantly between dogs with arthropathies and dogs with normal stifle joints. For the 14 dogs with unilateral CrCL rupture, a significant difference was found for IL-8 expression. Before reconstructive surgery, IL-8 expression differed significantly between the affected stifle joint and left shoulder joint or contralateral stifle joint. Six months after surgery, IL-8 expression was significantly increased in the unaffected contralateral stifle joint, compared with the shoulder joint. No conclusions can be made regarding the role of the examined cytokines in initiation of CrCL disease.
Changes in Abundance of Oral Microbiota Associated with Oral Cancer
Schmidt, Brian L.; Kuczynski, Justin; Bhattacharya, Aditi; Huey, Bing; Corby, Patricia M.; Queiroz, Erica L. S.; Nightingale, Kira; Kerr, A. Ross; DeLacure, Mark D.; Veeramachaneni, Ratna; Olshen, Adam B.; Albertson, Donna G.
2014-01-01
Individual bacteria and shifts in the composition of the microbiome have been associated with human diseases including cancer. To investigate changes in the microbiome associated with oral cancers, we profiled cancers and anatomically matched contralateral normal tissue from the same patient by sequencing 16S rDNA hypervariable region amplicons. In cancer samples from both a discovery and a subsequent confirmation cohort, abundance of Firmicutes (especially Streptococcus) and Actinobacteria (especially Rothia) was significantly decreased relative to contralateral normal samples from the same patient. Significant decreases in abundance of these phyla were observed for pre-cancers, but not when comparing samples from contralateral sites (tongue and floor of mouth) from healthy individuals. Weighted UniFrac principal coordinates analysis based on 12 taxa separated most cancers from other samples with greatest separation of node positive cases. These studies begin to develop a framework for exploiting the oral microbiome for monitoring oral cancer development, progression and recurrence. PMID:24887397
Kao, Johnny; Pettit, Jeffrey; Zahid, Soombal; Gold, Kenneth D; Palatt, Terry
2015-01-01
The optimal technique for performing lung IMRT remains poorly defined. We hypothesize that improved dose distributions associated with normal tissue-sparing IMRT can allow safe dose escalation resulting in decreased acute and late toxicity. We performed a retrospective analysis of 82 consecutive lung cancer patients treated with curative intent from 1/10 to 9/14. From 1/10 to 4/12, 44 patients were treated with the community standard of three-dimensional conformal radiotherapy or IMRT without specific esophagus or contralateral lung constraints (standard RT). From 5/12 to 9/14, 38 patients were treated with normal tissue-sparing IMRT with selective sparing of contralateral lung and esophagus. The study endpoints were dosimetry, toxicity, and overall survival. Despite higher mean prescribed radiation doses in the normal tissue-sparing IMRT cohort (64.5 vs. 60.8 Gy, p = 0.04), patients treated with normal tissue-sparing IMRT had significantly lower lung V20, V10, V5, mean lung, esophageal V60, and mean esophagus doses compared to patients treated with standard RT (p ≤ 0.001). Patients in the normal tissue-sparing IMRT group had reduced acute grade ≥3 esophagitis (0 vs. 11%, p < 0.001), acute grade ≥2 weight loss (2 vs. 16%, p = 0.04), and late grade ≥2 pneumonitis (7 vs. 21%, p = 0.02). The 2-year overall survival was 52% with normal tissue-sparing IMRT arm compared to 28% for standard RT (p = 0.015). These data provide proof of principle that suboptimal radiation dose distributions are associated with significant acute and late lung and esophageal toxicity that may result in hospitalization or even premature mortality. Strict attention to contralateral lung and esophageal dose-volume constraints are feasible in the community hospital setting without sacrificing disease control.
Aktaş, Gul Ege; Sarıkaya, Ali
2015-11-01
Children with unilateral hydronephrosis are followed up with anteroposterior pelvic diameter (APD), hydronephrosis grade, mercaptoacetyltriglycine (MAG-3) drainage pattern and differential renal function (DRF). Indeterminate drainage preserved DRF in higher grades of hydronephrosis, in some situations, complicating the decision-making process. Due to an asymmetric renal area ratio, falsely negative DRF estimations can result in missed optimal surgery times. This study was designed to assess whether correcting the DRF estimation according to kidney area could reflect the clinical situation of a hydronephrotic kidney better than a classical DRF calculation, concurrently with the hydronephrosis grade, APD and MAG-3 drainage pattern. We reviewed the MAG-3, dimercaptosuccinic acid (DMSA) scans and ultrasonography (US) of 23 children (6 girls, 17 boys, mean age: 29 ± 50 months) with unilateral hydronephrosis. MAG-3 and DMSA scans were performed within 3 months (mean 25.4 ± 30.7 days). The closest US findings (mean 41.5 ± 28.2 days) were used. DMSA DRF estimations were obtained using the geometric mean method. Secondary calculations were performed to correct the counts (the total counts divided by the number of pixels in ROI) according to kidney area. The renogram patterns of patients were evaluated and separated into subgroups. The visual assessment of DMSA scans was noted and the hydronephrotic kidney was classified in comparison to the normal contralateral kidney's uptake. The correlations of the DRF values of classical and area-corrected methods with MAG-3 renogram patterns, the visual classification of DMSA scan, the hydronephrosis grade and the APD were assessed. DRF estimations of two methods were statistically different (p: 0.001). The categories of 12 hydronephrotic kidneys were changed. There were no correlations between classical DRF estimations and the hydronephrosis grade, APD, visual classification of the DMSA scan and uptake evaluation. The DRF distributions according to MAG-3 drainage patterns were not different. Area-corrected DRF estimations correlated with all: with an increasing hydronephrosis grade and APD, DRF estimations decreased and MAG-3 drainage patterns worsened. A decrease in DRF (< 45 %) was determined when APD was ≥ 10 mm. When APD was ≥ 26 mm, a reduction of DRF below 40 % was determined. Our results suggest that correcting DRF estimation for asymmetric renal area ratio in unilateral hydronephrosis can be more robust than the classical method, especially for higher grades of hydronephrotic kidneys, under equivocal circumstances.
Herrmann, Sandra M S; Saad, Ahmed; Eirin, Alfonso; Woollard, John; Tang, Hui; McKusick, Michael A; Misra, Sanjay; Glockner, James F; Lerman, Lilach O; Textor, Stephen C
2016-03-07
Atherosclerotic renal artery stenosis (ARAS) can reduce renal blood flow, tissue oxygenation, and GFR. In this study, we sought to examine associations between renal hemodynamics and tissue oxygenation with single-kidney function, pressor hormones, and inflammatory biomarkers in patients with unilateral ARAS undergoing medical therapy alone or stent revascularization. Nonrandomized inpatient studies were performed in patients with unilateral ARAS (>60% occlusion) before and 3 months after revascularization (n=10) or medical therapy (n=20) or patients with essential hypertension (n=32) under identical conditions. The primary study outcome was change in single-kidney GFR. Individual kidney hemodynamics and volume were measured using multidetector computed tomography. Tissue oxygenation (using R(2)* as a measure of deoxyhemoglobin) was determined by blood oxygen level-dependent magnetic resonance imaging at 3 T. Renal vein neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), and plasma renin activity were measured. Total GFR did not change over 3 months in either group, but the stenotic kidney (STK) GFR rose over time in the stent compared with the medical group (+2.2[-1.8 to 10.5] versus -5.3[-7.3 to -0.3] ml/min; P=0.03). Contralateral kidney (CLK) GFR declined in the stent group (43.6±19.7 to 36.6±19.5 ml/min; P=0.03). Fractional tissue hypoxia fell in the STK (fraction R(2)* >30/s: 22.1%±20% versus 14.9%±18.3%; P<0.01) after stenting. Renal vein biomarkers correlated with the degree of hypoxia in the STK: NGAL(r=0.3; P=0.01) and MCP-1(r=0.3; P=0.02; more so after stenting). Renal vein NGAL was inversely related to renal blood flow in the STK (r=-0.65; P<0.001). Biomarkers were highly correlated between STK and CLK, NGAL (r=0.94; P<0.001), and MCP-1 (r=0.96; P<0.001). These results showed changes over time in single-kidney GFR that were not evident in parameters of total GFR. Furthermore, they delineate the relationship of measurable tissue hypoxia within the STK and markers of inflammation in human ARAS. Renal vein NGAL and MCP-1 indicated persistent interactions between the ischemic kidney and both CLK and systemic levels of inflammatory cytokines. Copyright © 2016 by the American Society of Nephrology.
Tinnitus Intensity Dependent Gamma Oscillations of the Contralateral Auditory Cortex
van der Loo, Elsa; Gais, Steffen; Congedo, Marco; Vanneste, Sven; Plazier, Mark; Menovsky, Tomas; Van de Heyning, Paul; De Ridder, Dirk
2009-01-01
Background Non-pulsatile tinnitus is considered a subjective auditory phantom phenomenon present in 10 to 15% of the population. Tinnitus as a phantom phenomenon is related to hyperactivity and reorganization of the auditory cortex. Magnetoencephalography studies demonstrate a correlation between gamma band activity in the contralateral auditory cortex and the presence of tinnitus. The present study aims to investigate the relation between objective gamma-band activity in the contralateral auditory cortex and subjective tinnitus loudness scores. Methods and Findings In unilateral tinnitus patients (N = 15; 10 right, 5 left) source analysis of resting state electroencephalographic gamma band oscillations shows a strong positive correlation with Visual Analogue Scale loudness scores in the contralateral auditory cortex (max r = 0.73, p<0.05). Conclusion Auditory phantom percepts thus show similar sound level dependent activation of the contralateral auditory cortex as observed in normal audition. In view of recent consciousness models and tinnitus network models these results suggest tinnitus loudness is coded by gamma band activity in the contralateral auditory cortex but might not, by itself, be responsible for tinnitus perception. PMID:19816597
The role of nervus intermedius in side specific nasal responses.
Nichani, J R; Malik, V; Woolford, T J; Ramsden, R T; Homer, J J
2010-03-02
Nervus intermedius (NI) dysfunction is common in patients who have had vestibular schwannoma (VS) surgery. Such patients have a unilateral parasympathetic-denervated nasal cavity. A number of side-specific nasal reflexes have been demonstrated in normal individuals, including hand cold-water immersion. It is not understood whether these reflexes have parasympathetic or sympathic efferent pathways. We aimed to evaluate the side specific nasal reflex to cold-water immersion in post-operative VS patients with NI dysfunction, in order to determine the nature of the efferent pathway of these reflexes. Side specific responses to cold-water immersion were tested by acoustic rhinometry in 10 normal individuals and 18 patients with NI dysfunction (proven by Schirmer s test) after VS surgery. A consistent pattern of ipsilateral congestion and contralateral decongestion after the cold-water immersion was seen in normal individuals (p smaller than 0.001). We found no consistent response in VS patients both ipsilateral and contralateral to the side of NI dysfunction. We confirm the consistent side-specific nasal reflexes to cold-water hand immersion in normal individuals. This is disturbed in patients with NI dysfunction. We have also shown unexpectantly that the contralateral side-specific reflex is disturbed in these patients. These data suggest that the reflex is parasympathetic and crosses the midline.
Gervasio, Sabata; Voigt, Michael; Kersting, Uwe G; Farina, Dario; Sinkjær, Thomas; Mrachacz-Kersting, Natalie
2017-01-01
A constant coordination between the left and right leg is required to maintain stability during human locomotion, especially in a variable environment. The neural mechanisms underlying this interlimb coordination are not yet known. In animals, interneurons located within the spinal cord allow direct communication between the two sides without the need for the involvement of higher centers. These may also exist in humans since sensory feedback elicited by tibial nerve stimulation on one side (ipsilateral) can affect the muscles activation in the opposite side (contralateral), provoking short-latency crossed responses (SLCRs). The current study investigated whether contralateral afferent feedback contributes to the mechanism controlling the SLCR in human gastrocnemius muscle. Surface electromyogram, kinematic and kinetic data were recorded from subjects during normal walking and hybrid walking (with the legs moving in opposite directions). An inverse dynamics model was applied to estimate the gastrocnemius muscle proprioceptors' firing rate. During normal walking, a significant correlation was observed between the magnitude of SLCRs and the estimated muscle spindle secondary afferent activity (P = 0.04). Moreover, estimated spindle secondary afferent and Golgi tendon organ activity were significantly different (P ≤ 0.01) when opposite responses have been observed, that is during normal (facilitation) and hybrid walking (inhibition) conditions. Contralateral sensory feedback, specifically spindle secondary afferents, likely plays a significant role in generating the SLCR. This observation has important implications for our understanding of what future research should be focusing on to optimize locomotor recovery in patient populations.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kozak, Kevin R.; Adams, Judith; Krejcarek, Stephanie J.
Purpose: We compared tumor and normal tissue dosimetry of proton radiation therapy with intensity-modulated radiation therapy (IMRT) for pediatric parameningeal rhabdomyosarcomas (PRMS). Methods and Materials: To quantify dosimetric differences between contemporary proton and photon treatment for pediatric PRMS, proton beam plans were compared with IMRT plans. Ten patients treated with proton radiation therapy at Massachusetts General Hospital had IMRT plans generated. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing. Results: Proton and IMRT plans provided acceptable and comparable target volume coverage, with atmore » least 99% of the CTV receiving 95% of the prescribed dose in all cases. Improved dose conformality provided by proton therapy resulted in significant sparing of all examined normal tissues except for ipsilateral cochlea and mastoid; ipsilateral parotid gland sparing was of borderline statistical significance (p = 0.05). More profound sparing of contralateral structures by protons resulted in greater dose asymmetry between ipsilateral and contralateral retina, optic nerves, cochlea, and mastoids; dose asymmetry between ipsilateral and contralateral parotids was of borderline statistical significance (p = 0.05). Conclusions: For pediatric PRMS, superior normal tissue sparing is achieved with proton radiation therapy compared with IMRT. Because of enhanced conformality, proton plans also demonstrate greater normal tissue dose distribution asymmetry. Longitudinal studies assessing the impact of proton radiotherapy and IMRT on normal tissue function and growth symmetry are necessary to define the clinical consequences of these differences.« less
Liu, W; Yan, B; An, D; Niu, R; Tang, Y; Tong, X; Gong, Q; Zhou, D
2017-12-01
This study aimed to assess the evolution of perinodular and contralateral white matter abnormalities in patients with periventricular nodular heterotopia (PNH) and epilepsy. Diffusion tensor imaging (DTI) (64 directions) and 3 T structural magnetic resonance imaging were performed in 29 PNH patients (mean age 27.3 years), and 16 patients underwent a second scan (average time between the two scans 1.1 years). Fractional anisotropy and mean diffusivity were measured within the perilesional and contralateral white matter. Longitudinal analysis showed that white matter located 10 mm from the focal nodule displayed characteristics intermediate to tissue 5 mm away, and normal-appearing white matter (NAWM) also established evolution profiles of perinodular white matter in different cortical lobes. Compared to 29 age- and sex-matched healthy controls, significant decreased fractional anisotropy and elevated mean diffusivity values were observed in regions 5 and 10 mm from nodules (P < 0.01), whilst DTI metrics of the remaining NAWM did not differ significantly from controls. Additionally, normal DTI metrics were shown in the contralateral region in patients with unilateral PNH. Periventricular nodular heterotopia is associated with microstructural abnormalities within the perilesional white matter and the extent decreases with increasing distance from the nodule. In the homologous contralateral region, white matter diffusion metrics were unchanged in unilateral PNH. These findings have clinical implications with respect to the medical and surgical interventions of PNH-related epilepsy. © 2017 EAN.
Wang, Jian; Wang, Weici; Jin, Bi; Zhang, Yanrong; Xu, Ping; Xiang, Feixiang; Zheng, Yi; Chen, Juan; Sheng, Shi; Ouyang, Chenxi; Li, Yiqing
2016-01-01
Purpose. To investigate the alternation in cerebral and ocular blood flow velocity (BFV) in patients of carotid stenosis (CS) with or without contralateral carotid occlusion (CO) early after carotid endarterectomy (CEA). Patients and Methods. Nineteen patients underwent CEA for ≥50% CS. Fourteen patients had the unilateral CS, and five patients had the ipsilateral CS and the contralateral CO. Transcranial Doppler (TCD) and Color Doppler Imaging (CDI) were performed before and early after CEA. Results. In patients with unilateral CS, significant improvements in BFV were observed in anterior cerebral artery (ACA) and middle cerebral artery (MCA) on the ipsilateral side after CEA. In patients of ipsilateral CS and contralateral CO, significant improvements in BFV were observed in the ACA and MCA not only on the ipsilateral side but also on the contralateral side postoperatively. The ipsilateral ophthalmic artery (OA) retrograde flows in two patients were recovered to anterograde direction following CEA. The BFV in short posterior ciliary artery (SPCA) of the ipsilateral side significantly increased postoperatively irrespective of the presence of contralateral CO. Conclusions. CEA improved cerebral anterior circulation hemodynamics especially in patients of unilateral CS and contralateral CO, normalized the OA reverse flow, and increased the blood perfusion of SPCA.
Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats.
Schmiedt, C W; Brainard, B M; Hinson, W; Brown, S A; Brown, C A
2016-01-01
The objectives of this study were to define the acute and chronic effects of 1-hour unilateral in vivo renal ischemia on renal function and histology in cats. Twenty-one adult purpose-bred research cats were anesthetized, and 1 kidney underwent renal artery and vein occlusion for 1 hour. Serum creatinine and urea concentrations, urine protein:creatinine ratio, urine-specific gravity, glomerular filtration rate, hematocrit, platelet concentration and function, and white blood cell count were measured at baseline and variable time points after ischemia. Renal histopathology was evaluated on days 3, 6, 12, 21, 42, and 70 postischemia; changes in smooth muscle actin and interstitial collagen were examined. Following ischemia, whole animal glomerular filtration rate was significantly reduced (57% of baseline on day 6; P < .05). At the early time points, the ischemic kidneys exhibited severe acute epithelial necrosis accompanied by evidence of regeneration of tubules predominantly within the corticomedullary junction. At later periods, postischemic kidneys had evidence of tubular atrophy and interstitial inflammation with significantly more smooth muscle actin and interstitial collagen staining and interstitial fibrosis when compared with the contralateral control kidneys. This study characterizes the course of ischemic acute kidney injury in cats and demonstrates that ischemic acute kidney injury triggers chronic fibrosis, interstitial inflammation, and tubular atrophy in feline kidneys. These late changes are typical of those observed in cats with naturally occurring chronic kidney disease. © The Author(s) 2015.
Bipolar radiofrequency ablation of the kidney: comparison with monopolar radiofrequency ablation.
Nakada, Stephen Y; Jerde, Travis J; Warner, Thomas F; Wright, Andrew S; Haemmerich, Dieter; Mahvi, David M; Lee, Fred T
2003-12-01
We report initial ex vivo and in vivo studies using bipolar radiofrequency (RF) ablation of porcine kidneys. An internal ground electrode is positioned in the kidney opposite the RF electrode, resulting in ablation of all the intervening renal tissue. Ex vivo preparations of 10 porcine kidneys were perfused continuously with Ringer's solution and treated with either standard external grounded RF (N = 3) or bipolar RF ablation with 1 (N = 2), 2 (N = 3), or 3 (N = 2) cm of separation between the ground probe and the RF probe using a Model 30 RITA generator (RITA, Mountain View, CA). Target temperatures were 90 degrees C for 8 minutes. Gross and histologic assessments were made acutely. Four domestic pigs were treated with monopolar RF ablation of the lower pole of one kidney and bipolar RF with a 12-mm separation between the probes of the contralateral lower pole. Animals were harvested 48 hours later to maximize tissue damage for gross measurements and histologic evaluation. Ex vivo studies revealed grossly monopolar lesions 1.5 cm in maximum diameter and 1.75 cm(3) in volume. In comparison, bipolar lesions were 2.8 cm in maximum diameter and 10.3 cm(3) in volume using 3 cm of electrode separation. There was histologic evidence of cell death in all specimens. In vivo studies showed two distinct gross lesions with RF: one blanched and one hemorrhagic. Using bipolar RF, larger blanched lesions were achievable than with monopolar RF (2.80 cm(3) v 1.63 cm(3)). Overall, the combinations of blanched and hemorrhagic lesions were similar with monopolar and bipolar RF (5.01 v 5.31 cm(3)). Histologic evaluation verified cell death in the blanched lesions and rare areas of normal tissue in the hemorrhagic lesions. As shown by ex vivo data, bipolar RF can create larger lesions than does monopolar RF. In vivo, at 48 hours, both blanched and hemorrhagic gross lesions were seen using RF. In this model, blanched lesions predominated when performing bipolar RF.
Central masking with bilateral cochlear implants
Lin, Payton; Lu, Thomas; Zeng, Fan-Gang
2013-01-01
Across bilateral cochlear implants, contralateral threshold shift has been investigated as a function of electrode difference between the masking and probe electrodes. For contralateral electric masking, maximum threshold elevations occurred when the position of the masker and probe electrode was approximately place-matched across ears. The amount of masking diminished with increasing masker-probe electrode separation. Place-dependent masking occurred in both sequentially implanted ears, and was not affected by the masker intensity or the time delay from the masker onset. When compared to previous contralateral masking results in normal hearing, the similarities between place-dependent central masking patterns suggest comparable mechanisms of overlapping excitation in the central auditory nervous system. PMID:23363113
Does the corticoadrenal adenoma with ''pre-Cushing's syndrome'' exist
DOE Office of Scientific and Technical Information (OSTI.GOV)
Charbonnel, B.; Chatal, J.F.; Ozanne, P.
1981-12-01
An adrenal tumor was discovered fortuitously in a patient with no clinical features of Cushing's syndrome. On adrenal imaging, there was good uptake in the nodule but no visualization of the contralateral adrenal. The latter was seen, however, in a second scan performed under ACTH treatment. In the hormone assessment, basal cortisol and 17-hydroxycorticoids were normal and cortisol diurnal variation was near normal, but a dexamethasone suppression test and ACTH responses to metyrapone and insulin hypoglycemia were abnormal. Eight months after excision of a spongiocytic-type adenoma, the remaining adrenal was visible on scintigram and the hormonal tests were normal. Thismore » pattern suggests that the clinical Cushing's syndrome was enough to partially suppress ACTH and, consequently, visualization of the contralateral gland.« less
Di Girolamo, S; d'Ecclesia, A; Quaranta, N; Garozzo, A; Evoli, A; Paludetti, G
2001-12-01
Myasthenia gravis (MG) induces a reduction of transient evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs) that reverses partially after administration of an acetylcholinesterase (AChE) inhibitor. In normal subjects a contralateral acoustic stimulation (CAS) produces an amplitude reduction of TEOAEs and DPOAEs. This effect, called contralateral suppression (CS), is mediated by the efferent auditory system. Twenty subjects affected by MG underwent DPOAE recording with and without contralateral white noise in a drug-free baseline period ('basal') and 1 h ('post') after administration of a reversible AChE inhibitor. In 'basal' condition CAS did not induce significant DPOAE amplitude changes but a paradoxical slight increase was observed. After drug administration, CAS produced a significant decrease of DPOAE amplitudes for middle frequencies (f(2) between 1306 and 2600 Hz). In normal controls CAS caused a significant decrease (P<0.001) for all frequencies. The amount of CS in controls and in the MG 'post' condition was not significantly different. The increased acetylcholine (ACh) availability following drug consumption seems to partially restore outer hair cell function and enhances their electromotility; a further influx of ACh due to CAS yields to restoration of the CS. These findings also suggest that DPOAEs may be useful in the diagnosis of MG and for monitoring the effectiveness of treatment.
Diagnostic accuracy of automatic normalization of CBV in glioma grading using T1- weighted DCE-MRI.
Sahoo, Prativa; Gupta, Rakesh K; Gupta, Pradeep K; Awasthi, Ashish; Pandey, Chandra M; Gupta, Mudit; Patir, Rana; Vaishya, Sandeep; Ahlawat, Sunita; Saha, Indrajit
2017-12-01
Aim of this retrospective study was to compare diagnostic accuracy of proposed automatic normalization method to quantify the relative cerebral blood volume (rCBV) with existing contra-lateral region of interest (ROI) based CBV normalization method for glioma grading using T1-weighted dynamic contrast enhanced MRI (DCE-MRI). Sixty patients with histologically confirmed gliomas were included in this study retrospectively. CBV maps were generated using T1-weighted DCE-MRI and are normalized by contralateral ROI based method (rCBV_contra), unaffected white matter (rCBV_WM) and unaffected gray matter (rCBV_GM), the latter two of these were generated automatically. An expert radiologist with >10years of experience in DCE-MRI and a non-expert with one year experience were used independently to measure rCBVs. Cutoff values for glioma grading were decided from ROC analysis. Agreement of histology with rCBV_WM, rCBV_GM and rCBV_contra respectively was studied using Kappa statistics and intra-class correlation coefficient (ICC). The diagnostic accuracy of glioma grading using the measured rCBV_contra by expert radiologist was found to be high (sensitivity=1.00, specificity=0.96, p<0.001) compared to the non-expert user (sensitivity=0.65, specificity=0.78, p<0.001). On the other hand, both the expert and non-expert user showed similar diagnostic accuracy for automatic rCBV_WM (sensitivity=0.89, specificity=0.87, p=0.001) and rCBV_GM (sensitivity=0.81, specificity=0.78, p=0.001) measures. Further, it was also observed that, contralateral based method by expert user showed highest agreement with histological grading of tumor (kappa=0.96, agreement 98.33%, p<0.001), however; automatic normalization method showed same percentage of agreement for both expert and non-expert user. rCBV_WM showed an agreement of 88.33% (kappa=0.76,p<0.001) with histopathological grading. It was inferred from this study that, in the absence of expert user, automated normalization of CBV using the proposed method could provide better diagnostic accuracy compared to the manual contralateral based approach. Copyright © 2017 Elsevier Inc. All rights reserved.
Reestablishment of radiographic kidney size in Miniature Schnauzer dogs
SOHN, Jungmin; YUN, Sookyung; LEE, Jeosoon; CHANG, Dongwoo; CHOI, Mincheol; YOON, Junghee
2016-01-01
Kidney size may be altered in renal diseases, and the detection of kidney size alteration has diagnostic and prognostic values. We hypothesized that radiographic kidney size, the kidney length to the second lumbar vertebra (L2) length ratio, in normal Miniature Schnauzer dogs may be overestimated due to their shorter vertebral length. This study was conducted to evaluate radiographic and ultrasonographic kidney size and L2 length in clinically normal Miniature Schnauzers and other dog breeds to evaluate the effect of vertebral length on radiographic kidney size and to reestablish radiographic kidney size in normal Miniature Schnauzers. Abdominal radiographs and ultrasonograms from 49 Miniature Schnauzers and 54 other breeds without clinical evidence of renal disease and lumbar vertebral abnormality were retrospectively evaluated. Radiographic kidney size, in the Miniature Schnauzer (3.31 ± 0.26) was significantly larger than that in other breeds (2.94 ± 0.27). Relative L2 length, the L2 length to width ratio, in the Miniature Schnauzer (1.11 ± 0.06) was significantly shorter than that in other breeds (1.21 ± 0.09). However, ultrasonographic kidney sizes, kidney length to aorta diameter ratios, were within or very close to normal range both in the Miniature Schnauzer (6.75 ± 0.67) and other breeds (7.16 ± 1.01). Thus, Miniature Schnauzer dogs have breed-specific short vertebrae and consequently a larger radiographic kidney size, which was greater than standard reference in normal adult dogs. Care should be taken when evaluating radiographic kidney size in Miniature Schnauzers to prevent falsely diagnosed renomegaly. PMID:27594274
Reestablishment of radiographic kidney size in Miniature Schnauzer dogs.
Sohn, Jungmin; Yun, Sookyung; Lee, Jeosoon; Chang, Dongwoo; Choi, Mincheol; Yoon, Junghee
2017-01-10
Kidney size may be altered in renal diseases, and the detection of kidney size alteration has diagnostic and prognostic values. We hypothesized that radiographic kidney size, the kidney length to the second lumbar vertebra (L2) length ratio, in normal Miniature Schnauzer dogs may be overestimated due to their shorter vertebral length. This study was conducted to evaluate radiographic and ultrasonographic kidney size and L2 length in clinically normal Miniature Schnauzers and other dog breeds to evaluate the effect of vertebral length on radiographic kidney size and to reestablish radiographic kidney size in normal Miniature Schnauzers. Abdominal radiographs and ultrasonograms from 49 Miniature Schnauzers and 54 other breeds without clinical evidence of renal disease and lumbar vertebral abnormality were retrospectively evaluated. Radiographic kidney size, in the Miniature Schnauzer (3.31 ± 0.26) was significantly larger than that in other breeds (2.94 ± 0.27). Relative L2 length, the L2 length to width ratio, in the Miniature Schnauzer (1.11 ± 0.06) was significantly shorter than that in other breeds (1.21 ± 0.09). However, ultrasonographic kidney sizes, kidney length to aorta diameter ratios, were within or very close to normal range both in the Miniature Schnauzer (6.75 ± 0.67) and other breeds (7.16 ± 1.01). Thus, Miniature Schnauzer dogs have breed-specific short vertebrae and consequently a larger radiographic kidney size, which was greater than standard reference in normal adult dogs. Care should be taken when evaluating radiographic kidney size in Miniature Schnauzers to prevent falsely diagnosed renomegaly.
Clark, Robert A.
2015-01-01
Vertical fusional vergence (VFV) normally compensates for slight vertical heterophorias. We employed magnetic resonance imaging to clarify extraocular muscle contributions to VFV induced by monocular two-prism diopter (1.15°) base-up prism in 14 normal adults. Fusion during prism viewing requires monocular infraduction. Scans were repeated without prism, and with prism shifted contralaterally. Contractility indicated by morphometric indexes was separately analyzed in medial and lateral vertical rectus and superior oblique (SO) putative compartments, and superior and inferior horizontal rectus extraocular muscle putative compartments, but in the whole inferior oblique (IO). Images confirmed appropriate VFV that was implemented by the inferior rectus (IR) medial compartment contracting ipsilateral and relaxing contralateral to prism. There was no significant contractility in the IR lateral compartment. The superior but not inferior lateral rectus (LR) compartment contracted significantly in the prism viewing eye, but not contralateral to prism. The IO contracted ipsilateral but not contralateral to the prism. In the infraducting eye, the SO medial compartment relaxed significantly, while the lateral compartment was unchanged; contralateral to prism, the SO lateral compartment contracted, while the medial compartment was unchanged. There was no contractility in the superior or medial rectus muscles in either eye. There was no globe retraction. We conclude that the vertical component of VFV is primarily implemented by IR medial compartment contraction. Since appropriate vertical rotation is not directly implemented, or is opposed, by associated differential LR and SO compartmental activity, and IO contraction, these actions probably implement a torsional component of VFV. PMID:25589593
Bilateral Activity-Dependent Interactions in the Developing Corticospinal System
Friel, Kathleen M.; Martin, John H.
2009-01-01
Activity-dependent competition between the corticospinal (CS) systems in each hemisphere drives postnatal development of motor skills and stable CS tract connections with contralateral spinal motor circuits. Unilateral restriction of motor cortex (M1) activity during an early postnatal critical period impairs contralateral visually guided movements later in development and in maturity. Silenced M1 develops aberrant connections with the contralateral spinal cord whereas the initially active M1, in the other hemisphere, develops bilateral connections. In this study, we determined whether the aberrant pattern of CS tract terminations and motor impairments produced by early postnatal M1 activity restriction could be abrogated by reducing activity-dependent synaptic competition from the initially active M1 later in development. We first inactivated M1 unilaterally between postnatal weeks 5–7. We next inactivated M1 on the other side from weeks 7–11 (alternate inactivation), to reduce the competitive advantage that this side may have over the initially inactivated side. Alternate inactivation redirected aberrant contralateral CS tract terminations from the initially silenced M1 to their normal spinal territories and reduced the density of aberrant ipsilateral terminations from the initially active side. Normal movement endpoint control during visually guided locomotion was fully restored. This reorganization of CS terminals reveals an unsuspected late plasticity after the critical period for establishing the pattern of CS terminations in the spinal cord. Our findings show that robust bilateral interactions between the developing CS systems on each side are important for achieving balance between contralateral and ipsilateral CS tract connections and visuomotor control. PMID:17928450
Trilla, E; Lorente, D; Salvador, C; Planas, J; Placer, J; Celma, A; Cantarell, C; Moreso, F; Seron, D; Morote, J
2014-10-01
To analyze and evaluate our experience in surgical treatment with the open approach of the complex ureteral stenosis after adult kidney transplantation in a tertiary level hospital in the last seven years. We have reviewed the different surgical options used. A total of 589 consecutive adult renal transplants were performed from January 2005 to December 2012. Of these, 1.1% showed some degree of symptomatic obstructive uropathy which after initial urinary diversion required open surgical approach using the ipsilateral or contralateral native urinary tract. Characteristics of the patient, clinical examinations performed and surgical technique performed as well as their results are presented. During the period under review, in 5 men and 2 women who had ureteral stenoses after renal transplant, 7 reparative surgeries were performed by open ureteropyelostomy, using ipsilateral native ureter in 6 cases and contralateral ureter in the remaining case. In one case, uretero-calicial anastomosis was performed due to severe pyelic shrinkage. There were no significant complications. Native kidney nephrectomy was not required for further complications. All the patients operated on had optimum plasma creatinine levels with resolution of previous dilatation. The initial percutaneous nephrostomy followed by open surgical repair using native ureter represents a definitive, valid and optimal alternative in terms of safety and preservation of renal function. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.
Contralateral migration of oculomotor neurons is regulated by Slit/Robo signaling.
Bjorke, Brielle; Shoja-Taheri, Farnaz; Kim, Minkyung; Robinson, G Eric; Fontelonga, Tatiana; Kim, Kyung-Tai; Song, Mi-Ryoung; Mastick, Grant S
2016-10-22
Oculomotor neurons develop initially like typical motor neurons, projecting axons out of the ventral midbrain to their ipsilateral targets, the extraocular muscles. However, in all vertebrates, after the oculomotor nerve (nIII) has reached the extraocular muscle primordia, the cell bodies that innervate the superior rectus migrate to join the contralateral nucleus. This motor neuron migration represents a unique strategy to form a contralateral motor projection. Whether migration is guided by diffusible cues remains unknown. We examined the role of Slit chemorepellent signals in contralateral oculomotor migration by analyzing mutant mouse embryos. We found that the ventral midbrain expresses high levels of both Slit1 and 2, and that oculomotor neurons express the repellent Slit receptors Robo1 and Robo2. Therefore, Slit signals are in a position to influence the migration of oculomotor neurons. In Slit 1/2 or Robo1/2 double mutant embryos, motor neuron cell bodies migrated into the ventral midbrain on E10.5, three days prior to normal migration. These early migrating neurons had leading projections into and across the floor plate. In contrast to the double mutants, embryos which were mutant for single Slit or Robo genes did not have premature migration or outgrowth on E10.5, demonstrating a cooperative requirement of Slit1 and 2, as well as Robo1 and 2. To test how Slit/Robo midline repulsion is modulated, we found that the normal migration did not require the receptors Robo3 and CXCR4, or the chemoattractant, Netrin 1. The signal to initiate contralateral migration is likely autonomous to the midbrain because oculomotor neurons migrate in embryos that lack either nerve outgrowth or extraocular muscles, or in cultured midbrains that lacked peripheral tissue. Overall, our results demonstrate that a migratory subset of motor neurons respond to floor plate-derived Slit repulsion to properly control the timing of contralateral migration.
Bates, Nathaniel A.; McPherson, April L.; Nesbitt, Rebecca J.; Shearn, Jason T.; Myer, Gregory D.; Hewett, Timothy E.
2017-01-01
Limb asymmetry is a known factor for increased ACL injury risk. These asymmetries are normally observed during in vivo testing. Prior studies have developed in vitro testing methodologies driven by in vivo kinematics to investigate knee mechanics relative to ACL injury. The objective of this study was to determine if mechanical side-to-side asymmetries persist in contralateral pairs during in vitro simulation testing. In vivo kinematics were recorded for male and female drop vertical jump and sidestep cutting tasks. The recorded kinematics were used to robotically simulate the motions on 7 contralateral pairs of cadaveric lower extremities specimens. ACL and MCL force, torque, and strains were recorded and analyzed for differences between contralateral pairs. There was a general lack of mechanical differences between limb sides. Adduction peak torque for the male sidestep cut movement was significantly different between limb sides (p = 0.04). However, this is consistent with ACL injury mechanics in that movement in the frontal plane (abduction/adduction) increases injury risk and it is possible loading differences in this plane may have resulted from tolerances within the setup process. The findings of this study indicate that contralateral knee joints were representative of each other during biomechanical in vitro tests. In future cadaveric robotic simulations, contralateral limbs can be used interchangeably. In addition, direct comparisons of the structural behaviors of isolated conditions for contralateral knee joints can be performed. PMID:28062120
O'Hagan, Emma; Mallett, Tamara; Convery, Mairead; McKeever, Karl
2015-01-01
Antiglomerular basement membrane (anti-GBM) antibody disease is uncommon in the pediatric population. There are no cases in the literature describing the development of anti-GBM disease following XGP or nephrectomy. We report the case of a 7-year-old boy with no past history of urological illness, treated with antimicrobials and nephrectomy for diffuse, unilateral xanthogranulomatous pyelonephritis (XGP). Renal function and ultrasound scan of the contralateral kidney postoperatively were normal. Three months later, the child represented in acute renal failure with rapidly progressive glomerulonephritis requiring hemodialysis. Renal biopsy showed severe crescentic glomerulonephritis with 95% of glomeruli demonstrating circumferential cellular crescents. Strong linear IgG staining of the glomerular basement membranes was present, in keeping with anti-GBM disease. Circulating anti-GBM antibodies were positive. Treatment with plasma exchange, methylprednisolone, and cyclophosphamide led to normalization of anti-GBM antibody titers. Frequency of hemodialysis was reduced as renal function improved, and he is currently independent of dialysis with estimated glomerular filtration rate 20.7 mls/min/1.73 m 2 . Case studies in the adult literature have reported the development of a rapidly progressive anti-GBM antibody-induced glomerulonephritis following renal surgery where patients expressed HLA DR2/HLA DR15 major histocompatibility (MHC) antigens. Of note, our patient also expresses the HLA DR15 MHC antigen.
The effect of prazosin on skin microcirculation as assessed by laser Doppler flowmetry.
Khan, F; Struthers, A D; Spence, V A
1988-01-01
1. Laser Doppler flowmetry was used in six normal volunteers to record changes in fingertip skin blood flow after the administration of prazosin to block postsynaptic alpha 1-adrenoceptors. 2. Prazosin (0.5 mg orally) did not alter systolic or diastolic blood pressure or heart rate. 3. Prazosin did significantly increase basal skin blood flow 2 h after its administration but this effect was no longer evident after contralateral hand warming. Prazosin markedly reduced the skin vasoconstrictor response to deep inspiration and to contralateral hand cooling. 4. This study suggests that postsynaptic alpha 1-adrenoceptors are involved in maintaining skin vasoconstrictor tone at rest and are also involved in the rapid skin vasoconstriction seen in response to a deep inspiration and to contralateral hand cooling. PMID:2846022
Ruptured ectopic pregnancy with contralateral adnexal torsion after spontaneous conception.
DiLuigi, Andrea J; Maier, Donald B; Benadiva, Claudio A
2008-11-01
To describe a case of ruptured ectopic pregnancy and contralateral adnexal torsion after spontaneous conception. Case report. Tertiary university medical center. A 23-year-old multiparous female with severe bilateral pelvic pain and a positive pregnancy test. Operative laparoscopy with detorsion of left adnexa, drainage of left ovarian hemorrhagic corpus luteum cyst, right salpingectomy, and dilation and curettage. Laparoscopy revealed a 5 cm hemorrhagic corpus luteum cyst of the left ovary, torsion of the left ovary and fallopian tube, and a ruptured right ampullary ectopic pregnancy. Normal perfusion of left ovary and fallopian tube after detorsion, resolution of left ovarian hemorrhagic corpus luteum cyst, patent left fallopian tube with chromopertubation, and successful removal of ectopic pregnancy. This is a unique case of adnexal torsion and contralateral ectopic pregnancy occurring after spontaneous conception.
van der Harst, J J; Gokeler, A; Hof, A L
2007-07-01
Anterior cruciate ligament (ACL) deficiency can be a major problem for athletes and subsequent reconstruction of the ACL may be indicated if a conservative regimen has failed. After ACL reconstruction signs of abnormality in the use of the leg remain for a long time. It is expected that the landing after a single-leg hop for distance (horizontal hop) might give insight in the differences in kinematics and kinetics between uninjured legs and ACL-reconstructed legs. Before the ACL-reconstructed leg can be compared with the contralateral leg, knowledge of differences between legs of uninjured subjects is needed. Kinematic and kinetic variables of both legs were measured with an optoelectronic system and a force plate and calculated by inverse dynamics. The dominant leg (the leg with biggest horizontal hop distance) and the contralateral leg of nine uninjured subjects were compared. No significant differences were found in most of the kinematic and kinetic variables between dominant leg and contralateral leg of uninjured subjects. Only hop distance and hip extension angles differed significantly. This study suggests that there are no important differences between dominant leg and contralateral leg in healthy subjects. As a consequence, the uninvolved leg of ACL-reconstructed patients can be used as a reference. The observed variables of this study can be used as a reference of normal values and normal differences between legs in healthy subjects.
NASA Technical Reports Server (NTRS)
Meehan, J. R.; Henry, J. P.
1973-01-01
Responses of an innervated and a contralateral chronically denervated kidney to mild positive pressure breathing are compared for saline volume expansions in chloralose anesthetized dogs. It is shown that mild pressure breathing significantly reduces sodium excretion, urine flow, free water clearance, and PAH clearance. After 20 minutes of positive pressure breathing, both kidney responses are identical suggesting the release of natriuretic hormone which reduces renal function in addition to the demonstrated change in renal nerve activity. Increase of the left atrial pressure through balloon obstruction of the mitral orifice increases urine flow, sodium excretion and PAH clearance; inflation of the balloon and positive pressure breathing again depresses renal function. Preliminary evidence indicates that receptors in the right atrium are more severely affected by pressure breathing than those in the left atrium.
Domagała, Piotr; Kwiatkowski, Artur; Drozdowski, Jakub; Ostrowski, Krzysztof; Wszola, Michal; Diuwe, Piotr; Durlik, Magdalena; Paczek, Leszek; Chmura, Andrzej
2012-12-01
Few reports describing the use of organs donated by transplant recipients have been published. In this case report, kidneys procured from a brain-dead liver recipient were transplanted successfully. A 21-year-old man was referred for liver transplant after an overdose of acetaminophen. The patient's kidney function was initially normal, with proper urine production and normal kidney laboratory parameters. On the third day after admission, the patient's kidney laboratory parameters became elevated and hepatic encephalopathy requiring mechanical ventilation developed. An orthotopic liver transplant was performed the next day. The patient did not recover consciousness, and brain death was diagnosed on the third day after the liver transplant surgery. The maximum serum concentration of creatinine was 5.8 mg/dL (513 μmol/L) before kidney recovery, and urine production was normal. The kidneys were recovered with organ-perfusion support and were preserved by using machine perfusion. The kidneys were transplanted into 2 male recipients. Twelve months after transplant, the recipients remained in good health with satisfactory kidney function. This case demonstrates that transplanting kidneys recovered from liver transplant recipients is possible and beneficial, thus expanding the pool of potential donors.
Aging and physiological changes of the kidneys including changes in glomerular filtration rate.
Musso, Carlos G; Oreopoulos, Dimitrios G
2011-01-01
In addition to the structural changes in the kidney associated with aging, physiological changes in renal function are also found in older adults, such as decreased glomerular filtration rate, vascular dysautonomia, altered tubular handling of creatinine, reduction in sodium reabsorption and potassium secretion, and diminished renal reserve. These alterations make aged individuals susceptible to the development of clinical conditions in response to usual stimuli that would otherwise be compensated for in younger individuals, including acute kidney injury, volume depletion and overload, disorders of serum sodium and potassium concentration, and toxic reactions to water-soluble drugs excreted by the kidneys. Additionally, the preservation with aging of a normal urinalysis, normal serum urea and creatinine values, erythropoietin synthesis, and normal phosphorus, calcium and magnesium tubular handling distinguishes decreased GFR due to normal aging from that due to chronic kidney disease. Copyright © 2011 S. Karger AG, Basel.
Schlotmann, Andreas; Clorius, John H; Rohrschneider, Wiltrud K; Clorius, Sandra N; Amelung, Folker; Becker, Kristianna
2008-07-01
The significance of delayed tissue tracer transit (TTT) of (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) has not been systematically evaluated in hydronephrosis. We sought to demonstrate that delayed TTT accompanies both functional decline and histomorphologic restructuring. Twenty 2- to 3-mo-old piglets with surgically induced partial unilateral ureteral stenosis were examined with magnetic resonance urography (MRU) to evaluate morphology and with (99m)Tc-MAG3 diuretic renography (DR) to determine single-kidney function (SKF), evaluate the response to furosemide stimulation (RFS), and assess TTT. All animals had DR and MRU before and after surgery and a third DR after surgery. Piglets were sacrificed after the final DR for renal histology. A total histologic score (THS) was generated. Preoperative DR demonstrated nonobstructive RFS, timely TTT, and balanced SKF in all 20 kidneys. After ureteral ligature, MRU demonstrated pelvic dilatation in all piglets. The postoperative DRs revealed 12 kidneys with delayed TTT in one or both follow-ups. In these 12 kidneys, the SKF declined from 51% +/- 4% to 18% +/- 14%, and the THS was 9.0 +/- 4.0. Three kidneys always had timely TTT, balanced SKF, and a THS of 1.8 +/- 0.3. The contralateral, nonoperated kidneys had timely TTT and a THS of 1.2 +/- 0.9. Postoperative scintigrams showed that 3 of 8 kidneys (38%) with an obstructive RFS had timely TTT, which demonstrates that TTT and RFS are not equivalent. In hydronephrosis, a delayed TTT of (99m)Tc-MAG3 accompanies both functional decline and histomorphologic restructuring in obstruction. According to the literature, a delayed TTT is determined by the filtration fraction of the kidneys and appears to identify an obstruction-mediated upregulated renin-angiotensin system.
Xu, Bo; Hu, Jinghai; Chen, Anxiang; Hao, Yuanyuan; Liu, GuoHui; Wang, Chunxi; Wang, Xiaoqing
2017-06-01
The present study was designed to investigate the risk factors affecting the conversion to open surgery in retroperitoneal laparoscopic nephrectomy of nonfunctioning renal tuberculosis (TB). The records of 144 patients who underwent a retroperitoneal laparoscopic nephrectomy procedure by a single surgeon were retrospectively reviewed. The following factors, including age, sex, body mass index (BMI), diabetes status, hypertension status, side of kidney, size of kidney, degree of calcification, mild perirenal extravasation, contralateral hydronephrosis, the time of anti-TB, and surgeon experience were analyzed. Univariate and multivariate logistic regression analyses were used for statistical assessment. Twenty-three patients were converted to open surgery and the conversion rate was 15.97%. In univariate analysis, BMI ≥35 kg/m 2 (p = 0.023), hypertension (p = 0.011), diabetes (p = 0.003), and kidney size (p = 0.032) were the main factors of conversion to open surgery. Sex, age, side, anti-TB time, calcification, mild extravasation, and surgeon experience were not significantly related. In multivariate regression analysis, BMI ≥35 kg/m 2 , hypertension, diabetes, and enlargement of kidney were the most important factors for conversion to open surgery. Depending on the results achieved by a single surgeon, BMI ≥30 kg/m 2 , diabetes, hypertension, and enlargement of kidney significantly increased the conversion risk in retroperitoneal laparoscopic nephrectomy for nonfunctioning renal TB.
Ranjit, Suman; Dobrinskikh, Evgenia; Montford, John; Dvornikov, Alexander; Lehman, Allison; Orlicky, David J.; Nemenoff, Raphael; Gratton, Enrico; Levi, Moshe; Furgeson, Seth
2017-01-01
All forms of progressive renal diseases develop a final pathway of tubulointerstitial fibrosis and glomerulosclerosis. Renal fibrosis is usually quantified using histological staining, a process that is time-consuming and pathologist dependent. The work described here shows the development of a fast and operator-independent method to measure fibrosis. To study renal fibrosis, the unilateral ureteral obstruction (UUO) model was chosen. Mice develop a time-dependent increase in obstructed kidneys; contralateral kidneys are used as controls. After UUO, kidneys were analyzed at three time points: 7 days, 14 days, and 21 days. Fibrosis was investigated using FLIM (Fluorescence Lifetime Imaging) and SHG (Second Harmonic Generation) in the deep tissue imaging microscope called DIVER (Deep Imaging via Enhanced photon Recovery). This microscope was developed for deep tissue and SHG and THG (Third Harmonic Generation) imaging and has extraordinary sensitivity towards harmonic generation. SHG data suggests the presence of more fibrillar collagen in the diseased kidneys. The combinations of short wavelength FLIM and SHG analysis results in a robust analysis procedure independent of observer interpretation and let us create a criterion to quantify the extent of fibrosis directly from the image. The progression of fibrosis in UUO model has been studied using this new FLIM-SHG technique and it shows remarkable improvement in quantification of fibrosis compared to standard histological techniques. PMID:27555119
Stuart, Andrew; Butler, Alyson K
2012-10-01
One purported role of the medial olivocochlear (MOC) efferent system is to reduce the effects of masking noise. MOC system functioning can be evaluated noninvasively in humans through contralateral suppression of otoacoustic emissions. It has been suggested that the strength of the MOC efferent activity should be positively associated with listening performance in noise. The objective of the study was to further explore this notion by examining contralateral suppression of transient evoked otoacoustic emissions (TEOAEs) and sentence recognition in two noises with normal hearing young adults. A repeated measures multivariate quasi-experimental design was employed. Thirty-two normal hearing young adult females participated. Reception thresholds for sentences (RTSs) were determined monaurally and binaurally in quiet and in competing continuous and interrupted noises. Both noises had an identical power spectrum and differed only in their temporal continuity. "Release from masking" was computed by subtracting RTS signal-to-noise ratios in interrupted from continuous noise. TEOAEs were evoked with 80 dB peSPL click stimuli. To examine contralateral suppression, TEOAEs were evaluated with 60 dB peSPL click stimuli with and without a contralateral 65 dB SPL white noise suppressor. A binaural advantage was observed for RTSs in quiet and noise (p < .0001) while there was no difference between ears (p >.05). In noise, performance was superior in the interrupted noise (i.e., RTSs were lower vs. continuous noise; p < .0001). There were no statistically significant differences in TEOAE levels between ears (p >.05). There was also no significant difference in the amount of suppression between ears (p = .41). There were no significant correlations or predictive linear relations between the amount of TEOAE suppression and any indices of sentence recognition in noise (i.e., RTS signal-to-noise ratios and release from masking; p > .05). The findings are not consistent with the notion that increased medial olivocochlear efferent feedback, as assessed via contralateral suppression of TEOAEs, is associated with improved speech perception in continuous and interrupted noise. American Academy of Audiology.
Shin, Choongsoo S; Carpenter, R Dana; Majumdar, Sharmila; Ma, C Benjamin
2009-11-01
The purpose of this study was to test whether (1) the 3-dimensional in vivo patellofemoral kinematics and patellofemoral contact area of anterior cruciate ligament (ACL)-deficient knees are different from those of normal, contralateral knees and (2) ACL reconstruction restores in vivo patellofemoral kinematics and contact area. Ten ACL-deficient knees and twelve ACL-reconstructed knees, as well as the contralateral uninjured knees, were tested. Magnetic resonance imaging was performed at full extension and 40 degrees of flexion under simulated partial weight-bearing conditions. Six-degrees of freedom patellofemoral kinematics, patellofemoral contact area, and contact location were analyzed by use of magnetic resonance image-based 3-dimensional patellofemoral knee models. The patella in the ACL-deficient knees underwent significantly more lateral tilt during flexion (P < .05) and tended to translate more laterally (P = .083) than the patella in contralateral knees. After ACL reconstruction, no kinematic parameters were significantly different from those in contralateral knees. The patellofemoral contact areas of ACL-deficient knees at both the extended and flexed positions (37 +/- 22 mm(2) and 357 +/- 53 mm(2), respectively) were significantly smaller than those of contralateral knees (78 +/- 45 mm(2) and 437 +/- 119 mm(2), respectively) (P < .05). After reconstruction, the patellofemoral contact area of ACL-reconstructed knees in the extended position (86 +/- 41 mm(2)) was significantly larger (P < .05) than that of contralateral knees (50 +/- 34 mm(2)), but no difference was detected in the flexed position. Reproducibility of all patellofemoral kinematic parameters, contact centroid translation, and contact area showed coefficients of variation of less than 6.8%. ACL injuries alter patellofemoral kinematics including patellar tilt and patellar lateral translation, but ACL reconstruction with hamstring or allograft restores altered patellar tilt. ACL injuries reduce the patellofemoral contact area at both the extended and flexed positions, but ACL reconstruction enlarges the patellofemoral contact area at extension and restores the normal contact area at low angles of flexion. Level III, case-control study.
Role of the plasma cascade systems in ischemia/reperfusion injury of bone.
Zhang, Shengye; Wotzkow, Carlos; Bongoni, Anjan K; Shaw-Boden, Jane; Siegrist, Mark; Taddeo, Adriano; Blank, Fabian; Hofstetter, Willy; Rieben, Robert
2017-04-01
Ischemia/reperfusion (I/R) injury has been extensively studied in organs such as heart, brain, liver, kidney, and lung. As a vascularized organ, bone is known to be susceptible to I/R injury too, but the respective mechanisms are not well understood to date. We therefore hypothesized that, similar to other organs, plasma cascade-induced inflammation also plays a role in bone I/R injury. Reperfusion injury in rat tibia was induced by unilateral clamping of the femoral artery and additional use of a tourniquet, while keeping the femoral vein patent to prevent venous congestion. Rats were subjected to 4h ischemia and 24h reperfusion. Deposition of complement fragment C3b/c and fibrin as well as expression of tissue factor (TF), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), and E-selectin was detected by immunohistochemistry. In plasma, the levels of high mobility group box1 (HMGB1) were measured by ELISA. The total level of complement in serum was assessed by the CH50 test. Our results show that deposition of C3b/c was significantly increased with respect to healthy controls in cortical bone as well as in marrow of reperfused limbs. C3b/c deposition was also increased in cortical bone, but not in bone marrow, of contralateral limbs. Deposition of fibrin, as well as expression of PAI-1, was significantly increased in bone after ischemia and reperfusion, whereas expression of tPA was reduced. These differences were most prominent in vessels of bone, both in marrow and cortical bone, and both in reperfused and contralateral limbs. However, PAI-1, was only increased in vessels of reperfused cortical bone and there were no significant changes in expression of E-selectin. With respect to solid bone tissue, a significant increase of C3b/c and fibrin deposition was shown in osteocytes, and for fibrin also in the bone matrix, in both contralateral and reperfused cortical bone compared with normal healthy controls. A slight expression of TF was visible in osteocytes of the normal healthy control group, while TF was not present in the experimental groups. Moreover, CH50 values in serum decreased over time and HMGB1 was significantly increased in plasma of animals at the end of reperfusion. We conclude that ischemia and reperfusion of bone leads to activation of the complement and coagulation systems and a downregulation of the fibrinolytic cascade. In the acute phase, a vascular inflammation induced by activation of the plasma cascade systems also occurs in the bone. This is similar to I/R injury of other vascularized organs and tissues. Copyright © 2017 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gebauer, Bernhard, E-mail: bernhard.gebauer@charite.de; Werk, Michael; Lopez-Haenninen, Enrique
Purpose. To evaluate the feasibility and safety of minimally invasive, percutaneous techniques in metachronous recurrent renal cell cancers (RCCs) in solitary kidneys. Methods. In 4 patients, recurrent RCC was treated by radiofrequency ablation (RFA) (RITA, StarBurst) alone, and in 2 patients by RFA in combination with superselective transarterial particle-lipiodol embolization using 3 Fr microcatheters. RFA was guided by computed tomography in 5 patients, and by magnetic resonance imaging in 1 patient. Mean tumor diameter was 26.7 mm (range 10-45 mm). All interventions were technically successful; during follow-up 1 patient developed recurrent RCC, which was retreated by RFA after embolization. Results.more » No major peri- or postprocedural complications occurred. Changes in creatinine (pre- vs. post-intervention, 122 vs. 127 {mu}mol/l) and calculated creatinine clearance (pre- vs. post-intervention, 78 vs. 73 ml/min) after ablation were minimal. Conclusion. In single kidneys, percutaneous, minimally invasive techniques are safe and feasible. In large tumors, or where there are adjacent critical structures, we prefer a combination of embolization and thermal ablation (RFA)« less
Wang, Jing; Fritzsch, Claire; Bernarding, Johannes; Krause, Thomas; Mauritz, Karl-Heinz; Brunetti, Maddalena; Dohle, Christian
2013-01-01
Mirror therapy (MT) was found to improve motor function after stroke, but its neural mechanisms remain unclear, especially in single stroke patients. The following imaging study was designed to compare brain activation patterns evoked by the mirror illusion in single stroke patients with normal subjects. Fifteen normal volunteers and five stroke patients with severe arm paresis were recruited. Cerebral activations during movement mirroring by means of a video chain were recorded with functional magnetic resonance imaging (fMRI). Single-subject analysis was performed using SPM 8. For normal subjects, ten and thirteen subjects displayed lateralized cerebral activations evoked by the mirror illusion while moving their right and left hand respectively. The magnitude of this effect in the precuneus contralateral to the seen hand was not dependent on movement speed or subjective experience. Negative correlation of activation strength with age was found for the right hand only. The activation pattern in stroke patients is comparable to that of normal subjects and present in four out of five patients. In summary, the mirror illusion can elicit cerebral activation contralateral to the perceived hand in the majority of single normal subjects, but not in all of them. This is similar even in stroke patients with severe hemiparesis.
Chaumoitre, K; Colavolpe, N; Shojai, R; Sarran, A; D' Ercole, C; Panuel, M
2007-01-01
To assess the use of diffusion-weighted magnetic resonance imaging (DW-MRI) in the evaluation of the fetal kidney and to estimate age-dependent changes in the apparent diffusion coefficient (ADC) of normal and pathological fetal kidneys. DW-MRI was performed on a 1.5-T machine at 23-38 gestational weeks in 51 pregnant women in whom the fetal kidneys were normal and in 10 whose fetuses had renal pathology (three with suspected nephropathy, three with renal tract dilatation, one with unilateral renal venous thrombosis, and three with twin-twin transfusion syndrome (TTTS)). The ADC was measured in an approximately 1-cm2 region of interest within the renal parenchyma. ADC values in normal renal parenchyma ranged from 1.1 to 1.8 10(-3) mm2 s-1. There was no significant age-dependent change in the ADC of normal kidneys. In cases of nephropathy, the ADC value was not always pathological but an ADC map could show abnormal findings. In cases of dilatation, the ADC value was difficult to determine when the dilatation was huge. In cases of TTTS, the ADC of the donor twin was higher than that of the recipient twin and the difference seemed to be related to the severity of the syndrome. Evaluation of the ADC for fetal kidneys is feasible. Fetal measurement of the ADC value and ADC maps may be useful tools with which to explore the fetal kidney when used in conjunction with current methods. DW-MR images, ADC value and ADC map seem to be useful in cases of suspected nephropathy (hyperechoic kidneys), dilated kidney and vascular pathology (renal venous thrombosis, TTTS). Copyright (c) 2006 ISUOG.
Tian, Natasha M; Pratt, Thomas; Price, David J
2008-12-01
Mammalian binocular vision relies on the divergence of retinal ganglion cell axons at the optic chiasm, with strictly controlled numbers projecting contralaterally and ipsilaterally. In mouse, contralateral projections arise from the entire retina, whereas ipsilateral projections arise from ventrotemporal retina. We investigate how development of these patterns of projection is regulated by the contralateral determinant Foxg1, a forkhead box transcription factor expressed in nasal retina and at the chiasm. In nasal retina, loss of Foxg1 causes increased numbers of ipsilateral projections and ectopic expression of the ipsilateral determinants Zic2, Ephb1 and Foxd1, indicating that nasal retina is competent to express an ipsilateral program that is normally suppressed by Foxg1. Using co-cultures that combine Foxg1-expressing with Foxg1-null retinal explants and chiasm cells, we provide functional evidence that Foxg1 promotes contralateral projections through actions in nasal retina, and that in chiasm cells, Foxg1 is required for the generation of a hitherto unrecognized activity supporting RGC axon growth.
Brown, Timothy S; Wimberly, Robert L; Birch, John G
2017-01-01
Congenital femoral deficiency is an uncommon clinical entity. We report 3 patients who developed avascular necrosis of the hip in the long (normal) leg during longitudinal observation and/or treatment of congenital femoral deficiency. Patients were identified in limb length discrepancy clinic and their charts were retrospectively reviewed for clinical and radiographic data collection. We describe the occurrence of idiopathic avascular necrosis in the normal limb in patients being followed for limb length discrepancy. Although no conclusion could be drawn about the etiology of the avascular necrosis, we describe a previously undocumented relationship between congenital femoral deficiency and avascular necrosis in the contralateral hip. This occurred in our congenital femoral deficiency population at a rate higher than expected compared with published incidences of avascular necrosis of the hip in children. Level IV-case series.
Zhang, Min; Sun, Xinhai; Zhang, Zhengjun; Meng, Qiang; Wang, Yuzhong; Chen, Jing; Ma, Xueqin; Geng, Houfa; Sun, Lin
2014-01-01
The aim of this study was to investigate the possible brain metabolic alterations in patients with type 2 diabetes mellitus (T2DM) and cerebral infarction (DMCI) using proton magnetic resonance spectroscopy (MRS). Thirty-four patients with T2DM and DMCI were scanned together with 33 patients with nondiabetic cerebral infarction (NDCI) on a 1.5-T MRI/MRS imager. Voxels were placed in the infarcted area and the contralateral normal area in the basal ganglia. N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and lactate (Lac)/Cr ratios were calculated. Cerebral NAA/Cr ratios in the infarcted area were lower than those in the contralateral normal area of the NDCI group. There was a significant decrease in NAA/Cr in the infarcted area of the DMCI group as compared with the infarcted area of the NDCI group. NAA/Cr ratios in the contralateral normal area of DMCI group were lower than those of the NDCI group. Lac/Cr ratios were increased in the infarcted area of both the DMCI group and NDCI group, and Lac/Cr ratios tended to be higher in the infarcted area of the DMCI group than those of the NDCI group. Glycosylated hemoglobin (HbA1c) levels were negatively correlated with NAA/Cr ratios. The study suggested that the metabolite changes were different between DMCI patients and NDCI patients, which may provide important information in the treatment of DMCI.
Al-Hunayan, A; Al-Ateeqi, A; Kehinde, E O; Thalib, L; Loutfi, I; Mojiminiyi, O A
2008-01-01
To determine the diagnostic accuracy of spot urine creatinine concentration (UCC) as a new test for the evaluation of differential renal function in obstructed kidneys (DRF(ok)) drained by percutaneous nephrostomy tube (PCNT). In patients with obstructed kidneys drained by PCNT, DRF(ok) was derived from UCC by comparing the value of UCC in the obstructed kidney to the value in the contralateral kidney, and was derived from dimercaptosuccinic acid (DMSA) renal scans and creatinine clearance (CCr) using standard methods. Subsequently, the results of UCC were compared to the results of DMSA and CCr. 61 patients were enrolled. Bland-Altman plots to compare DMSA and UCC showed that the upper limit of agreement was 14.8% (95% CI 10.7-18.5) and the lower limit was -19.9% (95% CI -23.8 to -16.1). The sensitivity and specificity of detecting DMSA DRF(ok) < or = 35% using UCC was 85.2 and 91.2%, respectively. When UCC was compared to CCr, Bland-Altman tests gave an upper limit of agreement of 10.4% (95% CI 7.9-12.8) and a lower limit of agreement of -11.3% (95% CI -13.8 to -8.9). UCC is accurate in the estimation of DRF(ok) drained by PCNT. 2008 S. Karger AG, Basel
... sudden blood loss, long-term diseases, kidney failure , aplastic anemia , or man-made heart valves). MCV above normal. ... sudden blood loss, long-term diseases, kidney failure, aplastic anemia, or man-made heart valves). MCH above normal. ...
Papazova, Diana A; Friederich-Persson, Malou; Joles, Jaap A; Verhaar, Marianne C
2015-01-01
Hypoxia is an acknowledged pathway to renal injury and ischemia-reperfusion (I/R) and is known to reduce renal oxygen tension (Po2). We hypothesized that renal I/R increases oxidative damage and induces mitochondrial uncoupling, resulting in increased oxygen consumption and hence kidney hypoxia. Lewis rats underwent syngenic renal transplantation (TX) and contralateral nephrectomy. Controls were uninephrectomized (1K-CON) or left untreated (2K-CON). After 7 days, urinary excretion of protein and thiobarbituric acid-reactive substances were measured, and after 14 days glomerular filtration rate (GFR), renal blood flow, whole kidney Qo2, cortical Po2, kidney cortex mitochondrial uncoupling, renal oxidative damage, and tubulointerstitial injury were assessed. TX, compared with 1K-CON, resulted in mitochondrial uncoupling mediated via uncoupling protein-2 (16 ± 3.3 vs. 0.9 ± 0.4 pmol O2 · s(-1)· mg protein(-1), P < 0.05) and increased whole kidney Qo2 (55 ± 16 vs. 33 ± 10 μmol O2/min, P < 0.05). Corticomedullary Po2 was lower in TX compared with 1K-CON (30 ± 13 vs. 47 ± 4 μM, P < 0.05) whereas no significant difference was observed between 2K-CON and 1K-CON rats. Proteinuria, oxidative damage, and the tubulointerstitial injury score were not significantly different in 1K-CON and TX. Treatment of donors for 5 days with mito-TEMPO reduced mitochondrial uncoupling but did not affect renal hemodynamics, Qo2, Po2, or injury. Collectively, our results demonstrate increased mitochondrial uncoupling as an early event after experimental renal transplantation associated with increased oxygen consumption and kidney hypoxia in the absence of increases in markers of damage. Copyright © 2015 the American Physiological Society.
Osthole ameliorates renal ischemia-reperfusion injury in rats.
Zheng, Yi; Lu, Min; Ma, Lulin; Zhang, Shudong; Qiu, Min; Wang, Yunpeng
2013-07-01
Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury. The pathogenetic mechanisms underlying I/R injury involve oxidative stress and apoptosis. Osthole, a natural coumarin derivative, has been reported to possess antioxidant and antiapoptotic activities. This study aimed to investigate the potential effects of osthole on renal I/R injury in an in vivo rat model. We induced renal I/R injury by clamping the left renal artery for 45 min followed by reperfusion, along with a contralateral nephrectomy. We randomly assigned 54 rats to three groups (18 rats/group): sham-operated, vehicle-treated I/R, and osthole-treated I/R. We treated rats intraperitoneally with osthole (40 mg/kg) or vehicle (40 mg/kg) 30 min before renal ischemia. We harvested serum and kidneys at 1, 6, and 24 h after reperfusion. Renal function and histological changes were assessed. We also determined markers of oxidative stress and cell apoptosis in kidneys. Osthole treatment significantly attenuated renal dysfunction and histologic damage induced by I/R injury. The I/R-induced elevation in kidney malondialdehyde level decreased, whereas reduced kidney superoxide dismutase and catalase activities were markedly increased. Moreover, osthole-treated rats had a dramatic decrease in apoptotic tubular cells, along with a decrease in caspase-3 and an increase in the Bcl-2/Bax ratio. Osthole treatment protects murine kidney from renal I/R injury by suppressing oxidative stress and cell apoptosis. Thus, osthole may represent a novel practical strategy to prevent renal I/R injury. Copyright © 2013 Elsevier Inc. All rights reserved.
Forbes, Michael S.; Thornhill, Barbara A.; Galarreta, Carolina I.; Minor, Jordan J.; Gordon, Katherine A.
2013-01-01
Unilateral ureteral obstruction (UUO) in the adult mouse is the most widely used model of progressive renal disease: the proximal tubule is the nephron segment most severely affected and atubular glomeruli are formed after only 7 days of UUO. To determine the proximal nephron response to UUO in the maturing kidney, neonatal mice were examined 7 to 28 days following complete UUO under general anesthesia. Proximal tubular mass and maturation were determined by staining with Lotus tetragolonobus lectin. Superoxide was localized by nitroblue tetrazolium and collagen by Sirius red. Cell proliferation, cell death, PAX-2, megalin, α-smooth muscle actin (α-SMA), renin, and fibronectin were identified by immunohistochemistry. During the first 14 days of ipsilateral UUO, despite oxidative stress (4-hydroxynonenal staining), glomerulotubular continuity was maintained and mitochondrial superoxide production persisted. However, from 14 to 28 days, papillary growth was impaired and proximal tubules collapsed with increased apoptosis, autophagy, mitochondrial loss, and formation of atubular glomeruli. Fibronectin, α-SMA, and collagen increased in the obstructed kidney. Oxidative stress was present also in the contralateral kidney: renin was decreased, glomerulotubular maturation and papillary growth were delayed, followed by increased cortical and medullary growth. We conclude that neonatal UUO initially delays renal maturation and results in oxidative stress in both kidneys. In contrast to the adult, proximal tubular injury in the neonatal obstructed kidney is delayed at 14 days, followed only later by the formation of atubular glomeruli. Antioxidant therapies directed at proximal tubular mitochondria during early renal maturation may slow progression of congenital obstructive nephropathy. PMID:24107422
DOE Office of Scientific and Technical Information (OSTI.GOV)
Krayenbuehl, Jerome; Hartmann, Matthias; Lomax, Anthony J.
Purpose: To perform comparative planning for intensity-modulated radiotherapy (IMRT) and proton therapy (PT) for malignant pleural mesothelioma after radical surgery. Methods and Materials: Eight patients treated with IMRT after extrapleural pleuropneumonectomy (EPP) were replanned for PT, comparing dose homogeneity, target volume coverage, and mean and maximal dose to organs at risk. Feasibility of PT was evaluated regarding the dose distribution with respect to air cavities after EPP. Results: Dose coverage and dose homogeneity of the planning target volume (PTV) were significantly better for PT than for IMRT regarding the volume covered by >95% (V95) for the high-dose PTV. The meanmore » dose to the contralateral kidney, ipsilateral kidney, contralateral lung, liver, and heart and spinal cord dose were significantly reduced with PT compared with IMRT. After EPP, air cavities were common (range, 0-850 cm{sup 3}), decreasing from 0 to 18.5 cm{sup 3}/day. In 2 patients, air cavity changes during RT decreased the generalized equivalent uniform dose (gEUD) in the case of using an a value of < - 10 to the PTV2 to <2 Gy in the presence of changing cavities for PT, and to 40 Gy for IMRT. Small changes were observed for gEUD of PTV1 because PTV1 was reached by the beams before air. Conclusion: Both PT and IMRT achieved good target coverage and dose homogeneity. Proton therapy accomplished additional dose sparing of most organs at risk compared with IMRT. Proton therapy dose distributions were more susceptible to changing air cavities, emphasizing the need for adaptive RT and replanning.« less
Loss of CD11b Exacerbates Murine Complement-Mediated Tubulointerstitial Nephritis
Wang, Ying; Chang, Anthony; Haas, Mark; Quigg, Richard John
2014-01-01
Acute complement activation occurs in the tubulointerstitium (TI) of kidneys transplanted from Crry−/−C3−/− mice into complement-sufficient wildtype mice, followed by marked inflammatory cell infiltration, tubular damage and interstitial fibrosis. We postulated iC3b-CD11b interactions were critical in this TI nephritis model. We transplanted Crry−/−C3−/− mouse kidneys into CD11b−/− and wildtype C57BL/6 mice. Surprisingly, there was greater inflammation in Crry−/−C3−/− kidneys in CD11b−/− recipients compared to those in wildtype hosts. Kidneys in CD11b−/− recipients had large numbers of CD11b−Ly6ChiCCR2hiF4/80+ cells consistent with inflammatory (M1) macrophages recruited from circulating monocytes of the host CD11b−/− animal. There was also an expanded population of CD11b+CD11c+Ly6C−F4/80hi cells. Since these cells were CD11b+, they must have originated from the transplanted kidney; their surface protein expression and appearance within the kidney were consistent with the intrinsic renal mononuclear cellular population. These cells were markedly expanded relative to all relevant controls, including the contralateral donor kidney and Crry−/−C3−/− mouse kidneys in CD11b+/+ wildtype recipients. Direct evidence for their in situ proliferation was the presence of nuclear Ki67 and PCNA in CD11b+F4/80+ cells. Thus, in this experimental model in which there is unrestricted C3 activation, CD11b+ monocytes limit their own infiltration into the kidney and prevent proliferation of endogenous mononuclear cells. This suggests a role for outside-in iC3b-CD11b signals in limiting intrinsic organ inflammation. PMID:24632830
Brantberg, Krister; Westin, Magnus; Löfqvist, Lennart; Verrecchia, Luca; Tribukait, Arne
2009-05-01
To explore the mechanisms for skull tap induced vestibular evoked myogenic potentials (VEMP). The muscular responses were recorded over both sternocleidomastoid (SCM) muscles using skin electrodes. A skull tapper which provided a constant stimulus intensity was used to test cervical vestibular evoked myogenic potentials (VEMP) in response to lateral skull taps in healthy subjects (n=10) and in patients with severe unilateral loss of vestibular function (n=10). Skull taps applied approximately 2 cm above the outer ear canal caused highly reproducible VEMP. There were differences in VEMP in both normals and patients depending on side of tapping. In normals, there was a positive-negative ("normal") VEMP on the side contra-lateral to the skull tapping, but no significant VEMP ipsi-laterally. In patients, skull taps above the lesioned ear caused a contra-lateral positive-negative VEMP (as it did in the normals), in addition there was an ipsi-lateral negative-positive ("inverted") VEMP. When skull taps were presented above the healthy ear there was only a small contra-lateral positive-negative VEMP but, similar to the normals, no VEMP ipsi-laterally. The present data, in conjunction with earlier findings, support a theory that skull-tap VEMP responses are mediated by two different mechanisms. It is suggested that skull tapping causes both a purely ipsi-lateral stimulus side independent SCM response and a bilateral and of opposite polarity SCM response that is stimulus side dependent. Possibly, the skull tap induced VEMP responses are the sum of a stimulation of two species of vestibular receptors, one excited by vibration (which is rather stimulus site independent) and one excited by translation (which is more stimulus site dependent). Skull-tap VEMP probably have two different mechanisms. Separation of the two components might reveal the status of different labyrinthine functions.
Gradinaru, S; Totir, M; Iancu, R; Leasu, C; Pricopie, S; Yasin, S; Ciuluvica, R; Ungureanu, E
2014-01-01
This study reports our results relating to palpebral eyelid fissure and orbital measurements following evisceration with orbital implantation of hydroxyapatite integrated implant and PMMA implant. This study is a prospective study of 43 patients that underwent evisceration for different ocular affections at University Emergency Hospital Bucharest, Ophthalmology department between January 2009 and September 2010 (Group A comprising of twenty patients had the coralline hydroxyapatite implant -Integrated Ocular Implants, USA and Group B comprising of twenty-three received non-integrated PMMA ocular implants) .The outcomes measured were the degree of exo /enophthalmos, horizontal eyelid fissure and palpebral fissure height at 4 years after surgical intervention related to measurement to the contralateral eye. Horizontal eyelid fissure (HEF) was suffering a shortening of 7.4% in the group B versus the contralateral eye, and only 1.9% in the group A related to the contralateral eye. Eyelid fissure height was greater in the group B with 5.2% regarding the contralateral eye, and 1.2% in group A. The degree of enophthalmia was higher in the group B of 4 mm versus the contralateral eye and lower in group A 1.5 mm regarding the contralateral eye. . Although a hydroxyapatite implant may be not as economic as a PMMA implant, a patient must be warned about the effect on its ocular structures in time and that cosmetic appearance over years will change more dramatically than in the fellow normal eye. Therefore preoperative counseling of the patient is crucial in long term patient satisfaction.
Renal Parenchymal Area Growth Curves for Children 0 to 10 Months Old.
Fischer, Katherine; Li, Chunming; Wang, Huixuan; Song, Yihua; Furth, Susan; Tasian, Gregory E
2016-04-01
Low renal parenchymal area, which is the gross area of the kidney in maximal longitudinal length minus the area of the collecting system, has been associated with increased risk of end stage renal disease during childhood in boys with posterior urethral valves. To our knowledge normal values do not exist. We aimed to increase the clinical usefulness of this measure by defining normal renal parenchymal area during infancy. In a cross-sectional study of children with prenatally detected mild unilateral hydronephrosis who were evaluated between 2000 and 2012 we measured the renal parenchymal area of normal kidney(s) opposite the kidney with mild hydronephrosis. Measurement was done with ultrasound from birth to post-gestational age 10 months. We used the LMS method to construct unilateral, bilateral, side and gender stratified normalized centile curves. We determined the z-score and the centile of a total renal parenchymal area of 12.4 cm(2) at post-gestational age 1 to 2 weeks, which has been associated with an increased risk of kidney failure before age 18 years in boys with posterior urethral valves. A total of 975 normal kidneys of children 0 to 10 months old were used to create renal parenchymal area centile curves. At the 97th centile for unilateral and single stratified curves the estimated margin of error was 4.4% to 8.8%. For bilateral and double stratified curves the estimated margin of error at the 97th centile was 6.6% to 13.2%. Total renal parenchymal area less than 12.4 cm(2) at post-gestational age 1 to 2 weeks had a z-score of -1.96 and fell at the 3rd percentile. These normal renal parenchymal area curves may be used to track kidney growth in infants and identify those at risk for chronic kidney disease progression. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Segmental Blood Flow and Hemodynamic State of Lymphedematous and Nonlymphedematous Arms
Montgomery, Leslie D.; Dietrich, Mary S.; Armer, Jane M.; Stewart, B. R.
2011-01-01
Abstract Background Findings regarding the influence hemodynamic factors, such as increased arterial blood flow or venous abnormalities, on breast cancer treatment-related lymphedema are mixed. The purpose of this study was to compare segmental arterial blood flow, venous blood return, and blood volumes between breast cancer survivors with treatment-related lymphedema and healthy normal individuals without lymphedema. Methods and Results A Tetrapolar High Resolution Impedance Monitor and Cardiotachometer were used to compare segmental arterial blood flow, venous blood return, and blood volumes between breast cancer survivors with treatment-related lymphedema and healthy normal volunteers. Average arterial blood flow in lymphedema-affected arms was higher than that in arms of healthy normal volunteers or in contralateral nonlymphedema affected arms. Time of venous outflow period of blood flow pulse was lower in lymphedema-affected arms than in healthy normal or lymphedema nonaffected arms. Amplitude of the venous component of blood flow pulse signal was lower in lymphedema-affected arms than in healthy or lymphedema nonaffected arms. Index of venular tone was also lower in lymphedema-affected arms than healthy or lymphedema nonaffected arms. Conclusions Both arterial and venous components may be altered in the lymphedema-affected arms when compared to healthy normal arms and contralateral arms in the breast cancer survivors. PMID:21417765
Preventive mechanisms of agmatine against ischemic acute kidney injury in rats.
Sugiura, Takahiro; Kobuchi, Shuhei; Tsutsui, Hidenobu; Takaoka, Masanori; Fujii, Toshihide; Hayashi, Kentaro; Matsumura, Yasuo
2009-01-28
The excitation of renal sympathetic nervous system plays an important role in the development of ischemic acute kidney injury in rats. Recently, we found that agmatine, an adrenaline alpha(2)/imidazoline I(1)-receptor agonist, has preventive effects on ischemic acute kidney injury by suppressing the enhanced renal sympathetic nerve activity during renal ischemia and by decreasing the renal venous norepinephrine overflow after reperfusion. In the present study, we investigated preventive mechanisms of agmatine against ischemic acute kidney injury in rats. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after the contralateral nephrectomy. Pretreatment with efaroxan (30 mumol/kg, i.v.), an alpha(2)/I(1)-receptor antagonist, abolished the suppressive effects of agmatine on the enhanced renal sympathetic nerve activity during renal ischemia and on the elevated norepinephrine overflow after reperfusion, and eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal dysfunction and histological damage. On the other hand, pretreatment with yohimbine (6 mumol/kg, i.v.), an alpha(2)-receptor antagonist, eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal injury and norepinephrine overflow, without affecting the lowering effect of agmatine on renal sympathetic nerve activity. These results indicate that agmatine prevents the ischemic renal injury by sympathoinhibitory effect probably via I(1) receptors in central nervous system and by suppressing the norepinephrine overflow through alpha(2) or I(1) receptors on sympathetic nerve endings.
Thapa, N B; Shah, S; Pradhan, A; Rijal, K; Pradhan, A; Basnet, S
2015-01-01
Background Ultrasonography is one of the most common imaging modality to measure dimensions of visceral organs in children. However, the normal limit of size of visceral organs according to age and body habitus has not been specified in the standard textbooks. This might result in under detection of organomegaly in pediatrics population. Objective The objective of this study was to determine the normal range of dimensions for the liver, spleen, and kidney in healthy children. Method This is prospective cross-sectional, hospital-based study done at Tertiary-care teaching hospital. Participants included 272 pediatric subjects (152 male and 120 female) with normal physical or sonographic findings who were examined because of problems unrelated to the measured organs. The subjects were one month to 15 year (180 months) old. All measured organs were sonographically normal. Relationships of the dimensions of these organs with sex, age, body weight and height were investigated. Limits of normal dimensions of these organs were defined. Result Normal length of liver, kidneys and spleen were obtained sonographically for 272 children (152 male [55.9%] and 120 female [44.1%]) in the age group from 1 months to 15 (180 months) years. The mean age was 45.78 months (SD, 44.73). The measured dimensions of all these organs showed highest correlation with height and age so the descriptive analysis of the organ dimensions (mean, minimum, and maximum values, SD and 5th and 95th percentiles) were expressed in 10 age groups along with height range of the included children. The mean length of right kidney was shorter than the left kidney length, and the difference was statistically significant (p = 0.001). Conclusion This study provides practical and comprehensive guide to the normal visceral organ dimension in pediatric population. The normal range limit of the liver, spleen, and kidney determined in this study could be used as a reference in daily practice in local radiology clinics.
Tachibana, Hidekazu; Takagi, Toshio; Kondo, Tsunenori; Ishida, Hideki; Tanabe, Kazunari
2018-04-01
To compare surgical outcomes, including renal function and the preserved renal parenchymal volume, between robot-assisted laparoscopic partial nephrectomy and laparoscopic partial nephrectomy using propensity score-matched analyses. In total, 253 patients, with a normal contralateral kidney, who underwent laparoscopic partial nephrectomy (n = 131) or robot-assisted laparoscopic partial nephrectomy (n = 122) with renal arterial clamping between 2010 and 2015, were included. Patients' background and tumor factors were adjusted by propensity score matching. Surgical outcomes, including postoperative renal function, complications, warm ischemia time and preserved renal parenchymal volume, evaluated by volumetric analysis, were compared between the surgical procedures. After matching, 64 patients were assigned to each group. The mean age was 56-57 years, and the mean tumor size was 22 mm. Approximately 50% of patients had low complexity tumors (RENAL nephrometry score 4-7). The incidence rate of acute kidney failure was significantly lower in the robot-assisted laparoscopic partial nephrectomy (11%) than laparoscopic partial nephrectomy (23%) group (P = 0.049), and warm ischemia time shorter in the robot-assisted laparoscopic partial nephrectomy (17 min) than laparoscopic partial nephrectomy (25 min) group (P < 0.0001). The preservation rate of renal function, measured by the estimated glomerular filtration rate, at 6 months post-surgery was 96% for robot-assisted laparoscopic partial nephrectomy and 90% for laparoscopic partial nephrectomy (P < 0.0001). The preserved renal parenchymal volume was higher for robot-assisted laparoscopic partial nephrectomy (89%) than laparoscopic partial nephrectomy (77%; P < 0.0001). The rate of perioperative complications, surgical margin status and length of hospital stay were equivalent for both techniques. Robot-assisted laparoscopic partial nephrectomy allows to achieve better preservation of renal function and parenchymal volume than laparoscopic partial nephrectomy. © 2018 The Japanese Urological Association.
The lateralized smell test for detecting Alzheimer's disease: failure to replicate.
Doty, Richard L; Bayona, Edgardo A; Leon-Ariza, Daniel S; Cuadros, Juan; Chung, Inna; Vazquez, Britney; Leon-Sarmiento, Fidias E
2014-05-15
A widely publicized study by Stamps, Bartoshuk and Heilman (2013) reported that a simple measure of left:right naris differences in the ability to detect the odor of peanut butter is a sensitive marker of Alzheimer's disease (AD). AD patients were said to have abnormal smell function on the left side of the nose and normal function on right side of the nose. In light of its implications for medical practice and the world-wide publicity that it engendered, we sought to replicate and expand this work. Two studies were performed. In the first, 15 AD patients were tested according to the procedures described by Stamps et al. in which the nostril contralateral to the tested side was occluded by the patient using lateral pressure from the index finger. Since this can potentially distort the contralateral naris, we repeated the testing using tape for naris occlusion. In the second, 20 AD patients were administered 20 odors of the University of Pennsylvania Smell Identification Test (UPSIT) to each side of the nose, with the contralateral naris being closed with tape. In both studies, the order of the side of testing was systematically counterbalanced. No evidence of a left:right asymmetry on any test measure was observed. Although hyposmia is well-established in AD, no meaningful asymmetry in smell perception is apparent. If olfactory function on the right side of the nose was normal as claimed, then AD patients should exhibit normal function when tested bilaterally, a phenomenon not seen in dozens of AD-related olfactory studies. Copyright © 2014 Elsevier B.V. All rights reserved.
Susceptibility weighted imaging of stroke brain in response to normobaric oxygen (NBO) therapy
NASA Astrophysics Data System (ADS)
Zhou, Iris Y.; Igarashi, Takahiro; Guo, Yingkun; Sun, Phillip Z.
2015-03-01
The neuroprotective effect of oxygen leads to recent interest in normobaric oxygen (NBO) therapy after acute ischemic stroke. However, the mechanism remains unclear and inconsistent outcomes were reported in human studies. Because NBO aims to improve brain tissue oxygenation by enhancing oxygen delivery to ischemic tissue, monitoring the oxygenation level changes in response to NBO becomes necessary to elucidate the mechanism and to assess the efficacy. Susceptibility weighted imaging (SWI) which provides a new MRI contrast by combining the magnitude and phase images is fit for purpose. SWI is sensitive to deoxyhemoglobin level changes and thus can be used to evaluate the cerebral metabolic rate of oxygen. In this study, SWI was used for in vivo monitoring of oxygenation changes in a rat model of permanent middle cerebral artery occlusion (MCAO) before, during and after 30 min of NBO treatment. Regions of interest in ischemic core, penumbra and contralateral normal area were generated based on diffusionweighted imaging and perfusion imaging. Significant differences in SWI indicating different oxygenation levels were generally found: contralateral normal > penumbra > ischemic core. Ischemic core showed insignificant increase in oxygenation during NBO and returned to pre-treatment level after termination of NBO. Meanwhile, the oxygenation levels slightly increased in contralateral normal and penumbra regions during NBO and significantly decreased to a level lower than pre-treatment after termination of NBO, indicating secondary metabolic disruption upon the termination of transient metabolic support from oxygen. Further investigation of NBO effect combined with reperfusion is necessary while SWI can be used to detect hemorrhagic transformation after reperfusion.
Spyridakou, Chrysa; Luxon, Linda M; Bamiou, Doris E
2012-07-01
To compare self-reported symptoms of difficulty hearing speech in noise and hyperacusis in adults with auditory processing disorders (APDs) and normal controls; and to compare self-reported symptoms to objective test results (speech in babble test, transient evoked otoacoustic emission [TEOAE] suppression test using contralateral noise). A prospective case-control pilot study. Twenty-two participants were recruited in the study: 10 patients with reported hearing difficulty, normal audiometry, and a clinical diagnosis of APD; and 12 normal age-matched controls with no reported hearing difficulty. All participants completed the validated Amsterdam Inventory for Auditory Disability questionnaire, a hyperacusis questionnaire, a speech in babble test, and a TEOAE suppression test using contralateral noise. Patients had significantly worse scores than controls in all domains of the Amsterdam Inventory questionnaire (with the exception of sound detection) and the hyperacusis questionnaire (P < .005). Patients also had worse TEOAE suppression test results in both ears than controls; however, this result was not significant after Bonferroni correction. Strong correlations were observed between self-reported symptoms of difficulty hearing speech in noise and speech in babble test results in the right ear (ρ = 0.624, P = .002), and between self-reported symptoms of hyperacusis and TEOAE suppression test results in the right ear (ρ = -0.597 P = .003). There was no significant correlation between the two tests. A strong correlation was observed between right ear speech in babble and patient-reported intelligibility of speech in noise, and right ear TEOAE suppression by contralateral noise and hyperacusis questionnaire. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.
Biomechanical Changes in the Sclera of Monkey Eyes Exposed to Chronic IOP Elevations
Girard, Michaël J. A.; Suh, J.-K. Francis; Bottlang, Michael; Burgoyne, Claude F.
2011-01-01
Purpose. To characterize scleral biomechanics in both eyes of eight monkeys in which chronic intraocular pressure (IOP) elevation was induced in one eye. Methods. Each posterior sclera was mounted on a pressurization apparatus, IOP was elevated from 5 to 45 mm Hg while the 3D displacements of the scleral surface were measured by speckle interferometry. Finite element (FE) models of each scleral shell were constructed that incorporated stretch-induced stiffening and multidirectionality of the collagen fibers. FE model predictions were then iteratively matched to experimental displacements to extract unique sets of scleral biomechanical properties. Results. For all eyes, the posterior sclera exhibited inhomogeneous, anisotropic, nonlinear biomechanical behavior. Biomechanical changes caused by chronic IOP elevation were complex and specific to each subject. Specifically: (1) Glaucomatous eyes in which the contralateral normal eyes displayed large modulus or thickness were less prone to biomechanical changes; (2) glaucomatous scleral modulus associated with an IOP of 10 mm Hg decreased (when compared with that of the contralateral normal) after minimal chronic IOP elevation; (3) glaucomatous scleral modulus associated with IOPs of 30 and 45 mm Hg increased (when compared with that of the contralateral normal) after moderate IOP elevation; and (4) FE-based estimates of collagen fiber orientation demonstrated no change in the glaucomatous eyes. Conclusions. Significant stiffening of the sclera follows exposure to moderate IOP elevations in most eyes. Scleral hypercompliance may precede stiffening or be a unique response to minimal chronic IOP elevation in some eyes. These biomechanical changes are likely to be the result of scleral extracellular matrix remodeling. PMID:21519033
[Renal dysplasia: clinico-pathologic review].
Cunha, A S; de Sousa, J F; Garcia, C
1992-05-01
Histology records from 63 nephrectomies were reviewed; 22 patients had unilateral totally dysplastic kidneys and 5 had polar or segmental dysplasia. A clinicopathological study of these cases was undertaken. In the first group, there was a slight male preponderance and 75% of the patients presented were under two years of age. Urinary tract infection was the most common complaint. 4 patients were diagnosed in utero by ultrasound and 5 infants presented an abdominal mass. Hypertension was documented in a newborn baby. Ipsilateral lower urinary tract anomalies were found in 12 patients and those of the contralateral kidney in 2 children. There were 3 cases of extrarenal anomalies. Histological examination revealed 13 cases of multicystic dysplasia and 9 of solid dysplasia. Metaplastic cartilage was found in 1 case. In the group of segmental dysplasia, age ranging from 27 weeks' gestation to 8 years, at the time of the diagnosis. They all had duplex kidneys and 4 had ureterocele. Histological study in these cases was similar to the one found in the previous series, although superimposed inflammatory changes were more pronounced. Some of the theories regarding the pathogenesis of this disorder are reviewed and the importance of its diagnosis is emphasised.
... be black. Other structures will be shades of gray. Veins are not normally seen in an x- ... Venogram - kidney; Renal vein thrombosis - venogram Images Kidney anatomy Kidney - blood and urine flow Renal veins References ...
Diffusion-weighted MR imaging findings of kidneys in patients with early phase of obstruction.
Bozgeyik, Zulkif; Kocakoc, Ercan; Sonmezgoz, Fitnet
2009-04-01
Diffusion-weighted (DW) magnetic resonance (MR) imaging is an MR technique used to show molecular diffusion. The apparent diffusion coefficient (ADC), as a quantitative parameter calculated from the DW MR images. The purpose of this study is to evaluate the ability of DW MR imaging in early phase of obstruction due to urolithiasis. Twenty-six patients with acute dilatation of the pelvicalyceal system detected by intravenous urography were included in this study. MR imaging was performed using a 1.5 T whole-body superconducting MR scanner. DW imaging can be performed using single-shot spin-echo, echo-planar imaging (EPI) sequences with the following diffusion gradient b values: 100, 600, 1000 s/mm(2). Circular region of interest (ROI) was placed in the renal parenchyma for the measurement of ADC values in the normal and obstructed kidney. For statistical analyses, Paired t test were used. In spite of obstructed kidneys had the lower ADC values compared to normal kidneys, these alterations were statistically insignificant. We did not observe significantly different ADC values of early phase of obstructed kidneys compared to normal kidneys.
Zachar, Rikke; Al-Mashhadi, Ammar; Dimke, Henrik; Svenningsen, Per; Jensen, Boye L; Carlström, Mattias
2018-05-16
Obstruction of urine flow at the level of the pelvo-ureteric junction (UPJO) and subsequent development of hydronephrosis is one of the most common congenital renal malformations. UPJO is associated with development of salt-sensitive hypertension, which is set by the obstructed kidney, and with a stimulated renin-angiotensin-aldosterone system (RAAS) in rodent models. This study aimed at investigating the hypothesis that i) in pediatric patients with UPJO the RAAS is activated prior to surgical relief of the obstruction; ii) in rats with UPJO the RAAS activation is reflected by increased abundance of renal aldosterone-stimulated Na+ transporters; and iii) the injured UPJO kidney allows aberrant filtration of plasminogen leading to proteolytic activation of the epithelial sodium channel gamma subunit (γ-ENaC). Hydronephrosis due to UPJO in pediatric patients and rats was associated with increased urinary plasminogen/creatinine ratio. In pediatric patients, plasma renin, angiotensin II, urine and plasma aldosterone and urine soluble pro-renin receptor did not differ significantly before and after surgery, or compared with controls. Increased plasmin/plasminogen ratio was seen in UPJO rats. Intact γ-ENaC abundance was not changed in UPJO kidney while low-molecular cleavage product abundance increased. The Na-Cl cotransporter (NCC) displayed significantly lower abundance in the UPJO kidney compared to the non-obstructed contralateral kidney. The Na-K-ATPase alpha-subunit was unaltered. Treatment with an angiotensin-converting enzyme inhibitor (8 days, captopril) significantly lowered blood pressure in UPJO rats. It is concluded that the RAAS contributes to hypertension following partial obstruction of urine flow at the pelvo-ureteric junction with potential contribution from proteolytic activation of ENaC.
Wahab, Suzaily; Abdul Rahman, Abdul Hamid; Sidek, Dinsuhaimi; Zakaria, Mohd. Normani
2016-01-01
Objective Electrophysiological studies, which are mostly focused on afferent pathway, have proven that auditory processing deficits exist in patients with schizophrenia. Nevertheless, reports on the suppressive effect of efferent auditory pathway on cochlear outer hair cells among schizophrenia patients are limited. The present, case-control, study examined the contralateral suppression of transient evoked otoacoustic emissions (TEOAEs) in patients with schizophrenia. Methods Participants were twenty-three healthy controls and sixteen schizophrenia patients with normal hearing, middle ear and cochlear outer hair cells function. Absolute non-linear and linear TEOAEs were measured in both ears by delivering clicks stimuli at 80 dB SPL and 60 dB SPL respectively. Subsequently, contralateral suppression was determined by subtracting the absolute TEOAEs response obtained at 60 dBpe SPL during the absence and presence of contralateral white noise delivered at 65 dB HL. No attention tasks were conducted during measurements. Results We found no significant difference in absolute TEOAEs responses at 80 dB SPL, in either diagnosis or ear groups (p>0.05). However, the overall contralateral suppression was significantly larger in schizophrenia patients (p<0.05). Specifically, patients with schizophrenia demonstrated significantly increased right ear contralateral suppression compared to healthy control (p<0.05). Conclusion The present findings suggest increased inhibitory effect of efferent auditory pathway especially on the right cochlear outer hair cells. Further studies to investigate increased suppressive effects are crucial to expand the current understanding of auditory hallucination mechanisms in schizophrenia patients. PMID:26766950
"Facilitated" amino acid transport is upregulated in brain tumors.
Miyagawa, T; Oku, T; Uehara, H; Desai, R; Beattie, B; Tjuvajev, J; Blasberg, R
1998-05-01
The goal of this study was to determine the magnitude of "facilitated" amino acid transport across tumor and brain capillaries and to evaluate whether amino acid transporter expression is "upregulated" in tumor vessels compared to capillaries in contralateral brain tissue. Aminocyclopentane carboxylic acid (ACPC), a non-metabolized [14C]-labeled amino acid, and a reference molecule for passive vascular permeability, [67Ga]-gallium-diethylenetriaminepentaacetic acid (Ga-DTPA), were used in these studies. Two experimental rat gliomas were studied (C6 and RG2). Brain tissue was rapidly processed for double label quantitative autoradiography 10 minutes after intravenous injection of ACPC and Ga-DTPA. Parametric images of blood-to-brain transport (K1ACPC and K1Ga-DTPA, microL/min/g) produced from the autoradiograms and the histology were obtained from the same tissue section. These three images were registered in an image array processor; regions of interest in tumor and contralateral brain were defined on morphologic criteria (histology) and were transferred to the autoradiographic images to obtain mean values. The facilitated component of ACPC transport (deltaK1ACPC) was calculated from the K1ACPC and K1Ga-DTPA data, and paired comparisons between tumor and contralateral brain were performed. ACPC flux, K1ACPC, across normal brain capillaries (22.6 +/- 8.1 microL/g/min) was >200-fold greater than that of Ga-DTPA (0.09 +/- 0.04 microL/g/min), and this difference was largely (approximately 90%) due to facilitated ACPC transport. Substantially higher K1ACPC values compared to corresponding K1DTPA values were also measured in C6 and RG2 gliomas. The deltaK1ACPC values for C6 glioma were more than twice that of contralateral brain cortex. K1ACPC and deltaK1ACPC values for RG2 gliomas was not significantly higher than that of contralateral cortex, although a approximately 2-fold difference in facilitated transport is obtained after normalization for differences in capillary surface area between RG2 tumors and contralateral cortex. K1ACPC, deltaK1ACPC, and K DTPA were directly related to tumor cell density, were higher in regions of "impending" necrosis, and the tumor/contralateral brain ACPC radio-activity ratios (0 to 10 minutes) were very similar to that obtained with 0 to 60 minutes experiments. These results indicate that facilitated transport of ACPC is upregulated across C6 and RG2 glioma capillaries, and that tumors can induce upregulation of amino acid transporter expression in their supporting vasculature. They also suggest that early imaging (e.g., 0 to 20 minutes) with radiolabeled amino acids in a clinical setting may be optimal for defining brain tumors.
The normal and pathologic renal medulla: a comprehensive overview.
López, José I; Larrinaga, Gorka; Kuroda, Naoto; Angulo, Javier C
2015-04-01
The renal medulla comprises an intricate system of tubules, blood vessels and interstitium that is not well understood by most general pathologists. We conducted an extensive review of the literature on the renal medulla, in both normal and pathologic conditions. We set out in detail the points of key interest to pathologists: normal and pathological development, physiology, microscopic anatomy, histology and immunohistochemistry; and the specific and most common other types of disease associated with this part of the kidney: developmental abnormalities, (multicystic dysplastic kidney, autosomal dominant and recessive polycystic kidney diseases, medullary cystic kidney disease), inflammatory conditions (xanthogranulomatous pyelonephritis, malakoplakia), hyperplasia and dysplasia, and neoplastic processes (oncocytoma, atypical oncocytic tumors, chromophobe cell carcinoma, collecting duct carcinoma, urothelial carcinoma, other carcinomas, renal medullary fibroma and metastatic tumors). This condensed overview of the origin, function and pathology of the renal medulla, both in terms of development, inflammation and neoplastic processes, should help focus the interest of clinical pathologists on this widely overlooked part of the kidney. Copyright © 2014 Elsevier GmbH. All rights reserved.
Potential Use of Autologous Renal Cells from Diseased Kidneys for the Treatment of Renal Failure.
George, Sunil K; Abolbashari, Mehran; Jackson, John D; Aboushwareb, Tamer; Atala, Anthony; Yoo, James J
2016-01-01
Chronic kidney disease (CKD) occurs when certain conditions cause the kidneys to gradually lose function. For patients with CKD, renal transplantation is the only treatment option that restores kidney function. In this study, we evaluated primary renal cells obtained from diseased kidneys to determine whether their normal phenotypic and functional characteristics are retained, and could be used for cell therapy. Primary renal cells isolated from both normal kidneys (NK) and diseased kidneys (CKD) showed similar phenotypic characteristics and growth kinetics. The expression levels of renal tubular cell markers, Aquaporin-1 and E-Cadherin, and podocyte-specific markers, WT-1 and Nephrin, were similar in both NK and CKD kidney derived cells. Using fluorescence- activated cell sorting (FACS), specific renal cell populations were identified and included proximal tubular cells (83.1% from NK and 80.3% from CKD kidneys); distal tubular cells (11.03% from NK and 10.9% from CKD kidneys); and podocytes (1.91% from NK and 1.78% from CKD kidneys). Ultra-structural analysis using scanning electron microscopy (SEM) revealed microvilli on the apical surface of cultured cells from NK and CKD samples. Moreover, transmission electron microscopy (TEM) analysis showed a similar organization of tight junctions, desmosomes, and other intracellular structures. The Na+ uptake characteristics of NK and CKD derived renal cells were also similar (24.4 mmol/L and 25 mmol/L, respectively) and no significant differences were observed in the protein uptake and transport characteristics of these two cell isolates. These results show that primary renal cells derived from diseased kidneys such as CKD have similar structural and functional characteristics to their counterparts from a normal healthy kidney (NK) when grown in vitro. This study suggests that cells derived from diseased kidney may be used as an autologous cell source for renal cell therapy, particularly in patients with CKD or end-stage renal disease (ESRD).
The MOC reflex during active listening to speech.
Garinis, Angela C; Glattke, Theodore; Cone, Barbara K
2011-10-01
The purpose of this study was to test the hypothesis that active listening to speech would increase medial olivocochlear (MOC) efferent activity for the right vs. the left ear. Click-evoked otoacoustic emissions (CEOAEs) were evoked by 60-dB p.e. SPL clicks in 13 normally hearing adults in 4 test conditions for each ear: (a) in quiet; (b) with 60-dB SPL contralateral broadband noise; (c) with words embedded (at -3-dB signal-to-noise ratio [SNR]) in 60-dB SPL contralateral noise during which listeners directed attention to the words; and (d) for the same SNR as in the 3rd condition, with words played backwards. There was greater suppression during active listening compared with passive listening that was apparent in the latency range of 6- to 18-ms poststimulus onset. Ear differences in CEOAE amplitude were observed in all conditions, with right-ear amplitudes larger than those for the left. The absolute difference between CEOAE amplitude in quiet and with contralateral noise, a metric of suppression, was equivalent for right and left ears. When the amplitude differences were normalized, suppression was greater for noise presented to the right and the effect measured for a probe in the left ear. The findings support the theory that cortical mechanisms involved in listening to speech affect cochlear function through the MOC efferent system.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Krayenbuehl, Jerome Dipl.Phys. E.T.H.; Oertel, Susanne; Davis, J. Bernard
Purpose: The optimal technique for postoperative radiotherapy (RT) after extrapleural pleuropneumonectomy (EPP) of malignant pleural mesothelioma (MPM) remains debated. Methods and Materials: The data from 8 right-sided and 9 left-sided consecutive cases of MPM treated with RT after radical EPP were reviewed. Of the 17 patients, 8 had been treated with three-dimensional (3D) conformal RT (3D-CRT) and 9 with intensity-modulated RT (IMRT) with 6-MV photons. The clinical outcome and adverse events were assessed. For comparative planning, each case was replanned with 3D-CRT using photons and electrons or with IMRT. Homogeneity, doses to the organs at risk, and target volume coveragemore » were analyzed. Results: Both techniques yielded acceptable plans. The dose coverage and homogeneity of IMRT increased by 7.7% for the first planning target volume and 9.7% for the second planning target volume, ensuring {>=}95% of the prescribed dose compared with 3D-CRT (p < 0.01). Compared with 3D-CRT, IMRT increased the dose to the contralateral lung, with an increase in the mean lung dose of 7.8 Gy and an increase in the volume receiving 13 Gy and 20 Gy by 20.5% and 7.2%, respectively (p < 0.01). A negligible dose increase to the contralateral kidney and liver was observed. No differences were seen for the spinal cord and ipsilateral kidney. Two adverse events of clinical relevant lung toxicity were observed with IMRT. Conclusion: Intensity-modulated RT and 3D-CRT are both suitable for adjuvant RT. IMRT improves the planning target volume coverage but delivered greater doses to the organs at risk. Rigid dose constraints for the lung should be respected.« less
Castro, Pedro; Azevedo, Elsa; Rocha, Isabel; Sorond, Farzaneh; Serrador, Jorge M
2018-03-02
Chronic kidney disease increases stroke incidence and severity but the mechanisms behind this cerebro-renal interaction are mostly unexplored. Since both vascular beds share similar features, microvascular dysfunction could be the possible missing link. Therefore, we examined the relationship between renal function and cerebral autoregulation in the early hours post ischemia and its impact on outcome. We enrolled 46 ischemic strokes (middle cerebral artery). Dynamic cerebral autoregulation was assessed by transfer function (coherence, phase and gain) of spontaneous blood pressure oscillations to blood flow velocity within 6 h from symptom-onset. Estimated glomerular filtration rate (eGFR) was calculated. Hemorrhagic transformation (HT) and white matter lesions (WML) were collected from computed tomography performed at presentation and 24 h. Outcome was evaluated with modified Rankin Scale at 3 months. High gain (less effective autoregulation) was correlated with lower eGFR irrespective of infarct side (p < 0.05). Both lower eGFR and higher gain correlated with WML grade (p < 0.05). Lower eGFR and increased gain, alone and in combination, progressively reduced the odds of a good functional outcome [ipsilateral OR = 4.39 (CI95% 3.15-25.6), p = 0.019; contralateral OR = 8.15 (CI95% 4.15-15.6), p = 0.002] and increased risk of HT [ipsilateral OR = 3.48 (CI95% 0.60-24.0), p = 0.132; contralateral OR = 6.43 (CI95% 1.40-32.1), p = 0.034]. Lower renal function correlates with less effective dynamic cerebral autoregulation in acute ischemic stroke, both predicting a bad outcome. The evaluation of serum biomarkers of renal dysfunction could have interest in the future for assessing cerebral microvascular risk and relationship with stroke complications.
Stability of the Medial Olivocochlear Reflex as Measured by Distortion Product Otoacoustic Emissions
Abdala, Carolina
2015-01-01
Purpose The purpose of this study was to assess the repeatability of a fine-resolution, distortion product otoacoustic emission (DPOAE)–based assay of the medial olivocochlear (MOC) reflex in normal-hearing adults. Method Data were collected during 36 test sessions from 4 normal-hearing adults to assess short-term stability and 5 normal-hearing adults to assess long-term stability. DPOAE level and phase measurements were recorded with and without contralateral acoustic stimulation. MOC reflex indices were computed by (a) noting contralateral acoustic stimulation-induced changes in DPOAE level (both absolute and normalized) at fine-structure peaks, (b) recording the effect as a vector difference, and (c) separating DPOAE components and considering a component-specific metric. Results Analyses indicated good repeatability of all indices of the MOC reflex in most frequency ranges. Short- and long-term repeatability were generally comparable. Indices normalized to a subject's own baseline fared best, showing strong short- and long-term stability across all frequency intervals. Conclusions These results suggest that fine-resolution DPOAE-based measures of the MOC reflex measured at strategic frequencies are stable, and natural variance from day-to-day or week-to-week durations is small enough to detect between-group differences and possibly to monitor intervention-related success. However, this is an empirical question that must be directly tested to confirm its utility. PMID:25320951
Urinary Virome Perturbations in Kidney Transplantation.
Sigdel, Tara K; Mercer, Neil; Nandoe, Sharvin; Nicora, Carrie D; Burnum-Johnson, Kristin; Qian, Wei-Jun; Sarwal, Minnie M
2018-01-01
The human microbiome is important for health and plays a role in essential metabolic functions and protection from certain pathogens. Conversely, dysbiosis of the microbiome is seen in the context of various diseases. Recent studies have highlighted that a complex microbial community containing hundreds of bacteria colonizes the healthy urinary tract, but little is known about the human urinary viruses in health and disease. To evaluate the human urinary virome in the context of kidney transplantation (tx), variations in the composition of the urinary virome were evaluated in urine samples from normal healthy volunteers as well as patients with kidney disease after they had undergone kidney tx. Liquid chromatography-mass spectrometry/mass spectrometry analysis was undertaken on a selected cohort of 142 kidney tx patients and normal healthy controls, from a larger biobank of 770 kidney biopsy matched urine samples. In addition to analysis of normal healthy control urine, the cohort of kidney tx patients had biopsy confirmed phenotype classification, coincident with the urine sample analyzed, of stable grafts (STA), acute rejection, BK virus nephritis, and chronic allograft nephropathy. We identified 37 unique viruses, 29 of which are being identified for the first time in human urine samples. The composition of the human urinary virome differs in health and kidney injury, and the distribution of viral proteins in the urinary tract may be further impacted by IS exposure, diet and environmental, dietary, or cutaneous exposure to various insecticides and pesticides.
Sergio, Maria; Galarreta, Carolina I.; Thornhill, Barbara A.; Forbes, Michael S.; Chevalier, Robert L.
2015-01-01
Purpose Urinary tract obstruction and reduced nephron number often occur together as a result of maldevelopment of kidneys and urinary tract. We wished to determine the role of nephron number on the adaptation of remaining nephrons of mice subjected to neonatal partial unilateral ureteral obstruction (UUO) and followed through adulthood. Materials and Methods Wild-type (WT) and Os/+ mice (with 50% fewer nephrons) were subjected to sham operation or partial UUO in the first 2 days of life. Additional mice underwent release of UUO at 7 days. All kidneys were harvested at 3 weeks (weaning) or 6 weeks (adulthood). Glomerular number and area, glomerulotubular junction integrity, proximal tubular volume fraction, and interstitial fibrosis were measured by histomorphometry. Results In the obstructed kidney, UUO caused additional nephron loss in Os/+ but not WT mice. Glomerular growth from 3 to 6 weeks was impaired by ipsilateral UUO and was not preserved by release in WT or Os/+. Proximal tubular growth was impaired and interstitial collagen was increased by ipsilateral UUO in all mice. These were attenuated by release of UUO in WT mice, but were not restored in Os/+ mice. UUO increased interstitial collagen in the contralateral kidney; release of UUO enhanced tubular growth and reduced interstitial collagen. Conclusions We conclude that UUO in early postnatal development impairs adaptation to reduced nephron number and induces additional nephron loss despite release of obstruction. Premature and low birth weight infants with congenital obstructive nephropathy are likely at increased risk for progression of chronic kidney disease. PMID:25912494
Hassan, E A; Ali, T Z; Abdulbaki, A; Ibrahim, I A; Almanae, H M; Aleid, H A
2017-10-01
Isolated microscopic hematuria (IMH) is not uncommon in potential kidney donors. The aim was to study the kidney biopsy findings of potential kidney donors with IMH and the impact of the histopathologic diagnoses on the decision to accept or decline such donors from kidney donation. In this retrospective study, all the potential kidney donors with IMH were identified from the medical records of patients who underwent kidney biopsies between January 2010 and December 2016. Forty-five such individuals were identified. The mean age of these potential donors was 32.6 years and 76% were male. All of them had normal blood pressure and no significant proteinuria. Seventeen (38%) biopsies showed histopathologic abnormalities; thin basement membrane disease (n = 13; 28%) was the most common cause followed by immunoglobulin (Ig)A nephropathy (n = 4; 9%). Donors with abnormal biopsy findings were excluded from donation. However, 62% of the potential donors had normal kidney biopsy findings and were accepted for kidney donation. IMH justifies extensive work-up including kidney biopsy to identify donors who may have underlying significant glomerular pathology excluding them from kidney donation. On the other hand, kidney biopsy also helps in accepting the donors if it does not show significant abnormality. Copyright © 2017 Elsevier Inc. All rights reserved.
The medial olivocochlear reflex in children during active listening.
Smith, Spencer B; Cone, Barbara
2015-08-01
To determine if active listening modulates the strength of the medial olivocochlear (MOC) reflex in children. Click-evoked otoacoustic emissions (CEOAEs) were recorded from the right ear in quiet and in four test conditions: one with contralateral broadband noise (BBN) only, and three with active listening tasks wherein attention was directed to speech embedded in contralateral BBN. Fifteen typically-developing children (ranging in age from 8 to14 years) with normal hearing. CEOAE levels were reduced in every condition with contralateral acoustic stimulus (CAS) when compared to preceding quiet conditions. There was an additional systematic decrease in CEOAE level with increased listening task difficulty, although this effect was very small. These CEOAE level differences were most apparent in the 8-18 ms region after click onset. Active listening may change the strength of the MOC reflex in children, although the effects reported here are very subtle. Further studies are needed to verify that task difficulty modulates the activity of the MOC reflex in children.
The medial olivocochlear reflex in children during active listening
Smith, Spencer B.; Cone, Barbara
2015-01-01
Objective To determine if active listening modulates the strength of the medial olivocochlear (MOC) reflex in children. Design Click-evoked otoacoustic emissions (CEOAEs) were recorded from the right ear in quiet and in four test conditions: one with contralateral broadband noise (BBN) only, and three with active listening tasks wherein attention was directed to speech embedded in contralateral BBN. Study sample Fifteen typically-developing children (ranging in age from 8 to 14 years) with normal hearing. Results CEOAE levels were reduced in every condition with contralateral acoustic stimulus (CAS) when compared to preceding quiet conditions. There was an additional systematic decrease in CEOAE level with increased listening task difficulty, although this effect was very small. These CEOAE level differences were most apparent in the 8–18 ms region after click onset. Conclusions Active listening may change the strength of the MOC reflex in children, although the effects reported here are very subtle. Further studies are needed to verify that task difficulty modulates the activity of the MOC reflex in children. PMID:25735203
Conditional ablation of glycogen synthase kinase 3β in postnatal mouse kidney.
Ge, Yan; Si, Jin; Tian, Li; Zhuang, Shougang; Dworkin, Lance D; Gong, Rujun
2011-01-01
Glycogen synthase kinase (GSK)3 is a ubiquitously expressed serine/threonine kinase existing in two isoforms, namely GSK3α and GSK3β. Aside from the long-recognized role in insulin signal transduction and glycogen biosynthesis, GSK3β has been recently coined as a master control molecule in nuclear factor-κB activation and inflammatory kidney injury. Nevertheless, previous studies are less conclusive because they relied greatly on small molecule inhibitors, which lack selectivity and barely distinguish between the GSK3 isoforms. In addition, early embryonic lethality after global knockout of GSK3β precludes interrogation of the biological role of GSK3β in the adult kidney. To circumvent these issues, the Cre/loxP system was used to generate a conditional knockout mouse model in which the GSK3β gene was specifically deleted in kidney cortical tubules at postnatal mature stage. Kidney-specific ablation of GSK3β resulted in a phenotype no different from control littermates. Knockout mice (KO) were viable and exhibited normal development and normal kidney physiology in terms of kidney function, urine albumin excretion, and urine-concentrating ability. It is noteworthy that apart from normal glomerular and tubulointerstitial morphology, the kidneys from KO demonstrated more glycogen accumulation in the renal cortical tubules as assessed by both periodic acid-Schiff staining for light microscopy and direct biochemical assay, consistent with an elevated glycogen synthetic activity as evidenced by diminished inhibitory phosphorylation of glycogen synthase that occurred subsequent to GSK3β ablation. This finding was further validated by electron microscopic observations of increased deposition of glycogen particles in the renal tubules of KO, suggesting that GSK3α could not fully compensate for the loss of GSK3β in regulating glycogen metabolism in the kidney. Collectively, our study suggests that kidney-specific ablation of GSK3β barely affects kidney function and histology under normal circumstances. Extended examinations of these KO under diseased conditions are merited to understand the role of GSK3β in renal pathophysiology.
History of Childhood Kidney Disease and Risk of Adult End-Stage Renal Disease.
Calderon-Margalit, Ronit; Golan, Eliezer; Twig, Gilad; Leiba, Adi; Tzur, Dorit; Afek, Arnon; Skorecki, Karl; Vivante, Asaf
2018-02-01
The long-term risk associated with childhood kidney disease that had not progressed to chronic kidney disease in childhood is unclear. We aimed to estimate the risk of future end-stage renal disease (ESRD) among adolescents who had normal renal function and a history of childhood kidney disease. We conducted a nationwide, population-based, historical cohort study of 1,521,501 Israeli adolescents who were examined before compulsory military service in 1967 through 1997; data were linked to the Israeli ESRD registry. Kidney diseases in childhood included congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease; all participants included in the primary analysis had normal renal function and no hypertension in adolescence. Cox proportional-hazards models were used to estimate the hazard ratio for ESRD associated with a history of childhood kidney disease. During 30 years of follow-up, ESRD developed in 2490 persons. A history of any childhood kidney disease was associated with a hazard ratio for ESRD of 4.19 (95% confidence interval [CI], 3.52 to 4.99). The associations between each diagnosis of kidney disease in childhood (congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease) and the risk of ESRD in adulthood were similar in magnitude (multivariable-adjusted hazard ratios of 5.19 [95% CI, 3.41 to 7.90], 4.03 [95% CI, 3.16 to 5.14], and 3.85 [95% CI, 2.77 to 5.36], respectively). A history of kidney disease in childhood was associated with younger age at the onset of ESRD (hazard ratio for ESRD among adults <40 years of age, 10.40 [95% CI, 7.96 to 13.59]). A history of clinically evident kidney disease in childhood, even if renal function was apparently normal in adolescence, was associated with a significantly increased risk of ESRD, which suggests that kidney injury or structural abnormality in childhood has long-term consequences.
Samuel, Susan M; Palacios-Derflingher, Luz; Tonelli, Marcello; Manns, Braden; Crowshoe, Lynden; Ahmed, Sofia B; Jun, Min; Saad, Nathalie; Hemmelgarn, Brenda R
2014-02-04
Despite a low prevalence of chronic kidney disease (estimated glomerular filtration rate [GFR]<60 mL/min per 1.73 m2), First Nations people have high rates of kidney failure requiring chronic dialysis or kidney transplantation. We sought to examine whether the presence and severity of albuminuria contributes to the progression of chronic kidney disease to kidney failure among First Nations people. We identified all adult residents of Alberta (age≥18 yr) for whom an outpatient serum creatinine measurement was available from May 1, 2002, to Mar. 31, 2008. We determined albuminuria using urine dipsticks and categorized results as normal (i.e., no albuminuria), mild, heavy or unmeasured. Our primary outcome was progression to kidney failure (defined as the need for chronic dialysis or kidney transplantation, or a sustained doubling of serum creatinine levels). We calculated rates of progression to kidney failure by First Nations status, by estimated GFR and by albuminuria category. We determined the relative hazard of progression to kidney failure for First Nations compared with non-First Nations participants by level of albuminuria and estimated GFR. Of the 1 816 824 participants we identified, 48 669 (2.7%) were First Nations. First Nations people were less likely to have normal albuminuria compared with non-First Nations people (38.7% v. 56.4%). Rates of progression to kidney failure were consistently 2- to 3-fold higher among First Nations people than among non-First Nations people, across all levels of albuminuria and estimated GFRs. Compared with non-First Nations people, First Nations people with an estimated GFR of 15.0-29.9 mL/min per 1.73 m2 had the highest risk of progression to kidney failure, with similar hazard ratios for those with normal and heavy albuminuria. Albuminuria confers a similar risk of progression to kidney failure for First Nations and non-First Nations people.
Radiographic kidney measurements in captive cheetahs (Acinonyx jubatus).
Hackendahl, Nicole C; Citino, Scott B
2005-06-01
The prevalence of chronic renal disease is substantial among captive cheetahs (Acinonyx jubatus). The purpose of this study was to determine kidney measurements from radiographs of captive cheetahs (n = 15) with normal renal function. The ratio of kidney length to length of the body of the second lumbar vertebrae has been established for domestic cats with normal renal function. The mean ratio of renal length to length of the second lumbar vertebra was 1.81 +/- 0.14 in cheetahs. This baseline data may allow an objective evaluation of radiographic kidney size in cheetahs. However, evaluation of a small number of cheetahs with confirmed renal failure resulted in a similar ratio.
Unilateral vs bilateral hip bone mineral density measurement for the diagnosis of osteoporosis.
Ikegami, Shota; Kamimura, Mikio; Uchiyama, Shigeharu; Mukaiyama, Keijiro; Kato, Hiroyuki
2014-01-01
It has not been established whether unilateral or bilateral hip dual-energy X-ray absorptiometry (DXA) is preferable for the diagnosis of osteoporosis. We investigated the discordance in DXA measurements in bilateral hips to determine whether unilateral DXA is valid for osteoporosis diagnosis. The subjects were 2964 Japanese patients without a previous diagnosis of primary osteoporosis. We measured bilateral femoral bone mineral density (BMD) and calculated indices, related to the unilateral results, for predicting contralateral hip osteoporosis. A likelihood ratio (LR) of a negative test (LR [-]) of less than 0.2 was considered to exclude the diagnosis. In the normal spinal BMD group, the sensitivity of unilateral DXA for women was 27-73% and LR (-) was 0.28-0.73; the sensitivity for men was 0-50% and LR (-) was 0.51-1.00; the diagnosis of contralateral osteoporosis was not excluded. Sensitivity increased and LR (-) increased with worsening spinal BMD status; however, LR (-) did not meet the cutoff for exclusion. We could exclude unilateral hip osteoporosis, in women only, by performing contralateral femoral DXA; this necessitated lowering the T-score cutoff from -2.5 to -2.0. Unilateral femoral DXA is not useful for excluding the diagnosis of contralateral hip osteoporosis. Copyright © 2014 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.
Purkait, Bimalesh; Sinha, Rahul Janak; Bansal, Ankur; Sokhal, Ashok Kumar; Singh, Kawaljit; Singh, Vishwajeet
2018-06-01
Pediatric population has increasing incidence of renal calculus and it is estimated to be around 50/10,000 population. The treatment of choice for large and complex stone in anomalous kidney is percutaneous nephrolithotomy (PCNL). The fate of insignificant residual fragment after PCNL in pediatric patients is not well documented. Here, we are reporting our long-term experience and follow-up of insignificant residual fragment in pediatric patients with anomalous kidney in comparison to normal kidney. Intuitional ethical approval was taken. A retrospective analysis of PCNL in pediatric (<18 years) anomalous kidney was performed from 2001 to 2013. The data of 52 pediatric patients with anomalous kidney (group B) have been compared to 251 normal kidneys (group A). The mean age of the patients was 7.83 + 3.45 (range 3-18) in group A and 8.21 ± 3.25 (range 5-18) in group B. The mean size of the insignificant residual fragment was 2.2 + 0.5 mm (1-4) in group A and 2.1 + 0.6 mm (range 1-4) in group B. Most of these residual fragments were single in number (72.55 vs. 67.30%, respectively). 54.98% children in group A and 67.30% in group B were symptomatic in the follow-up. Stone size was increased, stable and spontaneously passed in 49.8 vs. 71.15, 22.7 vs. 19.23 and 27.49 vs. 9.61% (p < 0.03), respectively, over mean follow-up of 50.34 months. Insignificant residual fragments in children are notorious for regrowth (49.8% in normal and 71.15% in anomalous kidney) in future. Most of the children will require symptomatic treatment (55.37 vs. 82.69%) or reintervention (39 vs. 46%) for insignificant residual fragment.
USDA-ARS?s Scientific Manuscript database
Background: Anticoagulation management is difficult in chronic kidney disease, with frequent supratherapeutic international normalized ratios (INRs >/= 4) increasing hemorrhagic risk. We evaluated whether the interaction of INR and lower estimated glomerular filtration rate (eGFR) increases hemorrha...
Pantoprazole-induced acute kidney injury: A case report.
Peng, Tao; Hu, Zhao; Zheng, Hongnan; Zhen, Junhui; Ma, Chengjun; Yang, Xiangdong
2018-06-01
The present study reports a case of pantoprazole-induced acute kidney disease. The patient was diagnosed with acute kidney injury with wide interstitial inflammation and eosinophil infiltration. Following 1 month of glucocorticoid therapy, the patient's serum creatinine and urea nitrogen decreased to within normal ranges. The presentation, clinical course, diagnosis and prognosis of pantoprazole-induced acute kidney injury are discussed herein to highlight the importance of early and correct diagnosis for good prognosis. Disease characteristics include short-term increased serum creatinine levels that respond to glucocorticoid treatment. The patient had no history of chronic kidney disease or proteinuria and presented with increased serum creatinine following treatment with pantoprazole. Following the end of pantoprazole treatment, short-term RRT and long-term prednisolone was administered, then serum creatinine returned to normal. Pantoprazole-induced acute kidney injury is commonly misdiagnosed and late diagnosis results in poor patient prognoses. Misdiagnosis leads to the administration of treatments that may exacerbate the condition, so appropriate diagnosis and treatment for pantoprazole-induced acute kidney injury is necessary.
Anatomy and ultrasonography of the normal kidney in brown lemurs: Eulemur fulvus.
Raharison, Fidiniaina; Mogicato, Giovanni; Sautet, Jean
2009-08-01
The purpose of this study is to describe the anatomy and obtain echographic measurements of normal kidneys in brown lemurs (Eulemur fulvus). The anatomical findings show that brown lemur kidneys are comparable to those of rats except for an elongated papilla. The kidneys of 16 (7 females and 9 males) lemurs were examined with two-dimensional and power Doppler ultrasonography under general anesthesia. Morphometrically, the left and right kidney surface areas are comparable (3.29 and 3.51 cm(2)). Kidney area has a significant linear correlation with body weight. Echo-Doppler findings show that the mean renal arterial blood flow speeds for the left and right kidneys are comparable (0.70 and 0.73 m/s). However, flow speed is higher in the male (0.79 m/s) than in the female (0.60 m/s). The renal arterial diameters are between 1.0 and 1.8 mm. The fact that anesthesia can have hemodynamic effects on renal vasculature should be taken into consideration when assessing these echographic results.
Determination of the toxicity of intravitreal minocycline in rabbit eyes.
Falavarjani, Khalil Ghasemi; Pourhabibi, Arash; Aghdam, Kaveh Abri; Hosseini, Seyed Bagher; Modarres, Mehdi; Pazouki, Abdolreza; Khanamiri, Hossein Nazari
2016-09-01
To evaluate the retinal toxicity of intravitreal minocycline in rabbit eyes. Intravitreal injection of minocycline with concentrations of 1000, 500, 250, 125 and 62.5 μg in 0.1 ml was performed in 10 New Zealand albino rabbits. Each concentration was injected into two rabbit eyes. For each dose, normal saline was injected in one contralateral eye and the other fellow eye remained non-injected. Electrophysiologic testing was performed before and 4 weeks after injections. The eyes were enucleated 4 weeks after injections and examined using light microscopy. The clinical examination was unremarkable after injections. Electroretinography recordings were significantly affected at all doses in at least one of the a- or b-waves of photopic or scotopic responses. Histopathologic examination revealed marked atrophy and loss of integrity in all retinal layers in all minocycline injected eyes. Contralateral eyes were normal. In our study, intravitreal minocycline was toxic to the retina in albino rabbits even at a concentration of 62.5 µg/0.1 ml.
... normal structure. What Abnormal Results Mean An abnormal result means there are changes in the kidney tissue. This may be due to: Infection Poor blood flow through the kidney Connective tissue diseases such as systemic lupus erythematosus Other diseases that may be affecting the ...
Neurogenic regulation of proximal bicarbonate and chloride reabsorption.
Cogan, M G
1986-01-01
Although a change in renal nerve activity is known to alter proximal reabsorption, it is unclear whether reabsorption of NaHCO3 or NaCl or both are affected. Sprague-Dawley rats (n = 10) were studied using free-flow micropuncture techniques during euvolemia and following acute ipsilateral denervation. Glomerular filtration rate and single nephron glomerular filtration rate were stable. Absolute proximal bicarbonate reabsorption fell following denervation (933 +/- 40 to 817 +/- 30 pmol/min) with a parallel reduction in chloride reabsorption (1,643 +/- 116 to 1,341 +/- 129 peq/min). Urinary sodium, potassium, bicarbonate, and chloride excretion all increased significantly. To further assess the physiological significance of neurogenic modulation of proximal transport, other rats (n = 6) were subjected to acute unilateral nephrectomy (AUN). There is evidence that AUN induces a contralateral natriuresis (renorenal reflex) at least partially by causing inhibition of efferent renal nerve traffic. AUN caused significant changes in proximal NaHCO3 and NaCl reabsorption as well as in whole kidney electrolyte excretion in the same pattern as had denervation. Prior denervation of the remaining kidney prevented the proximal and whole kidney response to AUN (n = 6). In conclusion, depression of renal nerve activity inhibits both NaHCO3 and NaCl reabsorption in the rat superficial proximal convoluted tubule. The data are consistent with the hypothesis that changes in renal nerve activity modify whole kidney electrolyte excretion under physiological conditions at least partially by regulating proximal transport.
Neural control of renal function.
Johns, Edward J; Kopp, Ulla C; DiBona, Gerald F
2011-04-01
The kidney is innervated with efferent sympathetic nerve fibers that directly contact the vasculature, the renal tubules, and the juxtaglomerular granular cells. Via specific adrenoceptors, increased efferent renal sympathetic nerve activity decreases renal blood flow and glomerular filtration rate, increases renal tubular sodium and water reabsorption, and increases renin release. Decreased efferent renal sympathetic nerve activity produces opposite functional responses. This integrated system contributes importantly to homeostatic regulation of sodium and water balance under physiological conditions and to pathological alterations in sodium and water balance in disease. The kidney contains afferent sensory nerve fibers that are located primarily in the renal pelvic wall where they sense stretch. Stretch activation of these afferent sensory nerve fibers elicits an inhibitory renorenal reflex response wherein the contralateral kidney exhibits a compensatory natriuresis and diuresis due to diminished efferent renal sympathetic nerve activity. The renorenal reflex coordinates the excretory function of the two kidneys so as to facilitate homeostatic regulation of sodium and water balance. There is a negative feedback loop in which efferent renal sympathetic nerve activity facilitates increases in afferent renal nerve activity that in turn inhibit efferent renal sympathetic nerve activity so as to avoid excess renal sodium retention. In states of renal disease or injury, there is activation of afferent sensory nerve fibers that are excitatory, leading to increased peripheral sympathetic nerve activity, vasoconstriction, and increased arterial pressure. Proof of principle studies in essential hypertensive patients demonstrate that renal denervation produces sustained decreases in arterial pressure. © 2011 American Physiological Society. Compr Physiol 1:699-729, 2011.
Osthole ameliorates renal ischemia-reperfusion injury by inhibiting inflammatory response.
Zheng, Yi; Lu, Min; Ma, Lulin; Zhang, Shudong; Qiu, Min; Ma, Xin
2013-01-01
Renal ischemia-reperfusion (I/R) injury is a primary cause of acute renal failure that results in high mortality. This study aimed to investigate the effect of osthole, a natural coumarin derivative, on renal I/R injury in a rat model. Rats were randomly allocated to the sham operation + vehicle, I/R + vehicle, and I/R + osthole groups. Renal I/R injury was induced by clamping the left renal artery for 45 min followed by 12 h of reperfusion and a contralateral nephrectomy. Osthole (40 mg/kg) was intraperitoneally injected 30 min before inducing I/R. Renal function and histological damage were determined subsequently. Myeloperoxidase activity, monocyte/macrophage infiltration, as well as tumor necrosis factor-α, IL-1β, and activated p38 mitogen-activated protein kinase expression in kidneys were also assessed. Osthole treatment significantly ameliorated I/R-induced renal functional and morphological injuries. Moreover, osthole treatment attenuated myeloperoxidase activity, monocyte/macrophage infiltration, and tumor necrosis factor-α, IL-1β, and activated p38 mitogen-activated protein kinase expression in kidneys. Osthole treatment ameliorates renal I/R injury by inhibiting inflammatory responses in kidneys. Thus, osthole may represent a novel practical strategy to prevent renal I/R injury. Copyright © 2013 S. Karger AG, Basel.
Contralateral Dpoae Suppression in Humans at Very Low Sound Intensities
NASA Astrophysics Data System (ADS)
Janssen, T.; Gehr, D. D.; Kevanishvili, Z.
2003-02-01
Different functions are attributed to the olivo-cochlear bundle system (OCBS) such as protecting the ear from acoustic injury, improving signal detection in noise, and mediating selective attention. OCBS reflex strength can be evaluated, in animals as well as in humans, by measuring the degree of suppression of an ipsilateral DPOAE by a contralateral sound. The purpose of the study was to evaluate OCBS reflex strength depending on ipsilateral stimulus level, especially at threshold, by means of extrapolated DPOAE I/O-functions. Additionally, DPOAE was measured at near-to-threshold contralateral stimulus levels when using low-level ipsilateral stimulation for investigating possible enhancement of outer hair cell motion in the presence of low-level contralateral sound. The recording of the 2f1-f2 DPOAE in the presence or absence of contralateral sound was performed in normally hearing human subjects at f2 = 2 kHz. DPOAE I/O-functions were measured in a primary tone level range from L2 = 20 to L2 = 65 dB SPL (L1 = 0.4L2 + 39, f2/f1=1.2). Broad-band noise (BBN), narrow-band noise from 1720 to 2320 Hz (NBN), and pure tones (PT) at f2, 2f1-f2, geometric mean of f1 and f2, and 0.1oct + f2 were used for contralateral stimulation. The contralateral stimulus level (Ls) was decreased from 70 down to 10 dB SPL in 10 dB steps. DPOAE suppression was highest at the lowest primary tone level and was more pronounced for BBN and NBN than for pure tones, suggesting a more diffuse than a strong tonotopic organisation of the OCBS. The contralateral stimulus level at which significant DPOAE suppression occurred (p < 0.05) was different for the different stimuli being 20, 40, and 70 dB SPL for BBN, NBN, and pure-tone (f2), respectively. Significant DPOAE suppression to BBN and NBN occurred at Ls well below audiological middle-ear reflex threshold. DPOAE time course was different for Ls below and above middle-ear reflex threshold. Thus, middle-ear muscle contraction is suggested not to be involved in DPOAE suppression at low Ls. No enhancement of DPOAE could be found. The findings suggest the OCBS to be functioning in a more protective way than for improving signal detection in noise.
Ozturk, Hakan; Karaaslan, Serap
2014-09-01
Metachronous adrenal metastasis from contralateral renal cell carcinoma (RCC) surgery is an extremely rare condition. Iatrogenic Addison's disease occurring after metastasectomy (adrenalectomy) is an even rarer clinical entity. We present a case of a 68-year-old male with hematuria and left flank pain 9 years prior. The patient underwent left transperitoneal radical nephrectomy involving the ipsilateral adrenal glands due to a centrally-located, 75-mm in diameter solid mass lesion in the upper pole of the left kidney. The tumour lesion was confined within the renal capsule, and the histo-pathological examination revealed a Fuhrman nuclear grade II clear cell carcinoma. The patient underwent transperitoneal right adrenalectomy. The histopathological examination revealed metastasis of clear cell carcinoma. The patient was diagnosed with iatrogenic Addison's disease based on the measurement of serum cortisol levels and the adrenocorticotropic hormone (ACTH) stimulation test, after which glucocorticoid and mineralocorticoid replacement was initiated. The patient did not have local recurrence or new metastasis in the first year of the follow-up. The decision to perform ipsilateral adrenalectomy during radical nephrectomy constitutes a challenge, and the operating surgeon must consider all these rare factors.
Stuart, Andrew; Daughtrey, Emma R
2016-04-01
The medial olivocochlear (MOC) efferent reflex that modulates outer hair cell function has been shown to be more robust in musicians versus nonmusicians as evidenced in greater contralateral suppression of transient-evoked otoacoustic emissions (TEOAEs). All previous research comparing musical ability and MOC efferent strength has defined musicianship dichotomously (i.e., high-level music students or professional classical musicians versus nonmusicians). The objective of the study was to further explore contralateral suppression of TEOAEs among adults with a full spectrum of musicianship ranging from no history of musicianship to professional musicians. Musicianship was defined by both self-report and with an objective test to quantify individual differences in perceptual music skills. A single-factor between-subjects and correlational research designs were employed. Forty-five normal-hearing young adults participated. Participants completed a questionnaire concerning their music experience and completed the Brief Profile of Music Perception Skills (PROMS) to quantify perceptual musical skills across multiple musical domains (i.e., accent, melody, tempo, and tuning). TEOAEs were evaluated with 60 dB peak equivalent sound pressure level click stimuli with and without a contralateral 65 dB sound pressure level white noise suppressor. TEOAE suppression was expressed in two ways, absolute TEOAE suppression in dB and a normalized index of TEOAE suppression (i.e., percentage of suppression). Participants who considered themselves musicians scored significantly higher on all subscales and total Brief PROMS score (p < 0.05). There was no statistically significant difference between musicians and nonmusicians in absolute TEOAE suppression or percentage of TEOAE suppression (p > 0.05). There were no statistically significant correlations or linear predictive relationships between subscale or total Brief PROMS scores with absolute and percentage of TEOAE suppression (p > 0.05). The findings do not support the notion of a graded enhancement of MOC efferent suppression among adults with varied degrees of musicianship from nonmusicians to professional musicians. American Academy of Audiology.
Ibrahim, Naser H M; Thandapilly, Sijo J; Jia, Yong; Netticadan, Thomas; Aukema, Harold
2016-05-01
Abnormalities in cardiac structure and function are very common among people with chronic kidney disease, in whom cardiovascular disease is the major cause of death. Dietary soy protein and fish oil reduce kidney disease progression in the Han:SPRD-Cy model of cystic renal disease. However, the effects of these dietary interventions in preventing alterations in cardiac structure and function due to kidney disease (reno-cardiac syndrome) in a cystic kidney disease model are not known. Therefore, weanling Han:SPRD-Cy diseased (Cy/+) and normal (+/+) rats were given diets containing either casein or soy protein, and either soy or fish oil in a three-way design for 8 weeks. Diseased rats had larger hearts, augmented left ventricular mass, and higher systolic and mean arterial blood pressure compared to the normal rats. Assessment of cardiac function using two-dimensional guided M-mode and pulse-wave Doppler echocardiography revealed that isovolumic relaxation time was prolonged in the diseased compared to normal rats, reflecting a diastolic heart dysfunction, and fish oil prevented this elevation. Soy protein resulted in a small improvement in systolic and mean arterial pressure but did not improve diastolic heart function, while fish oil prevented diastolic heart dysfunction in this model of cystic kidney disease.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Wei-Yu, E-mail: wychen624@cgmh.org.tw; Chang, Ya-Jen; Su, Chia-Hao
Interstitial fibrosis and loss of parenchymal tubular cells are the common outcomes of progressive renal diseases. Pro-inflammatory cytokines have been known contributing to the damage of tubular cells and fibrosis responses after renal injury. Interleukin (IL)-33 is a tissue-derived nucleus alarmin that drives inflammatory responses. The regulation and function of IL-33 in renal injury, however, is not well understood. To investigate the involvement of cytokines in the pathogenesis of renal injury and fibrosis, we performed the mouse renal injury model induced by unilateral urinary obstruction (UUO) and analyze the differentially upregulated genes between the obstructed and the contralateral unobstructed kidneysmore » using RNA sequencing (RNAseq). Our RNAseq data identified IL33 and its receptor ST2 were upregulated in the UUO kidney. Quantitative analysis confirmed that transcripts of IL33 and ST2 were upregulated in the obstructed kidneys. Immunofluorescent staining revealed that IL-33 was upregulated in Vimentin- and alpha-SMA-positive interstitial cells. By using genetically knockout mice, deletion of IL33 reduced UUO-induced renal fibrosis. Moreover, in combination with BrdU labeling technique, we observed that the numbers of proliferating tubular epithelial cells were increased in the UUO kidneys from IL33-or ST2-deficient mice compared to wild type mice. Collectively, our study demonstrated the upregulation of IL-33/ST2 signaling in the obstructed kidney may promote tubular cell injury and interstitial fibrosis. IL-33 may serve as a biomarker to detect renal injury and that IL-33/ST2 signaling may represent a novel target for treating renal diseases. -- Highlights: •Interleukin (IL)-33 was upregulated in obstructed kidneys. •Interstitial myofibroblasts expressed IL-33 after UUO-induced renal injury. •Deficiency of IL33 reduced interstitial fibrosis and promoted tubular cell proliferation.« less
Sergio, Maria; Galarreta, Carolina I; Thornhill, Barbara A; Forbes, Michael S; Chevalier, Robert L
2015-11-01
Urinary tract obstruction and reduced nephron number often occur together as a result of maldevelopment of the kidneys and the urinary tract. We determined the role of nephron number on adaptation of the remaining nephrons of mice subjected to neonatal partial unilateral ureteral obstruction followed through adulthood. Wild-type and Os/+ mice (the latter with 50% fewer nephrons) underwent sham operation or partial unilateral ureteral obstruction in the first 2 days of life. Additional mice underwent release of unilateral ureteral obstruction at 7 days. All kidneys were harvested at 3 weeks (weaning) or 6 weeks (adulthood). Glomerular number and area, glomerulotubular junction integrity, proximal tubular volume fraction and interstitial fibrosis were measured by histomorphometry. In the obstructed kidney unilateral ureteral obstruction caused additional nephron loss in Os/+ but not in wild-type mice. Glomerular growth from 3 to 6 weeks was impaired by ipsilateral obstruction and not preserved by release in wild-type or Os/+ mice. Proximal tubular growth was impaired and interstitial collagen was increased by ipsilateral obstruction in all mice. These conditions were attenuated by release of unilateral ureteral obstruction in wild-type mice but were not restored in Os/+ mice. Unilateral ureteral obstruction increased interstitial collagen in the contralateral kidney while release of obstruction enhanced tubular growth and reduced interstitial collagen. Unilateral ureteral obstruction in early postnatal development impairs adaptation to reduced nephron number and induces additional nephron loss despite release of obstruction. Premature and low birth weight infants with congenital obstructive nephropathy are likely at increased risk for progression of chronic kidney disease. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Wolter, Nikolaus E; Harrison, Robert V; James, Adrian L
2014-01-01
Mediated by the medial olivocochlear system (MOCS), distortion product otoacoustic emission (DPOAE) levels are reduced by presentation of contralateral acoustic stimuli. Such acoustic signals can also evoke a middle ear muscle reflex (MEMR) that also attenuates recorded DPOAE levels. Our aim is to clearly differentiate these two inhibitory mechanisms and to analyze each separately, perhaps allowing the development of novel tests of hearing function. DPOAE were recorded in real time from chinchillas with normal auditory brainstem response thresholds and middle ear function. Amplitude reduction and its onset latency caused by contralateral presentation of intermittent narrow-band noise (NBN) were measured. Stapedius and tensor tympani muscle tendons were divided without disturbing the ossicular chain, and DPOAE testing was repeated. Peak reduction of (2f1 - f2) DPOAE levels occurred when the center frequency of contralateral NBN approximated the primary tone f2, indicating an f2-frequency-specific response. For a 4.5-kHz centered NBN, DPOAE (f2 = 4.4 kHz) inhibition was 0.1 dB (p < 0.001). This response remained present after tendon division, consistent with an MOCS origin. Low-frequency NBN (center frequency: 0.5 kHz) reduced otoacoustic emission levels (0.1 dB, p < 0.001) across a wide range of DPOAE frequencies. This low-frequency response was abolished by division of the middle ear muscle tendons, clearly indicating MEMR involvement. Following middle ear muscle tendon division, DPOAE inhibition by contralateral stimuli approximating the primary tone f2 persists, whereas responses evoked by lower contralateral frequencies are abolished. This distinguishes the different roles of the MOCS (f2 frequency specific) and MEMR (low frequency only) in contralateral modulation of DPOAE. This analysis helps clarify the pathways involved in an objective test that might have clinical benefit in the testing of neonates.
Shariq, Omair A; Bancos, Irina; Cronin, Patricia A; Farley, David R; Richards, Melanie L; Thompson, Geoffrey B; Young, William F; McKenzie, Travis J
2018-01-01
We aimed to determine whether a greater degree of contralateral suppression of aldosterone secretion at adrenal venous sampling predicted the development of postoperative hyperkalemia after unilateral adrenalectomy for primary aldosteronism. A retrospective analysis of patients undergoing unilateral adrenalectomy for primary aldosteronism between 2004-2015 was performed. Clinical and biochemical parameters of patients who developed hyperkalemia (≥5.2 mmol/L) after unilateral adreanlectomy were compared with those who remained normokalemic. The contralateral suppression index was defined as the aldosterone-to-cortisol ratio from the nondominant adrenal vein divided by the aldosterone-to-cortisol ratio from the external iliac vein. Of 192 patients who met criteria for inclusion, 12 (6.3%) developed hyperkalemia (median serum potassium 5.5 mmol/L, range 5.2-6.2 mmol/L), with a median time to onset of 13.5 days (range 7-55 days). Five patients had transiently increased serum potassium concentrations that normalized spontaneously. Four patients received mineralocorticoid replacement therapy with fludrocortisone. On univariate analysis, hyperkalemic patients had slightly greater preoperative serum creatinine levels (1.2 vs 1.0 mg/dL, P = .01), higher postoperative creatinine (1.3 vs 1.0 mg/dL, P = .02), lesser median contralateral suppression index (0.14 vs 0.27, P = .03), and larger adenomas (1.9 vs 1.4 cm, P = .02). On multivariable logistic regression, the contralateral suppression index remained the only significant predictor of postoperative hyperkalemia (P = .04) with an optimal cut-off of <0.47. Hyperkalemia after unilateral adrenalectomy for primary aldosteronism is uncommon and usually transient, but may require mineralocorticoid supplementation. Patients with a contralateral suppression index of <0.47 require meticulous follow-up and monitoring of serum potassium concentrations after unilateral adrenalectomy. Copyright © 2017 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, H; Cape Breton Cancer Centre, Sydney, NS
Purpose: To perform the comparison of dose distributions and dosevolume- histograms generated by VMAT and conventional field-in-field technique for left-sided breast and chestwall cancers; to determine whether VMAT offers more dosimetric benefits than does the field-in-field technique. Methods: All VMAT and field-in-filed plans were produced in Eclipse(version 10). Five plans were generated for left-sided breast and leftsided chestwall with supraclavicular nodes, respectively. A clockwise arc (CW) and a counter-clockwise arc (CCW) were used with start and stop angles being 310o±10o and 140o±10o. Collimator angles were 30o for CW and 330o for CCW. The conformity index (CI) is the ratio ofmore » V95% over PTV. The homogeneity index (HI) is the ratio of the difference between D2% and D98% over the prescribed dose. The V5, as an indicator of low dose bath to organs-at-risk, was used for ipsilateral lung, heart, contralateral lung, and contralateral breast. The V20, as an indicator of radiation pneumonitis, was used for ipsilateral lung. Results: Breast/chestwall VMAT delivers much higher low dose bath to ipsilateral lung, contralateral lung and contralateral breast/chestwall for both intact breast and chestwall with nodes. V5 for heart is increased in VMAT plans. V20 for ipsilateral lung is lower in VMAT plans. PTV coverage is similar for both techniques. For one particular chestwall patient with supraclavicular and internal mammary nodes, VMAT offers superior dose coverage of PTVs with slightly more low-dose-wash to heart, contralateral lung and contralateral breast. Conclusion: This study indicates that there is generally no benefit using VMAT for left-sided intact breast, due to large low-dose-bath (5Gy) to normal tissues with insignificant improvement in PTV coverage. Dosimetric benefits will be seen in VMAT plans for some chestwall patients with large size, and/or internal mammary nodes, etc. Whether a chestwall patient is treated with VMAT should be carefully analyzed on an individual basis.« less
Piacenza, Francesco; Malavolta, Marco; Cipriano, Catia; Costarelli, Laura; Giacconi, Robertina; Muti, Elisa; Tesei, Silvia; Pierpaoli, Sara; Basso, Andrea; Bracci, Massimo; Bonacucina, Viviana; Santarelli, Lory; Mocchegiani, Eugenio
2009-09-28
Inorganic mercury (HgCl2) exposure provokes damage in many organs, especially kidney. Inducible nitric oxide synthase (iNOS) expression, total NOS activity and the profiles of zinc (Zn), copper (Cu) and Hg as well as their distribution when bound to specific intracellular proteins, including metallothioneins (MT), were studied during HgCl2 exposure and after l-arginine treatment in C57BL/6 mouse kidney. HgCl2 exposure modulates differently iNOS expression and NOS activity, increasing iNOS expression but, conversely, decreasing total NOS activity in the mouse kidney. Moreover, during Hg exposure an increased MT production occurs. The kidney damage leads to a loss of urinary proteins, increased plasma creatinine and high Zn mobilization with consequent increased urinary Zn excretion. l-arginine treatment recovers NOS activity and induces a normalization of MT induction, plasma creatinine values and urinary proteins excretion, suggesting that l-arginine may limit kidney damages by Hg exposure.
Yoshizawa, Nobuko; Ueda, Yukio; Nasu, Hatsuko; Ogura, Hiroyuki; Ohmae, Etsuko; Yoshimoto, Kenji; Takehara, Yasuo; Yamashita, Yutaka; Sakahara, Harumi
2016-11-01
Optical imaging and spectroscopy using near-infrared light have great potential in the assessment of tumor vasculature. We previously measured hemoglobin concentrations in breast cancer using a near-infrared time-resolved spectroscopy system. The purpose of the present study was to evaluate the effect of the chest wall on the measurement of hemoglobin concentrations in normal breast tissue and cancer. We measured total hemoglobin (tHb) concentration in both cancer and contralateral normal breast using a near-infrared time-resolved spectroscopy system in 24 female patients with breast cancer. Patients were divided into two groups based on menopausal state. The skin-to-chest wall distance was determined using ultrasound images obtained with an ultrasound probe attached to the spectroscopy probe. The apparent tHb concentration of normal breast increased when the skin-to-chest wall distance was less than 20 mm. The tHb concentration in pre-menopausal patients was higher than that in post-menopausal patients. Although the concentration of tHb in cancer tissue was statistically higher than that in normal breast, the contralateral normal breast showed higher tHb concentration than cancer in 9 of 46 datasets. When the curves of tHb concentrations as a function of the skin-to-chest wall distance in normal breast were applied for pre- and post-menopausal patients separately, all the cancer lesions plotted above the curves. The skin-to-chest wall distance affected the measurement of tHb concentration of breast tissue by near-infrared time-resolved spectroscopy. The tHb concentration of breast cancer tissue was more precisely evaluated by considering the skin-to-chest wall distance.
Gupta, Vipul; Feng, Kent; Cheruvu, Pavan; Boyer, Nathan; Yeghiazarians, Yerem; Ports, Thomas A; Zimmet, Jeffrey; Shunk, Kendrick; Boyle, Andrew J
2014-09-01
Recent advances in technology have led to an increase in the use of bilateral femoral artery access and the requirement for large-bore access. Optimal access is in the common femoral artery (CFA), rather than higher (in the external iliac artery) or lower (in one of the branches of the CFA). However, there is a paucity of data in the literature about the relationship between bifurcation level of one CFA and the contralateral CFA. To define the prevalence of high bifurcation of the CFA and the relationship between bifurcation level on both sides, we performed a retrospective analysis of all patients with bilateral femoral angiography. From 4880 femoral angiograms performed at UCSF cardiac catheterization laboratory between 2005-2013, a total of 273 patients had bilateral femoral angiograms. The prevalence of low/normal, high, and very-high femoral bifurcations was 70%, 26%, and 4%, respectively, with no difference between sides. A high or very-high bifurcation significantly increased the likelihood of a high bifurcation on the contralateral side (odds ratio >3.0). Multivariable logistic regression analysis revealed age, gender, self-reported race, height, weight, and body mass index were not predictive of high or very-high bifurcations on either side. In conclusion, high femoral artery bifurcations are common and increase the likelihood of a high bifurcation of the contralateral femoral artery.
Effects of kidney or kidney-pancreas transplantation on plasma pentosidine.
Hricik, D E; Schulak, J A; Sell, D R; Fogarty, J F; Monnier, V M
1993-02-01
Tissue and plasma concentrations of pentose-derived glycation end-products ("pentosidine") are elevated in diabetic patients with normal renal function and in both diabetic and nondiabetic patients with end-stage renal disease. To determine the effects of correcting hyperglycemia and/or renal failure on the accumulation of pentosidine, we used reverse phase and ion exchange high performance liquid chromatography to measure this advanced glycation end-product in plasma proteins of diabetic and nondiabetic transplant recipients at various time intervals after kidney-pancreas or kidney transplantation. Changes in plasma pentosidine levels after transplantation were compared to changes in simultaneously obtained glycohemoglobin levels. Both kidney and kidney-pancreas transplantation were accompanied by a dramatic, but incomplete, reduction of plasma pentosidine concentrations within three months of transplantation. Kidney-pancreas transplantation resulted in normal glycohemoglobin levels within three months but offered no advantage over kidney transplantation alone in the partial correction of plasma pentosidine levels. There was no correlation between posttransplant plasma pentosidine and glycohemoglobin levels in either diabetic or nondiabetic transplant recipients. We conclude that renal failure is the major factor accounting for the accumulation of pentosidine in both diabetic and nondiabetic patients with end-stage renal disease. Restoration of euglycemia after kidney-pancreas transplantation provides no additional benefit in reducing plasma pentosidine levels to that achieved by correction of renal failure after kidney transplantation alone.
Renal synthesis of leukaemia inhibitory factor (LIF), under normal and inflammatory conditions.
Morel, D S; Taupin, J L; Potier, M; Deminière, C; Potaux, L; Gualde, N; Moreau, J F
2000-03-01
Leukaemia inhibitory factor (LIF) is a pleiotropic cytokine that is particularly involved in nephrogenesis and repair of the extracellular matrix. Transgenic mice overexpressing LIF have mesangial proliferative glomerulonephritis. Also, during local inflammatory reactions, such as kidney graft rejection or urinary tract infections, urinary LIF excretion is enhanced. The aim of the study therefore was to study LIF production by normal and inflammatory diseased kidneys (glomerulonephritis or graft rejection), maintained in short cultures. To determine the responsibility of the kidney itself in LIF synthesis, we measured LIF secretion into the culture supernatants of human mesangial or renal tubular epithelial cells. Fragments from diseased kidneys, whether grafts or not, released more LIF than normal human kidney fragments, mesangial or renal tubular epithelial cells. However, LIF production was delayed in renal transplants compared to glomerulonephritic samples taken from untreated patients. In every case, LIF production was enhanced by interleukin 1beta (IL-1beta) and inhibited by IL-4 or dexamethasone, except in two severe rejection episodes. So, LIF appeared to respond to pro- and anti-inflammatory stimuli, in vitro and in vivo. Considering its biological effects, LIF could play a role in inflammatory renal diseases. Copyright 2000 Academic Press.
NASA Astrophysics Data System (ADS)
Haifler, Miki; Pence, Isaac J.; Zisman, Amnon; Uzzo, Robert G.; Greenberg, Richard; Kutikov, Alexander; Smaldone, Marc; Chen, David; Viterbo, Rosalia; Ristau, Benjamin; Mahadevan-Jansen, Anita; Dumont, Alexander; Patil, Chetan A.
2017-02-01
Kidney cancer affects 65,000 new patients every. As computerized tomography became ubiquitous, the number of small, incidentally detected renal masses increased. About 6,000 benign cases are misclassified radiographically as malignant and removed surgically. Raman spectroscopy (RS) has been widely demonstrated for disease discrimination, however intense near-infrared auto-fluorescence of certain tissues (e.g kidney) can present serious challenges to bulk tissue diagnosis. A 1064nm excitation dispersive detection RS system demonstrated the ability to collect spectra with superior quality in tissues with strong auto-fluorescence. Our objective is to develop a 1064 nm dispersive detection RS system capable of differentiating normal and malignant renal tissue. We will report on the design and development of a clinical system for use in nephron sparing surgeries. We will present pilot data that has been collected from normal and malignant ex vivo kidney specimens using a benchtop RS system. A total of 93 measurements were collected from 12 specimens (6 Renal Cell Carcinoma, 6 Normal ). Spectral classification was performed using sparse multinomial logistic regression (SMLR). Correct classification by SMLR was obtained in 78% of the trials with sensitivity and specificity of 82% and 75% respectively. We will present the association of spectral features with biological indicators of healthy and diseased kidney tissue. Our findings indicate that 1064nm RS is a promising technique for differentiation of normal and malignant renal tissue. This indicates the potential for accurately separating healthy and cancerous tissues and suggests implications for utilizing RS for optical biopsy and surgical guidance in nephron sparing surgery.
Szarmach, Arkadiusz; Halena, Grzegorz; Kaszubowski, Mariusz; Piskunowicz, Maciej; Studniarek, Michal; Lass, Piotr; Szurowska, Edyta; Winklewski, Pawel J
2017-05-08
Failure of the blood-brain barrier (BBB) is a critical event in the development and progression of diseases such as acute ischemic stroke, chronic ischemia or small vessels disease that affect the central nervous system. It is not known whether BBB breakdown in subjects with chronic carotid artery stenosis can be restrained with postoperative recovery of cerebral perfusion. The aim of the study was to assess the short-term effect of internal carotid artery stenting on basic perfusion parameters and permeability surface area-product (PS) in such a population. Forty subjects (23 males) with stenosis of >70% within a single internal carotid artery and neurological symptoms who underwent a carotid artery stenting procedure were investigated. Differences in the following computed tomography perfusion (CTP) parameters were compared before and after surgery: global cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP) and PS. PS acquired by CTP is used to measure the permeability of the BBB to contrast material. In all baseline cases, the CBF and CBV values were low, while MTT and TTP were high on both the ipsi- and contralateral sides compared to reference values. PS was approximately twice the normal value. CBF was higher (+6.14%), while MTT was lower (-9.34%) on the contralateral than on the ipsilateral side. All perfusion parameters improved after stenting on both the ipsilateral (CBF +22.66%; CBV +18.98%; MTT -16.09%, TTP -7.62%) and contralateral (CBF +22.27%, CBV +19.72%, MTT -14.65%, TTP -7.46%) sides. PS decreased by almost half: ipsilateral -48.11%, contralateral -45.19%. The decline in BBB permeability was symmetrical on the ipsi- and contralateral sides to the stenosis. Augmented BBB permeability can be controlled by surgical intervention in humans.
Wren, Tishya A L; Mueske, Nicole M; Brophy, Christopher H; Pace, J Lee; Katzel, Mia J; Edison, Bianca R; VandenBerg, Curtis D; Zaslow, Tracy L
2018-03-30
Study Design Retrospective cohort. Background Return to sport (RTS) protocols after anterior cruciate ligament reconstruction (ACLR) often include assessment of hop distance symmetry. However, it is unclear if movement deficits are present regardless of hop symmetry. Objectives To assess biomechanics and symmetry of adolescent athletes following ACLR during a single leg hop for distance. Methods Forty-six patients with ACLR (5-12 months post-surgery; 27 female; age 15.6, SD 1.7 years) were classified as asymmetric (operative limb hop distance <90% of non-operative limb; n=17) or symmetric (n=29). Lower extremity biomechanics were compared among operative and contralateral limbs and 24 symmetric controls (12 female; age 14.7, SD 1.5 years) using ANOVA. Results Compared to controls, asymmetric patients hopped a shorter distance on their operative limb (P<0.001), while symmetric patients hopped an intermediate distance on both sides (P≥0.12). During landing, operative limbs, regardless of hop distance, exhibited lower knee flexion moments compared to controls and the contralateral side (P≤0.04) with lower knee energy absorption than the contralateral side (P≤0.006). During take-off, both symmetric and asymmetric patients had less hip extension and smaller ankle range of motion on the operative side compared with controls (P≤0.05). Asymmetric patients also had lower hip range of motion on the operative, compared with the contralateral, side (P=0.001). Conclusion Both symmetric and asymmetric patients offloaded the operative knee; symmetric patients achieved symmetry in part by hopping a shorter distance on the contralateral side. Therefore, hop distance symmetry may not be an adequate test of single limb function and RTS readiness. Level of Evidence 2b. J Orthop Sports Phys Ther, Epub 30 Mar 2018. doi:10.2519/jospt.2018.7817.
Friel, KM; Chakrabarty, S; H-C, Kuo; Martin, JH
2012-01-01
This study investigated requirements for restoring motor function after corticospinal (CS) system damage during early postnatal development. Activity-dependent competition between the CS tracts (CST) of the two hemispheres is imperative for normal development. Blocking primary motor cortex (M1) activity unilaterally during a critical period (postnatal weeks-PW-5–7) produces permanent contralateral motor skill impairments, loss of M1 motor map, aberrant CS terminations, and decreases in CST presynaptic sites and spinal cholinergic interneuron numbers. To repair these motor systems impairments and restore function, we manipulated motor experience in three groups of cats after this CST injury produced by inactivation. One group wore a jacket restraining the limb ipsilateral to inactivation, forcing use of the contralateral, impaired, limb, for the month following M1 inactivation (PW8–13; “Restraint Alone”). A second group wore the restraint during PW8–13, and was also trained for 1 h/day in a reaching task with the contralateral forelimb (“Early Training”). To test the efficacy of intervention during adolescence, a third group wore the restraint and received reach training during PW20–24 (“Delayed Training”). Early training restored CST connections and the M1 motor map; increased cholinergic spinal interneurons numbers on the contralateral, relative to ipsilateral, side; and abrogated limb control impairments. Delayed training restored CST connectivity and the M1 motor map, but not contralateral spinal cholinergic cell counts or motor performance. Restraint alone only restored CST connectivity. Our findings stress the need to reestablish the integrated functions of the CS system at multiple hierarchical levels in restoring skilled motor function after developmental injury. PMID:22764234
Ginsberg, M D; Chang, J Y; Kelley, R E; Yoshii, F; Barker, W W; Ingenito, G; Boothe, T E
1988-02-01
To investigate local metabolic and hemodynamic interrelationships during functional activation of the brain, paired studies of local cerebral glucose utilization (lCMRGlc) and blood flow (lCBF) were carried out in 10 normal subjects (9 right-handed, 1 ambidextrous) at rest and during a unilateral discriminative somatosensory/motor task--palpation and sorting of mah-jongg tiles by engraved design. The extent of activation was assessed on the basis of percentage difference images following normalization to compensate for global shifts. The somatosensory stimulus elevated lCMRGlc by 16.9 +/- 3.5% (mean +/- standard deviation) and lCBF by 26.5 +/- 5.1% in the contralateral sensorimotor cortical focus; smaller increments were noted in the homologous ipsilateral site. The increments of lCMRGlc and lCBF correlated poorly with one another in individual subjects. Stimulation of the right hand resulted in significantly higher contralateral lCMRGlc activation (19.6%) than did stimulation of the left hand (14.1%) (p less than 0.005), whereas the lCBF response was independent of the hand stimulated. Our results indicate that both glycolytic metabolism and blood flow increase locally with the execution of an active sensorimotor task and suggest that both measures may serve as reliable markers of functional activation of the normal brain.
... this page: //medlineplus.gov/ency/presentations/100069.htm Kidney removal (nephrectomy) - series—Normal anatomy To use the sharing features on this page, please enable JavaScript. Go to slide 1 out of 5 Go to slide 2 out of ... to slide 5 out of 5 Overview The kidneys are paired organs that lie posterior to the ...
Plotnikov, E Y; Chupyrkina, A A; Jankauskas, S S; Pevzner, I B; Silachev, D N; Skulachev, V P; Zorov, D B
2011-01-01
Oxidative stress-related renal pathologies apparently include rhabdomyolysis and ischemia/reperfusion phenomenon. These two pathologies were chosen for study in order to develop a proper strategy for protection of the kidney. Mitochondria were found to be a key player in these pathologies, being both the source and the target for excessive production of reactive oxygen species (ROS). A mitochondria-targeted compound which is a conjugate of a positively charged rhodamine molecule with plastoquinone (SkQR1) was found to rescue the kidney from the deleterious effect of both pathologies. Intraperitoneal injection of SkQR1 before the onset of pathology not only normalized the level of ROS and lipid peroxidized products in kidney mitochondria but also decreased the level of cytochrome c in the blood, restored normal renal excretory function and significantly lowered mortality among animals having a single kidney exposed to ischemia/reperfusion. The SkQR1-derivative missing plastoquinone (C12R1) possessed some, although limited nephroprotective properties and enhanced animal survival after ischemia/reperfusion. SkQR1 was found to induce some elements of nephroprotective pathways providing ischemic tolerance such as an increase in erythropoietin levels and phosphorylation of glycogen synthase kinase 3β in the kidney. SkQR1 also normalized renal erythropoietin level lowered after kidney ischemia/reperfusion and injection of a well-known nephrotoxic agent gentamicin. Copyright © 2010 Elsevier B.V. All rights reserved.
Gu, Liubao; Huang, Liji; Wu, Haidi; Lou, Qinglin; Bian, Rongwen
2017-05-01
Serum uric acid has shown to be a predictor of renal disease progression in most but not all studies. This study aims to test whether renal function-normalized serum uric acid is superior to serum uric acid as the predictor of incident chronic kidney disease in type 2 diabetes mellitus patients. In this study, 1339 type 2 diabetes mellitus patients with estimated glomerular filtration rate ⩾60 mL/min/1.73 m 2 and normouricemia were included. Renal function-normalized serum uric acid was calculated using serum uric acid/creatinine. Cox regression analysis was used to estimate the association between serum uric acid, renal function-normalized serum uric acid and incident chronic kidney disease. In total, 74 (5.53%) patients developed to chronic kidney disease 3 or greater during a median follow-up of 4 years, with older ages, longer diabetes duration and lower estimated glomerular filtration rate at baseline. The decline rate of estimated glomerular filtration rate was positively correlated with serum uric acid/creatinine ( r = 0.219, p < 0.001), but not serum uric acid ( r = 0.005, p = 0.858). Moreover, multivariate analysis revealed that serum uric acid was not an independent risk factor for incident chronic kidney disease ( p = 0.055), whereas serum uric acid to creatinine ratio was significantly associated with incident chronic kidney disease independently of potential confounders including baseline estimated glomerular filtration rate. serum uric acid to creatinine ratio might be a better predictor of incident chronic kidney disease in type 2 diabetes mellitus patients.
Hojman, Pernille; Brolin, Camilla; Gissel, Hanne; Brandt, Claus; Zerahn, Bo; Pedersen, Bente Klarlund; Gehl, Julie
2009-06-12
Erythropoietin can be over-expressed in skeletal muscles by gene electrotransfer, resulting in 100-fold increase in serum EPO and significant increases in haemoglobin levels. Earlier studies have suggested that EPO improves several metabolic parameters when administered to chronically ill kidney patients. Thus we applied the EPO over-expression model to investigate the metabolic effect of EPO in vivo.At 12 weeks, EPO expression resulted in a 23% weight reduction (P<0.01) in EPO transfected obese mice; thus the mice weighed 21.9+/-0.8 g (control, normal diet,) 21.9+/-1.4 g (EPO, normal diet), 35.3+/-3.3 g (control, high-fat diet) and 28.8+/-2.6 g (EPO, high-fat diet). Correspondingly, DXA scanning revealed that this was due to a 28% reduction in adipose tissue mass.The decrease in adipose tissue mass was accompanied by a complete normalisation of fasting insulin levels and glucose tolerance in the high-fat fed mice. EPO expression also induced a 14% increase in muscle volume and a 25% increase in vascularisation of the EPO transfected muscle. Muscle force and stamina were not affected by EPO expression. PCR array analysis revealed that genes involved in lipid metabolism, thermogenesis and inflammation were increased in muscles in response to EPO expression, while genes involved in glucose metabolism were down-regulated. In addition, muscular fat oxidation was increased 1.8-fold in both the EPO transfected and contralateral muscles.In conclusion, we have shown that EPO when expressed in supra-physiological levels has substantial metabolic effects including protection against diet-induced obesity and normalisation of glucose sensitivity associated with a shift to increased fat metabolism in the muscles.
Hojman, Pernille; Brolin, Camilla; Gissel, Hanne; Brandt, Claus; Zerahn, Bo; Pedersen, Bente Klarlund; Gehl, Julie
2009-01-01
Erythropoietin can be over-expressed in skeletal muscles by gene electrotransfer, resulting in 100-fold increase in serum EPO and significant increases in haemoglobin levels. Earlier studies have suggested that EPO improves several metabolic parameters when administered to chronically ill kidney patients. Thus we applied the EPO over-expression model to investigate the metabolic effect of EPO in vivo. At 12 weeks, EPO expression resulted in a 23% weight reduction (P<0.01) in EPO transfected obese mice; thus the mice weighed 21.9±0.8 g (control, normal diet,) 21.9±1.4 g (EPO, normal diet), 35.3±3.3 g (control, high-fat diet) and 28.8±2.6 g (EPO, high-fat diet). Correspondingly, DXA scanning revealed that this was due to a 28% reduction in adipose tissue mass. The decrease in adipose tissue mass was accompanied by a complete normalisation of fasting insulin levels and glucose tolerance in the high-fat fed mice. EPO expression also induced a 14% increase in muscle volume and a 25% increase in vascularisation of the EPO transfected muscle. Muscle force and stamina were not affected by EPO expression. PCR array analysis revealed that genes involved in lipid metabolism, thermogenesis and inflammation were increased in muscles in response to EPO expression, while genes involved in glucose metabolism were down-regulated. In addition, muscular fat oxidation was increased 1.8-fold in both the EPO transfected and contralateral muscles. In conclusion, we have shown that EPO when expressed in supra-physiological levels has substantial metabolic effects including protection against diet-induced obesity and normalisation of glucose sensitivity associated with a shift to increased fat metabolism in the muscles. PMID:19521513
Clinical case report: a rare cause of acute kidney failure - tissue is the issue.
Heggermont, Ward A; Verhoef, Gregor; Evenepoel, Pieter; Sprangers, Ben; Lerut, Evelyn; Tousseyn, Thomas; Claes, Kathleen
2017-06-01
A patient was admitted to the medical emergency department by his family physician. His complaints were weakness and fatigue for more than one week. Four days before admission, he went to his general practitioner for these complaints and also for painful elbows. His physician prescribed diclofenac and esomeprazole. Upon presentation, he had high systolic/diastolic blood pressure (>180/>90 mm Hg, measured repeatedly), and otherwise normal parameters. He had gained 6.5 kg in body weight. Clinical examination was normal, except for very mild bilateral malleolar edema. Routine blood tests showed a strongly elevated serum creatinine, hyperkalemia, and elevated lactate dehydrogenase. Haptoglobin levels were normal. Urinalysis showed a normal sediment, urine and blood cultures remained sterile. Ophthalmoscopy was completely normal, as was a routine chest X-ray. Renal ultrasound demonstrated kidneys with a diameter of 13 cm. Due to uncontrollable hypertension, our patient was hospitalized at the intensive care department where intravenous nifedipine was started, with good instantaneous control of blood pressure. Because of increasing potassium levels acute hemodialysis was started within 24 h after admission. Differential diagnosis consisted of diclofenac- or esomeprazole-induced interstitial nephritis or rapidly progressive glomerulonephritis. A renal biopsy was performed within 72 h after admission. The kidney biopsy showed an overwhelming inflammatory cell infiltrate consisting of a monoclonal lymphocytic cell population. However, the numerous mitotic figures, polyploidy, and prominent nucleoli present, were indicative of a lymphoma. Additional stainings confirmed a non-Hodgkin diffuse large-cell B-cell lymphoma. Treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine, and prednisolone) was initiated with very good clinical and biochemical response, yet only mild recovery of kidney function. Occasionally the kidney is involved as an extranodal non-Hodgkin lymphoma (NHL) localization. However, a primary presentation of acute kidney failure due to lymphoma localization is extremely rare. Our case demonstrates that early renal biopsy is indispensable for fast and adequate diagnosis and treatment.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Scharpfenecker, Marion, E-mail: m.scharpfenecker@nki.nl; Floot, Ben; Russell, Nicola S.
Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent the development of late normal tissue damage and radiation nephropathy in the mouse kidney. Methods and Materials: Kidneys of C57Bl/6 mice were irradiated with a single dose of 14 Gy. Starting from week 16 after irradiation, the mice were fed with thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, andmore » 40 weeks after irradiation. Results: Thalidomide improved the vascular structure and vessel perfusion after irradiation, associated with a normalization of pericyte coverage. The drug also reduced infiltration of inflammatory cells but could not suppress the development of fibrosis. Irradiation-induced changes in hematocrit and blood urea nitrogen levels were not rescued by thalidomide. Moreover, thalidomide worsened tubular damage after irradiation and also negatively affected basal tubular function. Conclusions: Thalidomide improved the inflammatory and vascular side effects of kidney irradiation but could not reverse tubular toxicity, which probably prevented preservation of kidney function.« less
Berman, N E; Grant, S
1992-07-01
The callosal connections between visual cortical areas 17 and 18 in adult normally pigmented and "Boston" Siamese cats were studied using degeneration methods, and by transport of WGA-HRP combined with electrophysiological mapping. In normal cats, over 90% of callosal neurons were located in the supragranular layers. The supragranular callosal cell zone spanned the area 17/18 border and extended, on average, some 2-3 mm into both areas to occupy a territory which was roughly co-extensive with the distribution of callosal terminations in these areas. The region of the visual field adjoining the vertical meridian that was represented by neurons in the supragranular callosal cell zone was shown to increase systematically with decreasing visual elevation. Thus, close to the area centralis, receptive-field centers recorded from within this zone extended only up to 5 deg into the contralateral hemifield but at elevations of -10 deg and -40 deg they extended as far as 8 deg and 14 deg, respectively, into this hemifield. This suggests an element of visual non-correspondence in the callosal pathway between these cortical areas, which may be an essential substrate for "coarse" stereopsis at the visual midline. In the Siamese cats, the callosal cell and termination zones in areas 17 and 18 were expanded in width compared to the normal animals, but the major components were less robust. The area 17/18 border was often devoid of callosal axons and, in particular, the number of supragranular layer neurons participating in the pathway were drastically reduced, to only about 25% of those found in the normally pigmented adults. The callosal zones contained representations of the contralateral and ipsilateral hemifields that were roughly mirror-symmetric about the vertical meridian, and both hemifield representations increased with decreasing visual elevation. The extent and severity of the anomalies observed were similar across individual cats, regardless of whether a strabismus was also present. The callosal pathway between these visual cortical areas in the Siamese cat has been considered "silent," since nearly all neurons within its territory are activated only by the contralateral eye. The paucity of supragranular pyramidal neurons involved in the pathway may explain this silence.
Total hip arthroplasty using a short-stem prosthesis: restoration of hip anatomy.
Amenabar, Tomas; Marimuthu, Kanniraj; Hawdon, Gabrielle; Gildone, Alessandro; McMahon, Stephen
2015-04-01
To evaluate hip parameters such as vertical centre of rotation (VCR), horizontal centre of rotation (HCR), femoral offset, and leg length after total hip arthroplasty (THA) using the Nanos short-stem prosthesis. Medical records of 73 men and 74 women aged 25 to 92 (mean, 63) years who underwent THA using the Nanos short-stem prosthesis by a single surgeon were reviewed. Prior to the surgery, the optimal cup and stem size, head length, and level of the neck osteotomy were determined using radiographs. Intra-operatively, the leg length and femoral offset were checked, and the level of neck resection and head length were adjusted. VCR, HCR, femoral offset, and leg length of the operated and contralateral sides were compared. Functional outcomes were assessed using the Harris Hip Score (HHS). Compared with the normal contralateral hips, the operated hips had a mean increase of 0.4 mm in VCR (p=0.032), a mean decrease of 1.4 mm in HCR (p=0.027), a mean increase of 0.6 mm in femoral offset (p=0.043), and a mean increase of 0.36 mm in leg length (p=0.035). For these respective parameters, the difference between the normal contralateral side and the operated side was within 5 mm in 89%, 80%, 71%, and 96% of patients. The HHS improved from a mean of 53 to 91 at one year (p<0.001). THA using the Nanos short-stem prosthesis enabled restoration of hip anatomy (VCR, HCR, femoral offset, and leg length).
Vascular Dysfunction in Leukoaraiosis.
Sam, K; Crawley, A P; Poublanc, J; Conklin, J; Sobczyk, O; Mandell, D M; Duffin, J; Venkatraghavan, L; Fisher, J A; Black, S E; Mikulis, D J
2016-12-01
The pathogenesis of leukoaraiosis has long been debated. This work addresses a less well-studied mechanism, cerebrovascular reactivity, which could play a leading role in the pathogenesis of this disease. Our aim was to evaluate blood flow dysregulation and its relation to leukoaraiosis. Cerebrovascular reactivity, the change in the blood oxygen level-dependent 3T MR imaging signal in response to a consistently applied step change in the arterial partial pressure of carbon dioxide, was measured in white matter hyperintensities and their contralateral spatially homologous normal-appearing white matter in 75 older subjects (age range, 50-91 years; 40 men) with leukoaraiosis. Additional quantitative evaluation of regions of leukoaraiosis was performed by using diffusion (n = 75), quantitative T2 (n = 54), and DSC perfusion MRI metrics (n = 25). When we compared white matter hyperintensities with contralateral normal-appearing white matter, cerebrovascular reactivity was lower by a mean of 61.2% ± 22.6%, fractional anisotropy was lower by 44.9 % ± 6.9%, and CBF was lower by 10.9% ± 11.9%. T2 was higher by 61.7% ± 13.5%, mean diffusivity was higher by 59.0% ± 11.7%, time-to-maximum was higher by 44.4% ± 30.4%, and TTP was higher by 6.8% ± 5.8% (all P < .01). Cerebral blood volume was lower in white matter hyperintensities compared with contralateral normal-appearing white matter by 10.2% ± 15.0% (P = .03). Not only were resting blood flow metrics abnormal in leukoaraiosis but there is also evidence of reduced cerebrovascular reactivity in these areas. Studies have shown that reduced cerebrovascular reactivity is more sensitive than resting blood flow parameters for assessing vascular insufficiency. Future work is needed to examine the sensitivity of resting-versus-dynamic blood flow measures for investigating the pathogenesis of leukoaraiosis. © 2016 by American Journal of Neuroradiology.
Chen, Defu; Ren, Jie; Wang, Ying; Zhao, Hongyou; Li, Buhong; Gu, Ying
2016-03-01
Laser Doppler imaging (LDI) and laser speckle imaging (LSI) are two major optical techniques aiming at non-invasively imaging the skin blood perfusion. However, the relationship between perfusion values determined by LDI and LSI has not been fully explored. 8 healthy volunteers and 13 PWS patients were recruited. The perfusions in normal skin on the forearm of 8 healthy volunteers were simultaneously measured by both LDI and LSI during post-occlusive reactive hyperemia (PORH). Furthermore, the perfusions of port wine stains (PWS) lesions and contralateral normal skin of 10 PWS patients were also determined. In addition, the perfusions for PWS lesions from 3 PWS patients were successively monitored at 0, 10 and 20min during vascular-targeted photodynamic therapy (V-PDT). The average perfusion values determined by LSI were compared with those of LDI for each subject. In the normal skin during PORH, power function provided better fits of perfusion values than linear function: powers for individual subjects go from 1.312 to 1.942 (R(2)=0.8967-0.9951). There was a linear relationship between perfusion values determined by LDI and LSI in PWS and contralateral normal skin (R(2)=0.7308-0.9623), and in PWS during V-PDT (R(2)=0.8037-0.9968). The perfusion values determined by LDI and LSI correlate closely in normal skin and PWS over a broad range of skin perfusion. However, it still suggests that perfusion range and characteristics of the measured skin should be carefully considered if LDI and LSI measures are compared. Copyright © 2015 Elsevier B.V. All rights reserved.
Resistive index for kidney evaluation in normal and diseased cats.
Tipisca, Vlad; Murino, Carla; Cortese, Laura; Mennonna, Giuseppina; Auletta, Luigi; Vulpe, Vasile; Meomartino, Leonardo
2016-06-01
The objectives were to determine the resistive index (RI) in normal cats and in cats with various renal diseases, and to evaluate the effect of age on RI. The subjects were cats that had ultrasonography (US) of the urinary tract and RI measurement at our centre between January 2003 and April 2014. Based on clinical evaluation, biochemical and haematological tests, urinalysis and US, the cats were classified as healthy or diseased. RI measurements were made from the interlobar or arcuate arteries. Data were analysed for differences between the right and the left kidney, the two sexes, different age groups in healthy cats, and between healthy and diseased cats. A total of 116 cats (68 males, 48 females) were included: 24 healthy and 92 diseased. In the healthy cats, RI (mean ± SD) differed significantly (P = 0.02) between the right kidney (0.54 ± 0.07) and the left kidney (0.59 ± 0.08). For the left kidney, RI was significantly higher in cats with chronic kidney disease (0.73 ± 0.12) and acute kidney injury (0.72 ± 0.08) (P = 0.0008). For the right kidney, RI was significantly higher in cats with chronic kidney disease (0.72 ± 0.11), acute kidney injury (0.74 ± 0.08), polycystic kidney disease (0.77 ± 0.11) and renal tumour (0.74 ± 0.001) (P <0.0001). There was no significant effect on RI value in either kidney in terms of age or sex. RI could be considered a valuable diagnostic tool in cats, useful in the differential diagnosis of diffuse renal diseases. While it does not change with the age of the cat, ultrasonographers should be aware that RI may differ between the two kidneys. © ISFM and AAFP 2015.
Successful Surgical Treatment of Anuria Caused by Renal Artery Occlusion
Flye, M. Wayne; Anderson, Robert w.; Fish, Jay C.; Silver, Donald
1982-01-01
Anuria resulting from obstruction of the renal arteries to both Kidneys or to a solitary kidney is unusual. The tolerance of the kidney to this ischemia is largely dependent upon the presence of collaterals, stimulated by pre-existing arterial disease. Our experience with six patients with anuria caused by renal artery occlusion supports the role of revascularization in the recovery of significant renal function. Four of these patients had hypertension, impaired renal function, and the existence of collateral circulation to an ischemic kidney, prior to occlusion, while two patients had normal renal function (serum creatinine = 0.5 and 0.9 mg/dl) before occlusion. The intervals of anuria for the two previously normal kidneys were six hours and five days, and 2 to 14 days in the four patients with vascular disease. Isotope scanning suggested renal artery occlusion in two patients, but arteriograms confirmed the diagnosis in all six. A thrombectomy restored blood flow through the two previously normal renal arteries. Grafts from the aorta or celiax axis were used for three patients and the splenic artery was used for the sixth patient. Urine flow began during or soon after operation in all patients. Dialysis was necessary for 30 and 45 days in the two patients with normal kidneys, but in only one of the four patients with previous disease (for ten days). Serum creatinine decreased to <2.0 mg/dl after operation, except in the man with a solitary kidney, who five years later has a creatinine of 3 mg/dl. All four patients with previous arterial disease died from cardiac failure within 1 to 30 months after operation. Therefore, anuria of acute onset should be evaluated by renal scan and arteriogram to detect those patients with proximal renal artery occlusion in preparation for revascularization. ImagesFig. 2a.Fig. 2b.Fig. 3.Fig. 4a.Fig. 4b.Fig. 5.Fig. 6a.Fig. 6b. PMID:7059245
Code of Federal Regulations, 2011 CFR
2011-01-01
... kidneys and the lymph nodes which resemble lesions of hog cholera, they shall be regarded as those of hog... kidneys and lymph nodes of carcasses of hogs which appeared normal on ante-mortem inspection, further..., characteristic lesions of hog cholera are found in some organ or tissue in addition to those in the kidneys or in...
Code of Federal Regulations, 2010 CFR
2010-01-01
... kidneys and the lymph nodes which resemble lesions of hog cholera, they shall be regarded as those of hog... kidneys and lymph nodes of carcasses of hogs which appeared normal on ante-mortem inspection, further..., characteristic lesions of hog cholera are found in some organ or tissue in addition to those in the kidneys or in...
Uemura, Osamu; Iwata, Naoyuki; Nagai, Takuhito; Yamakawa, Satoshi; Hibino, Satoshi; Yamamoto, Masaki; Nakano, Masaru; Tanaka, Kazuki
2018-05-01
To determine the optimal method of evaluating kidney function in patients with thyroid dysfunction, this study compared the estimated glomerular filtration rate derived from serum creatinine, cystatin C, or β2-microglobulin with inulin or creatinine clearance in two pediatric patients, one with hypothyroidism and the other with hyperthyroidism. It was observed that the kidney function decreased in a hypothyroid child and enhanced in a hyperthyroid child, with their kidney function becoming normalized by treatment with drugs, which normalized their thyroid function. Kidney function cannot be accurately evaluated using cystatin C-based or β2-microglobulin-based estimated glomerular filtration rate in patients with thyroid dysfunction, as these tests overestimated glomerular filtration rate in a patient with hypothyroidism and underestimated glomerular filtration rate in a patient with hyperthyroidism, perhaps through a metabolic rate-mediated mechanism. In both our patients, 24-h urinary creatinine secretion was identical before and after treatment, suggesting that creatinine production is not altered in patients with thyroid dysfunction. Therefore, kidney function in patients with thyroid dysfunction should be evaluated using creatinine-based estimated glomerular filtration rate.
Periodontitis associated with chronic kidney disease among Mexican Americans.
Ioannidou, Effie; Hall, Yoshio; Swede, Helen; Himmelfarb, Jonathan
2013-01-01
In comparison to non-Hispanic whites, a number of health-care disparities, including poor oral health, have been identified among Hispanics in general and Mexican Americans in particular. We hypothesized that Mexican Americans with chronic kidney disease (CKD) would have higher prevalence of chronic periodontitis compared with Mexican Americans with normal kidney function, and that the level of kidney function would be inversely related to the prevalence of periodontal disease. We examined this hypothesis using the National Health and Nutrition Examination Survey 1988-1994 (NHANES III) data set. We followed the American Academy of Periodontology/Center for Disease Control and Prevention case definition for periodontitis. Glomerular filtration rate was estimated using the CKD-Epidemiology equation for Hispanic populations. The classification to CKD stages was based on the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Periodontitis prevalence increased across the kidney function groups showing a statistically significant dose-response association (P<0.001). Mexican Americans with reduced kidney function were twofold more likely to have periodontitis compared with Mexican Americans with normal kidney function after adjusting for potential confounders such as smoking, diabetes, and socioeconomic status. Multivariate adjusted odds ratio for periodontitis significantly increased with 1, 5, and 10 mL/minute estimated glomerular filtration rate reduction from the mean. This is the first report, to the best our knowledge, that showed an increase of periodontitis prevalence with decreased kidney function in this population. © 2012 American Association of Public Health Dentistry.
Periodontitis associated with Chronic Kidney Disease among Mexican Americans
Ioannidou, Effie; Hall, Yoshio; Swede, Helen; Himmelfarb, Jonathan
2012-01-01
Objective In comparison to non-Hispanic whites, a number of healthcare disparities, including poor oral health, have been identified among Hispanics in general and Mexican-Americans in particular. We hypothesized that Mexican-Americans with Chronic Kidney disease (CKD) would have higher prevalence of chronic periodontitis compared to Mexican Americans with normal kidney function, and that the level of kidney function would be inversely related to the prevalence of periodontal disease. Method We examined this hypothesis using the National Health and Nutrition Examination Survey 1988–1994 (NHANES III) dataset. We followed the American Academy of Periodontology (AAP)/Center for Disease Control and Prevention (CDC) case definition for periodontitis. Glomerular filtration rate was estimated using the CKD-Epidemiology (EPI) equation for Hispanic populations. The classification to CKD stages was based on the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Results Periodontitis prevalence increased across the kidney function groups showing a statistically significant dose-response association (p<0.001). Mexican Americans with reduced kidney function were 2-fold more likely to have periodontitis compared to Mexican Americans with normal kidney function after adjusting for potential confounders such as smoking, diabetes and socioeconomic status. Multivariate adjusted Odds Ratio for periodontitis significantly increased with 1, 5 and 10 mL/minute eGFR reduction from the mean. Conclusion This is the first report, to the best our knowledge, that showed an increase of periodontitis prevalence with decreased kidney function in this population. PMID:22775287
Li, Rui; Dai, Jinna; Kang, Hui
2018-03-01
Serum creatinine, urea, and cystatin-c are standardly used for the evaluation of renal function in the clinic. However, some patients have chronic kidney disease but still retain kidney function; a conventional serum index in these patients can be completely normal. Serum amino acid levels can reflect subtle changes in metabolism and are closely related to renal function. Here, we investigated how amino acids change as renal impairment increases. Subjects were divided into three groups by renal function glomerular filtration rate: healthy controls, patients with chronic kidney disease with normal kidney function, and patients with chronic kidney disease with decreased kidney function group. We identified 11 amino acids of interest using LC-MS/MS on MRM (+) mode. Statistical analysis indicated that alanine (ALA), valine (VAL), and tyrosine (TYR) decrease with renal function impairment, whereas phenylalanine (PHE) and citrulline (CIT) increase. We tried to construct a diagnostic model utilizing a combination of amino acids capable of identifying early chronic kidney disease patients. The accuracy, specificity, and sensitivity of the combining predictors were 86.9%, 84.6%, and 90.9%, respectively, which is superior to the reported values for serum creatinine, urea, and cystatin-c. Our data suggest that serum amino acid levels may supply important information for the early detection of chronic kidney disease. We are the first to establish a diagnostic model utilizing serum levels of multiple amino acids for the diagnosis of patients with early-stage chronic kidney disease. © 2017 Wiley Periodicals, Inc.
Idiopathic granulomatous mastitis: magnetic resonance imaging findings with diffusion MRI.
Aslan, Hulya; Pourbagher, Aysin; Colakoglu, Tamer
2016-07-01
Idiopathic granulomatous mastitis (IGM) is a rare benign breast disease with unknown etiology which can mimic breast carcinoma, both clinically and radiologically. Magnetic resonance imaging (MRI) findings of IGM have been previously described; however there is no study evaluating diffusion-weighted MRI findings of IGM. To analyze conventional, dynamic contrast-enhanced, and diffusion-weighted MRI signal characteristics of IGM by comparing it with the contralateral normal breast parenchyma. A total of 39 patients were included in the study. On dynamic contrast-enhanced MRI, the distribution and enhancement patterns of the lesions were evaluated. We also detected the frequencies of involving quadrants, retroareolar involvement, accompanying abscess, and skin edema. T2-weighted (T2W) and STIR signal intensities and both mean and minimum apparent diffusion coefficient (ADC) values were compared with the contralateral normal parenchyma. IGM showed significantly lower mean and minimum ADC values when compared with the normal parenchyma. Signal intensities on T2W and STIR sequences of the lesion were significantly higher than the normal parenchyma. On dynamic contrast-enhanced MRI, 7.7% of the patients had mass-like contrast enhancement, 92.3% of the patients had non-mass-like contrast enhancement. Abscess was positive in 33.3% of the patients. As a result, IGM showed commonly non-mass-like lesions with restricted diffusion. Although it is a benign pathology, it may show clustered ring-like enhancement like malignant lesions. © The Foundation Acta Radiologica 2015.
Suppression of Rabbit VX‐2 Subcutaneous Tumor Growth by Gadolinium Neutron Capture Therapy
Tokita, Nobuhiko; Tokuuye, Koichi; Satoh, Michinao; Churei, Hisahiko; Pechoux, Cécile Le; Kobayashi, Tooru; Kanda, Keiji
1993-01-01
VX‐2 tumors growing in hind legs of New Zealand White rabbits (n=4) were exposed to thermal neutrons for 40 min (2.1 × 1012 neutrons cm−2) while one of two hind leg tumors of each rabbit was infused continuously with meglumine gadopentetate through a branch of the left femoral artery. The contralateral (uninfused) tumors served as controls. Although no differential distribution of gadolinium was achieved between the tumor and its adjacent normal tissue, the gadolinium concentration in the infused tumor was approximately 5–6 fold higher than that in the contralateral tumor. Growth of gadolinium‐infused tumors was significantly inhibited compared to that of control tumors (P<0.05) between the 16th and 23rd days after treatment. PMID:8407547
Li, Jiang; Guo, Qing-Jun; Cai, Jin-Zhen; Pan, Cheng; Shen, Zhong-Yang; Jiang, Wen-Tao
2017-12-07
Simultaneous liver, pancreas-duodenum, and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis, renal failure, and insulin dependent diabetes mellitus (IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus, mycophenolate mofetil, and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15 th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation, and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.
Voronkova, Y S; Babiy, S O; Ivans'kar, L V; Shtemenko, O V; Shtemenko, N I
2015-01-01
Biochemical characteristics of kidneys, pe- ripheral blood and bone marrow of rats in model of tumor growth under introduction of cisplatin and cis-tetrachlorodi-μ-isobutyratodirhenium(III), cis-Re2(i-C3H7COO)2Cl4 (I) have been investigated. It was shown that introduction of I alone and together with cisplatin led to decrease of biochemical markers of oxidation of lipids and proteins in tissue homogenates of the kidneys, change of enzyme activity in the urea and tissue homogenates of the kidneys, by a decrease of filtration function of kidneys. Introduction of nanoliposomal forms of the rhenium cluster compound led to a practically normal morphological picture of bone marrow and increase of the RBC (by 60%) with normalization of hematocrit counts, and decrease of quantities of destructed RBC (3.2 times) in comparison with the tumor-bearing animals. A tentative scheme of influence of cluster rhenium compound on erythropoiesis through regulation of synthesis of erythropoietin in kidneys has been proposed.
Wilson, Patricia D.; Devuyst, Olivier; Li, Xiaohong; Gatti, Laura; Falkenstein, Doris; Robinson, Shawn; Fambrough, Douglas; Burrow, Christopher R.
2000-01-01
Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease of the kidney, characterized by cystic enlargement of renal tubules, aberrant epithelial proliferation, and ion and fluid secretion into the lumen. Previous studies have shown abnormalities in polarization of membrane proteins, including mislocalization of the NaK-ATPase to the apical plasma membranes of cystic epithelia. Apically located NaK-ATPase has previously been shown to be fully functional in vivo and in membrane-grown ADPKD epithelial cells in vitro, where basal-to-apical 22Na transport was inhibited by application of ouabain to the apical membrane compartment. Studies were conducted with polymerase chain reaction-generated specific riboprobes and polyclonal peptide antibodies against human sequences of α1, α3, β1, and β2 subunits of NaK-ATPase. High levels of expression of α1 and β1 messenger RNA were detected in ADPKD and age-matched normal adult kidneys in vivo, whereas β2 messenger RNA was detected only in ADPKD kidneys. Western blot analysis and immunocytochemical studies showed that, in normal adult kidneys, peptide subunit-specific antibodies against α1 and β1 localized to the basolateral membranes of normal renal tubules, predominantly thick ascending limbs of Henle’s loop. In ADPKD kidneys, α1 and β2 subunits were localized to the apical epithelial cell membranes, whereas β1 was distributed throughout the cytoplasm and predominantly in the endoplasmic reticulum, but was not seen associated with cystic epithelial cell membranes or in cell membrane fractions. Polarizing, renal-derived epithelial Madin Darby canine kidney cells, stably expressing normal or N-terminally truncated chicken β1 subunits, showed selective accumulation in the basolateral Madin Darby canine kidney cell surface, whereas c-myc epitope-tagged chicken β2 or human β2 subunits accumulated selectively in the apical cell surface. Similarly, human ADPKD epithelial cell lines, which endogenously expressed α1 and β2 NaK-ATPase subunits, showed colocalization at the apical cell surface and coassociation by immunoprecipitation analysis. These results are consistent with a model in which the additional transcription and translation of the β2 subunit of NaK-ATPase may result in the apical mislocalization of NaK-ATPase in ADPKD cystic epithelia. PMID:10623674
Lesions in mink (Mustela vison) infected with giant kidney worm (Dioctophyma renale).
Mace, T F
1976-01-01
Adult Dioctophyma renale occupied the enlarged renal pelvis of the right kidney of naturally infected mink. Lesions in the kidney parenchyma consisted of connective tissue proliferation in the interstitial tissue, tubular atrophy and fibrosis, and periglomerular fibrosis. The luminal surface of the renal pelvis wall was formed of numerous papillae covered with transitional epithelium. The nematodes in the lumen were bathed in an albuminous fluid containing red blood cells, epithelial cells and D. renale eggs. The left (uninfected) kidney was 60% larger than the left kidney of normal mink.
Pediatric Inflammatory Bowel Diseases: Should We Be Looking for Kidney Abnormalities?
Lauritzen, Didde; Andreassen, Bente Utoft; Heegaard, Niels Henrik H; Klinge, Lone Gabriels; Walsted, Anne-Mette; Neland, Mette; Nielsen, Rasmus Gaardskær; Wittenhagen, Per
2018-04-26
Kidney disease has been reported in adults with inflammatory bowel disease (IBD) and is regarded an extraintestinal manifestation or more rarely a side effect of the medical treatment. In this cross-sectional study we describe the extent of kidney pathology in a cohort of 56 children with IBD. Blood and urine samples were analyzed for markers of kidney disease and ultrasonography was performed to evaluate pole-to-pole kidney length. We found that 25% of the patients had either previously reported kidney disease or ultrasonographic signs of chronic kidney disease. The median kidney size compared with normal children was significantly reduced. In a multivariate linear mixed model, small kidneys significantly correlated with the use of infliximab, whereas the use of enteral nutritional therapy was associated with larger kidneys. Children with IBD are at risk of chronic kidney disease, and the risk seems to be increased with the severity of the disease.
... or monitor many types of kidney diseases. Normal Results For adults, normal urine sodium values are generally ... meaning of your specific test result. What Abnormal Results Mean A higher than normal urine sodium level ...
The Effect of Contralateral Acoustic Stimulation on Spontaneous Otoacoustic Emissions
Dhar, Sumitrajit
2009-01-01
Evoked otoacoustic emissions are often used to study the medial olivocochlear (MOC) efferents in humans. There has been concern that the emission-evoking stimulus may itself elicit efferent activity and alter the evoked otoacoustic emission. Spontaneous otoacoustic emissions (SOAEs) are hence advantageous as no external stimulation is necessary to record the response in the test ear. Contralateral acoustic stimulation (CAS) has been shown to suppress SOAE level and elevate SOAE frequency, but the time course of these effects is largely unknown. By utilizing the Choi–Williams distribution, here we report a gradual adaptation during the presence of CAS and an overshoot following CAS offset in both SOAE magnitude and frequency from six normal-hearing female human subjects. Furthermore, we have quantified the time constants of both magnitude and frequency shifts at the onset, presence, and offset of four levels of CAS. Most studies using contralateral elicitors do not stringently control the middle-ear muscle (MEM) reflex, leaving the results difficult to interpret. In addition to clinically available measures of the MEM reflex, we have incorporated a sensitive laboratory technique to monitor the MEM reflex in our subjects, allowing us to interpret the results with greater confidence. PMID:19798532
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jen, M; Johnson, J; Hou, P
Purpose: Cerebral blood flow quantification in arterial spin labeling (ASL) MRI requires an estimate of the equilibrium magnetization of blood, which is often obtained by a set of proton density (PD) reference image. Normally, a constant blood-brain partition coefficient is assumed across the brain. However, this assumption may not be valid for brain lesions. This study aimed to evaluate the impact of lesion-related PD variations on ASL quantification in patients with brain tumors. Methods: MR images for posttreatment evaluation of 42 patients with brain tumors were retrospectively analyzed. These images were acquired on a 3T MRI scanner, including T2-weighted FLAIR,more » 3D pseudo-continuous ASL and post-contrast T1-weighted images. Anatomical images were coregistered with ASL images using the SPM software. Regions of interest (ROIs) of the enhancing and FLAIR lesions were manually drawn on the coregistered images. ROIs of the contralateral normal appearing tissues were also determined, with the consideration of approximating coil sensitivity patterns in lesion ROIs. Relative lesion blood flow (lesion/contralateral tissue) was calculated from both the CBF map (dependent on the PD) and the ΔM map for comparison. Results: The signal intensities in both enhancing and FLAIR lesions were significantly different than contralateral tissues on the PD reference image (p<0.001). The percent signal difference ranged from −15.9 to 19.2%, with a mean of 5.4% for the enhancing lesion, and from −2.8 to 22.9% with a mean of 10.1% for the FLAIR lesion. The high/low lesion-related PD signal resulted in inversely proportional under-/over-estimation of blood flow in both enhancing and FLAIR lesions. Conclusion: Significant signal differences were found between lesions and contralateral tissues in the PD reference image, which introduced errors in blood flow quantification in ASL. The error can be up to 20% in individual patients with an average of 5- 10% for the group of patients with brain tumors.« less
Zomorrodi, Afshar; Buhluli, Abulfazel; Fathi, Samad
2010-07-01
At least 5% of women and 12% of men during their lives will experience renal colic, at least once. Many theories have been suggested for the etiology of renal stones and variations in the anatomy of the collecting system have been suggested to have a role in stone formation. This study was conducted to examine the role of variation of lower pole collecting system in patients with lower pole kidney stone and compared the same in normal persons (kidney donors). Investigation for the anatomy of the lower pole of the kidney (angle between lower infundibulum and pelvis, length and diameter of the infundibulum and number and pattern distribution of calyces) was carried out using intravenous pyelogram (IVP) in 100 cases with urinary stone (study cases) and 400 persons with normal kidneys (control subjects). The study was a retrospective cross-sectional case control study. Results were analyzed by Mann-Whitney and independent sample chi square tests. The mean infundibulum-pelvic angle (IPA) in control subjects and in patients was 112.5 +/- 10.7 and 96.6 +/- 28.8, respectively. There was significant correlation between reduced angle and stone formation (P= < 0.001). The mean infundibulum-uretero-pelvic angle (IUPA) in control subjects and study cases was 53.5 +/- 12.7 and 42.6 +/- 13.4, respectively. There was significant correlation between decreased angle and stone formation (P = or < 0.001). The mean length of infundibulum of lower pole of kidney (IPIL) in controls and study patients was 22.5 +/- 4.1 and 27.5 +/- 7.7, respectively, which was statistically significant (P< 0.001). The mean number of calyces in lower pole of the kidney (LPCN) in controls and study patients was 2.6 +/- 0.6 and 3 +/- 0.9, respectively, which was statistically significant (P = or < 0.002). There was no significant correlation between distribution of calyces and stone formation (P= 0.366). Our study suggests that abnormal renal anatomy was more common in patients with lower pole kidney stone and should be considered a risk factor for forming lower pole kidney stone.
Gender and urinary pH affect melamine-associated kidney stone formation risk
Lu, Xiuli; Wang, Jing; Cao, Xiangyu; Li, Mingxin; Xiao, Chunling; Yasui, Takahiro; Gao, Bing
2011-01-01
Objectives: Melamine was known as a new risk for kidney stone due to recent incidences of milk powder contamination in China. Here, we performed a retrospective study to investigate whether age, gender, and urinary pH affect melamine-associated kidney stone risk. Materials and Methods: A retrospective review was performed of 217 children aged less than 3 years old. All children had a history of being fed with Sanlu milk powder contaminated by melamine, and underwent a clinical screening on kidney stone in Shenyang from November 2008 to February 2009. A comparison with the Chi-square was conducted between 83 cases and 125 normal subjects. The difference between children's gender, age, and urinary pH was evaluated. Results: A total of 208 subjects, 136 boys and 72 girls, were included in the study. Significant association was observed between melamine-associated kidney stone risk and gender [odds ratio (OR), 2.03; 95% confidence interval (CI), 1.11-3.74; P=0.02] and urinary pH (OR, 1.78; 95% CI, 1.01-3.11; P=0.04), respectively. Male children were at about twofold increased melamine-associated kidney stone risk compared with female children. Acidic urine showed about 1.78-fold increased melamine-associated kidney stone risk compared with normal urine. Conclusions: Our investigation results showed an association of gender and urinary pH with melamine-associated kidney stone formation risk. PMID:21747595
Wu, Fiona Mei Wen; Tay, Melissa Hui Wen; Tai, Bee Choo; Chen, Zhaojin; Tan, Lincoln; Goh, Benjamin Yen Seow; Raman, Lata; Tiong, Ho Yee
2015-12-01
Surgically induced chronic kidney disease (CKD) has been found to have less impact on survival as well as function when compared to medical causes for CKD. The aim of this study is to evaluate whether preoperative remaining kidney volume correlates with renal function after nephrectomy, which represents an individual's renal reserve before surgically induced CKD. A retrospective review of 75 consecutive patients (29.3% females) who underwent radical nephrectomy (RN) (2000-2010) was performed. Normal side kidney parenchyma, excluding renal vessels and central sinus fat, was manually outlined in each transverse slice of CT image and multiplied by slice thickness to calculate volume. Estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Disease equation. CKD is defined as eGFR < 60 mL/min/1.73 m(2). Mean preoperative normal kidney parenchymal volume (mean age 55 [SD 13] years) is 150.7 (SD 36.4) mL. Over median follow-up of 36 months postsurgery, progression to CKD occurred in 42.6% (n = 32) of patients. On multivariable analysis, preoperative eGFR and preoperative renal volume <144 mL are independent predictors for postoperative CKD. On Kaplan-Meier analysis, median time to reach CKD postnephrectomy is 12.7 (range 0.03-43.66) months for renal volume <144 mL but not achieved if renal volume is >144 mL. Normal kidney parenchymal volume and preoperative eGFR are independent predictive factors for postoperative CKD after RN and may represent renal reserve for both surgically and medically induced CKD, respectively. Preoperative remaining kidney volume may be an adjunct representation of renal reserve postsurgery and predict later renal function decline due to perioperative loss of nephrons.
Welham, Simon J M; Sparrow, Alexander J; Gardner, David S; Elmes, Matthew J
2017-01-06
To evaluate the effects of the non-selective, non-steroidal anti-inflammatory drug (NSAID) acetylsalicylic acid (ASA), on ex vivo embryonic kidney growth and development. Pairs of fetal mouse kidneys at embryonic day 12.5 were cultured ex vivo in increasing concentrations of ASA (0.04-0.4 mg/mL) for up to 7 d. One organ from each pair was grown in control media and was used as the internal control for the experimental contralateral organ. In some experiments, organs were treated with ASA for 48 h and then transferred either to control media alone or control media containing 10 μmol/L prostaglandin E 2 (PGE 2 ) for a further 5 d. Fetal kidneys were additionally obtained from prostaglandin synthase 2 homozygous null or heterozygous (PTGS2 -/- and PTGS2 -/+ ) embryos and grown in culture. Kidney cross-sectional area was used to determine treatment effects on kidney growth. Whole-mount labelling to fluorescently detect laminin enabled crude determination of epithelial branching using confocal microscopy. Increasing ASA concentration (0.1, 0.2 and 0.4 mg/mL) significantly inhibited metanephric growth ( P < 0.05). After 7 d of culture, exposure to 0.2 mg/mL and 0.4 mg/mL reduced organ size to 53% and 23% of control organ size respectively ( P < 0.01). Addition of 10 μmol/L PGE 2 to culture media after exposure to 0.2 mg/mL ASA for 48 h resulted in a return of growth area to control levels. Application of control media alone after cessation of ASA exposure showed no benefit on kidney growth. Despite the apparent recovery of growth area with 10 μmol/L PGE 2 , no obvious renal tubular structures were formed. The number of epithelial tips generated after 48 h exposure to ASA was reduced by 40% (0.2 mg/mL; P < 0.05) and 47% (0.4 mg/mL; P < 0.01). Finally, growth of PTGS2 -/- and PTGS2 +/- kidneys in organ culture showed no differences, indicating that PTGS2 derived PGE 2 may at best have a minor role. ASA reduces early renal growth and development but the role of prostaglandins in this may be minor.
... week, and lasts 3 to 5 hours each time. Blood travels through the artificial kidney, where waste products are ... eat a more normal diet and have more time for work and travel. Peritoneal dialysis is not for everyone, however. A ...
Karaszewski, Bartosz; Carpenter, Trevor K; Thomas, Ralph G R; Armitage, Paul A; Lymer, Georgina Katherine S; Marshall, Ian; Dennis, Martin S; Wardlaw, Joanna M
2013-01-01
Pyrexia soon after stroke is associated with severe stroke and poor functional outcome. Few studies have assessed brain temperature after stroke in patients, so little is known of its associations with body temperature, stroke severity, or outcome. We measured temperatures in ischemic and normal-appearing brain using 1H-magnetic resonance spectroscopy and its correlations with body (tympanic) temperature measured four-hourly, infarct growth by 5 days, early neurologic (National Institute of Health Stroke Scale, NIHSS) and late functional outcome (death or dependency). Among 40 patients (mean age 73 years, median NIHSS 7, imaged at median 17 hours), temperature in ischemic brain was higher than in normal-appearing brain on admission (38.6°C-core, 37.9°C-contralateral hemisphere, P=0.03) but both were equally elevated by 5 days; both were higher than tympanic temperature. Ischemic lesion temperature was not associated with NIHSS or 3-month functional outcome; in contrast, higher contralateral normal-appearing brain temperature was associated with worse NIHSS, infarct expansion and poor functional outcome, similar to associations for tympanic temperature. We conclude that brain temperature is higher than body temperature; that elevated temperature in ischemic brain reflects a local tissue response to ischemia, whereas pyrexia reflects the systemic response to stroke, occurs later, and is associated with adverse outcomes. PMID:23571281
1998-01-01
Cells from kidneys lose some of their special features in conventional culture but form spheres replete with specialized cell microvilli (hair) and synthesize hormones that may be clinically useful. Ground-based research studies have demonstrated that both normal and neoplastic cells and tissues recreate many of the characteristics in the NASA bioreactor that they display in vivo. Proximal kidney tubule cells that normally have rich apically oriented microvilli with intercellular clefts in the kidney do not form any of these structures in conventional two-dimensional monolayer culture. However, when normal proximal renal tubule cells are cultured in three-dimensions in the bioreactor, both the microvilli and the intercellular clefts form. This is important because, when the morphology is recreated, the function is more likely also to be rejuvenated. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC).
Tissue grown in NASA Bioreactor
NASA Technical Reports Server (NTRS)
1998-01-01
Cells from kidneys lose some of their special features in conventional culture but form spheres replete with specialized cell microvilli (hair) and synthesize hormones that may be clinically useful. Ground-based research studies have demonstrated that both normal and neoplastic cells and tissues recreate many of the characteristics in the NASA bioreactor that they display in vivo. Proximal kidney tubule cells that normally have rich apically oriented microvilli with intercellular clefts in the kidney do not form any of these structures in conventional two-dimensional monolayer culture. However, when normal proximal renal tubule cells are cultured in three-dimensions in the bioreactor, both the microvilli and the intercellular clefts form. This is important because, when the morphology is recreated, the function is more likely also to be rejuvenated. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC).
DOE Office of Scientific and Technical Information (OSTI.GOV)
Konya, Andras, E-mail: akonya@mdanderson.org; Stephens, L. Clifton; Wright, Kenneth C.
2011-10-15
Purpose: To evaluate the efficacy of ablation with selective arterial injection of pure ethiodized oil followed by arterial occlusion with 9:1 ethanol-Ethiodol mixture (EEM) and coil placement in normal rabbit kidneys and kidneys inoculated with VX-2 carcinoma. Materials and Methods: All experiments were conducted with Animal Care and Use Committee approval. In six rabbits (group 1), one kidney was embolized with pure Ethiodol until capillary stasis, followed by injection of 9:1 EEM until arterial stasis and then coil placement into the main renal artery. In 12 other rabbits, one kidney was inoculated with VX-2 tumor. Ethiodol and EEM embolization andmore » coil placement followed 7 days later (group 2, n = 6) or 11-14 days later (group 3, n = 6). Kidneys were evaluated (angiography, computed tomography, macro- and microscopy) 7 days after treatment. Results: Capillary stasis was achieved in groups 1, 2, and 3 with (mean {+-} standard deviation) 0.47 {+-} 0.03, 0.53 {+-} 0.02, and 0.56 {+-} 0.04 ml of pure Ethiodol, followed by 0.47 {+-} 0.05, 0.42 {+-} 0.03, and 0.38 {+-} 0.04 ml of EEM, respectively, which caused complete arterial occlusion in 17 of 18 kidneys. In group 1, all but one kidney showed at least 95% generalized coagulative necrosis. In group 2, all six kidneys exhibited 100% coagulative necrosis, with no viable tumor present. In group 3, 100% coagulative necrosis was present in all kidneys, with a small viable tumor in one. Conclusion: In the rabbit, selective arterial injection of pure Ethiodol can cause complete renal parenchyma and tumor ablation when it is followed by prompt, contiguous, and permanent occlusion of the arterial compartment.« less
Mazeti-Felicio, Camila M.; Caldas, Heloisa C.; Fernandes-Charpiot, Ida M.M.; Dezotti, Camila Z.; Baptista, Maria A.S.F.; Abbud-Filho, Mario
2017-01-01
Background Donors after brain death develop a systemic proinflammatory state that may predispose the kidneys to injury after transplantation. Because it is not known whether this inflammatory environment similarly affects the kidneys from expanded criteria donor (ECD) and standard criteria donors (SCD), we sought to evaluate differences in the gene expression of inflammatory cytokines in preimplantation biopsies (PIBx) from ECD and SCD kidneys. Methods Cytokines gene expression was measured in 80 PIBx (SCD, 52; ECD, 28) and associated with donor variables. Results Normal histology and chronic histological lesions were not different between both types of kidneys. ECD kidneys showed significant increase in the transcripts of MCP-1, RANTES, TGF-β1, and IL-10 when compared with SCD. Kidneys presenting normal histology had similar inflammatory profile except by a higher expression of RANTES observed in ECD (P = 0.04). Interstitial fibrosis and tubular atrophy (interstitial fibrosis and tubular atrophy ≥ 1) were associated with higher expression of TGF-β1, RANTES, and IL-10 in ECD compared with SCD kidneys. Cold ischemia time of 24 hours or longer was significantly associated with upregulation of FOXP3, MCP-1, RANTES, and IL10, whereas longer duration of donor hospitalization significantly increased gene expression of all markers. High FOXP3 expression was also associated with lower level of serum creatinine at 1 year. Donor age was not associated with any of the transcripts studied. Conclusions PIBx of ECD exhibit a higher gene expression of inflammatory cytokines when compared with SCD kidneys. This molecular profile may be a specific ECD kidney response to brain death and may help to predict the posttransplant outcomes of ECD recipients. PMID:28706983
Gerber, Simon D.; Amann, Ruth; Wyder, Stefan; Trueb, Beat
2012-01-01
Fgfrl1 (fibroblast growth factor receptor-like 1) is a transmembrane receptor that is essential for the development of the metanephric kidney. It is expressed in all nascent nephrogenic structures and in the ureteric bud. Fgfrl1 null mice fail to develop the metanephric kidneys. Mutant kidney rudiments show a dramatic reduction of ureteric branching and a lack of mesenchymal-to-epithelial transition. Here, we compared the expression profiles of wildtype and Fgfrl1 mutant kidneys to identify genes that act downstream of Fgfrl1 signaling during the early steps of nephron formation. We detected 56 differentially expressed transcripts with 2-fold or greater reduction, among them many genes involved in Fgf, Wnt, Bmp, Notch, and Six/Eya/Dach signaling. We validated the microarray data by qPCR and whole-mount in situ hybridization and showed the expression pattern of candidate genes in normal kidneys. Some of these genes might play an important role during early nephron formation. Our study should help to define the minimal set of genes that is required to form a functional nephron. PMID:22432025
Endoplasmic Reticulum Stress in the Diabetic Kidney, the Good, the Bad and the Ugly.
Cunard, Robyn
2015-04-20
Diabetic kidney disease is the leading worldwide cause of end stage kidney disease and a growing public health challenge. The diabetic kidney is exposed to many environmental stressors and each cell type has developed intricate signaling systems designed to restore optimal cellular function. The unfolded protein response (UPR) is a homeostatic pathway that regulates endoplasmic reticulum (ER) membrane structure and secretory function. Studies suggest that the UPR is activated in the diabetic kidney to restore normal ER function and viability. However, when the cell is continuously stressed in an environment that lies outside of its normal physiological range, then the UPR is known as the ER stress response. The UPR reduces protein synthesis, augments the ER folding capacity and downregulates mRNA expression of genes by multiple pathways. Aberrant activation of ER stress can also induce inflammation and cellular apoptosis, and modify signaling of protective processes such as autophagy and mTORC activation. The following review will discuss our current understanding of ER stress in the diabetic kidney and explore novel means of modulating ER stress and its interacting signaling cascades with the overall goal of identifying therapeutic strategies that will improve outcomes in diabetic nephropathy.
Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease.
Zhao, Juanjuan; Lupino, Katherine; Wilkins, Benjamin J; Qiu, Chengxiang; Liu, Jian; Omura, Yasuhiro; Allred, Amanda L; McDonald, Caitlin; Susztak, Katalin; Barish, Grant D; Pei, Liming
2018-05-22
Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1β. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1β loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1β-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.
Kanai, Takahiro; Shiizaki, Kazuhiro; Betsui, Hiroyuki; Aoyagi, Jun; Yamagata, Takanori
2018-05-16
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder. ADPKD is characterized clinically by the presence of multiple bilateral renal cysts that lead to chronic renal failure. The cysts evolve from renal tubular epithelial cells that express the Klotho gene. Notably, Klotho acts as a co-receptor for fibroblast growth factor 23 (FGF23); in this context, it induces phosphaturia and maintains serum phosphate at a normal level. Many reports have shown that decreases in the soluble Klotho level and increases in the FGF23 level are associated with glomerular filtration rate (GFR) decline, but a recent study observed these changes in patient with normal eGFR. It remains unclear whether the decrease in the Klotho level precedes the increase in FGF23. Here, we present an ADPKD patient with enlarged kidneys due to multiple cysts who had a decreased soluble Klotho level but a normal eGFR and a normal FGF23 level. The patient's serum phosphate level was normal, as was the fractional excretion of phosphate (FEP). This appears to be the first reported case to show a decreased soluble Klotho level plus normal eGFR, FGF23, and FEP. These results suggest that Klotho decreases before FGF23 increases and further suggest that Klotho is not required to maintain normal serum phosphate levels in ADPKD if the FEP and serum phosphate levels are normal.
McQuaid, D; Dunlop, A; Nill, S; Franzese, C; Nutting, C M; Harrington, K J; Newbold, K L; Bhide, S A
2016-08-01
The aim of this study was to investigate potential advantages and disadvantages of three-dimensional conformal radiotherapy (3DCRT), multiple fixed-field intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) in terms of dose to the planning target volume (PTV), organs at risk (OARs) and normal tissue complication probability (NTCP) for delivering ipsilateral radiotherapy. 3DCRT, IMRT and VMAT were compared in patients with well-lateralised primary tonsillar cancers who underwent primary radical ipsilateral radiotherapy. The following parameters were compared: conformity index (CI); homogeneity index (HI); dose-volume histograms (DVHs) of PTVs and OARs; NTCP, risk of radiation-induced cancer and dose accumulation during treatment. IMRT and VMAT were superior to 3DCRT in terms of CI, HI and dose to the target volumes, as well as mandible and dose accumulation robustness. The techniques were equivalent in terms of dose and NTCP for the contralateral oral cavity, contralateral submandibular gland and mandible, when specific dose constraint objectives were used on the oral cavity volume. Although the volume of normal tissue exposed to low-dose radiation was significantly higher with IMRT and VMAT, the risk of radiation-induced secondary malignancy was dependant on the mathematical model used. This study demonstrates the superiority of IMRT/VMAT techniques over 3DCRT in terms of dose homogeneity, conformity and consistent dose delivery to the PTV throughout the course of treatment in patients with lateralised oropharyngeal cancers. Dosimetry and NTCP calculations show that these techniques are equivalent to 3DCRT with regard to the risk of acute mucositis when specific dose constraint objectives were used on the contralateral oral cavity OAR.
Shera, Christopher A.; Melcher, Jennifer R.
2014-01-01
Atypical medial olivocochlear (MOC) feedback from brain stem to cochlea has been proposed to play a role in tinnitus, but even well-constructed tests of this idea have yielded inconsistent results. In the present study, it was hypothesized that low sound tolerance (mild to moderate hyperacusis), which can accompany tinnitus or occur on its own, might contribute to the inconsistency. Sound-level tolerance (SLT) was assessed in subjects (all men) with clinically normal or near-normal thresholds to form threshold-, age-, and sex-matched groups: 1) no tinnitus/high SLT, 2) no tinnitus/low SLT, 3) tinnitus/high SLT, and 4) tinnitus/low SLT. MOC function was measured from the ear canal as the change in magnitude of distortion-product otoacoustic emissions (DPOAE) elicited by broadband noise presented to the contralateral ear. The noise reduced DPOAE magnitude in all groups (“contralateral suppression”), but significantly more reduction occurred in groups with tinnitus and/or low SLT, indicating hyperresponsiveness of the MOC system compared with the group with no tinnitus/high SLT. The results suggest hyperresponsiveness of the interneurons of the MOC system residing in the cochlear nucleus and/or MOC neurons themselves. The present data, combined with previous human and animal data, indicate that neural pathways involving every major division of the cochlear nucleus manifest hyperactivity and/or hyperresponsiveness in tinnitus and/or low SLT. The overactivation may develop in each pathway separately. However, a more parsimonious hypothesis is that top-down neuromodulation is the driving force behind ubiquitous overactivation of the auditory brain stem and may correspond to attentional spotlighting on the auditory domain in tinnitus and hyperacusis. PMID:25231612
Predicting Outcome in Patients with Anti-GBM Glomerulonephritis.
van Daalen, Emma E; Jennette, J Charles; McAdoo, Stephen P; Pusey, Charles D; Alba, Marco A; Poulton, Caroline J; Wolterbeek, Ron; Nguyen, Tri Q; Goldschmeding, Roel; Alchi, Bassam; Griffiths, Meryl; de Zoysa, Janak R; Vincent, Beula; Bruijn, Jan A; Bajema, Ingeborg M
2018-01-06
Large studies on long-term kidney outcome in patients with anti-glomerular basement membrane (anti-GBM) GN are lacking. This study aimed to identify clinical and histopathologic parameters that predict kidney outcome in these patients. This retrospective analysis included a total of 123 patients with anti-GBM GN between 1986 and 2015 from six centers worldwide. Their kidney biopsy samples were classified according to the histopathologic classification for ANCA-associated GN. Clinical data such as details of treatment were retrieved from clinical records. The primary outcome parameter was the occurrence of ESRD. Kidney survival was analyzed using the log-rank test and Cox regression analyses. The 5-year kidney survival rate was 34%, with an improved rate observed among patients diagnosed after 2007 ( P =0.01). In patients with anti-GBM GN, histopathologic class and kidney survival were associated ( P <0.001). Only one of 15 patients with a focal class biopsy sample (≥50% normal glomeruli) developed ESRD. Patients with a sclerotic class biopsy sample (≥50% globally sclerotic glomeruli) and patients with 100% cellular crescents did not recover from dialysis dependency at presentation. In multivariable analysis, dialysis dependency at presentation (hazard ratio [HR], 3.17; 95% confidence interval [95% CI], 1.59 to 6.32), percentage of normal glomeruli (HR, 0.97; 95% CI, 0.95 to 0.99), and extent of interstitial infiltrate (HR, 2.02; 95% CI, 1.17 to 3.50) were predictors of ESRD during follow-up. Dialysis dependency, low percentage of normal glomeruli, and large extent of interstitial infiltrate are associated with poor kidney outcome in anti-GBM GN. Kidney outcome has improved during recent years; the success rate doubled after 2007. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_11_21_CJASNPodcast_18_1_v.mp3. Copyright © 2018 by the American Society of Nephrology.
Weber, Gregory J; Foster, Jaleyea; Pushpakumar, Sathnur B; Sen, Utpal
2018-06-15
Hypertension affects nearly one third of the adult US population and is a significant risk factor for chronic kidney disease (CKD). An expanding body of recent studies indicates that gut microbiome has crucial roles in regulating physiological processes through, among other mechanisms, one mode of short chain fatty acids (SCFA) and their target receptors. In addition, these SCFA receptors are potential targets of regulation by host miRNAs, however, the mechanisms through which this occurs is not clearly defined. Hydrogen sulfide (H 2 S) is an important gasotransmitter involved in multiple physiological processes and is known to alleviate adverse effects of hypertension such as reducing inflammation in the kidney. To determine the role of host microRNAs in regulating short chain fatty acid receptors in the kidney as well as the gut, C57BL/6J wild-type mice were treated with or without Ang-II and H 2 S donor GYY4137 (GYY) for 4 weeks to assess whether GYY would normalize adverse effects observed in hypertensive mice and whether this was in part due to altered gut microbiome composition. We observed several changes of SCFA receptors, including Olfr78, Gpr41/43 and predicted microRNA regulators in the kidney among the different treatments. Increased expression of inflammatory markers Il6 and Rorc2, along with Tgfβ, were found in the hypertensive kidney. The glomerular filtration rate (GFR) was improved in mice treated with Ang-II + GYY compared with Ang-II only, indicating improved kidney function. The Erysipelotrichia class of bacteria, linked with high fat diets, was enriched in hypertensive animals but reduced with GYY supplementation. These data point towards a role for miRNA regulation of SCFA receptors in hypertensive kidney and are normalized by H 2 S supplementation. Copyright © 2018 Elsevier Ltd. All rights reserved.
Burgess, L Goodwin; Goyal, Nitin; Jones, G Morgan; Khorchid, Yasser; Kerro, Ali; Chapple, Kristina; Tsivgoulis, Georgios; Alexandrov, Andrei V; Chang, Jason J
2018-04-13
We sought to assess the risk of acute kidney injury (AKI) and mortality associated with intensive systolic blood pressure reduction in acute intracerebral hemorrhage. Patients with acute intracerebral hemorrhage had spontaneous cause and symptom onset within 24 hours. We excluded patients with structural causes, coagulopathy, thrombocytopenia, and preexisting end-stage renal disease. We defined AKI using the Acute Kidney Injury Network criteria. Chronic kidney disease status was included in risk stratification and was defined by Kidney Disease Outcomes Quality Initiative staging. Maximum systolic blood pressure reduction was defined over a 12-hour period and dichotomized using receiver operating characteristic curve analysis. Descriptive statistics were done using independent sample t tests, χ 2 tests, and Mann-Whitney U tests, whereas multivariable logistic regression analysis was used to evaluate for predictors for AKI and mortality. A total of 448 patients with intracerebral hemorrhage met inclusion criteria. Maximum systolic blood pressure reduction was dichotomized to 90 mm Hg and found to increase the risk of AKI in patients with normal renal function (odds ratio, 2.1; 95% confidence interval, 1.19-3.62; P =0.010) and chronic kidney disease (odds ratio, 3.91; 95% confidence interval, 1.26-12.15; P =0.019). The risk of AKI was not significantly different in normal renal function versus chronic kidney disease groups when adjusted for demographics, presentation characteristics, and medications associated with AKI. AKI positively predicted mortality for patients with normal renal function (odds ratio, 2.41; 95% confidence interval, 1.11-5.22; P =0.026) but not for patients with chronic kidney disease (odds ratio, 3.13; 95% confidence interval, 0.65-15.01; P =0.154). These results indicate that intensive systolic blood pressure reduction with a threshold >90 mm Hg in patients with acute intracerebral hemorrhage may be an independent predictor for AKI. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
Simple ectopic kidney in three dogs.
Choi, Jiyoung; Lee, Heechun; Lee, Youngwon; Choi, Hojung
2012-10-01
Simple ectopic kidney was diagnosed in three dogs by means of radiography and ultrasonography. A 2-year-old castrated male Schnauzer, a 13-year-old female Schnauzer and a 9-year-old male Jindo were referred with vomiting, hematuria and ocular discharge, respectively. In all three dogs, oval-shaped masses with soft tissue density were observed in the mid to caudal abdomen bilaterally or unilaterally, and kidney silhouettes were not identified at the proper anatomic places on abdominal radiographs. Ultrasonography confirmed the masses were malpositioned kidney. The ectopic kidneys had relatively small size, irregular shape and short ureter but showed normal function on excretory urography.
Bilateral Renal Anastomosing Hemangiomas: A Tale of Two Kidneys
Abboudi, Hamid; Tschobotko, Benjamin; Carr, Christopher
2017-01-01
Abstract Background: Renal anastomosing hemangioma (RAH) is an extremely rare benign vascular tumor first described in 2009. Making this diagnosis is fraught with challenges. Radiologically they share features consistent with renal cell carcinomas (RCCs). Their vascular nature poses risks if considering preoperative biopsy and histologically they share characteristics akin to angiosarcomas. The few reports published in the literature suggest presentation with hematuria, flank pain, and polycythemia although the majority are diagnosed at postnephrectomy histologic examination. This case represents the first metachronous RAH in the literature, and is the first RAH presenting with severe hemorrhage. Case Presentation: A 62-year-old woman of Albanian heritage presented to urology with visible hematuria and positive urine cytology. Three years before this presentation, she had undergone an elective radical right-sided nephrectomy for a suspected RCC detected on magnetic resonance imaging, which proved to be an RAH after postoperative histologic examination of the specimen. The patient was investigated with cystoscopy and ureteroscopy for this new hematuria presentation, both of which were unremarkable. Fourteen hours post ureteroscopy, the patient became severely hypotensive and developed acute kidney injury. A CT scan indicated a large left-sided renal subcapsular and retroperitoneal hematoma that was actively bleeding. The patient was hemodynamically unstable and, therefore, required an emergency open left-sided nephrectomy, rendering her anephric and dialysis dependent. Postoperative histologic examination proved that the left kidney also contained an RAH. Conclusion: The anastomosing hemangioma is an important subtype to differentiate from angiosarcoma before and after a nephrectomy. Urologists should carefully consider invasive tests in patients with previously diagnosed vascular lesions as there may be an increased risk of bleeding. Patients with a previously diagnosed anastomosing hemangioma may require surveillance of the contralateral kidney. PMID:29279869
Bilateral Renal Anastomosing Hemangiomas: A Tale of Two Kidneys.
Abboudi, Hamid; Tschobotko, Benjamin; Carr, Christopher; DasGupta, Ranan
2017-01-01
Background: Renal anastomosing hemangioma (RAH) is an extremely rare benign vascular tumor first described in 2009. Making this diagnosis is fraught with challenges. Radiologically they share features consistent with renal cell carcinomas (RCCs). Their vascular nature poses risks if considering preoperative biopsy and histologically they share characteristics akin to angiosarcomas. The few reports published in the literature suggest presentation with hematuria, flank pain, and polycythemia although the majority are diagnosed at postnephrectomy histologic examination. This case represents the first metachronous RAH in the literature, and is the first RAH presenting with severe hemorrhage. Case Presentation: A 62-year-old woman of Albanian heritage presented to urology with visible hematuria and positive urine cytology. Three years before this presentation, she had undergone an elective radical right-sided nephrectomy for a suspected RCC detected on magnetic resonance imaging, which proved to be an RAH after postoperative histologic examination of the specimen. The patient was investigated with cystoscopy and ureteroscopy for this new hematuria presentation, both of which were unremarkable. Fourteen hours post ureteroscopy, the patient became severely hypotensive and developed acute kidney injury. A CT scan indicated a large left-sided renal subcapsular and retroperitoneal hematoma that was actively bleeding. The patient was hemodynamically unstable and, therefore, required an emergency open left-sided nephrectomy, rendering her anephric and dialysis dependent. Postoperative histologic examination proved that the left kidney also contained an RAH. Conclusion: The anastomosing hemangioma is an important subtype to differentiate from angiosarcoma before and after a nephrectomy. Urologists should carefully consider invasive tests in patients with previously diagnosed vascular lesions as there may be an increased risk of bleeding. Patients with a previously diagnosed anastomosing hemangioma may require surveillance of the contralateral kidney.
Chen, Wenli; Woo, Peak; Murry, Thomas
2017-09-01
High-speed videoendoscopy captures the cycle-to-cycle vibratory motion of each individual vocal fold in normal and severely disordered phonation. Therefore, it provides a direct method to examine the specific vibratory changes following vocal fold surgery. The purpose of this study was to examine the vocal fold vibratory pattern changes in the surgically treated pathologic vocal fold and the contralateral vocal fold in three vocal pathologies: vocal polyp (n = 3), paresis or paralysis (n = 3), and scar (n = 3). Digital kymography was used to extract high-speed kymographic vocal fold images at the mid-membranous region of the vocal fold. Spectral analysis was subsequently applied to the digital kymography to quantify the cycle-to-cycle movements of each vocal fold, expressed as a spectrum. Surgical modification resulted in significantly improved spectral power of the treated pathologic vocal fold. Furthermore, the contralateral vocal fold also presented with improved spectral power irrespective of vocal pathology. In comparison with normal vocal fold spectrum, postsurgical vocal fold vibrations continued to demonstrate decreased vibratory amplitude in both vocal folds. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Peterson, Hannah M.; Hoang, Bang H.; Geller, David; Yang, Rui; Gorlick, Richard; Berger, Jeremy; Tingling, Janet; Roth, Michael; Gill, Jonathon; Roblyer, Darren
2017-12-01
Diffuse optical spectroscopic imaging (DOSI) is an emerging near-infrared imaging technique that noninvasively measures quantitative functional information in thick tissue. This study aimed to assess the feasibility of using DOSI to measure optical contrast from bone sarcomas. These tumors are rare and pose technical and practical challenges for DOSI measurements due to the varied anatomic locations and tissue depths of presentation. Six subjects were enrolled in the study. One subject was unable to be measured due to tissue contact sensitivity. For the five remaining subjects, the signal-to-noise ratio, imaging depth, optical properties, and quantitative tissue concentrations of oxyhemoglobin, deoxyhemoglobin, water, and lipids from tumor and contralateral normal tissues were assessed. Statistical differences between tumor and contralateral normal tissue were found in chromophore concentrations and optical properties for four subjects. Low signal-to-noise was encountered during several subject's measurements, suggesting increased detector sensitivity will help to optimize DOSI for this patient population going forward. This study demonstrates that DOSI is capable of measuring optical properties and obtaining functional information in bone sarcomas. In the future, DOSI may provide a means to stratify treatment groups and monitor chemotherapy response for this disease.
Lee, Chan Ho; Park, Young Joo; Ku, Ja Yoon; Ha, Hong Koo
2017-06-01
To evaluate the clinical application of computed tomography-based measurement of renal cortical volume and split renal volume as a single tool to assess the anatomy and renal function in patients with renal tumors before and after partial nephrectomy, and to compare the findings with technetium-99m dimercaptosuccinic acid renal scan. The data of 51 patients with a unilateral renal tumor managed by partial nephrectomy were retrospectively analyzed. The renal cortical volume of tumor-bearing and contralateral kidneys was measured using ImageJ software. Split estimated glomerular filtration rate and split renal volume calculated using this renal cortical volume were compared with the split renal function measured with technetium-99m dimercaptosuccinic acid renal scan. A strong correlation between split renal function and split renal volume of the tumor-bearing kidney was observed before and after surgery (r = 0.89, P < 0.001 and r = 0.94, P < 0.001). The preoperative and postoperative split estimated glomerular filtration rate of the operated kidney showed a moderate correlation with split renal function (r = 0.39, P = 0.004 and r = 0.49, P < 0.001). The correlation between reductions in split renal function and split renal volume of the operated kidney (r = 0.87, P < 0.001) was stronger than that between split renal function and percent reduction in split estimated glomerular filtration rate (r = 0.64, P < 0.001). The split renal volume calculated using computed tomography-based renal volumetry had a strong correlation with the split renal function measured using technetium-99m dimercaptosuccinic acid renal scan. Computed tomography-based split renal volume measurement before and after partial nephrectomy can be used as a single modality for anatomical and functional assessment of the tumor-bearing kidney. © 2017 The Japanese Urological Association.
Feasibility of Repairing Glomerular Basement Membrane Defects in Alport Syndrome
Lin, Xiaobo; Suh, Jung Hee; Go, Gloriosa
2014-01-01
Alport syndrome is a hereditary glomerular disease that leads to kidney failure. It is caused by mutations affecting one of three chains of the collagen α3α4α5(IV) heterotrimer, which forms the major collagen IV network of the glomerular basement membrane (GBM). In the absence of the α3α4α5(IV) network, the α1α1α2(IV) network substitutes, but it is insufficient to maintain normal kidney function. Inhibition of angiotensin-converting enzyme slows progression to kidney failure in patients with Alport syndrome but is not a cure. Restoration of the normal collagen α3α4α5(IV) network in the GBM, by either cell- or gene-based therapy, is an attractive and logical approach toward a cure, but whether or not the abnormal GBM can be repaired once it has formed and is functioning is unknown. Using a mouse model of Alport syndrome and an inducible transgene system, we found that secretion of α3α4α5(IV) heterotrimers by podocytes into a preformed, abnormal, filtering Alport GBM is effective at restoring the missing collagen IV network, slowing kidney disease progression, and extending life span. This proof-of-principle study demonstrates the plasticity of the mature GBM and validates the pursuit of therapeutic approaches aimed at normalizing the GBM to prolong kidney function. PMID:24262794
Feasibility of repairing glomerular basement membrane defects in Alport syndrome.
Lin, Xiaobo; Suh, Jung Hee; Go, Gloriosa; Miner, Jeffrey H
2014-04-01
Alport syndrome is a hereditary glomerular disease that leads to kidney failure. It is caused by mutations affecting one of three chains of the collagen α3α4α5(IV) heterotrimer, which forms the major collagen IV network of the glomerular basement membrane (GBM). In the absence of the α3α4α5(IV) network, the α1α1α2(IV) network substitutes, but it is insufficient to maintain normal kidney function. Inhibition of angiotensin-converting enzyme slows progression to kidney failure in patients with Alport syndrome but is not a cure. Restoration of the normal collagen α3α4α5(IV) network in the GBM, by either cell- or gene-based therapy, is an attractive and logical approach toward a cure, but whether or not the abnormal GBM can be repaired once it has formed and is functioning is unknown. Using a mouse model of Alport syndrome and an inducible transgene system, we found that secretion of α3α4α5(IV) heterotrimers by podocytes into a preformed, abnormal, filtering Alport GBM is effective at restoring the missing collagen IV network, slowing kidney disease progression, and extending life span. This proof-of-principle study demonstrates the plasticity of the mature GBM and validates the pursuit of therapeutic approaches aimed at normalizing the GBM to prolong kidney function.
Bulle, Saradamma; Reddy, Vaddi Damodara; Hebbani, Ananda Vardhan; Padmavathi, Pannuru; Challa, Chandrasekhar; Puvvada, Pavan Kumar; Repalle, Elisha; Nayakanti, Devanna; Aluganti Narasimhulu, Chandrakala; Nallanchakravarthula, Varadacharyulu
2016-12-01
The present study investigated the antioxidant potential of P. santalinus heartwood methanolic extract (PSE) against alcohol-induced nephro-toxicity. The results indicated an increase in the concentration of kidney damage plasma markers, urea and creatinine with a concomitant decrease in the concentration of uric acid in alcohol-administered rats. A significant decrease in plasma electrolytes and mineral levels with increased kidney thiobarbituric acid reactive substances (TBARS) and nitric oxide (NOx) levels was also observed. PSE treatment to alcohol-administered rats effectively prevented the elevation in TBARS and NOx levels. Decreased activity of Na + /K + -ATPase in alcohol administered rats was brought to near normal levels with treatment of PSE. Chronic alcohol consumption affects antioxidant enzymatic activity and reabsorption function of the kidney which is evident from the decreased level of GSH as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione s-transferase (GST). However, treatment with PSE to alcohol-administered rats significantly enhanced these enzymatic activities and reduced glutathione (GSH) content close to normal level. Alcohol-induced organ damage was evident from morphological changes in the kidney. Nevertheless, administration of PSE effectively restored these morphological changes to normal. The flavonoid and tannoid compounds might have protective activity against alcohol-induced oxidative/nitrosative stress mediated kidney damage. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Qu, H; Xia, P; Yu, N
Purpose: To study ventilation weighting effect on radiation doses to both side lungs for patients with advanced stage lung cancer. Methods: Fourteen patients with advanced stage lung cancer were included in this retrospective study. Proprietary software was developed to calculate the lung ventilation map based on 4DCT images acquired for radiation therapy. Two phases of inhale (0%) and exhale (50%) were used for the lung ventilation calculations. For each patient, the CT images were resampled to the same dose calculation resolution of 3mmx3mmx3mm. The ventilation distribution was then normalized by the mean value of the ventilation. The ventilation weighted dosemore » was calculated by applying linearly weighted ventilation to the dose of each pixel. The lung contours were automatically delineated from patient CT image with lung window, excluding the tumor and high density tissues. For contralateral and ipsilateral lungs, the mean lung doses from the original plan and ventilation weighted mean lung doses were compared using two tail t-Test. Results: The average of mean dose was 6.1 ±3.8Gy for the contralateral lungs, and 26.2 ± 14.0Gy for the ipsilateral lungs. The average of ventilation weighted dose was 6.3± 3.8Gy for the contralateral lungs and 24.6 ± 13.1Gy for the ipsilateral lungs. The statistics analysis shows the significance of the mean dose increase (p<0.015) for the contralateral lungs and decrease (p<0.005) for the ipsilateral lungs. Conclusion: Ventilation weighted doses were greater than the un-weighted doses for contralateral lungs and smaller for ipsilateral lungs. This Result may be helpful to understand the radiation dosimetric effect on the lung function and provide planning guidance for patients with advance stage lung cancer.« less
Chen, Bo; Wang, Xiaojun; Long, Xiao; Zhang, Mingzi; Huang, Jiuzuo; Yu, Nanze; Xu, Jing
2018-06-01
The authors aimed to analyze factors related to lipotransfer for localized scleroderma, and to explore the feasibility of cell-assisted lipotransfer for localized scleroderma treatment. Abdominal fat samples were taken from six scleroderma patients without corticosteroid therapy, five scleroderma patients with corticosteroid therapy, and 10 normal liposuction patients. Their quantity, morphology, and proliferation ability were measured. Blood flow was measured by laser speckle contrast imaging in localized scleroderma lesions and normal contralateral regions for eight localized scleroderma patients. Bleomycin-induced skin fibrosis nude mice were also used to investigate differences between lipotransfer and cell-assisted lipotransfer. Fat weight was measured, and expression of transforming growth factor (TGF)-β1 and type III collagen in the injected skin was determined by immunohistochemistry. The number of stem cells from scleroderma patients with corticosteroid treatment was significantly reduced. Mean blood perfusion in localized scleroderma lesions was not significantly different than in the contralateral normal regions. In normal nude mice, there were no significant changes in TGF-β1 and type III collagen between the control, lipotransfer, and cell-assisted lipotransfer groups, whereas in bleomycin-induced skin fibrosis nude mice, lipotransfer and cell-assisted lipotransfer reduced TGF-β1 and type III collagen expression. For scleroderma patients, fewer adipose-derived stem cells, because of a history of corticosteroid therapy and a local inflammatory microenvironment, are more important factors, whereas blood supply showed no significant change. Therefore, cell-assisted lipotransfer not only improves the survival rate of transplanted fat but also improves skin texture in bleomycin-induced skin fibrosis nude mice.
Se status in normal and pathological human individuals before and after Se supplementation
NASA Astrophysics Data System (ADS)
Bellisola, G.; Cinque, G.; Galassini, S.; Guidi, G. C.; Liu, N. Q.; Moschini, G.
1996-04-01
The determination of selenium in plasma and in urine samples has been suggested for the assessment of Se status in human individuals. The kidney is of fundamental importance in Se homeostasis: with low Se intake its excretion will be decreased and with high Se intake it will be increased. In 21 patients with kidney disease (8 with normal kidney function and 13 with moderate renal failure) Se was measured in 1 ml of urine by PIXE after preconcentration of the sample. The total urine volume was measured to calculate total daily Se excretion. The same procedure was applied to 14 normal individuals for comparison. All individuals were then supplemented orally with selenite for 8 weeks (Se = 600 μg/day) and the procedure was repeated. The behaviour of the major selenoproteins was also investigated by measuring glutathione peroxidase activities in plasma, in platelets and in erythrocyte samples. For renal function, serum and urine creatinine concentrations were utilised and creatinine clearances were calculated. Results obtained were compared before and after Se treatment and between groups. Some correlation studies were carried out between Se and kidney functions and/or selenoperoxidase activities.
Nakhoul, Nazih; Hering-Smith, Kathleen S.
2015-01-01
Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO3− and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO3− is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys. PMID:26597304
Contralateral Occlusion Test: The effect of external ear canal occlusion on hearing thresholds.
Reis, Luis Roque; Fernandes, Paulo; Escada, Pedro
Bedside testing with tuning forks may decrease turnaround time and improve decision making for a quick qualitative assessment of hearing loss. The purpose of this study was to quantify the effects of ear canal occlusion on hearing, in order to decide which tuning fork frequency is more appropriate to use for quantifying hearing loss with the Contralateral Occlusion Test. Twenty normal-hearing adults (forty ears) underwent sound field pure tone audiometry with and without ear canal occlusion. Each ear was tested with the standard frequencies. The contralateral ear was suppressed with by masking. Ear occlusion was performed by two examiners. Participants aged between 21 and 30 years (25.6±3.03 years) showed an increase in hearing thresholds with increasing frequencies from 19.94dB (250Hz) to 39.25dB (2000Hz). The threshold difference between occluded and unoccluded conditions was statistically significant and increased from 10.69dB (250Hz) to 32.12dB (2000Hz). There were no statistically significant differences according to gender or between the examiners. The occlusion effect increased the hearing thresholds and became more evident with higher frequencies. The occlusion method as performed demonstrated reproducibility. In the Contralateral Occlusion Test, 256Hz or 512Hz tuning forks should be used for diagnosis of mild hearing loss, and a 2048Hz tuning fork should be used for moderate hearing loss. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.
Malouf, Phillip A; Descallar, Joseph; Berney, Christophe R
2018-02-01
The aim of this series is to determine the clinical utility of routine ultrasound (US) of the contralateral, clinically normal groin when a unilateral inguinal hernia is referred for hernia repair-specifically assessing the morbidity and short-term change in quality-of-life (QoL) due to repair of this occult contralateral hernia when also repairing the symptomatic side. TEP inguinal hernia repair affords the opportunity to repair any groin hernia through the same small incisions. US detects 96.6% of groin hernias with 84.4% specificity. 234 consecutive male patients with clinically unilateral and clinically bilateral hernia were enrolled; those with a clinically unilateral hernia were sent for groin US and if positive, a bilateral TEP groin hernia repair was performed (USBH). If negative, a unilateral TEP groin hernia repair was performed (UNIH). Carolina's comfort scales (CCS) and visual analogue scores (VAS) were recorded at 2 and 6 weeks postoperatively, while a modified CCS (MCCS) was recorded for all patients preoperatively. Bilateral TEP repair resulted in higher VAS scores than unilateral repair at 2 weeks but not 6 weeks. CCS were worse in the USBH group than UNIH group at 2 weeks but were similar by 6 weeks. Complications' rates were similar amongst all 3 groups. Factors contributing to worse scores were: smaller hernia, complications, worse preoperative MCCS results, recurrent hernia and bilateral rather than unilateral repair. Bilateral TEP for the clinically unilateral groin hernia with an occult contralateral groin hernia can be performed without increased morbidity, accepting a minor and very temporary impairment of QoL.
The Mirror Illusion Increases Motor Cortex Excitability in Children With and Without Hemiparesis.
Grunt, Sebastian; Newman, Christopher J; Saxer, Stefanie; Steinlin, Maja; Weisstanner, Christian; Kaelin-Lang, Alain
2017-03-01
Mirror therapy provides a visual illusion of a normal moving limb by using the mirror reflection of the unaffected arm instead of viewing the paretic limb and is used in rehabilitation to improve hand function. Little is known about the mechanism underlying its effect in children with hemiparesis. To investigate the effect of the mirror illusion (MI) on the excitability of the primary motor cortex (M1) in children and adolescents. Twelve patients with hemiparesis (10-20 years) and 8 typically developing subjects (8-17 years) participated. Corticospinal reorganization was classified as contralateral (projection from contralateral hemisphere to affected hand) or ipsilateral (projection from ipsilateral hemisphere to affected hand). M1 excitability of the hemisphere projecting to the affected (nondominant in typically developing subjects) hand was obtained during 2 different conditions using single-pulse transcranial magnetic stimulation (TMS). Each condition (without/with mirror) consisted of a unimanual and a bimanual task. Motor-evoked potentials (MEPs) were recorded from the abductor pollicis brevis and flexor digitorum superficialis muscles. MEP amplitudes were significantly increased during the mirror condition ( P = .005) in typically developing subjects and in patients with contralateral reorganization. No significant effect of MI was found in subjects with ipsilateral reorganization. MI increased M1 excitability during active movements only. This increase was not correlated to hand function. MI increases the excitability of M1 in hemiparetic patients with contralateral corticospinal organization and in typically developing subjects. This finding provides neurophysiological evidence supporting the application of mirror therapy in selected children and adolescents with hemiparesis.
Determination of Single-Kidney Glomerular Filtration Rate in Human Subjects by Using CT
Kwon, Soon Hyo; Saad, Ahmed; Herrmann, Sandra M.; Textor, Stephen C.
2015-01-01
Purpose To test the hypothesis that computed tomography (CT)–derived measurements of single-kidney glomerular filtration rate (GFR) obtained in human subjects with 64-section CT agree with those obtained with iothalamate clearance, a rigorous reference standard. Materials and Methods The institutional review board approved this HIPAA-compliant study, and written informed consent was obtained. Ninety-six patients (age range, 51–73 years; 46 men, 50 women) with essential (n = 56) or renovascular (n = 40) hypertension were prospectively studied in controlled conditions (involving sodium intake and renin-angiotensin blockade). Single-kidney perfusion, volume, and GFR were measured by using multidetector CT time-attenuation curves and were compared with GFR measured by using iothalamate clearance, as assigned to the right and left kidney according to relative volumes. The reproducibility of CT GFR over a 3-month period (n = 21) was assessed in patients with renal artery stenosis who were undergoing stable medical treatment. Statistical analysis included the t test, Wilcoxon signed rank test, linear regression, and Bland-Altman analysis. Results CT GFR values were similar to those of iothalamate clearance (mean ± standard deviation, 38.2 mL/min ± 18 vs 41.6 mL/min ± 17; P = .062). Stenotic kidney CT GFR in patients with renal artery stenosis was lower than contralateral kidney GFR or essential hypertension single-kidney GFR (mean, 23.1 mL/min ± 13 vs 36.9 mL/min ± 17 [P = .0008] and 45.2 mL/min ± 16 [P = .019], respectively), as was iothalamate clearance (mean, 26.9 mL/min ± 14 vs 38.5 mL/min ± 15 [P = .0004] and 49.0 mL/min ± 14 [P = .001], respectively). CT GFR correlated well with iothalamate GFR (linear regression, CT GFR = 0.88*iothalamate GFR, r2 = 0.89, P < .0001), and Bland-Altman analysis was used to confirm the agreement. CT GFR was also moderately reproducible in medically treated patients with renal artery stenosis (concordance coefficient correlation, 0.835) but was unaffected by revascularization (mean, 25.3 mL/min ± 15.2 vs 30.3 mL/min ± 18.5; P = .097). Conclusion CT assessments of single-kidney GFR are reproducible and agree well with a reference standard. CT can be useful to obtain minimally invasive estimates of bilateral single-kidney function in human subjects. © RSNA, 2015 PMID:25848903
Renal glucose metabolism in normal physiological conditions and in diabetes.
Alsahli, Mazen; Gerich, John E
2017-11-01
The kidney plays an important role in glucose homeostasis via gluconeogenesis, glucose utilization, and glucose reabsorption from the renal glomerular filtrate. After an overnight fast, 20-25% of glucose released into the circulation originates from the kidneys through gluconeogenesis. In this post-absorptive state, the kidneys utilize about 10% of all glucose utilized by the body. After glucose ingestion, renal gluconeogenesis increases and accounts for approximately 60% of endogenous glucose release in the postprandial period. Each day, the kidneys filter approximately 180g of glucose and virtually all of this is reabsorbed into the circulation. Hormones (most importantly insulin and catecholamines), substrates, enzymes, and glucose transporters are some of the various factors influencing the kidney's role. Patients with type 2 diabetes have an increased renal glucose uptake and release in the fasting and the post-prandial states. Additionally, glucosuria in these patients does not occur at plasma glucose levels that would normally produce glucosuria in healthy individuals. The major abnormality of renal glucose metabolism in type 1 diabetes appears to be impaired renal glucose release during hypoglycemia. Copyright © 2017 Elsevier B.V. All rights reserved.
Falsetti, Lorenzo; Capeci, William; Tarquinio, Nicola; Viticchi, Giovanna; Silvestrini, Mauro; Catozzo, Vania; Fioranelli, Agnese; Buratti, Laura; Pellegrini, Francesco
2017-01-01
Chronic kidney disease and hyperuricemia have been associated to an increased risk and a worse prognosis in acute ischemic stroke. Several mechanisms, including platelet dysfunction, coagulation disorders, endothelial dysfunction, inflammation, and an increased risk of atrial fibrillation could be implicated. The role of serum uric acid in this setting is still object of debate. We enrolled all the consecutive patients admitted to our department for acute ischemic stroke. Cox regression analysis was used to evaluate the risk of in-hospital death considering serum uric acid levels and all the comorbidities. In the overall sample, hyperuricemia was independently associated to an increased risk of in-hospital mortality. This effect was stronger in patients with chronic kidney disease while, in the group of patients with normal renal function, the relationship between hyperuricemia and increased stroke mortality was not confirmed. Hyperuricemia could be associated to higher in-hospital mortality for ischemic stroke among elderly patients when affected by kidney disease. Survival does not seem to be affected by hyperuricemia in patients with normal kidney function. PMID:28461885
Insight into mechanism of oxidative DNA damage in angiomyolipomas from TSC patients
Habib, Samy L
2009-01-01
Background The tuberous sclerosis complex (TSC) is caused by defects in one of two tumor suppressor genes, TSC-1 or TSC-2. TSC-2 gene encodes tuberin, a protein involved in the pathogenesis of kidney tumors, both angiomyolipomas and renal cell carcinomas. Loss of heterozygosity at the 8-oxoG-DNA glycosylase (OGG1) allele is found in human kidney clear cell carcinoma identifying loss of OGG1 function as a possible contributor to tumorigenesis in the kidney. Tuberin regulates OGG1 through the transcription factor NF-YA in cultured cells. The purpose of this study is to determine the effect of tuberin-deficiency on OGG1 protein and mRNA levels as well as on 8-oxodG levels in kidney tumors from patients with TSC. In addition we evaluated the phophorylation level of downstream targets of mTOR, phospho-S70K, in kidney tumor tissue from TSC patients. Results Kidney angiomyolipoma tissue from TSC patients expresses significant levels of phopho-tuberin and low levels of tuberin compared to control kidney tissue. The increase in tuberin phosphorylation and the decrease tuberin expression are associated with decrease in OGG1 protein and mRNA levels in tumor samples compared to normal kidney samples. The decrease OGG1 expression is also associated with significant decrease in the transcription factor, NF-YA, expression in tumor samples compared to normal tissues. In addition, the levels of 8-oxodG are 4-fold higher in tumors compared to control samples. The significant increase of phospho-tuberin expression is associated with increase phosphorylation of S6K in tumor samples compared to controls. Cyclin D1 expression is also 3-fold higher in increase in the tumor tissues compared to normal kidney tissues. Conclusion These data indicate that tuberin deficiency in angiomyolipoma enhances mTOR activation by phosphorylation of S6K and downregulation of protein and mRNA expression of OGG1 resulted in accumulation of oxidized DNA in patients with TSC. These data suggest that tuberin and OGG1 are important proteins in the pathogenesis of angiomyolipoma in TSC patients. PMID:19265534
Mace, Maria L; Gravesen, Eva; Nordholm, Anders; Hofman-Bang, Jacob; Secher, Thomas; Olgaard, Klaus; Lewin, Ewa
2017-07-01
Fibroblast growth factor 23 (FGF23) secreted by osteocytes is a circulating factor essential for phosphate homeostasis. High plasma FGF23 levels are associated with cardiovascular complications and mortality. Increases of plasma FGF23 in uremia antedate high levels of phosphate, suggesting a disrupted feedback regulatory loop or an extra-skeletal source of this phosphatonin. Since induction of FGF23 expression in injured organs has been reported we decided to examine the regulation of FGF23 gene and protein expressions in the kidney and whether kidney-derived FGF23 contributes to the high plasma levels of FGF23 in uremia. FGF23 mRNA was not detected in normal kidneys, but was clearly demonstrated in injured kidneys, already after four hours in obstructive nephropathy and at 8 weeks in the remnant kidney of 5/6 nephrectomized rats. No renal extraction was found in uremic rats in contrast to normal rats. Removal of the remnant kidney had no effect on plasma FGF23 levels. Well-known regulators of FGF23 expression in bone, such as parathyroid hormone, calcitriol, and inhibition of the FGF receptor by PD173074, had no impact on kidney expression of FGF23. Thus, the only direct contribution of the injured kidney to circulating FGF23 levels in uremia appears to be reduced renal extraction of bone-derived FGF23. Kidney-derived FGF23 does not generate high plasma FGF23 levels in uremia and is regulated differently than the corresponding regulation of FGF23 gene expression in bone. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
Gao, Xiang; Huang, Lianghu; Grosjean, Fabrizio; Esposito, Vittoria; Wu, Jianxiang; Fu, Lili; Hu, Huimin; Tan, Jiangming; He, Cijian; Gray, Susan; Jain, Mukesh K; Zheng, Feng; Mei, Changlin
2011-05-01
Dietary protein restriction is an important treatment for chronic kidney disease. Herein, we tested the effect of low-protein or low-protein plus ketoacids (KA) diet in a remnant kidney model. Rats with a remnant kidney were randomized to receive normal protein diet (22%), low-protein (6%) diet (LPD), or low-protein (5%) plus KA (1%) diet for 6 months. Protein restriction prevented proteinuria, decreased blood urea nitrogen levels, and renal lesions; however, the LPD retarded growth and decreased serum albumin levels. Supplementation with KA corrected these abnormalities and provided superior renal protection compared with protein restriction alone. The levels of Kruppel-like factor-15 (KLF15), a transcription factor shown to reduce cardiac fibrosis, were decreased in remnant kidneys. Protein restriction, which increased KLF15 levels in the normal kidney, partially recovered the levels of KLF15 in remnant kidney. The expression of KLF15 in mesangial cells was repressed by oxidative stress, transforming growth factor-β, and tumor necrosis factor (TNF)-α. The suppressive effect of TNF-α on KLF15 expression was mediated by TNF receptor-1 and nuclear factor-κB. Overexpression of KLF15 in mesangial and HEK293 cells significantly decreased fibronectin and type IV collagen mRNA levels. Furthermore, KLF15 knockout mice developed glomerulosclerosis following uninephrectomy. Thus, KLF15 may be an antifibrotic factor in the kidney, and its decreased expression may contribute to the progression of kidney disease.
Mocroft, Amanda; Lundgren, Jens D; Ross, Michael; Fux, Christoph A; Reiss, Peter; Moranne, Olivier; Morlat, Philippe; Monforte, Antonella d'Arminio; Kirk, Ole; Ryom, Lene
2016-01-01
Whether or not the association between some antiretrovirals used in HIV infection and chronic kidney disease is cumulative is a controversial topic, especially in patients with initially normal renal function. In this study, we aimed to investigate the association between duration of exposure to antiretrovirals and the development of chronic kidney disease in people with initially normal renal function, as measured by estimated glomerular filtration rate (eGFR). In this prospective international cohort study, HIV-positive adult participants (aged ≥16 years) from the D:A:D study (based in Europe, the USA, and Australia) with first eGFR greater than 90 mL/min per 1·73 m(2) were followed from baseline (first eGFR measurement after Jan 1, 2004) until the occurrence of one of the following: chronic kidney disease; last eGFR measurement; Feb 1, 2014; or final visit plus 6 months (whichever occurred first). Chronic kidney disease was defined as confirmed (>3 months apart) eGFR lower than 60 mL/min per 1·73 m(2). The primary outcome was the occurrence of chronic kidney disease. Poisson regression was used to estimate the incidence rate of chronic kidney disease associated with cumulative exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, ritonavir-boosted lopinavir, other ritonavir-boosted protease inhibitors, or abacavir. Between Jan 1, 2004, and July 26, 2013, 23,905 eligible individuals from the D:A:D study were included. Participants had a median baseline eGFR of 110 mL/min per 1·73 m(2) (IQR 100-125), a median age of 39 years (33-45), and median CD4 cell count of 441 cells per mm(3) (294-628). During a median follow-up of 7·2 years (IQR 5·1-8·9), 285 (1%) of 23,905 people developed chronic kidney disease (incidence 1·76 per 1000 person-years of follow-up [95% CI 1·56-1·97]). After adjustment, we recorded a significant increase in chronic kidney disease associated with each additional year of exposure to tenofovir disoproxil fumarate (adjusted incidence rate ratio 1·14 [95% CI 1·10-1·19], p<0·0001), ritonavir-boosted atazanavir (1·20 [1·13-1·26], p<0·0001), and ritonavir-boosted lopinavir (1·11 [1·06-1·16], p<0·0001), but not other ritonavir-boosted protease inhibitors or abacavir. In people with normal renal function, the annual incidence of chronic kidney disease increased for up to 6 years of exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, or ritonavir-boosted lopinavir therapy. Although the absolute number of new cases of chronic kidney disease was modest, treatment with these antiretrovirals might result in an increasing and cumulative risk of chronic kidney disease. Patients on potentially nephrotoxic antiretrovirals or at high risk of chronic kidney disease should be closely monitored. The Highly Active Antiretroviral Therapy Oversight Committee. Copyright © 2016 Elsevier Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Harpool, K; Schnell, E; Herman, T
Purpose: To determine from retrospective study the most appropriate technique for targeting small borderline operable pancreatic cancer surrounding blood vessels by evaluating the dosimetry and normal tissue sparing achievable using Volumetric Modulated Arc Therapy (VMAT) and Intensity Modulated Radiation Therapy (IMRT). Methods: Treatment plans from ten patients who have undergone treatment with a prescribed dose of 4950 cGy, at 275 cGy per fraction, were analyzed. All plans were replanned using Eclipse TPS (Varian Medical Systems, Palo Alto, CA) with complementary VMAT or IMRT techniques to obtain paired data sets for comparison. The coverage to at least 95% of the plannedmore » target volume (PTV) was normalized to receive 100% of the prescription dose. The normal tissue constraints followed the quantitative analysis of normal tissue effects in the clinic (QUANTEC) guidelines and the organs at risks (OARs) were liver, kidneys, spinal cord and bowel. The plan evaluation was based on conformity index (CI), homogeneity index (HI), uniformity index (UI), DVH parameters, and student’s-t statistics (2 tails). Results: The VMAT technique delivered less maximum dose to the right kidney, left kidney, total kidney, liver, spinal cord, and bowel by 9.3%, 5.9%, 6.7%, 3.9%, 15.1%, 3.9%, and 4.3%, respectively. The averaged V15 for the total kidney was 10.21% for IMRT and 7.29% for VMAT. The averaged V20 for the bowel was 19.89% for IMRT and 14.06% for VMAT. On average, the CI for IMRT was 1.20 and 1.16 for VMAT (p = 0.20). The HI was 0.08 for both techniques (p = 0.91) and UI was 1.05 and 1.06 for IMRT and VMAT respectively (p = 0.59). Conclusion: Both techniques achieve adequate PTV coverage. Although VMAT techniques show better normal tissue sparing from excessive dose, no significant differences were observed. Slight discrepancies may rise from different versions of calculation algorithms.« less
Morandi, Luca; Gissi, Davide; Tarsitano, Achille; Asioli, Sofia; Gabusi, Andrea; Marchetti, Claudio; Montebugnoli, Lucio; Foschini, Maria Pia
2017-01-01
Oral squamous cell carcinoma (OSCC) is usually diagnosed at an advanced stage and is commonly preceded by oral premalignant lesions. The mortality rates have remained unchanged (50% within 5 years after diagnosis), and it is related to tobacco smoking and alcohol intake. Novel molecular markers for early diagnosis are urgently needed. The purpose of this study was to evaluate the diagnostic value of methylation level in a set of 18 genes by bisulfite next-generation sequencing. With minimally invasive oral brushing, 28 consecutive OSCC, one squamous cell carcinoma with sarcomatoid features, six high-grade squamous intraepithelial lesions (HGSIL), 30 normal contralateral mucosa from the same patients, and 65 healthy donors were evaluated for DNA methylation analyzing 18 target genes by quantitative bisulfite next-generation sequencing. We further evaluated an independent cohort (validation dataset) made of 20 normal donors, one oral fibroma, 14 oral lichen planus (OLP), three proliferative verrucous leukoplakia (PVL), and two OSCC. Comparing OSCC with normal healthy donors and contralateral mucosa in 355 CpGs, we identified the following epigenetically altered genes: ZAP70 , ITGA4 , KIF1A , PARP15 , EPHX3 , NTM , LRRTM1 , FLI1 , MIR193 , LINC00599 , PAX1 , and MIR137HG showing hypermethylation and MIR296 , TERT , and GP1BB showing hypomethylation . The behavior of ZAP70 , GP1BB , H19 , EPHX3 , and MIR193 fluctuated among different interrogated CpGs. The gap between normal and OSCC samples remained mostly the same (Kruskal-Wallis P values < 0.05), but the absolute values changed conspicuously. ROC curve analysis identified the most informative CpGs, and we correctly stratified OSCC and HGSIL from normal donors using a multiclass linear discriminant analysis in a 13-gene panel (AUC 0.981). Only the OSCC with sarcomatoid features was negative. Three contralateral mucosa were positive, a sign of a possible field cancerization. Among imprinted genes, only MIR296 showed loss of imprinting. DNMT1 , TERC , and H19 together with the global methylation of long interspersed element 1 were unchanged. In the validation dataset, values over the threshold were detected in 2/2 OSCC, in 3/3 PVL, and in 2/14 OLP. Our data highlight the importance of CpG location and correct estimation of DNA methylation level for highly accurate early diagnosis of OSCC.
Alvarado-García, Rafael; Gallego-Grijalva, Jorge; García-Arano, Gildardo
2004-01-01
Ureterocele is cystic dilation of the terminal part of the ureter located within the bladder of the urethra or both. In the majority of cases, it is accompanied by a double-collector system and affects 6:1 female child patients. We conducted an observational, longitudinal, transverse, descriptive, retrospective, and open study. Files of pediatric patients with diagnosed ureterocele from January 1, 1990 through December 31, 2002 were reviewed. Age, sex, symptomatology, type of ureterocele, side effects, and laboratory and image studies were analyzed. There were 40 cases, 50% male, average age 20 months; first clinical manifestation was urinary tract infection in 87.5%. Ectopic type was found more frequently with 62.3% and orthotopic or simple, in 37.5%. First surgical intervention was reimplantation in 80% of ectopic and in 66.7% in orthotopic cases. Ureterocele treatment depends to a great degree on status of affected kidney and capacity of functionality of the contralateral kidney. The spectrum of therapeutic modalities range from transureteral incision of ureterocele to nephrectomy and vesical reconstruction. Indication to proceed with endoscopy would be considered only in a patient with intravesical ureterocele with a simple collector system. We prefer to proceed in the majority of cases with ureteral reimplantation and resection of ureterocele.
Disruption of IFT Complex A Causes Cystic Kidneys without Mitotic Spindle Misorientation
Jonassen, Julie A.; SanAgustin, Jovenal; Baker, Stephen P.
2012-01-01
Intraflagellar transport (IFT) complexes A and B build and maintain primary cilia. In the mouse, kidney-specific or hypomorphic mutant alleles of IFT complex B genes cause polycystic kidneys, but the influence of IFT complex A proteins on renal development is not well understood. In the present study, we found that HoxB7-Cre–driven deletion of the complex A gene Ift140 from collecting ducts disrupted, but did not completely prevent, cilia assembly. Mutant kidneys developed collecting duct cysts by postnatal day 5, with rapid cystic expansion and renal dysfunction by day 15 and little remaining parenchymal tissue by day 20. In contrast to many models of polycystic kidney disease, precystic Ift140-deleted collecting ducts showed normal centrosomal positioning and no misorientation of the mitotic spindle axis, suggesting that disruption of oriented cell division is not a prerequisite to cyst formation in these kidneys. Precystic collecting ducts had an increased mitotic index, suggesting that cell proliferation may drive cyst expansion even with normal orientation of the mitotic spindle. In addition, we observed significant increases in expression of canonical Wnt pathway genes and mediators of Hedgehog and tissue fibrosis in highly cystic, but not precystic, kidneys. Taken together, these studies indicate that loss of Ift140 causes pronounced renal cystic disease and suggest that abnormalities in several different pathways may influence cyst progression. PMID:22282595
The gut-kidney axis in chronic renal failure: A new potential target for therapy.
Khoury, Tawfik; Tzukert, Keren; Abel, Roy; Abu Rmeileh, Ayman; Levi, Ronen; Ilan, Yaron
2017-07-01
Evidence is accumulating to consider the gut microbiome as a central player in the gut-kidney axis. Microbiome products, such as advanced glycation end products, phenols, and indoles, are absorbed into the circulation but are cleared by normal-functioning kidneys. These products then become toxic and contribute to the uremic load and to the progression of chronic kidney failure. In this review, we discuss the gut-kidney interaction under the state of chronic kidney failure as well as the potential mechanisms by which a change in the gut flora (termed gut dysbiosis) in chronic kidney disease (CKD) exacerbates uremia and leads to further progression of CKD and inflammation. Finally, the potential therapeutic interventions to target the gut microbiome in CKD are discussed. © 2016 International Society for Hemodialysis.
Role of AMP-activated protein kinase in kidney tubular transport, metabolism, and disease.
Rajani, Roshan; Pastor-Soler, Nuria M; Hallows, Kenneth R
2017-09-01
AMP-activated protein kinase (AMPK) is a metabolic sensor that regulates cellular energy balance, transport, growth, inflammation, and survival functions. This review explores recent work in defining the effects of AMPK on various renal tubular epithelial ion transport proteins as well as its role in kidney injury and repair in normal and disease states. Recently, several groups have uncovered additional functions of AMPK in the regulation of kidney and transport proteins. These new studies have focused on the role of AMPK in the kidney in the setting of various diseases such as diabetes, which include evaluation of the effects of the hyperglycemic state on podocyte and tubular cell function. Other recent studies have investigated how reduced kidney mass, polycystic kidney disease (PKD), and fibrosis affect AMPK activation status. A general theme of several conditions that lead to chronic kidney disease (CKD) is that AMPK activity is abnormally suppressed relative to that in normal kidneys. Thus, the idea that AMPK activation may be a therapeutic strategy to slow down the progression of CKD has emerged. In addition to drugs such as metformin and 5-aminoimidazole-4-carboxamide ribonucleotide that are classically used as AMPK activators, recent studies have identified the therapeutic potential of other compounds that function at least partly as AMPK activators, such as salicylates, statins, berberine, and resveratrol, in preventing the progression of CKD. AMPK in the kidney plays a unique role at the crossroads of energy metabolism, ion and water transport, inflammation, and stress. Its potential role in modulating recovery from vs. progression of acute and chronic kidney injury has been the topic of recent research findings. The continued study of AMPK in kidney physiology and disease has improved our understanding of these physiological and pathological processes and offers great hope for therapeutic avenues for the increasing population at risk to develop kidney failure.
Type 4 renal tubular acidosis in a kidney transplant recipient.
Kulkarni, Manjunath
2016-02-01
We report a case of a 66-year-old diabetic patient who presented with muscle weakness 2 weeks after kidney transplantation. Her immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and steroids. She was found to have hyperkalemia and normal anion gap metabolic acidosis. Tacrolimus levels were in therapeutic range. All other drugs such as beta blockers and trimethoprim - sulfamethoxazole were stopped. She did not respond to routine antikalemic measures. Further evaluation revealed type 4 renal tubular acidosis. Serum potassium levels returned to normal after starting sodium bicarbonate and fludrocortisone therapy. Though hyperkalemia is common in kidney transplant recipients, determining exact cause can guide specific treatment. Copyright © 2016 Chang Gung University. Published by Elsevier B.V. All rights reserved.
Luzanova, I S; Svetlolobov, D Iu; Zorin, Iu V
2014-01-01
The objective of the present work was to continue the studies of the sites of concentration of the chemical elements corresponding to normal homeostasis in human biological objects by mass spectrometry with inductively coupled plasma. The study yielded the data on the natural content of 27 elements in the cadaveric liver, kidney, and stomach. It is recommended to use these findings as the reference parameters corresponding to normal homeostasis.
Chuang, Connie; Ramaker, Megan A.; Kaur, Sirjaut; Csomos, Rebecca A.; Kroner, Kevin T.; Bleedorn, Jason A.; Schaefer, Susan L.; Muir, Peter
2014-01-01
Background Complete cranial cruciate ligament rupture (CR) is a common cause of pelvic limb lameness in dogs. Dogs with unilateral CR often develop contralateral CR over time. Although radiographic signs of contralateral stifle joint osteoarthritis (OA) influence risk of subsequent contralateral CR, this risk has not been studied in detail. Methodology/Principal Findings We conducted a retrospective longitudinal cohort study of client-owned dogs with unilateral CR to determine how severity of radiographic stifle synovial effusion and osteophytosis influence risk of contralateral CR over time. Detailed survival analysis was performed for a cohort of 85 dogs after case filtering of an initial sample population of 513 dogs. This population was stratified based on radiographic severity of synovial effusion (graded on a scale of 0, 1, and 2) and severity of osteophytosis (graded on a scale of 0, 1, 2, and 3) of both index and contralateral stifle joints using a reproducible scoring method. Severity of osteophytosis in the index and contralateral stifles was significantly correlated. Rupture of the contralateral cranial cruciate ligament was significantly influenced by radiographic OA in both the index and contralateral stifles at diagnosis. Odds ratio for development of contralateral CR in dogs with severe contralateral radiographic stifle effusion was 13.4 at one year after diagnosis and 11.4 at two years. Odds ratio for development of contralateral CR in dogs with severe contralateral osteophytosis was 9.9 at one year after diagnosis. These odds ratios were associated with decreased time to contralateral CR. Breed, age, body weight, gender, and tibial plateau angle did not significantly influence time to contralateral CR. Conclusion Subsequent contralateral CR is significantly influenced by severity of radiographic stifle effusion and osteophytosis in the contralateral stifle, suggesting that synovitis and arthritic joint degeneration are significant factors in the disease mechanism underlying the arthropathy. PMID:25254499
Mapping of Carboxypeptidase M in Normal Human Kidney and Renal Cell Carcinoma
Denis, Catherine J.; Van Acker, Nathalie; De Schepper, Stefanie; De Bie, Martine; Andries, Luc; Fransen, Erik; Hendriks, Dirk; Kockx, Mark M.
2013-01-01
Although the kidney generally has been regarded as an excellent source of carboxypeptidase M (CPM), little is known about its renal-specific expression level and distribution. This study provides a detailed localization of CPM in healthy and diseased human kidneys. The results indicate a broad distribution of CPM along the renal tubular structures in the healthy kidney. CPM was identified at the parietal epithelium beneath the Bowman’s basement membrane and in glomerular mesangial cells. Capillaries, podocytes, and most interstitial cells were CPM negative. Tumor cells of renal cell carcinoma subtypes lose CPM expression upon dedifferentiation. Tissue microarray analysis demonstrated a correlation between low CPM expression and tumor cell type. CPM staining was intense on phagocytotic tumor-associated macrophages. Immunoreactive CPM was also detected in the tumor-associated vasculature. The absence of CPM in normal renal blood vessels points toward a role for CPM in angiogenesis. Coexistence of CPM and the epidermal growth factor receptor (EGFR) was detected in papillary renal cell carcinoma. However, the different subcellular localization of CPM and EGFR argues against an interaction between these h proteins. The description of the distribution of CPM in human kidney forms the foundation for further study of the (patho)physiological activities of CPM in the kidney. PMID:23172796
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, H; Lan, L; Sennett, C
Purpose: To gain insight into the role of parenchyma stroma in the characterization of breast tumors by incorporating computerized mammographic parenchyma assessment into breast CADx in the task of distinguishing between malignant and benign lesions. Methods: This study was performed on 182 biopsy-proven breast mass lesions, including 76 benign and 106 malignant lesions. For each full-field digital mammogram (FFDM) case, our quantitative imaging analysis was performed on both the tumor and a region-of-interest (ROI) from the normal contralateral breast. The lesion characterization includes automatic lesion segmentation and feature extraction. Radiographic texture analysis (RTA) was applied on the normal ROIs tomore » assess the mammographic parenchymal patterns of these contralateral normal breasts. Classification performance of both individual computer extracted features and the output from a Bayesian artificial neural network (BANN) were evaluated with a leave-one-lesion-out method using receiver operating characteristic (ROC) analysis with area under the curve (AUC) as the figure of merit. Results: Lesion characterization included computer-extracted phenotypes of spiculation, size, shape, and margin. For parenchymal pattern characterization, five texture features were selected, including power law beta, contrast, and edge gradient. Merging of these computer-selected features using BANN classifiers yielded AUC values of 0.79 (SE=0.03) and 0.67 (SE=0.04) in the task of distinguishing between malignant and benign lesions using only tumor phenotypes and texture features from the contralateral breasts, respectively. Incorporation of tumor phenotypes with parenchyma texture features into the BANN yielded improved classification performance with an AUC value of 0.83 (SE=0.03) in the task of differentiating malignant from benign lesions. Conclusion: Combining computerized tumor and parenchyma phenotyping was found to significantly improve breast cancer diagnostic accuracy highlighting the need to consider both tumor and stroma in decision making. Funding: University of Chicago Dean Bridge Fund, NCI U24-CA143848-05, P50-CA58223 Breast SPORE program, and Breast Cancer Research Foundation. COI: MLG is a stockholder in R2 technology/Hologic and receives royalties from Hologic, GE Medical Systems, MEDIAN Technologies, Riverain Medical, Mitsubishi, and Toshiba. MLG is a cofounder and stockholder in Quantitative Insights.« less
Relation between measures of speech-in-noise performance and measures of efferent activity
NASA Astrophysics Data System (ADS)
Smith, Brad; Harkrider, Ashley; Burchfield, Samuel; Nabelek, Anna
2003-04-01
Individual differences in auditory perceptual abilities in noise are well documented but the factors causing such variability are unclear. The purpose of this study was to determine if individual differences in responses measured from the auditory efferent system were correlated to individual variations in speech-in-noise performance. The relation between behavioral performance on three speech-in-noise tasks and two objective measures of the efferent auditory system were examined in thirty normal-hearing, young adults. Two of the speech-in-noise tasks measured an acceptable noise level, the maximum level of speech-babble noise that a subject is willing to accept while listening to a story. For these, the acceptable noise level was evaluated using both an ipsilateral (story and noise in same ear) and a contralateral (story and noise in opposite ears) paradigm. The third speech-in-noise task evaluated speech recognition using monosyllabic words presented in competing speech babble. Auditory efferent activity was assessed by examining the resulting suppression of click-evoked otoacoustic emissions following the introduction of a contralateral, broad-band stimulus and the activity of the ipsilateral and contralateral acoustic reflex arc was evaluated using tones and broad-band noise. Results will be discussed relative to current theories of speech in noise performance and auditory inhibitory processes.
Fan, Xiaotong; Yan, Hao; Shan, Yi; Shang, Kun; Wang, Xiaocui; Wang, Peipei; Shan, Yongzhi; Lu, Jie; Zhao, Guoguang
2016-01-01
Occurrence of language impairment in mesial temporal lobe epilepsy (mTLE) patients is common and left mTLE patients always exhibit a primary problem with access to names. To explore different neuropsychological profiles between left and right mTLE patients, the study investigated both structural and effective functional connectivity changes within the semantic cognition network between these two groups and those from normal controls. We found that gray matter atrophy of left mTLE patients was more severe than that of right mTLE patients in the whole brain and especially within the semantic cognition network in their contralateral hemisphere. It suggested that seizure attacks were rather targeted than random for patients with hippocampal sclerosis (HS) in the dominant hemisphere. Functional connectivity analysis during resting state fMRI revealed that subregions of the anterior temporal lobe (ATL) in the left HS patients were no longer effectively connected. Further, we found that, unlike in right HS patients, increased causal linking between ipsilateral regions in the left HS epilepsy patients cannot make up for their decreased contralateral interaction. It suggested that weakened contralateral connection and disrupted effective interaction between subregions of the unitary, transmodal hub of the ATL may be the primary cause of anomia in the left HS patients.
Fan, Xiaotong; Shang, Kun; Wang, Xiaocui; Wang, Peipei; Shan, Yongzhi; Lu, Jie
2016-01-01
Occurrence of language impairment in mesial temporal lobe epilepsy (mTLE) patients is common and left mTLE patients always exhibit a primary problem with access to names. To explore different neuropsychological profiles between left and right mTLE patients, the study investigated both structural and effective functional connectivity changes within the semantic cognition network between these two groups and those from normal controls. We found that gray matter atrophy of left mTLE patients was more severe than that of right mTLE patients in the whole brain and especially within the semantic cognition network in their contralateral hemisphere. It suggested that seizure attacks were rather targeted than random for patients with hippocampal sclerosis (HS) in the dominant hemisphere. Functional connectivity analysis during resting state fMRI revealed that subregions of the anterior temporal lobe (ATL) in the left HS patients were no longer effectively connected. Further, we found that, unlike in right HS patients, increased causal linking between ipsilateral regions in the left HS epilepsy patients cannot make up for their decreased contralateral interaction. It suggested that weakened contralateral connection and disrupted effective interaction between subregions of the unitary, transmodal hub of the ATL may be the primary cause of anomia in the left HS patients. PMID:28018680
Messamore, William G.; Van Acker, Gustaf M.; Hudson, Heather M.; Zhang, Hongyu Y.; Kovac, Anthony; Nazzaro, Jules; Cheney, Paul D.
2016-01-01
While a large body of evidence supports the view that ipsilateral motor cortex may make an important contribution to normal movements and to recovery of function following cortical injury (Chollet et al. 1991; Fisher 1992; Caramia et al. 2000; Feydy et al. 2002), relatively little is known about the properties of output from motor cortex to ipsilateral muscles. Our aim in this study was to characterize the organization of output effects on hindlimb muscles from ipsilateral motor cortex using stimulus-triggered averaging of EMG activity. Stimulus-triggered averages of EMG activity were computed from microstimuli applied at 60–120 μA to sites in both contralateral and ipsilateral M1 of macaque monkeys during the performance of a hindlimb push–pull task. Although the poststimulus effects (PStEs) from ipsilateral M1 were fewer in number and substantially weaker, clear and consistent effects were obtained at an intensity of 120 μA. The mean onset latency of ipsilateral poststimulus facilitation was longer than contralateral effects by an average of 0.7 ms. However, the shortest latency effects in ipsilateral muscles were as short as the shortest latency effects in the corresponding contralateral muscles suggesting a minimal synaptic linkage that is equally direct in both cases. PMID:26088970
Effect of cochlear implantation on middle ear function: A three-month prospective study.
Wasson, Joseph D; Campbell, Luke; Chambers, Scott; Hampson, Amy; Briggs, Robert J S; O'Leary, Stephen J
2018-05-01
To determine if cochlear implantation has a delayed effect on the middle ear conductive hearing mechanism by measuring laser Doppler vibrometry (LDV) of the tympanic membrane (TM) in both implanted and contralateral control ears preoperatively and 3 months postoperatively, and then comparing the relative change in LDV outcome measures between implanted and control ears. Prospective cohort study. Eleven preoperative adult unilateral cochlear implant recipients in previously unoperated ears with normal anatomy and aerated temporal bones were included in this study. The magnitude and phase angle of umbo velocity transfer function in response to air- conduction (AC) stimulus, and the magnitude of umbo velocity in response to bone- conduction (BC) stimulus were measured in the implant ear and the contralateral control ear preoperatively and 3 months postoperatively and compared. No significant changes in the magnitude or phase angle of TM velocity in response to either AC or BC stimulus were observed in the implanted ear relative to the contralateral control ear 3 months following cochlear implantation. From the results of LDV measurements, it can be said that cochlear implantation has no significant delayed effect on the middle ear conductive mechanism. 4. Laryngoscope, 128:1207-1212, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.
Comparison of neuromuscular abnormalities between upper and lower extremities in hemiparetic stroke.
Mirbagheri, M M; AliBiglou, L; Thajchayapong, M; Lilaonitkul, T; Rymer, W Z
2006-01-01
We studied the neuromuscular mechanical properties of the elbow and ankle joints in chronic, hemiparetic stroke patients and healthy subjects. System identification techniques were used to characterize the mechanical abnormalities of these joints and to identify the contribution of intrinsic and reflex stiffness to these abnormalities. Modulation of intrinsic and reflex stiffness with the joint angle was studied by applying PRBS perturbations to the joint at different joint angles. The experiments were performed for both spastic (stroke) and contralateral (control) sides of stroke patients and one side of healthy (normal) subjects. We found reflex stiffness gain (GR) was significantly larger in the stroke than the control side for both elbow and ankle joints. GR was also strongly position dependent in both joints. However, the modulation of GR with position was slightly different in two joints. GR was also larger in the control than the normal joints but the differences were significant only for the ankle joint. Intrinsic stiffness gain (K) was also significantly larger in the stroke than the control joint at elbow extended positions and at ankle dorsiflexed positions. Modulation of K with the ankle angle was similar for stroke, control and normal groups. In contrast, the position dependency of the elbow was different. K was larger in the control than normal ankle whereas it was lower in the control than normal elbow. However, the differences were not significant for any joint. The findings demonstrate that both reflex and intrinsic stiffness gain increase abnormally in both upper and lower extremities. However, the major contribution of intrinsic and reflex stiffness to the abnormalities is at the end of ROM and at the middle ROM, respectively. The results also demonstrate that the neuromuscular properties of the contralateral limb are not normal suggesting that it may not be used as a suitable control at least for the ankle study.
Subcortical functional reorganization due to early blindness
Jiang, Fang; Fine, Ione; Watkins, Kate E.; Bridge, Holly
2015-01-01
Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a “visual” subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses. PMID:25673746
Subcortical functional reorganization due to early blindness.
Coullon, Gaelle S L; Jiang, Fang; Fine, Ione; Watkins, Kate E; Bridge, Holly
2015-04-01
Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a "visual" subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses. Copyright © 2015 the American Physiological Society.
Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma.
Ambrosio, Maria R; Rocca, Bruno J; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T; Tripodi, Sergio A; Tosi, Piero
2015-01-01
Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis.
Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma
Ambrosio, Maria R.; Rocca, Bruno J.; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T.; Tripodi, Sergio A.; Tosi, Piero
2015-01-01
Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis. PMID:26425551
Di Zazzo, Giacomo; Stringini, Gilda; Matteucci, Maria Chiara; Muraca, Maurizio; Malena, Saverio; Emma, Francesco
2011-01-01
Clinical and experimental data have shown that differences in nephron endowment result in differences in renal mass and predisposition to chronic renal failure, hypertension, and proteinuria. We hypothesized that a significant proportion of the variance in GFR, as estimated by serum creatinine, is attributable to differences in renal size in normal children. A total of 1748 normal renal ultrasounds that were performed in children older than 6 months were reviewed. For each ultrasound, serum creatinine, serum blood urea nitrogen, and systolic and diastolic office BP were recorded. Renal size was evaluated as a function of renal length and thickness. All data were normalized for height, weight, age, and gender. When expressed as SD scores, a significant correlation was found between kidney size and serum creatinine (P < 0.0001) and between kidney size and serum blood urea nitrogen (P < 0.002). When dividing kidney size data per quintiles, a difference of 0.51 SD score in serum creatinine was observed between the lowest and highest quintile. No significant correlation was found with office BP measurements. These data show that, even in the normal pediatric population, differences in renal function are significantly explained by differences in renal mass. Methodologic limitations of this study are likely to underestimate this relationship.
Sudden post-traumatic sciatica caused by a thoracic spinal meningioma.
Mariniello, Giuseppe; Malacario, Francesca; Dones, Flavia; Severino, Rocco; Ugga, Lorenzo; Russo, Camilla; Elefante, Andrea; Maiuri, Francesco
2016-10-01
Spinal meningiomas usually present with slowly progressive symptoms of cord and root compression, while a sudden clinical onset is very rare. A 35-year-old previously symptom-free woman presented sudden right sciatica and weakness of her right leg following a fall with impact to her left foot. A neurological examination showed paresis of the right quadriceps, tibial and sural muscles, increased bilateral knee and ankle reflexes and positive Babinski sign. Magnetic resonance imaging (MRI) revealed the presence of a spinal T11 meningioma in the left postero-lateral compartment of the spinal canal; at this level, the spinal cord was displaced to the contralateral side with the conus in the normal position. At surgery, a meningioma with dural attachment of the left postero-lateral dural surface was removed. The intervention resulted in rapid remission of both pain and neurological deficits. Spinal meningiomas may exceptionally present with sudden pain and neurological deficits as result of tumour bleeding or post-traumatic injury of the already compressed nervous structures, both in normal patients and in those with conus displacement or tethered cord. In this case, the traumatic impact of the left foot was transmitted to the spine, resulting in stretching of the already compressed cord and of the contralateral lombosacral roots. This case suggests that low thoracic cord compression should be suspected in patients with post-traumatic radicular leg pain with normal lumbar spine MRI. © The Author(s) 2016.
Kabadi, S J; Ruhl, D S; Mukherjee, S; Kesser, B W
2018-02-01
Middle ear space is one of the most important components of the Jahrsdoerfer grading system (J-score), which is used to determine surgical candidacy for congenital aural atresia. The purpose of this study was to introduce a semiautomated method for measuring middle ear volume and determine whether middle ear volume, either alone or in combination with the J-score, can be used to predict early postoperative audiometric outcomes. A retrospective analysis was conducted of 18 patients who underwent an operation for unilateral congenital aural atresia at our institution. Using the Livewire Segmentation tool in the Carestream Vue PACS, we segmented middle ear volumes using a semiautomated method for all atretic and contralateral normal ears on preoperative high-resolution CT imaging. Postsurgical audiometric outcome data were then analyzed in the context of these middle ear volumes. Atretic middle ear volumes were significantly smaller than those in contralateral normal ears ( P < .001). Patients with atretic middle ear volumes of >305 mm 3 had significantly better postoperative pure tone average and speech reception thresholds than those with atretic ears below this threshold volume ( P = .01 and P = .006, respectively). Atretic middle ear volume incorporated into the J-score offered the best association with normal postoperative hearing (speech reception threshold ≤ 30 dB; OR = 37.8, P = .01). Middle ear volume, calculated in a semiautomated fashion, is predictive of postsurgical audiometric outcomes, both independently and in combination with the conventional J-score. © 2018 by American Journal of Neuroradiology.
Functional visual acuity in patients with successfully treated amblyopia: a pilot study.
Hoshi, Sujin; Hiraoka, Takahiro; Kotsuka, Junko; Sato, Yumiko; Izumida, Shinya; Kato, Atsuko; Ueno, Yuta; Fukuda, Shinichi; Oshika, Tetsuro
2017-06-01
The aim of this study was to use conventional visual acuity measurements to quantify the functional visual acuity (FVA) in eyes with successfully treated amblyopia, and to compare the findings with those for contralateral normal eyes. Nineteen patients (7 boys, 12 girls; age 7.5 ± 2.2 years) with successfully treated unilateral amblyopia and the same conventional decimal visual acuity in both eyes (better than 1.0) were enrolled. FVA, the visual maintenance ratio (VMR), maximum and minimum visual acuity, and the average response time were recorded for both eyes of all patients using an FVA measurement system. The differences in FVA values between eyes were analyzed. The mean LogMAR FVA scores, VMR (p < 0.001 for both), and the LogMAR maximum (p < 0.005) and minimum visual acuity (p < 0.001) were significantly poorer for the eyes with treated amblyopia than for the contralateral normal eyes. There was no significant difference in the average response time. Our results indicate that FVA and VMR were poorer for eyes with treated amblyopia than for normal eyes, even though the treatment for amblyopia was considered successful on the basis of conventional visual acuity measurements. These results suggest that visual function is impaired in eyes with amblyopia, regardless of treatment success, and that FVA measurements can provide highly valuable diagnosis and treatment information that is not readily provided by conventional visual acuity measurements.
Bacak-Kocman, Iva; Peric, Mladen; Kastelan, Zeljko; Kes, Petar; Mesar, Ines; Basic-Jukic, Nikolina
2013-10-01
There is a widening gap between the needs and possibilities of kidney transplantation. In order to solve the problem of organ shortage, the selection criteria for kidney donors have been less stringent over the last years. Favorable outcome of renal transplantation from deceased donors with acute renal failure requiring dialysis may have an important role in expanding the pool of donors. We present the case of two renal transplantations from a polytraumatized 20-years old donor with acute renal failure requiring dialysis. One recipient established good diuresis from the first post-transplant day and did not require hemodialysis. The second recipient had delayed graft function and was treated with 8 hemodialysis sessions. The patient was discharged with good diuresis and normal serum creatinine. After two years of follow-up, both recipients have normal graft function. According to our experience, kidneys from deceased young donors with acute renal failure requiring dialysis may be transplanted, in order to decrease the number of patients on transplantation waiting lists.
Glomerular disease augments kidney accumulation of synthetic anionic polymers.
Liu, Gary W; Prossnitz, Alexander N; Eng, Diana G; Cheng, Yilong; Subrahmanyam, Nithya; Pippin, Jeffrey W; Lamm, Robert J; Ngambenjawong, Chayanon; Ghandehari, Hamidreza; Shankland, Stuart J; Pun, Suzie H
2018-06-02
Polymeric drug carriers can alter the pharmacokinetics of their drug cargoes, thereby improving drug therapeutic index and reducing side effects. Understanding and controlling polymer properties that drive tissue-specific accumulation is critical in engineering targeted drug delivery systems. For kidney disease applications, targeted drug delivery to renal cells that reside beyond the charge- and size-selective glomerular filtration barrier could have clinical potential. However, there are limited reports on polymer properties that might enhance kidney accumulation. Here, we studied the effects of molecular weight and charge on the in vivo kidney accumulation of polymers in health and disease. We synthesized a panel of well-defined polymers by atom transfer radical polymerization to answer several questions. First, the biodistribution of low molecular weight (23-27 kDa) polymers composed of various ratios of neutral:anionic monomers (1:0, 1:1, 1:4) in normal mice was determined. Then, highly anionic (1:4 monomer ratio) low molecular and high molecular weight (47 kDa) polymers were tested in both normal and experimental focal segmental glomerulosclerosis (FSGS) mice, a model that results in loss of glomerular filtration selectivity. Through these studies, we observed that kidney-specific polymer accumulation increases with anionic monomer content, but not molecular weight; experimental FSGS increases kidney accumulation of anionic polymers; and anionic polymers accumulate predominantly in proximal tubule cells, with some distribution in kidney glomeruli. These findings can be applied to the design of polymeric drug carriers to enhance or mitigate kidney accumulation. Copyright © 2018 Elsevier Ltd. All rights reserved.
... take the missing hormone as a pill. Other Reasons Why Kids Might Not Grow Normally Hormones play ... but kids might not grow normally for other reasons, including: Chronic diseases. These include heart and kidney ...
Peculiar Expression of CD3-Epsilon in Kidney of Ginbuna Crucian Carp.
Miyazawa, Ryuichiro; Murata, Norifumi; Matsuura, Yuta; Shibasaki, Yasuhiro; Yabu, Takeshi; Nakanishi, Teruyuki
2018-01-01
TCR/CD3 complex is composed of the disulfide-linked TCR-αβ heterodimer that recognizes the antigen as a peptide presented by the MHC, and non-covalently paired CD3γε- and δε-chains together with disulfide-linked ζ-chain homodimers. The CD3 chains play key roles in T cell development and T cell activation. In the present study, we found nor or extremely lower expression of CD3ε in head- and trunk-kidney lymphocytes by flow cytometric analysis, while CD3ε was expressed at the normal level in lymphocytes from thymus, spleen, intestine, gill, and peripheral blood. Furthermore, CD4-1 + and CD8α + T cells from kidney express Zap-70, but not CD3ε, while the T cells from other tissues express both Zap-70 and CD3ε, although expression of CD3ε was low. Quantitative analysis of mRNA expression revealed that the expression level of T cell-related genes including tcrb, cd3 ε, zap-70 , and lck in CD4-1 + and CD8α + T cells was not different between kidney and spleen. Western blot analysis showed that CD3ε band was detected in the cell lysates of spleen but not kidney. To be interested, CD3ε-positive cells greatly increased after 24 h in in vitro culture of kidney leukocytes. Furthermore, expression of CD3ε in both transferred kidney and spleen leukocytes was not detected or very low in kidney, while both leukocytes expressed CD3ε at normal level in spleen when kidney and spleen leukocytes were injected into the isogeneic recipient. Lower expression of CD3ε was also found in kidney T lymphocytes of goldfish and carp. These results indicate that kidney lymphocytes express no or lower level of CD3ε protein in the kidney, although the mRNA of the gene was expressed. Here, we discuss this phenomenon from the point of function of kidney as reservoir for T lymphocytes in teleost, which lacks lymph node and bone marrow.
Müller, Thiago R; Marcelino, Raquel S; de Souza, Livia P; Teixeira, Carlos R; Mamprim, Maria J
2017-02-01
Objectives The aim of the study was to describe the normal abdominal echoanatomy of the tigrina and to compare it with the abdominal echoanatomy of the domestic cat. Reference intervals for the normal abdominal ultrasonographic anatomy of individual species are important for accurate diagnoses and interpretation of routine health examinations. The hypothesis was that the echoanatomy of the tigrina was similar to that of the domestic cat. Methods Eighteen clinically healthy tigrina were selected for abdominal ultrasound examination, in order to obtain normal parameters of the bladder, spleen, adrenal gland, kidney, gastrointestinal tract, liver and gall bladder, and Doppler parameters of liver and kidney vessels. Results The splenic parenchyma was consistently hyperechoic to the kidneys and liver. The liver, kidneys and spleen had similar echotexture, shape and dimensions when compared with the domestic cat. The gall bladder was lobulated and surrounded by a clearly visualized thin, smooth, regular echogenic wall. The adrenal glands had a bilobulated shape. The urinary bladder had a thin echogenic wall. The Doppler parameters of the portal vein and renal artery were similar to the domestic cat. Conclusions and relevance The results support the hypothesis that the ultrasonographic parameters of the abdominal viscera of the southern tigrina are similar to those of the domestic cat.
Osumi, Tomoo; Awazu, Midori; Fujimura, Eriko; Yamazaki, Fumito; Hashiguchi, Akinori; Shimada, Hiroyuki
2013-06-01
Secondary polycythemia with increased production of erythropoietin (EPO) is known to occur in kidney diseases such as hydronephrosis and cystic disease, but the mechanism remains unclear. We report an 18-year-old female with isolated renal relapse of acute lymphoblastic leukemia accompanied by polycythemia. At the relapse, she presented with bilateral nephromegaly, mild renal dysfunction, and erythrocytosis with increased serum EPO levels up to 52.1 mIU/mL (9.1-32.8). Renal biopsy demonstrated diffuse lymphoblastic infiltration. The expression of hypoxia-inducible factor (HIF)-1α, which is undetectable in normal kidney, was observed in the renal tubule epithelium compressed by lymphoblastic cells. These findings suggest that erythrocytosis was caused by renal ischemia due to leukemic infiltration. Polycythemia probably became apparent because of the lack of leukemic involvement of the bone marrow. With chemotherapy, the serum EPO level rapidly decreased to normal range accompanied by the normalization of kidney size and function. Renal leukemic infiltration may enhance EPO production, although not recognized in the majority of cases because of bone marrow involvement. Our case has clarified the mechanism of previously reported polycythemia associated with renal diseases as renal ischemia. Furthermore, we have added renal ischemia resulting from tumor infiltration to the list of causes of secondary polycythemia.
Dynamic contrast-enhanced x-ray CT measurement of cerebral blood volume in a rabbit tumor model
NASA Astrophysics Data System (ADS)
Cenic, Aleksa; Lee, Ting-Yim; Craen, Rosemary A.; Gelb, Adrian W.
1998-07-01
Cerebral blood volume (CBV) is a major determinant of intracranial pressure (ICP). Hyperventilation is commonly employed to reduce raised ICP (e.g. in brain tumour patients) presumably through its effect on CBV. With the advent of slip- ring CT scanners, dynamic contrast-enhanced imaging allows for the measurement of CBV with high spatial resolution. Using a two-compartment model to characterize the distribution of X- ray contrast agent in the brain, we have developed a non- equilibrium CT method to measure CBV in normal and pathological regions. We used our method to investigate the effect of hyperventilation on CBV during propofol anaesthesia in rabbits with implanted brain tumours. Eight New Zealand White rabbits with implanted VX2 carcinoma brain tumours were studied. For each rabbit, regional CBV measurements were initially made at normocapnia (PaCO2 40 mmHg) and then at hyperventilation (PaCO2 25 mmHg) during propofol anaesthesia. The head was positioned such that a coronal image through the brain incorporated a significant cross-section of the brain tumour as well as a radial artery in a forelimb. Images at the rate of 1 per second were acquired for 2 minutes as Omnipaque 300 (1.5 ml/kg rabbit weight) was injected via a peripheral vein. In these CT images, regions of interest in the brain tissue (e.g. tumour, contra-lateral normal, and peri-tumoural) and the radial artery were drawn. For each region, the mean CT number in pre-contrast images was subtracted from the mean CT number in post-contrast images to produce either the tissue contrast concentration curve, or the arterial contrast concentration curve. Using our non- equilibrium analysis method based on a two-compartment model, regional CBV values were determined from the measured contrast concentration curves. From our study, the mean CBV values [+/- SD] in the tumour, peri-tumoural, and contra-lateral normal regions during normocapnia were: 5.47 plus or minus 1.97, 3.28 plus or minus 1.01, and 1.86 plus or minus 0.54 ml/100 g, respectively. Following hyperventilation, we found a significant decrease (p less than 0.025) of 10.4% in CBV in the peri-tumoural region, and no statistically significant change in CBV in the tumour or contra-lateral normal regions. We have developed a convenient method for measuring CBV in normal and pathological tissue using a slip-ring CT scanner. In a brain tumour model, we found that CBV was markedly increased in tumour and peri-tumoural regions compared to normal regions. Our results suggest that the reduction of raised ICP following hyperventilation during propofol anaesthesia may be mainly due to a reduction in CBV in the peri-tumoural tissue rather than in the bulk of the tumour or normal regions. Our method has the potential to provide further knowledge on the cerebral hemodynamics of space- occupying lesions during different anaesthetic interventions or treatment regiments.
de Almeida, Fernando Antonio; Ciambelli, Giuliano Serafino; Bertoco, André Luz; Jurado, Marcelo Mai; Siqueira, Guilherme Vasconcelos; Bernardo, Eder Augusto; Pavan, Maria Valeria; Gianini, Reinaldo José
2015-02-01
In Brazil hypertension and type 2 diabetes mellitus are responsible for 60% of cases of end-stage renal disease in renal replacement therapy. In the United States studies have identified family clustering of chronic kidney disease, predominantly in African-Americans. A single Brazilian study observed family clustering among patients with chronic kidney disease when compared with hospitalized patients with normal renal function. This article aims to assess whether there is family clustering of chronic kidney disease in relatives of individuals in renal replacement therapy caused by hypertension and/or diabetes mellitus. A case-control study with 336 patients in renal replacement therapy with diabetes mellitus or hypertension for at least 5 years (cases) and a control matched sample group of individuals with hypertension or diabetes mellitus and normal renal function (n = 389). Individuals in renal replacement therapy (cases) had a ratio of 2.35 (95% CI 1.42-3.89, p < 0.001) versus the control group in having relatives with chronic renal disease, irrespective of race or causative illness. There is family clustering of chronic kidney disease in the sample studied, and this predisposition is irrespective of race and underlying disease (hypertension or diabetes mellitus).
Effects of water uptake on melamine renal stone formation in mice.
Peng, Jiao; Li, Daxu; Chan, Yee Kwan; Chen, Yan; Lamb, Jonathan R; Tam, Paul K H; El-Nezami, Hani
2012-06-01
Melamine-tainted food can induce kidney stones both in humans and animals and in domestic animals, severe cases caused acute kidney failure and death. Although increasing water intake can ameliorate kidney stone formation, its effect on melamine (Mel)-induced kidney stones has not been studied. We have analysed the effect of restricted ingestion of drinking water on melamine stone formation in mice. They were given melamine and cyanuric acid orally and received drinking water either freely or for a restricted time. Kidney stone formation and renal function were monitored. Mice receiving drinking water for a restricted 10-h period initially lost body weight, which returned to normal within 2 days. No other abnormalities were observed. Ingestion of melamine alone failed to induce kidney stones even under conditions of restricted drinking water. In mice treated with melamine together with cyanuric acid for 3 days, no renal stones were formed when the supply of drinking was normal. However, when drinking water was limited, stone formation was observed and accompanied by high levels of serum urea and creatinine. An increase in urine haemoglobin and glucose levels was also found. The administration resulted in up-regulated tissue osteopontin, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin messenger RNA expression and macrophage infiltration. Our results indicate the importance of water intake in the formation of melamine-induced renal stone formation in the mouse and provide new information on the mechanisms of melamine stone formation.
Willenberg, Rafer; Zukor, Katherine; Liu, Kai; He, Zhigang; Steward, Oswald
2016-01-01
Corticospinal tract (CST) axons from one hemisphere normally extend and terminate predominantly in the contralateral spinal cord. We previously showed that deleting PTEN in the sensorimotor cortex enables CST axons to regenerate after spinal cord injury and that some regenerating axons extend along the “wrong” side. Here, we characterize the degree of specificity of regrowth in terms of laterality. PTEN was selectively deleted via cortical AAV-Cre injections in neonatal PTEN-floxed mice. As adults, mice received dorsal hemisection injuries at T12 or complete crush injuries at T9. CST axons from one hemisphere were traced by unilateral BDA injections in PTEN-deleted mice with spinal cord injury and in non-injured PTEN-floxed mice that had not received AAV-Cre. In non-injured mice, 97.9 ± 0.7% of BDA-labeled axons in white matter and 88.5 ± 1.0% of BDA-labeled axons in grey matter were contralateral to the cortex of origin. In contrast, laterality of CST axons that extended past a lesion due to PTEN deletion varied across animals. In some cases, regenerated axons extended predominantly on the ipsilateral side, in other cases, axons extended predominantly contralaterally, and in others, axons were similar in numbers on both sides. Similar results were seen in analyses of cases from previous studies using shRNA-mediated PTEN knock-down. These results indicate that CST axons that extend past a lesion due to PTEN deletion or knock-down do not maintain the contralateral rule of the non-injured CST, highlighting one aspect for how resultant circuitry from regenerating axons may differ from that of the uninjured CST. PMID:26878190
Impairments in prehension produced by early postnatal sensory motor cortex activity blockade.
Martin, J H; Donarummo, L; Hacking, A
2000-02-01
This study examined the effects of blocking neural activity in sensory motor cortex during early postnatal development on prehension. We infused muscimol, either unilaterally or bilaterally, into the sensory motor cortex of cats to block activity continuously between postnatal weeks 3-7. After stopping infusion, we trained animals to reach and grasp a cube of meat and tested behavior thereafter. Animals that had not received muscimol infusion (unilateral saline infusion; age-matched) reached for the meat accurately with small end-point errors. They grasped the meat using coordinated digit flexion followed by forearm supination on 82.7% of trials. Performance using either limb did not differ significantly. In animals receiving unilateral muscimol infusion, reaching and grasping using the limb ipsilateral to the infusion were similar to controls. The limb contralateral to infusion showed significant increases in systematic and variable reaching end-point errors, often requiring subsequent corrective movements to contact the meat. Grasping occurred on only 14.8% of trials, replaced on most trials by raking without distal movements. Compensatory adjustments in reach length and angle, to maintain end-point accuracy as movements were started from a more lateral position, were less effective using the contralateral limb than ipsilateral limb. With bilateral inactivations, the form of reaching and grasping impairments was identical to that produced by unilateral inactivation, but the magnitude of the reaching impairments was less. We discuss these results in terms of the differential effects of unilateral and bilateral inactivation on corticospinal tract development. We also investigated the degree to which these prehension impairments after unilateral blockade reflect control by each hemisphere. In animals that had received unilateral blockade between postnatal weeks (PWs) 3 and 7, we silenced on-going activity (after PW 11) during task performance using continuous muscimol infusion. We inactivated the right (previously active) and then the left (previously silenced) sensory motor cortex. Inactivation of the ipsilateral (right) sensory motor cortex produced a further increase in systematic error and less frequent normal grasping. Reinactivation of the contralateral (left) cortex produced larger increases in reaching and grasping impairments than those produced by ipsilateral inactivation. This suggests that the impaired limb receives bilateral sensory motor cortex control but that control by the contralateral (initially silenced) cortex predominates. Our data are consistent with the hypothesis that the normal development of skilled motor behavior requires activity in sensory motor cortex during early postnatal life.
Hanna, R M; Kamgar, M; Hasnain, H; Khorsan, R; Nsair, A; Kaldas, F; Baas, A; Bunnapradist, S; Wilson, J M
2018-04-01
We report a case of successful combined heart liver transplant in a patient with a congenital solitary kidney. The patient had normal renal function before combined heart-liver transplantation and developed acute kidney injury requiring slow continuous dialysis and subsequent intermittent dialysis for almost 8 weeks post transplantation. Her renal function recovered and she remains off dialysis now 7 months post transplantation. She only currently has mild chronic renal insufficiency. We believe this is the first reported case of successful heart liver transplant in a patient with a congenital solitary kidney. Published by Elsevier Inc.
Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans
2014-12-01
airway epithelium [1, 6, 7], and 2) these changes can be detected and serve as biomarker for early detection of lung cancer [8, 9], in the current...biospecimens from seven locations: nasal epithelium , proximal and distal bronchial airway epithelium obtained at bronchoscopy (ipsilateral and...contralateral to the tumor) as well as the tumor/benign lesion, adjacent normal parenchyma, and sub- segmental bronchial epithelium at time of lobectomy
Northoff, G; Braus, D F; Sartorius, A; Khoram-Sefat, D; Russ, M; Eckert, J; Herrig, M; Leschinger, A; Bogerts, B; Henn, F A
1999-07-01
Catatonia, a symptom complex with motor, affective and cognitive symptoms seen in a variety of psychotic conditions and with organic disease, was examined using a motor task using functional magnetic resonance imaging (fMRI). Two acute catatonic patients and two age- and sex-matched healthy controls performed sequential finger opposition (SFO) after being medicated with 2 mg of lorazepam (i.v.). Functional magnetic resonance images were collected using a gradient echo pulse sequence (EPI). Patients with catatonia showed reduced motor activation of the contralateral motor cortex during SFO of the right hand, ipsilateral activation was similar for patients and controls. There were no differences in the activation of the SMA. During left hand activation the right-handed catatonic patients showed more activation in the ipsilateral cortex, a reversal from the normal pattern of activation in which the contralateral side shows four to five times more activation than the ipsilateral side. In catatonic patients there is a decreased activation in motor cortex during a motor task compared to matched medicated healthy controls. In addition activation of the non-dominant side, left-handed activity in right-handed patients, results in a total reversal of the normal pattern of lateral activation suggesting a disturbance in hemispheric localization of activity during a catatonic state.
Reconstruction of the first web space in symbrachydactyly using the reverse radial forearm flap.
Gülgönen, Ayan; Güdemez, Eftal
2007-02-01
To present a new approach for the reconstruction of severe first web contractures using a distally based reverse radial forearm flap in symbrachydactyly patients. This study included 6 hands in 5 patients. Subjective evaluation included appearance, parent satisfaction (and patient satisfaction when appropriate), and ability to perform daily activities such as thumb-index grasp and pinch at follow-up evaluations. We measured the angle between the first and second rays using a goniometer at maximum radial abduction, and pinch and grasp strengths were evaluated as an objective assessment. The average follow-up period was 2 years. All parents and patients were happy with the aesthetic appearance. They were completely satisfied in their daily living activities. The average first web angle measurement was 56 degrees . An average of 39 degrees of improvement of web measurement was achieved. For the unilateral 4 patients, the average pinch strength measurement was 80% of the normal contralateral hand and the grip strength was 75% of the normal contralateral hand. The reverse radial forearm flap was found to be a safe and simple method in the reconstruction of severe first web contractures in symbrachydactyly patients. This method provided good coverage of appropriate thickness and skin quality, and supple soft tissue that filled the first web space. Therapeutic IV.
Autofluorescence dynamics during reperfusion following long-term renal ischemia in a rat model
DOE Office of Scientific and Technical Information (OSTI.GOV)
Raman, R N; Pivetti, C D; Matthews, D L
2008-02-08
Optical properties of near-surface kidney tissue were monitored in order to assess response during reperfusion to long (20 minutes) versus prolonged (150 minutes) ischemia in an in vivo rat model. Specifically, autofluorescence images of the exposed surfaces of both the normal and the ischemic kidneys were acquired during both injury and reperfusion alternately under 355 nm and 266 nm excitations. The temporal profile of the emission of the injured kidney during the reperfusion phase under 355 nm excitation was normalized to that under 266 nm as a means to account for changes in tissue optical properties independent of ischemia asmore » well as changes in the illumination/collection geometrical parameters in future clinical implementation of this technique using a hand-held probe. The scattered excitation light signal was also evaluated as a reference signal and found to be inadequate. Characteristic time constants were extracted using fit to a relaxation model and found to have larger mean values following 150 minutes of injury. The mean values were then compared with the outcome of a chronic survival study where the control kidney had been removed. Rat kidneys exhibiting longer time constants were much more likely to fail. This may lead to a method to assess kidney viability and predict its ability to recover in the initial period following transplantation or resuscitation.« less
Swallow, E A; Aref, M W; Chen, N; Byiringiro, I; Hammond, M A; McCarthy, B P; Territo, P R; Kamocka, M M; Winfree, S; Dunn, K W; Moe, S M; Allen, M R
2018-06-11
This work examines the skeletal accumulation of fluorescently tagged zoledronate in an animal model of chronic kidney disease. The results show higher accumulation in 24-h post-dose animals with lower kidney function due to greater amounts of binding at individual surfaces. Chronic kidney disease (CKD) patients suffer from increased rates of skeletal-related mortality from changes driven by biochemical abnormalities. Bisphosphonates are commonly used in reducing fracture risk in a variety of diseases, yet their use is not recommended in advanced stages of CKD. This study aimed to characterize the accumulation of a single dose of fluorescently tagged zoledronate (FAM-ZOL) in the setting of reduced kidney function. At 25 weeks of age, FAM-ZOL was administered to normal and CKD rats. Twenty-four hours later, multiple bones were collected and assessed using bulk fluorescence imaging, two-photon imaging, and dynamic histomorphometry. CKD animals had significantly higher levels of FAM-ZOL accumulation in the proximal tibia, radius, and ulna, but not in lumbar vertebral body or mandible, based on multiple measurement modalities. Although a majority of trabecular bone surfaces were covered with FAM-ZOL in both normal and CKD animals, the latter had significantly higher levels of fluorescence per unit bone surface in the proximal tibia. These results provide new data regarding how reduced kidney function affects drug accumulation in rat bone.
Galarreta, Carolina I.; Grantham, Jared J.; Forbes, Michael S.; Maser, Robin L.; Wallace, Darren P.; Chevalier, Robert L.
2015-01-01
In polycystic kidney disease (PKD), renal parenchyma is destroyed by cysts, hypothesized to obstruct nephrons. A signature of unilateral ureteral obstruction, proximal tubular atrophy leads to formation of atubular glomeruli. To determine whether this process occurs in PKD, kidneys from pcy mice (moderately progressive PKD), kidneys from cpk mice (rapidly progressive PKD), and human autosomal dominant PKD were examined in early and late stages. Integrity of the glomerulotubular junction and proximal tubular mass were determined in sections stained with Lotus tetragonolobus lectin. Development of proximal tubular atrophy and atubular glomeruli was determined in serial sections of individual glomeruli. In pcy mice, most glomerulotubular junctions were normal at 20 weeks, but by 30 weeks, 56% were atrophic and 25% of glomeruli were atubular; glomerulotubular junction integrity decreased with increasing cyst area (r = 0.83, P < 0.05). In cpk mice, all glomerulotubular junctions were normal at 10 days, but by 19 days, 26% had become abnormal. In early-stage autosomal dominant PKD kidneys, 50% of glomeruli were atubular or attached to atrophic tubules; in advanced disease, 100% were abnormal. Thus, proximal tubular injury in cystic kidneys closely parallels that observed with ureteral obstruction. These findings support the hypothesis that, in renal cystic disorders, cyst-dependent obstruction of medullary and cortical tubules initiates a process culminating in widespread destruction of proximal convoluted tubules at the glomerulotubular junction. PMID:24815352
Nickolas, Thomas L; O'Rourke, Matthew J; Yang, Jun; Sise, Meghan E; Canetta, Pietro A; Barasch, Nicholas; Buchen, Charles; Khan, Faris; Mori, Kiyoshi; Giglio, James; Devarajan, Prasad; Barasch, Jonathan
2008-06-03
A single serum creatinine measurement cannot distinguish acute kidney injury from chronic kidney disease or prerenal azotemia. To test the sensitivity and specificity of a single measurement of urinary neutrophil gelatinase-associated lipocalin (NGAL) and other urinary proteins to detect acute kidney injury in a spectrum of patients. Prospective cohort study. Emergency department of Columbia University Medical Center, New York, New York. 635 patients admitted to the hospital with acute kidney injury, prerenal azotemia, chronic kidney disease, or normal kidney function. Diagnosis of acute kidney injury was based on the RIFLE (risk, injury, failure, loss, and end-stage) criteria and assigned by researchers who were blinded to experimental measurements. Urinary NGAL was measured by immunoblot, N-acetyl-beta-d-glucosaminidase (NAG) by enzyme measurement, alpha1-microglobulin and alpha(1)-acid glycoprotein by immunonephelometry, and serum creatinine by Jaffe kinetic reaction. Experimental measurements were not available to treating physicians. Patients with acute kidney injury had a significantly elevated mean urinary NGAL level compared with the other kidney function groups (416 microg/g creatinine [SD, 387]; P = 0.001). At a cutoff value of 130 microg/g creatinine, sensitivity and specificity of NGAL for detecting acute injury were 0.900 (95% CI, 0.73 to 0.98) and 0.995 (CI, 0.990 to 1.00), respectively, and positive and negative likelihood ratios were 181.5 (CI, 58.33 to 564.71) and 0.10 (CI, 0.03 to 0.29); these values were superior to those for NAG, alpha1-microglobulin, alpha1-acid glycoprotein, fractional excretion of sodium, and serum creatinine. In multiple logistic regression, urinary NGAL level was highly predictive of clinical outcomes, including nephrology consultation, dialysis, and admission to the intensive care unit (odds ratio, 24.71 [CI, 7.69 to 79.42]). All patients came from a single center. Few kidney biopsies were performed. A single measurement of urinary NGAL helps to distinguish acute injury from normal function, prerenal azotemia, and chronic kidney disease and predicts poor inpatient outcomes.
Nickolas, Thomas L.; O’Rourke, Matthew J.; Yang, Jun; Sise, Meghan E.; Canetta, Pietro A.; Barasch, Nicholas; Buchen, Charles; Khan, Faris; Mori, Kiyoshi; Giglio, James; Devarajan, Prasad; Barasch, Jonathan
2010-01-01
Background A single serum creatinine measurement cannot distinguish acute kidney injury from chronic kidney disease or prerenal azotemia. Objective To test the sensitivity and specificity of a single measurement of urinary neutrophil gelatinase–associated lipocalin (NGAL) and other urinary proteins to detect acute kidney injury in a spectrum of patients. Design Prospective cohort study. Setting Emergency department of Columbia University Medical Center, New York, New York. Participants 635 patients admitted to the hospital with acute kidney injury, prerenal azotemia, chronic kidney disease, or normal kidney function. Measurements Diagnosis of acute kidney injury was based on the RIFLE (risk, injury, failure, loss, and end-stage) criteria and assigned by researchers who were blinded to experimental measurements. Urinary NGAL was measured by immunoblot, N-acetyl-β-D-glucosaminidase (NAG) by enzyme measurement, α1-microglobulin and α1-acid glycoprotein by immunonephelometry, and serum creatinine by Jaffe kinetic reaction. Experimental measurements were not available to treating physicians. Results Patients with acute kidney injury had a significantly elevated mean urinary NGAL level compared with the other kidney function groups (416 μg/g creatinine [SD, 387]; P = 0.001). At a cutoff value of 130 μg/g creatinine, sensitivity and specificity of NGAL for detecting acute injury were 0.900 (95% CI, 0.73 to 0.98) and 0.995 (CI, 0.990 to 1.00), respectively, and positive and negative likelihood ratios were 181.5 (CI, 58.33 to 564.71) and 0.10 (CI, 0.03 to 0.29); these values were superior to those for NAG, α1-microglobulin, α1-acid glycoprotein, fractional excretion of sodium, and serum creatinine. In multiple logistic regression, urinary NGAL level was highly predictive of clinical outcomes, including nephrology consultation, dialysis, and admission to the intensive care unit (odds ratio, 24.71 [CI, 7.69 to 79.42]). Limitations All patients came from a single center. Few kidney biopsies were performed. Conclusion A single measurement of urinary NGAL helps to distinguish acute injury from normal function, prerenal azotemia, and chronic kidney disease and predicts poor inpatient outcomes. PMID:18519927
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, H.B.; Blaufox, M.D.
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 pmore » 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.« less
Darwish, Mostafa A; Abo-Youssef, Amira M; Khalaf, Marwa M; Abo-Saif, Ali A; Saleh, Ibrahim G; Abdelghany, Tamer M
2017-01-01
Cisplatin (CP) is one of the most effective chemotherapeutic agents. Unfortunately, CP-induced nephrotoxicity hampered its use. This study aims to investigate the effect of vitamin E (Vit E) on CP-induced nephrotoxicity. Male white albino rats were divided to four group's six rats each and received either, 1% tween 80 in normal saline or Vit E (75 mg/kg) per day for 14 consecutive days or a single injection of CP (6 mg/kg) alone or CP (6 mg/kg) together with Vit E (75 mg/kg per day for 14 consecutive days). Five days after the CP injection, rats were euthanized; blood samples were collected; kidneys were dissected; and biochemical, immunohistochemical, and histological examinations were performed. Our results revealed that CP treatment significantly increased serum levels of creatinine and urea. Moreover, reduced glutathione (GSH) content as well as superoxide dismutase (SOD) and catalase (CAT) activities were significantly reduced with concurrent increase in kidney malondialdehyde (MDA) content following CP treatment. Vit E successfully lowered serum levels of urea and creatinine, enhanced creatinine clearance and diuresis, and normalized relative kidney/body weight. Furthermore, Vit E successfully normalized renal MDA and nitrite concentrations, elevated GSH level, and restored CAT and SOD activities in renal tissues. Histopathological examination of rat kidney revealed that Vit E significantly mitigated CP-induced renal damage. Importantly, administration of Vit E reduced kidney total platinum concentration indicating a role of platinum renal accumulation on the ability of Vit E to protect against CP nephrotoxicity. © 2016 Wiley Periodicals, Inc.
Vlassara, Helen; Torreggiani, Massimo; Post, James B; Zheng, Feng; Uribarri, Jaime; Striker, Gary E
2009-12-01
Oxidant stress (OS) and inflammation increase in normal aging and in chronic kidney disease (CKD), as observed in human and animal studies. In cross-sectional studies of the US population, these changes are associated with a decrease in renal function, which is exhibited by a significant proportion of the population. However, since many normal adults have intact renal function, and longitudinal studies show that some persons maintain normal renal function with age, the link between OS, inflammation, and renal decline is not clear. In aging mice, greater oxidant intake is associated with increased age-related CKD and mortality, which suggests that interventions that reduce OS and inflammation may be beneficial for older individuals. Both OS and inflammation can be readily lowered in normal subjects and patients with CKD stage 3-4 by a simple dietary modification that lowers intake and results in reduced serum and tissue levels of advanced glycation end products. Diabetic patients, including those with microalbuminuria, have a decreased ability to metabolize and excrete oxidants prior to observable changes in serum creatinine. Thus, OS and inflammation may occur in the diabetic kidney at an early time. We review the evidence that oxidants in the diet directly lead to increased serum levels of OS and inflammatory mediators in normal aging and in CKD. We also discuss a simple dietary intervention that helps reduce OS and inflammation, an important and achievable therapeutic goal for patients with CKD and aging individuals with reduced renal function.
DiBona, G F; Sawin, L L
2001-08-01
Sympathetic nerve activity, including that in the kidney, is increased in heart failure with increased plasma concentrations of norepinephrine and the vasoconstrictor cotransmitter neuropeptide Y (NPY). We examined the contribution of NPY to sympathetically mediated alterations in kidney function in normal and heart failure rats. Heart failure rats were created by left coronary ligation and myocardial infarction. In anesthetized normal rats, the NPY Y(1) receptor antagonist, H 409/22, at two doses, had no effect on heart rate, arterial pressure, or renal hemodynamic and excretory function. In conscious severe heart failure rats, high-dose H 409/22 decreased mean arterial pressure by 8 +/- 2 mm Hg but had no effect in normal and mild heart failure rats. During graded frequency renal sympathetic nerve stimulation (0 to 10 Hz), high-dose H 409/22 attenuated the decreases in renal blood flow only at 10 Hz (-36% +/- 5%, P <.05) in normal rats but did so at both 4 (-29% +/- 4%, P <.05) and 10 Hz (-33% +/- 5%, P <.05) in heart failure rats. The glomerular filtration rate, urinary flow rate, and sodium excretion responses to renal sympathetic nerve stimulation were not affected by high-dose H 409/22 in either normal or heart failure rats. NPY does not participate in the regulation of kidney function and arterial pressure in normal conscious or anesthetized rats. When sympathetic nervous system activity is increased, as in heart failure and intense renal sympathetic nerve stimulation, respectively, a small contribution of NPY to maintenance of arterial pressure and to sympathetic renal vasoconstrictor responses may be identified.
2014-01-01
Background Ultrasonography is an important diagnostic tool in the investigation of abdominal disease in the horse. Several factors may affect the ability to image different structures within the abdomen. The aim of the study was to describe the repeatability of identification of abdominal structures in normal horses using a detailed ultrasonographic examination technique and using a focused, limited preparation technique. Methods A detailed abdominal ultrasound examination was performed in five normal horses, repeated on five occasions (total of 25 examinations). The abdomen was divided into ten different imaging sites, and structures identified in each site were recorded. Five imaging sites were then selected for a single focused ultrasound examination in 20 normal horses. Limited patient preparation was performed. Structures were recorded as ‘identified’ if ultrasonographic features could be distinguished. The location of organs and their frequency of identification were recorded. Data from both phases were analysed to determine repeatability of identification of structures in each examination (irrespective of imaging site), and for each imaging site. Results Caecum, colon, spleen, liver and right kidney were repeatably identified using the detailed technique, and had defined locations. Large colon and right kidney were identified in 100% of examinations with both techniques. Liver, spleen, caecum, duodenum and other small intestine were identified more frequently with the detailed examination. Small intestine was most frequently identified in the ventral abdomen, its identification varied markedly within and between horses, and required repeated examinations in some horses. Left kidney could not be identified in every horse using either technique. Sacculated colon was identified in all ventral sites, and was infrequently identified in dorsal sites. Conclusions Caecum, sacculated large intestine, spleen, liver and right kidney were consistently identified with both techniques. There were some normal variations which should be considered when interpreting ultrasonographic findings in clinical cases: left kidney was not always identified, sacculated colon was occasionally identified in dorsal flank sites. Multiple imaging sites and repeated examinations may be required to identify small intestine. A focused examination identified most key structures, but has some limitations compared to a detailed examination. PMID:25238559
Lv, Yudan; Ma, Dihui; Meng, Hongmei; Zan, Wang; Li, Cui
2013-10-01
Schizencephaly is a congenital malformation of the cerebral hemispheres, with communication between the lateral ventricle and the subarachnoid space. Marinelli reported that schizencephaly may be associated with continuous involuntary hand movements, such as dystonia or epilepsia partialis continua (EPC). We describe a young Chinese patient with continuous involuntary movements of the contralateral hand affected by schizencephaly. He has a normal scalp electroencephalogram (EEG) but abnormal intracranial EEG, with synchronized periodic lateralized epileptiform discharges. The results obtained from these EEG investigations and the clinical features of the involuntary movements are in favor of a diagnosis of secondary EPC.
Johnson, Florence L; Patel, Nimesh S A; Purvis, Gareth S D; Chiazza, Fausto; Chen, Jianmin; Sordi, Regina; Hache, Guillaume; Merezhko, Viktoria V; Collino, Massimo; Yaqoob, Muhammed M; Thiemermann, Christoph
2017-07-03
Acute kidney injury (AKI) is a major risk factor for the development of chronic kidney disease. Nuclear factor-κB is a nuclear transcription factor activated post-ischemia, responsible for the transcription of proinflammatory proteins. The role of nuclear factor-κB in the renal fibrosis post-AKI is unknown. We used a rat model of AKI caused by unilateral nephrectomy plus contralateral ischemia (30 minutes) and reperfusion injury (up to 28 days) to show impairment of renal function (peak: 24 hours), activation of nuclear factor-κB (peak: 48 hours), and fibrosis (28 days). In humans, AKI is diagnosed by a rise in serum creatinine. We have discovered that the IκB kinase inhibitor IKK16 (even when given at peak serum creatinine) still improved functional and structural recovery and reduced myofibroblast formation, macrophage infiltration, transforming growth factor-β expression, and Smad2/3 phosphorylation. AKI resulted in fibrosis within 28 days (Sirius red staining, expression of fibronectin), which was abolished by IKK16. To confirm the efficacy of IKK16 in a more severe model of fibrosis, animals were subject to 14 days of unilateral ureteral obstruction, resulting in tubulointerstitial fibrosis, myofibroblast formation, and macrophage infiltration, all of which were attenuated by IKK16. Inhibition of IκB kinase at peak creatinine improves functional recovery, reduces further injury, and prevents fibrosis. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
Masking overshoot: Effects of ipsilateral, bilateral and contralateral priming
NASA Astrophysics Data System (ADS)
Connington, Maureen Catherine
This study was concerned with masking overshoot, the elevation of the threshold of a brief signal when it is presented at the onset of a masking noise rather than at its temporal center. More specifically, it was concerned with the release from overshoot (i.e., threshold improvement) produced by priming stimuli, presented ipsilaterally, bilaterally and contralaterally at primer- masker gaps of 20, 40 and 80 msec. The more general purpose of the study was to assess the contributions of peripheral and central factors to the overshoot and overshoot-release phenomena. The primers and masking stimuli consisted of white noise bursts of 200 and 400 msec duration, respectively. The probe signal was a 20 msec 4kHz tone. The tone and masker were always presented in one ear. There were, however, 3 modes of primer presentation: ipsilateral, bilateral (identical waveforms to both ears) and contralateral. Three primer-masker gaps of 20, 40 and 80 msec were used. Five normally hearing adults were tested at primer and masker levels of 80 dB HL. Four of the five subjects exhibited significant masking overshoot, when tested without priming. Ipsilateral priming with 20 and 40 msec gaps produced significant masking release from overshoot. Threshold became poorer, however with increasing gap duration and with increasing distance of the perceived primer from the test ear (i.e. ipsilateral priming produced better thresholds than did bilateral priming and bilateral priming produced better thresholds than contralateral priming). There was significant masking enhancement (i.e. threshold was significantly poorer than in the unprimed probe at onset condition) with the contralateral 80 msec primer. The fact that ipsilateral and bilateral primers performed differently does not support the theory that masking overshoot and its release are solely the results of peripheral adaptation. In fact, the group results support the conclusion that masking overshoot is influenced by central factors. However, there were marked inter-subject differences. It seems possible that masking overshoot and its release are influenced by both peripheral adaptation effects and central processes and that the balance between the two is subject-dependent.
Kanasaki, Keizo; Kanda, Yoshiko; Palmsten, Kristin; Tanjore, Harikrishna; Lee, Soo Bong; Lebleu, Valerie S; Gattone, Vincent H; Kalluri, Raghu
2008-01-15
The human kidneys filter 180 l of blood every day via about 2.5 million glomeruli. The three layers of the glomerular filtration apparatus consist of fenestrated endothelium, specialized extracellular matrix known as the glomerular basement membrane (GBM) and the podocyte foot processes with their modified adherens junctions known as the slit diaphragm (SD). In this study we explored the contribution of podocyte beta1 integrin signaling for normal glomerular function. Mice with podocyte specific deletion of integrin beta1 (podocin-Cre beta1-fl/fl mice) are born normal but cannot complete postnatal renal development. They exhibit detectable proteinuria on day 1 and die within a week. The kidneys of podocin-Cre beta1-fl/fl mice exhibit normal glomerular endothelium but show severe GBM defects with multilaminations and splitting including podocyte foot process effacement. The integrin linked kinase (ILK) is a downstream mediator of integrin beta1 activity in epithelial cells. To further explore whether integrin beta1-mediated signaling facilitates proper glomerular filtration, we generated mice deficient of ILK in the podocytes (podocin-Cre ILK-fl/fl mice). These mice develop normally but exhibit postnatal proteinuria at birth and die within 15 weeks of age due to renal failure. Collectively, our studies demonstrate that podocyte beta1 integrin and ILK signaling is critical for postnatal development and function of the glomerular filtration apparatus.
Separation of lymphocytes by electrophoresis under terrestrial conditions and at zero gravity
NASA Technical Reports Server (NTRS)
Rubin, A. L.
1977-01-01
Electrophoretic mobility (EPM) of human peripheral lymphocytes were examined with the following objectives: To determine differences in EPM of lymphocytes under immuno-stimulated and immuno-suppressed states. To define the conditions necessary for the separation of lymphocyte sub-populations in normal and pathological conditions; To investigate immunological active, charged chemical groups on lymphocyte surfaces; and to investigate pathophysiological mechanisms of immune responsiveness, as reflected by alterations in EPM. To evaluate the potential of lymphocyte electrophoresis as: (1) a means of monitoring the immune status of kidney transplant recipients, (2) in predicting the outcome of kidney transplants, and (3) as a method for separation of lymphocyte sub-populations, the EPM was studied for unfractionated human peripheral lymphocytes and of populations enriched with T and "B" cells from normal adults, hemodialysis patients and kidney transplant recipients.
Overexpression of esterase D in kidney from trisomy 13 fetuses.
Loughna, S; Bennett, P; Gau, G; Nicolaides, K; Blunt, S; Moore, G
1993-01-01
Human trisomy 13 (Patau syndrome) occurs in approximately 1 in 5,000 live births. It is compatible with life, but prolonged survival is rare. Anomalies often involve the urogenital, cardiac, craniofacial, and central nervous systems. It is possible that these abnormalities may be due to the overexpression of developmentally important genes on chromosome 13. The expression of esterase D (localized to chromosome 13q14.11) has been investigated in both muscle and kidney from trisomy 13 fetuses and has been compared with normal age- and sex-matched fetal tissues, by using northern analysis. More than a twofold increase in expression of esterase D was found in the kidney of two trisomy 13 fetuses, with normal levels in a third. Overexpression was not seen in the muscle tissues from these fetuses. Images Figure 1 Figure 2 Figure 3 PMID:8213811
Kaneda, H; Furuya, T; Sugito, K; Goto, S; Kawashima, H; Inoue, M; Hosoda, T; Masuko, T; Ohashi, K; Ikeda, T; Koshinaga, T; Hoshino, M; Goto, H
2015-08-01
The current study aimed to verify the usefulness of preoperative ultrasonographic evaluation of contralateral patent processus vaginalis (PPV) at the level of the internal inguinal ring. This was a prospective study of patients undergoing unilateral inguinal hernia repair at two institutions during 2010-2011. The sex, age at initial operation, birth weight, initial operation side, and the preoperative diameter of the contralateral PPV as determined using ultrasonography (US) were recorded. We analyzed the incidence of contralateral inguinal hernia, risk factors, and the usefulness of the preoperative major diameter of the contralateral PPV. The follow-up period was 36 months. All 105 patients who underwent unilateral hernia repair completed 36 months of follow-up, during which 11 patients (10.5 %) developed a contralateral hernia. The following covariates were not associated with contralateral hernia development: sex (p = 0.350), age (p = 0.185), birth weight (p = 0.939), and initial operation side (p = 0.350). The preoperative major diameter of the contralateral PPV determined using US was significantly wider among patients with a contralateral hernia than those without a contralateral hernia (p = 0.001). When the 105 patients were divided into two groups according to cut-off values of the preoperative major diameter of the contralateral PPV (wide group, >2.0 mm; narrow group, ≤2.0 mm), a significant association was observed between the preoperative major diameter of the contralateral PPV and patient outcomes (p = 0.001). We used US and confirmed the usefulness of a preoperative evaluation of the major diameter of the contralateral PPV at the level of the internal inguinal ring in pediatric patients with unilateral inguinal hernias.
En bloc transplantation of horseshoe kidney in Korea
Bang, Jun Bae; Lee, Jae Myeong; Oh, Chang-Kwon; Lee, Kyo Won; Park, Jae Berm; Kim, Sung Joo
2017-01-01
Transplantation of the horseshoe kidney can be performed en bloc or split into 2 grafts according to the vascular anomaly and the existence of the urinary collecting system in isthmus. From 2011 to 2014, there were 3 horseshoe kidney transplantations in Korea and transplantations were performed at 2 different centers. The transplantations were carried out successfully for all recipients without complications. All recipients have shown good graft kidney function after transplantation. No severe complication was revealed during follow-up period. We described the surgical technique used in the en bloc method to overcome various vascular anomalies and difficulties in choosing cannulation site and postoperative complications. En bloc transplantation of a horseshoe kidney is a useful strategy for patients with end-stage renal disease, and can provide favorable outcomes compared to the transplantation of a normal kidney. PMID:28289672
Ovbiagele, Bruce; Schwamm, Lee H; Smith, Eric E; Grau-Sepulveda, Maria V; Saver, Jeffrey L; Bhatt, Deepak L; Hernandez, Adrian F; Peterson, Eric D; Fonarow, Gregg C
2014-10-01
There is a paucity of information on clinical characteristics, care patterns, and clinical outcomes for hospitalized intracerebral hemorrhage (ICH) patients with chronic kidney disease (CKD). We assessed characteristics, care processes, and in-hospital outcome among ICH patients with CKD in the Get With the Guidelines-Stroke (GWTG-Stroke) program. We analyzed 113,059 ICH patients hospitalized at 1472 US centers participating in the GWTG-Stroke program between January 2009 and December 2012. In-hospital mortality and use of 2 predefined ICH performance measures were examined based on glomerular filtration rate. Renal dysfunction was categorized as a dichotomous (+CKD = estimated glomerular filtration rate <60) or rank ordered variable as CKD (<60), and by clinical stage: (normal [≥90], mild [≥60-<90], moderate [≥30-<60], severe [≥15-<30], and/or kidney failure [<15 or dialysis]). There were 33,219 (29%) ICH patients with CKD. Patients with CKD were more likely to be older, female, and with comorbid conditions such as diabetes. Compared with patients with normal kidney function, those with CKD were slightly less likely to receive deep venous thrombosis (DVT) prophylaxis but similarly received discharge smoking cessation intervention. Inpatient mortality was also higher for those with CKD (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.42-1.52), mild dysfunction (adjusted OR, 1.12; 95% CI, 1.08-1.16), moderate dysfunction (adjusted OR, 1.46; 95% CI, 1.39-1.53), severe dysfunction (adjusted OR, 1.96; 95% CI, 1.81-2.12), and kidney failure (adjusted OR, 2.22; 95% CI, 2.04-2.43) relative to those with normal renal function. Chronic kidney disease is present in nearly a third of patients hospitalized with ICH and is associated with slightly worse care and substantially higher mortality than those with normal renal function. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Spasojević-Dimitrijeva, Brankica; Kotur-Stevuljević, Jelena; Đukić, Milan; Paripović, Dušan; Miloševski-Lomić, Gordana; Spasojević-Kalimanovska, Vesna; Pavićević, Polina; Mitrović, Jadranka; Kostić, Mirjana
2017-01-01
Background New renal biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) show promise in early diagnosis of contrast media induced acute kidney injury (CI-AKI). The purpose of our study was to compare the subclinical nephrotoxicity (a condition without changes in standard renal biomarkers) of gadolinium-based contrast media (Gd-DTPA, gadopentetate dimeglumine) and iodinated-based contrast media (iopromide) in pediatric patients with normal kidney function. Material/Methods The first group (n=58) of patients included in the study were undergoing angiography with iopromide, and the second group (n=65) were undergoing magnetic resonance (MR) angiography/urography with Gd-DTPA administration. The concentrations of NGAL and KIM-1 were measured four times in the urine (pre-contrast, then at four hours, 24 hours, and 48 hours after contrast administration), and serum NGAL was measured at 0 (baseline), 24 hours, and 48 hours after contrast exposure. Results After 24 hours, serum NGAL increase of ≥25% was noticed in 32.6% of the patients in the iopromide group and in 25.45% of the patients in the gadolinium group, with significantly higher average percent of this increase in first group (62.23% vs. 36.44%, p=0.002). In the Gd-DTPA group, we observed a statistically significant increase in urinary KIM-1 24 hours after the procedure. Normalized urinary KIM-1, 24 hours after contrast exposure, was a better predictive factor for CI-AKI than other biomarkers (AUC 0.757, cut off 214 pg/mg, sensitivity 83.3%, specificity 54.2%, p=0.035). Conclusions In children with normal renal function, exposure to iodinated-based and gadolinium-based media might lead to subclinical nephrotoxicity, which could be detected using serum NGAL and urinary KIM-1. PMID:28874655
Effects of Perfusion on Radiofrequency Ablation in Swine Kidneys1
Chang, Isaac; Mikityansky, Igor; Wray-Cahen, Diane; Pritchard, William F.; Karanian, John W.; Wood, Bradford J.
2008-01-01
PURPOSE: To evaluate the effect of vascular occlusion on the size of radiofrequency (RF) ablation lesions and to evaluate embolization as an occlusion method. MATERIALS AND METHODS: The kidneys of six swine were surgically exposed. Fifteen RF ablation lesions were created in nine kidneys by using a 2-cm-tip single-needle ablation probe in varying conditions: Seven lesions were created with normal blood flow and eight were created with blood flow obstructed by means of vascular clamping (n = 5) or renal artery embolization (n = 3). The temperature, applied voltage, current, and impedance were recorded during RF ablation. Tissue-cooling curves acquired for 2 minutes immediately after the ablation were compared by using regression analysis. Lesions were bisected, and their maximum diameters were measured and compared by using analysis of variance. RESULTS: The mean diameter of ablation lesions created when blood flow was obstructed was 60% greater than that of lesions created when blood flow was normal (1.38 cm ± 0.05 [standard error of mean] vs 0.86 cm ± 0.07, P < .001). The two methods of flow obstruction yielded lesions of similar mean sizes: 1.40 cm ± 0.06 with vascular clamping and 1.33 cm ± 0.07 with embolization. The temperature at the probe tip when lesions were ablated with normal blood flow decreased more rapidly than did the temperature when lesions were ablated after flow obstruction (P < .001), but no significant differences in tissue-cooling curves between the two flow obstruction methods were observed. CONCLUSION: Obstruction of renal blood flow before and during RF ablation resulted in larger thermal lesions with potentially less variation in size compared with the lesions created with normal nonobstructed blood flow. Selective arterial embolization of the kidney vessels may be a useful adjunct to RF ablation of kidney tumors. PMID:15128994
Technetium-99m mercaptoacetyltriglycine clearance: reference values for infants and children.
Schofer, O; König, G; Bartels, U; Bockisch, A; Piepenburg, R; Beetz, R; Meyer, G; Hahn, K
1995-11-01
Six hundred and thirty-nine clearance studies performed in children aged 7 days to 19 years utilizing technetium-99m mercaptoacetyltriglycine (MAG 3) were retrospectively analysed. Standardized conditions for the investigation included: parenteral hydration (60 ml/hxm2 body surface) in addition to normal oral fluid intake, weight-related dose of 99mTc-MAG 3 (1 MBq/kg body weight, minimum 15 MBq) and calculation of clearance according to Bubeck et al. Of the 513 children, 169 included in this analysis could be classified as "normal" with regard to their renal function. Normal kidney function was judged by the following criteria: normal GFR for age, normal tubular function (absence of proteinuria and glucosuria), normal renal parenchyma (on ultrasonography, MAG 3 scan and intravenous pyelography), absence of significant obstruction and gross reflux (>grade I), no single kidney and no difference in split renal function >20%. Results showed increasing MAG 3 clearance values for infants during the first months of life, reaching the normal range for older children and adults between 7 and 12 months.
The cell biology of polycystic kidney disease
Chapin, Hannah C.
2010-01-01
Polycystic kidney disease is a common genetic disorder in which fluid-filled cysts displace normal renal tubules. Here we focus on autosomal dominant polycystic kidney disease, which is attributable to mutations in the PKD1 and PKD2 genes and which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis. The mechanisms that connect the underlying genetic defects to disease pathogenesis are poorly understood, but their exploration is shedding new light on interesting cell biological processes and suggesting novel therapeutic targets. PMID:21079243
Amer, Hatem; Griffin, Matthew D
2014-02-01
In follow-up to a recently published randomized controlled clinical trial, Issa et al. provide evidence that systemic activity and physiological responsiveness of the renin aldosterone angiotensin system (RAAS) are well within normal limits in most kidney recipients during the first 5 years post-transplant. Implications of the results include the need to better understand intra-renal RAAS activity in transplanted kidneys and to identify patients in which the graft-protective effects of RAAS blockade are most relevant.
Effects of monocular viewing and eye dominance on spatial attention.
Roth, Heidi L; Lora, Andrea N; Heilman, Kenneth M
2002-09-01
Observations in primates and patients with unilateral spatial neglect have suggested that patching of the eye ipsilateral to the injury and contralateral to the neglected space can sometimes improve attention to the neglected space. Investigators have generally attributed the effects of monocular eye patching to activation of subcortical centers that interact with cortical attentional systems. Eye patching is thought to produce preferential activation of attentional systems contralateral to the viewing eye. In this study we examined the effect of monocular eye patching on attentional biases in normal subjects. When normal subjects bisect vertical (radial) lines using both eyes, they demonstrate a far attentional bias, misbisecting lines away from their body. In a monocular viewing experiment, we found that the majority of subjects, who were right eye dominant, had relatively nearer bisections and a diminished far bias when they used their right eye (left eye covered) compared with when they used their left eye (right eye covered). The smaller group of subjects who were left eye dominant had relatively nearer bisections and a diminished far bias when they used their left eye compared with when they used their right eye. In the hemispatial placement experiment, we directly manipulated hemispheric engagement by having subjects perform the same task in right and left hemispace. We found that right eye dominant subjects had a diminished far bias in right hemispace relative to left hemispace. Left eye dominant subjects showed the opposite pattern and had a diminished far bias in left hemispace. For both groups, spatial presentation affected performance more for the non-dominant eye. The results suggest that monocular viewing is associated with preferential activation of attentional systems in the contralateral hemisphere, and that the right hemisphere (at least in right eye dominant subjects) is biased towards far space. Finally, the results suggest that the poorly understood phenomenon of eye dominance may be related to hemispheric specialization for visual attention.
Kidney Stones as an Underrecognized Clinical Sign in Pediatric Cushing Disease.
Rahman, Sara H; Papadakis, Georgios Z; Keil, Margaret F; Faucz, Fabio R; Lodish, Maya B; Stratakis, Constantine A
2016-03-01
To investigate the prevalence of kidney stones in a population of children with Cushing disease (CD) and to compare it with the prevalence of kidney stones in healthy children. Clinical and biochemical data from 139 pediatric patients with CD (68 females, 71 males) were analyzed retrospectively. Computed tomography scans were reviewed for kidney stones. Among 139 patients, 27 with CD (19.4%) had either radiographic evidence and/or a history of kidney stones. Those with kidney stones had higher urine free cortisol (P = .008) and transsphenoidal surgery at an older age (P = .007). The average urinary calcium/creatinine ratio was elevated in patients with CD (0.22 ± 0.11). The prevalence of kidney stones was higher in children with CD than in normal children (19.42% vs 1.0%; P < .001). Our results illustrate that kidney stones are an underestimated complication of pediatric CD, especially when compared with the prevalence of nephrolithiasis in the general pediatric population. Long-term consequences for kidney function are not known and need to be studied. Published by Elsevier Inc.
Assessing visual requirements for social context-dependent activation of the songbird song system
Hara, Erina; Kubikova, Lubica; Hessler, Neal A.; Jarvis, Erich D.
2008-01-01
Social context has been shown to have a profound influence on brain activation in a wide range of vertebrate species. Best studied in songbirds, when males sing undirected song, the level of neural activity and expression of immediate early genes (IEGs) in several song nuclei is dramatically higher or lower than when they sing directed song to other birds, particularly females. This differential social context-dependent activation is independent of auditory input and is not simply dependent on the motor act of singing. These findings suggested that the critical sensory modality driving social context-dependent differences in the brain could be visual cues. Here, we tested this hypothesis by examining IEG activation in song nuclei in hemispheres to which visual input was normal or blocked. We found that covering one eye blocked visually induced IEG expression throughout both contralateral visual pathways of the brain, and reduced activation of the contralateral ventral tegmental area, a non-visual midbrain motivation-related area affected by social context. However, blocking visual input had no effect on the social context-dependent activation of the contralateral song nuclei during female-directed singing. Our findings suggest that individual sensory modalities are not direct driving forces for the social context differences in song nuclei during singing. Rather, these social context differences in brain activation appear to depend more on the general sense that another individual is present. PMID:18826930
Dettoraki, Maria; Dimitropoulou, Chrisafoula; Nomikarios, Nikolaos; Moschos, Marilita M; Brοuzas, Dimitrios
2015-07-28
Retrobulbar block is a local anesthetic technique widely used for intraocular surgery. Although retrobulbar anesthesia is considered to be relatively safe, a number of serious adverse events have been reported. To our knowledge, immediate onset of generalized seizures with contralateral hemiparesis after retrobulbar anesthesia has not been reported. A 62-year-old Caucasian healthy male with a right eye retinal detachment was admitted for pars plana vitrectomy. During retrobulbar anesthesia with ropivacaine and before needle withdrawal, the patient developed twitching of the face which rapidly progressed to generalized tonic-clonic seizures. Arterial oxygen saturation decreased to 75 %. Chin lift was performed and 100 % oxygen was administrated via face mask, which increased saturation to 99 %. Midazolam 2 mg was administrated intravenously to control seizures. After cessation of seizures, left-sided hemiparesis was evident. Brain computed tomography and electroencephalogram were normal 3 h later. The patient underwent pars plana vitrectomy under general anesthesia 4 days later. Serious complications of local anesthesia for ophthalmic surgery are uncommon. We present a case in which generalized tonic-clonic seizures developed during retrobulbar anesthesia, followed by transient contralateral hemiparesis. The early onset of seizures indicated intra-arterial injection of the anesthetic. Our case suggested the need for close monitoring during the performance of retrobulbar anesthesia and the presence of well-trained personnel for early recognition and immediate management of the complications.
Hill, D L; Phillips, L M
1994-05-01
Unilateral chorda tympani nerve sectioning was combined with institution of a sodium-restricted diet in adult rats to determine the role that environment has on the functional properties of regenerating taste receptor cells. Rats receiving chorda tympani sectioning but no dietary manipulation (cut controls) and rats receiving only the dietary manipulation (diet controls) had normal responses to a concentration series of NaCl, sodium acetate (NaAc), and NH4Cl. However, responses from the regenerated nerve in NaCl-restricted rats (40-120 d postsectioning) to NaCl and NaAc were reduced by as much as 30% compared to controls, indicating that regenerating taste receptors are influenced by environmental (dietary) factors. Responses to NH4Cl were normal; therefore, the effect appears specific to sodium salts. Surprisingly, in the same rats, NaCl responses from the contralateral, intact chorda tympani were up to 40% greater than controls. Thus, in the same rat, there was over a twofold difference in sodium responses between the right and left chorda tympani nerves. A study of the time course of the functional alterations in the intact nerve revealed that responses to NaCl were extremely low immediately following sectioning (about 20% of the normal response), and then increased monotonically during the following 50 d until relative response magnitudes became supersensitive. This function occurred even when the cut chorda tympani was prevented from reinnervating lingual epithelia, demonstrating that events related to regeneration do not play a role in the functional properties of the contralateral side of the tongue.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of short malunion of the clavicle on in vivo scapular kinematics.
Kim, DooSup; Lee, DongWoo; Jang, YoungHwan; Yeom, JunSeop; Banks, Scott A
2017-09-01
Short malunion of the clavicle after fracture can change scapular kinematics and alter clinical outcome. However, the effects of malunion on kinematics and outcomes remains poorly understood because there have been no in vivo studies measuring changes during active motion with malunion. This study aimed to measure and to compare in vivo 3-dimensional (3D) scapular kinematics between normal shoulders and shoulders with short malunion using 3D-2-dimensional model image registration techniques. Fifteen patients with clavicle fracture who had been treated conservatively were enrolled in this study. In these patients, the angle of scapular upward rotation, posterior tilting, and external rotation were compared between shoulders with short malunion and contralateral, normal shoulders. A 3D-2-dimensional model image registration technique was used to determine the 3D orientation of the scapula. Scapular upward rotation increased following increase of the arm elevation angle and also showed a significant difference by arm elevation in both groups (P = .04). Posterior tilting of the scapula gradually increased as the arm abduction angle increased, and this varied significantly between groups (P = .01). Shoulders with short malunion also showed a more internally rotated position than the contralateral, normal shoulders between 100° and the maximum abduction angle (P = .04). Our results suggest that clavicle shortening of >10% greatly affects scapular kinematics in vivo. Further studies will be needed to determine the clinical implications of short malunion of the clavicle. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Co, F H; Skinner, H B; Cannon, W D
1993-09-01
Abnormal proprioception of the knee joint has been documented after rupture of the anterior cruciate ligament (ACL) and may result in the loss of muscular reflexes. Excessive loading from the lack of muscular control may predispose the joint to osteoarthrosis. To investigate this problem, 10 patients were studied at an average of 31.6 months after ACL reconstruction. Three tests of joint proprioception and measurements of the vertical component of heel strike force during normal gait were used. A normal control group also was studied. For two of the proprioception tests (reproduction of passive motion and relative reproduction), there were no statistical differences among the uninjured (control) limbs, the normal contralateral limb of patients with a reconstructed ACL, and the extremity with a reconstructed ACL. In the third test (threshold of detection of motion), which previously has been shown to be adversely affected by ACL injury, the measurements for both extremities of patients with a reconstructed ACL were more accurate than those for the control group. The reconstructed extremity performed less accurately than the contralateral extremity (p < 0.05). The heel strike transient (vertical component of ground reaction force at heel strike) for uninjured and ACL-reconstructed limbs was not significantly different. In fact, the extremity with the reconstructed ACL had a lower transient than the uninjured extremity. Heel strike transients in patients with a reconstructed ACL were higher than those in the controls, but the differences were significant only when corrected for velocity of gait.(ABSTRACT TRUNCATED AT 250 WORDS)
Kumar, Amandeep; Sharma, Raghavendra; Garg, Ajay; Sharma, Bhawani S
2016-03-01
Thalamopeduncular gliomas arise at the junction of the thalamus and cerebral peduncle and constitute a subgroup of thalamic gliomas. These are surgically challenging lesions because of close proximity to important neural structures including corticospinal tracts (CSTs) and the thalamus. These tumors usually displace CSTs anterolaterally or extend to the lateral ventricular surface. Such tumors can be removed by either temporal or transventricular approaches. However, if CSTs cover the entire lateral surface of tumor and tumor does not extend to the ventricular surface, temporal and transventricular approaches cannot be used because the trajectories of both approaches would pass through normal eloquent structures (CSTs and thalamus), and consequently there would be a very high risk of postoperative neurologic deficits developing. A 50-year-old woman presented with contralateral hemiparesis. Radiologic evaluation revealed a right Thalamopeduncular glioma that displaced CSTs laterally and was covered by normal thalamus superiorly. Some CST fibers passed through the tumor. Because both lateral and superior surfaces were covered by eloquent structures, we used an anterior interhemispheric transparaterminal gyrus approach to access the tumor successfully and achieved subtotal excision. The patient had transient neurologic deterioration postoperatively that recovered to preoperative level within 2 weeks. The anterior interhemispheric transparaterminal gyrus approach has not been described previously for accessing brainstem lesions. This approach can be used to access tumors of the cerebral peduncle that displace CSTs laterally and are covered by normal thalamus superiorly. The anterior interhemispheric transparaterminal gyrus approach adds to the armamentarium of neurosurgeons for treatment of cerebral peduncular lesions. Copyright © 2016 Elsevier Inc. All rights reserved.
Kidney Function in Obesity-Challenges in Indexing and Estimation.
Chang, Alex R; Zafar, Waleed; Grams, Morgan E
2018-01-01
As the prevalence of obesity continues to increase worldwide, an increasing number of people are at risk for kidney disease. Thus, there is a critical need to understand how best to assess kidney function in this population, and several challenges exist. The convention of indexing glomerular filtration rate (GFR) to body surface area (BSA) attempts to normalize exposure to metabolic wastes across populations of differing body size. In obese individuals, this convention results in a significantly lower indexed GFR than unindexed GFR, which has practical implications for drug dosing. Recent data suggest that "unindexing" estimated GFR (multiplying by BSA/1.73 m 2 ) for drug dosing may be acceptable, but pharmocokinetic data to support this practice are lacking. Beyond indexing, biomarkers commonly used for estimating GFR may induce bias. Creatinine is influenced by muscle mass, whereas cystatin C correlates with fat mass, both independent of kidney function. Further research is needed to evaluate the performance of estimating equations and other filtration markers in obesity, and determine whether unindexed GFR might better predict optimal drug dosing and clinical outcomes in patients whose BSA is very different than the conventional normalized value of 1.73 m 2 . Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Zand, Ladan; Torres, Vicente E.; Larson, Timothy S.; King, Bernard F.; Sethi, Sanjeev; Bergstralh, Eric J.; Angioi, Andrea; Fervenza, Fernando C.
2016-01-01
Background 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. Methods 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. Results 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. Conclusions 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. Clinical Trial Registration Number NCT02511418. PMID:26614268
Gianfranca, Cabiddu; Donatella, Spotti; Giuseppe, Gernone; Domenico, Santoro; Gabriella, Moroni; Gina, Gregorini; Franca, Giacchino; Rossella, Attini; Monica, Limardo; Linda, Gammaro; Tullia, Todros; Piccoli, Giorgina Barbara
2018-06-14
Kidney transplantation (KT) is often considered to be the method best able to restore fertility in a woman with chronic kidney disease (CKD). However, pregnancies in KT are not devoid of risks (in particular prematurity, small for gestational age babies, and the hypertensive disorders of pregnancy). An ideal profile of the potential KT mother includes "normal" or "good" kidney function (usually defined as glomerular filtration rate, GFR ≥ 60 ml/min), scant or no proteinuria (usually defined as below 500 mg/dl), normal or well controlled blood pressure (one drug only and no sign of end-organ damage), no recent acute rejection, good compliance and low-dose immunosuppression, without the use of potentially teratogen drugs (mycophenolic acid and m-Tor inhibitors) and an interval of at least 1-2 years after transplantation. In this setting, there is little if any risk of worsening of the kidney function. Less is known about how to manage "non-ideal" situations, such as a pregnancy a short time after KT, or one in the context of hypertension or a failing kidney. The aim of this position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology is to review the literature and discuss what is known about the clinical management of CKD after KT, with particular attention to women who start a pregnancy in non-ideal conditions. While the experience in such cases is limited, the risks of worsening the renal function are probably higher in cases with markedly reduced kidney function, and in the presence of proteinuria. Well-controlled hypertension alone seems less relevant for outcomes, even if its effect is probably multiplicative if combined with low GFR and proteinuria. As in other settings of kidney disease, superimposed preeclampsia (PE) is differently defined and this impairs calculating its real incidence. No specific difference between non-teratogen immunosuppressive drugs has been shown, but calcineurin inhibitors have been associated with foetal growth restriction and low birth weight. The clinical choices in cases at high risk for malformations or kidney function impairment (pregnancies under mycophenolic acid or with severe kidney-function impairment) require merging clinical and ethical approaches in which, beside the mother and child dyad, the grafted kidney is a crucial "third element".
Automatic detection of kidney in 3D pediatric ultrasound images using deep neural networks
NASA Astrophysics Data System (ADS)
Tabrizi, Pooneh R.; Mansoor, Awais; Biggs, Elijah; Jago, James; Linguraru, Marius George
2018-02-01
Ultrasound (US) imaging is the routine and safe diagnostic modality for detecting pediatric urology problems, such as hydronephrosis in the kidney. Hydronephrosis is the swelling of one or both kidneys because of the build-up of urine. Early detection of hydronephrosis can lead to a substantial improvement in kidney health outcomes. Generally, US imaging is a challenging modality for the evaluation of pediatric kidneys with different shape, size, and texture characteristics. The aim of this study is to present an automatic detection method to help kidney analysis in pediatric 3DUS images. The method localizes the kidney based on its minimum volume oriented bounding box) using deep neural networks. Separate deep neural networks are trained to estimate the kidney position, orientation, and scale, making the method computationally efficient by avoiding full parameter training. The performance of the method was evaluated using a dataset of 45 kidneys (18 normal and 27 diseased kidneys diagnosed with hydronephrosis) through the leave-one-out cross validation method. Quantitative results show the proposed detection method could extract the kidney position, orientation, and scale ratio with root mean square values of 1.3 +/- 0.9 mm, 6.34 +/- 4.32 degrees, and 1.73 +/- 0.04, respectively. This method could be helpful in automating kidney segmentation for routine clinical evaluation.
Barbas, Andrew S; Li, Yanhong; Zair, Murtuza; Van, Julie A; Famure, Olusegun; Dib, Martin J; Laurence, Jerome M; Kim, S Joseph; Ghanekar, Anand
2016-09-01
Living kidney donor evaluation commonly includes nuclear renography to assess split kidney function and computed tomography (CT) scan to evaluate anatomy. To streamline donor workup and minimize exposure to radioisotopes, we sought to assess the feasibility of using proportional kidney volume from CT volumetry in lieu of nuclear renography. We examined the correlation between techniques and assessed their ability to predict residual postoperative kidney function following live donor nephrectomy. In a cohort of 224 live kidney donors, we compared proportional kidney volume derived by CT volumetry with split kidney function derived from nuclear renography and found only modest correlation (left kidney R(2) =26.2%, right kidney R(2) =26.7%). In a subset of 88 live kidney donors with serum creatinine measured 6 months postoperatively, we compared observed estimated glomerular filtration rate (eGFR) at 6 months with predicted eGFR from preoperative imaging. Compared to nuclear renography, CT volumetry more closely approximated actual observed postoperative eGFR for Chronic Kidney Disease Epidemiology Collaboration (J-test: P=.02, Cox-Pesaran test: P=.01) and Mayo formulas (J-test: P=.004, Cox-Pesaran test: P<.001). These observations support the use of CT volumetry for estimation of split kidney function in healthy individuals with normal kidney function and morphology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Goker, Berna; Block, Joel A
2006-01-01
The risk of developing bilateral disease progressing to total hip arthroplasty (THA) among patients who undergo unilateral THA for non-traumatic avascular necrosis (AVN) remains poorly understood. An analysis of the time-course to contralateral THA, as well as the effects of underlying AVN risk factors, is presented. Forty-seven consecutive patients who underwent THA for AVN were evaluated. Peri-operative and annual post-operative antero-posterior pelvis radiographs were examined for evidence of contralateral involvement. Patient age, weight, height, underlying AVN risk factor(s), date of onset of contralateral hip pain if occurred, and date of contralateral THA if performed, were recorded. Bone scan, computerized tomography and magnetic resonance imaging data were utilized when available. Twenty-one patients (46.6%) underwent contralateral THA for AVN within a median of 9 months after the initial THA (range 0-93, interquartile range 28.5 months). The median follow-up for patients without contralateral THA was 75 months (range 3-109, interquartile range 69 months). Thirty-four patients had radiographic findings of contralateral AVN at study entry; 25 were symptomatic bilaterally at entry and 7 developed contralateral symptoms within a mean time of 12 months (median 10 months, interquartile range 12 months). None of the 13 patients who were free of radiographic evidence of contralateral AVN at study entry developed evidence of AVN during the follow-up. AVN associated with glucocorticoid use was more likely to manifest as bilateral disease than either idiopathic AVN or ethanol-associated AVN (P=0.02 and P=0.03 respectively). Radiographically-evident AVN in the contralateral hip at THA is unlikely to remain asymptomatic for a prolonged period of time. Conversely, asymptomatic contralateral hips without radiographic evidence of AVN are unlikely to develop clinically significant AVN.
Mitchell, Jane A; Knowles, Rebecca B; Kirkby, Nicholas S; Reed, Daniel M; Edin, Matthew L; White, William E; Chan, Melissa V; Longhurst, Hilary; Yaqoob, Magdi M; Milne, Ginger L; Zeldin, Darryl C; Warner, Timothy D
2018-02-16
The balance between vascular prostacyclin, which is antithrombotic, and platelet thromboxane A 2 , which is prothrombotic, is fundamental to cardiovascular health. Prostacyclin and thromboxane A 2 are formed after the concerted actions of cPLA 2 α (cytosolic phospholipase A 2 ) and COX (cyclooxygenase). Urinary 2,3-dinor-6-keto-PGF 1α (PGI-M) and 11-dehydro-TXB 2 (TX-M) have been taken as biomarkers of prostacyclin and thromboxane A 2 formation within the circulation and used to explain COX biology and patient phenotypes, despite concerns that urinary PGI-M and TX-M originate in the kidney. We report data from a remarkable patient carrying an extremely rare genetic mutation in cPLA 2 α, causing almost complete loss of prostacyclin and thromboxane A 2 , who was transplanted with a normal kidney resulting in an experimental scenario of whole-body cPLA 2 α knockout, kidney-specific knockin. By studying this patient, we can determine definitively the contribution of the kidney to the productions of PGI-M and TX-M and test their validity as markers of prostacyclin and thromboxane A 2 in the circulation. Metabolites were measured using liquid chromatography-tandem mass spectrometry. Endothelial cells were grown from blood progenitors. Before kidney transplantation, the patient's endothelial cells and platelets released negligible levels of prostacyclin (measured as 6-keto-prostaglandin F 1α ) and thromboxane A 2 (measured as TXB 2 ), respectively. Likewise, the urinary levels of PGI-M and TX-M were very low. After transplantation and the establishment of normal renal function, the levels of PGI-M and TX-M in the patient's urine rose to within normal ranges, whereas endothelial production of prostacyclin and platelet production of thromboxane A 2 remained negligible. These data show that PGI-M and TX-M can be derived exclusively from the kidney without contribution from prostacyclin made by endothelial cells or thromboxane A 2 by platelets in the general circulation. Previous work relying on urinary metabolites of prostacyclin and thromboxane A 2 as markers of whole-body endothelial and platelet function now requires reevaluation. © 2018 The Authors.
Sandilands, Euan A; Cameron, Sharon; Paterson, Frances; Donaldson, Sam; Briody, Lesley; Crowe, Jane; Donnelly, Julie; Thompson, Adrian; Johnston, Neil R; Mackenzie, Ivor; Uren, Neal; Goddard, Jane; Webb, David J; Megson, Ian L; Bateman, Nicholas; Eddleston, Michael
2012-02-03
Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18.
Muir, Peter; Schwartz, Zeev; Malek, Sarah; Kreines, Abigail; Cabrera, Sady Y.; Buote, Nicole J.; Bleedorn, Jason A.; Schaefer, Susan L.; Holzman, Gerianne; Hao, Zhengling
2011-01-01
Background Non-contact cranial cruciate ligament rupture (CrCLR) is an important cause of lameness in client-owned dogs and typically occurs without obvious injury. There is a high incidence of bilateral rupture at presentation or subsequent contralateral rupture in affected dogs. Although stifle synovitis increases risk of contralateral CrCLR, relatively little is known about risk factors for subsequent contralateral rupture, or whether therapeutic intervention may modify this risk. Methodology/Principal Findings We conducted a longitudinal study examining survival of the contralateral CrCL in client-owned dogs with unilateral CrCLR in a large baseline control population (n = 380), and a group of dogs that received disease-modifying therapy with arthroscopic lavage, intra-articular hyaluronic acid and oral doxycycline (n = 16), and were followed for one year. Follow-up in treated dogs included analysis of mobility, radiographic evaluation of stifle effusion and arthritis, and quantification of biomarkers of synovial inflammation. We found that median survival of the contralateral CrCL was 947 days. Increasing tibial plateau angle decreased contralateral ligament survival, whereas increasing age at diagnosis increased survival. Contralateral ligament survival was reduced in neutered dogs. Our disease-modifying therapy did not significantly influence contralateral ligament survival. Correlative analysis of clinical and biomarker variables with development of subsequent contralateral rupture revealed few significant results. However, increased expression of T lymphocyte-associated genes in the index unstable stifle at diagnosis was significantly related to development of subsequent non-contact contralateral CrCLR. Conclusion Subsequent contralateral CrCLR is common in client-owned dogs, with a median ligament survival time of 947 days. In this naturally occurring model of non-contact cruciate ligament rupture, cranial tibial translation is preceded by development of synovial inflammation. However, treatment with arthroscopic lavage, intra-articular hyaluronic acid and oral doxycycline does not significantly influence contralateral CrCL survival. PMID:21998650
Nicotine Enhances High-Fat Diet-Induced Oxidative Stress in the Kidney.
Arany, Istvan; Hall, Samuel; Reed, Dustin K; Reed, Caitlyn T; Dixit, Mehul
2016-07-01
Life expectancy of an obese smoker is 13 years less than a normal weight smoker, which could be linked to the increased renal risk imposed by smoking. Both smoking-through nicotine (NIC)-and obesity-by free fatty acid overload-provoke oxidative stress in the kidney, which ultimately results in development of chronic kidney injury. Their combined renal risk, however, is virtually unknown. We tested the hypothesis that chronic NIC exposure worsens renal oxidative stress in mice on high-fat diet (HFD) by altering the balance between expression of pro-oxidant and antioxidant genes. Nine-week-old male C57Bl/6J mice consumed normal diet (ND) or HFD and received either NIC (200 μg/ml) or vehicle (2% saccharine) in their drinking water. Body weight, plasma clinical parameters, renal lipid deposition, markers of renal oxidative stress and injury, as well as renal expression of the pro-oxidant p66shc and the antioxidant MnSOD were determined after 12 weeks. NIC significantly augmented levels of circulating free fatty acid, as well as lipid deposition, oxidative stress and sublethal injury in the kidneys of mice on HFD. In addition, NIC exposure suppressed HFD-mediated induction of MnSOD while increased expression of p66shc in the kidney. Tobacco smoking or the increasingly popular E-cigarettes-via NIC exposure-could worsen obesity-associated lipotoxicity in the kidney. Hence, our findings could help to develop strategies that mitigate adverse effects of NIC on the obese kidney. Life expectancy of an obese smoker is 13 years less than a normal weight smoker, which could be linked to the increased renal risk imposed by smoking. NIC-the main component of tobacco smoke, E-cigarettes and replacement therapies-links smoking to renal injury via oxidative stress, which could superimpose renal oxidative stress caused by obesity. Our results substantiate this scenario using a mouse model of diet induced obesity and NIC exposure and imply the augmented long-term renal risk in obese smokers. Also, our study may help to develop strategies that mitigate adverse effects of NIC on the obese kidney. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Mainra, Rahul; Elder, Grahame J
2010-01-01
Most patients who undergo kidney or kidney-pancreas transplantation have renal osteodystrophy, and immediately after transplantation bone mineral density (BMD) commonly falls. Together, these abnormalities predispose to an increased fracture incidence. Bisphosphonate or calcitriol therapy can preserve BMD after transplantation, but although bisphosphonates may be more effective, they pose potential risks for adynamic bone. A total of 153 kidney (61%) and kidney-pancreas (39%) transplant recipients were allocated to bisphosphonate (62%) or calcitriol (38%) therapy using an algorithm that incorporated BMD, prevalent vertebral fracture, biomarkers of bone turnover, and risk factor assessment. Patients received cholecalciferol and calcium as appropriate and were followed for 12 mo. Patients who were treated with bisphosphonates had lower BMD at the lumbar spine and femoral neck and longer time on dialysis. Age and gender were similar between the groups. At 12 mo, bisphosphonate-treated patients had significant BMD increases at the lumber spine and femoral neck and a negative trend at the wrist. Patients who were allocated to calcitriol, who were assessed to have lower baseline fracture risk, had no significant change in BMD at any site. At 1 yr, mean levels of bone turnover marker and intact parathyroid hormone normalized in both groups. Incident fracture rates did not differ significantly. With targeted treatment, BMD levels were stable or improved and bone turnover markers normalized. This algorithm provides a guide to targeting therapy after transplantation that avoids BMD loss and may reduce suppression of bone turnover.
MicroRNAs and Drug-induced Kidney Injury
Pavkovic, Mira; Vaidya, Vishal S.
2016-01-01
Drug-induced kidney injury (DIKI) is a severe complication in hospitalized patients associated with higher probabilities of developing progressive chronic kidney disease or end-stage renal diseases. Furthermore, DIKI is a problem during preclinical and clinical phases of drug development leading to high rates of project terminations. Understanding the molecular perturbations caused by DIKI would pave the way for a new class of therapeutics to mitigate the damage. Yet, another approach to ameliorate DIKI is identifying sensitive and specific translational biomarkers that outperform the current diagnostic analytes like serum creatinine and facilitate early diagnosis. MicroRNAs (miRNAs), a class of non-coding RNAs, are increasingly being recognized to have a two-pronged approach towards DIKI management: 1) miRNAs have a regulatory role in gene expression and signaling pathways thereby making them novel interventional targets and 2) miRNAs enable diagnosis and prognosis of DIKI because of their stable presence in biofluids. In this review, apart from summarizing the literature on miRNAs in DIKI, we report small RNA sequencing results showing miRNA expression profiles at baseline in normal kidney samples from mice and humans. Additionally, we also compared the miRNA expression in biopsies of normal human kidneys to patients with acute tubular necrosis, and found 76 miRNAs significantly downregulated and 47 miRNAs upregulated (FDR adjusted p<0.05, +/−2-fold change). In summary, we highlight the transformative potential of miRNAs in therapeutics and translational medicine with a focus on drug-induced kidney damage. PMID:27126472
Small renal size in newborns with spina bifida: possible causes.
Montaldo, Paolo; Montaldo, Luisa; Iossa, Azzurra Concetta; Cennamo, Marina; Caredda, Elisabetta; Del Gado, Roberto
2014-02-01
Previous studies reported that children with neural tube defects, but without any history of intrinsic renal diseases, have small kidneys when compared with age-matched standard renal growth. The aim of this study was to investigate the possible causes of small renal size in children with spina bifida by comparing growth hormone deficiency, physical limitations and hyperhomocysteinemia. The sample included 187 newborns with spina bifida. Renal sizes in the patients were assessed by using maximum measurement of renal length and the measurements were compared by using the Sutherland monogram. According to the results, the sample was divided into two groups--a group of 120 patients with small kidneys (under the third percentile) and a control group of 67 newborns with normal kidney size. Plasma total homocysteine was investigated in mothers and in their children. Serum insulin-like growth factor-1 (IGF-1) levels were measured. Serum IGF-1 levels were normal in both groups. Children and mothers with homocysteine levels >10 μmol/l were more than twice as likely to have small kidneys and to give to birth children with small kidneys, respectively, compared with newborns and mothers with homocysteine levels <10 μmol/l. An inverse correlation was also found between the homocysteine levels of mothers and kidney sizes of children (r = - 0.6109 P ≤ 0.01). It is highly important for mothers with hyperhomocysteinemia to be educated about benefits of folate supplementation in order to reduce the risk of small renal size and lower renal function in children.
Combined heart-kidney transplantation after total artificial heart insertion.
Ruzza, A; Czer, L S C; Ihnken, K A; Sasevich, M; Trento, A; Ramzy, D; Esmailian, F; Moriguchi, J; Kobashigawa, J; Arabia, F
2015-01-01
We present the first single-center report of 2 consecutive cases of combined heart and kidney transplantation after insertion of a total artificial heart (TAH). Both patients had advanced heart failure and developed dialysis-dependent renal failure after implantation of the TAH. The 2 patients underwent successful heart and kidney transplantation, with restoration of normal heart and kidney function. On the basis of this limited experience, we consider TAH a safe and feasible option for bridging carefully selected patients with heart and kidney failure to combined heart and kidney transplantation. Recent FDA approval of the Freedom driver may allow outpatient management at substantial cost savings. The TAH, by virtue of its capability of providing pulsatile flow at 6 to 10 L/min, may be the mechanical circulatory support device most likely to recover patients with marginal renal function and advanced heart failure. Copyright © 2015 Elsevier Inc. All rights reserved.
Gene transfer into the kidney: current status and limitations.
Moullier, P; Salvetti, A; Champion-Arnaud, P; Ronco, P M
1997-01-01
Gene therapy is obviously a controversial issue and a wave of suspicion has dampened the initial enthusiasm raised by this new therapeutic approach. It has now become fashionable to downplay the potential for gene therapy in most fields including kidney-related diseases. In our opinion, this is an unfair and unrealistic view of the future. In fact, gene therapy of well-selected kidney diseases will certainly become feasible, but a large data base on vectors and transfer methods both in the normal kidney and in disease models has first to be collected. Any significant progress in the biology of the vectors, in the cellular interactions of the newly introduced DNA, and in the regulation and persistency of the transgene should be rapidly translated to the kidney in relevant experimental models. Herein, we present the use and current limitations of gene transfer to the kidney and the potential therapeutic perspectives.
Hu, Hong-Tao; Ren, Liang; Sun, Xian-Ze; Liu, Feng-Yu; Yu, Jin-He; Gu, Zhen-Fang
2018-04-01
Transforaminal lumbar interbody fusion (TLIF) is an effective treatment for patients with degenerative lumbar disc disorder. Contralateral radiculopathy, as a complication of TLIF, has been recognized in this institution, but is rarely reported in the literature. In this article, we report 2 cases of contralateral radiculopathy after TLIF in our institution and its associated complications. In the 2 cases, the postoperative computed tomography (CT) and magnetic resonance image (MRI) showed obvious upward movement of the superior articular process, leading to contralateral foraminal stenosis. Revision surgery was done at once to partially resect the opposite superior facet and to relieve nerve root compression. After revision surgery, the contralateral radiculopathy disappeared. Contralateral radiculopathy is an avoidable potential complication. It is very important to create careful preoperative plans and to conscientiously plan the use of intraoperative techniques. In case of postoperative contralateral leg pain, the patients should be examined by CT and MRI. If CT and MRI show that the superior articular process significantly migrated upwards, which leads to contralateral foraminal stenosis, revision surgery should be done at once to partially resect the contralateral superior facet so as to relieve nerve root compression and avoid possible long-term impairment.
Overexpression of esterase D in kidney from trisomy 13 fetuses
DOE Office of Scientific and Technical Information (OSTI.GOV)
Loughna, S.; Moore, G.; Gau, G.
1993-10-01
Human trisomy 13 (Patau syndrome) occurs in approximately 1 in 5,000 live births. It is compatible with life, but prolonged survival is rare. Anomalies often involve the urogenital, cardiac, craniofacial, and central nervous systems. It is possible that these abnormalities may be due to the overexpression of developmentally important genes on chromosome 13. The expression of esterase D (localized to chromosome 13q14.11) has been investigated in both muscle and kidney from trisomy 13 fetuses and has been compared with normal age- and sex-matched fetal tissues, by using northern analysis. More than a twofold increase in expression of esterase D wasmore » found in the kidney of two trisomy 13 fetuses, with normal levels in a third. Overexpression was not seen in the muscle tissues from these fetuses. 34 refs., 3 figs., 2 tabs.« less
Devlin, Amy A; Halvorsen, Priya J; Miller, Jennifer C; Laster, Scott M
2017-05-01
Leptospira interrogans (L. interrogans), the causative agent of leptospirosis, is a widespread zoonotic spirochete that lives a dual lifestyle. L. interrogans infects mice, rats, and wildlife in a persistent and asymptomatic fashion, while also causing productive and acute infections in other mammals such as humans and hamsters. Infections in humans can be fatal, accompanied by a cytokine storm and shock-like symptoms. Production of IL-10 has been noted in both rodent and human infections which has led a number of investigators to hypothesize that IL-10 plays a role in the pathogenesis of this disease. To test this hypothesis we have compared bacteremia and the cytokine response of normal and IL-10 deficient C57Bl/6 mice following ip infection with L. interrogans. In normal mice bacterial 16s mRNA was detected in both lung and kidney tissues within a day after infection. Levels of 16s mRNA then dropped in both organs with complete elimination from the lung by day 3 but persistence in the kidney for 7days after infection. In contrast, in IL-10 deficient mice, the organism was eliminated more rapidly from the kidney. We found that infection of both control and IL-10 deficient mice produced similar levels of a number of pro-inflammatory cytokine mRNAs. On the other hand, IFN-γ mRNA was only induced in IL-10 deficient mice. These results support the hypothesis that L. interrogans ability to induce IL-10, which in turn prevents production of IFN-γ and inhibits T cell immunity, may contribute to the persistent growth of this microorganism in the murine kidney. Copyright © 2017 Elsevier GmbH. All rights reserved.
Elevated Cell Wall Chitin in Candida albicans Confers Echinocandin Resistance In Vivo
Lee, Keunsook K.; MacCallum, Donna M.; Jacobsen, Mette D.; Walker, Louise A.; Odds, Frank C.
2012-01-01
Candida albicans cells with increased cell wall chitin have reduced echinocandin susceptibility in vitro. The aim of this study was to investigate whether C. albicans cells with elevated chitin levels have reduced echinocandin susceptibility in vivo. BALB/c mice were infected with C. albicans cells with normal chitin levels and compared to mice infected with high-chitin cells. Caspofungin therapy was initiated at 24 h postinfection. Mice infected with chitin-normal cells were successfully treated with caspofungin, as indicated by reduced kidney fungal burdens, reduced weight loss, and decreased C. albicans density in kidney lesions. In contrast, mice infected with high-chitin C. albicans cells were less susceptible to caspofungin, as they had higher kidney fungal burdens and greater weight loss during early infection. Cells recovered from mouse kidneys at 24 h postinfection with high-chitin cells had 1.6-fold higher chitin levels than cells from mice infected with chitin-normal cells and maintained a significantly reduced susceptibility to caspofungin when tested in vitro. At 48 h postinfection, caspofungin treatment induced a further increase in chitin content of C. albicans cells harvested from kidneys compared to saline treatment. Some of the recovered clones had acquired, at a low frequency, a point mutation in FKS1 resulting in a S645Y amino acid substitution, a mutation known to confer echinocandin resistance. This occurred even in cells that had not been exposed to caspofungin. Our results suggest that the efficacy of caspofungin against C. albicans was reduced in vivo due to either elevation of chitin levels in the cell wall or acquisition of FKS1 point mutations. PMID:21986821
Taha, Doris; Barbar, Maha; Kanaan, Hassan; Williamson Balfe, John
2003-10-15
We report on two sibs (of 4) with a syndrome of minor facial anomalies, proportionate IUGR, neonatal non-autoimmune diabetes mellitus (NDM), severe congenital hypothyroidism (CH), cholestasis, congenital glaucoma, and polycystic kidneys. Liver disease progressed to hepatic fibrosis. The renal disease was characterized by large kidneys and multiple small cysts with deficient corticomedullary junction differentiation and normal kidney function. The phenotype observed in the two sibs was identical. Although a combination of liver, kidney, and pancreatic involvement has been described in Ivemark syndrome (hepato-renal-pancreatic syndrome), the coexistence of NDM, CH, and glaucoma in both sibs suggests the possibility that this combination of manifestations describes a new autosomal recessive syndrome. Mutation analysis for several candidate genes is warranted. Copyright 2003 Wiley-Liss, Inc.
A Case Report of Successful Kidney Donation After Brain Death Following Nicotine Intoxication.
Räsänen, M; Helanterä, I; Kalliomäki, J; Savikko, J; Parry, M; Lempinen, M
Nicotine intoxication is a rare cause of death and can lead to brain death after respiratory arrest and hypoxic-ischemic encephalopathy. To our knowledge, no previous reports regarding organ donation after nicotine intoxication have been described. We present a successful case of kidney donation after brain death caused by subcutaneous nicotine overdose from liquid nicotine from an e-cigarette cartridge in an attempted suicide. Both kidneys were transplanted successfully with immediate graft function, and both recipients were discharged at postoperative day 9 with normal plasma creatinine levels. Graft function has remained excellent in follow-up. This case suggests that kidneys from a donor with fatal nicotine intoxication may be successfully used for kidney transplantation in the absence of other contraindications for donation. Copyright © 2016 Elsevier Inc. All rights reserved.
Matrix metalloproteinases in kidney homeostasis and diseases
Tan, Roderick J.
2012-01-01
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have been increasingly linked to both normal physiology and abnormal pathology in the kidney. Collectively able to degrade all components of the extracellular matrix, MMPs were originally thought to antagonize the development of fibrotic diseases solely through digestion of excessive matrix. However, increasing evidence has shown that MMPs play a wide variety of roles in regulating inflammation, epithelial-mesenchymal transition, cell proliferation, angiogenesis, and apoptosis. We now have robust evidence for MMP dysregulation in a multitude of renal diseases including acute kidney injury, diabetic nephropathy, glomerulonephritis, inherited kidney disease, and chronic allograft nephropathy. The goal of this review is to summarize current findings regarding the role of MMPs in kidney diseases as well as the mechanisms of action of this family of proteases. PMID:22492945
The gut microbiota and the brain-gut-kidney axis in hypertension and chronic kidney disease.
Yang, Tao; Richards, Elaine M; Pepine, Carl J; Raizada, Mohan K
2018-07-01
Crosstalk between the gut microbiota and the host has attracted considerable attention owing to its involvement in diverse diseases. Chronic kidney disease (CKD) is commonly associated with hypertension and is characterized by immune dysregulation, metabolic disorder and sympathetic activation, which are all linked to gut dysbiosis and altered host-microbiota crosstalk. In this Review, we discuss the complex interplay between the brain, the gut, the microbiota and the kidney in CKD and hypertension and explain our brain-gut-kidney axis hypothesis for the pathogenesis of these diseases. Consideration of the role of the brain-gut-kidney axis in the maintenance of normal homeostasis and of dysregulation of this axis in CKD and hypertension could lead to the identification of novel therapeutic targets. In addition, the discovery of unique microbial communities and their associated metabolites and the elucidation of brain-gut-kidney signalling are likely to fill fundamental knowledge gaps leading to innovative research, clinical trials and treatments for CKD and hypertension.
Tain, You-Lin; Hsu, Chien-Ning
2018-06-12
Suboptimal early-life conditions affect the developing kidney, resulting in long-term programming effects, namely renal programming. Adverse renal programming increases the risk for developing hypertension and kidney disease in adulthood. Conversely, reprogramming is a strategy aimed at reversing the programming processes in early life. AMP-activated protein kinase (AMPK) plays a key role in normal renal physiology and the pathogenesis of hypertension and kidney disease. This review discusses the regulation of AMPK in the kidney and provides hypothetical mechanisms linking AMPK to renal programming. This will be followed by studies targeting AMPK activators like metformin, resveratrol, thiazolidinediones, and polyphenols as reprogramming strategies to prevent hypertension and kidney disease. Further studies that broaden our understanding of AMPK isoform- and tissue-specific effects on renal programming are needed to ultimately develop reprogramming strategies. Despite the fact that animal models have provided interesting results with regard to reprogramming strategies targeting AMPK signaling to protect against hypertension and kidney disease with developmental origins, these results await further clinical translation.
Abdominal Obesity, Race and Chronic Kidney Disease in Young Adults: Results from NHANES 1999-2010
Sarathy, Harini; Henriquez, Gabriela; Abramowitz, Matthew K.; Kramer, Holly; Rosas, Sylvia E.; Johns, Tanya; Kumar, Juhi; Skversky, Amy; Kaskel, Frederick; Melamed, Michal L.
2016-01-01
Objective Kidney dysfunction in obesity may be independent of and may precede the development of hypertension and/or diabetes mellitus. We aimed to examine if abdominal obesity is associated with early markers of CKD in a young healthy population and whether these associations differ by race and/or ethnicity. Methods We analyzed data from the NHANES 1999–2010 for 6918 young adults ages 20–40 years. Abdominal obesity was defined by gender criteria of waist circumference. CKD markers included estimated glomerular filtration rate and albuminuria ≥30 mg/g. Race stratified analyses were done overall and in subgroups with normal blood pressures, normoglycemia and normal insulin sensitivity. Awareness of CKD was assessed in participants with albuminuria. Results Abdominal obesity was present in over one-third of all young adults and was more prevalent among non-Hispanic blacks (45.4%) versus Mexican-Americans (40.6%) or non-Hispanic whites (37.4%) (P-value = 0.004). Mexican-American young adults with abdominal obesity had a higher odds of albuminuria even among those with normal blood pressure, normal glucose, and normal insulin sensitivity [adjusted odds ratio 4.5; 95% confidence interval (1.6–12.2), p = 0.004]. Less than 5% of young adults with albuminuria of all races and ethnicities had been told they had kidney disease. Conclusion Abdominal obesity in young adults, especially in Mexican-Americans, is independently associated with albuminuria even with normal blood pressures, normoglycemia and normal insulin levels. Greater awareness of CKD is needed to protect this young population from long-standing exposure to abdominal obesity and early progressive renal disease. PMID:27224643
Chronic epithelial kidney injury molecule-1 expression causes murine kidney fibrosis.
Humphreys, Benjamin D; Xu, Fengfeng; Sabbisetti, Venkata; Grgic, Ivica; Movahedi Naini, Said; Wang, Ningning; Chen, Guochun; Xiao, Sheng; Patel, Dhruti; Henderson, Joel M; Ichimura, Takaharu; Mou, Shan; Soeung, Savuth; McMahon, Andrew P; Kuchroo, Vijay K; Bonventre, Joseph V
2013-09-01
Acute kidney injury predisposes patients to the development of both chronic kidney disease and end-stage renal failure, but the molecular details underlying this important clinical association remain obscure. We report that kidney injury molecule-1 (KIM-1), an epithelial phosphatidylserine receptor expressed transiently after acute injury and chronically in fibrotic renal disease, promotes kidney fibrosis. Conditional expression of KIM-1 in renal epithelial cells (Kim1(RECtg)) in the absence of an injury stimulus resulted in focal epithelial vacuolization at birth, but otherwise normal tubule histology and kidney function. By 4 weeks of age, Kim1(RECtg) mice developed spontaneous and progressive interstitial kidney inflammation with fibrosis, leading to renal failure with anemia, proteinuria, hyperphosphatemia, hypertension, cardiac hypertrophy, and death, analogous to progressive kidney disease in humans. Kim1(RECtg) kidneys had elevated expression of proinflammatory monocyte chemotactic protein-1 (MCP-1) at early time points. Heterologous expression of KIM-1 in an immortalized proximal tubule cell line triggered MCP-1 secretion and increased MCP-1-dependent macrophage chemotaxis. In mice expressing a mutant, truncated KIM-1 polypeptide, experimental kidney fibrosis was ameliorated with reduced levels of MCP-1, consistent with a profibrotic role for native KIM-1. Thus, sustained KIM-1 expression promotes kidney fibrosis and provides a link between acute and recurrent injury with progressive chronic kidney disease.
García-Porrero, J A; Ojeda, J L; Hurlé, J M
1978-01-01
We have studied, by means of optic and electron microscopy, the normal and abnormal cell death that takes place during the postnatal morphogenesis of rabbit kidney, and in the experimental renal polycystosis produced by methylprednisolone acetate. In the normal kidney intertubular cell death can be observed during the first 20 days of the postnatal development. However, cell death in the normal metanephric blastema is a very rare event. In the polycystic kidney numerous dead cells can be seen between the third and forty eighth days after injection. The topography and morphology of the dead cells depend on the stage in the evolution of the disease. In the 'stage of renal immaturity', dying and dead cells are present in the nephrogenic tissue, in the dilating collecting tubules and in the intertubular spaces. In this stage the cellular pathology is essentially nuclear. In the stage of tubular cysts, the dead cells are mostly located in the walls of cysts, with some dead cells, but mostly cellular debris in their lumina. At this stage the cellular pathology is basically cytoplasmic. The dead cells are eventually digested by what appear to be phagocytes of tubular epithelial origin. It is suggested that cell death is an important factor in the evolution of the lesions of renal polycystosis induced by corticosteroids, and probably in the initiation of the pathological process as well. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 Fig. 18 Fig. 19 PMID:670065
Sejima, Takehiro; Yamaguchi, Noriya; Iwamoto, Hideto; Masago, Toshihiko; Morizane, Shuichi; Ono, Koji; Koumi, Tsutomu; Honda, Masashi; Takenaka, Atsushi
2015-08-01
To characterize the preoperative factors affecting renal cell carcinoma patients as predictive of post-radical nephrectomy (RN) mild (M-decline) or severe (S-decline) renal functional decline and to elucidate the histopathologic features of the resected normal kidney cortex, as well as the occurrence of cardiovascular disease (CVD) in both M-decline and S-decline patients. M-decline and S-decline were categorized as a percentage of postoperative estimated glomerular filtration rate decline of <20 and of >40, respectively. The preoperative factors analyzed were patient demographics, comorbidities, and radiographic findings, including remnant kidney status and tumor size. The factors based on postoperative information analyzed were tumor and normal cortex pathology and CVD events. In 175 patient cohort, 21 and 32 cases were categorized as M-decline and S-decline, respectively. Absence of comorbidities, larger remnant kidney volume (RKV)/body surface area (BSA) ratio, and larger tumor diameter were significantly predictive of M-decline, whereas smaller tumor diameter was significantly predictive of S-decline. The global glomerulosclerosis extent in nephrectomized normal cortex of S-decline cases was significantly higher than in other types of cases. No CVD event was observed in M-decline cases. This is the first report to identify the RKV/BSA ratio as a promising predictor of post-RN degree of renal functional decline. Post-RN prevention of life-threatening outcomes according to preoperative and postoperative information, including the degree of post-RN renal functional decline and histopathology of the nephrectomized normal cortex, should be considerable in future urological tasks. Copyright © 2015 Elsevier Inc. All rights reserved.
[A correlation between diffusion kurtosis imaging and the proliferative activity of brain glioma].
Tonoyan, A S; Pronin, I N; Pitshelauri, D I; Shishkina, L V; Fadeeva, L M; Pogosbekyan, E L; Zakharova, N E; Shults, E I; Khachanova, N V; Kornienko, V N; Potapov, A A
2015-01-01
The aim of the study was to assess the capabilities of diffusion kurtosis imaging (DKI) in diagnosis of the glioma proliferative activity and to evaluate a relationship between the glioma proliferative activity index and diffusion parameters of the contralateral normal appearing white matter (CNAWM). The study included 47 patients with newly diagnosed brain gliomas (23 low grade, 13 grade III, and 11 grade IV gliomas). We determined a relationship between absolute and normalized parameters of the diffusion tensor (mean (MD), axial (AD), and radial (RD) diffusivities; fractional (FA) and relative (RA) anisotropies) and diffusion kurtosis (mean (MK), axial (AK), and radial (RK) kurtosis; kurtosis anisotropy (KA)) and the proliferative activity index in the most malignant glioma parts (p<0.05). We also established a relationship between the tensor and kurtosis parameters of CNAWM and the glioma proliferative activity index (p<0.05). The correlation between all the absolute and normalized diffusion parameters and the glioma proliferative activity index, except absolute and normalized FA and RA values, was found to be statistically significant (p<0.05). Kurtosis (MK, AK, and RK) and anisotropy (KA, FA, RA) values increased, and diffusivity (MD, AD, RD) values decreased as the glioma proliferative activity index increased. A strong correlation between the proliferative activity index and absolute RK (r=0,71; p=0.000001) and normalized values of MK (r=0.8; p=0.000001), AK (r=0.71; p=0.000001), RK (r=0.81; p=0.000001), and RD (r=-0.71; p=0.000001) was found. A weak, but statistically significant correlation between the glioma proliferative activity index and diffusion values RK (r=-0.36; p=0.014), KA (r=-0.39; p=0.007), RD (r=0.35; p=0.017), FA (r=-0.42; p=0.003), and RA (r=-0.41; p=0.004) of CNAWM was found. DKI has good capabilities to detect immunohistochemical changes in gliomas. DKI demonstrated a high sensitivity in detection of microstructural changes in the contralateral normal appearing white matter in patients with brain gliomas.
Chai, Hann-Juang; Kiew, Lik-Voon; Chin, Yunni; Norazit, Anwar; Mohd Noor, Suzita; Lo, Yoke-Lin; Looi, Chung-Yeng; Lau, Yeh-Siang; Lim, Tuck-Meng; Wong, Won-Fen; Abdullah, Nor Azizan; Abdul Sattar, Munavvar Zubaid; Johns, Edward J; Chik, Zamri; Chung, Lip-Yong
2017-01-01
Poly-l-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier. 3 H-deoxycytidine-labeled PGs (17 or 41 kDa) and 3 H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats. The biodistribution of these compounds was determined over 24 h. Accumulation of PG in normal kidneys was also tracked using 5-(aminoacetamido) fluorescein (fluoresceinyl glycine amide)-labeled PG (PG-AF). To evaluate the potential of PGs in ferrying renal protective anti-oxidative stress compounds, the model drug 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) was conjugated to 41 kDa PG to form PG-AEBSF. PG-AEBSF was then characterized and evaluated for intracellular anti-oxidative stress efficacy (relative to free AEBSF). In the normal rat kidneys, 17 kDa radiolabeled PG (PG-Tr) presents a 7-fold higher, while 41 kDa PG-Tr shows a 15-fold higher renal accumulation than the free radiolabel after 24 h post injection. The accumulation of PG-AF was primarily found in the renal tubular tissues at 2 and 6 h after an intravenous administration. In the diabetic (oxidative stress-induced) kidneys, 41 kDa PG-Tr showed the greatest renal accumulation of 8-fold higher than the free compound 24 h post dose. Meanwhile, the synthesized PG-AEBSF was found to inhibit intracellular nicotinamide adenine dinucleotide phosphate oxidase (a reactive oxygen species generator) at an efficiency that is comparable to that of free AEBSF. This indicates the preservation of the anti-oxidative stress properties of AEBSF in the conjugated state. The favorable accumulation property of 41 kDa PG in normal and oxidative stress-induced kidneys, along with its capabilities in conserving the pharmacological properties of the conjugated renal protective drugs, supports its role as a potential renal targeting drug carrier.
Chai, Hann-Juang; Kiew, Lik-Voon; Chin, Yunni; Norazit, Anwar; Mohd Noor, Suzita; Lo, Yoke-Lin; Looi, Chung-Yeng; Lau, Yeh-Siang; Lim, Tuck-Meng; Wong, Won-Fen; Abdullah, Nor Azizan; Abdul Sattar, Munavvar Zubaid; Johns, Edward J; Chik, Zamri; Chung, Lip-Yong
2017-01-01
Background and purpose Poly-l-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier. Experimental approach 3H-deoxycytidine-labeled PGs (17 or 41 kDa) and 3H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats. The biodistribution of these compounds was determined over 24 h. Accumulation of PG in normal kidneys was also tracked using 5-(aminoacetamido) fluorescein (fluoresceinyl glycine amide)-labeled PG (PG-AF). To evaluate the potential of PGs in ferrying renal protective anti-oxidative stress compounds, the model drug 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) was conjugated to 41 kDa PG to form PG-AEBSF. PG-AEBSF was then characterized and evaluated for intracellular anti-oxidative stress efficacy (relative to free AEBSF). Results In the normal rat kidneys, 17 kDa radiolabeled PG (PG-Tr) presents a 7-fold higher, while 41 kDa PG-Tr shows a 15-fold higher renal accumulation than the free radiolabel after 24 h post injection. The accumulation of PG-AF was primarily found in the renal tubular tissues at 2 and 6 h after an intravenous administration. In the diabetic (oxidative stress-induced) kidneys, 41 kDa PG-Tr showed the greatest renal accumulation of 8-fold higher than the free compound 24 h post dose. Meanwhile, the synthesized PG-AEBSF was found to inhibit intracellular nicotinamide adenine dinucleotide phosphate oxidase (a reactive oxygen species generator) at an efficiency that is comparable to that of free AEBSF. This indicates the preservation of the anti-oxidative stress properties of AEBSF in the conjugated state. Conclusion/Implications The favorable accumulation property of 41 kDa PG in normal and oxidative stress-induced kidneys, along with its capabilities in conserving the pharmacological properties of the conjugated renal protective drugs, supports its role as a potential renal targeting drug carrier. PMID:28144140
Bojanic, Nebojsa; Bumbasirevic, Uros; Bojanic, Gordana; Vukovic, Ivan; Milojevic, Bogomir; Pekmezovic, Tatjana
2017-03-01
To evaluate the results of testis-sparing surgery (TSS) in patients, with small testicular lesions and a normal contralateral testicle. In all, 28 patients were treated with TSS for small testicular lesions and a normal contralateral testicle. TSS was considered in patients with testicular lesions smaller than 2 cm and no evidence of metastatic disease. The mean age of patients was 35.3 ± 7.3 years, while the mean diameter of the testicular lesions was 11.4 ± 3.7 mm. After pathological examination, 18 patients (64.3%) were diagnosed with stromal tumors and miscellaneous lesions, while 10 (35.7%) had a germ cell tumor. The median follow-up time for the former group was 33 months and no recurrences were observed. In one patient with germ cell tumor, immediate orchiectomy was performed, while the remaining nine were followed-up (median time, 45 months). One patient developed local recurrence after 39 months. Excellent outcomes for benign lesions could be achieved using TSS. TSS could be offered safely in highly selected patients with germ cell tumors, specifically within a clinical trial but there is more data needed regarding the potential risks and benefits. J. Surg. Oncol. 2017;115:287-290. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Apinorasethkul, Ontida, E-mail: Ontida.a@gmail.com; Kirk, Maura; Teo, Kevin
Patients diagnosed with head and neck cancer are traditionally treated with photon radiotherapy. Proton therapy is currently being used clinically and may potentially reduce treatment-related toxicities by minimizing the dose to normal organs in the treatment of postoperative oropharyngeal cancer. The finite range of protons has the potential to significantly reduce normal tissue toxicity compared to photon radiotherapy. Seven patients were planned with both proton and photon modalities. The planning goal for both modalities was achieving the prescribed dose to 95% of the planning target volume (PTV). Dose-volume histograms were compared in which all cases met the target coverage goals.more » Mean doses were significantly lower in the proton plans for the oral cavity (1771 cGy photon vs 293 cGy proton, p < 0.001), contralateral parotid (1796 cGy photon vs 1358 proton, p < 0.001), and the contralateral submandibular gland (3608 cGy photon vs 3251 cGy proton, p = 0.03). Average total integral dose was 9.1% lower in proton plans. The significant dosimetric sparing seen with proton therapy may lead to reduced side effects such as pain, weight loss, taste changes, and dry mouth. Prospective comparisons of protons vs photons for disease control, toxicity, and patient-reported outcomes are therefore warranted and currently being pursued.« less
Familial Congenital Unilateral Cerebral Ventriculomegaly: Delineation of a Distinct Genetic Disorder
Zaki, Maha S.; Afifi, Hanan H.; Barkovich, AJ.; Gleeson, Joseph G.
2016-01-01
We identified two female siblings, derived from healthy first cousin parents, with congenital unilateral cerebral ventriculomegaly detected prenatally. Patient 1 underwent ventriculoperitoneal shunt operation at 1 week old, while Patient 2 was followed without surgical intervention. Both patients presented with mild developmental delay and hemiparesis contralateral to the involved hemisphere. Focal seizures were observed in Patient 1, whose neuroimaging revealed posterior insular polymicrogyria in the normal sized ventricle hemisphere and retrocerebellar cyst. Both siblings displayed near absence of white matter with marked thinning of the overlying cortex in the affected hemisphere and very thin corpus callosum. Investigations revealed no other system involvement and karyotyping was normal. Normal TORCH screening in subsequent pregnancies, normal parental coagulation profile and undetectable maternal autoantibodies suggested against the possible role of extrinsic factors as an etiological factor for unilateral ventriculomegaly. Parents had normal brain imaging findings. We suggest delineation of a distinct developmental brain defect, most likely of autosomal recessive inheritance. PMID:19610102
Nagao, Ryan J; Xu, Jin; Luo, Ping; Xue, Jun; Wang, Yi; Kotha, Surya; Zeng, Wen; Fu, Xiaoyun; Himmelfarb, Jonathan; Zheng, Ying
2016-10-01
The kidney peritubular microvasculature is highly susceptible to injury from drugs and toxins, often resulting in acute kidney injury and progressive chronic kidney disease. Little is known about the process of injury and regeneration of human kidney microvasculature, resulting from the lack of appropriate kidney microvascular models that can incorporate the proper cells, extracellular matrices (ECMs), and architectures needed to understand the response and contribution of individual vascular components in these processes. In this study, we present methods to recreate the human kidney ECM (kECM) microenvironment by fabricating kECM hydrogels derived from decellularized human kidney cortex. The majority of native matrix proteins, such as collagen-IV, laminin, and heparan sulfate proteoglycan, and their isoforms were preserved in similar proportions as found in normal kidneys. Human kidney peritubular microvascular endothelial cells (HKMECs) became more quiescent when cultured on this kECM gel compared with culture on collagen-I-assessed using phenotypic, genotypic, and functional assays; whereas human umbilical vein endothelial cells became stimulated on kECM gels. We demonstrate for the first time that human kidney cortex can form a hydrogel suitable for use in flow-directed microphysiological systems. Our findings strongly suggest that selecting the proper ECM is a critical consideration in the development of vascularized organs on a chip and carries important implications for tissue engineering of all vascularized organs.
Adaptive remodeling at the pedicle due to pars fracture: a finite element analysis study.
İnceoğlu, Serkan; Mageswaran, Prasath; Modic, Michael T; Benzel, Edward C
2014-09-01
Spondylolysis is a common condition among the general population and a major cause of back pain in young athletes. This condition can be difficult to detect with plain radiography and has been reported to lead to contralateral pars fracture or pedicle fracture in the terminal stages. Interestingly, some patients with late-stage spondylolysis are observed to have radiographic or CT evidence of a sclerotic pedicle on the side contralateral to the spondylolysis. Although computational studies have shown stress elevation in the contralateral pedicle after a pars fracture, it is not known if these changes would cause sclerotic changes in the contralateral pedicle. The objective of this study was to investigate the adaptive remodeling process at the pedicle due to a contralateral spondylolysis using finite element analysis. A multiscale finite element model of a vertebra was obtained by combining a continuum model of the posterior elements with a voxel-based pedicle section. Extension loading conditions were applied with or without a fracture at the contralateral pars to analyze the stresses in the contralateral pedicle. A remodeling algorithm was used to simulate and assess density changes in the contralateral pedicle. The remodeling algorithm demonstrated an increase in bone formation around the perimeter of the contralateral pedicle with some localized loss of mass in the region of cancellous bone. The authors' results indicated that a pars fracture results in sclerotic changes in the contralateral pedicle. Such a remodeling process could increase overall bone mass. However, focal bone loss in the region of the cancellous bone of the pedicle might predispose the pedicle to microfractures. This phenomenon explains, at least in part, the origin of pedicle stress fractures in the sclerotic contralateral pedicles of patients with unilateral spondylolysis.
Joo, Y-H; Yoo, I-R; Cho, K-J; Park, J-O; Nam, I-C; Kim, C-S; Kim, S-Y; Kim, M-S
2014-12-01
The purpose of this study was to determine whether preoperative (18) F-FDG PET/CT is useful in assessing contralateral lymph node metastasis in the neck. A retrospective review of medical records was performed. Patients treated at a single institute. One hundred and fifty-seven patients whose pathology results were positive for unilateral node metastasis (N1-3) involvement and underwent preoperative (18) F-FDG PET/CT for head and neck squamous cell carcinoma (HNSCC) were reviewed. Prognostic factors and nodal SUVmax were studied to identify the risk of contralateral disease. Thirty-six (22.9%) patients had contralateral cervical lymph node metastases. The (18) F-FDG PET/CT had a sensitivity of 80% and a specificity of 96% in identifying the contralateral cervical lymph node metastases on a level-by-level basis. The median SUVmax values of the ipsilateral and contralateral lymph nodes were 3.99 ± 3.36 (range, 0-20.4) and 2.94 ± 2.04 (range, 0-8.7), respectively (P = 0.001). There was a significant difference in the median SUVmax of contralateral nodes between the benign and malignant cervical lymph nodes (2.31 ± 0.62 versus 3.28 ± 2.43, P = 0.014). The cut-off value of contralateral median SUVmax in the context of contralateral cervical metastasis was 2.5 with the sensitivity of 75% and the specificity of 94%. A median contralateral lymph node SUVmax ≥ 2.5 was associated with 5-year disease-specific survival (P = 0.038). (18) F-FDG PET/CT median SUVmax cut-off values of contralateral lymph nodes ≥2.5 were associated with contralateral cervical lymph node metastases and 5-year disease-specific survival in HNSCC patients with unilateral metastases. © 2014 John Wiley & Sons Ltd.
Jean, G; Chazot, C
2010-06-01
The new recommendations of "Kidney disease: improving global outcomes" for the definition and classification of chronic kidney disease and mineral and bone disorders were released in August 2009. We report the most important of these recommendations and a brief comment from a clinician's point of view. The main points to be noted with regard to the new recommendations are as follows: serum calcium should be in the normal range; phosphorus concentration should be lowered toward the normal range and serum parathyroid hormone (PTH) levels should be two to nine times the upper limit of the normal range; bone remodelling can be assessed using alkaline phosphatase; the use of calcium-phosphorus (Ca x P) product as an index is not recommended anymore; at any stage of CKD, vitamin D deficiency and insufficiency must be corrected; vascular calcification should be detected in a simple way using lateral abdominal radiography and echocardiography; a bone biopsy should be performed before therapy with bisphosphonates; the prescription of dialysate calcium should be individualized within the range of 1.25-1.5 mmol/l; the phosphate binder (calcium- or non-calcium-based) and the other treatments for secondary hyperparathyroidism should be individualized based on a global strategy. A majority of these recommendations are not based on evidence and their feasibility and relevance need to be assessed. Copyright 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
McAfee, J.G.; Krauss, D.J.; Subramanian, G.
The 3-hour biodistribution of /sup 99m/Tc complexes of five diphosphonates (HMDP, NMMDP, DMAD, DPD, and APD), imidodiphosphonate (IDP), and pyrophosphate (PYP) was compared in rats with segmental renal infarction induced by a 1-hour occlusion of a renal artery branch. /sup 95m/Tc labeled MDP was a reference substance in all animals. Three agents (APD, HMDP and IDP) had a higher infarct/normal kidney concentration ratio than MDP, the latter two by virtue of a lower content in normal kidney. HMDP, DPD, and IDP had very high liver concentrations. DPD showed relatively high concentrations in soft tissues and blood. The blood and kidneymore » levels of PYP were higher than those of MDP but the infarct/normal kidney ratios were similar. None of the agents had a higher uptake in bone than MDP: four had a significantly lower uptake. The increased concentration of /sup 99m/Tc MDP in the infarcts was readily seen in camera images one day after renal artery occlusion, but not at three or seven days. Increased diphosphonate uptake was accompanied by an influx of calcium in both cortex and medulla. The accumulation of diphosphonate in areas of infarction was not modified by infusions of verapamil or Captopril.« less
Rhabdomyolysis-Associated Acute Kidney Injury With Normal Creatine Phosphokinase.
Kamal, Faisal; Snook, Lindsay; Saikumar, Jagannath H
2018-01-01
Rhabdomyolysis is a syndrome characterized by the breakdown of skeletal muscle and leakage of intracellular myocyte contents, such as creatine phosphokinase (CPK) and myoglobin, into the interstitial space and plasma resulting in acute kidney injury (AKI). Elevated CPK of at least 5 times the upper limit of normal is an important diagnostic marker of Rhabdomyolysis. We present a case of rhabdomyolysis with severe AKI with a normal CPK at presentation. A 32-year-old man presented with acute respiratory failure and AKI after an overdose of recreational drugs. Urinalysis at presentation showed trace amounts of blood, identified as rare red blood cells under microscopy. CPK was 156 U/L at presentation. Workup for glomerulonephritis and vasculitis was negative. He was initiated on renal replacement therapy, and a kidney biopsy showed severe acute tubular injury with positive myoglobin casts. Supportive management and renal replacement therapy was provided, and renal function spontaneously improved after a few weeks. This is an uncommon clinical presentation of severe rhabdomyolysis complicated by AKI. This suggests that CPK alone may not be a sensitive marker for rhabdomyolysis-induced AKI in some cases. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.
Adler, S; Baker, P; Pritzl, P; Couser, W G
1985-07-01
Reduction of the negative charge of the glomerular capillary wall alters its charge- and size-selective properties. To investigate the effect of alteration in glomerular charge properties on antibody localization, we prepared cationic and anionic fractions of antibodies to subepithelial and glomerular basement membrane (GBM) antigens, and compared their deposition in normal rats and rats treated with protamine sulfate or aminonucleoside of puromycin to reduce capillary wall charge. IgG antibodies were eluted from kidneys of rats with active Heymann's nephritis (AICN), passive Heymann's nephritis (PHN), or anti-GBM nephritis (NTN), separated into cationic and anionic fractions, and radiolabeled with iodine 125 or iodine 131. Relative antibody content of each fraction was determined by incubation with an excess of glomerular antigen. Varying amounts of cationic and anionic IgG eluted from kidneys of rats with AICN or PHN were injected into 24 normal or protamine sulfate-treated rats. Glomerular binding of all antibodies was highly correlated with IgG delivery to the kidney. The ratio of cationic to anionic antibody deposited in the glomeruli of normal rats after 4 hours was 1.08 +/- 0.07 for AICN eluate and 0.37 +/- 0.04 for PHN eluate. The ratios were not significantly different in animals pretreated with protamine sulfate (1.15 +/- 0.06 and 0.44 +/- 0.06, respectively; P greater than 0.05). Varying amounts of cationic and anionic IgG eluted from kidneys of rats with NTN were injected into 10 normal rats and four rats treated with aminonucleoside of puromycin. Glomerular binding of antibody was again highly correlated with IgG delivery to the kidney. The ratio of cationic to anionic antibody deposited in the glomeruli of normal rats after 1 hour was 1.03 +/- 0.06, and was not significantly altered in rats treated with aminonucleoside of puromycin (1.05 +/- 0.03, P greater than 0.5). Proteinuria in PHN rats was also unaffected by treatment with protamine sulfate for 5 days (controls: 68 +/- 21 mg/day; protamine sulfate-treated: 65 +/- 14 mg/day; n = 25, P greater than 0.08). These results demonstrate that treatment to reduce glomerular polyanion does not significantly alter the ratio of cationic to anionic antibodies to fixed glomerular antigens that deposit in the glomerulus, or reduce proteinuria caused by deposition of antibody to a fixed subepithelial antigen.
Wang, He; Dou, Ke-feng; Yang, Xiao-jian; Qin, Wei-jun; Zhang, Geng; Yu, Lei; Kang, Fu-xia; Chen, Shao-yang; Xiong, Li-ze; Song, Zhen-shun; Liu, Zheng-cai
2006-09-12
To study the effect of triple organ transplantation (liver, kidney, and pancreas) in patient of end-stage liver disease with renal failure and diabetes, and to explore the optimal surgical procedure. Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation was performed on a 43-year-old male patient with exocrine pancreatic insufficiency and insulin-dependent diabetes related to chronic pancreatitis (CP) who developed hepatic and renal failure. The pancreatic exocrine secretions were drained enterically to the jejunum. Prednisone, tacrolimus, mycophenolate mofetil, and ATG were used as immunosuppression therapy. Good liver and pancreas allograft function recovery was achieved within 7 days after the operation. And the recovery of renal allograft function was delayed. The renal allograft was removed because of break-down of renal blood flow 16 days after the transplantation. A new renal transplantation was performed at the same position. The second kidney graft recovered its normal function 3 days later. Up to the writing of this paper no acute rejection of organs and such complications as pancreatitis, thrombosis, and localized infection occurred. The patient became insulin independent with normal liver and renal function. Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation can be a good method for the patients with exocrine pancreatic insufficiency and insulin-dependent diabetes combined with hepatic and renal failure.
Notoginsenoside R1 attenuates renal ischemia-reperfusion injury in rats.
Liu, Wen-Jun; Tang, Hong-Tai; Jia, Yi-Tao; Ma, Bing; Fu, Jin-Feng; Wang, Yu; Lv, Kai-Yang; Xia, Zhao-Fan
2010-09-01
Ischemia-reperfusion (I/R) injury of the kidney is a complex pathophysiological process and a major cause of acute renal failure. It has been shown that I/R injury is related to inflammatory responses and activation of apoptotic pathways. Inhibition of certain elements of inflammatory responses and apoptotic pathway seemed to ameliorate renal I/R injury. As an effective element of Panax notoginseng, NR1 has antioxidant, anti-inflammatory, antiapoptotic, and immune-stimulatory activities. Therefore, we speculate that NR1 can attenuate renal I/R injury. Ischemia-reperfusion injury was induced by renal pedicle ligation followed by reperfusion along with a contralateral nephrectomy. Male Sprague-Dawley rats were randomized to four groups: sham group, I/R control group, NR1-1 group (rats treated with NR1, 20 mg.kg.d) and NR1-2 group (rats treated with NR1, 40 mg.kg.d). All animals were killed 72 h after I/R induction. Blood and renal tissues were collected. Renal dysfunction was observed by the level of serum creatinine and histological evaluation. Apoptosis and inflammatory response in the tissue of kidney were detected mainly with molecular biological methods. NR1 attenuated I/R-induced renal dysfunction as indicated by the level of serum creatinine and histological evaluation. It prevented the I/R-induced increases in the levels of proinflammatory cytokine TNF-alpha, myeloperoxidase activity, phosphorylation of p38, and activation of nuclear factor kappaB with cell apoptosis in the kidney and enhanced expression of antiapoptosis cytokine bcl-2. Treatment with NR1 improves renal function after I/R associated with a significant reduction in cell apoptosis and inflammatory responses, which may be related to p38 and nuclear factor kappaB inhibition.
Darwish, Mostafa A; Abo-Youssef, Amira M; Khalaf, Marwa M; Abo-Saif, Ali A; Saleh, Ibrahim G; Abdelghany, Tamer M
2018-06-15
Cisplatin (CP) is a widely used drug in treatment of solid tumors. However, the use of CP was hampered by its serious side effects especially nephrotoxicity. This study aims to investigate the effect of resveratrol (RES) on CP-induced nephrotoxicity, particularly, the effect of RES on CP pharmacokinetics (PKs). Male white albino rats were divided to four group's six rats each. The first group received (1%) tween 80 in normal saline and served as control. The second group received RES (30 mg kg -1 ) per day for 14 consecutive day's i.p. The third and fourth groups were given a single i.p. injection of CP (6 mg kg -1 ) with or without pre-treatment of RES (30 mg kg -1 per day for 14 consecutive days), respectively. Following administration of CP, plasma, urine and kidney platinum concentration were monitored to study PKs of CP. Five days after the CP injection, rats were killed; blood samples were collected; kidneys were dissected; and biochemical, immunohistochemical, and histological examinations were performed. Our results revealed that CP treatment significantly deteriorated kidney functions with subsequent alteration in redox balance of the kidney. On the other hand, RES successfully ameliorated CP-induced kidney injury and recovered normal kidney tissue redox status. Importantly, while RES pre-treatment did not significantly alter the plasma CP level, it dramatically decreased the urine concentration of CP and lowered its accumulation into the kidneys. Moreover, it increased CP plasma half-life (t 1/2 ) with subsequent decrease in its elimination rate constant, indicating an important role of PKs modulation in RES protection against CP-induced renal damage. Taken together, RES may protect the kidney tissue from the deleterious effects of CP through constringe of CP renal accumulation and enhancement of CP-induced oxidative stress. Copyright © 2018 Elsevier B.V. All rights reserved.
Chattopadhyay, Saurabh; Kessler, Sean P; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C
2014-01-01
Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE.
Chattopadhyay, Saurabh; Kessler, Sean P.; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C.
2014-01-01
Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE. PMID:24475296
Gap junctions favor normal rat kidney epithelial cell adaptation to chronic hypertonicity.
Desforges, Bénédicte; Savarin, Philippe; Bounedjah, Ouissame; Delga, Stéphanie; Hamon, Loïc; Curmi, Patrick A; Pastré, David
2011-09-01
Upon hypertonic stress most often resulting from high salinity, cells need to balance their osmotic pressure by accumulating neutral osmolytes called compatible osmolytes like betaine, myo-inositol, and taurine. However, the massive uptake of compatible osmolytes is a slow process compared with other defense mechanisms related to oxidative or heat stress. This is especially critical for cycling cells as they have to double their volume while keeping a hospitable intracellular environment for the molecular machineries. Here we propose that clustered cells can accelerate the supply of compatible osmolytes to cycling cells via the transit, mediated by gap junctions, of compatible osmolytes from arrested to cycling cells. Both experimental results in epithelial normal rat kidney cells and theoretical estimations show that gap junctions indeed play a key role in cell adaptation to chronic hypertonicity. These results can provide basis for a better understanding of the functions of gap junctions in osmoregulation not only for the kidney but also for many other epithelia. In addition to this, we suggest that cancer cells that do not communicate via gap junctions poorly cope with hypertonic environments thus explaining the rare occurrence of cancer coming from the kidney medulla.
Pencil Beam Scanning Proton Therapy for Rhabdomyosarcoma of the Biliary Tract.
Pater, Luke; Turpin, Brian; Mascia, Anthony
2017-10-05
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood with 250-350 cases diagnosed annually in the United States. Biliary tract rhabdomyosarcoma is rare, representing <1% of the RMS cases. Due to its location, resection is clinically challenging, and functional complications exist and persist from biliary obstruction. The anatomical location of this tumor presents both opportunities and challenges for pencil beam scanning proton therapy. Proton therapy offers a dosimetric and clinical advantage by sparing the healthy liver, stomach, contra-lateral kidney and bowel. Motion management and anatomical variations, such as intestinal filling or weight loss, requiring routine dosimetric evaluation and possible adaptive treatment planning, present challenges for the use of proton therapy. By taking advantage of the superior dose distribution of proton radiation, assessing the impact of tumor and anatomy motion, and performing regular dose evaluations, biliary tract RMS is an ideal diagnosis for pencil beam scanning proton therapy.
Correlation of Fos expression and circling asymmetry during gerbil vestibular compensation
NASA Technical Reports Server (NTRS)
Kaufman, G. D.; Shinder, M. E.; Perachio, A. A.
1999-01-01
Vestibular compensation is a central nervous system process resulting in recovery of functional movement and control following a unilateral vestibular lesion. Small pressure injections of phosphorothioate 20mer oligonucleotides were used to probe the role of the Fos transcription protein during vestibular compensation in the gerbil brainstem. During isoflurane gas anesthesia, antisense probes against the c-fos mRNA sequence were injected into the medial vestibular and prepositus nuclei unilaterally prior to a unilateral surgical labyrinthectomy. Anionic dyes, which did not interact with the oligonucleotides, were used to mark the injection site and help determine the extent of diffusion. The antiFos oligonucleotide injections reduced Fos expression at the injection site in neurons which normally express Fos after the lesion, and also affected circling behavior induced by hemilabyrinthectomy. With both ipsilateral and contralateral medial vestibular and prepositus nuclei injections, less ipsilateral and more contralateral circling was noted in animals injected with antiFos injections as compared to non-injected controls. The degree of change in these behaviors was dependent upon the side of the injection. Histologically, antiFos injections reduced the number of Fos immunolabeled neurons around the injection site, and increased Fos expression contralaterally. The correlation of the number of neurons with Fos expression to turning behavior was stronger for contralateral versus ipsilateral turns, and for neurons in the caudal and ipsilateral sub-regions of the medial vestibular and prepositus nuclei. The results are discussed in terms of neuronal firing activity versus translational activity based on the asymmetrical expression of the Fos inducible transcription factor in the medial vestibular and prepositus nuclei. Although ubiquitous in the brain, transcription factors like Fos can serve localized and specific roles in sensory-specific adaptive stimuli. Antisense injections can be an effective procedure for localized intervention into complex physiological functions, e.g. vestibular compensation. Copyright 1999 Elsevier Science B.V.
Mathew, L; Castillo, R; Castillo, E; Yaremko, B; Rodrigues, G; Etemad-Rezai, R; Guerrero, T; Parraga, G
2012-07-01
Dynamic imaging methods such as four-dimensional computed tomography (4DCT) and static imaging methods such as noble gas magnetic resonance imaging (MRI) deliver direct and regional measurements of lung function even in lung cancer patients in whom global lung function measurements are dominated by tumour burden. The purpose of this study was to directly compare quantitative measurements of gas distribution from static hyperpolarized 3 He MRI and dynamic 4DCT in a small group of lung cancer patients. MRI and 4DCT were performed in 11 subjects prior to radiation therapy. MRI was performed at 3.0T in breath-hold after inhalation 1L of hyperpolarized 3 He gas. Gas distribution in 3 He MRI was quantified using a semi-automated segmentation algorithm to generate percent-ventilated volume (PVV), reflecting the volume of gas in the lung normalized to the thoracic cavity volume. 4DCT pulmonary function maps were generated using deformable image registration of six expiratory phase images. The correspondence between identical tissue elements at inspiratory and expiratory phases was used to estimate regional gas distribution and PVV was quantified from these images. After accounting for differences in lung volumes between 3 He MRI (1.9±0.5L ipsilateral, 2.3±0.7 contralateral) and 4DCT (1.2±0.3L ipsilateral, 1.3±0.4L contralateral) during image acquisition, there was no statistically significant difference in PVV between 3 He MRI (72±11% ipsilateral, 79±12% contralateral) and 4DCT (74±3% ipsilateral, 75±4% contralateral). Our results indicate quantitative agreement in the regional distribution of inhaled gas in both static and dynamic imaging methods. PVV may be considered as a regional surrogate measurement of lung function or ventilation. © 2012 American Association of Physicists in Medicine.
Burkhardt, Jan-Karl; Winkler, Ethan A; Lawton, Michael T
2017-07-21
OBJECTIVE Deep medial parietooccipital arteriovenous malformations (AVMs) and cerebral cavernous malformations (CCMs) are traditionally resected through an ipsilateral posterior interhemispheric approach (IPIA), which creates a deep, perpendicular perspective with limited access to the lateral margins of the lesion. The contralateral posterior interhemispheric approach (CPIA) flips the positioning, with the midline positioned horizontally for retraction due to gravity, but with the AVM on the upper side and the approach from the contralateral, lower side. The aim of this paper was to analyze whether the perpendicular angle of attack that is used in IPIA would convert to a parallel angle of attack with the CPIA, with less retraction, improved working angles, and no significant increase in risk. METHODS A retrospective review of pre- and postoperative clinical and radiographic data was performed in 8 patients who underwent a CPIA. RESULTS Three AVMs and 5 CCMs were resected using the CPIA, with an average nidus size of 2.3 cm and CCM diameter of 1.7 cm. All lesions were resected completely, as confirmed on postoperative catheter angiography or MRI. All patients had good neurological outcomes, with either stable or improved modified Rankin Scale scores at last follow-up. CONCLUSIONS The CPIA is a safe alternative approach to the IPIA for deep medial parietooccipital vascular malformations that extend 2 cm or more off the midline. Contralaterality and retraction due to gravity optimize the interhemispheric corridor, the surgical trajectory to the lesion, and the visualization of the lateral margin, without resection or retraction of adjacent normal cortex. Although the falx is a physical barrier to accessing the lesion, it stabilizes the ipsilateral hemisphere while gravity delivers the dissected lesion through the transfalcine window. Patient positioning, CSF drainage, venous preservation, and meticulous dissection of the deep margins are critical to the safety of this approach.
Cerezo, Laura; Martín, Margarita; López, Mario; Marín, Alicia; Gómez, Alberto
2009-01-01
Background In head and neck cancer, bilateral neck irradiation is the standard approach for many tumor locations and stages. Increasing knowledge on the pattern of nodal invasion leads to more precise targeting and normal tissue sparing. The aim of the present study was to evaluate the morbidity and tumor control for patients with well lateralized squamous cell carcinomas of the oral cavity and oropharynx treated with ipsilateral radiotherapy. Methods Twenty consecutive patients with lateralized carcinomas of the oral cavity and oropharynx were treated with a prospective management approach using ipsilateral irradiation between 2000 and 2007. This included 8 radical oropharyngeal and 12 postoperative oral cavity carcinomas, with Stage T1-T2, N0-N2b disease. The actuarial freedom from contralateral nodal recurrence was determined. Late xerostomia was evaluated using the European Organization for Research and Treatment of Cancer QLQ-H&N35 questionnaire and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3. Results At a median follow-up of 58 months, five-year overall survival and loco-regional control rates were 82.5% and 100%, respectively. No local or contralateral nodal recurrences were observed. Mean dose to the contralateral parotid gland was 4.72 Gy and to the contralateral submandibular gland was 15.30 Gy. Mean score for dry mouth was 28.1 on the 0-100 QLQ-H&N35 scale. According to CTCAE v3 scale, 87.5% of patients had grade 0-1 and 12.5% grade 2 subjective xerostomia. The unstimulated salivary flow was > 0.2 ml/min in 81.2% of patients and 0.1-0.2 ml/min in 19%. None of the patients showed grade 3 xerostomia. Conclusion In selected patients with early and moderate stages, well lateralized oral and oropharyngeal carcinomas, ipsilateral irradiation treatment of the primary site and ipsilateral neck spares salivary gland function without compromising loco-regional control. PMID:19723329
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ding, Chuxiong; Chun, Stephen G.; Sumer, Baran D.
The purpose of this study was to commission and clinically test a robotic stereotactic delivery system (CyberKnife, Sunnyvale, CA) to treat early-stage glottic laryngeal cancer. We enrolled 15 patients with cTis-T2N0M0 carcinoma of the glottic larynx onto an institutional review board (IRB)-approved clinical trial. Stereotactic body radiotherapy (SBRT) plans prescribed 45 Gy/10 fractions to the involved hemilarynx. SBRT dosimetry was compared with (1) standard carotid-sparing laryngeal intensity-modulated radiation therapy (IMRT) and (2) selective hemilaryngeal IMRT. Our results demonstrate that SBRT plans improved sparing of the contralateral arytenoid (mean 20.0 Gy reduction, p <0.001), ipsilateral carotid D{sub max} (mean 20.6 Gy reduction, p <0.001), contralateral carotidmore » D{sub max} (mean 28.1 Gy reduction, p <0.001), and thyroid D{sub mean} (mean 15.0 Gy reduction, p <0.001) relative to carotid-sparing IMRT. SBRT also modestly improved dose sparing to the contralateral arytenoid (mean 4.8 Gy reduction, p = 0.13) and spinal cord D{sub max} (mean 4.9 Gy reduction, p = 0.015) relative to selective hemilaryngeal IMRT plans. This “phantom-to-clinic” feasibility study confirmed that hypofractionated SBRT treatment for early-stage laryngeal cancer can potentially spare dose to adjacent normal tissues relative to current IMRT standards. Clinical efficacy and toxicity correlates continue to be collected through an ongoing prospective trial.« less
Lee, Sul A; Noel, Sanjeev; Sadasivam, Mohanraj; Allaf, Mohamad E; Pierorazio, Phillip M; Hamad, Abdel R A; Rabb, Hamid
2018-01-01
Kidney immune cells play important roles in pathogenesis of many diseases, including ischemia-reperfusion injury (IRI) and transplant rejection. While studying murine kidney T cells, we serendipitously identified a kidney mononuclear phagocytic cell (MPC) subset characterized by intermediate surface expression of CD45 and CD11b. These CD45intCD11bint MPCs were further identified as F4/80+MHCII+CX3CR1+Ly6C- cells, comprising ~17% of total CD45+ cells in normal mouse kidney (P < 0.01) and virtually absent from all other organs examined except the heart. Systemic clodronate treatment had more significant depletive effect on the CD45intCD11bint population (77.3%±5.9%, P = 0.03) than on CD45highCD11b+ population (14.8%±16.6%, P = 0.49). In addition, CD45intCD11bint MPCs had higher phagocytic function in the normal kidney (35.6%±3.3% vs. 24.1%±2.2%, P = 0.04), but lower phagocytic capacity in post-ischemic kidney (54.9%±1.0% vs. 67.8%±1.9%, P < 0.01) compared to the CD45highCD11b+ population. Moreover, the CD45intCD11bint population had higher intracellular production of the pro-inflammatory tumor necrosis factor (TNF)-α (58.4%±5.2% vs. 27.3%±0.9%, P < 0.001) after lipopolysaccharide (LPS) stimulation and lower production of the anti-inflammatory interleukin (IL)-10 (7.2%±1.3% vs. 14.9%±2.2%, P = 0.02) following kidney IRI, suggesting a functional role under inflammatory conditions. The CD45intCD11bint cells increased early after IRI, and then abruptly decreased 48h later, whereas CD45highCD11b+ cells steadily increased after IRI before declining at 72h (P = 0.03). We also identified the CD45intCD11bint MPC subtype in human kidney. We conclude that CD45intCD11bint F4/80+MHCII+CX3CR1+Ly6C-population represent a unique subset of MPCs found in both mouse and human kidneys. Future studies will further characterize their role in kidney health and disease.
Shi, Xiaolei; Peng, Yonghan; Li, Ling; Li, Xiao; Wang, Qi; Zhang, Wei; Dong, Hao; Shen, Rong; Lu, Chaoyue; Liu, Min; Gao, Xiaofeng; Sun, Yinghao
2018-05-26
To evaluate renal function changes and risk factors for acute kidney injury (AKI) after percutaneous nephrolithotomy (PCNL) in patients with renal calculi with a solitary kidney (SK) or normal bilateral kidneys (BKs). Between 2012 and 2016, 859 patients undergoing PCNL were retrospectively reviewed at Changhai Hospital. In all, 53 patients with a SK were paired with 53 patients with normal BKs via a propensity score-matched analysis. Data for the following variables were collected: age, sex, body mass index, stone size, distribution, operation time, perioperative outcomes, and complications. The complications were graded according to the modified Clavien-Dindo system. Univariable and multivariable logistic regression models were constructed to evaluate risk factors for predicting AKI. The SK and BKs groups were comparable in terms of age, sex ratio, stone size, stone location distribution, comorbidities, and American Society of Anesthesiologists Physical Status classification. The initial and final stone-free rates were comparable between the SK and BKs groups (initial: 52.83% vs 58.49%, P = 0.696; final: 84.91% vs 92.45%, P = 0.359). There was no difference between the two groups for complications, according to the Clavien-Dindo grades. The estimated glomerular filtration rate (eGFR) increased dramatically after the stone burden was immediately relieved, and during the 6-month follow-up eGFR was lower in the SK group compared with the BKs group. We found a modest improvement in renal function immediately after PCNL in the BKs group, and renal function gain was delayed in the SK group. Through logistic regression analysis, we discovered that a SK, preoperative creatinine and diabetes were independent risk factors for predicting AKI after PCNL. Considering the overall complication rates, PCNL is generally a safe procedure for treating renal calculi amongst patients with a SK or normal BKs. Follow-up renal function analysis showed a modest improvement in patients of both groups. Compared to patients with normal BKs, patients with a SK were more likely to develop AKI after PCNL. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.
Yılmaz, Taner; Süslü, Nilda; Atay, Gamze; Günaydın, Rıza Önder; Bajin, Münir Demir; Özer, Serdar
2015-05-01
The degree of midline crossing of lateral supraglottic cancer does not significantly change its rate of contralateral cervical metastasis. The rate of occult metastasis is too high to take the risk of contralateral regional recurrence. We support routine bilateral neck dissection even in lateral supraglottic cancers with no or minimal midline crossing. Data on the rate of contralateral cervical metastasis of laterally located supraglottic cancer, the effect of its degree of midline crossing on contralateral cervical metastasis, and its treatment are still controversial. This was a retrospective cohort, chart review involving 305 surgically treated patients with T1-3 squamous cell carcinoma of the supraglottic larynx. In all, 184 patients had bilateral neck dissection; 86 N0 contralateral necks were followed up. Thirty-five patients who needed postoperative radiation therapy because of the primary tumor or ipsilateral neck dissection specimen also received radiation therapy to the contralateral neck. The degree of midline crossing at the epiglottis was measured on a laryngectomy specimen with a ruler and expressed as 'no,' '<5 mm' or '≥5 mm.' The rates of occult and overall contralateral metastasis in our series were 16% and 28%, respectively. There was no statistically significant difference between contralateral neck metastasis and recurrence rates in the neck dissection, follow-up, and irradiation groups according to the degree of midline crossing.
Study of Methylene Blue Ototoxicity in the Guinea Pig.
Belhassen, Sarah; Alzahrani, Musaed; Nader, Marc-Elie; Gaboury, Louis; Saliba, Issam
2017-11-01
Methylene blue is widely used in the medical field, especially as a blue dye for staining. It is also used as a photosensitizing agent in antimicrobial photodynamic therapy, which once photoactivated is effective for the eradication of several multi-resistant bacteria. The objective of this study was to investigate the ototoxic potential of methylene blue and precise its use in otology. It was a prospective animal study performed on guinea pigs in our tertiary medical center. We divided the animals into two groups: an experimental group and a control group, who underwent a series of three intratympanic (IT) injections. In the control group (n = 10), they received injections of gentamicin in one ear (positive control) and normal saline in the contralateral ear (negative control). The experimental group (n = 10) received injections of methylene blue in one ear, compared to injections of normal saline in the contralateral ear. We conducted auditory-evoked brainstem response (ABR) before and 1 week after the injection series. Once this is completed, the cochlea was dissected and caspase-3 was analyzed by immunohistochemistry. The mean difference of hearing loss in the methylene blue group compared to normal saline was 1.50 dB, and it was not shown to be statistically significant (P = 0.688). For the positive control group, which received IT injections of gentamicin, the mean threshold of hearing loss difference for all the frequencies combined was 66.25 dB (P < 0.001). Furthermore, uptake of caspase-3 by immunohistochemistry (apoptotic marker) was negative in our group, which received injections of methylene blue. In light of our results, IT injections of methylene blue did not demonstrate an ototoxic potential. We recommend further studies to precise its use in the otologic field.
Whisker motor cortex reorganization after superior colliculus output suppression in adult rats.
Veronesi, Carlo; Maggiolini, Emma; Franchi, Gianfranco
2013-10-01
The effect of unilateral superior colliculus (SC) output suppression on the ipsilateral whisker motor cortex (WMC) was studied at different time points after tetrodotoxin and quinolinic acid injections, in adult rats. The WMC output was assessed by mapping the movement evoked by intracortical microstimulation (ICMS) and by recording the ICMS-evoked electromyographic (EMG) responses from contralateral whisker muscles. At 1 h after SC injections, the WMC showed: (i) a strong decrease in contralateral whisker sites, (ii) a strong increase in ipsilateral whisker sites and in ineffective sites, and (iii) a strong increase in threshold current values. At 6 h after injections, the WMC size had shrunk to 60% of the control value and forelimb representation had expanded into the lateral part of the normal WMC. Thereafter, the size of the WMC recovered, returning to nearly normal 12 h later (94% of control) and persisted unchanged over time (1-3 weeks). The ICMS-evoked EMG response area decreased at 1 h after SC lesion and had recovered its baseline value 12 h later. Conversely, the latency of ICMS-evoked EMG responses had increased by 1 h and continued to increase for as long as 3 weeks following the lesion. These findings provide physiological evidence that SC output suppression persistently withdrew the direct excitatory drive from whisker motoneurons and induced changes in the WMC. We suggest that the changes in the WMC are a form of reversible short-term reorganization that is induced by SC lesion. The persistent latency increase in the ICMS-evoked EMG response suggested that the recovery of basic WMC excitability did not take place with the recovery of normal explorative behaviour. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Little, W B; Jean, G St; Sithole, F; Little, E; Jean, K Yvorchuk-St
2016-06-01
The use of corneal anaesthesia is necessary for a range of clinical purposes. Therefore, we assessed and compared the efficacy of corneal anaesthesia after application of 0.4% oxybuprocaine hydrochloride and 0.5% proparacaine hydrochloride ophthalmic solution in clinically normal cattle. The 24 clinically normal cows were allocated into two groups. Cows in group 1 (n = 12) received 0.2 mL of 0.4% oxybuprocaine hydrochloride with fluorescein ophthalmic solution in one eye and 0.2 mL of sterile saline (0.9% NaCl) with fluorescein in the contralateral eye (control). Group 2 (n = 12) received 0.2 mL of 0.4% oxybuprocaine hydrochloride with fluorescein ophthalmic solution in one eye and 0.2 mL of 0.5% proparacaine hydrochloride with fluorescein in the contralateral eye (control). In each group, corneal touch threshold was determined by Cochet-Bonnet aesthesiometer for both eyes immediately prior to topical administration of solutions, at 1 min and 5 min after administration of topical solutions and every 5 min thereafter for a total of 75 min. Significant corneal anaesthesia was noted immediately following topical application of both oxybuprocaine and proparacaine as compared with controls, with maximal corneal anaesthesia noted 1 min after administration. Both oxybuprocaine and proparacaine produced significant corneal anaesthesia for the duration of the 75-min study. Neither oxybuprocaine hydrochloride nor proparacaine hydrochloride treatment resulted in visible adverse effects. There are limited data available demonstrating the efficacy and duration of corneal anaesthetic agents in cattle. Both oxybuprocaine hydrochloride and proparacaine hydrochloride should be considered practical options for providing corneal anaesthesia in cattle in a clinical setting. © 2016 Australian Veterinary Association.
Study of Methylene Blue Ototoxicity in the Guinea Pig
Belhassen, Sarah; Alzahrani, Musaed; Nader, Marc-Elie; Gaboury, Louis; Saliba, Issam
2017-01-01
Background Methylene blue is widely used in the medical field, especially as a blue dye for staining. It is also used as a photosensitizing agent in antimicrobial photodynamic therapy, which once photoactivated is effective for the eradication of several multi-resistant bacteria. The objective of this study was to investigate the ototoxic potential of methylene blue and precise its use in otology. Methods It was a prospective animal study performed on guinea pigs in our tertiary medical center. We divided the animals into two groups: an experimental group and a control group, who underwent a series of three intratympanic (IT) injections. In the control group (n = 10), they received injections of gentamicin in one ear (positive control) and normal saline in the contralateral ear (negative control). The experimental group (n = 10) received injections of methylene blue in one ear, compared to injections of normal saline in the contralateral ear. We conducted auditory-evoked brainstem response (ABR) before and 1 week after the injection series. Once this is completed, the cochlea was dissected and caspase-3 was analyzed by immunohistochemistry. Results The mean difference of hearing loss in the methylene blue group compared to normal saline was 1.50 dB, and it was not shown to be statistically significant (P = 0.688). For the positive control group, which received IT injections of gentamicin, the mean threshold of hearing loss difference for all the frequencies combined was 66.25 dB (P < 0.001). Furthermore, uptake of caspase-3 by immunohistochemistry (apoptotic marker) was negative in our group, which received injections of methylene blue. Conclusion In light of our results, IT injections of methylene blue did not demonstrate an ototoxic potential. We recommend further studies to precise its use in the otologic field. PMID:29038666
Three-dimensional shoulder kinematics normalize after rotator cuff repair.
Kolk, Arjen; de Witte, Pieter Bas; Henseler, Jan Ferdinand; van Zwet, Erik W; van Arkel, Ewoud R A; van der Zwaal, Peer; Nelissen, Rob G H H; de Groot, Jurriaan H
2016-06-01
Patients with a rotator cuff (RC) tear often exhibit scapular dyskinesia with increased scapular lateral rotation and decreased glenohumeral elevation with arm abduction. We hypothesized that in patients with an RC tear, scapular lateral rotation, and thus glenohumeral elevation, will be restored to normal after RC repair. Shoulder kinematics were quantitatively analyzed in 26 patients with an electromagnetic tracking device (Flock of Birds) before and 1 year after RC repair in this observational case series. We focused on humeral range of motion and scapular kinematics during abduction. The asymptomatic contralateral shoulder was used as the control. Changes in scapular kinematics were associated with the gain in range of motion. Shoulder kinematics were analyzed using a linear mixed model. Mean arm abduction and forward flexion improved after surgery by 20° (95% confidence interval [CI], 2.7°-36.5°; P = .025) and 13° (95% CI, 1.2°-36.5°; P = .044), respectively. Kinematic analyses showed decreases in mean scapular protraction (ie, internal rotation) and lateral rotation (ie, upward rotation) during abduction by 3° (95% CI, 0.0°-5.2°; P = .046) and 4° (95% CI, 1.6°-8.4°; P = .042), respectively. Glenohumeral elevation increased by 5° (95% CI, 0.6°-9.7°; P = .028) at 80°. Humeral range of motion increased when scapular lateral rotation decreased and posterior tilt increased. Scapular kinematics normalize after RC repair toward a symmetrical scapular motion pattern as observed in the asymptomatic contralateral shoulder. The observed changes in scapular kinematics are associated with an increased overall range of motion and suggest restored function of shoulder muscles. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.
Liu, Lihua; Long, Miaomiao; Wang, Junping; Liu, Ning; Ge, Xihong; Hu, Zhandong; Shen, Wen
2015-02-01
Puerperal breast abscess after polyacrylamide hydrogel (PAAG) augmentation mammoplasty can induce breast auto-inflation resulting in serious consequences. Mammography, ultrasound, and conventional MRI are poor at detecting related PAAG abnormality histologically. We evaluated the value of diffusion-weighted imaging (DWI) in the quantitative analysis of puerperal PAAG abscess after augmentation mammoplasty. This was a retrospective study, and a waiver for informed consent was granted. Sixteen puerperal women with breast discomfort underwent conventional breast non-enhanced MRI and axial DWI using a 3T MR scanner. Qualitative analysis of the signal intensity on DWI and conventional sequences was performed. The apparent diffusion coefficient (ADC) values of the affected and contralateral normal PAAG cysts were measured quantitatively. Paired t test was used to evaluate whether there was significant difference. Both affected and normal PAAG cysts showed equal signal intensity on conventional T1WI and fat saturation T2WI, which were not helpful in detecting puerperal PAAG abscess. However, the affected PAAG cysts had a significantly decreased ADC value of 1.477 ± 0.332 × 10(-3)mm(2)/s and showed obvious hypo-intensity on the ADC map and increased signal intensity on DWI compared with the ADC value of 2.775 ± 0.233 × 10(-3)mm(2)/s of the contralateral normal PAAG cysts. DWI and quantitative measurement of ADC values are of great value for the diagnosis of puerperal PAAG abscess. Standardized MRI should be suggested to these puerperal women with breast discomfort or just for the purpose of check up. DWI should be selected as the essential MRI sequence.
Stratum corneum integrity as a predictor for peristomal skin problems in ostomates.
Nybaek, H; Lophagen, S; Karlsmark, T; Bang Knudsen, D; Jemec, G B E
2010-02-01
Peristomal skin problems are common, most often the result is disruption of the skin barrier and this may account for more than one in three visits to ostomy nurses. Therefore a specific assessment of individual risk factors relating to the skin barrier function would be of great interest. Skin barrier integrity in ostomy patients with peristomal skin problems (PSP) was compared with that of ostomy patients with normal skin (controls) using transepidermal water loss (TEWL). Mechanical barrier disruption was determined by a tape stripping test and chemical barrier disruption [sodium lauryl sulphate (SLS) 0.25%]. Patients and controls had a highly significant increase in TEWL value in the peristomal area compared with nonperistomal contralateral abdominal skin (P < 0.0001 for both groups). The skin barrier of normal-looking contralateral skin of ostomates was found to be borderline impaired in patients with PSP compared with those without. A linear association was seen between the number of tape strips removed and TEWL for both cases and controls. Tape stripping suggested that patients with PSP had less resilient skin (P = 0.002). A significant difference in TEWL value between cases and controls was also seen for the SLS patch test on the dorsal skin (P = 0.02). Successive tape stripping, a situation analogous to the normal use of a pouching system, caused a higher degree of barrier damage more rapidly in patients with PSP, indicating an impaired mechanical quality of the barrier. The SLS exposure test suggested a generally increased susceptibility to irritant dermatitis as assessed by TEWL. Our findings suggest tape stripping and SLS testing may have a role as predictive tests to identify patients at risk of PSP.
Li, Hai; Liu, Jianbin; Feng, Xiujuan; Liu, Liehua; Wei, Guohong; Cao, Xiaopei; Li, Yanbing
2017-12-01
To test the efficacy of a strategy based on CT imaging and clinical characteristics on lateralizing origin of excess aldosterone secretion in primary aldosteronism. Consecutive patients with diagnosed primary hyperaldosteronism from June 2006 to July 2012 in our center underwent adrenal surgeries without pre-operational adrenal venous sampling (AVS) if all the three criteria were met: (1) round- or oval-shaped occupational lesion of low density after contrast enhancement with diameter >1 cm on CT scan was located in one adrenal gland; (2) unequivocally normal contralateral adrenal gland; (3) serum potassium level lower than 3.5 mmol/L. Subjects who had received operation were taken into analysis and follow-ups. One hundred and twenty-five patients fulfilled the criteria and were recruited into our research. One hundred and twenty-two operated patients (97.6%) experienced complete resolution of hypokalemia as well as resolution or improvement in hypertension with reduction in antihypertensive medication, while 3 patients (2.4%) failed to obtain normal kalemia and continued on spironolactone therapy. At a median of 65-month (range 21-93) follow-up of these 122 subjects, 27 patients dropped out (22.1%). The 95 responding patients reported no episodes of paralysis or confirmed hypokalemia or any supplementation of potassium. Multivariate linear correlation analysis showed that plasma potassium level was correlated inversely with tumor diameter (r = -0.258, 95% CI -0.076, -0.514, p = 0.037) and basal plasma aldosterone level (r = -0.251, 95% CI -0.040, -0.464, p = 0.042). Most patients with typical unilateral adrenal macroadenomas, normal contralateral glands and hypokalemia could attain favorable surgical therapeutic outcomes without pre-operational AVS lateralization.
Male infertility associated with adult dominant polycystic kidney disease: a case series.
Shefi, Shai; Levron, Jacob; Nadu, Andrei; Raviv, Gil
2009-09-01
Although described earlier, the association of male infertility with adult dominant polycystic kidney disease (ADPKD) is quite rare and unfamiliar to some of the multidisciplinary team members caring for affected men. Infertile men diagnosed to have ADPKD were evaluated by clinical characteristics including testis volume, as well as serum hormone levels, semen analysis, and transrectal ultrasonography (TRUS) because of low volume ejaculate. Semen analysis revealed low-normal volume, normal pH, and azoospermia/virtual azoospermia. Serum hormones were within the normal range. Transrectal ultrasonography demonstrated cystic dilatation of the seminal vesicles in all three men. Patients should be referred for andrological evaluation of a presentation similar to obstructive azoospermia. Their potential to achieve paternity by surgical sperm retrieval combined with assisted reproductive technology is another example of cooperation between andrologists and gynecologists.
Nas, Omer Fatih; Hacikurt, Kadir; Kaya, Ahmet; Dogan, Nurullah; Sanal, Bekir; Ozkaya, Guven; Dundar, Halit Ziya; Erdogan, Cuneyt
2017-06-01
To evaluate long-term clinical follow-up results of implanting subcutaneous port catheters (SPCs) on ipsilateral or contralateral with mastectomy side in patients with axillary lymph node dissection. A total of 73 patients composed of ipsilateral (34 catheters) and contralateral (39 catheters) groups, with SPCs were included. All patients had lumpectomy or modified radical mastectomy for breast cancer. Ipsilateral and contralateral groups had similar patient characteristics. Five late complications were seen in the ipsilateral group and 2 late complications in the contralateral group. No statistical significant difference was seen between two groups in regard to late complications. Four complications of the ipsilateral group were classified as major group C and 1 as major group D, while 1 complication of the contralateral group was classified as minor group B and 1 as major group C according to Society of Interventional Radiology (SIR) classification. No statistical significant difference was seen between complication rates of two groups in regard to SIR classification. SPC related complications do not differ in regard to ipsilateral or contralateral side selection on mastectomized patients with breast cancer and lymph node dissection. SPCs can be implanted on ipsilateral or contralateral sides of the operation in these patients.
Li, Hongjie; Wu, Xiaoyan; Bai, Yanrui; Huang, Yan; He, Wenting; Dong, Zhifang
2012-05-01
It is well documented that bilateral hippocampal lesions or unilateral hippocampal lesion at birth causes impairment of contralateral LTP and long-term memory. However, effects of unilateral hippocampal lesion in adults on contralateral in vivo LTP and memory are not clear. We here examined the influence of unilateral electrolytic dorsal hippocampal lesion in adult rats on contralateral LTP in vivo and spatial memory during different postoperative phases. We found that acute unilateral hippocampal lesion had no effect on contralateral LTP. However, contralateral LTP was impaired at 1 week after lesion, and was restored to the control level at postoperative week 4. Similarly, spatial memory was also impaired at postoperative week 1, and was restored at postoperative week 4. In addition, the rats at postoperative week 1 showed stronger spatial exploratory behavior in a novel open-field environment. The sham operation had no effects on contralateral LTP, spatial memory and exploration at either postoperative week 1 or week 4. These results suggest that unilateral dorsal hippocampal lesion in adult rats causes transient contralateral LTP impairment and spatial memory deficit. Copyright © 2012 Elsevier B.V. All rights reserved.
Hypertension in kidney transplantation is associated with an early renal nerve sprouting
Rovella, Valentina; Borri, Filippo; Anemona, Lucia; Giannini, Elena; Giacobbi, Erica; Saggini, Andrea; Palmieri, Giampiero; Anselmo, Alessandro; Bove, Pierluigi; Melino, Gerry; Valentina, Guardini; Tesauro, Manfredi; Gabriele, D’Urso; Di Daniele, Nicola
2017-01-01
Abstract Background. Normalization of arterial pressure occurs in just a few patients with hypertensive chronic kidney disease undergoing kidney transplantation. Hypertension in kidney transplant recipients may be related to multiple factors. We aimed to assess whether hypertension in kidney-transplanted patients may be linked to reinnervation of renal arteries of the transplanted kidney. Methods. We investigated renal arteries innervation from native and transplanted kidneys in three patients 5 months, 2 years and 11 years after transplantation, respectively. Four transplanted kidneys from non-hypertensive patients on immunosuppressive treatment without evidence of hypertensive arteriolar damage were used as controls. Results. Evidence of nerve sprouting was observed as early as 5 months following transplantation, probably originated from ganglions of recipient patient located near the arterial anastomosis and was associated with mild hypertensive arteriolar damage. Regeneration of periadventitial nerves was already complete 2 years after transplantation. Nerve density tended to reach values observed in native kidney arteries and was associated with hypertension-related arteriolar lesions in transplanted kidneys. Control kidneys, albeit on an immunosuppressive regimen, presented only a modest regeneration of sympathetic nerves. Conclusions. Our results suggest that the considerable increase in sympathetic nerves, as found in patients with severe arterial damage, may be correlated to hypertension rather than to immunosuppressive therapy, thus providing a morphological basis for hypertension recurrence despite renal denervation. PMID:28498963
Sittivarakul, Wantanee; Benjhawaleemas, Thanyapat; Aui-Aree, Nipat; Jirarattanasopa, Pichai; Liabsuetrakul, Tippawan
2016-10-01
To calculate the incidence of, and to identify the risk factors for developing contralateral eye involvement among patients with AIDS and unilateral cytomegalovirus retinitis (CMV retinitis), who were treated, in the era of highly-active antiretroviral therapy (HAART), with repetitive intravitreal ganciclovir injections. The clinical records of 119 patients were included. The main outcome measurement was the occurrence of contralateral eye involvement. Over a mean follow-up period of 1.6 years, the overall incidence rate of contralateral involvement was 0.17/person-year. The cumulative incidence of contralateral involvement at 6 months and 1 year was 23.8% and 28.4%, respectively. Receiving HAART at the visit before the event was associated with a decreased risk of developing contralateral retinitis (hazard ratio [HR] = 0.26, P = 0.002). The use of HAART, associated with subsequent immune recovery, significantly reduced the incidence of contralateral eye involvement by approximately 75% among patients in our setting.
Papsin, Blake C.; Paludetti, Gaetano; Gordon, Karen A.
2015-01-01
Children using unilateral cochlear implants abnormally rely on tempo rather than mode cues to distinguish whether a musical piece is happy or sad. This led us to question how this judgment is affected by the type of experience in early auditory development. We hypothesized that judgments of the emotional content of music would vary by the type and duration of access to sound in early life due to deafness, altered perception of musical cues through new ways of using auditory prostheses bilaterally, and formal music training during childhood. Seventy-five participants completed the Montreal Emotion Identification Test. Thirty-three had normal hearing (aged 6.6 to 40.0 years) and 42 children had hearing loss and used bilateral auditory prostheses (31 bilaterally implanted and 11 unilaterally implanted with contralateral hearing aid use). Reaction time and accuracy were measured. Accurate judgment of emotion in music was achieved across ages and musical experience. Musical training accentuated the reliance on mode cues which developed with age in the normal hearing group. Degrading pitch cues through cochlear implant-mediated hearing induced greater reliance on tempo cues, but mode cues grew in salience when at least partial acoustic information was available through some residual hearing in the contralateral ear. Finally, when pitch cues were experimentally distorted to represent cochlear implant hearing, individuals with normal hearing (including those with musical training) switched to an abnormal dependence on tempo cues. The data indicate that, in a western culture, access to acoustic hearing in early life promotes a preference for mode rather than tempo cues which is enhanced by musical training. The challenge to these preferred strategies during cochlear implant hearing (simulated and real), regardless of musical training, suggests that access to pitch cues for children with hearing loss must be improved by preservation of residual hearing and improvements in cochlear implant technology. PMID:26317976
Giannantonio, Sara; Polonenko, Melissa J; Papsin, Blake C; Paludetti, Gaetano; Gordon, Karen A
2015-01-01
Children using unilateral cochlear implants abnormally rely on tempo rather than mode cues to distinguish whether a musical piece is happy or sad. This led us to question how this judgment is affected by the type of experience in early auditory development. We hypothesized that judgments of the emotional content of music would vary by the type and duration of access to sound in early life due to deafness, altered perception of musical cues through new ways of using auditory prostheses bilaterally, and formal music training during childhood. Seventy-five participants completed the Montreal Emotion Identification Test. Thirty-three had normal hearing (aged 6.6 to 40.0 years) and 42 children had hearing loss and used bilateral auditory prostheses (31 bilaterally implanted and 11 unilaterally implanted with contralateral hearing aid use). Reaction time and accuracy were measured. Accurate judgment of emotion in music was achieved across ages and musical experience. Musical training accentuated the reliance on mode cues which developed with age in the normal hearing group. Degrading pitch cues through cochlear implant-mediated hearing induced greater reliance on tempo cues, but mode cues grew in salience when at least partial acoustic information was available through some residual hearing in the contralateral ear. Finally, when pitch cues were experimentally distorted to represent cochlear implant hearing, individuals with normal hearing (including those with musical training) switched to an abnormal dependence on tempo cues. The data indicate that, in a western culture, access to acoustic hearing in early life promotes a preference for mode rather than tempo cues which is enhanced by musical training. The challenge to these preferred strategies during cochlear implant hearing (simulated and real), regardless of musical training, suggests that access to pitch cues for children with hearing loss must be improved by preservation of residual hearing and improvements in cochlear implant technology.
SU-F-T-416: Dosimetric Comparison of Coplanar and Non-Coplanar IMRT Plans for Peripheral Lung Lesion
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kang, J; Zhang, S; Philbrook, S
2016-06-15
Purpose: The purpose of this study was to compare dosimetric parameters of treatment plans between coplanar and non-coplanar techniques for treating peripheral lung lesions. Methods: The planning CT scans of 6 patients in supine positions were used in this study. The size of the PTV ranges from 163 c.c. to 782 c.c.. The locations of PTV are mostly at the peripheral of Lung, some spreading to the mediastinum. For each patient, we generated two IMRT plans, one with and the other without non-coplanar beams. The non-coplanar beams were carefully selected so that the beams would never exit patient bodies throughmore » the contralateral lung. The IMRT plans were generated with Pinnacle 9.8 treatment planning software. The IMRT optimization objectives were kept the same for the corresponding pairs of plans. All plans were normalized such that 95% of PTV receives the prescription dose (full dose). Results: The conformity index (mean±standard deviation of the mean) is 1.49±0.14 and 1.58±0.23 for the coplanar and noncoplanar plans, respectively. The heterogeneity index (mean±standard deviation of the mean) is 7.74 ±2.33 and 6.34±1.40 for the coplanar and non-coplanar plans, respectively. The maximum heart dose is 60.94±6.22 and 60.42±7.21 Gy, and mean heart dose is 10.22 ±7.57, 9.07 ±6.32 Gy, for the coplanar and non-coplanar plans, respectively. The ipsilateral lung V20 is 48.0%±2.4% and 47.5%±3.3%, and V5 is 68.2%±10.0% and 69.1%±7.3%, for the coplanar and noncoplanar plans, respectively. Furthermore, with the non-coplanar beam arrangement, the contralateral lung V20 was reduced from 3.3%±3.7% to 1.3%±0.8%, and the contralateral Lung V5 is reduced significantly from 65.6%±9.3% to 33.5%±20.9% (p value =0.008). Conclusion: The IMRT plans with non-coplanar beam arrangement could reduce the exit dose to the contralateral lung, and therefore reduce the contralateral lung V5 significantly. This method is especially helpful while the lung lesion doesn’t have a symmetric shape.« less
Petras, Dimitrios; Koutroutsos, Konstantinos; Kordalis, Athanasios; Tsioufis, Costas; Stefanadis, Christodoulos
2013-08-01
The kidney has been shown to be critically involved as both trigger and target of sympathetic nervous system overactivity in both experimental and clinical studies. Renal injury and ischemia, activation of renin angiotensin system and dysfunction of nitric oxide system have been implicated in adrenergic activation from kidney. Conversely, several lines of evidence suggest that sympathetic overactivity, through functional and morphological alterations in renal physiology and structure, may contribute to kidney injury and chronic kidney disease progression. Pharmacologic modulation of sympathetic nervous system activity has been found to have a blood pressure independent renoprotective effect. The inadequate normalization of sympathoexcitation by pharmacologic treatment asks for novel treatment options. Catheter based renal denervation targets selectively both efferent and afferent renal nerves and functionally denervates the kidney providing blood pressure reduction in clinical trials and renoprotection in experimental models by ameliorating the effects of excessive renal sympathetic drive. This review will focus on the role of sympathetic overactivity in the pathogenesis of kidney injury and CKD progression and will speculate on the effect of renal denervation to these conditions.
First successful combined heart and kidney transplant in Iran: a case report.
Ahmadi, Zargham-Hossein; Mirhosseini, Seyed Mohsen; Fakhri, Mohammad; Mozaffary, Amirhossein; Lotfaliany, Mojtaba; Nejatollahi, Seyed Mohammad Reza; Marashi, Seyed-Ali; Behzadnia, Neda; Sharif-Kashani, Babak
2013-08-01
Combined heart and kidney transplant has become an accepted therapy for patients with coexisting heart and kidney failure. This method, compared with single-organ transplant, has a better outcome. Here, we report the first successful combined heart and kidney transplant in Iran. The patient was a 36-year-old man with end-stage renal disease owing to IgA nephropathy, admitted to Masih Daneshvari Hospital in Tehran, Iran for progressive dyspnea and chest pain. In-patient evaluations revealed cardiomyopathy leading to end-stage heart failure. Owing to concurrent heart and kidney end-stage diseases, combined cardiorenal transplant was done. Eight months after his transplant, routine follow-ups have not shown any signs of acute rejection. He is now New York Heart Association functional class I. Both cardiac and renal functions are within normal ranges. Good outcome during follow-up for this case justifies simultaneous heart plus kidney transplants as an alternate treatment for patients with advanced disease of both organs.
Snaebjörnsson, Thorkell; Hamrin Senorski, Eric; Sundemo, David; Svantesson, Eleonor; Westin, Olof; Musahl, Volker; Alentorn-Geli, Eduard; Samuelsson, Kristian
2017-12-01
The impact of different surgical techniques in index ACL reconstruction for patients undergoing contralateral ACL reconstruction was investigated. The study was based on data from the Swedish National Knee Ligament Register. Patients undergoing index ACL reconstruction and subsequent contralateral ACL reconstruction using hamstring graft under the study period were included. The following variables were evaluated: age at index surgery, gender, concomitant meniscal or cartilage injury registered at index injury, transportal femoral bone tunnel drilling and transtibial femoral bone tunnel drilling. The end-point of primary contralateral ACL surgery was analysed as well as the time-to-event outcomes using survivorship methods including Kaplan-Meier estimation and Cox proportional hazards regression models. A total of 17,682 patients [n = 10,013 males (56.6%) and 7669 females (43.4%)] undergoing primary ACL reconstruction from 1 January 2005 through 31 December 2014 were included in the study. A total of 526 (3.0%) patients [n = 260 males (49.4%) and 266 females (50.6%)] underwent primary contralateral ACL reconstruction after index ACL reconstruction during the study period. Females had a 33.7% greater risk of contralateral ACL surgery [HR 1.337 (95% CI 1.127-1.586); (P = 0 0.001)]. The youngest age group (13-15 years) showed an increased risk of contralateral ACL surgery compared with the reference (36-49) age group [HR 2.771 (95% CI 1.456-5.272); (P = 0.002)]. Decreased risk of contralateral ACL surgery was seen amongst patients with concomitant cartilage injury at index surgery [HR 0.765 (95% CI 0.623-0.939); (P = 0.010)]. No differences in terms of the risk of contralateral ACL surgery were found between anatomic and non-anatomic techniques of primary single-bundle ACL reconstruction, comparing transportal anatomic technique to transtibial non-anatomic, anatomic and partial-anatomic. Age and gender were identified as risk factors for contralateral ACL reconstruction; hence young individuals and females were more prone to undergo contralateral ACL reconstruction. Patients with concomitant cartilage injury at index ACL reconstruction had lower risk for contralateral ACL reconstruction. No significant differences between various ACL reconstruction techniques could be related to increased risk of contralateral ACL reconstruction. Retrospective Cohort Study, Level III.
Creatine pretreatment prevents birth asphyxia-induced injury of the newborn spiny mouse kidney.
Ellery, Stacey J; Ireland, Zoe; Kett, Michelle M; Snow, Rod; Walker, David W; Dickinson, Hayley
2013-02-01
Acute kidney injury (AKI) is a major complication for infants following an asphyxic insult at birth. We aimed to determine if kidney structure and function were affected in an animal model of birth asphyxia and if maternal dietary creatine supplementation could provide an energy reserve to the fetal kidney, maintaining cellular respiration during asphyxia and preventing AKI. Pregnant spiny mice were maintained on normal chow or chow supplemented with creatine from day 20 gestation. On day 38 (term ~39 d), pups were delivered by cesarean section (c-section) or subjected to intrauterine asphyxia. Twenty-four hours after insult, kidneys were collected for histological or molecular analysis. Urine and plasma were also collected for biochemical analysis. AKI was evident at 24 h after birth asphyxia, with a higher incidence of shrunken glomeruli (P < 0.02), disturbance to tubular arrangement, tubular dilatation, a twofold increase (P < 0.02) in expression of Ngal (early marker of kidney injury), and decreased expression of the podocyte differentiation marker nephrin. Maternal creatine supplementation prevented the glomerular and tubular abnormalities observed in the kidney at 24 h and the increased expression of Ngal. Maternal creatine supplementation may prove useful in ameliorating kidney injury associated with birth asphyxia.
Diagnosis of hyperthyroidism in cats with mild chronic kidney disease.
Wakeling, J; Moore, K; Elliott, J; Syme, H
2008-06-01
In cats with concurrent hyperthyroidism and non-thyroidal illnesses such as chronic kidney disease, total thyroxine concentrations are often within the laboratory reference range (19 to 55 nmol/l). The objective of the study was to determine total thyroxine, free thyroxine and/or thyroid-stimulating hormone concentrations in cats with mild chronic kidney disease. Total thyroxine, free thyroxine and thyroid-stimulating hormone were measured in three groups. The hyperthyroidism-chronic kidney disease group (n=16) had chronic kidney disease and clinical signs compatible with hyperthyroidism but a plasma total thyroxine concentration within the reference range. These cats were subsequently confirmed to be hyperthyroid at a later date. The chronic kidney disease-only group (n=20) had chronic kidney disease but no signs of hyperthyroidism. The normal group (n=20) comprised clinically healthy senior (>8 years) cats. In 4 of 20 euthyroid chronic kidney disease cats, free thyroxine concentrations were borderline or high (> or =40 pmol/l). In the hyperthyroidism-chronic kidney disease group, free thyroxine was high in 15 of 16 cats, while thyroid-stimulating hormone was low in 16 of 16 cats. Most hyperthyroidism-chronic kidney disease cats (14 of 16) had total thyroxine greater than 30 nmol/l, whereas all the chronic kidney disease-only cats had total thyroxine less than 30 nmol/l. The combined measurement of free thyroxine with total thyroxine or thyroid-stimulating hormone may be of merit in the diagnosis of hyperthyroidism in cats with chronic kidney disease.
RAAS-mediated Redox effects in Chronic Kidney Disease
Nistala, Ravi; Wei, Yongzhong; Sowers, James R; Whaley-Connell, Adam
2009-01-01
The renin-angiotensin-aldosterone-system (RAAS) is central to the pathogenesis of hypertension, cardiovascular and kidney disease. Emerging evidence support various pathways through which a local renal RAAS can affect kidney function, hypertension, and cardiovascular disease. A prominent mechanism appears to be loss of redox homeostasis and formation of excessive free radicals. Free radicals such as reactive oxygen species (ROS) are necessary in normal physiologic processes including development of nephrons, erythropoeisis and tubular sodium transport. However, loss of redox homeostasis contributes to pro-inflammatory and pro-fibrotic pathways in the kidney that in turn lead to reduced vascular compliance, podocyte pathology and proteinuria. Both blockade of the RAAS and oxidative stress produces salutary effects on hypertension and glomerular filtration barrier injury. Thus, the focus of current research is on understanding the pathophysiology of chronic kidney disease in the context of an elevated RAAS and unbalanced redox mechanisms. PMID:19218092
Kidney injury in a dog following bee sting-associated anaphylaxis
Buckley, Gareth James; Corrie, Christopher; Bandt, Carsten; Schaer, Michael
2017-01-01
This report describes a case of honeybee envenomation in a dog that developed anaphylaxis after being stung by approximately 10 bees. The dog subsequently developed acute kidney injury. The dog had a previous mild increase in blood urea nitrogen with normal creatinine, possibly indicating an insidious chronic renal degenerative process that went into acute decompensation at the time of bee envenomation. PMID:28246414
2012-01-01
Background Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. Methods/Design We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. Discussion Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. Trial registration Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18. PMID:22305183
Nava, Maurizio B; Rocco, Nicola; Catanuto, Giuseppe; Falco, Giuseppe; Capalbo, Emanuela; Marano, Luigi; Bordoni, Daniele; Spano, Andrea; Scaperrotta, Gianfranco
2015-08-01
The ultimate goal of breast reconstruction is to achieve symmetry with the contra-lateral breast. Contra-lateral procedures with wide parenchymal rearrangements are suspected to impair mammographic surveillance. This study aims to evaluate the impact on mammographic detection of mastopexies and breast reductions for contralateral adjustment in breast reconstruction. We retrospectively evaluated 105 women affected by uni-lateral breast cancer who underwent mastectomy and immediate two-stage reconstruction between 2002 and 2007. We considered three groups according to the contra-lateral reshaping technique: mastopexy or breast reduction with inferior dermoglandular flap (group 1); mastopexy or breast reduction without inferior dermoglandular flap (group 2); no contra-lateral reshaping (group 3). We assessed qualitative mammographic variations and breast density in the three groups. Statistically significant differences have been found when comparing reshaped groups with non reshaped groups regarding parenchymal distortions, skin thickening and stromal edema, but these differences did not affect cancer surveillance. The surveillance mammography diagnostic accuracy in contra-lateral cancer detection was not significantly different between the three groups (p = 0.56), such as the need for MRI for equivocal findings at mammographic contra-lateral breast (p = 0.77) and the need for core-biopsies to confirm mammographic suspect of contra-lateral breast cancer (p = 0.90). This study confirms previous reports regarding the safety of mastopexies and breast reductions when performed in the setting of contra-lateral breast reshaping after breast reconstruction. Mammographic accuracy, sensitivity and specificity are not affected by the glandular re-arrangement. These results provide a further validation of the safety of current reconstructive paradigms. Copyright © 2015 Elsevier Ltd. All rights reserved.
Rodriguez-Lorenzo, Andres; Audolfsson, Thorir; Wong, Corrine; Cheng, Angela; Arbique, Gary; Nowinski, Daniel; Rozen, Shai
2015-10-01
The aim of this study was to evaluate the contribution of a single unilateral facial vein in the venous outflow of total-face allograft using three-dimensional computed tomographic imaging techniques to further elucidate the mechanisms of venous complications following total-face transplant. Full-face soft-tissue flaps were harvested from fresh adult human cadavers. A single facial vein was identified and injected distally to the submandibular gland with a radiopaque contrast (barium sulfate/gelatin mixture) in every specimen. Following vascular injections, three-dimensional computed tomographic venographies of the faces were performed. Images were viewed using TeraRecon Software (Teracon, Inc., San Mateo, CA, USA) allowing analysis of the venous anatomy and perfusion in different facial subunits by observing radiopaque filling venous patterns. Three-dimensional computed tomographic venographies demonstrated a venous network with different degrees of perfusion in subunits of the face in relation to the facial vein injection side: 100% of ipsilateral and contralateral forehead units, 100% of ipsilateral and 75% of contralateral periorbital units, 100% of ipsilateral and 25% of contralateral cheek units, 100% of ipsilateral and 75% of contralateral nose units, 100% of ipsilateral and 75% of contralateral upper lip units, 100% of ipsilateral and 25% of contralateral lower lip units, and 50% of ipsilateral and 25% of contralateral chin units. Venographies of the full-face grafts revealed better perfusion in the ipsilateral hemifaces from the facial vein in comparison with the contralateral hemifaces. Reduced perfusion was observed mostly in the contralateral cheek unit and contralateral lower face including the lower lip and chin units. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
Study of Nephrotoxic Potential of Acetaminophen in Birds
Jayakumar, K.; Mohan, K.; Swamy, H. D. Narayana; Shridhar, N. B.; Bayer, M. D.
2010-01-01
The present study was designed to evaluate the effect of acetaminophen on kidneys of birds by comparison with diclofenac that is used as positive control. The birds of Group I served as negative control and received normal saline, whereas Group II birds received diclofenac injection (2.5 mg/kg IM) and Group III birds received acetaminophen injection (10 mg/kg IM) for a period of seven days daily. The birds treated with diclofenac showed severe clinical signs of toxicity accompanied with high mortality and significant increase (P<0.001) in serum creatinine and uric acid concentration. The creatinine and uric acid concentrations were consistent with gross and histopathological findings. The negative control and acetaminophen-treated groups showed no adverse clinical signs, serum creatinine and uric acid concentrations were normal, and no gross or histopathological changes in kidneys were observed. Thus, it was concluded that acetaminophen can be used for treatment in birds without any adverse effect on kidneys. PMID:21170252
Sabbagh, Robert; Chawla, Arun; Tisdale, Britton; Kwan, Kevin; Chatterjee, Suman; Kwiecien, Jacek M.; Kapoor, Anil
2011-01-01
Background Thirty minutes has been considered as the threshold for tolerable warm ischemic time (WIT). Recent reports demonstrate recovery of renal function after longer WIT. We assessed renal histology according to different WIT in a 2-kidney porcine model. Methods Twelve female pigs were randomized to an open or laparoscopic group. Each pig was further randomized within each group to clamping the left renal artery for 5, 15, 30, 45, 60 or 180 minutes. Preclamping left renal biopsies were performed on each pig. The contralateral kidney in each animal was used as an individual control. On postoperative day 14, all animals underwent bilateral nephrectomies. Preclamping left renal biopsies and all renal specimens were evaluated by a blinded veterinary pathologist. Results One pig died in the open group after 180 minutes of clamping. Histopathology did not show any significant changes between the two groups and across clamp times from 5 to 60 minutes. After 180 minutes of laparoscopic clamping, there was evidence of diffuse necrosis. Interpretation Sixty minutes of ischemia did not show any permanent renal damage in both groups. Further studies are needed to verify these findings in humans. A prolonged ischemic time without permanent renal damage would be helpful in partial nephrectomy. Warm ischemic time of 180 minutes exceeded the renal ischemic burden based on histological features. PMID:21470513
Leong, S K
1980-08-04
The present study shows that 3--5 days following lesions of the dentate and interposed nuclei in normal adult rats degenerating axons and axon terminals can be detected in the contralateral pontine gray. The degenerating axon terminals form Gray's type I axo-dendritic contacts with fine and intermediate dendrites measuring between 0.8--2.4 microns. The present study also investigates, by electron microscopy, the synaptic rearrangement of the sensorimotor corticopontine projections following neonatal left cerebellar hemispherectomy. Following neonatal left cerebellar hemispherectomy, the right sensorimotor and adjacent cortex (SMC) presents a very dense ipsilateral and a modest amount of contralateral corticopontine projections in contrast with a predominantly ipsilateral corticopontine projection seen in the normal adult rat. As with the ipsilateral corticopontine projection seen in the normal adult animal, the bilateral corticopontine projections seen in the experimental animals form contacts with dendrites suggestive of Gray's type I synapses. While the corticopontine projections in normal control animals form synapses with fine dendrites measuring 0.2--1.2 micron the corticopontine projections in the experimental animals form synaptic relations with fine dendrites and with intermediate dendrites measuring 0.2--2.4 microns. As the normal cerebellopontine fibers from the dentate and interposed nuclei also form axo-dendritic synapses on fine and intermediate dendrites and the contracts formed are also of Gray's type I synapses, it is possible that some of the newly formed corticopontine fibers in the experimental animals might have replaced the cerebellopontine fibers synapsing on intermediate dendrites. Synaptic rearrangement appears to take place as suggested by the presence of synaptic complexes in which one axon terminal contacts two or more dendrites or two or more axon terminals contact one dendrite. Such complexes are frequently seen to undergo degeneration following the right SMC lesion in the experimental animals. Other complex synaptic structures are also present in both the right and left pontine gray in the experimental animals. They are not seen to undergo degeneration following the right SMC lesions. Occasional features of neuronal reaction could still be seen in both sides of the pontine gray for as long as 3--6 months after the neonatal cerebellar lesions.
Ultrasonographic abdominal anatomy of healthy captive caracals (Caracal caracal).
Makungu, Modesta; du Plessis, Wencke M; Barrows, Michelle; Koeppel, Katja N; Groenewald, Hermanus B
2012-09-01
Abdominal ultrasonography was performed in six adult captive caracals (Caracal caracal) to describe the normal abdominal ultrasonographic anatomy. Consistently, the splenic parenchyma was hyperechoic to the liver and kidneys. The relative echogenicity of the right kidney's cortex was inconsistent to the liver. The gall bladder was prominent in five animals and surrounded by a clearly visualized thin, smooth, regular echogenic wall. The wall thickness of the duodenum measured significantly greater compared with that of the jejunum and colon. The duodenum had a significantly thicker mucosal layer compared with that of the stomach. Such knowledge of the normal abdominal ultrasonographic anatomy of individual species is important for accurate diagnosis and interpretation of routine health examinations.
Metabolomic analysis of urine samples by UHPLC-QTOF-MS: Impact of normalization strategies.
Gagnebin, Yoric; Tonoli, David; Lescuyer, Pierre; Ponte, Belen; de Seigneux, Sophie; Martin, Pierre-Yves; Schappler, Julie; Boccard, Julien; Rudaz, Serge
2017-02-22
Among the various biological matrices used in metabolomics, urine is a biofluid of major interest because of its non-invasive collection and its availability in large quantities. However, significant sources of variability in urine metabolomics based on UHPLC-MS are related to the analytical drift and variation of the sample concentration, thus requiring normalization. A sequential normalization strategy was developed to remove these detrimental effects, including: (i) pre-acquisition sample normalization by individual dilution factors to narrow the concentration range and to standardize the analytical conditions, (ii) post-acquisition data normalization by quality control-based robust LOESS signal correction (QC-RLSC) to correct for potential analytical drift, and (iii) post-acquisition data normalization by MS total useful signal (MSTUS) or probabilistic quotient normalization (PQN) to prevent the impact of concentration variability. This generic strategy was performed with urine samples from healthy individuals and was further implemented in the context of a clinical study to detect alterations in urine metabolomic profiles due to kidney failure. In the case of kidney failure, the relation between creatinine/osmolality and the sample concentration is modified, and relying only on these measurements for normalization could be highly detrimental. The sequential normalization strategy was demonstrated to significantly improve patient stratification by decreasing the unwanted variability and thus enhancing data quality. Copyright © 2016 Elsevier B.V. All rights reserved.
Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model
Wang, Xuexiang; Johnson, Ashley C.; Williams, Jan M.; White, Tiffani; Chade, Alejandro R.; Zhang, Jie; Liu, Ruisheng; Roman, Richard J.; Lee, Jonathan W.; Kyle, Patrick B.; Solberg-Woods, Leah
2015-01-01
Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%–75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. PMID:25349207
Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model.
Wang, Xuexiang; Johnson, Ashley C; Williams, Jan M; White, Tiffani; Chade, Alejandro R; Zhang, Jie; Liu, Ruisheng; Roman, Richard J; Lee, Jonathan W; Kyle, Patrick B; Solberg-Woods, Leah; Garrett, Michael R
2015-07-01
Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. Copyright © 2015 by the American Society of Nephrology.
Urinary biomarkers predict advanced acute kidney injury after cardiovascular surgery.
Wang, Jian-Jhong; Chi, Nai-Hsin; Huang, Tao-Min; Connolly, Rory; Chen, Liang Wen; Chueh, Shih-Chieh Jeff; Kan, Wei-Chih; Lai, Chih-Cheng; Wu, Vin-Cent; Fang, Ji-Tseng; Chu, Tzong-Shinn; Wu, Kwan-Dun
2018-04-26
Acute kidney injury (AKI) after cardiovascular surgery is a serious complication. Little is known about the ability of novel biomarkers in combination with clinical risk scores for prediction of advanced AKI. In this prospectively conducted multicenter study, urine samples were collected from 149 adults at 0, 3, 6, 12 and 24 h after cardiovascular surgery. We measured urinary hemojuvelin (uHJV), kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL), α-glutathione S-transferase (uα-GST) and π-glutathione S-transferase (uπ-GST). The primary outcome was advanced AKI, under the definition of Kidney Disease: Improving Global Outcomes (KDIGO) stage 2, 3 and composite outcomes were KDIGO stage 2, 3 or 90-day mortality after hospital discharge. Patients with advanced AKI had significantly higher levels of uHJV and uKIM-1 at 3, 6 and 12 h after surgery. When normalized by urinary creatinine level, uKIM-1 in combination with uHJV at 3 h post-surgery had a high predictive ability for advanced AKI and composite outcome (AUC = 0.898 and 0.905, respectively). The combination of this biomarker panel (normalized uKIM-1, uHJV at 3 h post-operation) and Liano's score was superior in predicting advanced AKI (AUC = 0.931, category-free net reclassification improvement of 1.149, and p < 0.001). When added to Liano's score, normalized uHJV and uKIM-1 levels at 3 h after cardiovascular surgery enhanced the identification of patients at higher risk of progression to advanced AKI and composite outcomes.
Impact of Momordica charantia extract on kidney function and structure in mice.
Mardani, Saeed; Nasri, Hamid; Hajian, Shabnam; Ahmadi, Ali; Kazemi, Reyhane; Rafieian-Kopaei, Mahmoud
2014-01-01
Bitter Melon (BM) is known for its hypoglycemic effect and is commonly used in populations. This study examined the effects and safety of bitter melon fruit in laboratory mice. In this experimental study 70 male mice (25-30 gr) were randomly divided into 7 groups. The mice were injected intraperitoneally with single doses of 0, 100, 500, 1000, 2000 and 4000 mg/kg and multiple doses 500 mg/kg daily for 7 days. The mice were then observed for 72 hours before sacrificing. Immediately kidneys were taken out for histological examinations. Tubular cell vacuolization and flattening as well as hyaline casts, debris and dilatation of tubular lumen were the morphologic lesions which were assessed with scores from 0 to 4, while zero score addressed normal renal tissue. Serum samples were assayed for kidney function (creatinine; Cr and Blood Urea Nitrogen; BUN). Blood and bitter melon antioxidant activities were measured, too. Data were analyzed with Stata software (Stata Corp. 2011. Stata Statistical Software: Release 12. College Station, TX: Stata Corp LP)using ANOVA and Bonferroni tests. All single dose groups showed normal behavior after the dosing and no statistical changes were observed in blood parameters (p>0.05). Histological examinations revealed normal organ structures, however, the group treated for 7 days showed statistically a significant change in BUN (p=0.002) and a borderline significance in Cr (p=0.051). Administration of up to 4000 mg/kg did not have any effect on the mice kidney function and histology, however chronic administration were nephrotoxic. More studies with different dosage regimens are suggested.
Contralateral pulmonary metastases in lung cancer
Onuigbo, Wilson I. B.
1974-01-01
Onuigbo, W. I. B. (1974).Thorax, 29, 132-133. Contralateral pulmonary metastases in lung cancer. It has long been known that lung cancer may attack many organs and yet spare the opposite lung. In 100 cases of this tumour studied at necropsy, only 22 showed contralateral pulmonary spread. Contralateral deposits are generally small and may be related to damaged tissues. Although tissue unsuitability is supposed to underlie the limitation of metastases in recipient organs, this does not apply to the contralateral lung. Since lung tissue is readily accessible to bloodborne cancer cells, research should be directed towards explaining the paradoxical paucity of the metastases. PMID:4825544
Hyperfunctioning thyroid nodules in children.
Abe, K; Konno, M; Sato, T; Matsuura, N
1980-10-01
We studied two cases of hyperfunctioning thyroid nodules in children. A 9-year-old girl and an 11-year-old girl had thyroid masses in otherwise nonpalpable thyroid glands. Scintiscan showed hyperfunctioning thyroid nodules. The former patient had elevated values for T4 and T3, and plasma thyrotropin (TSH) level failed to respond to stimulation with thyrotropin releasing hormone (TRH), whereas the latter patient had normal values for T4, and T3 and plasma TSH response to TRH was normal. After the surgical removal of nodules, scintiscan exhibited radioactivity in the contralateral lobe of the thyroid gland in the former and in the ectopic thyroid tissue in the latter. Results of microscopic examinations of thyroid nodules were consistent with adenomatous goiter.
Sharma, S C; Tsai, C
1991-01-01
In normal goldfish, optic axons innervate only the contralateral optic tectum. When one eye was enucleated and the optic nerve of the other eye crushed, the regenerating optic axons innervated both optic tecta. We studied the presence of bilaterally projecting retinal ganglion cells by double retrograde cell labeling methods using Nuclear Yellow and True Blue dyes. About 10% of the retinal ganglion cells were double labeled and these cells were found throughout the retina. In addition, HRP application to the ipsilateral tectum revealed retrogradely-labeled retinal ganglion cells of all morphological types. These results suggest that induced ipsilateral projections are formed by regenerating axon collaterals and that all cell types are involved in the generation of normal mirror image typography.
Akyuz, Sukru; Karaca, Mehmet; Kemaloglu Oz, Tugba; Altay, Servet; Gungor, Baris; Yaylak, Baris; Yazici, Selcuk; Ozden, Kivilcim; Karakus, Gultekin; Cam, Nese
2014-01-01
Efficacy of intravenous (IV) volume expansion in preventing contrast-induced acute kidney injury (CI-AKI) is well known. However, the role of oral hydration has not been well established. The aim of this work was to evaluate the efficacy of oral hydration in preventing CI-AKI. We prospectively randomized 225 patients undergoing coronary angiography and/or percutaneous coronary intervention in either oral hydration or IV hydration groups. Patients who have at least one of the high-risk factors for developing CI-AKI (advanced age, type 2 diabetes mellitus, anemia, hyperuricemia, a history of cardiac failure or systolic dysfunction) were included in the study. All patients had normal renal function or stage 1-2 chronic kidney disease. Patients in the oral hydration group were encouraged to drink unrestricted amounts of fluids freely whereas isotonic saline infusion was performed by the standard protocol in the IV hydration group. CI-AKI occurred in 8/116 patients (6.9%) in the oral hydration group and 8/109 patients (7.3%) in the IV hydration group (p = 0.89). There was also no statistically significant difference between the two groups when different CI-AKI definitions were taken into account. Oral hydration is as effective as IV hydration in preventing CI-AKI in patients with normal kidney function or stage 1-2 chronic kidney disease, and who also have at least one of the other high-risk factors for developing CI-AKI. © 2014 S. Karger AG, Basel.
Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules
Armour, Eric A.; Carson, Robert P.
2012-01-01
Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia. PMID:22674026
Elbarbry, Fawzy; Ragheb, Ahmed; Attia, Ahmed; Chibbar, Rajni; Marfleet, Travis; Shoker, Ahmed
2010-11-01
This study investigates the mechanism of cyclosporine A (CsA)-mediated nephrotoxicity by examining the hypothesis that CsA toxicity is mediated through its effect on the kidney drug metabolizing enzymes in a hyperlipemic rabbit model. Twenty-four female New Zealand white rabbits divided into four groups. Group 1 received regular diet. Group 2 received 1% cholesterol diet. Group 3 received CsA (25 mg/kg, orally once daily) and group 4 received 1% cholesterol diet and CsA (25 mg/kg, orally once daily). Cytochrome P450 2E1 (CYP2E1) activity in kidney microsomes was assessed by measuring p-nitrophenol hydroxylase activity. Generation of reactive oxygen species (ROS) was assessed by measuring malondialdehyde (MDA) and the protein carbonyl. Effect of CsA and hyperlipidemia on the antioxidant proteins were also assessed using standard techniques. CsA but not the high-cholesterol diet induced significant elevation in MDA, protein carbonyl and CYP2E1 activities in the kidney. The addition of cholesterol to CsA normalized ROS markers without affecting the CsA-enhanced CYP2E1 activity. Alone, CsA caused characteristic tubular injury, whereas the addition of high-cholesterol diet to CsA nearly abolished the tubular damage. CsA-enhanced rabbit kidney ROS and CYP2E1 activities. Hyperlipidemia attenuates CsA tubular injury, most probably due to normalization of renal ROS, but not CYP2E1 activity.
Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules.
Armour, Eric A; Carson, Robert P; Ess, Kevin C
2012-08-15
Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia.
Elevated plasma TGF-beta1 in renal diseases: cause or consequence?
Junker, U; Haufe, C C; Nuske, K; Rebstock, K; Steiner, T; Wunderlich, H; Junker, K; Reinhold, D
2000-07-01
We previously reported elevated levels of TGF-beta1 in patients with renal carcinoma. Certain aspects led us to ask whether they might be caused by chronic damage to the kidney(s). Here we report on an extended set of patients with various renal diseases, lung cancer, humoral immunodeficiency and controls. For latent TGF-beta1 in plasma, we find that the control, immunodeficiency, lung cancer and kidney transplant groups do not differ significantly (means, 7.0-8.8 ng/ml). Also, acute short-term renal stress (extracorporal lithotrypsy) does not lead to an increase of TGF-beta1. However, the pyelonephritis patients present with levels of 19.0 ng/ml, chronic extracorporal dialysis patients with 15.5 ng/ml, and renal cell carcinoma patients with 22.8 ng/ml. For active TGF-beta1 these findings are exactly recovered. For serum levels, only the renal carcinoma group presents with significantly elevated levels of TGF-beta1. Kidney transplantation seems to normalize TGF-beta1 levels, while in the kidney cancer patients surgery has an effect only in part of the group. We conclude that elevated plasma TGF-beta1 levels are common in at least two chronic renal disease conditions, and that it normalizes with restoration of renal function. It is tempting to speculate that chronic elevation of TGF-beta1 in these patients may be critically involved in these conditions predisposing to renal cancer. Copyright 2000 Academic Press.
RADIOGRAPHIC AND ULTRASONOGRAPHIC ABDOMINAL ANATOMY IN CAPTIVE RING-TAILED LEMURS (LEMUR CATTA).
Makungu, Modesta; du Plessis, Wencke M; Barrows, Michelle; Groenewald, Hermanus B; Koeppel, Katja N
2016-06-01
The ring-tailed lemur (Lemur catta) is primarily distributed in south and southwestern Madagascar. It is classified as an endangered species by the International Union for Conservation of Nature. Various abdominal diseases, such as hepatic lipidosis, intestinal ulcers, cystitis, urinary tract obstruction, and neoplasia (e.g., colonic adenocarcinoma and cholangiocarcinoma), have been reported in this species. The aim of this study was to describe the normal radiographic and ultrasonographic abdominal anatomy in captive ring-tailed lemurs to provide guidance for clinical use. Radiography of the abdomen and ultrasonography of the liver, spleen, kidneys, and urinary bladder were performed in 13 and 9 healthy captive ring-tailed lemurs, respectively, during their annual health examinations. Normal radiographic and ultrasonographic reference ranges for abdominal organs were established and ratios were calculated. The majority (12/13) of animals had seven lumbar vertebrae. The sacrum had mainly (12/13) three segments. Abdominal serosal detail was excellent in all animals, and hypaxial muscles were conspicuous in the majority (11/13) of animals. The spleen was frequently (12/13) seen on the ventrodorsal (VD) view and rarely (3/13) on the right lateral (RL) view. The liver was less prominent and well contained within the ribcage. The pylorus was mostly (11/13) located to the right of the midline. The right and left kidneys were visible on the RL and VD views, with the right kidney positioned more cranial and dorsal to the left kidney. On ultrasonography, the kidneys appeared ovoid on transverse and longitudinal views. The medulla was hypoechoic to the renal cortex. The renal cortex was frequently (8/9) isoechoic and rarely (1/9) hyperechoic to the splenic parenchyma. The liver parenchyma was hypoechoic (5/5) to the renal cortex. Knowledge of the normal radiographic and ultrasonographic abdominal anatomy of ring-tailed lemurs may be useful in the diagnosis of diseases and in routine health examinations.
Bueters, Ruud R G; Jeronimus-Klaasen, Annelies; Brüggemann, Roger J M; van den Heuvel, Lambertus P; Schreuder, Michiel F
2017-09-01
Up to two-thirds of premature born neonates are treated for infections with aminoglycosides such as gentamicin. Although acute toxicities are well described, there is uncertainty on developmental changes after treatment of premature born neonates. We studied the effect of gentamicin and ceftazidime on kidney development in the rat. Additionally, we evaluated the modulating effect of extrauterine growth restriction. On postnatal day (PND) 2, Wistar rats were cross-fostered into normal sized litters (12 pups) or large litters (20 pups) to create normal food (NF) or food restricted (FR) litters to simulate growth restriction and dosed daily intraperitoneally with placebo, 4 mg/kg of gentamicin or 50 mg/kg ceftazidime until PND 8. Gentamicin pharmacokinetics were studied in a separate group of animals. Kidneys were weighed. Renal expression of 18 developmental genes was evaluated by quantitative PCR on PND 8. On PND 35, glomerular number was assessed by stereology and glomerular generations were counted. Food restricted litters showed 22% less body weight compared with controls by day 35 (p < 0.001), 1.4- to 1.5-fold down regulation of Renin, Oat1, and Agtr1a (p < 0.05) expression and a 12% reduction in glomerular numbers (mean 30841 vs. 35187, p < 0.001), whereas glomerular generation count was unaffected. Gentamicin pharmacokinetic parameters were found to be in a human clinical range (mean maximum concentration in plasma of 4.88 mg/L and mean area under the plasma-concentration time curve up to the last measured concentration after 4 hr of 10.71 mg.h/L for sexes combined) and all endpoints were unaffected. Ceftazidime reduced Renin expression by 1.7-fold (p < 0.01). Our experiments showed that gentamicin at clinical levels did not disturb kidney development, ceftazidime can affect Renin expression, and extrauterine growth restriction impairs kidney development, but did not modulate potential drug toxicity. Birth Defects Research 109:1228-1235, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Ošiņa, Kristīne; Rostoka, Evita; Isajevs, Sergejs; Sokolovska, Jelizaveta; Sjakste, Tatjana; Sjakste, Nikolajs
2016-11-01
Development of complications of diabetes mellitus (DM), including diabetic nephropathy, is a complex multi-stage process, dependent on many factors including the modification of nitric oxide (NO) production and an impaired DNA repair. The goal of this work was to study in vivo effects of 1,4-dihydropyridine AV-153, known as antimutagen and DNA binder, on the expression of several genes and proteins involved in NO metabolism and DNA repair in the kidneys of rats with a streptozotocin (STZ)-induced model of DM. Transcription intensity was monitored by means of real-time RT-PCR and the expression of proteins by immunohistochemistry. Development of DM significantly induced PARP1 protein expression, while AV-153 (0.5 mg/kg) administration decreased it. AV-153 increased the expression of Parp1 gene in the kidneys of both intact and diabetic animals. Expression of H2afx mRNA and γH2AX histone protein, a marker of DNA breakage, was not changed in diabetic animals, but AV-153 up-regulated the expression of the gene without any impact on the protein expression. Development of DM was followed by a significant increase in iNOS enzyme expression, while AV-153 down-regulated the enzyme expression up to normal levels. iNos gene expression was also found to be increased in diabetic animals, but unlike the protein, the expression of mRNA was found to be enhanced by AV-153 administration. Expression of both eNOS protein and eNos gene in the kidneys was down-regulated, and the administration of AV-153 normalized the expression level. The effects of the compound in the kidneys of diabetic animals appear to be beneficial, as a trend for the normalization of expression of NO synthases is observed. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chan, Raymond W., E-mail: rwc3b@alumni.virginia.edu; Podgorsak, Matthew B.
Recent research has shown treating pancreatic cancer with volumetric-modulated arc therapy (VMAT) to be superior to either intensity-modulated radiation therapy or 3-dimensional conformal radiotherapy (3D-CRT), with respect to reducing normal tissue toxicity, monitor units, and treatment time. Furthermore, using avoidance sectors with RapidArc planning can further reduce normal tissue dose while maintaining target conformity. This study looks at the methods in reducing dose to the ipsilateral kidney, in pancreatic head cases, while observing dose received by other critical organs using avoidance sectors. Overall, 10 patients were retrospectively analyzed. Each patient had preoperative/unresectable pancreatic tumor and were selected based on themore » location of the right kidney being situated within the traditional 3D-CRT treatment field. The target planning target volume (286.97 ± 85.17 cm{sup 3}) was prescribed to 50.4 Gy using avoidance sectors of 30°, 40°, and 50° and then compared with VMAT as well as 3D-CRT. Analysis of the data shows that the mean dose to the right kidney was reduced by 11.6%, 15.5%, and 21.9% for avoidance angles of 30°, 40°, and 50°, respectively, over VMAT. The mean dose to the total kidney also decreased by 6.5%, 8.5%, and 11.0% for the same increasing angles. Spinal cord maximum dose, however, increased as a function of angle by 3.7%, 4.8%, and 6.1% compared with VMAT. Employing avoidance sector angles as a complement to VMAT planning can significantly reduce high dose to the ipsilateral kidney while not greatly overdosing other critical organs.« less
Machura, Katharina; Iankilevitch, Elina; Neubauer, Björn; Theuring, Franz; Kurtz, Armin
2013-03-01
On the basis of evidence that within the adult kidney, the aldo-keto reductase AKR1B7 (aldo-keto reductase family 1, member 7, also known as mouse vas deferens protein, MVDP) is selectively expressed in renin-producing cells, we aimed to define a possible role of AKR1B7 for the regulation and function of renin cells in the kidney. We could confirm colocalization and corecruitment of renin and of AKR1B7 in wild-type kidneys. Renin cells in AKR1B7-deficient kidneys showed normal morphology, numbers, and intrarenal distribution. Plasma renin concentration (PRC) and renin mRNA levels of AKR1B7-deficient mice were normal at standard chow and were lowered by a high-salt diet directly comparable to wild-type mice. Treatment with a low-salt diet in combination with an angiotensin-converting enzyme inhibitor strongly increased PRC and renin mRNA in a similar fashion both in AKR1B7-deficient and wild-type mice. Under this condition, we also observed a strong retrograde recruitment of renin-expressing cell along the preglomerular vessels, however, without a difference between AKR1B7-deficient and wild-type mice. The isolated perfused mouse kidney model was used to study the acute regulation of renin secretion by ANG II and by perfusion pressure. Regarding these parameters, no differences were observed between AKR1B7-deficient and wild-type kidneys. In summary, our data suggest that AKR1B7 is not of major relevance for the regulation of renin production and secretion in spite of its striking coregulation with renin expression.
Proteome profiling in the aorta and kidney of type 1 diabetic rats
Zhu, Rui; Jaffa, Miran A.; Zhao, Jingfu; Mirzaei, Parvin; Ahmed, Adnan; Kobeissy, Firas; Ziyadeh, Fuad N.; Mechref, Yehia
2017-01-01
Diabetes is associated with a number of metabolic and cardiovascular risk factors that contribute to a high rate of microvascular and macrovascular complications. The risk factors and mechanisms that contribute to the development of micro- and macrovascular disease in diabetes are not fully explained. In this study, we employed mass spectrometric analysis using tandem LC-MS/MS to generate a proteomic profile of protein abundance and post-translational modifications (PTM) in the aorta and kidney of diabetic rats. In addition, systems biology analyses were employed to identify key protein markers that can provide insights into molecular pathways and processes that are differentially regulated in the aorta and kidney of type 1 diabetic rats. Our results indicated that 188 (111 downregulated and 77 upregulated) proteins were significantly identified in the aorta of diabetic rats compared to normal controls. A total of 223 (109 downregulated and 114 upregulated) proteins were significantly identified in the kidney of diabetic rats compared to normal controls. When the protein profiles from the kidney and aorta of diabetic and control rats were analyzed by principal component analysis, a distinct separation of the groups was observed. In addition, diabetes resulted in a significant increase in PTM (oxidation, phosphorylation, and acetylation) of proteins in the kidney and aorta and this effect was partially reversed by insulin treatment. Ingenuity pathway analysis performed on the list of differentially expressed proteins depicted mitochondrial dysfunction, oxidative phosphorylation and acute phase response signaling to be among the altered canonical pathways by diabetes in both tissues. The findings of the present study provide a global proteomics view of markers that highlight the mechanisms and putative processes that modulate renal and vascular injury in diabetes. PMID:29121074
Proteome profiling in the aorta and kidney of type 1 diabetic rats.
Al Hariri, Moustafa; Elmedawar, Mohamad; Zhu, Rui; Jaffa, Miran A; Zhao, Jingfu; Mirzaei, Parvin; Ahmed, Adnan; Kobeissy, Firas; Ziyadeh, Fuad N; Mechref, Yehia; Jaffa, Ayad A
2017-01-01
Diabetes is associated with a number of metabolic and cardiovascular risk factors that contribute to a high rate of microvascular and macrovascular complications. The risk factors and mechanisms that contribute to the development of micro- and macrovascular disease in diabetes are not fully explained. In this study, we employed mass spectrometric analysis using tandem LC-MS/MS to generate a proteomic profile of protein abundance and post-translational modifications (PTM) in the aorta and kidney of diabetic rats. In addition, systems biology analyses were employed to identify key protein markers that can provide insights into molecular pathways and processes that are differentially regulated in the aorta and kidney of type 1 diabetic rats. Our results indicated that 188 (111 downregulated and 77 upregulated) proteins were significantly identified in the aorta of diabetic rats compared to normal controls. A total of 223 (109 downregulated and 114 upregulated) proteins were significantly identified in the kidney of diabetic rats compared to normal controls. When the protein profiles from the kidney and aorta of diabetic and control rats were analyzed by principal component analysis, a distinct separation of the groups was observed. In addition, diabetes resulted in a significant increase in PTM (oxidation, phosphorylation, and acetylation) of proteins in the kidney and aorta and this effect was partially reversed by insulin treatment. Ingenuity pathway analysis performed on the list of differentially expressed proteins depicted mitochondrial dysfunction, oxidative phosphorylation and acute phase response signaling to be among the altered canonical pathways by diabetes in both tissues. The findings of the present study provide a global proteomics view of markers that highlight the mechanisms and putative processes that modulate renal and vascular injury in diabetes.
Ichiki, Tomoko; Huntley, Brenda K; Harty, Gail J; Sangaralingham, S Jeson; Burnett, John C
2017-05-01
Heart failure (HF) is a major health problem with worsening outcomes when renal impairment is present. Therapeutics for early phase HF may be effective for cardiorenal protection, however the detailed characteristics of the kidney in early-stage HF (ES-HF), and therefore treatment for potential renal protection, are poorly defined. We sought to determine the gene and protein expression profiles of specific maladaptive pathways of ES-HF in the kidney and heart. Experimental canine ES-HF, characterized by de-novo HF with atrial remodeling but not ventricular fibrosis, was induced by right ventricular pacing for 10 days. Kidney cortex (KC), medulla (KM), left ventricle (LV), and left atrial (LA) tissues from ES-HF versus normal canines ( n = 4 of each) were analyzed using RT-PCR microarrays and protein assays to assess genes and proteins related to inflammation, renal injury, apoptosis, and fibrosis. ES-HF was characterized by increased circulating natriuretic peptides and components of the renin-angiotensin-aldosterone system and decreased sodium and water excretion with mild renal injury and up-regulation of CNP and renin genes in the kidney. Compared to normals, widespread genes, especially genes of the inflammatory pathways, were up-regulated in KC similar to increases seen in LA Protein expressions related to inflammatory cytokines were also augmented in the KC Gene and protein changes were less prominent in the LV and KM The ES-HF displayed mild renal injury with widespread gene changes and increased inflammatory cytokines. These changes may provide important clues into the pathophysiology of ES-HF and for therapeutic molecular targets in the kidney of ES-HF. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
Hydronephrosis in the Wnt5a-ablated kidney is caused by an abnormal ureter-bladder connection.
Yun, Kangsun; Perantoni, Alan O
The Wnt5a null mouse is a complex developmental model which, among its several posterior-localized axis defects, exhibits multiple kidney phenotypes, including duplex kidney and loss of the medullary zone. We previously reported that ablation of Wnt5a in nascent mesoderm causes duplex kidney formation as a result of aberrant development of the nephric duct and abnormal extension of intermediate mesoderm. However, these mice also display a loss of the medullary region late in gestation. We have now genetically isolated duplex kidney formation from the medullary defect by specifically targeting the progenitors for both the ureteric bud and metanephric mesenchyme. The conditional mutants fail to form a normal renal medulla but no longer exhibit duplex kidney formation. Approximately 1/3 of the mutants develop hydronephrosis in the kidneys either uni- or bilaterally when using Dll1Cre. The abnormal kidney phenotype becomes prominent at E16.5, which approximates the time when urine production begins in the mouse embryonic kidney, and is associated with a dramatic increase in apoptosis only in mutant kidneys with hydronephrosis. Methylene blue dye injection and histologic examination reveal that aberrant cell death likely results from urine toxicity due to an abnormal ureter-bladder connection. This study shows that Wnt5a is not required for development of the renal medulla and that loss of the renal medullary region in the Wnt5a-deleted kidney is caused by an abnormal ureter-bladder connection. Published by Elsevier B.V.
NASA Astrophysics Data System (ADS)
van Breugel, J. M. M.; de Greef, M.; Wijlemans, J. W.; Schubert, G.; van den Bosch, M. A. A. J.; Moonen, C. T. W.; Ries, M. G.
2017-07-01
The incidence of small renal masses (SRMs) sized <4 cm has increased over the decades (as co-findings/or due to introduction of cross sectional imaging). Currently, partial nephrectomy (PN) or watchful waiting is advised in these patients. Ultimately, 80-90% of these SRMs require surgical treatment and PN is associated with a 15% complication rate. In this aging population, with possible comorbidities and poor health condition, both PN and watchful waiting are non-ideal treatment options. This resulted in an increased need for early, non-invasive treatment strategies such as MR-guided high intensity focused ultrasound (MR-HIFU). (i) To investigate the feasibility of creating a confluent lesion in the kidney using respiratory-gated MR-HIFU under clinical conditions in a pre-clinical study and (ii) to evaluate the reproducibility of the MR-HIFU ablation strategy. Healthy pigs (n = 10) under general anesthesia were positioned on a clinical MR-HIFU system with integrated cooling. A honeycomb pattern of seven overlapping ablation cells (4 × 4 × 10 mm3, 450 W, <30 s) was ablated successively in the cortex of the porcine kidney. Both MR thermometry and acoustic energy delivery were respiratory gated using a pencil beam navigator on the contralateral kidney. The non-perfused volume (NPV) was visualized after the last sonication by contrast-enhanced (CE) T 1-weighted MR (T 1 w) imaging. Cell viability staining was performed to visualize the extent of necrosis. Results: a median NPV of 0.62 ml was observed on CE-T 1 w images (IQR 0.58-1.57 ml, range 0.33-2.75 ml). Cell viability staining showed a median damaged volume of 0.59 ml (IQR 0.24-1.35 ml, range 0-4.1 ml). Overlooking of the false rib, shivering of the pig, and too large depth combined with a large heat-sink effect resulted in insufficient heating in 4 cases. The NPV and necrosed volume were confluent in all cases in which an ablated volume could be observed. Our results demonstrated the feasibility of creating a confluent volume of ablated kidney cortical tissue in vivo with MR-HIFU on a clinically available system using respiratory gating and near-field cooling and showed its reproducibility.
Local inhibition of GABA affects precedence effect in the inferior colliculus
Wang, Yanjun; Wang, Ningyu; Wang, Dan; Jia, Jun; Liu, Jinfeng; Xie, Yan; Wen, Xiaohui; Li, Xiaoting
2014-01-01
The precedence effect is a prerequisite for faithful sound localization in a complex auditory environment, and is a physiological phenomenon in which the auditory system selectively suppresses the directional information from echoes. Here we investigated how neurons in the inferior colliculus respond to the paired sounds that produce precedence-effect illusions, and whether their firing behavior can be modulated through inhibition with gamma-aminobutyric acid (GABA). We recorded extracellularly from 36 neurons in rat inferior colliculus under three conditions: no injection, injection with saline, and injection with gamma-aminobutyric acid. The paired sounds that produced precedence effects were two identical 4-ms noise bursts, which were delivered contralaterally or ipsilaterally to the recording site. The normalized neural responses were measured as a function of different inter-stimulus delays and half-maximal interstimulus delays were acquired. Neuronal responses to the lagging sounds were weak when the inter-stimulus delay was short, but increased gradually as the delay was lengthened. Saline injection produced no changes in neural responses, but after local gamma-aminobutyric acid application, responses to the lagging stimulus were suppressed. Application of gamma-aminobutyric acid affected the normalized response to lagging sounds, independently of whether they or the paired sounds were contralateral or ipsilateral to the recording site. These observations suggest that local inhibition by gamma-aminobutyric acid in the rat inferior colliculus shapes the neural responses to lagging sounds, and modulates the precedence effect. PMID:25206830
Lalaki, Panagiota; Hatzopoulos, Stavros; Lorito, Guiscardo; Kochanek, Krzysztof; Sliwa, Lech; Skarzynski, Henryk
2011-07-01
Subjective tinnitus is an auditory perception that is not caused by external stimulation, its source being anywhere in the auditory system. Furthermore, evidence exists that exposure to noise alters cochlear micromechanics, either directly or through complex feed-back mechanisms, involving the medial olivocochlear efferent system. The aim of this study was to assess the role of the efferent auditory system in noise-induced tinnitus generation. Contralateral sound-activated suppression of TEOAEs was performed in a group of 28 subjects with noise-induced tinnitus (NIT) versus a group of 35 subjects with normal hearing and tinnitus, without any history of exposure to intense occupational or recreational noise (idiopathic tinnitus-IT). Thirty healthy, normally hearing volunteers were used as controls for the efferent suppression test. Suppression of the TEOAE amplitude less than 1 dB SPL was considered abnormal, giving a false positive rate of 6.7%. Eighteen out of 28 (64.3%) patients of the NIT group and 9 out of 35 (25.7%) patients of the IT group showed abnormal suppression values, which were significantly different from the controls' (p<0.0001 and p<0.045, respectively). The abnormal activity of the efferent auditory system in NIT cases might indicate that either the activity of the efferent fibers innervating the outer hair cells (OHCs) is impaired or that the damaged OHCs themselves respond abnormally to the efferent stimulation.
Douet, Jean-Yves; Michel, Julien; Regnier, Alain
2013-10-01
To assess the anesthetic efficacy and local tolerance of topically applied 0.4% oxybuprocaine ophthalmic solution to in dogs and compare its effects with those of 1% tetracaine solution. 34 ophthalmically normal Beagles. Dogs were assigned to 2 groups, and baseline corneal touch threshold (CTT) was measured bilaterally with a Cochet-Bonnet aesthesiometer. Dogs of group 1 (n = 22) received a single drop of 0.4% oxybuprocaine ophthalmic solution in one eye and saline (0.9% NaCl) solution (control treatment) in the contralateral eye. Dogs of group 2 (n = 12) received a single drop of 0.4% oxybuprocaine ophthalmic solution in one eye and 1% tetracaine ophthalmic solution in the contralateral eye. The CTT of each eye was measured 1 and 5 minutes after topical application and then at 5-minute intervals until 75 minutes after topical application. CTT changes over time differed significantly between oxybuprocaine-treated and control eyes. After instillation of oxybuprocaine, maximal corneal anesthesia (CTT = 0) was achieved within 1 minute, and CTT was significantly decreased from 1 to 45 minutes, compared with the baseline value. No significant difference in onset, depth, and duration of corneal anesthesia was found between oxybuprocaine-treated and tetracaine-treated eyes. Conjunctival hyperemia and chemosis were detected more frequently in tetracaine-treated eyes than in oxybuprocaine-treated eyes. Topical application of oxybuprocaine and tetracaine similarly reduced corneal sensitivity in dogs, but oxybuprocaine was less irritating to the conjunctiva than was tetracaine.
Han, Won Gue; Yoo, Jun; Rah, Yoon Chan; Chang, Jiwon; Im, Gi Jung; Song, Jae-Jun; Chae, Sung Won; Jung, Hak Hyun; Choi, June
2017-01-01
Objectives Eustachian tube dysfunction has been associated with most cases of middle-ear disease. We aimed to assess the effectiveness of dynamic slow motion video endoscopy (DSVE) as a test of eustachian tube dysfunction. Furthermore, we assessed the correlation of the test with the Valsalva maneuver, the seven-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7), and intraoperative findings of the eustachian tube. Methods We retrospectively reviewed medical records from April to September 2014 to identify patients who were diagnosed with chronic otitis media (COM) at Korea University Ansan Hospital. They all underwent surgery because of COM without cholesteatoma and were assessed via the DSVE and ETDQ-7 to determine eustachian tube function. Results We reviewed 46 COM patients and examined 46 ears with COM and 46 ears on the contralateral side to COM that were thought to be normal. The mean DSVE grade in COM ears was 1.57±0.96, while the mean DSVE grade in contralateral ears was 1.15±0.94. The difference in DSVE between COM ears and normal ears was statistically significant (P=0.006). In the ETDQ-7, a higher score was related to intraoperative obstruction of the eustachian tube (P=0.012). Conclusion DSVE and ETDQ-7 can provide information regarding preoperative status of eustachian tube dysfunction by measuring dynamic structural changes of the eustachian tube in combination with other diagnostic tests. PMID:28602066
Regulation of oxygen utilization by angiotensin II in chronic kidney disease
Deng, Aihua; Tang, Tong; Singh, Prabhleen; Wang, Chen; Satriano, Joe; Thomson, Scott C; Blantz, Roland C
2010-01-01
Angiotensin II (ANG II) blockade delays progression of chronic kidney disease (CKD) by modifying intrarenal hemodynamics, but the effect on metabolic adaptations has not been examined. Using renal ablation/infarction (A/I) model of CKD in rats at one week, the effects of ANG II blockade by captopril (CAP) and losartan (LOS) on renal O2 consumption (QO2), renal nitric oxide (NO) activity and nitric oxide synthase (NOS) protein expression was examined. A/I kidneys exhibited proteinuria, reduced GFR, renal blood flow (RBF) and NOS-1 protein expression, while QO2 factored by sodium reabsorption (QO2/TNa) was markedly increased. CAP + LOS treatment increased GFR, RBF, and TNa, while QO2 remained unchanged, thus normalizing QO2/TNa. NOS-1 expression was normalized with CAP + LOS, as was proteinuria. Triple antihypertensive therapy administered to control for the blood pressure reduction, and lysine administration to increase GFR and RBF, did not normalize QO2/TNa, suggesting a specific effect of ANG II in elevating QO2/TNa. NOS blockade, to test functional NO activity on QO2 and QO2/TNa, increased QO2 in shams, but not in untreated A/I. The increase in QO2 was restored in CAP + LOS treated A/I. CAP + LOS treatment normalized the increased QO2/TNa and functional NO activity in A/I independent of the blood pressure and GFR effects, providing evidence for an additional mechanism underlying the benefits of ANG II inhibition therapy. PMID:18818681
Soliman, Mohamed Mohamed; Abdo Nassan, Mohamed; Ismail, Tamer Ahmed
2016-01-01
The present study was conducted to test the effect of Origanum Majoranum Extract (OME) of leaves on alterations induced in a model of type 2 diabetic rats. Adult male Wistar rats were fed high fat diet for 3 weeks and injected a single dose of streptozotocin (35 mg/kg) intraperitoneally to induce type 2 diabetic rats. Diabetic rats were given aqueous extract of OME in a dose of 20 mg/kg orally for 3 weeks. Changes in lipid profiles, glucose, insulin, expression of some genes related to glucose metabolism and histopathological changes in liver and kidney were examined. Administration of OME improved and normalized dyslipidemia recorded in type 2 diabetic rats together with reduction in glucose and insulin levels. OME induced up-regulation in gene expression of glucose [adiponectin and glucose transporter-2 (GLUT-2)] and lipid metabolism [lipoprotein lipase (LPL)]. Moreover, OME normalized histopathological changes occurred in liver and kidney of diabetic rats. OME decreased lipids accumulation in liver and kidney and increased regeneration of hepatic parenchyma and restored normal renal architecture with disappearance of fat droplets. In conclusion, OME improved dyslipidemia associated with type 2 diabetes through regulation of genes related to glucose and lipid metabolism. PMID:28228803
Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease
Newman, Christopher L.; Creecy, Amy; Granke, Mathilde; Nyman, Jeffry S.; Tian, Nannan; Hammond, Max A.; Wallace, Joseph M.; Brown, Drew M.; Chen, Neal; Moe, Sharon M.; Allen, Matthew R.
2015-01-01
Patients with chronic kidney disease (CKD) have an increased risk of fracture. Raloxifene is a mild anti-resorptive agent that reduces fracture risk in the general population. Here we assessed the impact of raloxifene on the skeletal properties of animals with progressive CKD. Male Cy/+ rats that develop autosomal dominant cystic kidney disease were treated with either vehicle or raloxifene for five weeks. They were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole bone mechanics, and material properties). Their normal littermates served as controls. Animals with CKD had significantly higher parathyroid hormone levels compared to normal controls as well as inferior structural and mechanical skeletal properties. Raloxifene treatment resulted in lower bone remodeling rates and higher cancellous bone volume in the rats with CKD. While it had little effect on cortical bone geometry it resulted in higher energy to fracture and modulus of toughness values than vehicle-treated rats with CKD, achieving levels equivalent to normal controls. Animals treated with raloxifene had superior tissue-level mechanical properties as assessed by nanoindentation and higher collagen D-periodic spacing as assessed by atomic force microscopy. Thus, raloxifene can positively impact whole bone mechanical properties in CKD through its impact on skeletal material properties. PMID:26489025
Ito, Katsuyoshi; Hayashida, Minoru; Kanki, Akihiko; Yamamoto, Akira; Tamada, Tsutomu; Yoshida, Koji; Tanabe, Masahiro
2018-05-17
To evaluate dynamic changes in apparent diffusion coefficient (ADC) values of the kidney at different time points during the cardiac cycle using electrocardiographic (ECG)-triggered diffusion-weighted MR imaging in normal subjects, and to elucidate the differences in ADC values between the right and left kidneys during a cardiac cycle. The study was approved by our institutional review board and informed consent was obtained from subjects. Twenty healthy volunteers who underwent ECG-triggered diffusion-weighted MR imaging of the kidney were included. The differences in ADC values of each kidney during different cardiac phases were compared. Additionally, the differences in maximum and minimum ADC values between the right and left kidney were also evaluated. ADC values in the right and left kidney changed significantly during the cardiac cycle (P < 0.00001). Maximum and minimum ADC values during the cardiac cycle of the left kidney were significantly higher (P = 0.026 and 0.017, respectively) than those of the right kidney. Maximum ADC value in the left kidney had a significantly strong positive correlation with the left renal vein ratio (r = 0.83, P < 0.00001). In the right kidney, maximum ADC showed a weakly positive correlation with the diameter of the right renal vein (r = 0.45, P = 0.048). ADC values of the kidney obtained using ECG-triggered diffusion-weighted MR imaging change significantly during the cardiac cycle. Maximum (systolic) ADC during the cardiac cycle of the left kidney was significantly higher than that of the right kidney, probably due to the anatomical difference in the renal vein. Copyright © 2018 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Seong, Myeongsu; Myoung, NoSoung; Yim, Sang-Youp; Kim, Jae G.
2015-02-01
Because mammography, the gold standard of breast cancer screening and monitoring treatment efficacy, has limitations, there is a necessity to have a new method for breast cancer patients. Raman spectroscopy is considered as one of the best alternative approaches due to its ability of visualizing (bio)chemical information of a matter. In this study, we hypothesized that the change of biochemical composition occurs earlier than morphological change in breast cancer during chemotherapy, and attempted to prove it by employing fiber-optic Raman spectroscopy for longitudinal Raman measurement in small animal breast cancer model. To confirm the hypothesis, we measured Raman spectra of a tumor breast and the contralateral breast during chemotherapy for 4 fisher 344 female rats longitudinally. Principal component analysis and Raman spectral differences between breast tumor and contralateral normal breast did not show a clear difference between them which may have been caused by interference from skin. Thus, spatially-offset Raman spectroscopy will be employed in order to acquire the Raman signal directly from tumor while suppressing Raman signal from skin for the future study.
Kurihara, T; Higashi, Y; Suemasu, K; Kanoh, T; Tabei, T; Inoue, K
1993-05-01
We examined temperature differences between a cancerous breast and its counterpart normal one by contact thermography before and after preoperative chemotherapy, and evaluated the relationship between the changes in the thermograms and response to chemotherapy in six patients with breast cancer. We used the following definitions: 1) delta Tmean: temperature differences between a mean temperature of a cancerous breast and that of the contralateral healthy breast; 2) delta Tmax: temperature differences between a cancer-related hyperthermic area in a breast and the mirror area of contralateral breast; 3) and the thermal patterns in thermogram were estimated by the criteria of Tada et al. In responders the thermograms after chemotherapy indicated an improvement in the hyperthermic vascular pattern (HVP) or hyperthermic area and a decrease of delta Tmean and delta Tmax. In contrast, little or no changes were observed in the thermograms of non-responders. Degrees of changes in thermograms reflected the effectiveness of chemotherapy. Our study showed that chemotherapeutic effectiveness may be better evaluated by combining contact thermography with the present method measuring tumor sizes than by only the present one.
Status of the contralateral rotator cuff in patients undergoing rotator cuff repair.
Ro, Kyung-Han; Park, Jong-Hoon; Lee, Soon-Hyuck; Song, Dong-Ik; Jeong, Ha-Joon; Jeong, Woong-Kyo
2015-05-01
Although the prevalence of rotator cuff tear (RCT) in the general population has been analyzed, little information is available on the status of the opposite-side rotator cuff in patients who have undergone arthroscopic rotator cuff repair. To identify the characteristics of the contralateral shoulder and to identify factors associated with RCT of the contralateral shoulder in patients who underwent surgery for symptomatic RCT. The hypothesis was that the prevalence of RCT in the contralateral shoulder would be higher in patients with increasingly larger cuff tears requiring surgical intervention. Case series; Level of evidence, 4. The study cohort consisted of 140 patients with RCT who underwent arthroscopic rotator cuff repair. Opposite-shoulder rotator cuff tendons of all patients were evaluated by ultrasonography. Demographic information and factors related to contralateral RCT were investigated, and risk factors associated with contralateral RCT were assessed. Of the 140 patients who underwent arthroscopic rotator cuff repair, 54 (38.6%) had an RCT of the contralateral shoulder. Of 51 patients with partial-thickness and small-sized full-thickness tears of the operated shoulder, 35 (68.6%) had no tears; 14 (27.5%) had partial-thickness tears; and 2 (3.9%) had small-sized full-thickness tears of the contralateral shoulder. Of 75 patients with medium-sized full-thickness tears, 43 (57.3%) had no tears; 12 (16%) had partial-thickness tears; and 20 (26.7%) had full-thickness tears of the contralateral shoulder. Of 14 patients with large to massive full-thickness tears, 8 (57.1%) had no tears; 1 (7.1%) had a partial-thickness tear; and 5 (35.7%) had full-thickness tears of the contralateral shoulder. The prevalence of RCT of the contralateral shoulder differed significantly among groups classified by tear size (P=.007). The mean American Shoulder and Elbow Surgeons score was significantly lower in the RCT than in the nontear group (55.8±16.9 vs 61.6±13.3; P=.03). Of 29 subjects with symptomatic tears involving the nondominant arm, 17 (58.6%) had contralateral asymptomatic RCT, compared with 37 of 111 (33.3%) subjects with symptomatic tears involving the dominant arm (P=.007). The prevalence of RCT of the contralateral asymptomatic shoulder tends to be higher in patients with more symptomatic RCT on one side, in patients with medium-sized or larger RCT in the operated shoulder, and in patients with symptomatic RCT in the nondominant arm. © 2015 The Author(s).
Williamson, Lydia; New, David
2014-01-01
Serum creatinine is a widely used marker in the assessment of renal function. Elevated creatinine levels suggest kidney dysfunction, prompting the need for further investigation. This report describes a case in which the consumption of the bodybuilding supplement creatine ethyl ester resulted in raised serum creatinine in the absence of true underlying kidney pathology. The abnormalities reversed after discontinuation of the supplement. A case of pseudo renal failure was recognised and kidney function was concluded to be normal. This report aims to address the mechanisms by which the ingestion of creatine ethyl ester can mimic the blood results expected in advanced renal failure, and confronts the problems faced when relying on serum creatinine as a diagnostic tool. PMID:25239988
Williamson, Lydia; New, David
2014-09-19
Serum creatinine is a widely used marker in the assessment of renal function. Elevated creatinine levels suggest kidney dysfunction, prompting the need for further investigation. This report describes a case in which the consumption of the bodybuilding supplement creatine ethyl ester resulted in raised serum creatinine in the absence of true underlying kidney pathology. The abnormalities reversed after discontinuation of the supplement. A case of pseudo renal failure was recognised and kidney function was concluded to be normal. This report aims to address the mechanisms by which the ingestion of creatine ethyl ester can mimic the blood results expected in advanced renal failure, and confronts the problems faced when relying on serum creatinine as a diagnostic tool. 2014 BMJ Publishing Group Ltd.
Computational analysis of kidney scintigrams
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vrincianu, D.; Puscasu, E.; Creanga, D.
The scintigraphic investigation of normal and pathological kidneys was carried out using specialized gamma-camera device from nuclear medicine hospital department. Technetium 90m isotope with gamma radiation emission, coupled with vector molecules for kidney tissues was introduced into the subject body, its dynamics being recorded as data source for kidney clearance capacity. Two representative data series were investigated, corresponding to healthy and pathological organs respectively. The semi-quantitative tests applied for the comparison of the two distinct medical situations were: the shape of probability distribution histogram, the power spectrum, the auto-correlation function and the Lyapunov exponent. While power spectrum led to similarmore » results in both cases, significant differences were revealed by means of distribution probability, Lyapunov exponent and correlation time, recommending these numerical tests as possible complementary tools in clinical diagnosis.« less
Aging and the Kidneys: Anatomy, Physiology and Consequences for Defining Chronic Kidney Disease.
Glassock, Richard J; Rule, Andrew D
2016-01-01
The varied functions of the kidneys are influenced by the complex process of aging. The glomerular filtration rate (GFR) steadily declines with normal aging, and the progress of this process can be influenced by superimposed diseases. Microscopically, nephron numbers decrease as global glomerulosclerosis becomes more evident. The precise mechanisms underlying nephron loss with aging are not well understood, but derangements in podocyte biology appear to be involved. Classifications of chronic kidney disease (CKD) incorporate GFR values and attendant risk of adverse events. Arbitrary and fixed thresholds of GFR for defining CKD have led to an overdiagnosis of CKD in the elderly. An age-sensitive definition of CKD could offer a solution to this problem and more meaningfully capture the prognostic implications of CKD. © 2016 S. Karger AG, Basel.
It was/wasn't everything I had imagined: advantages and disadvantages after kidney transplantation.
Santos, Bianca Pozza Dos; Viegas, Aline da Costa; Feijó, Aline Machado; Lise, Fernanda; Schwartz, Eda
2016-10-31
To know the advantages and difficulties that people with chronic kidney disease experience after renal transplantation. A qualitative and descriptive study with 20 kidney transplant patients in a city in Southern Brazil, from May to July of 2013. Semi-structured interviews were used, analyzed according to the critical incident technique. The main advantages were presented in the similarity to "normal" living: advantages resulting from the kidney transplant category, related to the patient's discharge from dialysis, food and water restriction, among others. The difficulties were presented in the permanent chronic condition and the need for care category. The advantages and disadvantages depend on each person's experience. The health professionals need to understand and promote health actions that promote the uniqueness and context of renal transplant.
Le, Trong Binh; Lee, Taeg Ki; Park, Keun-Myoung; Jeon, Yong Sun; Hong, Kee Chun; Cho, Soon Gu
2018-04-25
To investigate the incidence and potential causes of contralateral deep vein thrombosis (DVT) after common iliac vein (CIV) stent placement in patients with May-Thurner syndrome (MTS). Data of 111 patients (women: 73%) who had CIV stent implantation for symptomatic MTS at a single center were retrospectively analyzed. Mean patient age was 63.1 ± 15.2 years. Median follow-up was 36 months (range, 1-142 months). Stent location was determined by venogram and classified as extended to the inferior vena cava (IVC), covered the confluence, or confined to the iliac vein. Potential causes of contralateral DVT were presumed based on venographic findings. The relationship between stent location and contralateral DVT was analyzed. Ten patients (9%, men/women: 4/6) exhibited contralateral DVT at a median timing of 40 months (range, 6-98 months). Median age was 69 years (range, 42-85 years). Median follow-up was 73.5 months (range, 20-134 months). Potential causes were venous intimal hyperplasia (VIH) (n = 7), "jailing" (n = 2), and indeterminate (n = 1). All patients with VIH had previous CIV stents overextended to the IVC. Overextension of CIV stent was associated with contralateral DVT (P < .001). The primary patency rate of the contralateral CIV stent was 70% at 20 months. Contralateral DVT after CIV stent implantation has a relatively high incidence and often occurs late during follow-up. Overextension of the CIV stent to the IVC is associated with development of contralateral DVT, and VIH should be considered a potential cause. Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.
NASA Technical Reports Server (NTRS)
Rubin, A. L.; Stenzel, K. H.; Cheigh, J. S.; Seaman, G. V. F.; Novogrodsky, A.
1977-01-01
Electrophoretic mobilities (EPM) of peripheral lymphocytes were studied from normal subjects, chronic hemodialysis patients and kidney transplant recipients. A technique to separate B lymphocytes and null cells from non-T lymphocyte preparation was developed. The experiments were designed to determine which subpopulation of the non-T lymphocytes is primarily affected and shows a decreased EPM in chronic hemodialysis patients and kidney transplant recipients.
Cyclodextrin Protects Podocytes in Diabetic Kidney Disease
Merscher-Gomez, Sandra; Guzman, Johanna; Pedigo, Christopher E.; Lehto, Markku; Aguillon-Prada, Robier; Mendez, Armando; Lassenius, Mariann I.; Forsblom, Carol; Yoo, TaeHyun; Villarreal, Rodrigo; Maiguel, Dony; Johnson, Kevin; Goldberg, Ronald; Nair, Viji; Randolph, Ann; Kretzler, Matthias; Nelson, Robert G.; Burke, George W.; Groop, Per-Henrik; Fornoni, Alessia
2013-01-01
Diabetic kidney disease (DKD) remains the most common cause of end-stage kidney disease despite multifactorial intervention. We demonstrated that increased cholesterol in association with downregulation of ATP-binding cassette transporter ABCA1 occurs in normal human podocytes exposed to the sera of patients with type 1 diabetes and albuminuria (DKD+) when compared with diabetic patients with normoalbuminuria (DKD−) and similar duration of diabetes and lipid profile. Glomerular downregulation of ABCA1 was confirmed in biopsies from patients with early DKD (n = 70) when compared with normal living donors (n = 32). Induction of cholesterol efflux with cyclodextrin (CD) but not inhibition of cholesterol synthesis with simvastatin prevented podocyte injury observed in vitro after exposure to patient sera. Subcutaneous administration of CD to diabetic BTBR (black and tan, brachiuric) ob/ob mice was safe and reduced albuminuria, mesangial expansion, kidney weight, and cortical cholesterol content. This was followed by an improvement of fasting insulin, blood glucose, body weight, and glucose tolerance in vivo and improved glucose-stimulated insulin release in human islets in vitro. Our data suggest that impaired reverse cholesterol transport characterizes clinical and experimental DKD and negatively influences podocyte function. Treatment with CD is safe and effective in preserving podocyte function in vitro and in vivo and may improve the metabolic control of diabetes. PMID:23835338
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, H.B.; Blaufox, M.D.
This study evaluated the use of captopril which has been suggested as a therapeutic test for renal artery stenosis (RAS). Unilateral RAS was induced in rats by clamping the artery of the left kidney (LK) with a 0.76 (group a) or a 0.58mm (group b) I.D. polyethylene tube. The right kidney (RK) was the control. After clamping (1 wk) individual GFR was measured by continuous infusion in the normal and clamped kidney using Tc-99m DTPA. GFR was determined 3 times before (pc) and after (sc) i.v. injection of 10mg captopril/350g body weight. The mean of all 3 values was usedmore » for the analysis. Blood pressure (BP) in normal rats (130mmHg) was significantly different from group (a) and (b) (p<0.01 and p<0.005). The level of hypertension in the rats did not depend on the severity of renal artery constriction. Pre and post captopril GFR of the LK was significantly different both in (a) and (b) (p<0.01 and p<0.005), but GFR of the RK was not significantly changed. The administration of captopril showed an alteration of GFR in the clamped kidney. This finding suggests that captopril induced GFR changes may aid the diagnosis of RAS (Renal artery stenosis).« less
The influence of contrast media on kidney function in patients with stable coronary artery disease.
Reuter, Simon Bertram; Harutyunyan, Marina; Mygind, Naja Dam; Jørgensen, Erik; Kastrup, Jens
2014-08-01
To investigate the incidence of contrast media-induced nephropathy (CIN) in patients with stable coronary artery disease (CAD) referred for elective coronary intervention following hydration routines. The reversibility of CIN was followed in a 6 month-period. A total of 447 patients referred for elective coronary intervention due to suspected CAD were included. Blood samples were collected before and 24 h after intervention and medical records were obtained. Patients had no drinking fluid restrictions and were routinely treated with a 1000 ml saline infusion. All patients were invited to a 6-month examination and collection of blood samples. A total of 19 patients (4.3%) developed CIN. CIN patients had a pre-investigation higher estimated glomerular filtration rate (eGRF), lower level of kidney failure and lower creatinine level than non-CIN patients. Kidney function was not normalized in CIN patients 6 months after the intervention. Two patients still met the definition of CIN. With no restriction in fluid intake and supplementary infusion of saline, only a few patients with stable CAD developed early indications of CIN during elective coronary interventions. Kidney function and the amount of contrast media used was not a predictor of CIN development. The induced CIN was not completely normalized in a 6-month follow-up period.
Quantification of single-kidney glomerular filtration rate with electron-beam computed tomography
NASA Astrophysics Data System (ADS)
Lerman, Lilach O.; Ritman, Erik L.; Pelaez, Laura I.; Sheedy, Patrick F., II; Krier, James D.
2000-04-01
The ability to accurately and noninvasively quantify single- kidney GFR could be invaluable for assessment of renal function. We developed a model that enables this measurement with EBCT. To examine the reliability of this method, EBCT renal flow and volume studies after contrast media administration were performed in pigs with unilateral renal artery stenosis (Group 1), controls (Group 2), and simultaneously with inulin clearance (Group 3). Renal flow curves, obtained from the bilateral renal cortex and medulla, depicted transit of the contrast through the vascular and tubular compartments, and were fitted using extended gamma- variate functions. Renal blood flow was calculated as the sum of products of cortical and medullary perfusions and volumes. Normalized GFR (mL/min/cc) was calculated using the rate (maximal slope) of proximal tubular contrast accumulation, and EBCT-GFR as normalized GFR* cortical volume. In Group 1, the decreased GFR of the stenotic kidney correlated well with its decreased volume and RBF, and with the degree of stenosis (r equals -0.99). In Group 3, EBCT-GFR correlated well with inulin clearance (slope 1.1, r equals 0.81). This novel approach can be very useful for quantification of concurrent regional hemodynamics and function in the intact kidneys, in a manner potentially applicable to humans.
Pancreas transplantation: review
Meirelles, Roberto Ferreira; Salvalaggio, Paolo; Pacheco-Silva, Alvaro
2015-01-01
ABSTRACT Vascularized pancreas transplantation is the only treatment that establishes normal glucose levels and normalizes glycosylated hemoglobin levels in type 1 diabetic patients. The first vascularized pancreas transplant was performed by William Kelly and Richard Lillehei, to treat a type 1 diabetes patient, in December 1966. In Brazil, Edison Teixeira performed the first isolated segmental pancreas transplant in 1968. Until the 1980s, pancreas transplants were restricted to a few centers of the United States and Europe. The introduction of tacrolimus and mycophenolate mofetil in 1994, led to a significant outcome improvement and consequently, an increase in pancreas transplants in several countries. According to the International Pancreas Transplant Registry, until December 31st, 2010, more than 35 thousand pancreas transplants had been performed. The one-year survival of patients and pancreatic grafts exceeds 95 and 83%, respectively. The better survival of pancreatic (86%) and renal (93%) grafts in the first year after transplantation is in the simultaneous pancreas-kidney transplant group of patients. Immunological loss in the first year after transplant for simultaneous pancreas-kidney, pancreas after kidney, and pancreas alone are 1.8, 3.7, and 6%, respectively. Pancreas transplant has 10 to 20% surgical complications requiring laparotomy. Besides enhancing quality of life, pancreatic transplant increases survival of uremic diabetic patient as compared to uremic diabetic patients on dialysis or with kidney transplantation alone. PMID:26154551
Preoperative Low Serum Bicarbonate Levels Predict Acute Kidney Injury After Cardiac Surgery.
Jung, Su-Young; Park, Jung Tak; Kwon, Young Eun; Kim, Hyung Woo; Ryu, Geun Woo; Lee, Sul A; Park, Seohyun; Jhee, Jong Hyun; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook
2016-03-01
Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23 to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a protective role in preventing further AKI development.
Yoshida, Yutaka; Miyazaki, Kenji; Kamiie, Junichi; Sato, Masao; Okuizumi, Seiji; Kenmochi, Akihisa; Kamijo, Ken'ichi; Nabetani, Takuji; Tsugita, Akira; Xu, Bo; Zhang, Ying; Yaoita, Eishin; Osawa, Tetsuo; Yamamoto, Tadashi
2005-03-01
To contribute to physiology and pathophysiology of the glomerulus of human kidney, we have launched a proteomic study of human glomerulus, and compiled a profile of proteins expressed in the glomerulus of normal human kidney by two-dimensional gel electrophoresis (2-DE) and identification with matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and/or liquid chromatography-tandem mass spectrometry (LC-MS/MS). Kidney cortices with normal appearance were obtained from patients under surgical nephrectomy due to renal tumor, and glomeruli were highly purified by a standard sieving method followed by picking-up under a phase-contrast microscope. The glomerular proteins were separated by 2-DE with 24 cm immobilized pH gradient strips in the 3-10 range in the first dimension and 26 x 20 cm sodium dodecyl sulfate polyacrylamide electrophoresis gels of 12.5% in the second dimension. Gels were silver-stained, and valid spots were processed for identification through an integrated robotic system that consisted of a spot picker, an in-gel digester, and a MALDI-TOF MS and / or a LC-MS/MS. From 2-DE gel images of glomeruli of four subjects with no apparent pathologic manifestations, a synthetic gel image of normal glomerular proteins was created. The synthetic gel image contained 1713 valid spots, of which 1559 spots were commonly observed in the respective 2-DE gels. Among the 1559 spots, 347 protein spots, representing 212 proteins, have so far been identified, and used for the construction of an extensible markup language (XML)-based database. The database is deposited on a web site (http://www.sw.nec.co.jp/bio/rd/hgldb/index.html) in a form accessible to researchers to contribute to proteomic studies of human glomerulus in health and disease.
Yang, Yang; Liu, Zhong-Yu; Zhang, Liang-Ming; Dong, Jian-Wen; Xie, Pei-Gen; Chen, Rui-Qiang; Yang, Bu; Liu, Chang; Liu, Bin; Rong, Li-Min
2017-12-08
Microendoscopy-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is an advantageous method for treating lumbar degenerative disease; however, some patients show contralateral radiculopathy postoperatively. This study aims to investigate its risk factor. A total of 130 cases who underwent microendoscopy-assisted MIS-TLIF at L4-5 level were divided into symptomatic and asymptomatic groups according to the presence of postoperative contralateral radiculopathy. Both preoperative and postoperative radiographic parameters, as well as their changes were compared between the two groups, including lumbar lordosis (LL), surgical segmental angle (SSA), disc height (DH), contralateral foramen area (CFA) and contralateral canal area (CCA). Screw breach on contralateral L4 pedicle and decompression method (ipsilateral or bilateral canal decompression through unilateral route) were also analyzed as potential risk factors. Receiver operating characteristic (ROC) curve was drawn for the risk factor to determine the optimal threshold for predicting postoperative contralateral radiculopathy. Besides, clinical outcome assessment, involving Visual Analog Score (VAS) for back and leg, Japanese Orthopaedics Association Score (JOA) and Oswestry Disability Index (ODI), was also compared between the two groups before surgery and at final follow-up (at least 3 months after the surgery for asymptomatic patients or final treatments of contralateral radiculopathy for symptomatic cases). Postoperative contralateral radiculopathy occurred in 11 (8.5%) of the 130 patients. Both preoperative and postoperative CFA as well as its change were significantly decreased in symptomatic group compared with asymptomatic group (all P < 0.05). For the remaining four parameters (LL, SSA, DH, CCA), their preoperative, postoperative and change values showed no statistical difference between the two groups (all P > 0.05). Neither screw breach nor decompression method revealed statistical association with this complication (both P > 0.05). Based on ROC curve, the optimal threshold of preoperative CFA was 0.76 cm 2 . At final follow-up, significant improvement in VAS (back and leg), JOA and ODI was observed in both groups compared with preoperative baseline (all P < 0.05), while no difference was found between the two groups (all P > 0.05). Preoperative contralateral foramen stenosis is the risk factor of contralateral radiculopathy following microendoscopy-assisted MIS-TLIF. If preoperative CFA at L4-5 level is not larger than 0.76 cm 2 , prophylactic measures, including both indirect and direct decompression of contralateral foramen, are recommended.
Strichartz, Gary R; Khodorova, Alla; Wang, Jeffrey Chi-Fei; Chen, Yu-Wen; Huang, Chuan-Chin
2015-10-01
Contralateral hyperalgesia, occurring after unilateral injury, is usually explained by central sensitization in spinal cord and brain. We previously reported that injection of endothelin-1 (ET-1) into one rat hindpaw induces prolonged mechanical and chemical sensitization of the contralateral hindpaw. Here, we examined the role of contralateral efferent activity in this process. ET-1 (2 nmol, 10 μL) was injected subcutaneously into the plantar surface of right (ipsilateral) hindpaw (ILP), and the thermal response latency and mechanical threshold for nocifensive withdrawal were determined by the use of, respectively, plantar radiant heating and von Frey filaments, for both ILP and contralateral hindpaws (CLP). Either paw was anesthetized for 60 minutes by direct injection of bupivacaine (0.25%, 40 μL), 30 minutes before ET-1. Alternatively, the contralateral sciatic nerve was blocked for 6 to 12 hours by percutaneous injection of bupivacaine-releasing microspheres 30 minutes before injection of ET-1. Systemic actions of these bupivacaine formulations were simulated by subcutaneous injection at the nuchal midline. After the injection of ET-1, the mechanical threshold of both ILP and CLP decreased by 2 hours, appeared to be lowest around 24 hours, and recovered through 48 hours to preinjection baseline at 72 hours. These hypersensitive responses were suppressed by bupivacaine injected into the ipsilateral paw before ET-1. Injection of the CLP by bupivacaine also suppressed the hypersensitivity of the CLP at all test times, and that of the ILP, except at 2 hours when it increased the sensitivity. This same pattern of change occurred when the contralateral sciatic nerve was blocked by bupivacaine-releasing microspheres. The systemic actions of these bupivacaine formulations were much smaller and only reached significance at 24 hours post-ET-1. Thermal hypersensitivity after ET-1 injection also occurred in both ILP and CLP and showed the same pattern in response to the 2 contralateral anesthetic procedures. These results show that efferent transmission through the contralateral innervation into the paw is necessary for contralateral sensitization by ET-1, suggesting that the release of substances by distal nerve endings is involved. The release of substances in the periphery is essential for contralateral sensitization by ET-1 and may also contribute to secondary hyperalgesia, occurring at loci distant from the primary injury, that occurs after surgery or nerve damage.
Different methods of hilar clamping during partial nephrectomy: Impact on renal function.
Lee, Jeong Woo; Kim, Hwanik; Choo, Minsoo; Park, Yong Hyun; Ku, Ja Hyeon; Kim, Hyeon Hoe; Kwak, Cheol
2014-03-01
To evaluate the impact of different hilar clamping methods on changes in renal function after partial nephrectomy. We analyzed the clinical data of 369 patients who underwent partial nephrectomy for a single renal tumor of size ≤4.0 cm and a normal contralateral kidney. Patients were separated into three groups depending on hilar clamping method: non-clamping, cold ischemia and warm ischemia. Estimated glomerular filtration rate was examined at preoperative, nadir and 1 year postoperatively. Percent change in estimated glomerular filtration rate was used as the parameter to assess the renal functional outcome. Percent change in nadir estimated glomerular filtration rate in the non-clamping group was significantly less compared with the cold ischemia and warm ischemia groups (P < 0.001). However, no significant differences among the groups were noted in percent change of estimated glomerular filtration rate at 1 year (P = 0.348). The cold ischemia group had a similar serial change of postoperative renal function compared with the warm ischemia group. Percent change in 1-year estimated glomerular filtration rate increased with increasing ischemia time in the cold ischemia (P for trend = 0.073) and warm ischemia groups (P for trend = 0.010). On multivariate analysis, hilar clamping (both warm ischemia and cold ischemia) were significantly associated with percent change in nadir estimated glomerular filtration rate, but not in 1-year estimated glomerular filtration rate. Non-clamping partial nephrectomy results in a lower percent change in nadir estimated glomerular filtration rate, whereas it carries an estimated glomerular filtration rate change at 1 year that is similar to partial nephrectomy with cold ischemia and warm ischemia. Cold ischemia and warm ischemia provide a similar effect on renal function. Therefore, when hilar clamping is required, minimization of ischemia time is necessary. © 2013 The Japanese Urological Association.
Restricted Field IMRT Dramatically Enhances IMRT Planning for Mesothelioma
DOE Office of Scientific and Technical Information (OSTI.GOV)
Allen, Aaron M.; Schofield, Deborah; Hacker, Fred
2007-12-01
Purpose: To improve the target coverage and normal tissue sparing of intensity-modulated radiotherapy (IMRT) for mesothelioma after extrapleural pneumonectomy. Methods and Materials: Thirteen plans from patients previously treated with IMRT for mesothelioma were replanned using a restricted field technique. This technique was novel in two ways. It limited the entrance beams to 200{sup o} around the target and three to four beams per case had their field apertures restricted down to the level of the heart or liver to further limit the contralateral lung dose. New constraints were added that included a mean lung dose of <9.5 Gy and volumemore » receiving {>=}5 Gy of <55%. Results: In all cases, the planning target volume coverage was excellent, with an average of 97% coverage of the planning target volume by the target dose. No change was seen in the target coverage with the new technique. The heart, kidneys, and esophagus were all kept under tolerance in all cases. The average mean lung dose, volume receiving {>=}20 Gy, and volume receiving {>=}5 Gy with the new technique was 6.6 Gy, 3.0%, and 50.8%, respectively, compared with 13.8 Gy, 15%, and 90% with the previous technique (p < 0.0001 for all three comparisons). The maximal value for any case in the cohort was 8.0 Gy, 7.3%, and 57.5% for the mean lung dose, volume receiving {>=}20 Gy, and volume receiving {>=}5 Gy, respectively. Conclusion: Restricted field IMRT provides an improved method to deliver IMRT to a complex target after extrapleural pneumonectomy. An upcoming Phase I trial will provide validation of these results.« less
Incidental kidney stones: a single center experience with kidney donor selection
Kim, Irene K.; Tan, Jane C.; Lapasia, Jessica; Elihu, Arvand; Busque, Stephan; Melcher, Marc L.
2014-01-01
The presence of kidney stones has been a relative contraindication for living donation. With the widespread use of more sensitive imaging techniques as part of the routine living donor workup, kidney stones are more frequently detected, and their clinical significance in this setting is largely unknown. Records from 325 potential kidney donors who underwent MRA or CT-angiography were reviewed; 294 proceeded to donation. The prevalence of kidney stones found incidentally during donor evaluation was 7.4% (24 of 325). Sixteen donors with stones proceeded with kidney donation. All incidental calculi were nonobstructing and small (median 2 mm; range 1–9 mm). Eleven recipients were transplanted with allografts containing stones. One recipient developed symptomatic nephrolithasis after transplantation. This recipient was found to have newly formed stones secondary to hyperoxaluria, suggesting a recipient-driven propensity for stone formation. The remaining ten recipients have stable graft function, postoperative ultrasound negative for nephrolithiasis, and no sequelae from stones. No donor developed symptomatic nephrolithiasis following donation. Judicious use of allografts with small stones in donors with normal metabolic studies may be acceptable, and careful follow-up in recipients of such allografts is warranted. PMID:22168332
Mami, Iadh; Bouvier, Nicolas; El Karoui, Khalil; Gallazzini, Morgan; Rabant, Marion; Laurent-Puig, Pierre; Li, Shuping; Tharaux, Pierre-Louis; Beaune, Philippe; Thervet, Eric; Chevet, Eric; Hu, Guo-Fu
2016-01-01
Endoplasmic reticulum (ER) stress is involved in the pathophysiology of kidney disease and aging, but the molecular bases underlying the biologic outcomes on the evolution of renal disease remain mostly unknown. Angiogenin (ANG) is a ribonuclease that promotes cellular adaptation under stress but its contribution to ER stress signaling remains elusive. In this study, we investigated the ANG-mediated contribution to the signaling and biologic outcomes of ER stress in kidney injury. ANG expression was significantly higher in samples from injured human kidneys than in samples from normal human kidneys, and in mouse and rat kidneys, ANG expression was specifically induced under ER stress. In human renal epithelial cells, ER stress induced ANG expression in a manner dependent on the activity of transcription factor XBP1, and ANG promoted cellular adaptation to ER stress through induction of stress granules and inhibition of translation. Moreover, the severity of renal lesions induced by ER stress was dramatically greater in ANG knockout mice (Ang−/−) mice than in wild-type mice. These results indicate that ANG is a critical mediator of tissue adaptation to kidney injury and reveal a physiologically relevant ER stress-mediated adaptive translational control mechanism. PMID:26195817
Unilateral hearing during development: hemispheric specificity in plastic reorganizations
Kral, Andrej; Heid, Silvia; Hubka, Peter; Tillein, Jochen
2013-01-01
The present study investigates the hemispheric contributions of neuronal reorganization following early single-sided hearing (unilateral deafness). The experiments were performed on ten cats from our colony of deaf white cats. Two were identified in early hearing screening as unilaterally congenitally deaf. The remaining eight were bilaterally congenitally deaf, unilaterally implanted at different ages with a cochlear implant. Implanted animals were chronically stimulated using a single-channel portable signal processor for two to five months. Microelectrode recordings were performed at the primary auditory cortex under stimulation at the hearing and deaf ear with bilateral cochlear implants. Local field potentials (LFPs) were compared at the cortex ipsilateral and contralateral to the hearing ear. The focus of the study was on the morphology and the onset latency of the LFPs. With respect to morphology of LFPs, pronounced hemisphere-specific effects were observed. Morphology of amplitude-normalized LFPs for stimulation of the deaf and the hearing ear was similar for responses recorded at the same hemisphere. However, when comparisons were performed between the hemispheres, the morphology was more dissimilar even though the same ear was stimulated. This demonstrates hemispheric specificity of some cortical adaptations irrespective of the ear stimulated. The results suggest a specific adaptation process at the hemisphere ipsilateral to the hearing ear, involving specific (down-regulated inhibitory) mechanisms not found in the contralateral hemisphere. Finally, onset latencies revealed that the sensitive period for the cortex ipsilateral to the hearing ear is shorter than that for the contralateral cortex. Unilateral hearing experience leads to a functionally-asymmetric brain with different neuronal reorganizations and different sensitive periods involved. PMID:24348345
Unilateral hearing during development: hemispheric specificity in plastic reorganizations.
Kral, Andrej; Heid, Silvia; Hubka, Peter; Tillein, Jochen
2013-01-01
The present study investigates the hemispheric contributions of neuronal reorganization following early single-sided hearing (unilateral deafness). The experiments were performed on ten cats from our colony of deaf white cats. Two were identified in early hearing screening as unilaterally congenitally deaf. The remaining eight were bilaterally congenitally deaf, unilaterally implanted at different ages with a cochlear implant. Implanted animals were chronically stimulated using a single-channel portable signal processor for two to five months. Microelectrode recordings were performed at the primary auditory cortex under stimulation at the hearing and deaf ear with bilateral cochlear implants. Local field potentials (LFPs) were compared at the cortex ipsilateral and contralateral to the hearing ear. The focus of the study was on the morphology and the onset latency of the LFPs. With respect to morphology of LFPs, pronounced hemisphere-specific effects were observed. Morphology of amplitude-normalized LFPs for stimulation of the deaf and the hearing ear was similar for responses recorded at the same hemisphere. However, when comparisons were performed between the hemispheres, the morphology was more dissimilar even though the same ear was stimulated. This demonstrates hemispheric specificity of some cortical adaptations irrespective of the ear stimulated. The results suggest a specific adaptation process at the hemisphere ipsilateral to the hearing ear, involving specific (down-regulated inhibitory) mechanisms not found in the contralateral hemisphere. Finally, onset latencies revealed that the sensitive period for the cortex ipsilateral to the hearing ear is shorter than that for the contralateral cortex. Unilateral hearing experience leads to a functionally-asymmetric brain with different neuronal reorganizations and different sensitive periods involved.
[Lower limb salvage with a free fillet fibula flap harvested from the contralateral amputated leg].
Bouyer, M; Corcella, D; Forli, A; Mesquida, V; Semere, A; Moutet, F
2015-06-01
We report a unusual case of "fillet flap" to reconstruct the lower limb with the amputated contralateral leg. This kind of procedure was first described by Foucher et al. in 1980 for traumatic hand surgery as the "bank finger". A 34-year-old man suffered a microlight accident with bilateral open legs fractures. A large skin defect of the left leg exposed the ankle, the calcaneus and a non-vascularized part of the tibial nerve (10 cm). The patient came to the OR for surgical debridement and had massive bone resection of the left calcaneus. The right leg showed limited skin defect at the lower part, exposing the medial side of the ankle and a tibial bone defect, measuring 10 cm. Salvage the left leg was impossible due to complex nerve, bones and skin associated injuries, so this leg was sacrificed and used as a donor limb, to harvest a free fibula flap for contralateral tibial reconstruction. At 18 months of follow-up, the patient was very satisfied, the clinical result was very good on both lower limbs and X-rays showed excellent integration of the free fibula flap. The patient had normal dailies occupations, can run and have bicycle sport practice with a functional left leg fit prosthesis. This case showed an original application of the "fillet flap concept" to resolve complex and rare traumatic situations interesting the both lower limbs. In our opinion, this strategy must be a part of the plastic surgeon skills in uncommon situations. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Barmack, N.H.; Yakhnitsa, V.
2011-01-01
Cerebellar Purkinje cells have two distinct action potentials: Complex spikes (CSs) are evoked by single climbing fibers that originate from the contralateral inferior olive. Simple spikes (SSs) are often ascribed to mossy fiber---granule cell---parallel fiber inputs to Purkinje cells. Although generally accepted, this view lacks experimental support. Vestibular stimulation independently activates primary afferent mossy fibers and tertiary afferent climbing fibers that project to theuvula-nodulus (folia 8-10). CSs and SSs normally discharge antiphasically during sinusoidal roll-tilt. When CSs increase, SSs decrease. We tested the relative independence of these pathways in mice by making electrolytic microlesions of the two inferior olivary nuclei from which vestibular climbing fibers originate; the β-nucleus and dorsomedial cell column (DMCC). This reduced vestibular climbing fiber signaling to the contralateral folia 8-10, while leaving intact vestibular primary and secondary afferent mossy fibers. We recorded from Purkinje cells and interneurons in folia 8-10, identified by juxtacellular labeling with neurobiotin. Microlesions of the inferior olive increased the spontaneous discharge of SSs in contralateral folia 8-10, but blocked their modulation during vestibular stimulation. The vestibularly-evoked discharge of excitatory cerebellar interneurons (granule cells and unipolar brush cells) was not modified by olivary microlesions. The modulated discharge of stellate cells, but not Golgi cells was reduced by olivary microlesions. We conclude that vestibular modulation of CSs and SSs depends on intact climbing fibers. The absence of vestibularly-modulated SSs following olivary microlesions reflects the loss of climbing fiber-evoked stellate cell discharge. PMID:21734274
Reliability of measures of transient evoked otoacoustic emissions with contralateral suppression.
Stuart, Andrew; Cobb, Kensi M
2015-01-01
The reliability of measures of transient evoked otoacoustic emissions (TEOAEs) with contralateral suppression was examined. The effect of test session (i.e., initial test; retest without probe removal; retest with probe removal; and retest 1-2 days post initial test), gender, and ear was examined in 14 young adult females and 14 young adult males. TEOAEs were obtained bilaterally with 60 dB peSPL linear click stimuli with and without a contralateral 65 dB SPL broadband noise suppressor. Absolute TEOAE suppression and a normalized index of TEOAE suppression (i.e., percentage of suppression) were examined. Reliability of these measures was assessed with repeated measures linear mixed model analysis of variance, a coefficient of reliability, and Bland-Altman analyses. There were no statistically significant (p>0.05) main effects of test, gender, and ear or interactions for both absolute dB and % TEOAE suppression values. Cronbach's α were greater than 0.90 across the four tests for both TEOAE measures. Mean test differences or bias (i.e., between the initial and subsequent tests) for absolute and % TEOAE suppression ranged from -0.05 to 0.11 dB and -1.5% to 1.1%, respectively. There was no proportional/systematic bias with the mean differences of the first and subsequent measurements. Data herein were consistent with the view that bilateral TEOAE suppression measures are reliable across test sessions of 1-2 days among females and males and may provide a method to monitor medial olivocochlear efferent reflex status over time. Copyright © 2015 Elsevier Inc. All rights reserved.
Starbuck, M J; Poole, D H; Inskeep, E K
2006-07-15
The local relationship between the pregnant uterine horn and the CL during maternal recognition of pregnancy is well-documented. It continues beyond that time; pregnancies were maintained in lutectomized cows when CL were induced on the ovary ipsilateral, but not contralateral, to the uterine horn of pregnancy during Days 28-53. This study evaluated factors affecting maintenance of pregnancy by CL induced after Day 53, in lutectomized cows that had received exogenous progesterone from Day 29 to 15 days after induction of a CL. Twenty-four suckled beef cows were lutectomized on Day 29 of gestation; pregnancy was maintained with progesterone from two controlled internal drug releasing (CIDR) inserts, exchanged every 5 days. Beginning on Day 53, ovaries and viability of pregnancy were evaluated by ultrasonography every 5 days. When a follicle >or=10 mm in diameter was present ipsilateral to the fetus, each cow received 1,000 IU of hCG. Following induction of a CL (20 of 24), progesterone was reduced to a single CIDR for 5 days, then removed. Retention of pregnancy was confirmed by rectal palpation and calving. Cows with induced CL maintained pregnancy to term, including four with the CL contralateral to the fetus. Three cows failed to form normal CL by Day 98 and lost pregnancy after removal of exogenous progesterone. One cow that did not respond to hCG lost pregnancy during exogenous progesterone. In conclusion, CL induced after Day 53 maintained pregnancy to term, even when induced contralateral to the pregnant uterine horn.
Watanabe, Hironori; Kanehisa, Hiroaki; Yoshitake, Yasuhide
2017-10-01
The present study aimed to examine (1) the effect of task difficulty on unintended muscle activation (UIMA) levels in contralateral homologous muscle, (2) the difference between young and old adults in degree of UIMA with respect to task difficulty, and (3) temporal correlations between intended and contralateral unintended muscle activity at low frequency during unilateral intended force-matching tasks. Twelve young (21.8 ± 2.4 years) and twelve old (69.9 ± 5.3 years) adult men performed steady isometric abductions with the left index finger at 20-80% of maximal voluntary contraction force. Two task difficulties were set by adjusting the spacing between two bars centered about the target force used for visual feedback on a monitor. The amplitude of surface electromyogram (aEMG) for both hands was calculated and normalized with respect to the maximal value. To determine if oscillations between intended and unintended muscle activities were correlated, cross-correlation function (CCF) of rectified EMG for both hands at low frequency was calculated for samples deemed adequate. The unintended aEMG (right hand) had significant main effects in task difficulty, age, and target force (all P < 0.05) without any interactions. Distinct significant peaks in CCF (0.38 on average, P < 0.05) with small time lags were present between rectified EMGs of intended and unintended muscles in 14 of the 17 samples. The current results indicate that UIMA increases with greater task difficulty regardless of age, and temporal correlations exist between intended and contralateral unintended muscle activities at low frequency.
Pinto, Lecio F; Adda, Carla C; Silva, Liliane C A; Banaskiwitz, Natalie H C; Passarelli, Valmir; Jorge, Carmen L; Valerio, Rosa M; Castro, Luiz H
2017-03-01
Memory impairment is a recognized complication of mesial temporal sclerosis (MTS). Epileptiform activity may negatively impact on cognition. We evaluated the impact of contralateral EEG involvement on memory in unilateral MTS (uMTS) patients. Retrospective review of 121 right-handed uMTS patients (69 left) evaluated with prolonged video-EEG and verbal and nonverbal memory tests (Rey Auditory Verbal Learning Test and Rey-Osterrieth Complex figure), with additional very delayed trials. Patients were classified according to ictal/interictal EEG findings and MTS side as left or right concordant or discordant. Thirty-nine normal individuals who underwent the same neuropsychological battery served as controls. Demographic, disease, and treatment features did not differ among groups. On the 7-day verbal memory free recall, left discordant performed significantly worse than controls and right concordant, recognized fewer words, and had more recognition errors than all other groups, including left concordant. For nonverbal memory, right discordant performed significantly worse than controls on delayed recall, and attained lower scores than other groups on immediate and 7-day recall, but this difference did not reach statistical significance. Left discordant had higher scores of memory complaints than controls and disclosed a trend toward accentuated memory impairment compared with the other groups over time. Our results suggest that contralateral electrographic involvement in uMTS was associated with more pronounced memory impairment for verbal material in left discordant patients, and to a lesser extent, for nonverbal material in right discordant patients. Left discordant group also had increased memory complaints. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Antigravity suit inflation - Kidney function and cardiovascular and hormonal responses in men
NASA Technical Reports Server (NTRS)
Geelen, Ghislaine; Kravik, Stein E.; Hadj-Aissa, Aoumeur; Leftheriotis, Georges; Vincent, Madeleine
1989-01-01
The effect of the lower body positive pressure (LBPP) on kidney function in normal men was investigated in experiments in which the subjects underwent 30 min of sitting and then were subjected to 4.5 h of 70-deg head-up tilt. During the last 3 h of the tilt period, an antigravity suit (60 T legs, 30 T abdomen) was applied. The results showed that LBPP induces a significant increase in effective renal plasma flow and significant changes in the kidney excretory patterns, which were similar to those observed during a water immersion or the early phase of bed rest.
Khan, S A; Sattar, M Z A; Abdullah, N A; Rathore, H A; Abdulla, M H; Ahmad, A; Johns, E J
2015-07-01
This study investigated the role of the renal innervation in arterial and cardiopulmonary baroreflex regulation of renal sympathetic nerve activity (RSNA) and heart rate (HR) in rats fed a high-fat diet to induce obesity. Rats received either a normal (12% kcal) or high (45% kcal) fat diet for 60 days. On day 61, rats were anesthetized and prepared for recording left RSNA. In one group, the renal nerves remained intact, while in the other, both kidneys were denervated. Baroreflex gain curves for RSNA and HR were generated by increasing and decreasing blood pressure. Low-pressure baroreceptors were challenged by infusing a saline load. Mean blood pressure was 135 mmHg in the fat-fed and 105 mmHg (P < 0.05) in normal rats. Weight gain, adiposity index and creatinine clearance were 37, 82 and 55% higher (P < 0.05-0.001), but urine flow rate and fractional sodium excretions were 53 and 65% (both P < 0.001) lower, respectively, in the fat-fed compared to normal rats. In fat-fed rats with innervated kidneys, RSNA and HR arterial baroreflex sensitivities were reduced by 73 and 72% (both P < 0.05) but were normal in renally denervated rats. Volume expansion decreased RSNA by 66% (P < 0.001) in normal rats, but not in the intact fat-fed rats and by 51% (P < 0.01) in renally denervated fat-fed rats. Feeding a high-fat diet caused hypertension associated with dysregulation of the arterial and cardiopulmonary baroreflexes which was dependent on an intact renal innervation. This suggests that in obese states neural signals arising from the kidney contribute to a deranged autonomic control. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
Schuchardt, Christiane; Kulkarni, Harshad R; Prasad, Vikas; Zachert, Carolin; Müller, Dirk; Baum, Richard P
2013-01-01
The objective of this study is to analyze the in vivo behavior of the (177)Lu-labeled peptides DOTATATE, DOTANOC, and DOTATOC used for peptide receptor radionuclide therapy (PRRNT) of neuroendocrine tumors (NETs), by measuring organ and tumor kinetics and by performing dosimetric calculations. Two hundred fifty-three patients (group 1) with metastasized NET who underwent PRRNT were examined. Out of these, 185 patients received (177)Lu-DOTATATE, 9 were treated with (177)Lu-DOTANOC, and 59 with (177)Lu-DOTATOC. Additionally, 25 patients receiving, in consecutive PRRNT cycles, DOTATATE followed by DOTATOC (group 2) and 3 patients receiving DOTATATE and DOTANOC (group 3) were analyzed. Dosimetric calculations (according to MIRD scheme) were performed using OLINDA software. In group 1, DOTATOC exhibited the lowest and DOTANOC the highest uptake and therefore mean absorbed dose in normal organs (whole body, kidney, and spleen). In group 2, there was a significant difference between DOTATATE and DOTATOC concerning kinetics and normal organ doses. (177)Lu-DOTATOC had the lowest uptake/dose delivered to normal organs and highest tumor-to-kidney ratio. There were no significant differences between the three peptides concerning tumor kinetics and mean absorbed tumor dose. The study demonstrates a correlation between high affinity of DOTANOC in vitro and high uptake in normal organs/whole body in vivo, resulting in a higher whole-body dose. DOTATOC exhibited the lowest uptake and dose delivered to normal tissues and the best tumor-to-kidney ratio. Due to large interpatient variability, individual dosimetry should be performed for each therapy cycle.
Bai, Shaochun; Wang, Hongwei; Shen, Jikun; Zhou, Randal; Bushinsky, David A; Favus, Murray J
2010-01-01
Patients with idiopathic hypercalciuria (IH) and genetic hypercalciuric stone-forming (GHS) rats, an animal model of IH, are both characterized by normal serum Ca, hypercalciuria, Ca nephrolithiasis, reduced renal Ca reabsorption, and increased bone resorption. Serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels are elevated or normal in IH and are normal in GHS rats. In GHS rats, vitamin D receptor (VDR) protein levels are elevated in intestinal, kidney, and bone cells, and in IH, peripheral blood monocyte VDR levels are high. The high VDR is thought to amplify the target-tissue actions of normal circulating 1,25(OH)2D levels to increase Ca transport. The aim of this study was to elucidate the molecular mechanisms whereby Snail may contribute to the high VDR levels in GHS rats. In the study, Snail gene expression and protein levels were lower in GHS rat tissues and inversely correlated with VDR gene expression and protein levels in intestine and kidney cells. In human kidney and colon cell lines, ChIP assays revealed endogenous Snail binding close to specific E-box sequences within the human VDR promoter region, whereas only one E-box specifically bound Snail in the rat promoter. Snail binding to rat VDR promoter E-box regions was reduced in GHS compared with normal control intestine and was accompanied by hyperacetylation of histone H3. These results provide evidence that elevated VDR in GHS rats likely occurs because of derepression resulting from reduced Snail binding to the VDR promoter and hyperacetylation of histone H3. © 2010 American Society for Bone and Mineral Research. PMID:19929616
Soetikno, Vivian; Sari, Shinta Dewi Permata; Ul Maknun, Lulu; Sumbung, Nielda Kezia; Rahmi, Deliana Nur Ihsani; Pandhita, Bashar Adi Wahyu; Louisa, Melva; Estuningtyas, Ari
2018-06-26
In addition to oxidative stress, inflammation and apoptosis have an important role in the pathogenesis of cisplatin-induced kidney damage. This study aimed to investigate the molecular mechanisms of protective effects of curcumin against cisplatin-induced kidney inflammation and apoptosis in rats. Eighteen rats were equally divided into three groups; normal (0.5% CMC-Na), cisplatin (CDPP) (7 mg/kg i.p.), and cisplatin+curcumin (CMN100) groups. Curcumin was given at a dose of 100 mg/kg orally for nine days, starts one week before giving a single dose of cisplatin. Kidney and plasma were taken for analysis. Cisplatin challenged rats demonstrated kidney injury as shown by reduced creatinine clearance, increased of plasma BUN, plasma creatinine, and kidney MDA, decreased of kidney GSH levels, and kidney histopathology alterations. Also, cisplatin increased ERK1/2 phosphorylation and NF-κB expression, which subsequently increased mRNA expression of TNF-α, IL-6, KIM-1, NGAL, and Bax/Bcl-2 ratio as well as decreased mRNA expression of IL-10 in kidney tissues. Pre-treatment with curcumin significantly ameliorated inflammation and apoptosis induced by cisplatin. In addition, curcumin downregulated Ctr1 and OCT2 drug transporters as compared to cisplatin group. Histopathological examination furthers confirmed the kidney damage protection effect of curcumin. These data indicate that curcumin has nephroprotective properties against cisplatin-induced kidney damage in rats and this effect is associated with its anti-inflammatory and anti-apoptosis profiles, in addition to its antioxidant. Hence, curcumin may be useful for preventing kidney damage against cisplatin administration. © Georg Thieme Verlag KG Stuttgart · New York.
Wang, Zhen; do Carmo, Jussara M; Aberdein, Nicola; Zhou, Xinchun; Williams, Jan M; da Silva, Alexandre A; Hall, John E
2017-05-01
Diabetes mellitus and hypertension are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. In this study, we assessed interactions of hypertension and diabetes mellitus in causing kidney dysfunction and injury and the role of endoplasmic reticulum (ER) stress. Hypertension was induced by aorta constriction (AC) between the renal arteries in 6-month-old male Goto-Kakizaki (GK) type 2 diabetic and control Wistar rats. Fasting plasma glucose averaged 162±11 and 87±2 mg/dL in GK and Wistar rats, respectively. AC produced hypertension in the right kidney (above AC) and near normal blood pressure in the left kidney (below AC), with both kidneys exposed to the same levels of glucose, circulating hormones, and neural influences. After 8 weeks of AC, blood pressure above the AC (and in the right kidney) increased from 109±1 to 152±5 mm Hg in GK rats and from 106±4 to 141±5 mm Hg in Wistar rats. The diabetic-hypertensive right kidneys in GK-AC rats had much greater increases in albumin excretion and histological injury compared with left kidneys (diabetes mellitus only) of GK rats or right kidneys (hypertension only) of Wistar-AC rats. Marked increases in ER stress and oxidative stress indicators were observed in diabetic-hypertensive kidneys of GK-AC rats. Inhibition of ER stress with tauroursodeoxycholic acid for 6 weeks reduced blood pressure (135±4 versus 151±4 mm Hg), albumin excretion, ER and oxidative stress, and glomerular injury, while increasing glomerular filtration rate in hypertensive-diabetic kidneys. These results suggest that diabetes mellitus and hypertension interact synergistically to promote kidney dysfunction and injury via ER stress. © 2017 American Heart Association, Inc.
The effect of cholesterol overload on mouse kidney and kidney-derived cells.
Honzumi, Shoko; Takeuchi, Miho; Kurihara, Mizuki; Fujiyoshi, Masachika; Uchida, Masashi; Watanabe, Kenta; Suzuki, Takaaki; Ishii, Itsuko
2018-11-01
Dyslipidemia is one of the onset and risk factors of chronic kidney disease and renal function drop is seen in lipoprotein abnormal animal models. However, the detailed molecular mechanism of renal lipotoxicity has not been clarified. Therefore, the present study aimed to investigate the influence of cholesterol overload using mouse kidney tissue and kidney-derived cultured cells. C57BL/6 mice were fed normal diet (ND) or 1.25% cholesterol-containing high-cholesterol diet (HCD) for 11 weeks, and we used megalin as a proximal tubule marker for immunohistology. We added beta-very low density lipoprotein (βVLDL) to kidney-derived cells and examined the effect of cholesterol overload on megalin protein and mRNA expression level, cell proliferation and cholesterol content in cells. In the kidney of HCD mice, the gap between glomerulus and the surrounding Bowman's capsule decreased and the expression level of megalin decreased. After βVLDL treatment to the cells, the protein expression and mRNA expression level of megalin decreased and cell proliferation was restrained. We also observed an increase in cholesterol accumulation in the cell and free cholesterol/phospholipid ratios increased. These findings suggest that the increased cholesterol load on kidney contribute to the decrease of megalin and the overloaded cholesterol is taken into the renal tubule epithelial cells, causing suppression on cell proliferation, which may be the cause of kidney damage.
The Leaf of Diospyros kaki Thumb Ameliorates Renal Oxidative Damage in Mice with Type 2 Diabetes
Choi, Myung-Sook; Jeong, Mi Ji; Park, Yong Bok; Kim, Sang Ryong; Jung, Un Ju
2016-01-01
Diabetic kidney disease is the most common and severe chronic complication of diabetes. The leaf of Diospyros kaki Thumb (persimmon) has been commonly used for herbal tea and medicinal purposes to treat a variety of conditions, including hypertension and atherosclerosis. However, the effect of persimmon leaf on kidney failure has not been investigated. This study aimed to examine the role of persimmon leaf in protecting the diabetes-associated kidney damage in a mouse model of type 2 diabetes. Mice were fed either a normal chow diet with or without powered persimmon leaf (5%, w/w) for 5 weeks. In addition to kidney morphology and blood markers of kidney function, we assessed levels of oxidative stress markers as well as antioxidant enzymes activities and mRNA expression in the kidney. Supplementation of the diet with powered persimmon leaf not only decreased the concentration of blood urea nitrogen in the plasma but also improved glomerular hypertrophy. Furthermore, the persimmon leaf significantly decreased the levels of hydrogen peroxide and lipid peroxide in the kidney. The activities of superoxide dismutase, catalase, and glutathione peroxidase and the mRNA expression of their respective genes were also increased in the kidney of persimmon leaf-supplemented db/db mice. Taken together, these results suggest that supplementation with the persimmon leaf may have protective effects against type 2 diabetes-induced kidney dysfunction and oxidative stress. PMID:28078262
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ji, Jiayao; Medical College of NanKai University, Tianjin; Li, Qinggang
2012-05-11
Highlights: Black-Right-Pointing-Pointer Overexpression of Robo2 caused reduced UB branching and glomerular number. Black-Right-Pointing-Pointer Fewer MM cells surrounding the UB after overexpression of Robo2 in vitro. Black-Right-Pointing-Pointer No abnormal Epithelial Morphology of UB or apoptosis of mm cells in the kidney. Black-Right-Pointing-Pointer Overexpression of Robo2 affected MM cells migration and caused UB deficit. Black-Right-Pointing-Pointer The reduced glomerular number can also be caused by fewer MM cells. -- Abstract: Roundabout 2 (Robo2) is a member of the membrane protein receptor family. The chemorepulsive effect of Slit2-Robo2 signaling plays vital roles in nervous system development and neuron migration. Slit2-Robo2 signaling is also importantmore » for maintaining the normal morphogenesis of the kidney and urinary collecting system, especially for the branching of the ureteric bud (UB) at the proper site. Slit2 or Robo2 mouse mutants exhibit multilobular kidneys, multiple ureters, and dilatation of the ureter, renal pelvis, and collecting duct system, which lead to vesicoureteral reflux. To understand the effect of Robo2 on kidney development, we used microinjection and electroporation to overexpress GFP-Robo2 in an in vitro embryonic kidney model. Our results show reduced UB branching and decreased glomerular number after in vitro Robo2 overexpression in the embryonic kidneys. We found fewer metanephric mesenchymal (MM) cells surrounding the UB but no abnormal morphology in the branching epithelial UB. Meanwhile, no significant change in MM proliferation or apoptosis was observed. These findings indicate that Robo2 is involved in the development of embryonic kidneys and that the normal expression of Robo2 can help maintain proper UB branching and glomerular morphogenesis. Overexpression of Robo2 leads to reduced UB branching caused by fewer surrounding MM cells, but MM cell apoptosis is not involved in this effect. Our study demonstrates that overexpression of Robo2 by microinjection in embryonic kidneys is an effective approach to study the function of Robo2.« less
Li, Wenliang; Kessler, Patricia; Williams, Bryan R G
2005-01-13
Anaplasia (unfavorable histology) is associated with therapy resistance and poor prognosis of Wilms tumor, but the molecular basis for this phenotype is unclear. Here, we used a cDNA array with 9240 clones relevant to cancer biology and/or kidney development to examine the expression profiles of 54 Wilms tumors, five normal kidneys and fetal kidney. By linking genes differentially expressed between fetal kidney and Wilms tumors to kidney morphogenesis, we found that genes expressed at a higher level in Wilms tumors tend to be expressed more in uninduced metanephrogenic mesenchyme or blastema than in their differentiated structures. Conversely, genes expressed at a lower level in Wilms tumors tend to be expressed less in uninduced metanephrogenic mesenchyme or blastema. We also identified 97 clones representing 76 Unigenes or unclustered ESTs that clearly separate anaplastic Wilms tumors from tumors with favorable histology. Genes in this set provide insight into the nature of the abnormal nuclear morphology of anaplastic tumors and may facilitate identification of molecular targets to improve their responsiveness to treatment.
New approaches in renal microscopy: volumetric imaging and superresolution microscopy.
Kim, Alfred H J; Suleiman, Hani; Shaw, Andrey S
2016-05-01
Histologic and electron microscopic analysis of the kidney has provided tremendous insight into structures such as the glomerulus and nephron. Recent advances in imaging, such as deep volumetric approaches and superresolution microscopy, have the capacity to dramatically enhance our current understanding of the structure and function of the kidney. Volumetric imaging can generate images millimeters below the surface of the intact kidney. Superresolution microscopy breaks the diffraction barrier inherent in traditional light microscopy, enabling the visualization of fine structures. Here, we describe new approaches to deep volumetric and superresolution microscopy of the kidney. Rapid advances in lasers, microscopic objectives, and tissue preparation have transformed our ability to deep volumetric image the kidney. Innovations in sample preparation have allowed for superresolution imaging with electron microscopy correlation, providing unprecedented insight into the structures within the glomerulus. Technological advances in imaging have revolutionized our capacity to image both large volumes of tissue and the finest structural details of a cell. These new advances have the potential to provide additional profound observations into the normal and pathologic functions of the kidney.
Matsumura, Kazuya; Sugii, Kyoko; Awazu, Midori
2018-06-07
Children with a solitary functioning kidney have a risk of renal injury caused by hyperfiltration. Timely intervention with renin-angiotensin inhibitors may be beneficial. We examined whether trajectory of estimated glomerular filtration rate (eGFR) would predict renal injury, defined as microalbuminuria/proteinuria, hypertension, and/or a decline in eGFR. Seventeen patients (male 7, female 10) with multicystic dysplastic kidney (MCDK; median age 13 years, range 6-19 years) followed in our clinic were examined retrospectively. An eGFR decline was defined as a fall to < 90 mL/min/1.73 m2 or a decline of > 5 mL/min/1.73 m2/year for those with baseline eGFR of ≥90 or < 90 mL/min/1.73 m2 respectively. Nine patients had renal injury at the time of investigation. Compared with 8 patients without renal injury, those with renal injury tended to be older (14.7 ± 4.2 vs. 11.4 ± 4.6 years) and the birth weight was smaller (2,538 ± 281 vs. 2,966 ± 361 g, p < 0.05). The frequency of contralateral congenital anomaly of kidney and urinary tract (cyst, hydronephrosis, or vesicoureteral reflux) were not different. The trajectory of eGFR in those without renal injury was either an increase (n = 3) or unidentifiable (n = 5), whereas that in the renal injury group was exclusively an increase followed by decline (p < 0.05). The average age of the onset of eGFR decline was 9.4 ± 4.2 years and that of the start of renal injury (albuminuria/proteinuria 5, eGFR decline 4, hypertension 1) was 12.5 ± 4.2 years. All the children with MCDK who developed renal injury had eGFR trajectory of increase followed by decline. Renal injury followed the peak eGFR by 3 years on average. This observation is in agreement with the hyperfiltration theory and underscores the importance of following eGFR trajectory closely. © 2018 S. Karger AG, Basel.
Päivärinta, Johanna; Koivuviita, Niina; Oikonen, Vesa; Iida, Hidehiro; Liukko, Kaisa; Manner, Ilkka; Löyttyniemi, Eliisa; Nuutila, Pirjo; Metsärinne, Kaj
2018-06-11
Microvascular function plays an important role in ARVD (atherosclerotic renovascular disease). RFR (renal flow reserve), the capacity of renal vasculature to dilate, is known to reflect renal microvascular function. In this pilot study, we assessed PET (positron emission tomography)-based RFR values of healthy persons and renal artery stenosis patients. Seventeen patients with ARVD and eight healthy subjects were included in the study. Intravenous enalapril 1 mg was used as a vasodilatant, and the maximum response (blood pressure and RFR) to it was measured at 40 min. Renal perfusion was measured by means of oxygen-15-labeled water PET. RFR was calculated as a difference of stress flow and basal flow and was expressed as percent [(stress blood flow - basal blood flow)/basal blood flow] × 100%. RFR of the healthy was 22%. RFR of the stenosed kidneys of bilateral stenosis patients (27%) was higher than that of the stenosed kidneys of unilateral stenosis patients (15%). RFR of the contralateral kidneys of unilateral stenosis patients was 21%. There was no difference of statistical significance between RFR values of ARVD subgroups or between ARVD subgroups and the healthy. In the stenosed kidneys of unilateral ARVD patients, stenosis grade of the renal artery correlated negatively with basal (p = 0.04) and stress flow (p = 0.02). Dispersion of RFR values was high. This study is the first to report [ 15 O]H 2 O PET-based RFR values of healthy subjects and ARVD patients in humans. The difference between RFR values of ARVD patients and the healthy did not reach statistical significance perhaps because of high dispersion of RFR values. [ 15 O]H 2 O PET is a valuable non-invasive and quantitative method to evaluate renal blood flow though high dispersion makes imaging challenging. Larger studies are needed to get more information about [ 15 O]H 2 O PET method in evaluation of renal blood flow.
Jungmann, P M; Nevitt, M C; Baum, T; Liebl, H; Nardo, L; Liu, F; Lane, N E; McCulloch, C E; Link, T M
2015-07-01
To evaluate the association of prevalent unilateral total hip arthroplasty (THA) with worsening of degenerative knee abnormalities and clinical outcomes in the ipsilateral and contralateral knee. Both knees of 30 individuals in the Osteoarthritis Initiative (OAI) with unilateral THA (n = 14 left, n = 16 right) at baseline were assessed at baseline and at 4-year follow-up for Whole-organ MR Imaging Scores (WORMS), cartilage T2 relaxation times (only available for right knees), Western Ontario and McMasters Universities Arthritis Index (WOMAC) scores and upper leg isometric strength. Right knees of 30 individuals without THA were analyzed as controls. Contralateral knees were compared to ipsilateral knees with paired t-tests and to control knees with multivariate regression analysis adjusting for covariates. In paired analyses, compared to ipsilateral knees, contralateral knees had higher WORMS total (P = 0.008) and cartilage scores (P = 0.007) at baseline. Over 4 years contralateral knees worsened more on WORMS total score (P = 0.008). Cartilage T2 values were higher in knees contralateral to the THA (baseline, P = 0.02; follow-up, P < 0.001). Contralateral knees had greater declines in knee extension strength (P = 0.04) and had a trend for greater worsening in WOMAC pain, stiffness, function and total scores (P = 0.04-0.09). Similar results were found comparing contralateral knees with control knees in multivariate regression models. Prevalent unilateral THA is associated with an greater progression of degenerative findings for the knee contralateral to THA. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Drewniak, Tomasz; Rzepecki, Maciej; Juszczak, Kajetan; Kwiatek, Wojciech; Bielecki, Jakub; Zieliński, Krzysztof; Ruta, Andrzej; Czekierda, Łukasz; Moczulskis, Zbigniew
2011-01-01
The main problem in nephron sparing surgery (NSS) is to preserve renal tumors oncological purity during the removal of the tumor with a margin of macroscopically unchanged kidney tissue while keeping the largest possible amount of normal parenchyma of the operated kidney. The development of imaging techniques, in particular IGT (Image Guided Therapy) allows precise imaging of the surgical field and, therefore, is essential in improving the effectiveness of NSS (increase of nephron sparing with the optimal radicality). The aim of this study was to develop a method of the three-dimensional (3D) imaging of the kidney tumor and its lodge in the operated kidney using 3D laser scanner during NSS procedure. Additionally, the animal model of visualization was developed. The porcine kidney model was used to test the set built up with HD cameras and linear laser scanner connected to a laptop with graphic software (David Laser Scanner, Germany) showing the surface of the kidney and the lodge after removal the chunk of renal parenchyma. Additionally, the visualization and reconstruction was performed on animal porcine model. Moreover, 5 patients (3 women, 2 men) aged from 37 to 68 years (mean 56), diagnosed with kidney tumors in CT scans with a diameter of 3.7-6.9 cm (mean 4.9) were operated in our Department this year, scanning the surface during the treatment with the kidney tumor and kidney tumor after it is removed with a margin of renal tissue. In one case, the lodge of removed tumor was scanned. Dimensions in 3D reconstruction images of laser scans in the study of animal model and the images obtained intraoperatively were compared with the dimensions evaluated during preoperative CT scans, intraoperative measurements. Three-dimensional imaging laser scanner operating field loge resected tumor and the tumor on the kidney of animal models and during NSS treatments for patients with kidney tumors is possible in real time with an accuracy of -2 mm do +9 mm (+/- 3 mm). The duration of data acquisition by laser scanner and obtain three-dimensional image of the operating field takes an average of 13 seconds +/- 2 seconds. Movements associated with breathing and heart rate did not affect on the quality of the reconstruction. The imposition of the scanned surface texture occurs in real time, allowing you to identify renal parenchymal structures such as renal cortex, pyramids, pyelo-calices complex. Imaging control of NSS procedures is possible in animal models and in real time intraoperatively. The comparison of tumor size and the tumor lodge obtained in preoperative CT scans with the measurements during NSS procedure provide the surgeon to assess the extent of macroscopic estimation of the resection. This procedure helps the surgeon in obtaining oncological radicality with saving as much normal tissue kidney as possible. Performance of the imaging methods should be evaluated on a larger group of patients with kidney tumors eligible for NSS treatment.
Contralateral limb during total contact casting. A dynamic pressure and thermometric analysis.
Armstrong, D G; Liswood, P J; Todd, W F
1995-12-01
The authors draw attention to the importance of evaluation of the contralateral limb when treating unilateral sequelae secondary to distal symmetrical polyneuropathy. Plantar pressure measurements of the contralateral limb during total contact casting are reviewed. The results of thermometric evaluation before and after initiation of repetitive stress were reviewed. The results suggest that the patient walking in a total contact cast may experience a reduced focal pressure on the contralateral limb when compared with uncasted walking and three-point walking with crutches. Dermal thermometry may be a highly sensitive tool in evaluating even mild increases in repetitive stress. To explain this decrease in contralateral stress, the authors examine the features inherent to the total contact cast and propose the concept of proprioceptive stability.
Dysphagia caused by a lateral medullary infarction syndrome (Wallenberg's syndrome)
El Mekkaoui, Amine; Irhoudane, Hanane; Ibrahimi, Adil; El Yousfi, Mounia
2012-01-01
A 68-year-old man was referred to our hospital for a dysphagia evolving for 10 days. Clinical examination had found neurological signs as contralateral Horner's syndrome, ipsilateral palatal paresis, gait ataxia and hoarseness. Video-fluoroscopy showed a lack of passage of contrast medium to the distal esophagus. Esogastroduodenoscopy was normal. The cranial MRI had shown an acute ischemic stroke in the left lateral medullar region and the diagnosis of Wallenberg syndrome (WS) was established. WS remains an unknown cause of dysphagia in the clinical practice of the gastroenterologist. PMID:23077713
Lande, Marc B; Gerson, Arlene C; Hooper, Stephen R; Cox, Christopher; Matheson, Matt; Mendley, Susan R; Gipson, Debbie S; Wong, Cynthia; Warady, Bradley A; Furth, Susan L; Flynn, Joseph T
2011-08-01
Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction, and over half have hypertension. Data on the potential contribution of hypertension to CKD-associated neurocognitive deficits in children are limited. Our objective was to determine whether children with CKD and elevated BP (EBP) had decreased performance on neurocognitive testing compared with children with CKD and normal BP. This was a cross-sectional analysis of the relation between auscultatory BP and neurocognitive test performance in children 6 to 17 years enrolled in the Chronic Kidney Disease in Children (CKiD) project. Of 383 subjects, 132 (34%) had EBP (systolic BP and/or diastolic BP ≥90(th) percentile). Subjects with EBP had lower mean (SD) scores on Wechsler Abbreviated Scales of Intelligence (WASI) Performance IQ than those with normal BP (normal BP versus EBP, 96.1 (16.7) versus 92.4 (14.9), P = 0.03) and WASI Full Scale IQ (97.0 (16.2) versus 93.4 (16.5), P = 0.04). BP index (subject's BP/95(th) percentile BP) correlated inversely with Performance IQ score (systolic, r = -0.13, P = 0.01; diastolic, r = -0.19, P < 0.001). On multivariate analysis, the association between lower Performance IQ score and increased BP remained significant after controlling for demographic and disease-related variables (EBP, β = -3.7, 95% confidence interval [CI]: -7.3 to -0.06; systolic BP index, β = -1.16 to 95% CI: -2.1, -0.21; diastolic BP index, β = -1.17, 95% CI: -1.8 to -0.55). Higher BP was independently associated with decreased WASI Performance IQ scores in children with mild-to-moderate CKD.
Abeysekera, R A; Wijetunge, S; Nanayakkara, N; Wazil, A W M; Ratnatunga, N V I; Jayalath, T; Medagama, A
2015-12-17
Star fruit (Averrhoa carambola) is commonly consumed as a herbal remedy for various ailments in tropical countries. However, the dangers associated with consumption of star fruit are not commonly known. Although star fruit induced oxalate nephrotoxicity in those with existing renal impairment is well documented, reports on its effect on those with normal renal function are infrequent. We report two unique clinical presentation patterns of star fruit nephrotoxicity following consumption of the fruit as a remedy for diabetes mellitus-the first, in a patient with normal renal function and the second case which we believe is the first reported case of chronic kidney disease (CKD) due to prolonged and excessive consumption of star fruits. The first patient is a 56-year-old female diabetic patient who had normal renal function prior to developing acute kidney injury (AKI) after consuming large amount of star fruit juice at once. The second patient, a 60-year-old male, also diabetic presented with acute on chronic renal failure following ingestion of a significant number of star fruits in a short duration with a background history of regular star fruit consumption over the past 2-3 years. Both had histologically confirmed oxalate induced renal injury. The former had histological features of acute tubulo-interstitial disease whilst the latter had acute-on-chronic interstitial disease; neither had histological evidence of diabetic nephropathy. Both recovered over 2 weeks without the need for haemodialysis. These cases illustrate the importance of obtaining the patient's detailed history with respect to ingestion of herbs, traditional medication and health foods such as star fruits especially in AKI or CKD of unknown cause.
Doyon, Anke; Fischer, Dagmar-Christiane; Bayazit, Aysun Karabay; Canpolat, Nur; Duzova, Ali; Sözeri, Betül; Bacchetta, Justine; Balat, Ayse; Büscher, Anja; Candan, Cengiz; Cakar, Nilgun; Donmez, Osman; Dusek, Jiri; Heckel, Martina; Klaus, Günter; Mir, Sevgi; Özcelik, Gül; Sever, Lale; Shroff, Rukshana; Vidal, Enrico; Wühl, Elke; Gondan, Matthias; Melk, Anette; Querfeld, Uwe; Haffner, Dieter; Schaefer, Franz
2015-01-01
Objectives The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort. Methods Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6–18 years with an estimated glomerular filtration rate (eGFR) of 10–60 ml/min/1.73m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Results Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score. Conclusion Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity. PMID:25659076
Zhang, Yiyi; Chang, Yoosoo; Ryu, Seungho; Cho, Juhee; Lee, Won-Young; Rhee, Eun-Jung; Kwon, Min-Jung; Pastor-Barriuso, Roberto; Rampal, Sanjay; Han, Won Kon; Shin, Hocheol; Guallar, Eliseo
2014-10-01
Overt and subclinical hypothyroidism are associated with higher levels of serum creatinine and with increased risk of chronic kidney disease (CKD). The prospective association between thyroid hormones and kidney function in euthyroid individuals,however, is largely unexplored. We conducted a prospective cohort study in 104 633 South Korean men and women who were free of CKD and proteinuria at baseline and had normal thyroid hormone levels and no history of thyroid disease or cancer. At each annual or biennial follow-up visit, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxin (FT4) levels were measured by radioimmunoassay. The study outcome was incident CKD, defined as an estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. After a median follow-up of 3.5 years, 1032 participants developed incident CKD.There was a positive association between high-normal levels of TSH and increased risk of incident CKD. In fully-adjusted models including baseline eGFR, the hazard ratio comparing the highest vs the lowest quintiles of TSH was 1.26 [95% confidence interval (CI) 1.02 to 1.55; P for linear trend=0.03]. In spline models, FT3 levels below 3 pg/ml were also associated with increased risk of incident CKD. There was no association between FT4 levels and CKD. In a large cohort of euthyroid men and women, high levels of TSH and low levels of FT3, even within the normal range, were modestly associated with an increased risk of incident CKD.
Gimenes, Lilian R.; Gomes, Mayara S.; do Vale, Bruno N.; Cardoso, Cristina R. B.; de Oliveira, Ana M.; Moreira, Josimar D.
2017-01-01
Temporal consequences of neurocompensation to balloon injury on endothelinergic functionality in rat contralateral carotid were evaluated. Rats underwent balloon injury in left carotid and were treated with CP-96345 (NK1 antagonist). Concentration-response curves for endothelin-1 were obtained in contralateral (right) carotid at 2, 8, 16, 30, or 45 days after surgery in the absence or presence of BQ-123 (ETA antagonist), BQ-788 (ETB antagonist), or Tempol (superoxide-dismutase mimic). Endothelin-1-induced calcium mobilization was evaluated in functional assays carried out with BQ-123, BQ-788, or Tempol. Endothelin-1-induced NADPH oxidase-driven superoxide generation was measured by lucigenin chemiluminescence assays performed with BQ-123 or BQ-788. Endothelin-1-induced contraction was increased in contralateral carotid from the sixteenth day after surgery. This response was restored in CP-96345-treated rats. Endothelium removal or BQ-123 did not change endothelin-1-induced contraction in contralateral carotid. This response was restored by BQ-788 or Tempol. Contralateral carotid exhibited an increased endothelin-1-induced calcium mobilization, which was restored by BQ-788 or Tempol. Contralateral carotid exhibited an increased endothelin-1-induced lucigenin chemiluminescence, which was restored by BQ-788. We conclude that the NK1-mediated neurocompensatory response to balloon injury elicits a contractile hyperreactivity to endothelin-1 in rat contralateral carotid by enhancing the muscular ETB-mediated NADPH oxidase-driven generation of superoxide, which activates calcium channels. PMID:29062837
Chen, Bing; Aruin, Alexander S
2013-11-27
The magnitude of grip force used to lift and transport a hand-held object is decreased if a light finger touch from the contralateral arm is provided to the wrist of the target arm. We investigated whether the type of contralateral arm sensory input that became available with the finger touch to the target arm affects the way grip force is reduced. Nine healthy subjects performed the same task of lifting and transporting an instrumented object with no involvement of the contralateral arm and when an index finger touch of the contralateral arm was provided to the wrist, elbow, and shoulder. Touching the wrist and elbow involved movements of the contralateral arm; no movements were produced while touching the shoulder. Grip force was reduced by approximately the same amount in all conditions with the finger touch compared to the no touch condition. This suggests that information from the muscle and joint receptors of the contralateral arm is used in control of grip force when a finger touch is provided to the wrist and elbow, and cutaneous information is utilized when lifting an object while touching the shoulder. The results of the study provide additional evidence to support the use of a second arm in the performance of activities of daily living and stress the importance of future studies investigating contralateral arm sensory input in grip force control. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Mullaji, Arun B; Shah, Siddharth; Shetty, Gautam M
2017-01-01
Background and purpose — Medial unicompartmental knee arthroplasty (UKA) is undertaken in patients with a passively correctable varus deformity. We investigated whether restoration of natural soft tissue tension would result in a lower limb alignment similar to that of the contralateral unaffected lower limb after mobile-bearing medial UKA. Patients and methods — In this retrospective study, hip-knee-ankle (HKA) angle, position of the weight-bearing axis (WBA), and knee joint line obliquity (KJLO) after mobile-bearing medial UKA was compared with that of the unaffected (clinically and radiologically) contralateral lower limb in 123 patients. Results — Postoperatively, HKA angle was restored to within ±3° of the contralateral lower limb in 87% of the patients and the WBA passed within ±1 Kennedy and White’s tibial zone of the unaffected contralateral lower limb in 95% of the patients. The mean KJLO in the operated limbs was not significantly different from that in the unaffected lower limbs (p = 0.07) and the KJLO in the operated limb was restored to within ±3° of that in the contralateral lower limb in 96% of the patients. Interpretation — Lower limb alignment and knee joint line obliquity after mobile-bearing medial UKA were comparable to that of the unaffected contralateral limb in most patients. Comparison with the contralateral unaffected lower limb is a reliable method for evaluation and validation of limb mechanical alignment after mobile-bearing medial UKA. PMID:27794622
Zhao, Di; Ku, Yixuan
2018-05-01
Neural activity in the dorsolateral prefrontal cortex (DLPFC) has been suggested to integrate information from distinct sensory areas. However, how the DLPFC interacts with the bilateral primary somatosensory cortices (SIs) in tactile-visual cross-modal working memory has not yet been established. In the present study, we applied single-pulse transcranial magnetic stimulation (sp-TMS) over the contralateral DLPFC and bilateral SIs of human participants at various time points, while they performed a tactile-visual delayed matching-to-sample task with a 2-second delay. sp-TMS over the contralateral DLPFC or the contralateral SI at either an sensory encoding stage [i.e. 100 ms after the onset of a vibrotactile sample stimulus (200-ms duration)] or an early maintenance stage (i.e. 300 ms after the onset), significantly impaired the accuracy of task performance; sp-TMS over the contralateral DLPFC or the ipsilateral SI at a late maintenance stage (1600 ms and 1900 ms) also significantly disrupted the performance. Furthermore, at 300 ms after the onset of the vibrotactile sample stimulus, there was a significant correlation between the deteriorating effects of sp-TMS over the contralateral SI and the contralateral DLPFC. These results imply that the DLPFC and the bilateral SIs play causal roles at distinctive stages during cross-modal working memory, while the contralateral DLPFC communicates with the contralateral SI in the early delay, and cooperates with the ipsilateral SI in the late delay. Copyright © 2018 Elsevier B.V. All rights reserved.
Coucha, Maha; Li, Weiguo; Hafez, Sherif; Abdelsaid, Mohammed; Johnson, Maribeth H.; Fagan, Susan C.
2014-01-01
Admission hyperglycemia (HG) amplifies vascular injury and neurological deficits in acute ischemic stroke, but the mechanisms remain controversial. We recently reported that ischemia-reperfusion (I/R) injury impairs the myogenic response in both hemispheres via increased nitration. However, whether HG amplifies contralateral myogenic dysfunction and whether loss of tone in the contralateral hemisphere contributes to stroke outcomes remain to be determined. Our hypothesis was that contralateral myogenic dysfunction worsens stroke outcomes after acute hyperglycemic stroke in an oxidative stress-dependent manner. Male wild-type or SOD1 transgenic rats were injected with saline or 40% glucose solution 10 min before surgery and then subjected to 30 min of ischemia/45 min or 24 h of reperfusion. In another set of animals (n = 5), SOD1 was overexpressed only in the contralateral hemisphere by stereotaxic adenovirus injection 2–3 wk before I/R. Myogenic tone and neurovascular outcomes were determined. HG exacerbated myogenic dysfunction in contralateral side only, which was associated with infarct size expansion, increased edema, and more pronounced neurological deficit. Global and selective SOD1 overexpression restored myogenic reactivity in ipsilateral and contralateral sides, respectively, and enhanced neurovascular outcomes. In conclusion, our results show that SOD1 overexpression nullified the detrimental effects of HG on myogenic tone and stroke outcomes and that the contralateral hemisphere may be a novel target for the management of acute hyperglycemic stroke. PMID:25552308
... return the body temperature to normal Monitoring any excess fluid in older people with heart or kidney disease Medicines to manage agitation Vitamins and glucose The final goal of treatment is ...
[Proteomic analysis of myocardial hypertrophy induced by left kidney artery coarctation in rats].
Lv, Yuan-yuan; Sun, Biao; Ma, Ji-zheng
2009-05-01
To identify the expression of proteins in cardiomyocytes in rats with left kidney artery coarctation. 16 male SD rats were separated into 2 groups (n=8): 2 kidney 1 Clip group (2K1C) and sham operation group (SO). The postoperational 8th week, after examination by normal doppler and tissue doppler echocardiography, the extracted proteins from cardiomyocytes were isolated by two-dimensional gel electrophoresis with staining. The gel images were acquired by scanner and 2-DE analysis software. Different spots observed on two 2D gels were selected and identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Overall, 21 protein spots showed significant difference, and 14 out of which were identified. Kidney artery coactation-induced cardiac hypertrophy displays different expression of proteins in cardiomyocytes.
Huang, Ching-Ying; Ho, Ming-Ching; Lee, Jia-Jung; Hwang, Daw-Yang; Ko, Hui-Wen; Cheng, Yu-Che; Hsu, Yu-Hung; Lu, Huai-En; Chen, Hung-Chun; Hsieh, Patrick C H
2017-10-01
Autosomal dominant polycystic kidney disease is one of the most prevalent forms of inherited cystic kidney disease, and can be characterized by kidney cyst formation and enlargement. Here we report the generation of a Type 1 ADPKD disease iPS cell line, IBMS-iPSC-012-12, which retains the conserved deletion of PKD1, normal karyotype and exhibits the properties of pluripotent stem cells such as ES-like morphology, expression of pluripotent markers and capacity to differentiate into all three germ layers. Our results show that we have successfully generated a patient-specific iPS cell line with a mutation in PKD1 for study of renal disease pathophysiology. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Juxtaglomerular cell tumor of the kidney: report of two cases with a papillary pattern.
Têtu, B; Vaillancourt, L; Camilleri, J P; Bruneval, P; Bernier, L; Tourigny, R
1993-11-01
We report the clinicopathologic, immunohistochemical, and electron microscopic study of two cases of juxtaglomerular cell tumor of the kidney with a hitherto unreported dominant papillary pattern. Both tumors were associated with high blood pressure that did not respond to medical therapy, but that returned to normal after removal of the kidney. They were well delineated, tan, and had no necrosis. The cores of the papillary structures consisted of polygonal cells found to express renin by immunohistochemistry and to contain renin protogranules by electron microscopy. The papillary fronds were covered by one layer of cuboidal epithelial cells that did not stain for renin and had ultrastructural features reminiscent of the collecting duct epithelium. These tumors must be differentiated from malignant papillary tumors of the kidney, such as papillary clear cell carcinoma, transitional cell carcinoma, and collecting duct carcinoma.
Understanding Kidney Disease: Toward the Integration of Regulatory Networks Across Species
Ju, Wenjun; Brosius, Frank C.
2010-01-01
Animal models have long been useful in investigating both normal and abnormal human physiology. Systems biology provides a relatively new set of approaches to identify similarities and differences between animal models and humans that may lead to a more comprehensive understanding of human kidney pathophysiology. In this review, we briefly describe how genome-wide analyses of mouse models have helped elucidate features of human kidney diseases, discuss strategies to achieve effective network integration, and summarize currently available web-based tools that may facilitate integration of data across species. The rapid progress in systems biology and orthology, as well as the advent of web-based tools to facilitate these processes, now make it possible to take advantage of knowledge from distant animal species in targeted identification of regulatory networks that may have clinical relevance for human kidney diseases. PMID:21044762
An in vivo photodynamic therapy with diode laser to cell activation of kidney dysfunction
NASA Astrophysics Data System (ADS)
Dyah Astuti, Suryani; Indra Prasaja, Brahma; Anggono Prijo, Tri
2017-05-01
This study aims to analyze the effect of photodynamic therapy (PDT) low level laser therapy (LLLT) 650 nm in the experimental animals mice (Musmuculus) suffering from kidney organ damage in mice (Musmuculus) in vivo. Exposure laser acupuncture was performed on the kidney BL-23. The conditioning of kidney damage in mice used carbofuraan 35 at a dose of 0.041697 mg/mice. LLLT 650 nm exposure was done on a wide variety of energy (0.5; 1.0; 1.5; 2.0; 4.0; 5.0; 6.0; 7.0) J. The histopathological kidney cells in mice renal impairment showed that exposure to 650 nm laser energy 1 Joule resulted in the reduction of damaged cells (necrosis) and normal cells were increased with the improvement of renal tubular cells (64.14 ± 8:02)%. Therefore, exposure to 650 nm LLLT on acupuncture points Shenshu (BL-23) has the ability to proliferation of renal tubular cells of mice.
NASA Astrophysics Data System (ADS)
Heinert, G.; Mondorf, W.
1982-11-01
High speed image processing was used to analyse morphologic and metabolic characteristics of clinically relevant kidney tissue alterations.Qualitative computer-assisted histophotometry was performed to measure alterations in levels of the enzymes alkaline phosphatase (Ap),alanine aminopeptidase (AAP),g-glutamyltranspepti-dase (GGTP) and A-glucuronidase (B-G1) and AAP and GGTP immunologically determined in prepared renal and cancer tissue sections. A "Mioro-Videomat 2" image analysis system with a "Tessovar" macroscope,a computer-assisted "Axiomat" photomicroscope and an "Interactive Image Analysis System (IBAS)" were employed for analysing changes in enzyme activities determined by changes in absorbance or transmission.Diseased kidney as well as renal neoplastic tissues could be distinguished by significantly (wilcoxon test,p<0,05) decreased enzyme concentrations as compared to those found in normal human kidney tissues.This image analysis techniques might be of potential use in diagnostic and prognostic evaluation of renal cancer and diseased kidney tissues.