Sample records for orthotopic neobladder replacement

  1. Laparoscopic radical cystectomy with intracorporeal orthotopic ileal neobladder: technique and clinical outcomes.

    PubMed

    Shao, Pengfei; Li, Pu; Ju, Xiaobing; Qin, Chao; Li, Jie; Lv, Qiang; Meng, Xiaoxin; Yin, Changjun

    2015-02-01

    To study the feasibility and safety of laparoscopic radical cystectomy with intracorporeal orthotopic ileal neobladder and to evaluate the role of endoscopic stapling in neobladder construction. Fifty-five patients with bladder cancer who underwent laparoscopic radical cystectomy were retrospectively examined. Extended pelvic lymph node dissection was performed before cystectomy. An ileal segment of 50 cm was harvested to construct a U-shaped reservoir. The bottom of the reservoir was anastomosed with the posterior urethra. Twenty-five patients underwent neobladder construction by manual suturing and 30 patients by endoscopic stapler suturing. The mean operative time was 346 minutes, and mean neobladder construction time was 230 minutes. The median estimated blood loss was 500 mL, and 17 patients received intraoperative transfusion. Postoperative complications included 2 cases of urine leakage, 7 cases of pyelonephritis, 4 cases of incomplete bowel obstruction, 1 case of anastomotic stricture, and 1 case of death. Endoscopic stapler suturing for neobladder construction took significantly less time than manual suturing. However, neobladder stones were found in 2 patients who underwent operation using endoscopic suturing, and the stones were removed cystoscopically. The functional outcomes of the 2 constructive methods were comparable. Laparoscopic radical cystectomy with intracorporeal orthotopic neobladder is safe and feasible for experienced laparoscopic surgeons. Application of endoscopic stapler simplifies the surgical procedure while increasing the risk of neobladder stone formation. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Randomized Trial of Studer Pouch versus T-Pouch Orthotopic Ileal Neobladder in Patients with Bladder Cancer.

    PubMed

    Skinner, Eila C; Fairey, Adrian S; Groshen, Susan; Daneshmand, Siamak; Cai, Jie; Miranda, Gus; Skinner, Donald G

    2015-08-01

    The need to prevent reflux in the construction of an orthotopic ileal neobladder is controversial. We designed the USC-STAR trial to determine whether the T-pouch neobladder that included an antireflux mechanism was superior to the Studer pouch in patients with bladder cancer undergoing radical cystectomy. This single center, randomized, controlled trial recruited patients with clinically nonmetastatic bladder cancer scheduled to undergo radical cystectomy with neobladder. Eligible patients were randomly assigned to undergo T-pouch or Studer ileal orthotopic neobladder. Treatment assignment was not masked. The primary end point was change in renal function from baseline to 3 years. The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation was used to calculate the estimated glomerular filtration rate. Between February 2002 and November 2009, 237 patients were randomly assigned to T-pouch ileal orthotopic neobladder and 247 to Studer ileal orthotopic neobladder. Baseline characteristics did not differ between the groups. Between baseline and 3 years the estimated glomerular filtration rate decreased by 6.4 ml/minute/1.73 m(2) in the Studer group and 6.6 ml/minute/1.73 m(2) in the T-pouch group (p=0.35). Multivariable analysis showed that type of ileal orthotopic neobladder was not independently associated with 3-year renal function (p=0.63). However, baseline estimated glomerular filtration rate, age and urinary tract obstruction were independently associated with 3-year decline in renal function. Cumulative risk of urinary tract infection and overall late complications were not different between the groups, but the T-pouch was associated with an increased risk of secondary diversion related surgeries. T-pouch ileal orthotopic neobladder with an antireflux mechanism did not prevent a moderate reduction in renal function observed at 3 years compared to the Studer pouch, but did result in an increase in diversion related secondary surgical procedures

  3. Postoperative bacteriuria, pyuria and urinary tract infection in patients with an orthotopic sigmoid colon neobladder replacement.

    PubMed

    Shigemura, Katsumi; Tanaka, Kazushi; Arakawa, Soichi; Miyake, Hideaki; Fujisawa, Masato

    2014-02-01

    The purpose of this study is to investigate the prevalence of postoperative bacteriuria, pyuria and urine culture in patients with an orthotopic sigmoid colon neobladder replacement. Urine samples for bacteriuria, pyuria and urine culture, if necessary, were collected at 1, 3, 6, 9 and 12 months after surgery and the presence of blood culture and antibiotic-resistant strains, and their treatments on positive urine culture cases were investigated. Of 209 for bacteriuria and 207 for pyuria urine samples with evaluable data, 95 (45.5%) were positive for bacteriuria and 76 (36.7%) had pyuria (10 or more white blood cells per high-power field). Totally, 30 bacteria were isolated from urine culture of urinary tract infection (UTI) and Klebisiella pneumoniae, Escherichia coli, Staphylococcos aureus and Enterococcus spp. strains were representatively isolated. The incidence of pyuria significantly decreased over time (P=0.041) but that of bacteriuria did not (P=0.107). In them, there were six bacteria (20.7%) with antibiotic-resistant strains. The antibiotics used for their treatments representatively were levofloxacin in five cases, tazobactam/piperacillin in three cases and sulfamethoxazole/trimethoprim and cefepime, meropenem in two cases, respectively. In conclusion, these findings suggest that physicians taking care of sigmoid colon neobladder patients need to be aware of these high ratios of bacteriuria, pyuria and UTI, including bacteremia.

  4. Evolution of robot-assisted orthotopic ileal neobladder formation: a step-by-step update to the University of Southern California (USC) technique.

    PubMed

    Chopra, Sameer; de Castro Abreu, Andre Luis; Berger, Andre K; Sehgal, Shuchi; Gill, Inderbir; Aron, Monish; Desai, Mihir M

    2017-01-01

    To describe our, step-by-step, technique for robotic intracorporeal neobladder formation. The main surgical steps to forming the intracorporeal orthotopic ileal neobladder are: isolation of 65 cm of small bowel; small bowel anastomosis; bowel detubularisation; suture of the posterior wall of the neobladder; neobladder-urethral anastomosis and cross folding of the pouch; and uretero-enteral anastomosis. Improvements have been made to these steps to enhance time efficiency without compromising neobladder configuration. Our technical improvements have resulted in an improvement in operative time from 450 to 360 min. We describe an updated step-by-step technique of robot-assisted intracorporeal orthotopic ileal neobladder formation. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

  5. Cluster analysis identifies three urodynamic patterns in patients with orthotopic neobladder reconstruction.

    PubMed

    Kim, Kwang Hyun; Yoon, Hyun Suk; Song, Wan; Choo, Hee Jung; Yoon, Hana; Chung, Woo Sik; Sim, Bong Suk; Lee, Dong Hyeon

    2017-01-01

    To classify patients with orthotopic neobladder based on urodynamic parameters using cluster analysis and to characterize the voiding function of each group. From January 2012 to November 2015, 142 patients with bladder cancer underwent radical cystectomy and Studer neobladder reconstruction at our institute. Of the 142 patients, 103 with complete urodynamic data and information on urinary functional outcomes were included in this study. K-means clustering was performed with urodynamic parameters which included maximal cystometric capacity, residual volume, maximal flow rate, compliance, and detrusor pressure at maximum flow rate. Three groups emerged by cluster analysis. Urodynamic parameters and urinary function outcomes were compared between three groups. Group 1 (n = 44) had ideal urodynamic parameters with a mean maximal bladder capacity of 513.3 ml and mean residual urine volume of 33.1 ml. Group 2 (n = 42) was characterized by small bladder capacity with low compliance. Patients in group 2 had higher rates of daytime incontinence and nighttime incontinence than patients in group 1. Group 3 (n = 17) was characterized by large residual urine volume with high compliance. When we examined gender differences in urodynamics and functional outcomes, residual urine volume and the rate of daytime incontinence were only marginally significant. However, females were significantly more likely to belong to group 2 or 3 (P = 0.003). In multivariate analysis to identify factors associated with group 1 which has the most ideal urodynamic pattern, age (OR 0.95, P = 0.017) and male gender (OR 7.57, P = 0.003) were identified as significant factors. While patients with ileal neobladder present with various voiding symptoms, three urodynamic patterns were identified by cluster analysis. Approximately half of patients had ideal urodynamic parameters. The other two groups were characterized by large residual urine and small capacity bladder with low compliance. Young age and male

  6. Post-operative infection and prophylactic antibiotic administration after radical cystectomy with orthotopic neobladder urinary diversion.

    PubMed

    Shigemura, Katsumi; Tanaka, Kazushi; Matsumoto, Minori; Nakano, Yuzo; Shirakawa, Toshiro; Miyata, Masahiro; Yamashita, Masuo; Arakawa, Soichi; Fujisawa, Masato

    2012-08-01

    The purpose of this study was to investigate the association between prophylactic antibiotic administration (PAA) and post-operative infection in radical cystectomy with orthotopic neobladder urinary diversion carried out for patients with bladder cancer. Fifty-seven consecutive cases were analyzed retrospectively. Post-operative infections were categorized as urinary tract, wound, and remote infections. We used the antibiotics tazobactam/piperacillin (TAZ/PIPC), sulbactam/ampicillin (SBT/ABPC), flomoxef (FMOX), cefazolin (CEZ), cefotiam (CTM), and cefmetazole (CMZ). Twenty-five (43.9%) patients had post-operative infections. Five of these (8.77%) patients had wound infections, 22 (38.6%) patients had urinary tract infections, and 2 (3.51%) had remote infections. Our statistical analysis demonstrated that the patients with TAZ/PIPC used for PAA (5/18: 27.8%) had a significantly lower post-operative infection rate than patients with other antibiotics (24/39: 61.5%) (p = 0.0442). In addition, the patients with a shorter-duration PAA (within 72 h after the operation (48-72 h)) had a significantly lower rate of post-operative infections (12/33: 36.4%) than those with longer-duration PAA (longer than 72-96 h after the operation) (16/24: 66.7%) (p = 0.0239). Taken together, these results suggest that TAZ/PIPC with shorter PAA duration (within 72 h) might lead to a lower rate of post-operative infections. In conclusion, our data showed that PAA with TAZ/PIPC with a shorter duration PAA (within 72 h) might be recommended for radical cystectomy with orthotopic neobladder reconstruction. A prospective study based on our data is desirable to establish or revise guidelines for prophylactic medication for preventing post-operative infection after radical cystectomy with orthotopic neobladder urinary diversion.

  7. Successful Management of Neobladder Variceal Bleeding

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Atwal, Dinesh; Chatterjee, Kshitij, E-mail: kchatterjee@uams.edu; Osborne, Scott

    Hematuria from a neobladder can occur due to a variety of pathologies including tumors, stones, and fistulas. Variceal bleeding in a neobladder is a very rare condition with only one case reported in literature. We present a case of a patient with cirrhosis and portal hypertension and an ileocolic orthotopic neobladder presenting with hematuria. Computed tomographic angiography showed dilated varices around the neobladder which were successfully embolized. To the best of our knowledge, this is the first report case of variceal bleeding in a neobladder successfully managed with the combination of TIPS (transjugular intrahepatic portosystemic shunt) procedure and embolization.

  8. Radical cystectomy with W-shaped orthotopic ileal neobladder constructed with non-absorbable titanium staples-long term follow-up.

    PubMed

    Kravchick, Sergey; Lobik, Leonid; Paz, Adrian; Stepnov, Eugeny; Ben-Dor, David; Cytron, Shmuel

    2013-01-01

    We retrospectively assessed our experience with the W-shaped orthotopic ileal pouch, which was constructed with non-absorbable titanium staples. For these purpose, we discuss the results of bladder capacity, urinary continence and early and long-term postoperative complications. We included in the study 17 patients who underwent radical cystoprostatectomy followed by construction of an orthotopic W-shaped ileal pouch between October 2000 and November 2009. A 65-70 cm segment of ileum was isolated and prearranged into a W-configuration, leaving two 10 cm intact segments on both sides of the ileal fragment. In our technique we entirely anatomized all adjacent limbs in order to create a sphere-shaped pouch. The ureters were directly anastomized to both intact segments of the ileal division. All our patients underwent pouchscopy 6 months after operation and annually. Mean operative time for neobladder reconstruction and ureteral anastomoses was 87 ± 7.67 minutes. In one patient a leak from the ileo-ileal anastomosis was confirmed on the 3rd day after operation. In 2 cases unilateral stricture of the ureteral-neobladder anastomosis was documented. Staple lines were mostly covered with ileal mucosa after 6 months. The mean functional bladder capacity was 340 ± 27.6 mL and 375 ± 43.4 mL at 6 and 12 months, respectively. First-year daytime and nighttime continence was good and acceptable in 90% and 78% of patients, while it increased to 95% during the 2nd year. The long term follow-up shows that non-absorbable titanium staples can be safely used for creation of an orthotopic ileal neobladder. However, these data should be further validated in a larger series of patients.

  9. Ultrastructural basis for the efficiency of an ileal orthotopic neobladder 27 years after surgery.

    PubMed

    Orlandini, G; Guizzardi, S; Ferretti, S; Simonazzi, M; Bucci, G; Gatti, R

    2002-01-01

    The morphological and functional basis of the excellent clinical outcome of ileal orthotopic neobladders are largely unknown. Only long-term follow-up studies will provide an adequate answer to this unsettled question. We have studied a patient who underwent this type of surgery over 27 years ago. Besides an important secretive adaptation we have found, at the ultrastructural level, that the monolayered epithelium does not show signs of true metaplasia and that changes had occurred in the intercellular junctions, namely that desmosomes are significantly increased. Although limited to a single case, these features, if confirmed by further observations, suggest a working hypothesis for the understanding of the definitive phenotypic adaptation of the ileal epithelium to the new aggressive environment. Copyright 2002 S. Karger AG, Basel

  10. Correlation between urodynamic function and 3D cat scan anatomy in neobladders: does it exist?

    PubMed

    Crivellaro, S; Mami, E; Wald, C; Smith, J J; Kocjancic, E; Stoffel, J; Bresette, J; Libertino, J A

    2009-01-01

    We compared the functional and anatomical differences among three different orthotopic neobladders, utilizing video urodynamics and 3D CT to determine what parameters, if any, correlate to function. Thirty-four patients were able to participate in the evaluation of their neobladder by 3D CT and video urodynamics. Three different orthotopic neobladders were identified (12 ileal, 7 ileocecal, 15 sigmoid). Multiple measurements, observations and functional data have been obtained. Statistical analysis for this study employed a linear regression test and an odds ratio calculation (using StatSoft V. 5.1). In comparing three different neobladders, no significant differences were noted. Looking at the entire population, the following association was statistically significant in linear correlation: the maximal capacity and the neobladder volume; the pressure at the maximal capacity and the distance from the symphysis, the pressure at maximal flow and both the distance from the symphysis and the thickness of the neobladder. The distance from the left femoral head was directly correlated with the post void residual and inversely correlated with the maximal flow. The Odds ratio calculation revealed (with significant P < 0.05) that the further the center of the neobladder is from the right femoral head, the higher risk of incontinence. The study seems to show no significant anatomical or functional difference among the three different types of neobladders. A possible correlation between the position of the neobladder and urinary incontinence is suggested, recognizing further study in a larger population is required.

  11. Presence of transient hydronephrosis immediately after surgery has a limited influence on renal function 1 year after ileal neobladder construction.

    PubMed

    Narita, Takuma; Hatakeyama, Shingo; Koie, Takuya; Hosogoe, Shogo; Matsumoto, Teppei; Soma, Osamu; Yamamoto, Hayato; Yoneyama, Tohru; Tobisawa, Yuki; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Ohyama, Chikara

    2017-08-31

    Urinary tract obstruction and postoperative hydronephrosis are risk factor for renal function deterioration after orthotopic ileal neobladder construction. However, reports of relationship between transient hydronephrosis and renal function are limited. We assess the influence of postoperative transient hydronephrosis on renal function in patients with orthotopic ileal neobladder construction. Between January 2006 and June 2013, we performed radical cystectomy in 164 patients, and 101 received orthotopic ileal neobladder construction. This study included data available from 64 patients with 128 renal units who were enrolled retrospectively. The hydronephrosis grade of each renal unit scored 0-4. The patients were divided into 4 groups according to the grade of hydronephrosis: control, low, intermediate, and high. The grade of postoperative hydronephrosis was compared with renal function 1 month and 1 year after surgery. There were no significant differences in renal function before surgery between groups. One month after surgery, the presence of hydronephrosis was significantly associated with decreased renal function. However, 1 year after urinary diversion hydronephrosis grades were improved significantly, and renal function was comparable between groups. Postoperative hydronephrosis at 1 month had no significant influence on renal function 1 year after ileal neobladder construction. Limitations include retrospective design, short follow-up periods, and a sample composition. The presence of transient hydronephrosis immediately after surgery may have limited influence on renal function 1 year after ileal neobladder construction.

  12. Is Health-Related Quality of Life after Radical Cystectomy Using Validated Questionnaires Really Better in Patients with Ileal Orthotopic Neobladder Compared to Ileal Conduit: A Meta-Analysis of Retrospective Comparative Studies

    PubMed Central

    Cerruto, Maria A.; D'Elia, Carolina; Siracusano, Salvatore; Porcaro, Antonio B.; Cacciamani, Giovanni; De Marchi, Davide; Niero, Mauro; Lonardi, Cristina; Iafrate, Massimo; Bassi, Pierfrancesco; Belgrano, Emanuele; Imbimbo, Ciro; Racioppi, Marco; Talamini, Renato; Ciciliato, Stefano; Toffoli, Laura; Rizzo, Michele; Visalli, Francesco; Verze, Paolo; Artibani, Walter

    2017-01-01

    Introduction From the most recent systematic revision of the literature, an orthotopic neobladder would seem to show marginally better health related quality of life (HR-QoL) scores compared with an ileal conduit. The aim of this study was to review all relevant published studies about the comparison between ileal orthotopic neobladder (IONB) and ileal conduit using validated HR-QoL questionnaires. Materials and Methods Studies were identified by searching multiple literature databases. Data were synthesized using meta-analytic methods conformed to the PRISMA statement. Results The literature search identified 10 papers; pooled effect sizes of combined quality of life outcomes for ileal conduit versus IONB showed a significantly better HR-QoL in patients with IONB (Hedges' g = 0.278; p = 0.000);. The present study has an important limitation due to the type of the analyzed comparative studies, all retrospective and not randomized. Conclusion This meta-analysis of not-randomized, retrospective comparative studies on the impact of ileal conduit versus IONB on HR-QoL showed a significant advantage of IONB subgroups. PMID:28785189

  13. Is Health-Related Quality of Life after Radical Cystectomy Using Validated Questionnaires Really Better in Patients with Ileal Orthotopic Neobladder Compared to Ileal Conduit: A Meta-Analysis of Retrospective Comparative Studies.

    PubMed

    Cerruto, Maria A; D'Elia, Carolina; Siracusano, Salvatore; Porcaro, Antonio B; Cacciamani, Giovanni; De Marchi, Davide; Niero, Mauro; Lonardi, Cristina; Iafrate, Massimo; Bassi, Pierfrancesco; Belgrano, Emanuele; Imbimbo, Ciro; Racioppi, Marco; Talamini, Renato; Ciciliato, Stefano; Toffoli, Laura; Rizzo, Michele; Visalli, Francesco; Verze, Paolo; Artibani, Walter

    2017-07-01

    From the most recent systematic revision of the literature, an orthotopic neobladder would seem to show marginally better health related quality of life (HR-QoL) scores compared with an ileal conduit. The aim of this study was to review all relevant published studies about the comparison between ileal orthotopic neobladder (IONB) and ileal conduit using validated HR-QoL questionnaires. Studies were identified by searching multiple literature databases. Data were synthesized using meta-analytic methods conformed to the PRISMA statement. The literature search identified 10 papers; pooled effect sizes of combined quality of life outcomes for ileal conduit versus IONB showed a significantly better HR-QoL in patients with IONB (Hedges' g = 0.278; p = 0.000);. The present study has an important limitation due to the type of the analyzed comparative studies, all retrospective and not randomized. This meta-analysis of not-randomized, retrospective comparative studies on the impact of ileal conduit versus IONB on HR-QoL showed a significant advantage of IONB subgroups.

  14. Late recurrent urothelial carcinoma in the Studer neobladder: conversion to continent reservoir

    PubMed Central

    Kotb, AF; Alkosiry, M; AbdElkawy, N; Atta, MA

    2012-01-01

    Bladder cancer represents a considerable issue in Egypt and the Middle East. Radical cystectomy and orthotopic neobladder represent the standard of care for managing cases with invasive bladder tumour. There are few cases reported in the literature considering the urothelial recurrence in the urethra, connected to neobladder. We are presenting a rare case of a young female patient, with an aggressive urothelial tumour, recurring 13-year post-radical cystectomy, and the Studer neobladder. Our case was managed by urethrectomy and conversion of the neobladder into continent reservoir, with good short-term oncological and functional outcomes. We can conclude that bladder cancer cases should be followed thoroughly throughout their life. Follow-up urethroscopy and cytology should be done for all cases of post-radical cystectomy, regardless of patients’ symptoms. Key message Late urothelial recurrence of post-radical cystectomy is possible and, in our case, happened 13 years following surgery. The Studer neobladder can be safely converted into continent reservoir, allowing good functional outcomes. Also, recurrence in the Studer neobladder can be safely managed, allowing good oncological outcomes, without the need for any ureteroileal interventions. PMID:22973413

  15. Our Experiences with Robot-Assisted Laparoscopic Radical Cystectomy: Orthotopic Neobladder by the Suprapubic Incision Method

    PubMed Central

    Cho, Byung Chul; Jung, Ha Bum; Cho, Sung Tae; Kim, Ki Kyung; Han, Jun Hyun; Lee, Yong Seong

    2012-01-01

    Purpose To report our technique for and experience with robot-assisted laparoscopic radical cystectomy (RARC) with orthotopic neobladder (ON) formation in a cohort of bladder cancer patients. Materials and Methods Between December 2007 and December 2011, a total of 35 patients underwent RARC. The patients' mean age was 63.3 years and their mean body mass index was 23.7 kg/m2. Thirty patients had a clinical stage of T2 or higher. Postoperative mean follow-up duration was 25.5 months. In 5 patients, a 4-cm midline infraumbilical skin incision was made for an ileal conduit (IC) and the stoma formation was similar to the open procedure. In 30 patients undergoing the ON procedure, the skin for specimen removal and extracorporeal enterocystoplasty was incised infraumbilically in the early 5 cases with redocking (ON-I) and suprapubically in the latter 25 cases without redocking (ON-S). Results The mean operative times of the IC, ON-I, and ON-S groups were 442.5, 646.0, and 531.3 minutes, respectively (p=0.001). Mean console and lymph node dissection time were not significantly different between the groups. Mean urinary diversion times in each group were 68.8, 125.0, and 118.8 minutes, respectively (p=0.001). In the comparison between the ON-I and ON-S group, only operative time was significant. Four patients required a blood transfusion. We had no cases of intraabdominal organ injury or open conversion. Thiry-three patients (94.2%) had a pathologic stage of T2 or higher. Two patients (5.7%) had lymph node-positive disease. Postoperative complications included ileus (n=4), stricture in the uretero-ileal junction (n=2), and vesicovaginal fistula (n=1). Conclusions Our robotic neobladder-suprapubic incision without redocking procedure is easier and more rapid than that of infraumbilical incision with redocking. PMID:23185668

  16. Incidence and Patient Outcomes in Renal Replacement Therapy After Orthotopic Liver Transplant.

    PubMed

    Ayhan, Asude; Ersoy, Zeynep; Ulas, Aydin; Zeyneloglu, Pinar; Pirat, Arash; Haberal, Mehmet

    2017-02-01

    Our objective was to evaluate the incidence of renal replacement therapy after orthotopic liver transplant and to evaluate and analyze patient outcomes. We performed a retrospective analysis of 177 consecutive patients at a tertiary care unit who underwent orthotopic liver transplant between January 2010 and June 2016. Patients who were admitted to the intensive care unit after orthotopic liver transplant and who required renal replacement therapy were included. A total of 177 (79 adult, 98 pediatric) orthotopic liver transplants were performed during the study period. Of these, 35 patients (19%) required renal replacement therapy during the early posttransplantation period. After excluding 5 patients with previous chronic renal failure, 30 patients (17%; 20 adult [25% ], 10 pediatric [10% ]) with acute kidney injury required renal replacement therapy. The mean patient age was 31.1 ± 20.0 years, with a mean Model for End-stage Liver Disease score of 16.7 ± 12.3. Of the patients with acute kidney injury who underwent renal replacement therapy, in-hospital mortality was 23.3% (7 of 30 patients), and 40% remained on dialysis. No significant difference was seen in mortality between early versus delayed initiation of renal replacement therapy in patients with stage 3 acute kidney injury (P = .17). Of liver transplant recipients who present with acute kidney injury, 19% require renal replacement therapy, and in-hospital mortality is 20% in the early postoperative period.

  17. Orthotopic neo- bladder in women.

    PubMed

    Schettini, Manlio

    2010-12-01

    Radical cystectomy is the most effective treatment madality for high grade urinary bladder carcinoma and orthotopic reconstruction is the better urinary diversion modality also in women. From 2002 to 2007 we performed 14 radical cystectomies followed by orthotopic reconstruction in women aged between 47 and 68 years (mean age 56) affected by urinary bladder carcinoma. Our reconstructive technique requires the preparation of two strips of the recti muscles fascia, the sectioning of the bladder neck and, when the uterus is present, hysteroannessiectomy and cystectomy en block leaving intact the lateral and inferior vaginal walls. The pelvic floor is stabilized by a colposacropexis with a prosthesis and placing an omental flap over the prosthesis. The orthotopic reconstruction is achieved via a neobladder according to the Padovana technique. The ureters are anastomized to the neobladder and splinted with single J stents. The pathological examination demonstrated in all patients the presence of a high grade carcinoma (G3): more specifically 4 patients had a full thickness intramural infiltration (T2), 2 patients had involvment of the perivescical fat (T3) ad 8 patients were in T1 stage. Lymphnodes were negative for tumour (NO). In 8 patients blood transfusions were necessary to treat post surgical anemia. No significant intra-, peri- or post operative complications were noted. The mean follow-up was 45 months: a patient died for diffuse metastatic disease after 11 months. The remaining patients are still alive and report normal lifestyle: 10 with normal micturition and 4 with urinary retention treated with intermittent self-catetherization. Two patients report nocturnal incontinence treated with hourly micturition and one pad. The five patients who had normal preoperative sexual intercourse resumed a normal sexual activity. The possibility to orthotopically recontruct the female urinary bladder has been established long time after the introduction of orthotopic

  18. [Stress urinary incontinence after radical cystectomy: neobladder construction and placement of the functional retrourethral sling].

    PubMed

    Mayer, M; Bauer, R M; Walther, S; Becker, A J; Stief, C G; Bastian, P J; Gozzi, C

    2009-06-01

    Stress urinary incontinence (SUI) following radical cystectomy and orthotopic ileal neobladder construction represents a challenging problem. The incidence of incontinence following this surgery is reported to be 30-60% and is - despite a better understanding of the male (and female) pelvic anatomy - still regarded as an adverse outcome of this surgery.Therapeutic options have been limited up until now and include pharmacological agents, surgical treatment and pelvic floor training with only moderate amelioration of the symptoms and often unacceptable side effects. Nevertheless, urinary continence is probably the most important key to patient satisfaction. Here we introduce the perineal approach of the functional retrourethral mesh as a new and innovative sling suspension based on a non-obstructive procedure in a patient with urinary stress incontinence after ileal neobladder. The sling adjusts the changed anatomy after radical cystectomy returning it to the former preoperative position and thus continence can be achieved again. The approach of the sling in a patient with ileal neobladder is safe and the good result concerning continence is promising.

  19. Clinical experience with the N-shaped ileal neobladder: assessment of complications, voiding patterns, and quality of life in our series of 58 patients.

    PubMed

    Joniau, S; Benijts, J; Van Kampen, M; De Waele, M; Ooms, J; Van Cleynenbreugel, B; Van Poppel, H

    2005-05-01

    The purpose of this retrospective study was to assess complications, voiding patterns, and quality of life in patients with an orthotopic bladder substitution, using an N-shaped ileal neobladder. Between May 1996 and December 2002, 58 patients (52 men and 6 women) underwent an orthotopic ileal neobladder reconstruction after radical cystectomy. The mean age was 47 for the female and 60 for the male patients. In all patients an N-shaped ileal pouch was constructed. This pouch has not yet been described in the literature before. All procedures were performed by the same surgeon (HVP) and the mean follow-up was 38 months. Complications were registered as early (occurring within 3 months) or late (occurring after 3 months), and as pouch-related and non-pouch-related. The patients took part in a pelvic floor re-education programme for as long as they were incontinent. All patients completed a retrospective Quality of Life questionnaire, based on the QLQ-C30 questionnaire, which was validated by the EORTC's Study Group on Quality of Life. In 38% of the patients, early complications occurred, whereas 48% had late complications. The most frequent early complications were diarrhea (24%) and pyelonephritis (9%). Diarrhea was again the most frequently mentioned non-pouch-related complication (19%). The most frequently observed pouch-related late complication was ileo-urethral stenosis. This occurred in five patients. All of these 5 patients were re-operated using a minimally invasive approach. Daytime continence was achieved in 95% of patients and nighttime continence in 66%. Hyper-continence with subsequent need for CISC was observed in 5 out of 6 women (83%) and 0 out of 52 men (0%). The retrospective QoL questionnaire learned that the impact of bladder removal and orthotopic bladder substitution has acceptable impact on patient's everyday life. Diarrhea was mentioned as being the most discomforting complication by most of the patients. We describe a modified orthotopic

  20. Perioperative and mid-term oncologic outcomes of robotic assisted radical cystectomy with totally intracorporeal neobladder: Results of a propensity score matched comparison with open cohort from a single-centre series.

    PubMed

    Simone, Giuseppe; Tuderti, Gabriele; Misuraca, Leonardo; Anceschi, Umberto; Ferriero, Mariaconsiglia; Minisola, Francesco; Guaglianone, Salvatore; Gallucci, Michele

    2018-04-17

    In this study, we compared perioperative and oncologic outcomes of patients treated with either open or robot-assisted radical cystectomy and intracorporeal neobladder at a tertiary care center. The institutional prospective bladder cancer database was queried for "cystectomy with curative intent" and "neobladder". All patients underwent robot-assisted radical cystectomy and intracorporeal neobladder or open radical cystectomy and orthotopic neobladder for high-grade non-muscle invasive bladder cancer or muscle invasive bladder cancer with a follow-up length ≥2 years were included. A 1:1 propensity score matching analysis was used. Kaplan-Meier method was performed to compare oncologic outcomes of selected cohorts. Survival rates were computed at 1,2,3 and 4 years after surgery and the log rank test was applied to assess statistical significance between the matched groups. Overall, 363 patients (299 open and 64 robotic) were included. Open radical cystectomy patients were more frequently male (p = 0.08), with higher pT stages (p = 0.003), lower incidence of urothelial histologies (p = 0.05) and lesser adoption of neoadjuvant chemotherapy (<0.001). After applying the propensity score matching, 64 robot-assisted radical cystectomy patients were matched with 46 open radical cystectomy cases (all p ≥ 0.22). Open cohort showed a higher rate of perioperative overall complications (91.3% vs 42.2%, p 0.001). At Kaplan-Meier analysis robotic and open cohorts displayed comparable disease-free survival (log-rank p = 0.746), cancer-specific survival (p = 0.753) and overall-survival rates (p = 0.909). Robot-assisted radical cystectomy and intracorporeal neobladder provides comparable oncologic outcomes of open radical cystectomy and orthotopic neobladder at intermediate term survival analysis. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  1. Febrile Urinary Tract Infection after Radical Cystectomy and Ileal Neobladder in Patients with Bladder Cancer.

    PubMed

    Kim, Kwang Hyun; Yoon, Hyun Suk; Yoon, Hana; Chung, Woo Sik; Sim, Bong Suk; Lee, Dong Hyeon

    2016-07-01

    Urinary tract infection (UTI) is one of the most common complications after radical cystectomy and orthotopic neobladder reconstruction. This study investigated the incidence and implicated pathogen of febrile UTI after ileal neobladder reconstruction and identify clinical and urodynamic parameters associated with febrile UTI. From January 2001 to May 2015, 236 patients who underwent radical cystectomy and ileal neobladder were included in this study. Fifty-five episodes of febrile UTI were identified in 46 patients (19.4%). The probability of febrile UTI was 17.6% and 19.8% at 6 months and 24 months after surgery, respectively. While, Escherichia coli was the most common implicated pathogen (22/55, 40.0%), Enterococcus spp. were the most common pathogen during the first month after surgery (18/33, 54.5%). In multivariate logistic regression analysis, ureteral stricture was an independent risk factor associated with febrile UTI (OR 5.93, P = 0.023). However, ureteral stricture accounted for only 6 episodes (10.9%, 6/55) of febrile UTI. Most episodes of febrile UTI occurred within 6 months after surgery. Thus, to identify risk factors associated with febrile UTI in the initial postoperative period, we assessed videourodynamics within 6 months after surgery in 38 patients. On videourodyamic examination, vesicoureteral reflux (VUR) was identified in 16 patients (42.1%). The rate of VUR presence in patients who had febrile UTI was not significantly different from those in patients without febrile UTI (50% vs. 39.3%, P = 0.556). Patients with febrile UTI had significantly larger residual urine volume (212.0 ± 193.7 vs. 90.5 ± 148.2, P = 0.048) than those without. E. coli and Enterococcus spp. are common pathogens and ureteral stricture and residual urine are risk factors for UTI after ileal neobladder reconstruction.

  2. Orthotopic sigmoid vs. ileal neobladders in Japanese patients: a comparative assessment of complications, functional outcomes, and quality of life.

    PubMed

    Miyake, Hideaki; Furukawa, Junya; Sakai, Iori; Muramaki, Mototsugu; Yamashita, Masuo; Inoue, Taka-Aki; Fujisawa, Masato

    2013-10-01

    To compare the clinical outcomes of sigmoid and ileal neobladders (NBs) created following radical cystectomy. This study included 90 and 144 Japanese patients undergoing radical cystectomy and orthotopic NB reconstruction with a sigmoid and ileal segment, respectively. Postoperative clinical outcomes between the sigmoid and ileal NB groups (SNBG and INBG) were compared. In this series, 110 early and 51 late complications occurred in 71 and 41 patients, respectively; however, there was no significant difference in the incidence of complications between SNBG and INBG. At 1 year postoperatively, there were no significant differences in the proportion of spontaneous voiders and the continence status between these 2 groups; however, despite the lack of significant differences in the maximal flow rate and voided volume, the post-void residual in SNBG was significantly smaller than that in INBG. Voiding functional outcomes at 5 years postoperatively were also obtained from 28 and 49 in SNBG and INBG, respectively. Although there were no significant changes in the functional outcomes in SNBG, the proportion of spontaneous voiders and post-void residual in INBG at 5 years postoperatively were significantly poorer than those at 1 year postoperatively. Furthermore, the postoperative health-related quality of life assessed by a Short-Form 36 survey did not show any significant differences in all 8 scores between these 2 groups. Both types of NB reconstruction resulted in comparatively satisfactory outcomes; however, the voiding function, particularly that on long-term follow-up, in SNBG appeared to be more favorable than that in INBG. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Quality of Life Assessment With Orthotopic Ileal Neobladder Reconstruction After Radical Cystectomy: Results From a Prospective Italian Multicenter Observational Study.

    PubMed

    Imbimbo, Ciro; Mirone, Vincenzo; Siracusano, Salvatore; Niero, Mauro; Cerruto, Maria Angela; Lonardi, Cristina; Artibani, Walter; Bassi, Pierfrancesco; Iafrate, Massimo; Racioppi, Marco; Talamini, Renato; Ciciliato, Stefano; Toffoli, Laura; Visalli, Francesco; Massidda, Davide; D'Elia, Carolina; Cacciamani, Giovanni; De Marchi, Davide; Silvestri, Tommaso; Creta, Massimiliano; Belgrano, Emanuele; Verze, Paolo

    2015-11-01

    To assess health-related quality of life (HRQoL) parameters in patients who received radical cystectomy (RC) with ileal orthotopic neobladder (IONB) reconstruction and to identify clinic-pathologic predictors of HRQoL. From January 2010 to December 2013, a multicenter, retrospective on 174 RC-IONB patients was carried out. All patients completed the following questionnaires: the European Organization for Research and Treatment of Cancer (EORTC) generic (QLQ-C30) and bladder cancer-specific instruments (QLQ-BLM30) and the IONB-Patient Reported Outcome (IONB-PRO). Univariate and multivariate analyses were computed to identify clinic-pathologic predictors of HRQoL. Median age was 66 years (range, 31-83), and 91.4% of patients were men. Median follow-up period was 37 months (range, 3-247). The EORTC QLQ-C30 revealed that age >65 years, absence of urinary incontinence, and absence of peripheral vascular disease were independent predictors of deteriorated body image. A follow-up > 36 months and the presence of urinary incontinence were independent predictors of worsened urinary symptoms, whereas the absence of urinary incontinence was an independent predictor of a worsened body image according to EORTC QLQ-BLM30 results. A follow-up >36 months and the absence of urinary incontinence were independent predictors of better functioning in terms of relational life, emotional life, and fatigue as revealed by the IONB-PRO. Age, presence of urinary incontinence, length of follow-up, and comorbidity status may influence postoperative HRQoL and should all be taken into account when counseling RC-IONB patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Internal versus external ureteric stents for uretero-ileal anastomosis after laparoscopic radical cystectomy with orthotopic neobladder: A prospective comparative study.

    PubMed

    Abdel Hakim, Mahmoud A; Abdalla, Ahmed A; Saad, Ismail R; ElSheemy, Mohammed S; El Feel, Ahmed S; Salem, Hosni K; Abdel Hakim, Amr M

    2016-06-01

    To prospectively compare the use of external ureteric stents with internal JJ stenting of the uretero-ileal anastomosis in patients undergoing laparoscopic radical cystectomy (LRC) with a Y-shaped ileal orthotopic neobladder (ON). The study included 69 patients undergoing LRC with ON. Patients were grouped according to the type of uretero-ileal stents used. An external ureteric stent was used in Group A (33 patients) and a JJ stent was used in Group B (36). We prospectively compared the duration of hospital stay, the incidence of short- and intermediate-term complications in the two study groups. The mean (SD) follow-up periods were 29.18 (3.94) and 28.19 (3.37) months for patients in Groups A and B, respectively. Perioperative patient characteristics were comparable in the two study groups. The use of JJ stenting was associated with a shorter hospital stay compared with external stenting, at a mean (SD) of 14.63 (3.74) and 6.8 (3.03) days in Groups A and B, respectively (P < 0.001). The incidence of urinary leakage was comparable in the two study groups, at 6.1% in Group A vs 8.3% in Group B (P = 1.0). Strictures of the uretero-ileal anastomosis occurred in two patients (6%) in Group A and confirmed by intravenous urography. All strictures were treated with antegrade JJ fixation. JJ stents could be used as an effective alternative to external ureteric stents to support the uretero-ileal anastomosis. JJ stenting is associated with a shorter hospital stay and similar complication rates compared with external stenting in patients undergoing LRC with ON.

  5. Total Pelvic Supralevator Exenteration with Ileo-Colic Orthotopic Neobladder for Locoregional Recurrence after Cervical Cancer - A Case Report.

    PubMed

    Bacalbaşa, Nicolae; Bălescu, Irina; Braşoveanu, Vladislav

    2016-01-01

    Pelvic exenteration is one of the most aggressive surgical interventions in gynaecologic surgical oncology, but, in the same time, is the only potentially curative treatment of locoregional recurrence after cervical cancer. Due to improvements in surgical technique and postoperative management, the overall survival increased signifficantly in the last decades. Trying to improve the quality of life, multiple models of reconstruction of urinary and digestive tract have been developed. In this report we present the case of a 51 years old female who underwent a total supralevator exenteration with ileo colic neobladder reconstruction with good oncologic and functional outcomes. Celsius.

  6. Health-related Quality of Life After Radical Cystectomy: A Cross-sectional Study With Matched-pair Analysis on Ileal Conduit vs Ileal Orthotopic Neobladder Diversion.

    PubMed

    Cerruto, Maria Angela; D'Elia, Carolina; Siracusano, Salvatore; Saleh, Omar; Gacci, Mauro; Cacciamani, Giovanni; De Marco, Vincenzo; Porcaro, Antonio Benito; Balzarro, Matteo; Niero, Mauro; Lonardi, Cristina; Iafrate, Massimo; Bassi, Pierfrancesco; Imbimbo, Ciro; Racioppi, Marco; Talamini, Renato; Ciciliato, Stefano; Serni, Sergio; Carini, Marco; Verze, Paolo; Artibani, Walter

    2017-10-01

    To examine the different and health-related quality of life (HR-QoL) outcomes between ileal conduit (IC) and ileal orthotopic neobladder (IONB) in patients who underwent radical cystectomy (RC), by using validated self-reported cancer-specific instruments. This retrospective, cross-sectional, multicenter cohort study included 148 and 171 patients with either IC or IONB. HR-QoL was evaluated with Quality of Life Core Questionnaire and bladder module (BLM)-30 European Organisation for Research and Treatment of Cancer questionnaires. Baseline HR-QoL scores were dichotomized at the median to give "good" or "poor" score profiles. A matched-pair analysis compared HR-QoL aspects between 79 IC patients and 79 IONB patients. At univariate analysis IONB resulted favorable for physical functioning, emotional functioning, cognitive functioning (CF), fatigue, dyspnea, appetite loss, constipation (CO), and abdominal bloating flatulence (AB). At multivariate analyses, IONB showed better scores for emotional functioning (85 vs 79, P = .023), CF (93 vs 85, P <.001), CO (16 vs 31, P <.001), and AB (12 vs 25, P <.001). A significant worsening of sexual and urinary function was observed for IONB patients in the long-term. At matched-pair analysis, global health status was similar (65 vs 62, P = .385). Significantly better scores were observed in the IONB group for the following items: CF (P = .007), fatigue (P = .003), pain (P = .019), dyspnea (P = .016), CO (P = .001), and AB (P = .00). IONB and IC after RC were similar in terms of global health status. IONB provides better results in some aspects of HR-QoL related to bowel function, but a worsening of urinary and sexual functions. Further randomized controlled trials are needed to confirm these data. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Health-Related Quality of Life after Radical Cystectomy for Bladder Cancer in Elderly Patients with Ileal Orthotopic Neobladder or Ileal Conduit: Results from a Multicentre Cross-Sectional Study Using Validated Questionnaires.

    PubMed

    Cerruto, Maria Angela; D'Elia, Carolina; Siracusano, Salvatore; Saleh, Omar; Gacci, Mauro; Cacciamani, Giovanni; De Marco, Vincenzo; Porcaro, Antonio Benito; Balzarro, Matteo; Niero, Mauro; Lonardi, Cristina; Iafrate, Massimo; Bassi, Pierfrancesco; Imbimbo, Ciro; Racioppi, Marco; Talamini, Renato; Ciciliato, Stefano; Serni, Sergio; Carini, Marco; Verze, Paolo; Artibani, Walter

    2018-01-01

    To evaluate health-related quality of life (HR-QoL) outcomes in elderly patients with different type of urinary diversion (UD), ileal conduit (IC) and ileal orthotopic neobladder (IONB), after radical cystectomy (RC) for bladder cancer, by using validated self-reported cancer-specific instruments. We retrospectively reviewed 77 patients who received an IC or an IONB after RC. HR-QoL was assessed with specific and validated disease questionnaires, administered at last follow-up. At univariate analysis, at a mean follow-up of 60.91 ± 5.63 months, IONB results were favourable with regard to the following HR-QoL aspects: nausea and vomiting (p = 0.045), pain (p = 0.049), appetite loss (p = 0.03), constipation (p = 0.000), financial impact (p = 0.012) and cognitive functioning (p = 0.000). This last functional aspect was significantly worse in female patients (p = 0.029). Emotional functioning was significantly better in patients without long-term complications (p = 0.016). At multivariate analysis, male gender and IONB were independent predictors of better cognitive functioning, while long-term complications negatively affected emotional functioning. Obtained results suggest that an IONB can also be suitable for elderly patients compared with an IC with few and selected advantages in favour of the former UD. Preoperative patient's selection, counselling, education and active participation in the decision-making process lead to a more suitable choice of treatment. © 2018 S. Karger AG, Basel.

  8. Robot-assisted radical cystectomy with intracorporeal neobladder diversion: The Karolinska experience.

    PubMed

    Collins, Justin W; Sooriakumaran, P; Sanchez-Salas, R; Ahonen, R; Nyberg, T; Wiklund, N P; Hosseini, A

    2014-07-01

    The aim of this report is to describe our surgical technique of totally intracorporeal robotic assisted radical cystectomy (RARC) with neobladder formation. Between December 2003 and March 2013, a total of 147 patients (118 male, 29 female) underwent totally intracorporeal RARC for urinary bladder cancer. We also performed a systematic search of Medline, Embase and PubMed databases using the terms RARC, robotic cystectomy, robot-assisted, totally intracorporeal RARC, intracorporeal neobladder, intracorporeal urinary diversion, oncological outcomes, functional outcomes, and complication rates. The mean age of our patients was 64 years (range 37-87). On surgical pathology 47% had pT1 or less disease, 27% had pT2, 16% had pT3 and 10% had pT4. The mean number of lymph nodes removed was 21 (range 0-60). 24% of patients had lymph node positive dAQ1isease. Positive surgical margins occurred in 6 cases (4%). Mean follow-up was 31 months (range 4-115 months). Two patients (1.4%) died within 90 days of their operation. Using Kaplan-Meier analysis, overall survival and cancer specific survival at 60 months was 68% and 69.6%, respectively. 80 patients (54%) received a continent diversion with totally intracorporeal neobladder formation. In the neobladder subgroup median total operating time was 420 minutes (range 265-760). Daytime continence and satisfactory sexual function or potency at 12 months ranged between 70-90% in both men and women. Our experience with totally intracorporeal RARC demonstrates acceptable oncological and functional outcomes that suggest this is a viable alternative to open radical cystectomy.

  9. Ileal conduit vs orthotopic neobladder: Which one offers the best health-related quality of life in patients undergoing radical cystectomy? A systematic review of literature and meta-analysis.

    PubMed

    Ziouziou, I; Irani, J; Wei, J T; Karmouni, T; El Khader, K; Koutani, A; Iben Attya Andaloussi, A

    2018-04-01

    Orthotopic neobladder (ONB) and ileal conduit (IC) are the most commonly practiced techniques of urinary diversion (UD) after radical cystectomy (RC) in bladder cancer patients. Data in the literature is still discordant regarding which UD technique offers the best HR-QoL. The objective was to compare HR-QoL in patients undergoing ONB and IC after RC, through a systematic review of the literature and meta-analysis. We performed a literature search of PubMed, ScienceDirect, CochraneLibrary and ClinicalTrials.Gov in September 2017 according to the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes. The studies were evaluated according to the "Oxford Center for Evidence-Based Medicine" criteria. The outcome measures evaluated were subdomains' scores of Bladder Cancer Index BCI: urinary function (UF), urinary bother (UB), bowel function (BF), bowel bother (BB), sexual function (SF) and sexual bother (SB). Continuous outcomes were compared using weighted means differences, with 95% confidence intervals. The presence of publication bias was examined by funnel plots. Four studies met the inclusion criteria. The pooled results demonstrated better UF and UB scores in IC patients: differences were -18.17 (95% CI: -27.49, -8.84, P=0.0001) and -3.72 (95% CI: -6.66, -0.79, P=0.01) respectively. There was no significant difference between IC and ONB patients in terms of BF and BB. SF was significantly better in ONB patients: the difference was 12.7 (95% CI, 6.32, 19.08, P<0.0001). However no significant difference was observed regarding SB. This meta-analysis of non-randomized studies demonstrated a better HR-QoL in urinary outcomes in IC patients compared with ONB patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  10. Systematic review and meta-analysis of non RCT's on health related quality of life after radical cystectomy using validated questionnaires: Better results with orthotopic neobladder versus ileal conduit.

    PubMed

    Cerruto, M A; D'Elia, C; Siracusano, S; Gedeshi, X; Mariotto, A; Iafrate, M; Niero, M; Lonardi, C; Bassi, P; Belgrano, E; Imbimbo, C; Racioppi, M; Talamini, R; Ciciliato, S; Toffoli, L; Rizzo, M; Visalli, F; Verze, P; Artibani, W

    2016-03-01

    The current literature on the impact of different urinary diversions on patients' health related quality of life (HR-QoL) showed a marginally better quality of life scores of orthotopic neobladder (ONB) compared to ileal conduit (IC). The aim of this study was to update the review of all relevant published studies on the comparison between ONB and IC. Studies were identified by searching multiple literature databases, including MEDLINE, CINAHL, the Cochrane Library, PubMed Data were synthesized using meta-analytic methods conformed to the PRISMA statement. The current meta-analysis was based on 18 papers that reported a HR-QoL comparison between IC and ONB using at least a validate questionnaire. Pooled effect sizes of combined QoL outcomes for IC versus ONB showed a slight, but not significant, better QoL in patients with ONB (Hedges' g = 0.150; p = 0.066). Patients with ileal ONB showed a significant better QoL than those with IC (Hedges' g = 0.278; p = 0.000); in case series with more than 65% males, ONB group showed a slight significant better QoL than IC (Hedges' g = 0.190; p = 0.024). Pooled effects sizes of all EORTC-QLQ-C30 aspects showed a significant better QoL in patients with ONB (Hedges' g = 0.400; p = 0.0000). This meta-analysis of not-randomized comparative studies on the impact of different types of urinary diversions on HR-QoL showed demonstrated a significant advantage of ileal ONB compared to IC in terms of HR-QoL. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Health information quality on the internet for bladder cancer and urinary diversion: a multi-lingual analysis.

    PubMed

    Corfield, Julia M; Abouassaly, Robert; Lawrentschuk, Nathan

    2018-04-01

    Bladder cancer patients undergoing radical cystectomy and urinary diversion are faced with difficult decisions regarding mode of urinary diversion. Although these patients may use the Internet as a guide to diagnosis and treatment options, online resources remain largely unregulated leading to a great variation in quality of medical information. Further variation in quality is seen between languages. Fortunately, tools such as an automated toolbar developed by the World Health Organization Health on the Net (HON) Foundation exist to assist physicians in recommending quality online health information to patients. We set out to compare and assess the quality of bladder cancer, ileal conduit and orthotopic neobladder web sites in 2016 on the basis of the HON principles for English language. The Google search engine imbedded with the HON toolbar was used to assess 1350 Web sites using the keywords "bladder cancer", "ileal conduit" and "orthotopic neobladder" in English, Italian and Spanish. The first 150 results of each search were identified and screened. A further analysis was completed comparing results between 2009 and 2016. Less than 20% of English, Italian and Spanish "bladder cancer" and urinary diversion ("ileal conduit" and "orthotopic neobladder") web sites are HON-accredited. HON-accredited web sites featured preferentially in the first 50 search results for bladder cancer (P=0.0001) and ileal conduit (P=0.03) web sites. Comparing 2016 results to 2009, percentage of HON-accreditation has not shown statistically significant change (-13%, P=0.23), while overall number of search results has increased (+44%). A lack of validation of bladder cancer sites is present, which is consistent across modes of urinary diversion (orthotopic neobladder and ileal conduit) and languages. It is important that physicians involved in the care of bladder cancer patients undergoing radical cystectomy and urinary diversion participate in the development of informative, ethical, and

  12. Orthotopic bladder substitution in men revisited: identification of continence predictors.

    PubMed

    Koraitim, M M; Atta, M A; Foda, M K

    2006-11-01

    We determined the impact of the functional characteristics of the neobladder and urethral sphincter on continence results, and determined the most significant predictors of continence. A total of 88 male patients 29 to 70 years old underwent orthotopic bladder substitution with tubularized ileocecal segment (40) and detubularized sigmoid (25) or ileum (23). Uroflowmetry, cystometry and urethral pressure profilometry were performed at 13 to 36 months (mean 19) postoperatively. The correlation between urinary continence and 28 urodynamic variables was assessed. Parameters that correlated significantly with continence were entered into a multivariate analysis using a logistic regression model to determine the most significant predictors of continence. Maximum urethral closure pressure was the only parameter that showed a statistically significant correlation with diurnal continence. Nocturnal continence had not only a statistically significant positive correlation with maximum urethral closure pressure, but also statistically significant negative correlations with maximum contraction amplitude, and baseline pressure at mid and maximum capacity. Three of these 4 parameters, including maximum urethral closure pressure, maximum contraction amplitude and baseline pressure at mid capacity, proved to be significant predictors of continence on multivariate analysis. While daytime continence is determined by maximum urethral closure pressure, during the night it is the net result of 2 forces that have about equal influence but in opposite directions, that is maximum urethral closure pressure vs maximum contraction amplitude plus baseline pressure at mid capacity. Two equations were derived from the logistic regression model to predict the probability of continence after orthotopic bladder substitution, including Z1 (diurnal) = 0.605 + 0.0085 maximum urethral closure pressure and Z2 (nocturnal) = 0.841 + 0.01 [maximum urethral closure pressure - (maximum contraction amplitude

  13. Quality of life after radical cystectomy for bladder cancer in men with an ileal conduit or continent urinary diversion: A comparative study

    PubMed Central

    Asgari, M. A.; Safarinejad, M. R.; Shakhssalim, N.; Soleimani, M.; Shahabi, A.; Amini, E.

    2013-01-01

    Aim: To investigate quality of life (QoL) domains with three forms of urinary diversions, including ileal conduit, MAINZ pouch, and orthotopic ileal neobladder after radical cystectomy in men with muscle-invasive bladder cancer. Materials and Methods: In a prospective study, 149 men underwent radical cystectomy and urinary diversion (70 ileal conduit, 16 MAINZ pouch, and 63 orthotopic ileal neobladder). Different domains of QoL, including general and physical conditions, psychological status, social status, sexual life, diversion-related symptoms, and satisfaction with the treatment were assessed using an author constructed questionnaire. Assessment was performed at three months postoperatively. Results: In questions addressing psychological status, social status, and sexual life, patients with continent diversion had a more favorable outcome (P = 0.002, P = 0.01, and P = 0.002, respectively). The rate of erectile dysfunction did not differ significantly between the three groups (P = 0.21). The rate and global satisfaction was higher with the MAINZ pouch (68.7%) and ileal neobladder (76.2%) as compared with the ileal conduit group (52.8%) (P = 0.002). Conclusion: Continent urinary diversion after radical cystectomy provides better results in terms of QoL as compared with ileal conduit diversion. PMID:24049384

  14. Introduction of an enhanced recovery protocol to reduce short-term complications following radical cystectomy and intestinal urinary diversion with vescica ileale Padovana neobladder.

    PubMed

    Cerruto, Maria Angela; De Marco, Vincenzo; D'Elia, Carolina; Bizzotto, Leonardo; Curti, Pierpaolo; Baldassarre, Roberto; Artibani, Walter

    2014-01-01

    To reduce short-term complications of radical cystectomy (RC) and intestinal urinary diversion with vescica ileale Padovana (VIP) neobladder, we described and assessed an enhanced recovery protocol (ERP) in a series of consecutive patients. An ERP was introduced focusing on reduced bowel preparation, standardized feeding and analgesic regimens. We analyzed the outcomes with all patients consecutively undergoing RC and VIP neobladder who met the following inclusion criteria: American Society of Anesthesiologists score <3; absence of malnutrition according to the Mini Nutritional Assessment-Short Form criteria; absence of inflammatory bowel diseases. Thirty-one consecutive patients were recruited to undergo our ERP. Mean age of patients was 62.16 years. No patients died due to surgical complications. Nine of 31 patients experienced complications (29.03%), none requiring surgical intervention. According to Clavien grading, all complications were grade <2. The application of our ERP to our patients undergoing RC and VIP neobladder contributed to reduce postoperative morbidity. Copyright © 2013 S. Karger AG, Basel.

  15. Risk of in-hospital complications after radical cystectomy for urinary bladder carcinoma: population-based follow-up study of 7608 patients

    PubMed Central

    Hemelrijck, Mieke; Thorstenson, Andreas; Smith, Philip; Adolfsson, Jan; Akre, Olof

    2013-01-01

    Objective To evaluate the risk of different in-hospital complications for patients undergoing a radical cystectomy (RC), as limited nationwide population data on short- and long-term complications after RC is available, despite it being the standard treatment for localised muscle-invasive urinary bladder cancer (UBC). Patients and Methods In all, 7608 persons underwent a RC after UBC diagnosis, as registered in the Swedish National Patient Register between 1964 and 2008. We estimated the frequency and incidences and calculated hazard ratios (HR) and 95% confidence intervals (CI) using multivariate Cox proportional hazards models. Results Urinary tract infection/septicaemia was the most common complication following radical cystectomy, with an incidence of 90.4 per 1,000 person years. There was a higher risk of urinary tract infection among patients who had a continent cutaneous reservoir (HR: 1.11 (0.94–1.30) or orthotopic neobladder 1.21 (1.05–1.39) than among those with ileal conduit. Similarly, continent cutaneous reservoir and orthotopic neobladder were associated with increased risks for wound and abdominal wall hernias, stones in the urinary tract, hydronephrosis and nephrostomy tube treatment, and kidney failure. In contrast, risk of bowel obstruction was lower among those with orthotopic neobladder than those with ileal conduit (HR: 0.64 (0.50–0.81)) and those with continent cutaneous reservoir (HR: 0.92 (0.73–1.16). Conclusions In-hospital complications after RC are numerous and continue to accumulate for many years after surgery, indicating the need for life-long follow-up of these patients. Comparison between different types of diversion should, however, be made with care because of potential confounding by indication. PMID:23906011

  16. Studer orthotopic ileal bladder substitute construction - surgical technique and complication management: one-center and 12-year experience.

    PubMed

    Wyczółkowski, M; Juszczak, K; Rzepecki, M; Drewniak, T; Klima, W

    2010-01-01

    We have performed Studer neobladder creation in 61 patients (53 male and 8 female). The aims of this study were to evaluate the clinical outcomes, to review the surgical technique modification, postoperative complications management and metabolic disturbances. All patients were retrospectively studied and followed-up. The follow-up: 12 years to 2 months. 44 patients (41 male and 3 female) returned for a control visit. All completed IIQ-7 questionnaire. Continence was analysed. Kidney ultrasound, post void residual and uroflowmetry, blood tests (electrolytes, kidney markers, acid-base balance) were performed. All patients were divided into two groups: I (with Zuber mineral water intake) and group II (without Zuber mineral water intake) for acid-base balance analysis. Early complications occurred in 13.1% (enterocolitis, neobladder-urethral anastomosis leakage, pyelonephritis, and lymphorrhoea). Late complications occurred in 14.0% (stricture of the neobladder-urethra anastomosis, urosepsis secondarily to bilateral hydronephrosis, stone formation, and pyonephrosis). In the follow-up 88.6% of patients revealed normal continence. The nocturnal incontinence, nocturia, and external or indwelling catheter were reported in 9, 6 and 5 patients, respectively). In IIQ-7 the mean negative impact of continence level on patients quality of life was 10.08% ± 14.47%. The mean Qmax., Qave., post void residual were 15.8 ± 4.9 ml/s, 7.9 ± 3.0 ml/s, and 151.2 ± 139.2 ml, respectively. Patients who regularly intake the Zuber present significant decrease of BE deficiency as compared to patient without Zuber usage. The Studer neobladder is the alternative urinary diversion. This is the difficult, skill demanding procedure, nevertheless gaining experience with self modifications resulted in decrease of complications. The Zuber mineral water intake ameliorates the base excess deficiency after Studer creation.

  17. Orthotopic liver transplantation in an adult with cholesterol ester storage disease.

    PubMed

    Ambler, Graeme K; Hoare, Matthew; Brais, Rebecca; Shaw, Ashley; Butler, Andrew; Flynn, Paul; Deegan, Patrick; Griffiths, William J H

    2013-01-01

    Cholesterol ester storage disease (CESD) is a rare autosomal recessive lipid storage disorder associated with mutations of the gene encoding lysosomal acid lipase, manifestations of which include chronic liver disease and early atherosclerosis. Although normally presenting in childhood, severity is variable and the condition can occasionally remain undetected until middle age. Typical presentation is with asymptomatic hepatosplenomegaly and hyperlipidaemia, though the condition is probably underdiagnosed. Treatment is supportive and may include attention to cardiovascular risk factors. Phase I/II trials of enzyme replacement therapy are ongoing, but this approach remains experimental. We present the case of a 42-year-old woman diagnosed with CESD in childhood who ran an indolent course until re-presentation with cirrhotic hydrothorax. She underwent orthotopic liver transplantation but required re-transplantation for hepatic artery thrombosis. She remains well with excellent graft function 2 years later. Although atherosclerosis was apparent at assessment, and may have contributed to hepatic artery thrombosis, partial correction of the metabolic defect and restoration of liver function by transplantation together with ongoing medical therapy should permit reasonable survival over the longer term from both a liver and a vascular perspective. This is the first reported case of orthotopic liver transplantation for CESD in an adult, which was the only available option to improve survival. The case highlights the importance of monitoring patients with CESD through adulthood and suggests that liver replacement at a later stage may yet be indicated and remain of benefit.

  18. Predictors of renal function recovery among patients undergoing renal replacement therapy following orthotopic liver transplantation.

    PubMed

    Andreoli, Maria Claudia Cruz; Souza, Nádia Karina Guimarães de; Ammirati, Adriano Luiz; Matsui, Thais Nemoto; Carneiro, Fabiana Dias; Ramos, Ana Claudia Mallet de Souza; Iizuca, Ilson Jorge; Coelho, Maria Paula Vilela; Afonso, Rogério Carballo; Ferraz-Neto, Ben-Hur; Almeida, Marcio Dias de; Durão, Marcelino; Batista, Marcelo Costa; Monte, Julio Cesar; Pereira, Virgílio Gonçalves; Santos, Oscar Pavão Dos; Santos, Bento Cardoso Dos

    2017-01-01

    Renal dysfunction frequently occurs during the periods preceding and following orthotopic liver transplantation (OLT), and in many cases, renal replacement therapy (RRT) is required. Information regarding the duration of RRT and the rate of kidney function recovery after OLT is crucial for transplant program management. We evaluated a sample of 155 stable patients undergoing post-intensive care hemodialysis (HD) from a patient population of 908 adults who underwent OLT. We investigated the average time to renal function recovery (duration of RRT required) and determined the risk factors for remaining on dialysis > 90 days after OLT. Log-rank tests were used for univariate analysis, and Cox proportional hazards models were used to identify factors associated with the risk of remaining on HD. The results of our analysis showed that of the 155 patients, 28% had pre-OLT diabetes mellitus, 21% had pre-OLT hypertension, and 40% had viral hepatitis. Among the patients, the median MELD (Model for End-Stage Liver Disease) score was 27 (interquartile range [IQR] 22-35). When they were listed for liver transplantation, 32% of the patients had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD, and 50% had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD at the time of OLT. Of the transplanted patients, 25% underwent pre-OLT intermittent HD, and 14% and 41% underwent continuous renal replacement therapy (CRRT) pre-OLT and post-OLT, respectively. At 90 days post-OLT, 118 (76%) patients had been taken off dialysis, and 16 (10%) patients had died while undergoing HD. The median recovery time of these post-OLT patients was 33 (IQR 27-39) days. In the multivariate analysis, fulminant hepatic failure as the cause of liver disease (p<0.001), the absence of pre-OLT hypertension (p = 0.016), a lower intraoperative fresh-frozen plasma (FFP) transfusion volume (p = 0.019) and not undergoing pre-OLT intermittent HD (p = 0.032) were associated with performing RRT for less than

  19. Predictors of renal function recovery among patients undergoing renal replacement therapy following orthotopic liver transplantation

    PubMed Central

    de Souza, Nádia Karina Guimarães; Ammirati, Adriano Luiz; Matsui, Thais Nemoto; Carneiro, Fabiana Dias; Ramos, Ana Claudia Mallet de Souza; Iizuca, Ilson Jorge; Afonso, Rogério Carballo; Ferraz-Neto, Ben-Hur; de Almeida, Marcio Dias; Durão, Marcelino; Batista, Marcelo Costa; Monte, Julio Cesar; Pereira, Virgílio Gonçalves; dos Santos, Oscar Pavão

    2017-01-01

    Renal dysfunction frequently occurs during the periods preceding and following orthotopic liver transplantation (OLT), and in many cases, renal replacement therapy (RRT) is required. Information regarding the duration of RRT and the rate of kidney function recovery after OLT is crucial for transplant program management. We evaluated a sample of 155 stable patients undergoing post-intensive care hemodialysis (HD) from a patient population of 908 adults who underwent OLT. We investigated the average time to renal function recovery (duration of RRT required) and determined the risk factors for remaining on dialysis > 90 days after OLT. Log-rank tests were used for univariate analysis, and Cox proportional hazards models were used to identify factors associated with the risk of remaining on HD. The results of our analysis showed that of the 155 patients, 28% had pre-OLT diabetes mellitus, 21% had pre-OLT hypertension, and 40% had viral hepatitis. Among the patients, the median MELD (Model for End-Stage Liver Disease) score was 27 (interquartile range [IQR] 22-35). When they were listed for liver transplantation, 32% of the patients had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD, and 50% had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD at the time of OLT. Of the transplanted patients, 25% underwent pre-OLT intermittent HD, and 14% and 41% underwent continuous renal replacement therapy (CRRT) pre-OLT and post-OLT, respectively. At 90 days post-OLT, 118 (76%) patients had been taken off dialysis, and 16 (10%) patients had died while undergoing HD. The median recovery time of these post-OLT patients was 33 (IQR 27–39) days. In the multivariate analysis, fulminant hepatic failure as the cause of liver disease (p<0.001), the absence of pre-OLT hypertension (p = 0.016), a lower intraoperative fresh-frozen plasma (FFP) transfusion volume (p = 0.019) and not undergoing pre-OLT intermittent HD (p = 0.032) were associated with performing RRT for less

  20. Marine Collagen Scaffolds for Nasal Cartilage Repair: Prevention of Nasal Septal Perforations in a New Orthotopic Rat Model Using Tissue Engineering Techniques

    PubMed Central

    Bermueller, Christian; Elsaesser, Alexander F.; Sewing, Judith; Baur, Nina; von Bomhard, Achim; Scheithauer, Marc; Notbohm, Holger; Rotter, Nicole

    2013-01-01

    Autologous grafts are frequently needed for nasal septum reconstruction. Because they are only available in limited amounts, there is a need for new cartilage replacement strategies. Tissue engineering based on the use of autologous chondrocytes and resorbable matrices might be a suitable option. So far, an optimal material for nasal septum reconstruction has not been identified. The aim of our study was to provide the first evaluation of marine collagen for use in nasal cartilage repair. First, we studied the suitability of marine collagen as a cartilage replacement matrix in the context of in vitro three dimensional cultures by analyzing cell migration, cytotoxicity, and extracellular matrix formation using human and rat nasal septal chondrocytes. Second, we worked toward developing a suitable orthotopic animal model for nasal septum repair, while simultaneously evaluating the biocompatibility of marine collagen. Seeded and unseeded scaffolds were transplanted into nasal septum defects in an orthotopic rat model for 1, 4, and 12 weeks. Explanted scaffolds were histologically and immunohistochemically evaluated. Scaffolds did not induce any cytotoxic reactions in vitro. Chondrocytes were able to adhere to marine collagen and produce cartilaginous matrix proteins, such as collagen type II. Treating septal cartilage defects in vivo with seeded and unseeded scaffolds led to a significant reduction in the number of nasal septum perforations compared to no replacement. In summary, we demonstrated that marine collagen matrices provide excellent properties for cartilage tissue engineering. Marine collagen scaffolds are able to prevent septal perforations in an autologous, orthotopic rat model. This newly described experimental surgical procedure is a suitable way to evaluate new scaffold materials for their applicability in the context of nasal cartilage repair. PMID:23621795

  1. Orthotopic Patient-Derived Glioblastoma Xenografts in Mice.

    PubMed

    Xu, Zhongye; Kader, Michael; Sen, Rajeev; Placantonakis, Dimitris G

    2018-01-01

    Patient-derived xenografts (PDX) provide in vivo glioblastoma (GBM) models that recapitulate actual tumors. Orthotopic tumor xenografts within the mouse brain are obtained by injection of GBM stem-like cells derived from fresh surgical specimens. These xenografts reproduce GBM's histologic complexity and hallmark biological behaviors, such as brain invasion, angiogenesis, and resistance to therapy. This method has become essential for analyzing mechanisms of tumorigenesis and testing the therapeutic effect of candidate agents in the preclinical setting. Here, we describe a protocol for establishing orthotopic tumor xenografts in the mouse brain with human GBM cells.

  2. Venous outflow obstruction and portopulmonary hypertension after orthotopic liver transplantation

    PubMed Central

    Aguirre-Avalos, Guadalupe; Covarrubias-Velasco, Marco Antonio; Rojas-Sánchez, Antonio Gerardo

    2013-01-01

    Patient: Female, 54 Final Diagnosis: Suprahepatic inferior vena cava anastomosis stricture Symptoms: Ascites • fatigue • lower limb edema • hepatomegaly Medication: — Clinical Procedure: — Specialty: Transplantology • Critical Care Medicine Objective: Unusual clinical course Background: Suprahepatic inferior vena cava anastomosis stricture is an unusual vascular complication after orthotopic liver transplantation with the “piggyback” technique. Clinical manifestations are dependent upon the severity of the stenosis. Portopulmonary hypertension after orthotopic liver transplantation is a complication that carries high mortality due to cardiopulmonary dysfunction. The pathogenesis of pulmonary vascular disorders after orthotopic liver transplantation remains uncertain. Case Report: We report a case of acute right heart pressure overload after surgical correction of the suprahepatic inferior vena cava anastomotic stricture in a 54-year-old woman who had preexisting pulmonary arterial hypertension associated with portal hypertension after orthotopic liver transplantation. Twenty months posttransplantation, she developed fatigue and progressive ascites. On admission, the patient had hepatomegaly, ascites, and lower limb edema. Symptoms in the patient developed gradually over time. Conclusions: Recurrent portal hypertension by vascular complications is a cause of pulmonary arterial hypertension after orthotopic liver transplantation. Clinical manifestations of suprahepatic inferior vena cava anastomotic stenosis are dependent upon their severity. Sildenafil is an effective drug for treatment of pulmonary arterial hyper-tension after portal hypertension by vascular complications. PMID:24046802

  3. Infections After Orthotopic Liver Transplantation

    PubMed Central

    Pedersen, Mark; Seetharam, Anil

    2014-01-01

    Opportunistic infections are a leading cause of morbidity and mortality after orthotopic liver transplantation. Systemic immunosuppression renders the liver recipient susceptible to de novo infection with bacteria, viruses and fungi post-transplantation as well to reactivation of pre-existing, latent disease. Pathogens are also transmissible via the donor organ. The time from transplantation and degree of immunosuppression may guide the differential diagnosis of potential infectious agents. However, typical systemic signs and symptoms of infection are often absent or blunted after transplant and a high index of suspicion is needed. Invasive procedures are often required to procure tissue for culture and guide antimicrobial therapy. Antimicrobial prophylaxis reduces the incidence of opportunistic infections and is routinely employed in the care of patients after liver transplant. In this review, we survey common bacterial, fungal, and viral infections after orthotopic liver transplantation and highlight recent developments in their diagnosis and management. PMID:25755581

  4. Silencing Intersectin 1 Slows Orthotopic Neuroblastoma Growth in Mice.

    PubMed

    Harris, Jamie; Herrero-Garcia, Erika; Russo, Angela; Kajdacsy-Balla, Andre; O'Bryan, John P; Chiu, Bill

    2017-11-01

    Neuroblastoma accounts for 15% of all pediatric cancer deaths. Intersectin 1 (ITSN1), a scaffold protein involved in phosphoinositide 3-kinase (PI3K) signaling, regulates neuroblastoma cells independent of MYCN status. We hypothesize that by silencing ITSN1 in neuroblastoma cells, tumor growth will be decreased in an orthotopic mouse tumor model. SK-N-AS neuroblastoma cells transfected with empty vector (pSR), vectors expressing scrambled shRNA (pSCR), or shRNAs targeting ITSN1 (sh#1 and sh#2) were used to create orthotopic neuroblastoma tumors in mice. Volume was monitored weekly with ultrasound. End-point was tumor volume >1000 mm. Tumor cell lysates were analyzed with anti-ITSN1 antibody by Western blot. Orthotopic tumors were created in all cell lines. Twenty-five days post injection, pSR tumor size was 917.6±247.7 mm, pSCR was 1180±159.9 mm, sh#1 was 526.3±212.8 mm, and sh#2 was 589.2±74.91 mm. sh#1-tumors and sh#2-tumors were smaller than pSCR (P=0.02), no difference between sh#1 and sh#2. Survival was superior in sh#2-tumors (P=0.02), trended towards improved survival in sh#1-tumors (P=0.09), compared with pSCR-tumors, no difference in pSR tumors. Western blot showed decreased ITSN1 expression in sh#1 and sh#2 compared with pSR and pSCR. Silencing ITSN1 in neuroblastoma cells led to decreased tumor growth in an orthotopic mouse model. Orthotopic animal models can provide insight into the role of ITSN1 pathways in neuroblastoma tumorigenesis.

  5. [Astigmatism after keratoplasty: influence of orthotopic transplantation].

    PubMed

    Feuerstacke, J; Hellwinkel, O; Naydis, I; Linke, S; Klemm, M

    2014-09-01

    Patients undergoing corneal transplantation often suffer from postoperative reduced vision due to high astigmatism. This retrospective study analyzed the influence of heterotopic or orthotopic transplantation on astigmatism and visual outcome. In this study 373 eyes of 334 patients were analyzed. Group 1 (OT) contained 186 eyes, which underwent orthotopic transplantation (side of recipient and donor corresponded), whereas group 2 (HT) included 187 heterotopic keratoplasties (donor cornea placed in the recipient's contralateral side). After 1, 3, 6, 12 and 24 months the median of keratometric astigmatism, objective astigmatism, topographic astigmatism and best corrected visual acuity (BCVA) were assessed and compared between groups. The long-term results showed no statistically significant differences regarding keratometric and objective astigmatism, whereas topographic astigmatism differed significantly (p = 0.04) after 3 months. We observed a lower astigmatism of 5.7 dpt (range 3.08-7.78 dpt) in group OT than in the group HT with 7.1 dpt (range 3.9-10.7 dpt). No differences were found at the other time points. The BCVA showed a significantly better effect after 1 month (p = 0.01) in the OT group of 0.2 (0.1-0.3) than in HT group of 0.1 (0.05/0.25). In the postoperative course no additional significant dissimilarities were documented. Heterotopic and orthotopic keratoplasty show no significant long-term differences in astigmatism and visual outcom.

  6. Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats

    PubMed Central

    Sjöqvist, Sebastian; Jungebluth, Philipp; Ling Lim, Mei; Haag, Johannes C.; Gustafsson, Ylva; Lemon, Greg; Baiguera, Silvia; Angel Burguillos, Miguel; Del Gaudio, Costantino; Rodríguez, Antonio Beltrán; Sotnichenko, Alexander; Kublickiene, Karolina; Ullman, Henrik; Kielstein, Heike; Damberg, Peter; Bianco, Alessandra; Heuchel, Rainer; Zhao, Ying; Ribatti, Domenico; Ibarra, Cristián; Joseph, Bertrand; Taylor, Doris A.; Macchiarini, Paolo

    2014-01-01

    A tissue-engineered oesophageal scaffold could be very useful for the treatment of pediatric and adult patients with benign or malignant diseases such as carcinomas, trauma or congenital malformations. Here we decellularize rat oesophagi inside a perfusion bioreactor to create biocompatible biological rat scaffolds that mimic native architecture, resist mechanical stress and induce angiogenesis. Seeded allogeneic mesenchymal stromal cells spontaneously differentiate (proven by gene-, protein and functional evaluations) into epithelial- and muscle-like cells. The reseeded scaffolds are used to orthotopically replace the entire cervical oesophagus in immunocompetent rats. All animals survive the 14-day study period, with patent and functional grafts, and gain significantly more weight than sham-operated animals. Explanted grafts show regeneration of all the major cell and tissue components of the oesophagus including functional epithelium, muscle fibres, nerves and vasculature. We consider the presented tissue-engineered oesophageal scaffolds a significant step towards the clinical application of bioengineered oesophagi. PMID:24736316

  7. Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors

    PubMed Central

    2013-01-01

    Background Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs. Methods We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated. Results TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth. Conclusions We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies. PMID:23937707

  8. BK virus associated pronounced hemorrhagic cystoureteritis after bone marrow transplantation.

    PubMed

    Haab, Alexander C; Keller, Isabelle S; Padevit, Christian; John, Hubert

    2015-10-01

    Ureteral stenosis due to reactivation of the BK virus (BKV) in a state of immunodeficiency is very rare. More common is the appearance of a hemorrhagic cystitis. This report not only shows bilateral ureteral stenosis after bone marrow transplantation, but also presents severe complications as chronic pelvic pain and impaired kidney function as well as irreparable damage to the whole urinary tract leading to nephroureterectomy, subtrigonal cystectomy and orthotopic ileal neobladder. Finally renal transplantation was required. To our knowledge this is the first case in the literature where such a severe course of BKV associated hemorrhagic cystoureteritis is described.

  9. Role of airway epithelial injury in murine orthotopic tracheal allograft rejection.

    PubMed

    Kuo, Elbert; Bharat, Ankit; Shih, Jennifer; Street, Tyler; Norris, Jenyi; Liu, Wei; Parks, William; Walter, Michael; Patterson, G Alexander; Mohanakumar, T

    2006-10-01

    Murine tracheal transplantation is a model used to study bronchiolitis obliterans syndrome, a major cause of morbidity and mortality after lung transplantation. Unlike murine heterotopic tracheal transplants, orthotopic transplantation does not cause luminal obliteration despite major histocompatibility antigen mismatch. Repopulation of the tracheal allografts with recipient-derived epithelium confers protection against luminal obliteration. The purpose of this study was to determine whether (1) orthotopic tracheal transplantation showed signs of allograft rejection, and (2) airway epithelial cell injury promoted orthotopic tracheal allograft rejection. Forty isogeneic (C57BL/6 to C57BL/6) and 40 allogeneic (BALB/c to C57BL/6) orthotopic tracheal transplants were performed. Damage to airway epithelial cells was induced by Sendai viral (SdV) infection and tracheal transplantation into non-reepithelializing matrix metalloproteinase-7 knockout (MMP7-KO) recipient mice. Percent fibrosis and lamina propria to cartilage ratio were calculated with computer assistance on harvested allografts. Allografts showed significantly more intramural fibrosis compared with isografts at 30, 60, and 180 days after transplant without luminal occlusion. Tracheal allografts infected with SdV showed an increase in fibrosis and lamina propria to cartilage ratio compared with noninfected controls. Allografts retrieved from MMP7-KO recipients also showed a significant increase in fibrosis and lamina propria to cartilage ratio. Although orthotopic tracheal transplantation does not cause luminal obliteration, it results in increased fibrosis in allografts. Damage to the respiratory epithelium by viral infection or defective reepithelialization after transplant as seen in MMP7-KO recipient mice leads to changes consistent with chronic allograft rejection, suggesting a role for epithelial injury in bronchiolitis obliterans syndrome development.

  10. Establishment of a patient-derived orthotopic osteosarcoma mouse model.

    PubMed

    Blattmann, Claudia; Thiemann, Markus; Stenzinger, Albrecht; Roth, Eva K; Dittmar, Anne; Witt, Hendrik; Lehner, Burkhard; Renker, Eva; Jugold, Manfred; Eichwald, Viktoria; Weichert, Wilko; Huber, Peter E; Kulozik, Andreas E

    2015-04-30

    Osteosarcoma (OS) is the most common pediatric primary malignant bone tumor. As the prognosis for patients following standard treatment did not improve for almost three decades, functional preclinical models that closely reflect important clinical cancer characteristics are urgently needed to develop and evaluate new treatment strategies. The objective of this study was to establish an orthotopic xenotransplanted mouse model using patient-derived tumor tissue. Fresh tumor tissue from an adolescent female patient with osteosarcoma after relapse was surgically xenografted into the right tibia of 6 immunodeficient BALB/c Nu/Nu mice as well as cultured into medium. Tumor growth was serially assessed by palpation and with magnetic resonance imaging (MRI). In parallel, a primary cell line of the same tumor was established. Histology and high-resolution array-based comparative genomic hybridization (aCGH) were used to investigate both phenotypic and genotypic characteristics of different passages of human xenografts and the cell line compared to the tissue of origin. A primary OS cell line and a primary patient-derived orthotopic xenotranplanted mouse model were established. MRI analyses and histopathology demonstrated an identical architecture in the primary tumor and in the xenografts. Array-CGH analyses of the cell line and all xenografts showed highly comparable patterns of genomic progression. So far, three further primary patient-derived orthotopic xenotranplanted mouse models could be established. We report the first orthotopic OS mouse model generated by transplantation of tumor fragments directly harvested from the patient. This model represents the morphologic and genomic identity of the primary tumor and provides a preclinical platform to evaluate new treatment strategies in OS.

  11. Orthotopic heart transplant versus left ventricular assist device: A national comparison of cost and survival

    PubMed Central

    Mulloy, Daniel P.; Bhamidipati, Castigliano M.; Stone, Matthew L.; Ailawadi, Gorav; Kron, Irving L.; Kern, John A.

    2012-01-01

    Objectives Orthotopic heart transplantation is the standard of care for end-stage heart disease. Left ventricular assist device implantation offers an alternative treatment approach. Left ventricular assist device practice has changed dramatically since the 2008 Food and Drug Administration approval of the HeartMate II (Thoratec, Pleasanton, Calif), but at what societal cost? The present study examined the cost and efficacy of both treatments over time. Methods All patients who underwent either orthotopic heart transplantation (n = 9369) or placement of an implantable left ventricular assist device (n = 6414) from 2005 to 2009 in the Nationwide Inpatient Sample were selected. The trends in treatment use, mortality, and cost were analyzed. Results The incidence of orthotopic heart transplantation increased marginally within a 5-year period. In contrast, the annual left ventricular assist device implantation rates nearly tripled. In-hospital mortality from left ventricular assist device implantation decreased precipitously, from 42% to 17%. In-hospital mortality for orthotopic heart transplantation remained relatively stable (range, 3.8%–6.5%). The mean cost per patient increased for both orthotopic heart transplantation and left ventricular assist device placement (40% and 17%, respectively). With the observed increase in both device usage and cost per patient, the cumulative Left ventricular assist device cost increased 232% within 5 years (from $143 million to $479 million). By 2009, Medicare and Medicaid were the primary payers for nearly one half of all patients (orthotopic heart transplantation, 45%; left ventricular assist device, 51%). Conclusions Since Food and Drug Administration approval of the HeartMate II, mortality after left ventricular assist device implantation has decreased rapidly, yet has remained greater than that after orthotopic heart transplantation. The left ventricular assist device costs have continued to increase and have been

  12. Postoperative gastrointestinal bleeding after an orthotopic liver transplant: a single-center experience.

    PubMed

    Fidan, Cihan; Kırnap, Mahir; Akdur, Aydıncan; Özçay, Figen; Selçuk, Haldun; Arslan, Gülnaz; Moray, Gökhan; Haberal, Mehmet

    2014-03-01

    The overall incidence, causes, and treatment of posttransplant gastrointestinal bleeding, have been previously described. In this study, we examined the causes and treatment of postoperative gastrointestinal bleeding after orthotopic liver transplant. Clinical data of 335 patients who underwent an orthotopic liver transplant at our institution between September 2001 and December 2012 were analyzed retrospectively. The diagnosis and treatment of postoperative gastrointestinal bleeding after an orthotopic liver transplant were reviewed. Gastrointestinal bleeding occurred in 13 patients (3.8%) after an orthotopic liver transplant. Five patients (38.4%) were adult and 8 patients (61.6%) were pediatric. The sites of the bleeding were Roux-en-Y anastomosis bleeding in 5 cases, peptic ulcer in 3 cases, erosive gastritis in 3 cases, gastric and esophageal varices in 1 case, and hemobilia in 1 case. These 13 patients with gastrointestinal bleeding were managed with conservative treatment, endoscopic treatment, radiologic interventional embolism, or exploratory laparotomy. No patients died because of gastro--intestinal bleeding. During follow-up, 4 patients died because of sepsis and 1 patient died of recurrence of hepatocellular carcinoma. Gastrointestinal bleeding after liver transplant and its incidence, causes, and treatment are not well-described in the literature. Diagnosis and management of gastrointestinal bleeding requires a multidisciplinary approach involving surgeons, hepatologists, advanced and experienced endoscopists, and interventional radiologists.

  13. Simplified technique for auxiliary orthotopic liver transplantation using a whole graft

    PubMed Central

    ROCHA-SANTOS, Vinicius; NACIF, Lucas Souto; PINHEIRO, Rafael Soares; DUCATTI, Liliana; ANDRAUS, Wellington; D'ALBURQUERQUE, Luiz Carneiro

    2015-01-01

    Background Acute liver failure is associated with a high mortality rate and the main purposes of treatment are to prevent cerebral edema and infections, which often are responsible for patient death. The orthotopic liver transplantation is the gold standard treatment and improves the 1-year survival. Aim To describe an alternative technique to auxiliary liver transplant on acute liver failure. Method Was performed whole auxiliary liver transplantation as an alternative technique for a partial auxiliary liver transplantation using a whole liver graft from a child removing the native right liver performed a right hepatectomy. The patient met the O´Grady´s criteria and the rational to indicate an auxiliary orthotopic liver transplantation was the acute classification without hemodynamic instability or renal failure in a patient with deterioration in consciousness. Results The procedure improved liver function and decreased intracranial hypertension in the postoperative period. Conclusion This technique can overcome some postoperative complications that are associated with partial grafts. As far as is known, this is the first case of auxiliary orthotopic liver transplantation in Brazil. PMID:26176253

  14. Ferret lung transplant: an orthotopic model of obliterative bronchiolitis.

    PubMed

    Sui, H; Olivier, A K; Klesney-Tait, J A; Brooks, L; Tyler, S R; Sun, X; Skopec, A; Kline, J; Sanchez, P G; Meyerholz, D K; Zavazava, N; Iannettoni, M; Engelhardt, J F; Parekh, K R

    2013-02-01

    Obliterative bronchiolitis (OB) is the primary cause of late morbidity and mortality following lung transplantation. Current animal models do not reliably develop OB pathology. Given the similarities between ferret and human lung biology, we hypothesized an orthotopic ferret lung allograft would develop OB. Orthotopic left lower lobe transplants were successfully performed in 22 outbred domestic ferrets in the absence of immunosuppression (IS; n = 5) and presence of varying IS protocols (n = 17). CT scans were performed to evaluate the allografts. At intervals between 3-6 months the allografts were examined histologically for evidence of acute/chronic rejection. IS protects allografts from acute rejection and early graft loss. Reduction of IS dosage by 50% allowed development of controlled rejection. Allografts developed infiltrates on CT and classic histologic acute rejection and lymphocytic bronchiolitis. Cycling of IS, to induce repeated episodes of controlled rejection, promoted classic histologic hallmarks of OB including fibrosis-associated occlusion of the bronchiolar airways in all allografts of long-term survivors. In conclusion, we have developed an orthotopic lung transplant model in the ferret with documented long-term functional allograft survival. Allografts develop acute rejection and lymphocytic bronchiolitis, similar to humans. Long-term survivors develop histologic changes in the allografts that are hallmarks of OB. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

  15. Infections Complicating Orthotopic Liver Transplantation

    PubMed Central

    Schröter, Gerhard P. J.; Hoelscher, Manfred; Putnam, Charles W.; Porter, Kendrick A.; Hansbrough, John F.; Starzl, Thomas E.

    2011-01-01

    In 93 recipients of 102 orthotopic liver homografts, the incidence of bacteremia or fungemia exceeded 70%. The graft itself was usually an entry site for systemic infection after both immunologic and nonimmunologic parenchymal injury, especially if there was defective biliary drainage. The role of the homograft itself as the special infectious risk factor has prompted increased use of defunctionalized jejunal Roux limbs to reduce graft contamination. It has also stimulated very aggressive postoperative diagnostic efforts to rule out remedial mechanical complications of the transplant. PMID:793568

  16. OB glue paste technique for establishing nude mouse human gastric cancer orthotopic transplantation models

    PubMed Central

    Shi, Jun; Wei, Pin-Kang; Zhang, Shen; Qin, Zhi-Feng; Li, Jun; Sun, Da-Zhi; Xiao, Yan; Yu, Zhi-Hong; Lin, Hui-Ming; Zheng, Guo-Jing; Su, Xiao-Mei; Chen, Ya-Lin; Liu, Yan-Fang; Xu, Ling

    2008-01-01

    AIM: To establish nude mouse human gastric cancer orthotopic transplantation models using OB glue paste technique. METHODS: Using OB glue paste technique, orthotopic transplantation models were established by implanting SGC-7901 and MKN-45 human gastric cancer cell strains into the gastric wall of nude mice. Biological features, growth of the implanted tumors, the success rate of transplantation and the rate of auto-metastasis of the two models were observed. RESULTS: The success rates of orthotopic transplan-tation of the two models were 94.20% and 96%. The rates of hepatic metastasis, pulmonary metastasis, peritoneal metastasis, lymphocytic metastasis and splenic metastasis were 42.13% and 94.20%, 48.43% and 57.97%, 30.83% and 36.96%, 67.30% and 84.06%, and 59.75% and 10.53%, respectively. The occurrence of ascites was 47.80% and 36.96%. CONCLUSION: OB glue paste technique is easy to follow. The biological behaviors of the nude mouse human gastric cancer orthotopic transplantation models established with this technique are similar to the natural processes of growth and metastasis of human gastric cancer, and, therefore, can be used as an ideal model for experimental research of proliferative metastasis of tumors. PMID:18720543

  17. EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice.

    PubMed

    Yi, Diao; Hua, Tian Xin; Lin, Huang Yan

    2011-03-01

    Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.

  18. Sodium-reduced continuous venovenous hemodiafiltration (CVVHDF) for the prevention of central pontine myelinolysis (CPM) in hyponatremic patients scheduled for orthotopic liver transplantation.

    PubMed

    Lenk, Marcus R; Kaspar, Michael

    2012-08-01

    Two patients in end-stage hepatic failure presented for orthotopic liver transplantation with longstanding severe hyponatremia (121 and 122 mmol/L). Both patients underwent liver transplantation with the concomitant use of continuous venovenous hemodiafiltration. Replacement and dialysate solutions were prepared individually to contain a sodium level that was individually considered safe with regard to the development of central pontine myelinolysis. The sodium increase in both patients was within the expected and planned limits despite a situation of mass transfusion. Both patients did well postoperatively and neither patient suffered neurological deficits. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Superficial and muscle-invasive bladder cancer: principles of management for outcomes assessments.

    PubMed

    Parekh, Dipen J; Bochner, Bernard H; Dalbagni, Guido

    2006-12-10

    Bladder cancer is a heterogeneous disease. Non-muscle-invasive bladder cancer embraces a spectrum of tumors with varying degrees of clinical behavior. Transurethral resection remains the surgical mainstay for the treatment of non-muscle-invasive bladder cancer. In an attempt to decrease the recurrence or progression rate, intravesical chemotherapy or immunotherapy is also used. Radical cystectomy with bilateral pelvic lymph node dissection remains the gold standard for treating muscle-invasive bladder cancer. Over the last decade, the orthotopic neobladder has gained widespread popularity as the preferred mode of urinary diversion in both males and females with similar oncologic and functional outcomes. Well-designed trials with effective chemotherapy have shown a beneficial role for neoadjuvant chemotherapy.

  20. Impact of intraoperative factor concentrates on blood product transfusions during orthotopic liver transplantation.

    PubMed

    Colavecchia, A Carmine; Cohen, David A; Harris, Jesse E; Thomas, Jeena M; Lindberg, Scott; Leveque, Christopher; Salazar, Eric

    2017-12-01

    Major bleeding in orthotopic liver transplantation is associated with significant morbidity and mortality. Limited literature exists regarding comparative effectiveness of prothrombin complex concentrate and fibrinogen concentrate during orthotopic liver transplantation on blood product utilization. This retrospective, single-institution study evaluated the impact of prothrombin complex concentrate and fibrinogen concentrate on blood product utilization during orthotopic liver transplantation from December 2013 to April 2016. This study included patients age 18 years or older and excluded patients who received simultaneous heart or lung transplantation or did not meet documentation criteria. A propensity score matching technique was used to match patients who were exposed to prothrombin complex concentrate with unexposed patients, at a 2 to 1 ratio, to control for selection bias. During this study, 212 patients received orthotopic liver transplantation with 39 prothrombin complex concentrate exposures. The matched study population included 39 patients who were exposed to prothrombin complex concentrate and 78 unexposed patients. Overall, 84.6% of patients who were exposed to prothrombin complex concentrate also received concomitant fibrinogen concentrate, whereas only 2% of patients in the control group received fibrinogen concentrate. After propensity score matching, no other factors that were included in the model differed significantly or had a standardized mean difference of 0.11 or greater. There was no statistical difference in the utilization of red blood cells or fresh frozen plasma for the exposed group versus the unexposed group after matching (mean ± standard deviation: red blood cell units, 12.4 ± 8.0 units vs. 9.7 ± 5.6 units [p = 0.058]; fresh-frozen plasma units, 10.0 ± 6.3 vs. 12.7 ± 9.7 units [p = 0.119], respectively). The intraoperative use of prothrombin complex concentrate and fibrinogen concentrate during

  1. Orthotopic tumorgrafts in nude mice: A new method to study human prostate cancer.

    PubMed

    Saar, Matthias; Körbel, Christina; Linxweiler, Johannes; Jung, Volker; Kamradt, Jörn; Hasenfus, Andrea; Stöckle, Michael; Unteregger, Gerhard; Menger, Michael D

    2015-10-01

    In vivo model systems in prostate cancer research that authentically reproduce tumor growth are still sparse. While orthotopic implantation is technically difficult, particularly in the mouse, most models favor subcutaneous tumor growth. This however provides little information about natural tumor growth behavior and tumor stroma interaction. Furthermore, established prostate cancer cell lines grown as in vivo xenografts are not able to reflect the variety of tumor specific growth patterns and growth behavior in men. Primary cell cultures are difficult to handle and an induction of orthotopic tumors has not been successful yet. Therefore, a tumorgraft model using tumor tissue from prostatectomy specimens was developed. Balb/c nude mice were used to graft fresh prostate tumor tissue by renal subcapsular and orthotopic implantation. Testosterone propionate was supplemented. Animals were tracked by means of 30 MHz ultrasound to monitor tumor engraftment and growth. Autopsy, histology, PSA measurements as well as immunostaining and PCR for human tissue were performed to confirm orthotopic tumor growth. Renal subcapsular engraftment was seen in 2 of 3 mice. Orthotopic engraftment was observed in 7 of 11 animals (63.6%) with an overall engraftment of 5 out of 9 patient specimens (55.6%). Ultrasound confirmed the tumor growth over time. Of interest, the tumorgrafts not only retained essential features of the parental tumors, but also stained positive for tumor specific markers such as AR, PSA, and AMACR. Tumor positive animals showed highly elevated serum PSA levels with confirmation of a human specific PCR sequence and a human endothelial cell lining in the tumor vessels. Standardized implantation of fresh tumor tissue in nude mice prostates generates tumorgrafts with histological properties of organ-confined prostate cancer. These tumorgrafts display a new approach for an optimized in vivo model of prostate cancer and will allow further investigations on specific

  2. A true orthotopic gastric cancer murine model using electrocoagulation.

    PubMed

    Bhullar, Jasneet Singh; Makarawo, Tafadzwa; Subhas, Gokulakkrishna; Alomari, Ahmed; Silberberg, Boris; Tilak, Jacqueline; Decker, Milessa; Mittal, Vijay K

    2013-07-01

    Orthotopic mouse models of human gastric cancer represent an important in vivo tool for testing chemotherapeutic agents and for studying intraluminal factors. Currently, orthotopic mouse models of gastric cancer require an operative procedure involving either injection or implantation of tumor cells in stomach layers. The resultant tumor does not grow from the stomach's mucosal surface, so it does not mimic the human disease process. A low-dose gastric mucosal coagulation was done transorally in the body of stomach using a specially designed polyethylene catheter in 16 female severe combined immunodeficient mice. This was followed by the instillation of SNU-16 human gastric cancer tumor cells (1 × 10(6) cells). Five mice each were euthanized at 1 and 2 months, and 6 mice were euthanized at 3 months. Three control mice underwent electrocoagulation alone and 3 mice underwent cell line instillation alone. Tumors were detected in 11 of 16 experimental mice, but not in the control mice. Tumors were noted in mice at 1 month. Over time, there was an increase in tumor growth and metastasis to lymph nodes and surrounding organs. Histopathologic evaluation showed that the tumors grew from the gastric mucosa. Our model is easy to create and overcomes the limitations of the existing models, as the tumor arises from the stomach's mucosal layer and mimics the human disease in terms of morphology and biologic behavior. This is the first report of a true orthotopic gastric cancer murine model. This model opens new doors for additional studies that were not possible earlier. Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  3. Real-time Non-invasive Spectral Imaging of Orthotopic Red Fluorescent Protein-expressing Lung Tumor Growth in Nude Mice.

    PubMed

    Zhang, Yong; Zhang, Nan; Zhao, Ming; Hoffman, Robert M

    2015-07-01

    Orthotopic implantation of cancer allows metastasis to occur. The most patient-like metastatic orthotopic models are developed with surgical orthotopic implantation using intact tissue in order to preserve the natural tissue structure of the tumor which contains both cancer cells and stroma. In the present study, we performed a simple thoracotomy by making an intercostal incision between the fourth and fifth ribs on the left side of the chest of nude mice. Lung tumor fragments expressing red fluorescent protein were then implanted on the left lung. It was possible to monitor tumor formation in the lung non-invasively by spectral imaging using the Maestro system with a liquid tunable filter. The model described here has high tumorigenicity in the lung (100%) and a low mortality rate (5%). This imageable nude mouse model using surgical orthotopic implantation of lung cancer will be useful for all types of longitudinal studies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  4. Bombesin functionalized 64Cu-copper sulfide nanoparticles for targeted imaging of orthotopic prostate cancer.

    PubMed

    Cai, Huawei; Xie, Fang; Mulgaonkar, Aditi; Chen, Lihong; Sun, Xiankai; Hsieh, Jer-Tsong; Peng, Fangyu; Tian, Rong; Li, Lin; Wu, Changqiang; Ai, Hua

    2018-05-22

    To synthesize and evaluate the imaging potential of Bom-PEG-[ 64 Cu]CuS nanoparticles (NPs) in orothotopic prostate tumor. [ 64 Cu]CuS NPs were synthesized in aqueous solution by 64 CuCl 2 and Na 2 S reaction. Then PEG linker with or without bombesin peptide were conjugated to the surface of [ 64 Cu]CuS NPs to produce Bom-PEG-[ 64 Cu]CuS and PEG-[ 64 Cu]CuS NPs. These two kinds of NPs were used for testing specific uptake in prostate cancer cells in vitro and imaging of orthotopic prostate tumor in vivo. Bom-PEG-[ 64 Cu]CuS and PEG-[ 64 Cu]CuS NPs were successfully synthesized with core diameter of approximately 5 nm. Radioactive cellular uptake revealed that Bom-PEG-[ 64 Cu]CuS was able to specifically bind to prostate cancer cells, and the microPET-CT imaging indicated clear visualization of orthotopic prostate tumors. Radiolabeled Bom-PEG-[ 64 Cu]CuS NPs have potential as an ideal agent for orthotopic prostate tumor imaging by microPET-CT.

  5. Predictors of the use of orthotopic bladder reconstruction after radical cystectomy for bladder cancer: data from a pilot study of 1756 cases 2004-2011.

    PubMed

    Hounsome, Luke S; Abel, Gary A; Verne, Julia; Neal, David E; Lyratzopoulos, Georgios

    2013-06-01

    WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: How often orthotopic reconstruction should be used after radical cystectomy is uncertain. Male sex, younger age, affluence, white ethnicity and treatment in specialist hospitals may be associated with more frequent use. More evidence about the level and likely variation in the use of orthotopic surgery is needed to establish whether there are inequalities and unmet need. In England during the study period orthotopic bladder reconstruction was likely to be used in about one in 15 patients treated by radical cystectomy. This is lower than previously reported in US series or European studies. Men and younger patients were more likely to be treated by orthotopic reconstruction, as were more affluent patients and those with less advanced disease. Whether clinical reasons or patient choice can explain some of this variation is unclear. There was no evidence for variation between different English cancer networks. A specific procedure code to allow routine analysis of population-based nationwide data would be invaluable for ongoing monitoring of potential inequalities and unmet need. To examine variation in the use of orthotopic bladder reconstruction. Variability in the use of orthotopic reconstruction may indicate potential for quality improvement. We analysed data from the British Association of Urological Surgeons Cancer Registry Complex Operations data set and Hospital Episode Statistics, covering the period 2004-2011. Three-level (patient, consultant and cancer network) mixed effect logistic regression models were used to examine sociodemographic and organizational variation in use of orthotopic reconstruction. The primary outcome was the odds ratio for use of orthotopic reconstruction for different patient groups. The final analysis sample included 1756 patients with bladder cancer who were treated by cystectomy by 121 consultants in 17 cancer networks. Of these, 120 (6.8%) were treated by orthotopic

  6. Patient-specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ.

    PubMed

    Joo, Kyeung Min; Kim, Jinkuk; Jin, Juyoun; Kim, Misuk; Seol, Ho Jun; Muradov, Johongir; Yang, Heekyoung; Choi, Yoon-La; Park, Woong-Yang; Kong, Doo-Sik; Lee, Jung-Il; Ko, Young-Hyeh; Woo, Hyun Goo; Lee, Jeongwu; Kim, Sunghoon; Nam, Do-Hyun

    2013-01-31

    Frequent discrepancies between preclinical and clinical results of anticancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable "patient tumor's phenocopy" that represents molecular and functional heterogeneity of GBMs. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Orthotopic Esophageal Cancers: Intraesophageal Hyperthermia-enhanced Direct Chemotherapy in Rats

    PubMed Central

    Shi, Yaoping; Zhang, Feng; Bai, Zhibin; Wang, Jianfeng; Qiu, Longhua; Li, Yonggang; Meng, Yanfeng; Valji, Karim

    2017-01-01

    Purpose To determine the feasibility of using intraesophageal radiofrequency (RF) hyperthermia to enhance local chemotherapy in a rat model with orthotopic esophageal squamous cancers. Materials and Methods The animal protocol was approved by the institutional animal care and use committee and the institutional review board. Human esophageal squamous cancer cells were transduced with luciferase lentiviral particles. Cancer cells, mice with subcutaneous cancer esophageal xenografts, and nude rats with orthotopic esophageal cancers in four study groups of six animals per group were treated with (a) combination therapy of magnetic resonance imaging heating guidewire–mediated RF hyperthermia (42°C) plus local chemotherapy (cisplatin and 5-fluorouracil), (b) chemotherapy alone, (c) RF hyperthermia alone, and (d) phosphate-buffered saline. Bioluminescent optical imaging and transcutaneous ultrasonographic imaging were used to observe bioluminescence signal and changes in tumor size among the groups over 2 weeks, which were correlated with subsequent histologic results. The nonparametric Mann-Whitney U test was used for comparisons of variables. Results Compared with chemotherapy alone, RF hyperthermia alone, and phosphate-buffered saline, combination therapy with RF hyperthermia and chemotherapy induced the lowest cell proliferation (relative absorbance of formazan: 23.4% ± 7, 44.6% ± 7.5, 95.8% ± 2, 100%, respectively; P < .0001), rendered the smallest relative tumor volume (0.65 mm3 ± 0.15, P < .0001) and relative bioluminescence optical imaging photon signal (0.57 × 107 photons per second per square millimeter ± 0.15, P < .001) of mice with esophageal cancer xenografts, as well as the smallest relative tumor volume (0.68 mm3 ± 0.13, P < .05) and relative photon signal (0.56 × 107 photons per second per square millimeter ± 0.11. P < .001) of rat orthotopic esophageal cancers. Conclusion Intraesophageal RF hyperthermia can enhance the effect of chemotherapy

  8. Orthotopic Implantation of Intact Tumor Tissue Leads to Metastasis of OCUM-2MD3 Human Gastric Cancer in Nude Mice Visualized in Real Time by Intravital Fluorescence Imaging.

    PubMed

    Murakami, Takashi; Zhang, Yong; Wang, Xiaoen; Hiroshima, Yukihiko; Kasashima, Hiroaki; Yashiro, Masakazu; Hirakawa, Kosei; Miwa, Atsushi; Kiyuna, Tasuku; Matsuyama, Ryusei; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

    2016-05-01

    Orthotopic (literally "correct place") implantation of cancer in nude mice has long been known to be superior to subcutaneous transplantation because the orthotopic tumor can metastasize. We reported previously on surgical orthotopic implantation (SOI) of gastric cancer tissue in nude mice resulting in the formation of metastases in 100% of the mice with extensive primary growth to the regional lymph nodes, liver, and lung. In contrast, when cell suspensions were used to inject gastric cancer cells orthotopically, metastases occurred in only 6.7% of the mice with local tumor formation, emphasizing the importance of orthotopically implanting intact tissue to allow full expression of metastatic potential. However, the different behavior of tumors implanted orthotopically by the two methods has not been visualized in real time. OCUM-2MD3 human gastric cancer cells labeled with the fluorescent protein Azami-Green were implanted orthotopically as cells or tissue in nude mice. Orthotopic implantation of cells resulted in local spread on the stomach. In contrast, SOI of tumor tissue of OCUM-2MD3 resulted in vessel spread of the Azami-Green-expressing cancer cells. Metastasis was also observed in the left lobe of the liver after SOI. These results demonstrate the physiological importance of intact cancer tissue for orthotopic implantation in order for tumors to properly grow and express their metastatic potential. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. Orthotopic Liver Transplantation for Urea Cycle Enzyme Deficiency

    PubMed Central

    Todo, Satoru; Starzl, Thomas E.; Tzakis, Andreas; Benkov, Keith J.; Kalousek, Frantisek; Saheki, Takeyori; Tanikawa, Kyuichi; Fenton, Wayne A.

    2010-01-01

    Hyperammonemia, abnormalities in plasma amino acids and abnormalities of standard liver functions were corrected by orthotopic liver transplantation in a 14-day-old boy with carbamyl phosphate synthetase-I deficiency and in a 35-yr-old man with argininosuccinic acid synthetase deficiency. The first patient had high plasma glutamine levels and no measureable citrulline, whereas citrulline values were markedly increased in Patient 2. Enzyme analysis of the original livers showed undetectable activity of carbamyl phosphate synthetase-I in Patient 1 and arginosuccinic acid synthetase in Patient 2. Both patients were comatose before surgery. Intellectual recovery of patient 1 has been slightly retarded because of a brain abscess caused by Aspergillus infection after surgery. Both patients are well at 34 and 40 mo, respectively, after surgery. Our experience has shown that orthotopic liver transplantation corrects the life-threatening metabolic abnormalities caused by deficiencies in the urea cycle enzymes carbamyl phosphate synthetase-I and arginosuccinic acid synthetase. Seven other patients–six with ornithine transcarbamylase deficiency and another with carbamyl phosphate synthetase-I deficiency–are known to have been treated elsewhere with liver transplantation 1½ yr or longer ago. Four of these seven recipients also are well, with follow-ups of 1½ to 5 yr. Thus liver transplantation corrects the metabolic abnormalities of three of the six urea cycle enzyme deficiencies, and presumably would correct all. PMID:1544622

  10. [Establishment of a nude mouse model of highly metastatic gastric lymphoma constructed with orthotopic transplantation of surgical specimen].

    PubMed

    Yang, Bo; Tuo, Shuai; Tuo, Chao-wei; Zhang, Ning; Liu, Qiu-zhen

    2010-06-01

    To construct a mouse model of highly metastatic gastric lymphoma with orthotopic transplantation of human primary gastric lymphoma specimen. A fresh surgical specimen of primary gastric lymphoma was obtained intraoperatively and implanted into the submucosa of stomach in nude mice. Tumor formation, invasion, metastasis, morphological characteristics under light microscopy and electron microscopy, immunohistochemistry,and the karyotype of orthotopically transplanted tumor cells were studied. An orthotopic highly metastatic model of human primary gastric lymphoma in nude mice(HGBL-0305) was successfully established. Histopathology of transplanted tumors showed primary gastric diffuse large B cell lymphoma. CD19, CD20, CD22 and CD79alpha were positive, while CD3 and CD7 were negative. The number of chromosome ranged from 56 to 69. DNA index(DI) was 1.47+/-0.12(i.e. heteroploid). Until now, HGBL-0305 model has been maintained for 45 generations by orthotopic passage for almost 4 years in nude mice. A total of 156 nude mice were used for transplantation. The growth rate and resuscitation rate of liquid nitrogen cryopreservation of transplanted tumor cells were both 100%. The autonomic growth of the transplanted tumor cells invaded and destructed all the layers of the nude mice stomach. The metastasis rates of liver, spleen, lymph node, and peritoneal seeding were 69.5%, 55.6%, 45.7%, and 30.5%, respectively. An orthotopic highly metastatic model of human primary gastric lymphoma in nude mice is successfully established. HGBL-0305 model may simulate the natural course of primary gastric lymphoma in human and provides an ideal animal model for studies on pathogenesis, metastasis biology and anti-metastatic therapies of primary gastric lymphoma.

  11. Antitumor effect of novel anti-podoplanin antibody NZ-12 against malignant pleural mesothelioma in an orthotopic xenograft model.

    PubMed

    Abe, Shinji; Kaneko, Mika Kato; Tsuchihashi, Yuki; Izumi, Toshihiro; Ogasawara, Satoshi; Okada, Naoto; Sato, Chiemi; Tobiume, Makoto; Otsuka, Kenji; Miyamoto, Licht; Tsuchiya, Koichiro; Kawazoe, Kazuyoshi; Kato, Yukinari; Nishioka, Yasuhiko

    2016-09-01

    Podoplanin (aggrus) is highly expressed in several types of cancers, including malignant pleural mesothelioma (MPM). Previously, we developed a rat anti-human podoplanin mAb, NZ-1, and a rat-human chimeric anti-human podoplanin antibody, NZ-8, derived from NZ-1, which induced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against podoplanin-positive MPM cell lines. In this study, we showed the antitumor effect of NZ-1, NZ-8, and NZ-12, a novel rat-human chimeric anti-human podoplanin antibody derived from NZ-1, in an MPM orthotopic xenograft SCID mouse model. Treatment with NZ-1 and rat NK (CD161a(+) ) cells inhibited the growth of tumors and the production of pleural effusion in NCI-H290/PDPN or NCI-H226 orthotopic xenograft mouse models. NZ-8 and human natural killer (NK) (CD56(+) ) cells also inhibited tumor growth and pleural effusion in MPM orthotopic xenograft mice. Furthermore, NZ-12 induced potent ADCC mediated by human MNC, compared with either NZ-1 or NZ-8. Antitumor effects were observed following treatment with NZ-12 and human NK (CD56(+) ) cells in MPM orthotopic xenograft mice. In addition, combined immunotherapy using the ADCC activity of NZ-12 mediated by human NK (CD56(+) ) cells with pemetrexed, led to enhanced antitumor effects in MPM orthotopic xenograft mice. These results strongly suggest that combination therapy with podoplanin-targeting immunotherapy using both NZ-12 and pemetrexed might provide an efficacious therapeutic strategy for the treatment of MPM. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  12. Orthotopic lung cancer murine model by nonoperative transbronchial approach.

    PubMed

    Nakajima, Takahiro; Anayama, Takashi; Matsuda, Yasushi; Hwang, David M; McVeigh, Patrick Z; Wilson, Brian C; Zheng, Gang; Keshavjee, Shaf; Yasufuku, Kazuhiro

    2014-05-01

    The aim of this work was to establish a novel orthotopic human non-small cell lung cancer (NSCLC) murine xenograft model by a nonsurgical, transbronchial approach. Male athymic nude mice and human NSCLC cell lines, including A549, H460, and H520 were used. Under direct visualization of the vocal cords, a 23-gauge blunt-tip slightly curved metal catheter was introduced into the trachea to the bronchus, and 2.5×10(5) tumor cells mixed with Matrigel (BD Biosciences, Mississauga, Ontario, Canada) were administered into the lung. Mice were monitored using weekly microcomputed tomography scans for tumor formation. When the tumor size reached more than 4 mm in diameter, the animals were euthanized, and the tumor tissue was evaluated histopathologically. Of 37 mice studied, 34 were confirmed to have tumor formation: 29 developed solitary tumors and 5 had multifocal lesions. There was no evidence of extrapleural dissemination or effusion. Transbronchial delivery of tumor cells enabled the establishment of a novel orthotopic human NSCLC murine xenograft model. This clinically relevant preclinical model bearing a solitary nodule is of value for a variety of in vivo research studies. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  13. [Orthotopic cartilage transplantation. Morphologic, angiography and histochemical studies of the vitality of free septum transplants].

    PubMed

    Gubisch, W; Donath, K

    1999-11-01

    Orthotopic cartilage transplantation is a technique frequently used in modern septal surgery. The prerequisite for a stable long-term result is viability of the transplanted cartilage. Therefore, we studied the healing process histologically, angiographically, and histochemically. We found a characteristic picture. Due to chondronal structure of the cartilage, the healing process varied in time and location. Reintegration took place by chondroneogenesis, commencing at the inner perichondrium. Reintegration depended directly on the distance of the cartilage cells to the surrounding vessels. Histochemically, we found an intact respiratory chain in the mitochondria and thus, we were able to demonstrate the preservation of viability in orthotopic transplanted cartilage.

  14. Prevalence, Cause, and Treatment of Respiratory Insufficiency After Orthotopic Heart Transplant.

    PubMed

    Savaş Bozbaş, Şerife; Ulubay, Gaye; Öner Eyüboğlu, Füsun; Sezgin, Atilla; Haberal, Mehmet

    2015-11-01

    Heart transplant is the best treatment for end-stage heart failure. Respiratory insufficiency after heart transplant is a potentially serious complication. Pulmonary complications, pulmonary hypertension, allograft failure or rejection, and structural heart defects in the donor heart are among the causes of hypoxemia after transplant. In this study, we evaluated the prevalence of hypoxemia and respiratory insufficiency in patients with orthotopic heart transplant during the early postoperative period. We retrospectively evaluated the medical records of 45 patients who had received orthotopic heart transplant at our center. Clinical and demographic variables and laboratory data were noted. Oxygen saturation values from patients in the first week and the first month after transplant were analyzed. We also documented the cause of respiratory insufficiency and the type of treatment. Mean age was 35.3 ± 15.3 years (range, 12-61 y), with males comprising 32 of 45 patients (71.1%). Two patients had mild chronic obstructive pulmonary disease and 1 had asthma. Twenty-five patients (55.6%) had a history of smoking. Respiratory insufficiency was noted in 9 patients (20%) during the first postoperative week. Regarding cause, 5 of these patients (11.1%) had pleural effusion, 2 (4.4%) had atelectasis, 1 (2.2%) had pneumonia, and 1 (2.2%) had acute renal failure. Therapies administered to patients with respiratory insufficiency were as follows: 5 patients had oxygen therapy with nasal canula/mask, 3 patients had continuous positive airway pressure, and 1 patient had mechanical ventilation. One month after transplant, 2 patients (4.4%) had respiratory insufficiency 1 (2.2%) due to pleural effusion and 1 (2.2%) due to atelectasis. Respiratory insufficiency is a common complication in the first week after orthotopic heart transplant. Identification of the underlying cause is an important indicator for therapy. With appropriate care, respiratory insufficiency can be treated

  15. Acquired toxoplasmosis after orthotopic heart transplantation in a sulfonamide-allergic patient.

    PubMed

    Sanchez Mejia, Aura; Debrunner, Mark; Cox, Elaine; Caldwell, Randall

    2011-01-01

    We report the case of a young adult with a history of an allergic reaction to a sulfonamide antibiotic who developed toxoplasmosis after his second orthotopic heart transplant. As a result of this drug allergy, the patient did not receive prophylaxis with trimethoprim and sulfamethoxazole. He was successfully treated with clindamycin, pyrimethamine, and folic acid.

  16. Hybrid liposomes showing enhanced accumulation in tumors as theranostic agents in the orthotopic graft model mouse of colorectal cancer.

    PubMed

    Okumura, Masaki; Ichihara, Hideaki; Matsumoto, Yoko

    2018-11-01

    Hybrid liposomes (HLs) can be prepared by simply sonicating a mixture of vesicular and micellar molecules in a buffer solution. This study aimed to elucidate the therapeutic effects and ability of HLs to detect (diagnosis) cancer in an orthotopic graft mouse model of colorectal cancer with HCT116 cells for the use of HLs as theranostic agents. In the absence of a chemotherapeutic drug, HLs exhibited therapeutic effects by inhibiting the growth of HCT116 colorectal cancer cells in vitro, possibly through an increase in apoptosis. Intravenously administered HLs also caused a remarkable reduction in the relative cecum weight in an orthotopic graft mouse model of colorectal cancer. A decrease in tumor size in the cecal sections was confirmed by histological analysis using HE staining. TUNEL staining indicated an induction of apoptosis in HCT116 cells in the orthotopic graft mouse model of colorectal cancer. For the detection (diagnosis) of colorectal cancer by HLs, the accumulation of HLs encapsulating a fluorescent probe (ICG) was observed in HCT116 cells in the in vivo colorectal cancer model following intravenous administration. These data indicate that HLs can accumulate in tumor cells in the cecum of the orthotopic graft mouse model of colorectal cancer for a prolonged period of time, and inhibit the growth of HCT116 cells.

  17. Impact of intraoperative cytokine adsorption on outcome of patients undergoing orthotopic heart transplantation-an observational study.

    PubMed

    Nemeth, Endre; Kovacs, Eniko; Racz, Kristof; Soltesz, Adam; Szigeti, Szabolcs; Kiss, Nikolett; Csikos, Gergely; Koritsanszky, Kinga B; Berzsenyi, Viktor; Trembickij, Gabor; Fabry, Szabolcs; Prohaszka, Zoltan; Merkely, Bela; Gal, Janos

    2018-04-01

    The aim of this study was to assess the influence of intraoperative cytokine adsorption on the perioperative vasoplegia, inflammatory response and outcome during orthotopic heart transplantation (OHT). Eighty-four OHT patients were separated into the cytokine adsorption (CA)-treated group or controls. Vasopressor demand, inflammatory response described by procalcitonin and C-reactive protein, and postoperative outcome were assessed performing propensity score matching. In the 16 matched pairs, the median noradrenaline requirement was significantly less in the CA-treated patients than in the controls on the first and second postoperative days (0.14 vs 0.3 μg*kg -1 *min -1 , P = .039 and 0.06 vs 0.32 μg*kg -1 *min -1 , P = .047). The inflammatory responses were similar in the two groups. There was a trend toward shorter length of mechanical ventilation and intensive care unit (ICU) stay in the CA-treated group compared to the controls. No difference in adverse events was observed between the two groups. However, the frequency of renal replacement therapy was significantly less in the CA-treated patients than in the controls (P = .031). Intraoperative CA treatment was associated with reduced vasopressor demand and less frequent renal replacement therapy with a favorable tendency in length of mechanical ventilation and ICU stay. CA treatment was not linked to higher rates of adverse events. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Establishment of an orthotopic lung cancer model in nude mice and its evaluation by spiral CT.

    PubMed

    Liu, Xiang; Liu, Jun; Guan, Yubao; Li, Huiling; Huang, Liyan; Tang, Hailing; He, Jianxing

    2012-04-01

    To establish a simple and highly efficient orthotopic animal model of lung cancer cell line A549 and evaluate the growth pattern of intrathoracic tumors by spiral CT. A549 cells (5×10(6) mL(-1)) were suspended and inoculated into the right lung of BALB/c nude mice via intrathoracic injection. Nude mice were scanned three times each week by spiral CT after inoculation of lung cancer cell line A549. The survival time and body weight of nude mice as well as tumor invasion and metastasis were examined. Tissue was collected for subsequent histological assay after autopsia of mice. The tumor-forming rate of the orthotopic lung cancer model was 90%. The median survival time was 30.7 (range, 20-41) days. The incidence of tumor metastasis was 100%. The mean tumor diameter and the average CT value gradually increased in a time-dependent manner. The method of establishing the orthotopic lung cancer model through transplanting A549 cells into the lung of nude mice is simple and highly successful. Spiral CT can be used to evaluate intrathoracic tumor growth in nude mice vividly and dynamically.

  19. Establishment of an orthotopic lung cancer model in nude mice and its evaluation by spiral CT

    PubMed Central

    Liu, Xiang; Liu, Jun; Guan, Yubao; Li, Huiling; Huang, Liyan; Tang, Hailing

    2012-01-01

    Objective To establish a simple and highly efficient orthotopic animal model of lung cancer cell line A549 and evaluate the growth pattern of intrathoracic tumors by spiral CT. Methods A549 cells (5×106 mL-1) were suspended and inoculated into the right lung of BALB/c nude mice via intrathoracic injection. Nude mice were scanned three times each week by spiral CT after inoculation of lung cancer cell line A549. The survival time and body weight of nude mice as well as tumor invasion and metastasis were examined. Tissue was collected for subsequent histological assay after autopsia of mice. Results The tumor-forming rate of the orthotopic lung cancer model was 90%. The median survival time was 30.7 (range, 20-41) days. The incidence of tumor metastasis was 100%. The mean tumor diameter and the average CT value gradually increased in a time-dependent manner. Conclusions The method of establishing the orthotopic lung cancer model through transplanting A549 cells into the lung of nude mice is simple and highly successful. Spiral CT can be used to evaluate intrathoracic tumor growth in nude mice vividly and dynamically. PMID:22833819

  20. Progression of Neurovisceral Storage Disease With Supranuclear Ophthalmoplegia Following Orthotopic Liver Transplantation

    PubMed Central

    Gartner, J. Carlton; Bergman, Ira; Malatack, J. Jeffrey; Zitelli, Basil J.; Jaffe, Ronald; Watkins, John B.; Shaw, Byers W.; Iwatsuki, Shunzaburo; Starzl, Thomas E.

    2011-01-01

    A 7-year-old girl with progressive ataxia, spasticity, supranuclear ophthalmoplegia, and sea-blue histiocytes in her bone marrow underwent orthotopic liver transplantation for hepatocellular carcinoma. After an initial period of stabilization, she has shown progression of neurologic symptoms with recurrence of storage material in the transplanted liver. PMID:2999691

  1. Safe and effective treatment of early suprahepatic inferior vena caval outflow compromise following orthotopic liver transplantation using percutaneous transluminal angioplasty and stent placement.

    PubMed

    Tasse, Jordan; Borge, Marc; Pierce, Kenneth; Brems, John

    2011-01-01

    To describe the safety and efficacy of percutaneous transluminal angioplasty and stent placement in patients presenting with suprahepatic inferior vena cava (IVC) outflow compromise in the early postoperative period following orthotopic liver transplantation. Between October 2002 and April 2009, 3 patients presented with IVC outflow compromise in the first 2 months following orthotopic liver transplantation. All 3 underwent percutaneous transluminal angioplasty and stent placement without complication and showed significant clinical improvement at short and intermediate term follow-up. Percutaneous transluminal angioplasty and Gianturco stent placement is a safe and effective treatment for IVC outflow compromise in the early postoperative period following orthotopic liver transplantation.

  2. Vesicovaginal fistula repair with rectus abdominus myofascial interposition flap.

    PubMed

    Reynolds, W Stuart; Gottlieb, Lawrence J; Lucioni, Alvaro; Rapp, David E; Song, David H; Bales, Gregory T

    2008-06-01

    Complex, recurrent vesicovaginal fistulas (VVFs) can be very challenging to repair and often require interposition of nonirradiated, well-vascularized tissue between the urinary system and vagina. We report our experience using a rectus abdominus myofascial (RAM) interposition flap for VVF repair. A retrospective analysis was performed to identify patients who had undergone VVF repair with RAM interposition. Data were collected focusing on preoperative patient characteristics, etiology of VVF, intraoperative parameters, including surgical techniques, and postoperative patient outcomes. We used a RAM interposition flap for VVF repair in 5 patients. All VVFs had developed postoperatively; no patient had received radiotherapy. VVF developed after total abdominal hysterectomy (TAH) or radical cystectomy in 3 and 2 cases, respectively. Both cases of VVF after radical cystectomy occurred in conjunction with orthotopic diversion (neobladder-vaginal fistula). In 3 patients with post-TAH VVF, a total of five previous failed repairs were attempted before RAM interposition. In 1 patient with a neobladder-vaginal fistula, who had received adjuvant chemotherapy, RAM interposition failed, and the patient ultimately required cutaneous urinary diversion after two subsequent failed attempts at repair (68 months of follow-up). The remaining 4 patients (80%) had no evidence of recurrent VVF or voiding abnormalities at a mean follow-up of 19 months (range 8 to 32). Rectus abdominus muscle can be a successful interposition flap during repair of complex, recurrent VVF. In our experience, this has been successful in most cases, particularly in younger patients with nonmalignant processes.

  3. Inhibiting platelet-derived growth factor beta reduces Ewing's sarcoma growth and metastasis in a novel orthotopic human xenograft model.

    PubMed

    Wang, Yong Xin; Mandal, Deendayal; Wang, Suizhau; Hughes, Dennis; Pollock, Raphael E; Lev, Dina; Kleinerman, Eugenie; Hayes-Jordan, Andrea

    2009-01-01

    Despite aggressive therapy, Ewing's sarcoma (ES) patients have a poor five-year overall survival of only 20-40%. Pulmonary metastasis is the most common form of demise in these patients. The pathogenesis of pulmonary metastasis is poorly understood and few orthotopic models exist that allow study of spontaneous pulmonary metastasis in ES. We have developed a novel orthotopic xenograft model in which spontaneous pulmonary metastases develop. While the underlying biology of ES is incompletely understood, in addition to the EWS-FLI-1 mutation, it is known that platelet-derived growth factor receptor beta (PDGFR-beta) is highly expressed in ES. Hypothesizing that PDGFR-beta expression is indicative of a specific role for this receptor protein in ES progression, the effect of PDGFR-beta inhibition on ES growth and metastasis was assessed in this novel orthotopic ES model. Silencing PDGFR-beta reduced spontaneous growth and metastasis in ES. Preclinical therapeutically relevant findings such as these may ultimately lead to new treatment initiatives in ES.

  4. Postoperative Pleural Effusions After Orthotopic Heart Transplant: Cause, Clinical Manifestations, and Course.

    PubMed

    Ulubay, Gaye; Küpeli, Elif; Er Dedekargınoğlu, Balam; Savaş Bozbaş, Şerife; Alekberov, Mahal; Salman Sever, Özlem; Sezgin, Atilla

    2016-11-01

    Postoperative pleural effusions are common in patients who undergo cardiac surgery and orthotopic heart transplant. Postoperative pleural effusions may also occur as postcardiac injury syndrome. Most of these effusions are nonspecific and develop as a harmless complication of the surgical procedure itself and generally have a benign course. Here, we investigated the cause and clinical and laboratory features of postoperative early and late pleural effusions in orthotopic heart transplant patients. We retrospectively reviewed the medical records of 50 patients who underwent orthotopic heart transplant between 2004 and 2015 at Baskent University. Patient demographics and clinical and laboratory data, including cause of heart failure, presence of pleural effusions at chest radiography in the first year after transplant, timing of onset, microbiologic and biochemical analyses of pleural effusions, and treatment strategies were noted. Mean age of patients was 39.22 ± 13.83 years (39 men, 11 women). Reason for heart failure was dilated cardiomyopathy in most patients (76%). Nineteen patients (38%) had postoperative pleural effusions, with 15 patients (78.9%) with pleural effusion during the first week after transplant. Of these, 4 patients had recurrent pleural effusion. A diagnostic thoracentesis was performed in 10 patients, with 4 showing transudative effusion and 6 showing exudative effusion secondary to infection (2 patients), postcardiac injury syndrome (1 patient), and hemothorax (3 patients). Aspergillus fumigatus was detected by quantitative culture from pleural effusion in 1 patient. Tube thoracoscopy drainage was performed in 10 patients (25%), and 2 patients received antibiotic therapy. Pleural effusions are frequent after cardiac transplant. Complications may occur in a small portion of patients, with most effusions being nonspecific and having a benign course with spontaneous resolution. Early diagnostic thoracentesis could improve postoperative outcomes

  5. Temozolomide combined with PD-1 Antibody therapy for mouse orthotopic glioma model.

    PubMed

    Dai, Bailing; Qi, Na; Li, Junchao; Zhang, Guilong

    2018-07-02

    Temozolomide (TMZ) is the most frequent adjuvant chemotherapy drug in gliomas. PDL1 expresses on various tumors, including gliomas, and anti-PD-1 antibodies have been approved for treating some tumors by FDA. This study was to evaluate the therapeutical potential of combined TMZ with anti-PD-1 antibody therapy for mouse orthotopic glioma model. We performed C57BL/6 mouse orthotopic glioma model by stereotactic intracranial implantation of glioma cell line GL261, mice were randomly divided into four groups: (1) control group; (2) TMZ group; (3) anti-PD-1 antibody group; (4) TMZ combined with anti-PD-1 antibody group. Then the volume or size of tumor was assessed by 7.0 T MRI and immunohistochemistry, and the number of CD4 and CD8 infiltrating cells in brain tumor and spleen was evaluated by immunohistochemistry. Western blot was used to evaluate the expression of PDL1. Furthermore, Overall survival of each group mice was also evaluated. Overall survival was significantly improved in combined group compared to other groups (χ2 = 32.043, p < 0.01). The volume or size of tumor was significantly decreased in combined group compared with other groups (F = 42.771, P < 0.01). And the number of CD4 and CD8 infiltrating cells in brain tumor was also obviously increased in combined group (CD4 F = 45.67, P < 0.01; CD8 F = 53.75, P < 0.01). Anti-PD1 antibody combined with TMZ therapy for orthotopic mouse glioma model could significantly improve the survival time of tumor-bear mice. Thus, this study provides the effective preclinical evidence for support clinical chemotherapy combined with immunotherapy for glioma patients. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. CETUXIMAB AND IRINOTECAN INTERACT SYNERGISTICALLY TO INHIBIT THE GROWTH OF ORTHOTOPIC ANAPLASTIC THYROID CARCINOMA XENOGRAFTS IN NUDE MICE

    PubMed Central

    Kim, Seungwon; Prichard, Christopher N.; Younes, Maher N.; Yazici, Yasemin D.; Jasser, Samar A.; Bekele, B. Nebiyou; Myers, Jeffrey N.

    2006-01-01

    Objective Anaplastic thyroid carcinoma (ATC) remains one of the most lethal known human cancers. Targeted molecular therapy with cetuximab, a monoclonal antibody against EGFR, offers new treatment potentials for patient with ATC. Cetuximab has also been reported to have synergistic effects when combined with irinotecan, a topoisomerase inhibitor. Therefore, we hypothesized that cetuximab and irinotecan would be effective in inhibiting the growth and progression of ATC in a murine orthotopic model. Design The in vitro anti-proliferative effects of cetuximab and irinotecan on ATC cell line ARO were examined. We also studied the in vivo effects of cetuximab and irinotecan on the growth, invasion, and metastasis of orthotopic ATC tumors in nude mice. The in vivo antitumor efficacy of cetuximab/irinotecan combination was also compared with that of doxorubicin. Results Cetuximab alone did not show any anti-proliferative or pro-apoptotic effect on this cell line. However, when combined with irinotecan, cetuximab potentiated the in vitro anti-proliferative and pro-apoptotic effect of irinotecan. Cetuximab, irinotecan, and cetuximab/irinotecan combination resulted in 77%, 79%, and 93% in vivo inhibition of tumor growth, respectively. Incidences of lymph node metastasis, laryngeal invasion, and tumor microvessel density were also significantly decreased in these treatment groups. Furthermore, the cetuximab/irinotecan combination was significantly more effective than doxorubicin in inhibiting the growth of orthotopic ATC xenografts. Conclusions Combination therapy with cetuximab/irinotecan inhibits the growth and progression of orthotopic ATC xenografts in nude mice. Given the lack of curative options for patients with ATC, combination therapy with cetuximab and irinotecan treatment warrants further study. PMID:16428506

  7. Characterization of thyroid cancer cell lines in murine orthotopic and intracardiac metastasis models.

    PubMed

    Morrison, Jennifer A; Pike, Laura A; Lund, Greg; Zhou, Qiong; Kessler, Brittelle E; Bauerle, Kevin T; Sams, Sharon B; Haugen, Bryan R; Schweppe, Rebecca E

    2015-06-01

    Thyroid cancer incidence has been increasing over time, and it is estimated that ∼1950 advanced thyroid cancer patients will die of their disease in 2015. To combat this disease, an enhanced understanding of thyroid cancer development and progression as well as the development of efficacious, targeted therapies are needed. In vitro and in vivo studies utilizing thyroid cancer cell lines and animal models are critically important to these research efforts. In this report, we detail our studies with a panel of authenticated human anaplastic and papillary thyroid cancer (ATC and PTC) cell lines engineered to express firefly luciferase in two in vivo murine cancer models-an orthotopic thyroid cancer model as well as an intracardiac injection metastasis model. In these models, primary tumor growth in the orthotopic model and the establishment and growth of metastases in the intracardiac injection model are followed in vivo using an IVIS imaging system. In the orthotopic model, the ATC cell lines 8505C and T238 and the PTC cell lines K1/GLAG-66 and BCPAP had take rates >90 % with final tumor volumes ranging 84-214 mm(3) over 4-5 weeks. In the intracardiac model, metastasis establishment was successful in the ATC cell lines HTh74, HTh7, 8505C, THJ-16T, and Cal62 with take rates ≥70 %. Only one of the PTC cell lines tested (BCPAP) was successful in the intracardiac model with a take rate of 30 %. These data will be beneficial to inform the choice of cell line and model system for the design of future thyroid cancer studies.

  8. Salinomycin nanoparticles interfere with tumor cell growth and the tumor microenvironment in an orthotopic model of pancreatic cancer.

    PubMed

    Daman, Zahra; Faghihi, Homa; Montazeri, Hamed

    2018-05-02

    Recently, salinomycin (SAL) has been reported to inhibit proliferation and induce apoptosis in various tumors. The aim of this study was to deliver SAL to orthotopic model of pancreatic cancer by the aid of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). The NPs were physico-chemically characterized and evaluated for cytotoxicity on luciferase-transduced AsPC-1 cells in vitro as well as implanted orthotopically into the pancreas of nude mice. SAL (3.5 mg/kg every other day) blocked tumor growth by 52% compared to the control group after 3 weeks of therapy. Western blotting of tumor protein extracts indicated that SAL treatment leads to up-regulation of E-cadherin, β-catenin, and transforming growth factor beta receptor (TGFβR) expressions in AsPC-1 orthotopic tumor. Noteworthy, immunofluorescence staining of adjacent tumor sections showed that treatment with SAL NPs cause significant apoptosis in the tumor cells rather than the stroma. Further investigations also revealed that TGFβR2 over-expression was induced in stroma cells after treatment with SAL NPs. These results highlight SAL-loaded PLGA NPs as a promising system for pancreatic cancer treatment, while the mechanistic questions need to be subsequently tested.

  9. [To the issue of postreperfusion syndrome predictors in orthotopic liver transplantation (OLT)].

    PubMed

    Kiseleva, E A; Ushakova, I A; Kim, E F; Matveev, G P; Biriulina, N Iu; Vabishchevich, A V

    2012-01-01

    The aim of the study is revelation of postperfusion syndrome (pPS) predictors in orthotopic liver transplantation (OLT). Was conducted a retrospective analysis of anesthesia maintainance protocols during orthotopic liver transplantation in 261 patients aged from 6 months to 60 years. Investigated the effect of various factors on the development of PPS by the application of methods of non-parametric statistics. Significantly more frequent development of the PPS is noted in the age group from 3 to 18 years (up to 30% of patients). In recipients older than 18 years the frequency of the development of the PPS does not depend on age, with an average of 14%. The development of the PPS does not depend on the recipient sex, the nature of the pathology which served as an indication to the OTP, the initial severity of the state, type of OTP (living related donor or cadaveric transplantation, primary or re-transplantation), the transplant warm ischemia duration, use, or the lack of venous-venous bypass, metabolic status of the patient. The obtained results do not contradict to the data of foreign publications. Among parameters available for screening, predictor of PPS was not detected.

  10. Perfluorocarbon emulsions radiosensitise brain tumors in carbogen breathing mice with orthotopic GL261 gliomas

    PubMed Central

    Feldman, Lisa A.; Fabre, Marie-Sophie; Grasso, Carole; Reid, Dana; Broaddus, William C.; Lanza, Gregory M.; Spiess, Bruce D.; Garbow, Joel R.; McConnell, Melanie J.

    2017-01-01

    Background Tumour hypoxia limits the effectiveness of radiation therapy. Delivering normobaric or hyperbaric oxygen therapy elevates pO2 in both tumour and normal brain tissue. However, pO2 levels return to baseline within 15 minutes of stopping therapy. Aim To investigate the effect of perfluorocarbon (PFC) emulsions on hypoxia in subcutaneous and intracranial mouse gliomas and their radiosensitising effect in orthotopic gliomas in mice breathing carbogen (95%O2 and 5%CO2). Results PFC emulsions completely abrogated hypoxia in both subcutaneous and intracranial GL261 models and conferred a significant survival advantage orthotopically (Mantel Cox: p = 0.048) in carbogen breathing mice injected intravenously (IV) with PFC emulsions before radiation versus mice receiving radiation alone. Carbogen alone decreased hypoxia levels substantially and conferred a smaller but not statistically significant survival advantage over and above radiation alone. Conclusion IV injections of PFC emulsions followed by 1h carbogen breathing, radiosensitises GL261 intracranial tumors. PMID:28873460

  11. Orthotopic Transplantation of Achilles Tendon Allograft in Rats

    PubMed Central

    Aynardi, Michael; Zahoor, Talal; Mitchell, Reed; Loube, Jeffrey; Feltham, Tyler; Manandhar, Lumanti; Paudel, Sharada; Schon, Lew; Zhang, Zijun

    2018-01-01

    The biology and function of orthotopic transplantation of Achilles tendon allograft are unknown. Particularly, the revitalization of Achilles allograft is a clinical concern. Achilles allografts were harvested from donor rats and stored at −80 °C. Subcutaneous adipose tissue was harvested from the would-be allograft recipient rats for isolation of mesenchymal stem cells (MSCs). MSCs were cultured with growth differentiation factor-5 (GDF-5) and applied onto Achilles allografts on the day of transplantation. After the native Achilles tendon was resected from the left hind limb of the rats, Achilles allograft, with or without autologous MSCs, was implanted and sutured with calf muscles proximally and calcaneus distally. Animal gait was recorded presurgery and postsurgery weekly. The animals were sacrificed at week 4, and the transplanted Achilles allografts were collected for biomechanical testing and histology. The operated limbs had altered gait. By week 4, the paw print intensity, stance time, and duty cycle (percentage of the stance phase in a step cycle) of the reconstructed limbs were mostly recovered to the baselines recorded before surgery. Maximum load of failure was not different between Achilles allografts, with or without MSCs, and the native tendons. The Achilles allograft supplemented with MSCs had higher cellularity than the Achilles allograft without MSCs. Deposition of fine collagen (type III) fibers was active in Achilles allograft, with or without MSCs, but it was more evenly distributed in the allografts that were incubated with MSCs. In conclusion, orthotopically transplanted Achilles allograft healed with host tissues, regained strength, and largely restored Achilles function in 4 wk in rats. It is therefore a viable option for the reconstruction of a large Achilles tendon defect. Supplementation of MSCs improved repopulation of Achilles allograft, but large animal models, with long-term follow up and cell tracking, may be required to fully

  12. Anesthetic management in pediatric orthotopic liver transplant for fulminant hepatic failure and end-stage liver disease.

    PubMed

    Camkıran, Aynur; Araz, Coşkun; Seyhan Ballı, Sevgi; Torgay, Adnan; Moray, Gökhan; Pirat, Arash; Arslan, Gülnaz; Haberal, Mehmet

    2014-03-01

    We assessed the anesthetic management and short-term morbidity and mortality in pediatrics patients who underwent an orthotopic liver transplant for fulminant hepatic failure or end-stage liver disease in a university hospital. We retrospectively analyzed the records of children who underwent orthotopic liver transplant from May 2002 to May 2012. Patients were categorized into 2 groups: group fulminant hepatic failure (n=22) and group end-stage liver disease (n=19). Perioperative data related to anesthetic management and intraoperative events were collected along with information related to postoperative course and survival to hospital discharge. Mean age and weight for groups fulminant hepatic failure and end-stage liver disease were 8.6 ± 2.7 years and 10.8 ± 3.8 years (P = .04) and 29.2 ± 11.9 kg and 33.7 ± 16.9 kg (P = .46). There were no differences between the groups regarding length of anhepatic phase (65 ± 21 min vs 73 ± 18 min, P = .13) and operation time (9.1 ± 1.6 h vs 9.5 ± 1.8 h, P = .23). When compared with the patients in group fulminant hepatic failure, those in group end-stage liver disease more commonly had a Glasgow Coma score of 7 or less (32% vs 6%, P = .04). Compared with patients in group fulminant hepatic failure, those in group end-stage liver disease were more frequently extubated in the operating room (31.8% versus 89.5% P < .001). Postoperative duration of mechanical ventilation (2.78 ± 4.02 d vs 2.85 ± 10.21 d, P = .05), and the mortality rates at 1 year after orthotopic liver transplant (7.3% vs 0%, P = .09) were similar between the groups. During pediatric orthotopic liver transplant, those children with fulminant hepatic failure require more intraoperative fluids and more frequent perioperative mechanical ventilation than those with end-stage liver disease.

  13. An alternative technique for orthotopic cardiac transplantation, with preservation of the normal anatomy of the right atrium.

    PubMed

    Sievers, H H; Weyand, M; Kraatz, E G; Bernhard, A

    1991-04-01

    The standard technique for orthotopic cardiac transplantation implies large atrial anastomoses which do not preserve the anatomical integrity of the donor atria. This may become a potential source of electrophysiological and mechanical atrial dysfunction, especially in the right atrium with the sinus node and the sensitive low-pressure atrioventricular valve. As an improvement we suggest an alternative technique which we have recently developed for orthotopic cardiac transplantation; it combines the simple, convenient left atrial connection of the standard technique with individual anastomoses of the superior and inferior venae cavae, preserving the right atrium of the donated heart intact. This technique and our first results in two cases are described. Postoperatively, no arrhythmias and no signs of tricuspid insufficiency were observed.

  14. Isolation of Circulating Tumor Cells in an Orthotopic Mouse Model of Colorectal Cancer.

    PubMed

    Kochall, Susan; Thepkaysone, May-Linn; García, Sebastián A; Betzler, Alexander M; Weitz, Jürgen; Reissfelder, Christoph; Schölch, Sebastian

    2017-07-18

    Despite the advantages of easy applicability and cost-effectiveness, subcutaneous mouse models have severe limitations and do not accurately simulate tumor biology and tumor cell dissemination. Orthotopic mouse models have been introduced to overcome these limitations; however, such models are technically demanding, especially in hollow organs such as the large bowel. In order to produce uniform tumors which reliably grow and metastasize, standardized techniques of tumor cell preparation and injection are critical. We have developed an orthotopic mouse model of colorectal cancer (CRC) which develops highly uniform tumors and can be used for tumor biology studies as well as therapeutic trials. Tumor cells from either primary tumors, 2-dimensional (2D) cell lines or 3-dimensional (3D) organoids are injected into the cecum and, depending on the metastatic potential of the injected tumor cells, form highly metastatic tumors. In addition, CTCs can be found regularly. We here describe the technique of tumor cell preparation from both 2D cell lines and 3D organoids as well as primary tumor tissue, the surgical and injection techniques as well as the isolation of CTCs from the tumor-bearing mice, and present tips for troubleshooting.

  15. Laparoscopic kidney orthotopic transplant: preclinical study in the pig model.

    PubMed

    He, B; Musk, G C; Mou, L; Waneck, G L; Delriviere, L

    2013-06-01

    Laparoscopic surgery has rapidly expanded in clinical practice replacing conventional open surgery over the last three decades. Laparoscopic donor nephrectomy has been favored due to its multiple benefits. The aim of this study was to explore the safety and feasibility of kidney transplantation by a laparoscopic technique in a pig model. The study was approved by the university animal ethics committee. Eight female pigs (Sus Scrofra, weighing 45-50 kg) were divided into 2 groups: group I included 4 animals that underwent laparoscopic kidney orthotopic transplantation on the left side. The right kidney was remained functional in situ. The pigs recovered and were observed for 1 week. In the 4 hosts group II pigs underwent a laparoscopic kidney transplantation on the left side. With simultaneous clipping of the right ureter. After recovery, the pigs were observed for 4 weeks. A laparotomy for examination was performed prior to euthanasia. All 4 group I pigs survived for 1 week. The laparotomy showed normal graft perfusion with wall patent renal artery and vein as well as satisfactory urine output upon transection of ureter in 3 hosts. Renal artery stenosis occurred in one pig. In The Immediate kidney graft function was achieved in 3 group II pigs. The fourth died following extubation due to laryngospasm despite a functional graft. The average creatinine levels were 195.5 μmol/L on day 3; 224.5 μmol/L at week 1; 127 μmol/L at week 2; 182.7 umol/L at week 3; and 154.7 umol/L at week 4. Laparoscopic kidney transplantation was feasible and safe in a pig model with immediate graft function. This study will provide further evidence to support application of laparoscopic technique to human kidney transplant. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Periosteum tissue engineering in an orthotopic in vivo platform.

    PubMed

    Baldwin, J G; Wagner, F; Martine, L C; Holzapfel, B M; Theodoropoulos, C; Bas, O; Savi, F M; Werner, C; De-Juan-Pardo, E M; Hutmacher, D W

    2017-03-01

    The periosteum plays a critical role in bone homeostasis and regeneration. It contains a vascular component that provides vital blood supply to the cortical bone and an osteogenic niche that acts as a source of bone-forming cells. Periosteal grafts have shown promise in the regeneration of critical size defects, however their limited availability restricts their widespread clinical application. Only a small number of tissue-engineered periosteum constructs (TEPCs) have been reported in the literature. A current challenge in the development of appropriate TEPCs is a lack of pre-clinical models in which they can reliably be evaluated. In this study, we present a novel periosteum tissue engineering concept utilizing a multiphasic scaffold design in combination with different human cell types for periosteal regeneration in an orthotopic in vivo platform. Human endothelial and bone marrow mesenchymal stem cells (BM-MSCs) were used to mirror both the vascular and osteogenic niche respectively. Immunohistochemistry showed that the BM-MSCs maintained their undifferentiated phenotype. The human endothelial cells developed into mature vessels and connected to host vasculature. The addition of an in vitro engineered endothelial network increased vascularization in comparison to cell-free constructs. Altogether, the results showed that the human TEPC (hTEPC) successfully recapitulated the osteogenic and vascular niche of native periosteum, and that the presented orthotopic xenograft model provides a suitable in vivo environment for evaluating scaffold-based tissue engineering concepts exploiting human cells. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  17. Orthotopic Patient-Derived Pancreatic Cancer Xenografts Engraft Into the Pancreatic Parenchyma, Metastasize, and Induce Muscle Wasting to Recapitulate the Human Disease.

    PubMed

    Go, Kristina L; Delitto, Daniel; Judge, Sarah M; Gerber, Michael H; George, Thomas J; Behrns, Kevin E; Hughes, Steven J; Judge, Andrew R; Trevino, Jose G

    2017-07-01

    Limitations associated with current animal models serve as a major obstacle to reliable preclinical evaluation of therapies in pancreatic cancer (PC). In an effort to develop more reliable preclinical models, we have recently established a subcutaneous patient-derived xenograft (PDX) model. However, critical aspects of PC responsible for its highly lethal nature, such as the development of distant metastasis and cancer cachexia, remain underrepresented in the flank PDX model. The purpose of this study was to evaluate the degree to which an orthotopic PDX model of PC recapitulates these aspects of the human disease. Human PDX-derived PC tumors were implanted directly into the pancreas of NOD.Cg-Prkdc Il2rg/SzJ mice. Tumor growth, metastasis, and muscle wasting were then evaluated. Orthotopically implanted PDX-derived tumors consistently incorporated into the murine pancreatic parenchyma, metastasized to both the liver and lungs and induced muscle wasting directly proportional to the size of the tumor, consistent of the cancer cachexia syndrome. Through the orthotopic implantation technique described, we demonstrate a highly reproducible model that recapitulates both local and systemic aspects of human PC.

  18. Highly Effective Auger-Electron Therapy in an Orthotopic Glioblastoma Xenograft Model using Convection-Enhanced Delivery

    PubMed Central

    Thisgaard, Helge; Halle, Bo; Aaberg-Jessen, Charlotte; Olsen, Birgitte Brinkmann; Therkelsen, Anne Sofie Nautrup; Dam, Johan Hygum; Langkjær, Niels; Munthe, Sune; Någren, Kjell; Høilund-Carlsen, Poul Flemming; Kristensen, Bjarne Winther

    2016-01-01

    Glioblastoma, the most common and malignant primary brain tumor, always recurs after standard treatment. Therefore, promising new therapeutic approaches are needed. Short-range Auger-electron-emitters carry the ability of causing highly damaging radiation effects in cells. The aim of this study was to test the effect of [125I]5-Iodo-2'-deoxyuridine (125I-UdR, a radioactive Auger-electron-emitting thymidine analogue) Auger-therapy on immature glioblastoma spheroid cultures and orthotopic xenografted glioblastoma-bearing rats, the latter by means of convection-enhanced delivery (CED). Moreover, we aimed to determine if the therapeutic effect could be enhanced when combining 125I-UdR therapy with the currently used first-line chemotherapeutic agent temozolomide. 125I-UdR significantly decreased glioblastoma cell viability and migration in vitro and the cell viability was further decreased by co-treatment with methotrexate and/or temozolomide. Intratumoral CED of methotrexate and 125I-UdR with and without concomitant systemic temozolomide chemotherapy significantly reduced the tumor burden in orthotopically xenografted glioblastoma-bearing nude rats. Thus, 100% (8/8) of the animals survived the entire observation period of 180 days when subjected to the combined Auger-chemotherapy while 57% (4/7) survived after the Auger-therapy alone. No animals (0/8) treated with temozolomide alone survived longer than 50 days. Blood samples and post-mortem histology showed no signs of dose-limiting adverse effects. In conclusion, the multidrug approach consisting of CED of methotrexate and 125I-UdR with concomitant systemic temozolomide was safe and very effective leading to 100% survival in an orthotopic xenograft glioblastoma model. Therefore, this therapeutic strategy may be a promising option for future glioblastoma therapy. PMID:27924163

  19. Highly Effective Auger-Electron Therapy in an Orthotopic Glioblastoma Xenograft Model using Convection-Enhanced Delivery.

    PubMed

    Thisgaard, Helge; Halle, Bo; Aaberg-Jessen, Charlotte; Olsen, Birgitte Brinkmann; Therkelsen, Anne Sofie Nautrup; Dam, Johan Hygum; Langkjær, Niels; Munthe, Sune; Någren, Kjell; Høilund-Carlsen, Poul Flemming; Kristensen, Bjarne Winther

    2016-01-01

    Glioblastoma, the most common and malignant primary brain tumor, always recurs after standard treatment. Therefore, promising new therapeutic approaches are needed. Short-range Auger-electron-emitters carry the ability of causing highly damaging radiation effects in cells. The aim of this study was to test the effect of [ 125 I]5-Iodo-2'-deoxyuridine ( 125 I-UdR, a radioactive Auger-electron-emitting thymidine analogue) Auger-therapy on immature glioblastoma spheroid cultures and orthotopic xenografted glioblastoma-bearing rats, the latter by means of convection-enhanced delivery (CED). Moreover, we aimed to determine if the therapeutic effect could be enhanced when combining 125 I-UdR therapy with the currently used first-line chemotherapeutic agent temozolomide. 125 I-UdR significantly decreased glioblastoma cell viability and migration in vitro and the cell viability was further decreased by co-treatment with methotrexate and/or temozolomide. Intratumoral CED of methotrexate and 125 I-UdR with and without concomitant systemic temozolomide chemotherapy significantly reduced the tumor burden in orthotopically xenografted glioblastoma-bearing nude rats. Thus, 100% (8/8) of the animals survived the entire observation period of 180 days when subjected to the combined Auger-chemotherapy while 57% (4/7) survived after the Auger-therapy alone. No animals (0/8) treated with temozolomide alone survived longer than 50 days. Blood samples and post-mortem histology showed no signs of dose-limiting adverse effects. In conclusion, the multidrug approach consisting of CED of methotrexate and 125 I-UdR with concomitant systemic temozolomide was safe and very effective leading to 100% survival in an orthotopic xenograft glioblastoma model. Therefore, this therapeutic strategy may be a promising option for future glioblastoma therapy.

  20. In vivo bioluminescence imaging using orthotopic xenografts towards patient's derived-xenograft Medulloblastoma models.

    PubMed

    Asadzadeh, Fatemeh; Ferrucci, Veronica; DE Antonellis, Pasqualino; Zollo, Massimo

    2017-03-01

    Medulloblastoma is a cerebellar neoplasia of the central nervous system. Four molecular subgrups have been identified (MBWNT, MBSHH, MBgroup3 and MBgroup4) with distinct genetics and clinical outcome. Among these, MBgroup3-4 are highly metastatic with the worst prognosis. The current standard therapy includes surgery, radiation and chemotherapy. Thus, specific treatments adapted to cure those different molecular subgroups are needed. The use of orthotopic xenograft models, together with the non-invasive in vivo biolumiscence imaging (BLI) technology, is emerging during preclinical studies to test novel therapeutics for medulloblastoma treatment. Orthotopic MB xenografts were performed by injection of Daoy-luc cells, that had been previously infected with lentiviral particles to stably express luciferase gene, into the fourth right ventricle of the cerebellum of ten nude mice. For the implantation, specific stereotactic coordinates were used. Seven days after the implantation the mice were imaged by acquisitions of bioluminescence imaging (BLI) using IVIS 3D Illumina Imaging System (Xenogen). Tumor growth was evaluated by quantifying the bioluminescence signals using the integrated fluxes of photons within each area of interest using the Living Images Software Package 3.2 (Xenogen-Perkin Elmer). Finally, histological analysis using hematoxylin-eosin staining was performed to confirm the presence of tumorigenic cells into the cerebellum of the mice. We describe a method to use the in vivo bioluminescent imaging (BLI) showing the potential to be used to investigate the potential antitumorigenic effects of a drug for in vivo medulloblastoma treatment. We also discuss other studies in which this technology has been applied to obtain a more comprehensive knowledge of medulloblastoma using orthotopic xenograft mouse models. There is a need to develop patient's derived-xenograft (PDX) model systems to test novel drugs for medulloblastoma treatment within each molecular sub

  1. Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

    PubMed

    Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

    2014-04-16

    The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P < 0.05) and higher than in middle and remote paraneoplastic tissue (P < 0.01). There was no statistically significant difference between the expression of these genes in middle and proximal paraneoplastic tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

  2. [A simple and efficient method for establishing a mouse model of orthotopic MB49 bladder cancer].

    PubMed

    Liang, Zhong-kun; Zhang, Lin; Hu, Zhi-ming; Chen, Zhong; Huang, Xin; Shi, Xiang-hua; Tan, Wan-long; Gao, Ji-min

    2009-04-01

    To establish a simple and efficient method for establishing a mouse model of orthotopic superficial bladder cancer. C57BL/6 mice were anesthetized with sodium pentobarbital and catheterized with modified IV catheter (24 G). The mice were intravesically pretreated with HCl and then with NaOH, and after washing the bladders with phosphate-buffered saline (PBS), 100 microl (1 x 10(7)) MB49 cells were infused and allowed to incubate in the bladder for 2 h followed intravesical mitomycin C (MMC) administration. The tumor formation rate, survival, gross hematuria, and bladder weight were determined as the outcome variables, and the pathology of the bladders was observed. Instillation of MB49 tumor cells resulted in a tumor formation rates of 100% in all the pretreated groups while 0% in the control group without pretreatment. MMC significantly reduced the bladder weight as compared to PBS. We have successfully established a stable, reproducible, and reliable orthotopic bladder cancer model in mice.

  3. Porphyrin lipid nanoparticles for enhanced photothermal therapy in a patient-derived orthotopic pancreas xenograft cancer model

    NASA Astrophysics Data System (ADS)

    MacLaughlin, Christina M.; Ding, Lili; Jin, Cheng; Cao, Pingjiang; Siddiqui, Iram; Hwang, David M.; Chen, Juan; Wilson, Brian C.; Zheng, Gang; Hedley, David W.

    2016-03-01

    Local disease control is a major problem in the treatment of pancreatic cancer, because curative-intent surgery is only possible in a minority of patients, and radiotherapy cannot be delivered in curative doses. Despite the promise of photothermal therapy (PTT) for ablation of pancreatic tumors, this approach remains under investigated. Using photothermal sensitizers in combination with laser light for PTT can result in more efficient conversion of light energy to heat, and confinement of thermal destruction to the tumor, thus sparing adjacent organs and vasculature. Porphyrins have been previously employed as photosensitizers for PDT and PTT, however their incorporation in to "porphysomes", lipid-based nanoparticles each containing ~80,000 porphyrins through conjugation of pyropheophorbide to phospholipids, carries two distinct advantages: 1) high-density porphyrin packing imparts the nanoparticles with enhanced photonic properties for imaging and phototherapy; 2) the enhanced permeability and retention effect may be exploited for optimal delivery of porphysomes to the tumor region thus high payload porphyrin delivery. The feasibility of porphysome-enhanced PTT for pancreatic cancer treatment was investigated using a patient-derived orthotopic pancreas xenograft tumor model. Uptake of porphysomes at the orthotopic tumor site was validated using ex vivo fluorescence imaging of intact organs of interest. The accumulation of porphysomes in orthotopic tumor microstructure was also confirmed by fluorescence imaging of excised tissue slices. PTT progress was monitored as changes in tumor surface temperature using IR optical imaging. Histological analyses were conducted to examine microstructure changes in tissue morphology, and the viability of remaining tumor tissues following exposure to heat. These studies may also provide insight as to the contribution of heat sink in application of thermal therapies to highly vascularized pancreatic tumors.

  4. The Next Generation of Orthotopic Thyroid Cancer Models: Immunocompetent Orthotopic Mouse Models of BRAFV600E-Positive Papillary and Anaplastic Thyroid Carcinoma

    PubMed Central

    Vanden Borre, Pierre; McFadden, David G.; Gunda, Viswanath; Sadow, Peter M.; Varmeh, Shohreh; Bernasconi, Maria; Jacks, Tyler

    2014-01-01

    Background: While the development of new treatments for aggressive thyroid cancer has advanced in the last 10 years, progress has trailed headways made with other malignancies. A lack of reliable authenticated human cell lines and reproducible animal models is one major roadblock to preclinical testing of novel therapeutics. Existing xenograft and orthotopic mouse models of aggressive thyroid cancer rely on the implantation of highly passaged human thyroid carcinoma lines in immunodeficient mice. Genetically engineered models of papillary and undifferentiated (anaplastic) thyroid carcinoma (PTC and ATC) are immunocompetent; however, slow and stochastic tumor development hinders high-throughput testing. Novel models of PTC and ATC in which tumors arise rapidly and synchronously in immunocompetent mice would facilitate the investigation of novel therapeutics and approaches. Methods: We characterized and utilized mouse cell lines derived from PTC and ATC tumors arising in genetically engineered mice with thyroid-specific expression of endogenous BrafV600E/WT and deletion of either Trp53 (p53) or Pten. These murine thyroid cancer cells were transduced with luciferase- and GFP-expressing lentivirus and implanted into the thyroid glands of immunocompetent syngeneic B6129SF1/J mice in which the growth characteristics were assessed. Results: Large locally aggressive thyroid tumors form within one week of implantation. Tumors recapitulate their histologic subtype, including well-differentiated PTC and ATC, and exhibit CD3+, CD8+, B220+, and CD163+ immune cell infiltration. Tumor progression can be followed in vivo using luciferase and ex vivo using GFP. Metastatic spread is not detected at early time points. Conclusions: We describe the development of the next generation of murine orthotopic thyroid cancer models. The implantation of genetically defined murine BRAF-mutated PTC and ATC cell lines into syngeneic mice results in rapid and synchronous tumor formation. This

  5. Antitumor immune activity by chemokine CX3CL1 in an orthotopic implantation of lung cancer model in vivo.

    PubMed

    Kee, Ji-Ye; Arita, Yoshihisa; Shinohara, Kanna; Ohashi, Yasukata; Sakurai, Hiroaki; Saiki, Ikuo; Koizumi, Keiichi

    2013-01-01

    Due to their chemoattractant properties stimulating the accumulation of infiltrating immune cells in tumors, chemokines are known to have antitumor effects. Fractalkine, a unique CX3C chemokine, is expressed in activated endothelial cells, while its receptor, CX3CR1, is expressed in cytolytic immune cells, such as natural killer cells, monocytes and some CD8 + T cells. The biological properties of cancer cells are affected by the implantation organ and differences in immune systems, requiring cancer implantation in orthotopic organs in an in vivo experiment. To develop new therapy strategies for lung cancer, an animal model reflecting the clinical features of lung cancer was previously established. This study aimed to determine whether CX3CL1-induced biological functions should be used for immune cell-based gene therapy of lung cancer in the orthotopic implantation model. An orthotopic intrapulmonary implantation of CX3CL1-stable expression in mouse lung cancer (LLC-CX3CL1) was performed to analyze growth. Results showed a significant decrease in tumor growth in the lung compared to the control cells (LLC-mock). Furthermore, the antitumor effects of CX3CL1 were derived from natural killer cell activities in the depletion experiment in vivo . Therefore, CX3CL1 has the potential of a useful therapeutic target in lung cancer.

  6. Respiratory viral infection in obliterative airway disease after orthotopic tracheal transplantation.

    PubMed

    Kuo, Elbert; Bharat, Ankit; Goers, Trudie; Chapman, Will; Yan, Le; Street, Tyler; Lu, Wei; Walter, Michael; Patterson, Alexander; Mohanakumar, Thalachallour

    2006-09-01

    The long-term survival after human lung transplantation is limited by bronchiolitis obliterans syndrome (BOS). Clinically, community-acquired respiratory viral infections have been correlated with an increased incidence of BOS. The goal of this study was to investigate the role of respiratory viral infections in chronic lung allograft rejection using the murine orthotopic tracheal transplantation model. Eighty orthotopic tracheal transplants were performed using BALB/c and C57BL/6 mice. Recipient mice were infected intranasally with Sendai virus (SdV), a murine parainfluenza type I virus. Experiments altering the infectious dose, infection time, harvest time, allogeneic response, and viral response were performed. Tracheal allograft rejection was monitored using percent fibrosis and lamina propria to cartilage ratio measurements. Interferon-gamma ELISPOT analysis against irradiated donor (BALB/c) splenocytes was used as immunologic indicator of alloreactivity after transplantation. Sendai virus infection revealed a dose-dependent transient suppression of alloreactivity with a decrease in tracheal allograft fibrosis and frequency of alloreactive T cells at 30 days. This immunosuppression was reversed by day 60, leading to increased tracheal allograft fibrosis with a concomitant increase in the frequency of interferon-gamma producing alloreactive T cells. Pretransplant sensitization with donor antigens prevented the initial suppression of alloreactivity due to SdV infection. Furthermore, pretransplant immunization against SdV infection resulted in rapid clearing of the infection and reduced the immunopathology of rejection. Respiratory viral infections can cause enhanced tracheal allograft rejection despite the initial phase of transient immunosuppression. Early treatment or vaccination against the respiratory infections may represent a viable intervention to reduce the risk of chronic rejection.

  7. Nanoparticle-assisted photothermal ablation of brain tumor in an orthotopic canine model

    NASA Astrophysics Data System (ADS)

    Schwartz, Jon A.; Shetty, Anil M.; Price, Roger E.; Stafford, R. Jason; Wang, James C.; Uthamanthil, Rajesh K.; Pham, Kevin; McNichols, Roger J.; Coleman, Chris L.; Payne, J. Donald

    2009-02-01

    We report on a pilot study demonstrating a proof of concept for the passive delivery of nanoshells to an orthotopic tumor where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photo-thermal ablation of canine Transmissible Venereal Tumor (cTVT) in a canine brain model. cTVT fragments grown in SCID mice were successfully inoculated in the parietal lobe of immuno-suppressed, mixed-breed hound dogs. A single dose of near-infrared absorbing, 150 nm nanoshells was infused intravenously and allowed time to passively accumulate in the intracranial tumors which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the intracranial cTVT suggesting that its neo-vasculature represented an interruption of the normal blood-brain barrier. Tumors were thermally ablated by percutaneous, optical fiber-delivered, near-infrared radiation using a 3.5 W average, 3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8+/-4.1ºC. Identical laser doses applied to normal white and gray matter on the contralateral side of the brain yielded sub-lethal temperatures of 48.6+/-1.1ºC. The laser dose was designed to minimize thermal damage to normal brain tissue in the absence of nanoshells and compensate for variability in the accumulation of nanoshells in tumor. Post-mortem histopathology of treated brain sections demonstrated the effectiveness and selectivity of the nanoshell-assisted thermal ablation.

  8. The Role of Lymphangiogenesis in Orthotopic Prostatic Tumor-Environment on Regional and Systemic Metastasis

    DTIC Science & Technology

    2008-01-01

    expressing Renilla luciferase and VEGF-C shRNA or irrelevant firefly luciferase shRNA (Ctrl) were implanted orthotopically as before. To determine the...on metastasis in Pten knockout model (Month 10-24): a) Generate Ubc/sVEGFR-3 and Ubc/ Renilla luciferase (RL) lentiviral vectors by subcloning...progression (month 10-12) c) Monitor efficiency of Ubc/lentiviral transduction and expression in Pten (-/-) prostate using optical imaging of Renilla

  9. Combination radiotherapy in an orthotopic mouse brain tumor model.

    PubMed

    Kramp, Tamalee R; Camphausen, Kevin

    2012-03-06

    Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors. In recent years there has been substantial progress in the understanding of the mechanics of tumor invasion, and direct intracerebral inoculation of tumor provides the opportunity of observing the invasive process in a physiologically appropriate environment. As far as human brain tumors are concerned, the orthotopic models currently available are established either by stereotaxic injection of cell suspensions or implantation of a solid piece of tumor through a complicated craniotomy procedure. In our technique we harvest cells from tissue culture to create a cell suspension used to implant directly into the brain. The duration of the surgery is approximately 30 minutes, and as the mouse needs to be in a constant surgical plane, an injectable anesthetic is used. The mouse is placed in a stereotaxic jig made by Stoetling (figure 1). After the surgical area is cleaned and prepared, an incision is made; and the bregma is located to determine the location of the craniotomy. The location of the craniotomy is 2 mm to the right and 1 mm rostral to the bregma. The depth is 3 mm from the surface of the skull, and cells are injected at a rate of 2 μl every 2 minutes. The skin is sutured with 5-0 PDS, and the mouse is allowed to wake up on a heating pad. From our experience, depending on the cell line, treatment can take place from 7-10 days after surgery. Drug delivery is dependent on the drug composition. For radiation treatment the mice are anesthetized, and put into a custom made jig. Lead covers the mouse's body and exposes only the brain of the mouse. The study of tumorigenesis and the evaluation of new therapies for GBM require accurate and reproducible brain tumor animal models. Thus we use this orthotopic brain model to study the interaction of the microenvironment of the brain and the tumor, to test the effectiveness of different therapeutic agents with and without

  10. Radiation Dose Uncertainty and Correction for a Mouse Orthotopic and Xenograft Irradiation Model

    PubMed Central

    Gan, Gregory N.; Altunbas, Cem; Morton, John J.; Eagles, Justin; Backus, Jennifer; Dzingle, Wayne; Raben, David; Jimeno, Antonio

    2016-01-01

    Purpose In animal irradiation models, reported dose can vary significantly from the actual doses delivered. We describe an effective method for in vivo dose verification. Materials and Methods Mice bearing commercially-available cell line or patient-derived tumor cell orthotopic or flank xenografts were irradiated using a 160 kVp, 25 mA X-ray source. Entrance dose was evaluated using optically-stimulated luminescence dosimeters (OSLD) and exit dose was assessed using radiochromic film dosimetry. Results Tumor position within the irradiation field was validated using external fiducial markers. The average entrance dose in orthotopic tumors from 10 OSLDs placed on 2 different animal irradiation days was 514±37 cGy (range: 437–545). Exit dose measurements taken from 7 radiochromic films on two separate days were 341±21 cGy (a 34% attenuation). Flank tumor irradiation doses measured by OSLD were 368±9 cGy compared to exit doses of 330 cGy measured by radiochromic film. Conclusion Variations related to the irradiation model can lead to significant under or over- dosing in vivo which can affect tumor control and/or biologic endpoints that are dose dependent. We recommend that dose measurements be determined empirically based on the mouse model and irradiator used and dose compensation adjustments performed to ensure correct and appropriate doses. PMID:26689828

  11. Radiation dose uncertainty and correction for a mouse orthotopic and xenograft irradiation model.

    PubMed

    Gan, Gregory N; Altunbas, Cem; Morton, John J; Eagles, Justin; Backus, Jennifer; Dzingle, Wayne; Raben, David; Jimeno, Antonio

    2016-01-01

    In animal irradiation models, reported dose can vary significantly from the actual doses delivered. We describe an effective method for in vivo dose verification. Mice bearing commercially-available cell line or patient-derived tumor cell orthotopic or flank xenografts were irradiated using a 160 kVp, 25 mA X-ray source. Entrance dose was evaluated using optically-stimulated luminescence dosimeters (OSLD) and exit dose was assessed using radiochromic film dosimetry. Tumor position within the irradiation field was validated using external fiducial markers. The average entrance dose in orthotopic tumors from 10 OSLDs placed on two different animal irradiation days was 514 ± 37 cGy (range: 437-545). Exit dose measurements taken from seven radiochromic films on two separate days were 341 ± 21 cGy (a 34% attenuation). Flank tumor irradiation doses measured by OSLD were 368 ± 9 cGy compared to exit doses of 330 cGy measured by radiochromic film. Variations related to the irradiation model can lead to significant under or overdosing in vivo which can affect tumor control and/or biologic endpoints that are dose-dependent. We recommend that dose measurements be determined empirically based on the mouse model and irradiator used and dose compensation adjustments performed to ensure correct and appropriate doses.

  12. [Highly metastatic nude mouse model of human primary gastric lymphoma constructed by surgical orthotopic transplantation and in vivo continuous screening method].

    PubMed

    Yang, Bo; Tuo, Shuai; Tuo, Chao-wei; Zhang, Ning; Liu, Qiu-zhen

    2010-02-09

    To develop a series of high metastatic models of human gastric malignant lymphoma in nude mice by orthotopic transplantation. Two histologically intact primary and hepatic metastatic fragments derived from surgical specimen of a patient with primary gastric lymphoma were implanted into the submucosa of stomach in nude mice. Highly metastatic and specific organ metastatic models were screened by selective orthotopic passage in nude mice. Transplantability, invasion, metastasis, morphological characteristics (light microscopy, electron microscopy and immunohistochemistry), karyotypic analysis and DNA content of orthotopically transplanted tumors were studied. Primary and hepatic metastatic fragments of primary gastric lymphoma were successfully transplanted in nude mice. Two nude mouse models of human primary gastric lymphoma, termed HGBL-0304 (hepatic metastasis model) and HGBL-0305 (high metastasis model), were developed, exhibiting different metastasis biology. Histopathology of transplanted tumors showed primary gastric diffuse large B cell lymphoma. Two models have been maintained for 45 generations by orthotopic passage in nude mice. A total of 419 nude mice were used for transplantation. The growth rate and resuscitation rate of liquid nitrogen cryopreservation of transplanted tumors were both 100%. Significant difference in metastasis biology was exhibited in four aspects of metastasis time, organ metastatic rate, the extent of hepatic metastasis and survival of cancer-bearing mice. The metastatic rates of liver, spleen, lymph nodes and peritoneal seeding in HGBL-0304 and HGBL-0305 models were 100% and 69.5%, 94.3% and 55.6%, 62.6% and 45.7%, and 43.5% and 30.5%. The onset time for metastases of liver, spleen, lymph nodes and peritoneal seeding was 2 w and 5 w, 3 w and 6 w, 2 w and 3 w, 3 w and 6 w respectively. The extent of hepatic metastasis in HGBL-0304 and HGBL-0305 models displayed diffuse involvement of the whole liver and mainly right lobe invasion of

  13. Multi-Modal Imaging in a Mouse Model of Orthotopic Lung Cancer.

    PubMed

    Patel, Priya; Kato, Tatsuya; Ujiie, Hideki; Wada, Hironobu; Lee, Daiyoon; Hu, Hsin-Pei; Hirohashi, Kentaro; Ahn, Jin Young; Zheng, Jinzi; Yasufuku, Kazuhiro

    2016-01-01

    Investigation of CF800, a novel PEGylated nano-liposomal imaging agent containing indocyanine green (ICG) and iohexol, for real-time near infrared (NIR) fluorescence and computed tomography (CT) image-guided surgery in an orthotopic lung cancer model in nude mice. CF800 was intravenously administered into 13 mice bearing the H460 orthotopic human lung cancer. At 48 h post-injection (peak imaging agent accumulation time point), ex vivo NIR and CT imaging was performed. A clinical NIR imaging system (SPY®, Novadaq) was used to measure fluorescence intensity of tumor and lung. Tumor-to-background-ratios (TBR) were calculated in inflated and deflated states. The mean Hounsfield unit (HU) of lung tumor was quantified using the CT data set and a semi-automated threshold-based method. Histological evaluation using H&E, the macrophage marker F4/80 and the endothelial cell marker CD31, was performed, and compared to the liposomal fluorescence signal obtained from adjacent tissue sections. The fluorescence TBR measured when the lung is in the inflated state (2.0 ± 0.58) was significantly greater than in the deflated state (1.42 ± 0.380 (n = 7, p<0.003). Mean fluorescent signal in tumor was highly variable across samples, (49.0 ± 18.8 AU). CT image analysis revealed greater contrast enhancement in lung tumors (a mean increase of 110 ± 57 HU) when CF800 is administered compared to the no contrast enhanced tumors (p = 0.0002). Preliminary data suggests that the high fluorescence TBR and CT tumor contrast enhancement provided by CF800 may have clinical utility in localization of lung cancer during CT and NIR image-guided surgery.

  14. Biological intervertebral disc replacement: an in vivo model and comparison of two surgical techniques to approach the rat caudal disc

    PubMed Central

    Gebhard, Harry; James, Andrew R.; Bowles, Robby D.; Dyke, Jonathan P.; Saleh, Tatianna; Doty, Stephen P.; Bonassar, Lawrence J.; Härtl, Roger

    2011-01-01

    Study design: Prospective randomized animal study. Objective: To determine a surgical technique for reproducible and functional intervertebral disc replacement in an orthotopic animal model. Methods: The caudal 3/4 intervertebral disc (IVD) of the rat tail was approached by two surgical techniques: blunt dissection, stripping and retracting (Technique 1) or incising and repairing (Technique 2) the dorsal longitudinal tendons. The intervertebral disc was dissected and removed, and then either discarded or reinserted. Outcome measures were perioperative complications, spontaneous tail movement, 7T MRI (T1- and T2-sequences for measurement of disc space height (DSH) and disc hydration). Microcomputed tomographic imaging (micro CT) was additionally performed postmortem. Results: No vascular injuries occurred and no systemic or local infections were observed over the course of 1 month. Tail movements were maintained. With tendon retraction (Technique 1) gross loss of DSH occurred with both discectomy and reinsertion. Tendon division (Technique 2) maintained DSH with IVD reinsertion but not without. The DSH was demonstrated on MRI measurement. A new scoring system to assess IVD appearances was described. Conclusions: The rat tail model, with a tendon dividing surgical technique, can function as an orthotopic animal model for IVD research. Mechanical stimulation is maintained by preserved tail movements. 7T MRI is a feasible modality for longitudinal monitoring for the rat caudal disc. PMID:22956934

  15. Pregnancy after orthotopic continent urinary diversion.

    PubMed

    Kennedy, W A; Hensle, T W; Reiley, E A; Fox, H E; Haus, T

    1993-10-01

    Continent urinary diversion has become a common form of bladder management for the female exstrophy patient in whom primary reconstruction has failed. Reported are the results of successful pregnancies in four young adult females, who had previously undergone a flap vaginoplasty as part of earlier management and more recently a continent right colonic urinary reservoir with a perineal stoma (Indiana pouch). Pregnancy in each of these patients was characterized by several urinary tract infections, cervical prolapse and mild to severe maternal hydronephrosis. All of the patients had some degree of difficulty with clean intermittent catheterization. One patient required an indwelling catheter with prolonged bed rest. Maternal hydronephrosis resolved after delivery in all instances. All four patients delivered their infants by way of cesarean section, either emergently for maternal or fetal distress or electively. Cervical prolapse did not resolve in three patients and will require surgical repair. After delivery, all patients returned to their previous pattern of clean intermittent catheterization without loss of continence. All the infants delivered were healthy with appropriate weights and high Apgar scores (more than 8). Orthotopic (perineal stoma) continent urinary diversion is not a contraindication to pregnancy. However, our experience mandates delivery by cesarean section with close monitoring for maternal or fetal distress during gestation.

  16. A deimmunized bispecific ligand directed toxin that shows an impressive anti-pancreatic cancer effect in a systemic nude mouse orthotopic model

    PubMed Central

    Oh, Seunguk; Todhunter, Deborah A.; Panoskaltsis-Mortari, Angela; Buchsbaum, Donald J.; Toma, Shoko; Vallera, Daniel A.

    2011-01-01

    Objective The objective was to test a bispecific ligand directed toxin (BLT), with reduced immunogenicity for enhanced efficacy in targeting orthotopic pancreatic cancer in vivo. Method A new BLT was created in which both human EGF and IL-4 cytokines were cloned onto the same single chain molecule with deimmunized pseudomonas exotoxin (dEGF4KDEL). Key amino acids dictating B cell generation of neutralizing anti-toxin antibodies were mutated. Bioassays were used to determine whether mutation reduced potency, and ELISA studies were performed to determine whether anti-toxin antibodies were reduced. A genetically altered luciferase MIA PaCa-2 xenograft model was used to image in real time and determine affects on systemic malignant human cancer. BLTs targeting B cells were used as specificity controls. Results dEGF4KDEL was significantly effective following systemic injection against established orthotopic MIA PaCa-2 pancreatic cancer and selectively prevented metastasis. Mutagenesis significantly reduced anti-toxin levels in vivo with no apparent activity loss in vitro. The drug was effective against three human pancreatic cancer lines in vitro, MIA PaCa-2, SW1990, and S2VP10. Conclusions Despite the metastatic nature of the MIA PaCa-2 orthotopic tumor xenografted in nude mice, high percentages of tumors responded to extended dEGFKDEL treatment resulting in significant anti-cancer effects and disease-free survivors. PMID:22258068

  17. Orthotopic xenografts of RCC retain histological, immunophenotypic and genetic features of tumors in patients

    PubMed Central

    Grisanzio, Chiara; Seeley, Apryle; Chang, Michelle; Collins, Michael; Di Napoli, Arianna; Cheng, Su-Chun; Percy, Andrew; Beroukhim, Rameen; Signoretti, Sabina

    2013-01-01

    Renal cell carcinoma (RCC) is an aggressive malignancy with limited responsiveness to existing treatments. In vivo models of human cancer, including RCC, are critical for developing more effective therapies. Unfortunately, current RCC models do not accurately represent relevant properties of the human disease. The goal of this study was to develop clinically relevant animal models of RCC for preclinical investigations. We transplanted intact human tumor tissue fragments orthotopically in immunodeficient mice. The xenografts were validated by comparing the morphologic, phenotypic, and genetic characteristics of the kidney tumor tissues before and after implantation. Twenty kidney tumors were transplanted into mice. Successful tumor growth was detected in 19 cases (95%). The histopathologic and immunophenotypic features of the xenografts and those of the original tumors largely overlapped in all the cases. Evaluation of genetic alterations in a subset of 10 cases demonstrated that the grafts largely retained the genetic features of the pre-implantation RCC tissues. Indeed, primary tumors and corresponding grafts displayed identical VHL mutations. Moreover, an identical pattern of DNA copy amplification or loss was observed in 6 of 10 cases (60%). In summary, orthotopic engrafting of RCC tissue fragments can be successfully used to generate animal models that closely resemble RCC in patients. These models will be invaluable for in vivo preclinical drug testing, and for deeper understanding of kidney carcinogenesis. PMID:21710693

  18. Multi-Modal Imaging in a Mouse Model of Orthotopic Lung Cancer

    PubMed Central

    Patel, Priya; Kato, Tatsuya; Ujiie, Hideki; Wada, Hironobu; Lee, Daiyoon; Hu, Hsin-pei; Hirohashi, Kentaro; Ahn, Jin Young; Zheng, Jinzi; Yasufuku, Kazuhiro

    2016-01-01

    Background Investigation of CF800, a novel PEGylated nano-liposomal imaging agent containing indocyanine green (ICG) and iohexol, for real-time near infrared (NIR) fluorescence and computed tomography (CT) image-guided surgery in an orthotopic lung cancer model in nude mice. Methods CF800 was intravenously administered into 13 mice bearing the H460 orthotopic human lung cancer. At 48 h post-injection (peak imaging agent accumulation time point), ex vivo NIR and CT imaging was performed. A clinical NIR imaging system (SPY®, Novadaq) was used to measure fluorescence intensity of tumor and lung. Tumor-to-background-ratios (TBR) were calculated in inflated and deflated states. The mean Hounsfield unit (HU) of lung tumor was quantified using the CT data set and a semi-automated threshold-based method. Histological evaluation using H&E, the macrophage marker F4/80 and the endothelial cell marker CD31, was performed, and compared to the liposomal fluorescence signal obtained from adjacent tissue sections Results The fluorescence TBR measured when the lung is in the inflated state (2.0 ± 0.58) was significantly greater than in the deflated state (1.42 ± 0.380 (n = 7, p<0.003). Mean fluorescent signal in tumor was highly variable across samples, (49.0 ± 18.8 AU). CT image analysis revealed greater contrast enhancement in lung tumors (a mean increase of 110 ± 57 HU) when CF800 is administered compared to the no contrast enhanced tumors (p = 0.0002). Conclusion Preliminary data suggests that the high fluorescence TBR and CT tumor contrast enhancement provided by CF800 may have clinical utility in localization of lung cancer during CT and NIR image-guided surgery. PMID:27584018

  19. A novel method for RNA extraction from FFPE samples reveals significant differences in biomarker expression between orthotopic and subcutaneous pancreatic cancer patient-derived xenografts.

    PubMed

    Hoover, Malachia; Adamian, Yvess; Brown, Mark; Maawy, Ali; Chang, Alexander; Lee, Jacqueline; Gharibi, Armen; Katz, Matthew H; Fleming, Jason; Hoffman, Robert M; Bouvet, Michael; Doebler, Robert; Kelber, Jonathan A

    2017-01-24

    Next-generation sequencing (NGS) can identify and validate new biomarkers of cancer onset, progression and therapy resistance. Substantial archives of formalin-fixed, paraffin-embedded (FFPE) cancer samples from patients represent a rich resource for linking molecular signatures to clinical data. However, performing NGS on FFPE samples is limited by poor RNA purification methods. To address this hurdle, we developed an improved methodology for extracting high-quality RNA from FFPE samples. By briefly integrating a newly-designed micro-homogenizing (mH) tool with commercially available FFPE RNA extraction protocols, RNA recovery is increased by approximately 3-fold while maintaining standard A260/A280 ratios and RNA quality index (RQI) values. Furthermore, we demonstrate that the mH-purified FFPE RNAs are longer and of higher integrity. Previous studies have suggested that pancreatic ductal adenocarcinoma (PDAC) gene expression signatures vary significantly under in vitro versus in vivo and in vivo subcutaneous versus orthotopic conditions. By using our improved mH-based method, we were able to preserve established expression patterns of KRas-dependency genes within these three unique microenvironments. Finally, expression analysis of novel biomarkers in KRas mutant PDAC samples revealed that PEAK1 decreases and MST1R increases by over 100-fold in orthotopic versus subcutaneous microenvironments. Interestingly, however, only PEAK1 levels remain elevated in orthotopically grown KRas wild-type PDAC cells. These results demonstrate the critical nature of the orthotopic tumor microenvironment when evaluating the clinical relevance of new biomarkers in cells or patient-derived samples. Furthermore, this new mH-based FFPE RNA extraction method has the potential to enhance and expand future FFPE-RNA-NGS cancer biomarker studies.

  20. A New Cone-Shaped Aortic Valve Prosthesis for Orthotopic Position: An Experimental Study in Swine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sochman, Jan, E-mail: jan.sochman@medicon.c; Peregrin, Jan H.; Pulda, Zdenek

    The aim of this experimental study was to evaluate a newly designed cone-shaped aortic valve prosthesis (CAVP) for one-step transcatheter placement in an orthotopic position. The study was conducted in 15 swine using either the transcarotid (11 animals) or the transfemoral (4 animals) artery approach. A 12- or 13-Fr sheath was inserted via arterial cutdown. The CAVP was deployed under fluoroscopic control and its struts, by design, induced significant native valve insufficiency. CAVP function was evaluated by aortography and aortic pressure curve tracing. In 11 of 15 swine the CAVP was properly deployed and functioned well throughout the scheduled periodmore » of 2-3 h. In three swine the CAVPs were placed lower than intended, however, they were functional even in the left ventricular outflow tract position. One swine expired due to inadvertent low CAVP placement that caused both aortic regurgitation and immobilization of the anterior mitral valve leaflet by the valve struts. We conclude that this design of CAVP is relatively easy to deploy, works well throughout a short time period (2-3 h), and, moreover, seems to be reliable even in a lower-than-orthotopic position (e.g., infra-annulary space). Longer-term studies are needed for its further evaluation.« less

  1. Welfare Assessment following Heterotopic or Orthotopic Inoculation of Bladder Cancer in C57BL/6 Mice.

    PubMed

    Miller, Amy; Burson, Hannah; Söling, Ariane; Roughan, Johnny

    2016-01-01

    Few studies have assessed whether mice used as cancer models experience pain. Despite this possibility, the usual practice is to withhold analgesics as these are generally viewed as confounding. However, pain also alters cancer progression, so preventing it might not only be beneficial to welfare but also to study validity. Establishing the extent to which different cancer models result in pain is an important first step towards their refinement. We used conditioned place preference (CPP) testing and body-weight and behaviour analyses to evaluate the assumption that heterotopically implanted tumours result in less pain and fewer welfare concerns than those implanted orthotopically. C57Bl/6 mice received MB49Luc luciferase expressing bladder cancer cells or saline implanted subcutaneously or into the bladder. These tumour-bearing or control groups underwent 2 daily 45 minute conditioning trials to saline or morphine (2mg/kg) and then a 15 minute drug-free preference test on day 3 of a 3 day cycle, continuing until the study ended. Tumours were imaged and behaviour data obtained following preference tests. Development of preference for the morphine-paired chamber (morphine-seeking) was determined over time. Heterotopic tumour development had no effect on morphine-seeking, and although the restraint used for heterotopic inoculation caused greater initial weight losses than anaesthesia, these mice steadily gained weight and behaved comparatively normally throughout the study. Orthotopic tumour inoculation caused no initial weight losses, but over the final 7 days these mice became less active and lost more body weight than cancer-free controls. This indicated orthotopic implantation probably caused a more negative impact on welfare or conceivably pain; but only according to the current test methods. Pain could not be confirmed because morphine-seeking in the tumour-bearing groups was similar to that seen in controls. Imaging was not found to be an effective method of

  2. Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction.

    PubMed

    Iglesias, Jose; Frank, Elliot; Mehandru, Sushil; Davis, John M; Levine, Jerrold S

    2013-07-13

    Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction.

  3. Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction

    PubMed Central

    2013-01-01

    Background Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Methods Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Results Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. Conclusion These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction. PMID:23849513

  4. Using Dual Fluorescence Reporting Genes to Establish an In Vivo Imaging Model of Orthotopic Lung Adenocarcinoma in Mice.

    PubMed

    Lai, Cheng-Wei; Chen, Hsiao-Ling; Yen, Chih-Ching; Wang, Jiun-Long; Yang, Shang-Hsun; Chen, Chuan-Mu

    2016-12-01

    Lung adenocarcinoma is characterized by a poor prognosis and high mortality worldwide. In this study, we purposed to use the live imaging techniques and a reporter gene that generates highly penetrative near-infrared (NIR) fluorescence to establish a preclinical animal model that allows in vivo monitoring of lung cancer development and provides a non-invasive tool for the research on lung cancer pathogenesis and therapeutic efficacy. A human lung adenocarcinoma cell line (A549), which stably expressed the dual fluorescence reporting gene (pCAG-iRFP-2A-Venus), was used to generate subcutaneous or orthotopic lung cancer in nude mice. Cancer development was evaluated by live imaging via the NIR fluorescent signals from iRFP, and the signals were verified ex vivo by the green fluorescence of Venus from the gross lung. The tumor-bearing mice received miR-16 nucleic acid therapy by intranasal administration to demonstrate therapeutic efficacy in this live imaging system. For the subcutaneous xenografts, the detection of iRFP fluorescent signals revealed delicate changes occurring during tumor growth that are not distinguishable by conventional methods of tumor measurement. For the orthotopic xenografts, the positive correlation between the in vivo iRFP signal from mice chests and the ex vivo green fluorescent signal from gross lung tumors and the results of the suppressed tumorigenesis by miR-16 treatment indicated that lung tumor size can be accurately quantified by the emission of NIR fluorescence. In addition, orthotopic lung tumor localization can be accurately visualized using iRFP fluorescence tomography in vivo, thus revealing the trafficking of lung tumor cells. We introduced a novel dual fluorescence lung cancer model that provides a non-invasive option for preclinical research via the use of NIR fluorescence in live imaging of lung.

  5. Liver Stiffness Measurements Using Acoustic Radiation Force Impulse in Recipients of Living-Donor and Deceased-Donor Orthotopic Liver Transplant.

    PubMed

    Haberal, Kemal Murat; Turnaoğlu, Hale; Özdemir, Adnan; Uslu, Nihal; Haberal Reyhan, Asuman Nihan; Moray, Gökhan; Haberal, Mehmet

    2017-08-24

    The aim of this study was to evaluate the diagnostic efficiency of the acoustic radiation force impulse (Siemens Medical Solutions, Erlangen, Germany) elastography in assessment of fibrosis in orthotopic liver transplant patients. We enrolled 28 orthotopic liver transplant patients (deceased and living donors), whose biopsy decision had been prospectively given clinically. Ten acoustic radiation force impulse elastographic measurements were applied before the biopsy or within 3 days after the biopsy by 2 radiologists. After the core tissue needle biopsy, specimens of all patients were analyzed according to the modified Ishak scoring system. Measurements of acoustic radiation force impulse elastography and pathology specimen results were compared. From 28 biopsies, fibrosis scores of 4 biopsies were evaluated as F0 (14.3%), 16 as F1 (57.1%), 4 as F2 (14.3%), and 4 as F3 (14.3%). Mean results of acoustic radiation force impulse measurements were calculated as 1.4 ± 0.07 in F0, 1.74 ± 0.57 in F1, 2.19 ± 0.7 in F2, and 2.18 ± 0.35 in F3. There were no significant correlations of mean acoustic radiation force impulse values between the F0 versus F1 (P = .956) and F0 versus F2 stages (P = .234). A statistically significant correlation of mean acoustic radiation force impulse values was found between the F0 and F3 fibrosis stages (P = .046). Acoustic radiation force impulse imaging is a promising screening test for detecting significant liver fibrosis (≥ F3 in modified Ishak) in living-donor or deceased-donor orthotopic liver transplant recipients.

  6. Development of a novel preclinical pancreatic cancer research model: bioluminescence image-guided focal irradiation and tumor monitoring of orthotopic xenografts.

    PubMed

    Tuli, Richard; Surmak, Andrew; Reyes, Juvenal; Hacker-Prietz, Amy; Armour, Michael; Leubner, Ashley; Blackford, Amanda; Tryggestad, Erik; Jaffee, Elizabeth M; Wong, John; Deweese, Theodore L; Herman, Joseph M

    2012-04-01

    We report on a novel preclinical pancreatic cancer research model that uses bioluminescence imaging (BLI)-guided irradiation of orthotopic xenograft tumors, sparing of surrounding normal tissues, and quantitative, noninvasive longitudinal assessment of treatment response. Luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were orthotopically injected in nude mice. BLI was compared to pathologic tumor volume, and photon emission was assessed over time. BLI was correlated to positron emission tomography (PET)/computed tomography (CT) to estimate tumor dimensions. BLI and cone-beam CT (CBCT) were used to compare tumor centroid location and estimate setup error. BLI and CBCT fusion was performed to guide irradiation of tumors using the small animal radiation research platform (SARRP). DNA damage was assessed by γ-H2Ax staining. BLI was used to longitudinally monitor treatment response. Bioluminescence predicted tumor volume (R = 0.8984) and increased linearly as a function of time up to a 10-fold increase in tumor burden. BLI correlated with PET/CT and necropsy specimen in size (P < .05). Two-dimensional BLI centroid accuracy was 3.5 mm relative to CBCT. BLI-guided irradiated pancreatic tumors stained positively for γ-H2Ax, whereas surrounding normal tissues were spared. Longitudinal assessment of irradiated tumors with BLI revealed significant tumor growth delay of 20 days relative to controls. We have successfully applied the SARRP to a bioluminescent, orthotopic preclinical pancreas cancer model to noninvasively: 1) allow the identification of tumor burden before therapy, 2) facilitate image-guided focal radiation therapy, and 3) allow normalization of tumor burden and longitudinal assessment of treatment response.

  7. Analysis of Stroma Labeling During Multiple Passage of a Sarcoma Imageable Patient-Derived Orthotopic Xenograft (iPDOX) in Red Fluorescent Protein Transgenic Nude Mice.

    PubMed

    Kiyuna, Tasuku; Murakami, Takashi; Tome, Yasunori; Kawaguchi, Kei; Igarashi, Kentaro; Miyake, Kentaro; Kanaya, Fuminori; Singh, Arun; Eilber, Fritz C; Hoffman, Robert M

    2017-10-01

    A patient-derived orthotopic xenograft (PDOX) model of undifferentiated pleomorphic sarcoma (UPS) was previously established that acquired red fluorescent protein (RFP)-expressing stroma by growth in an RFP transgenic nude mouse. In the present study, an imageable PDOX model (iPDOX) of UPS was established by orthotopic implantation in the biceps femoris of transgenic RFP nude mice. After the tumors grew to a diameter of 10 mm, they were harvested and the brightest portion of the tumors were subsequently orthotopically transplanted to both RFP and non-colored nude mice. The UPS PDOX tumor was again transplanted to RFP transgenic and non-colored nude mice, and finally a 3rd passage was made in the same manner. Five UPS tumors from each passage in both RFP and non-colored mouse models were harvested. The FV1,000 confocal microscope was used to visualize and quantitate the RFP area of the resected tumors. The average percent fluorescent area in the first passage of RFP mice was 34 ± 22%; in the second passage, 34 ± 20%; and 36 ± 11% in the third passage of RFP transgenic nude mice. The average tumor RFP area in the first passage from RFP mice to non-colored mice was 20 ± 7%; in the second passage, 28 ± 11%; in the third passage was 27 ± 13%. The present results demonstrate the extensive and stable acquisition of stroma by the UPS-tumor growing orthotopically in transgenic RFP nude mice (iPDOX). This model can be used for screening for effective drugs for individual patients and drug discovery. J. Cell. Biochem. 118: 3367-3371, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Orthotopic model of canine osteosarcoma in athymic rats for evaluation of stereotactic radiotherapy.

    PubMed

    Schwartz, Anthony L; Custis, James T; Harmon, Joseph F; Powers, Barbara E; Chubb, Laura S; LaRue, Susan M; Ehrhart, Nicole P; Ryan, Stewart D

    2013-03-01

    To develop an orthotopic model of canine osteosarcoma in athymic rats as a model for evaluating the effects of stereotactic radiotherapy (SRT) on osteosarcoma cells. 26 athymic nude rats. 3 experiments were performed. In the first 2 experiments, rats were injected with 1 × 10(6) Abrams canine osteosarcoma cells into the proximal aspect of the tibia (n = 12) or distal aspect of the femur (6). Tumor engraftment and progression were monitored weekly via radiography, luciferase imaging, and measurement of urine pyridinoline concentration for 5 weeks and histologic evaluation after euthanasia. In the third experiment, 8 rats underwent canine osteosarcoma cell injection into the distal aspect of the femur and SRT was administered to the affected area in three 12-Gy fractions delivered on consecutive days (total radiation dose, 36 Gy). Percentage tumor necrosis and urinary pyridinoline concentrations were used to assess local tumor control. The short-term effect of SRT on skin was also evaluated. Tumors developed in 10 of 12 tibial sites and all 14 femoral sites. Administration of SRT to rats with femoral osteosarcoma was feasible and successful. Mean tumor necrosis of 95% was achieved histologically, and minimal adverse skin effects were observed. The orthotopic model of canine osteosarcoma in rats developed in this study was suitable for evaluating the effects of local tumor control and can be used in future studies to evaluate optimization of SRT duration, dose, and fractionation schemes. The model could also allow evaluation of other treatments in combination with SRT, such as chemotherapy or bisphosphonate, radioprotectant, or parathyroid hormone treatment.

  9. Virotherapy of the Malignant U87 Human Glioblastoma in the Orthotopic Xenotransplantation Mouse SCID Model.

    PubMed

    Shchelkunov, S N; Razumov, I A; Kolosova, I V; Romashchenko, A V; Zavjalov, E L

    2018-01-01

    The possibility of glioblastoma virotherapy at intravenous injection of the LIVP-GFP recombinant virus was studied in experimental model of orthotopic xenotransplantation of human glioblastoma cell line U87 to SCID laboratory mice. The LIVP-GFP recombinant virus deficient for thymidine kinase exhibited a significantly greater oncolytic capacity than the original LIVP virus, and an intravenous injection of LIVP-GFP at the early stages of tumorigenesis in mouse brain in most cases resulted in the lysis of the tumor.

  10. Successful Pregnancies in Two Orthotopic Liver Transplant (OLT) Recipients in Iran; Two Case Reports.

    PubMed

    Zahra, Tayebi; Seyyed Alireza, Taqhavi; Shirin, Shahbazi

    2009-10-01

    Pregnancy and parenting have been part of human life throughout history and liver transplant recipients are not any exception. This paper reports successful pregnancies in two liver transplant recipients in Iran. The first case was a 34-year old woman who had undergone orthotopic liver transplantation (OLT) at Shiraz Namazi Educational Hospital in 2002. She decided to get pregnant seven years after the operation. During pregnancy, immunosuppressive therapy continued, except Mycophenolate Mofetil which has an absolute contra-indication in pregnancy. The patient was followed up during pregnancy by the transplant team as well as a gynecologist. She faced no significant complications and the liver function was stable during pregnancy. She later underwent a Cesarean section in the 38(th) week of gestation and the newborn was a healthy girl weighing 2480g with an Apgar score of 8 at the time of birth. There were no evidences of prematurity or structural abnormalities in the newborn. The second case was a 31-year old primipara who had received an orthotopic liver transplant (OLT) in Shiraz in 2002. She had a smooth pregnancy without any complications and the newborn was a boy weighing 3100g with Apgar scores of 8 and 10 at the time of birth and 5 minutes thereafter, respectively. As the number of transplant recipients is growing along with the number of recipients who are in their fertility years, it is vital to ensure a proper medical care by a coordinated multidisciplinary team during pregnancy.

  11. Percutaneous Transluminal Angioplasty of Hepatic Artery Stenosis in Patients After Orthotopic Liver Transplantation: Mid-term Results

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jarmila, Lastovickova, E-mail: jala@ikem.cz; Jan, Peregrin

    2011-12-15

    Purpose: This study was designed to present our experience with percutaneous treatment of hepatic artery stenosis in orthotopic liver transplant patients and to evaluate the efficacy, technical outcomes, and mid-term clinical results of the procedure. Methods: Twenty-two percutaneous transluminal angioplasties (PTAs) were performed in 19 liver transplant recipients at our institution between 1998 and 2010. Stents were placed into the hepatic/celiac artery in 16 PTAs, but balloon dilatation alone was performed in 6 because of the anatomical condition of the vessel. PTA/stenting was indicated in 17 patients because of elevated liver enzymes; 2 patients were asymptomatic. The objective of treatingmore » stenosis was prevention of long-term complications, including thrombosis. Results: Technical success was achieved in all patients. There was only one complication: dissection of the treated artery without any subsequent adverse effects. In all patients, elevated liver enzyme levels improved after treatment. No restenosis was observed in any patient during a mean follow-up of 2.6 years (1 month to 5.5 years). Conclusions: Percutaneous angioplasty/stent placement is a safe method for the treatment of hepatic artery stenosis after orthotopic liver transplantation, with a high technical success rate and promising mid-term results.« less

  12. Dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation in humans

    PubMed Central

    Weng, Xiao-chuan; Zhou, Liang; Fu, Yin-yan; Zhu, Sheng-mei; He, Hui-liang; Wu, Jian

    2005-01-01

    Objective: To compare the dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation (OLT) in humans. Methods: Twenty male patients undergoing liver transplantation were randomly assigned to two comparable groups of 10 patients each to receive a continuous infusion of rocuronium or atracurium under intravenous balanced anesthesia. The response of adductor pollicis to train-of-four (TOF) stimulation of unlar nerve was monitored. The infusion rates of rocuronium and atracurium were adjusted to maintain T1/Tc ratio of 2%~10%. The total dose of each drug given during each of the three phases of OLT was recorded. Results: Rocuronium requirement, which were (0.468±0.167) mg/(kg·h) during the paleohepatic phase, decreased significantly during the anhepatic phase to (0.303±0.134) mg/(kg·h) and returned to the initial values at the neohepatic period ((0.429±0.130) mg/(kg·h)); whereas atracuruim requirements remained unchanged during orthotopic liver transplantation. Conclusions: This study showed that the exclusion of the liver from the circulation results in the significantly reduced requirement of rocuronium while the requirement of atracurium was not changed, which suggests that the liver is of major importance in the clearance of rocuronium. A continuous infusion of atracurium with constant rate can provide stable neuromuscular blockade during the three stages of OLT. PMID:16130187

  13. Robotic radical cystectomy and intracorporeal urinary diversion: The USC technique.

    PubMed

    Abreu, Andre Luis de Castro; Chopra, Sameer; Azhar, Raed A; Berger, Andre K; Miranda, Gus; Cai, Jie; Gill, Inderbir S; Aron, Monish; Desai, Mihir M

    2014-07-01

    Radical cystectomy is the gold-standard treatment for muscle-invasive and refractory nonmuscle-invasive bladder cancer. We describe our technique for robotic radical cystectomy (RRC) and intracorporeal urinary diversion (ICUD), that replicates open surgical principles, and present our preliminary results. Specific descriptions for preoperative planning, surgical technique, and postoperative care are provided. Demographics, perioperative and 30-day complications data were collected prospectively and retrospectively analyzed. Learning curve trends were analyzed individually for ileal conduits (IC) and neobladders (NB). SAS(®) Software Version 9.3 was used for statistical analyses with statistical significance set at P < 0.05. Between July 2010 and September 2013, RRC and lymph node dissection with ICUD were performed in 103 consecutive patients (orthotopic NB=46, IC 57). All procedures were completed robotically replicating the open surgical principles. The learning curve trends showed a significant reduction in hospital stay for both IC (11 vs. 6-day, P < 0.01) and orthotopic NB (13 vs. 7.5-day, P < 0.01) when comparing the first third of the cohort with the rest of the group. Overall median (range) operative time and estimated blood loss was 7 h (4.8-13) and 200 mL (50-1200), respectively. Within 30-day postoperatively, complications occurred in 61 (59%) patients, with the majority being low grade (n = 43), and no patient died. Median (range) nodes yield was 36 (0-106) and 4 (3.9%) specimens had positive surgical margins. Robotic radical cystectomy with totally ICUD is safe and feasible. It can be performed using the established open surgical principles with encouraging perioperative outcomes.

  14. Orthotopic mouse models for the preclinical and translational study of targeted therapies against metastatic human thyroid carcinoma with BRAFV600E or wild-type BRAF

    PubMed Central

    Antonello, ZA; Nucera, C

    2015-01-01

    Molecular signature of advanced and metastatic thyroid carcinoma involves deregulation of multiple fundamental pathways activated in the tumor microenvironment. They include BRAFV600E and AKT that affect tumor initiation, progression and metastasis. Human thyroid cancer orthotopic mouse models are based on human cell lines that generally harbor genetic alterations found in human thyroid cancers. They can reproduce in vivo and in situ (into the thyroid) many features of aggressive and refractory human advanced thyroid carcinomas, including local invasion and metastasis. Humanized orthotopic mouse models seem to be ideal and commonly used for preclinical and translational studies of compounds and therapies not only because they may mimic key aspects of human diseases (e.g. metastasis), but also for their reproducibility. In addition, they might provide the possibility to evaluate systemic effects of treatments. So far, human thyroid cancer in vivo models were mainly used to test single compounds, non selective and selective. Despite the greater antitumor activity and lower toxicity obtained with different selective drugs in respect to non-selective ones, most of them are only able to delay disease progression, which ultimately could restart with similar aggressive behavior. Aggressive thyroid tumors (for example, anaplastic or poorly differentiated thyroid carcinoma) carry several complex genetic alterations that are likely cooperating to promote disease progression and might confer resistance to single-compound approaches. Orthotopic models of human thyroid cancer also hold the potential to be good models for testing novel combinatorial therapies. In this article, we will summarize results on preclinical testing of selective and nonselective single compounds in orthotopic mouse models based on validated human thyroid cancer cell lines harboring the BRAFV600E mutation or with wild-type BRAF. Furthermore, we will discuss the potential use of this model also for

  15. Efficacy of PARP inhibitor rucaparib in orthotopic glioblastoma xenografts is limited by ineffective drug penetration into the central nervous system

    PubMed Central

    Parrish, Karen E.; Cen, Ling; Murray, James; Calligaris, David; Kizilbash, Sani; Mittapalli, Rajendar K.; Carlson, Brett L.; Schroeder, Mark A.; Sludden, Julieann; Boddy, Alan V.; Agar, Nathalie Y.R.; Curtin, Nicola J.; Elmquist, William F.; Sarkaria, Jann N.

    2015-01-01

    Poly (ADP-ribose) polymerase (PARP) inhibition can enhance the efficacy of temozolomide (TMZ) and prolong survival in orthotopic glioblastoma (GBM) xenografts. The aim of this study was to evaluate the combination of the PARP inhibitor rucaparib with TMZ and to correlate pharmacokinetic and pharmacodynamic studies with efficacy in patient-derived GBM xenograft models. The combination of rucaparib with TMZ was highly effective in vitro in short-term explant cultures derived from GBM12, and similarly, the combination of rucaparib and TMZ (dosed for 5 days every 28 days × 3 cycles) significantly prolonged the time to tumor regrowth by 40% in heterotopic xenografts. In contrast, the addition of rucaparib had no impact on the efficacy of TMZ in GBM12 or GBM39 orthotopic models. Using Madin-Darby canine kidney (MDCK) II cells stably expressing murine BCRP1 or human MDR1, cell accumulation studies demonstrated that rucaparib is transported by both transporters. Consistent with the influence of these efflux pumps on central nervous system drug distribution, Mdr1a/b−/−Bcrp1−/− knockout mice had a significantly higher brain to plasma ratio for rucaparib (1.61 ± 0.25) than wild-type mice (0.11 ± 0.08). A pharmacokinetic and pharmacodynamic evaluation after a single dose confirmed limited accumulation of rucaparib in the brain associated with substantial residual PARP enzymatic activity. Similarly, matrix-assisted laser desorption/ionization mass spectrometric imaging demonstrated significantly enhanced accumulation of drug in flank tumor compared to normal brain or orthotopic tumors. Collectively, these results suggest that limited drug delivery into brain tumors may significantly limit the efficacy of rucaparib combined with TMZ in GBM. PMID:26438157

  16. Efficacy of PARP Inhibitor Rucaparib in Orthotopic Glioblastoma Xenografts Is Limited by Ineffective Drug Penetration into the Central Nervous System.

    PubMed

    Parrish, Karen E; Cen, Ling; Murray, James; Calligaris, David; Kizilbash, Sani; Mittapalli, Rajendar K; Carlson, Brett L; Schroeder, Mark A; Sludden, Julieann; Boddy, Alan V; Agar, Nathalie Y R; Curtin, Nicola J; Elmquist, William F; Sarkaria, Jann N

    2015-12-01

    PARP inhibition can enhance the efficacy of temozolomide and prolong survival in orthotopic glioblastoma (GBM) xenografts. The aim of this study was to evaluate the combination of the PARP inhibitor rucaparib with temozolomide and to correlate pharmacokinetic and pharmacodynamic studies with efficacy in patient-derived GBM xenograft models. The combination of rucaparib with temozolomide was highly effective in vitro in short-term explant cultures derived from GBM12, and, similarly, the combination of rucaparib and temozolomide (dosed for 5 days every 28 days for 3 cycles) significantly prolonged the time to tumor regrowth by 40% in heterotopic xenografts. In contrast, the addition of rucaparib had no impact on the efficacy of temozolomide in GBM12 or GBM39 orthotopic models. Using Madin-Darby canine kidney (MDCK) II cells stably expressing murine BCRP1 or human MDR1, cell accumulation studies demonstrated that rucaparib is transported by both transporters. Consistent with the influence of these efflux pumps on central nervous system drug distribution, Mdr1a/b(-/-)Bcrp1(-/-) knockout mice had a significantly higher brain to plasma ratio for rucaparib (1.61 ± 0.25) than wild-type mice (0.11 ± 0.08). A pharmacokinetic and pharmacodynamic evaluation after a single dose confirmed limited accumulation of rucaparib in the brain is associated with substantial residual PARP enzymatic activity. Similarly, matrix-assisted laser desorption/ionization mass spectrometric imaging demonstrated significantly enhanced accumulation of drug in flank tumor compared with normal brain or orthotopic tumors. Collectively, these results suggest that limited drug delivery into brain tumors may significantly limit the efficacy of rucaparib combined with temozolomide in GBM. ©2015 American Association for Cancer Research.

  17. Preconditioning methods influence tumor property in an orthotopic bladder urothelial carcinoma rat model

    PubMed Central

    MIYAZAKI, KOZO; MORIMOTO, YUJI; NISHIYAMA, NOBUHIRO; SATOH, HIROYUKI; TANAKA, MASAMITSU; SHINOMIYA, NARIYOSHI; ITO, KEIICHI

    2014-01-01

    Urothelial carcinoma (UC) is an extremely common type of cancer that occurs in the bladder. It has a particularly high rate of recurrence. Therefore, preclinical studies using animal models are essential to determine effective forms of treatment. In the present study, in order to establish an orthotopic bladder UC animal model with clinical relevance, the effects of preconditioning methods on properties of the developed tumor were evaluated. The bladder cavity was pretreated with phosphate-buffered saline (PBS), acid-base, trypsin (TRY) or poly (L-lysine) (PLL) and then rat UC cells (AY-27) (4×106 cells) were inoculated. The results demonstrated that, two weeks later, the tumorigenic rate (88%) and tumor count (2.3 per rat) were not significantly different among the preconditioning methods, whereas tumor volume and invasion depth into bladder tissue were significantly different. Average tumor volumes were >50 mm3 in the PBS and acid-base-treated groups and <10 mm3 in the TRY- and PLL-treated groups. The percentage of invasive tumors (T2 or more advanced stage) was ∼75% of total tumors in the PBS- and acid-base-treated groups, whereas the percentages were reduced in the TRY- and PLL-treated groups (58 and 32%, respectively). Non-invasive tumors (Ta or T1) accounted for 54% of tumors in the PLL-treated group, which was 2-5-fold higher than the percentages in the remaining groups. Properties of the developed tumor in the rat orthotopic UC model were different depending on preconditioning methods. Therefore, different animal models suitable for a discrete preclinical examination may be established by using the appropriate preconditioning condition. PMID:24649309

  18. Ischaemia-reperfusion injury in orthotopic mouse lung transplants - a scanning electron microscopy study.

    PubMed

    Draenert, Alice; Marquardt, Klaus; Inci, Ilhan; Soltermann, Alex; Weder, Walter; Jungraithmayr, Wolfgang

    2011-02-01

    Lung ischaemia-reperfusion (I/R) injury remains a major cause of graft failure in lung transplantation (Tx). With the implementation of orthotopic lung Tx in mice, a physiological model on the base of a perfused and ventilated graft became available for the investigation of I/R injury. Using the scanning electron microscopy (SEM) technique, we here present an analysis of early and late morphological changes of pulmonary I/R injury. Syngeneic lungs were orthotopically transplanted between C57BL/6 mice. Grafts were exposed to 2 h of cold ischaemia. Transplants and right lungs were examined by SEM with corresponding haematoxylin-eosin histology 30 min and 4 h after reperfusion. Thirty minutes after reperfusion, the alveolar surface of transplants showed a discontinued lining of surfactant, while the lining of the non-transplanted lung was normal. Within the graft, leucocytes displayed an irregular surface with development of pseudopodia, and microvilli were detected on the membrane of pneumocytes. At 4 h after reperfusion, leucocytes significantly increased in numbers within the alveolar space. Also, the number of microvilli on pneumocytes increased significantly. Similar to these, the endothelium of vessels increasingly developed microvilli from 30 min towards 4 h after reperfusion. The airways of transplanted grafts showed mild changes with thickening of the bronchial epithelium and a destruction of kinocilia. Taken together, SEM detects pathological events of I/R that are previously not described in normal histology. These findings may influence the interpretation of studies investigating the I/R injury in the mouse model of lung Tx. © 2011 The Authors. International Journal of Experimental Pathology © 2011 International Journal of Experimental Pathology.

  19. Comparison of a chimeric anti-carcinoembryonic antigen antibody conjugated with visible or near-infrared fluorescent dyes for imaging pancreatic cancer in orthotopic nude mouse models

    NASA Astrophysics Data System (ADS)

    Maawy, Ali A.; Hiroshima, Yukihiko; Kaushal, Sharmeela; Luiken, George A.; Hoffman, Robert M.; Bouvet, Michael

    2013-12-01

    The aim of this study was to evaluate a set of visible and near-infrared dyes conjugated to a tumor-specific chimeric antibody for high-resolution tumor imaging in orthotopic models of pancreatic cancer. BxPC-3 human pancreatic cancer was orthotopically implanted into pancreata of nude mice. Mice received a single intravenous injection of a chimeric anti-carcinoembryonic antigen antibody conjugated to one of the following fluorophores: 488-nm group (Alexa Fluor 488 or DyLight 488); 550-nm group (Alexa Fluor 555 or DyLight 550); 650-nm group (Alexa Fluor 660 or DyLight 650), or the 750-nm group (Alexa Fluor 750 or DyLight 755). After 24 h, the Olympus OV100 small-animal imaging system was used for noninvasive and intravital fluorescence imaging of mice. Dyes were compared with respect to depth of imaging, resolution, tumor-to-background ratio (TBR), photobleaching, and hemoglobin quenching. The longer wavelength dyes had increased depth of penetration and ability to detect the smallest tumor deposits and provided the highest TBRs, resistance to hemoglobin quenching, and specificity. The shorter wavelength dyes were more photostable. This study showed unique advantages of each dye for specific cancer imaging in a clinically relevant orthotopic model.

  20. A liver-metastatic model of human primary gastric lymphoma in nude mice orthotopically constructed by using histologically intact patient specimens.

    PubMed

    Yang, Bo; Tuo, Shuai; Tuo, Chao-Wei; Zhang, Ning; Liu, Qiu-Zhen

    2010-06-01

    In recent years, incidence and mortality of lymphoma are markedly increasing worldwide. However, the pathogenesis and mechanism of invasion and metastasis for lymphoma are not yet fully clarified. It is mainly due to the lack of ideal animal models, which can precisely simulate the invasion and metastasis of lymphoma in the human body. So, it is very necessary to establish a highly metastatic nude mouse model of human lymphoma. This study developed a liver-metastatic model of primary gastric lymphoma in nude mice by using orthotopic surgical implantation of histologically intact patient specimens into the corresponding organs of the recipient small animals. A histologically intact fragment of liver metastasis derived from a surgical specimen of a patient with primary gastric lymphoma was implanted into the submucosa of the stomach in nude mice. Tumorigenicity, invasion, metastasis, morphologic characteristics (via light microscopy, electron microscopy, and immunohistochemistry), karyotype analysis, and DNA content of the orthotopically transplanted tumors were studied. An orthotopic liver metastatic model of human primary gastric lymphoma in nude mice (termed HGBL-0304) was successfully established. The histopathology of the transplanted tumors showed primary gastric diffuse large B-cell lymphoma. CD19, CD20, CD22, and CD79alpha were positive, but CD3 and CD7 were negative. The serum level of lactate dehydrogenase (LDH) was elevated [(1010.56+/-200.85) U/L]. The number of chromosomes ranged from 75 to 89. The DNA index (DI) was 1.45+/-0.25 (that is, heteroploid). So far, the HGBL-0304 model has been passed on for 45 generations of nude mice. A total of 263 nude mice were used for the transplantation. Both the growth and resuscitation rates of liquid nitrogen cryopreservation of the transplanted tumors were 100%. The transplanted tumors autonomically invasively grew and damaged a whole layer in the stomach of nude mice. The metastasis rates of liver, spleen, lymph

  1. Pleiotrophin and N-syndecan promote perineural invasion and tumor progression in an orthotopic mouse model of pancreatic cancer.

    PubMed

    Yao, Jun; Zhang, Lu-Lin; Huang, Xu-Mei; Li, Wen-Yao; Gao, She-Gan

    2017-06-07

    To detect the expression of pleiotrophin (PTN) and N-syndecan in pancreatic cancer and analyze their association with tumor progression and perineural invasion (PNI). An orthotopic mouse model of pancreatic cancer was created by injecting tumor cells subcapsularly in a root region of the pancreas beneath the spleen. Pancreatic cancer tissues were taken from 36 mice that survived for more than 90 d. PTN and N-syndecan proteins were detected by immunohistochemistry and analyzed for their correlation with pathological features, PNI, and prognosis. The expression rates of PTN and N-syndecan proteins were 66.7% and 61.1%, respectively, in cancer tissue. PTN and N-syndecan expression was associated with PNI ( P = 0.019 and P = 0.032, respectively). High PTN expression was closely associated with large bloody ascites ( P = 0.009), liver metastasis ( P = 0.035), and decreased survival time ( P = 0.022). N-syndecan expression was significantly associated with tumor size ( P = 0.025), but not with survival time ( P = 0.539). High PTN and N-syndecan expression was closely associated with metastasis and poor prognosis, suggesting that they may promote tumor progression and PNI in the orthotopic mouse model of pancreatic cancer.

  2. Biological characterization of preclinical Bioluminescent Osteosarcoma Orthotopic Mouse (BOOM) model: A multi-modality approach

    PubMed Central

    Garimella, Rama; Eskew, Jeff; Bhamidi, Priyanka; Vielhauer, George; Hong, Yan; Anderson, H. Clarke; Tawfik, Ossama; Rowe, Peter

    2013-01-01

    Osteosarcoma (OS) is a bone malignancy that affects children and adolescents. It is a highly aggressive tumor and typically metastasizes to lungs. Despite aggressive chemotherapy and surgical treatments, the current 5 year survival rate is 60–70%. Clinically relevant models are needed to understand OS pathobiology, metastatic progression from bones to lungs, and ultimately, to develop more efficacious treatment strategies and improve survival rates in OS patients with metastasis. The main goal of this study was to develop and characterize an in vivo OS model that will allow non-invasive tracking of tumor progression in real time, and aid in studying OS pathobiology, and screening of potential therapeutic agents against OS. In this study, we have used a multi-modality approach using bioluminescent imaging, electron microscopy, micro-computed tomography, and histopathology to develop and characterize a preclinical Bioluminescent Osteosarcoma Orthotopic Mouse (BOOM) model, using 143B human OS cell line. The results of this study clearly demonstrate that the BOOM model represents the clinical disease as evidenced by a spectrum of changes associated with tumor establishment, progression and metastasis, and detection of known OS biomarkers in the primary and metastatic tumor tissue. Key novel findings of this study include: (a) multimodality approach for extensive characterization of the BOOM model using 143B human OS cell line; (b) evidence of renal metastasis in OS orthotopic model using 143B cells; (c) evidence of Runx2 expression in the metastatic lung tissue; and (d) evidence of the presence of extracellular membrane vesicles and myofibroblasts in the BOOM model. PMID:25688332

  3. Ischaemia-reperfusion injury in orthotopic mouse lung transplants – a scanning electron microscopy study

    PubMed Central

    Draenert, Alice; Marquardt, Klaus; Inci, Ilhan; Soltermann, Alex; Weder, Walter; Jungraithmayr, Wolfgang

    2011-01-01

    Lung ischaemia-reperfusion (I/R) injury remains a major cause of graft failure in lung transplantation (Tx). With the implementation of orthotopic lung Tx in mice, a physiological model on the base of a perfused and ventilated graft became available for the investigation of I/R injury. Using the scanning electron microscopy (SEM) technique, we here present an analysis of early and late morphological changes of pulmonary I/R injury. Syngeneic lungs were orthotopically transplanted between C57BL/6 mice. Grafts were exposed to 2 h of cold ischaemia. Transplants and right lungs were examined by SEM with corresponding haematoxylin–eosin histology 30 min and 4 h after reperfusion. Thirty minutes after reperfusion, the alveolar surface of transplants showed a discontinued lining of surfactant, while the lining of the non-transplanted lung was normal. Within the graft, leucocytes displayed an irregular surface with development of pseudopodia, and microvilli were detected on the membrane of pneumocytes. At 4 h after reperfusion, leucocytes significantly increased in numbers within the alveolar space. Also, the number of microvilli on pneumocytes increased significantly. Similar to these, the endothelium of vessels increasingly developed microvilli from 30 min towards 4 h after reperfusion. The airways of transplanted grafts showed mild changes with thickening of the bronchial epithelium and a destruction of kinocilia. Taken together, SEM detects pathological events of I/R that are previously not described in normal histology. These findings may influence the interpretation of studies investigating the I/R injury in the mouse model of lung Tx. PMID:21272104

  4. Intravital imaging of a spheroid-based orthotopic model of melanoma in the mouse ear skin

    PubMed Central

    Chan, Keefe T.; Jones, Stephen W.; Brighton, Hailey E.; Bo, Tao; Cochran, Shelly D.; Sharpless, Norman E.; Bear, James E.

    2017-01-01

    Multiphoton microscopy is a powerful tool that enables the visualization of fluorescently tagged tumor cells and their stromal interactions within tissues in vivo. We have developed an orthotopic model of implanting multicellular melanoma tumor spheroids into the dermis of the mouse ear skin without the requirement for invasive surgery. Here, we demonstrate the utility of this approach to observe the primary tumor, single cell actin dynamics, and tumor-associated vasculature. These methods can be broadly applied to investigate an array of biological questions regarding tumor cell behavior in vivo. PMID:28748125

  5. Development of a Novel Preclinical Pancreatic Cancer Research Model: Bioluminescence Image-Guided Focal Irradiation and Tumor Monitoring of Orthotopic Xenografts1

    PubMed Central

    Tuli, Richard; Surmak, Andrew; Reyes, Juvenal; Hacker-Prietz, Amy; Armour, Michael; Leubner, Ashley; Blackford, Amanda; Tryggestad, Erik; Jaffee, Elizabeth M; Wong, John; DeWeese, Theodore L; Herman, Joseph M

    2012-01-01

    PURPOSE: We report on a novel preclinical pancreatic cancer research model that uses bioluminescence imaging (BLI)-guided irradiation of orthotopic xenograft tumors, sparing of surrounding normal tissues, and quantitative, noninvasive longitudinal assessment of treatment response. MATERIALS AND METHODS: Luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were orthotopically injected in nude mice. BLI was compared to pathologic tumor volume, and photon emission was assessed over time. BLI was correlated to positron emission tomography (PET)/computed tomography (CT) to estimate tumor dimensions. BLI and cone-beam CT (CBCT) were used to compare tumor centroid location and estimate setup error. BLI and CBCT fusion was performed to guide irradiation of tumors using the small animal radiation research platform (SARRP). DNA damage was assessed by γ-H2Ax staining. BLI was used to longitudinally monitor treatment response. RESULTS: Bioluminescence predicted tumor volume (R = 0.8984) and increased linearly as a function of time up to a 10-fold increase in tumor burden. BLI correlated with PET/CT and necropsy specimen in size (P < .05). Two-dimensional BLI centroid accuracy was 3.5 mm relative to CBCT. BLI-guided irradiated pancreatic tumors stained positively for γ-H2Ax, whereas surrounding normal tissues were spared. Longitudinal assessment of irradiated tumors with BLI revealed significant tumor growth delay of 20 days relative to controls. CONCLUSIONS: We have successfully applied the SARRP to a bioluminescent, orthotopic preclinical pancreas cancer model to noninvasively: 1) allow the identification of tumor burden before therapy, 2) facilitate image-guided focal radiation therapy, and 3) allow normalization of tumor burden and longitudinal assessment of treatment response. PMID:22496923

  6. Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity

    PubMed Central

    Garcia, Emmanuel; Becker, Veronika G. C.; McCullough, Danielle J.; Stabley, John N.; Gittemeier, Elizabeth M.; Opoku-Acheampong, Alexander B.; Sieman, Dietmar W.

    2016-01-01

    Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10−9 to 10−4 M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%. Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes. PMID:27125846

  7. Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity.

    PubMed

    Garcia, Emmanuel; Becker, Veronika G C; McCullough, Danielle J; Stabley, John N; Gittemeier, Elizabeth M; Opoku-Acheampong, Alexander B; Sieman, Dietmar W; Behnke, Bradley J

    2016-07-01

    Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10(-9) to 10(-4) M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%. Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes. Copyright © 2016 the American Physiological Society.

  8. Orthotopic heart transplantation in the prince sultan cardiac center.

    PubMed

    Al Fagih, M R

    1996-01-01

    In this report we attempt to demonstrate the efforts involved in establishing and organizing the heart transplant program at the Armed Forces Hospital in Riyadh, Saudi Arabia. From 1986 to date, 25 orthotopic heart transplants were performed at this center. Patient age ranged from 22 months to 57 years; 4 patients were below 12 years of age and 4 aged 50 years and above. The incidations for transplantation were cardiomyopathy in 15 patients, ischemic heart disease in 6 patients, and valvular heart disease in 4 patients. Fourteen recipients have died. Three of them were classified as hospital deaths, occuring before the patient could be discharged after the procedure; the reminder died from rejection and associated problems. Eight patients of them died within the first year. The longest survival period was almost 8 years. The overall 8 years survival rate was 45%, which is comparable to the international figures. Shortage of donors may affect the future of the transplant programs. Increasing the awareness of the public about the importance of organ donation and transplantation is crucial in this regard.

  9. Glucose metabolism via the pentose phosphate pathway, glycolysis and Krebs cycle in an orthotopic mouse model of human brain tumors.

    PubMed

    Marin-Valencia, Isaac; Cho, Steve K; Rakheja, Dinesh; Hatanpaa, Kimmo J; Kapur, Payal; Mashimo, Tomoyuki; Jindal, Ashish; Vemireddy, Vamsidhara; Good, Levi B; Raisanen, Jack; Sun, Xiankai; Mickey, Bruce; Choi, Changho; Takahashi, Masaya; Togao, Osamu; Pascual, Juan M; Deberardinis, Ralph J; Maher, Elizabeth A; Malloy, Craig R; Bachoo, Robert M

    2012-10-01

    It has been hypothesized that increased flux through the pentose phosphate pathway (PPP) is required to support the metabolic demands of rapid malignant cell growth. Using orthotopic mouse models of human glioblastoma (GBM) and renal cell carcinoma metastatic to brain, we estimated the activity of the PPP relative to glycolysis by infusing [1,2-(13) C(2) ]glucose. The [3-(13) C]lactate/[2,3-(13) C(2) ]lactate ratio was similar for both the GBM and brain metastasis and their respective surrounding brains (GBM, 0.197 ± 0.011 and 0.195 ± 0.033, respectively (p = 1); metastasis: 0.126 and 0.119 ± 0.033, respectively). This suggests that the rate of glycolysis is significantly greater than the PPP flux in these tumors, and that the PPP flux into the lactate pool is similar in both tumors. Remarkably, (13) C-(13) C coupling was observed in molecules derived from Krebs cycle intermediates in both tumor types, denoting glucose oxidation. In the renal cell carcinoma, in contrast with GBM, (13) C multiplets of γ-aminobutyric acid (GABA) differed from its precursor glutamate, suggesting that GABA did not derive from a common glutamate precursor pool. In addition, the orthotopic renal tumor, the patient's primary renal mass and brain metastasis were all strongly immunopositive for the 67-kDa isoform of glutamate decarboxylase, as were 84% of tumors on a renal cell carcinoma tissue microarray of the same histology, suggesting that GABA synthesis is cell autonomous in at least a subset of renal cell carcinomas. Taken together, these data demonstrate that (13) C-labeled glucose can be used in orthotopic mouse models to study tumor metabolism in vivo and to ascertain new metabolic targets for cancer diagnosis and therapy. Copyright © 2012 John Wiley & Sons, Ltd.

  10. Societal reintegration following cadaveric orthotopic liver transplantation.

    PubMed

    Kelly, Ryan; Hurton, Scott; Ayloo, Subhashini; Cwinn, Mathew; De Coutere-Bosse, Sarah; Molinari, Michele

    2016-06-01

    Studies on patients' societal reintegration following orthotopic liver transplantation (OLT) are scarce. Between September 2006 and January 2008, all adults who were alive after 3 years post OLT were included in this prospective cohort study. Validated questionnaires were administered to all candidates with the primary aim of investigating the rate of their social re-integration following OLT and potential barriers they might have encountered. Among 157 eligible patients 110 (70%) participated. Mean participants' age was 57 years (SD 11.4) and 43% were females. Prior to OLT, 75% of patients were married and 6% were divorced. Following OLT there was no significant difference in marital status. Employment rate fell from 72% to 30% post-OLT. Patients who had been employed in either low-skill or advanced-skill jobs were less likely to return to work. After OLT, personal income fell an average of 4,363 Canadian dollars (CAN$) (SD 20,733) (P=0.03) but the majority of recipients (80%) reported high levels of satisfaction for their role in society. Although patients' satisfaction post-OLT is high, employment status is likely to be negatively affected for individuals who are not self-employed. Strategies to assist recipients in returning to their pre-OLT jobs should be developed to improve patients' economical status and societal ability to recoup resources committed for OLT.

  11. AshwaMAX and Withaferin A inhibits gliomas in cellular and murine orthotopic models

    PubMed Central

    Pohling, Christoph; Natarajan, Arutselvan; Witney, Timothy H.; Kaur, Jasdeep; Xu, Lingyun; Gowrishankar, Gayatri; D’Souza, Aloma L; Murty, Surya; Schick, Sophie; Chen, Liyin; Wu, Nicholas; Khaw, Phoo; Mischel, Paul; Abbasi, Taher; Usmani, Shahabuddin; Mallick, Parag

    2017-01-01

    Glioblastoma multiforme (GBM) is an aggressive, malignant cancer Johnson and O’Neill (J Neurooncol 107: 359–364, 2012). An extract from the winter cherry plant (Withania somnifera), AshwaMAX, is concentrated (4.3 %) for Withaferin A; a steroidal lactone that inhibits cancer cells Vanden Berghe et al. (Cancer Epidemiol Biomark Prev 23: 1985–1996, 2014). We hypothesized that AshwaMAX could treat GBM and that bioluminescence imaging (BLI) could track oral therapy in orthotopic murine models of glioblastoma. Human parietal-cortical glioblastoma cells (GBM2, GBM39) were isolated from primary tumors while U87-MG was obtained commercially. GBM2 was transduced with lentiviral vectors that express Green Fluorescent Protein (GFP)/firefly luciferase fusion proteins. Mutational, expression and proliferative status of GBMs were studied. Intracranial xenografts of glioblastomas were grown in the right frontal regions of female, nude mice (n = 3–5 per experiment). Tumor growth was followed through BLI. Neurosphere cultures (U87-MG, GBM2 and GBM39) were inhibited by AshwaMAX at IC50 of 1.4, 0.19 and 0.22 μM equivalent respectively and by Withaferin A with IC50 of 0.31, 0.28 and 0.25 μM respectively. Oral gavage, every other day, of AshwaMAX (40 mg/kg per day) significantly reduced bioluminescence signal (n = 3 mice, p < 0.02, four parameter non-linear regression analysis) in preclinical models. After 30 days of treatment, bioluminescent signal increased suggesting onset of resistance. BLI signal for control, vehicle-treated mice increased and then plateaued. Bioluminescent imaging revealed diffuse growth of GBM2 xenografts. With AshwaMAX, GBM neurospheres collapsed at nanomolar concentrations. Oral treatment studies on murine models confirmed that AshwaMAX is effective against orthotopic GBM. AshwaMAX is thus a promising candidate for future clinical translation in patients with GBM. PMID:26650066

  12. AshwaMAX and Withaferin A inhibits gliomas in cellular and murine orthotopic models.

    PubMed

    Chang, Edwin; Pohling, Christoph; Natarajan, Arutselvan; Witney, Timothy H; Kaur, Jasdeep; Xu, Lingyun; Gowrishankar, Gayatri; D'Souza, Aloma L; Murty, Surya; Schick, Sophie; Chen, Liyin; Wu, Nicholas; Khaw, Phoo; Mischel, Paul; Abbasi, Taher; Usmani, Shahabuddin; Mallick, Parag; Gambhir, Sanjiv S

    2016-01-01

    Glioblastoma multiforme (GBM) is an aggressive, malignant cancer Johnson and O'Neill (J Neurooncol 107: 359-364, 2012). An extract from the winter cherry plant (Withania somnifera ), AshwaMAX, is concentrated (4.3 %) for Withaferin A; a steroidal lactone that inhibits cancer cells Vanden Berghe et al. (Cancer Epidemiol Biomark Prev 23: 1985-1996, 2014). We hypothesized that AshwaMAX could treat GBM and that bioluminescence imaging (BLI) could track oral therapy in orthotopic murine models of glioblastoma. Human parietal-cortical glioblastoma cells (GBM2, GBM39) were isolated from primary tumors while U87-MG was obtained commercially. GBM2 was transduced with lentiviral vectors that express Green Fluorescent Protein (GFP)/firefly luciferase fusion proteins. Mutational, expression and proliferative status of GBMs were studied. Intracranial xenografts of glioblastomas were grown in the right frontal regions of female, nude mice (n = 3-5 per experiment). Tumor growth was followed through BLI. Neurosphere cultures (U87-MG, GBM2 and GBM39) were inhibited by AshwaMAX at IC50 of 1.4, 0.19 and 0.22 µM equivalent respectively and by Withaferin A with IC50 of 0.31, 0.28 and 0.25 µM respectively. Oral gavage, every other day, of AshwaMAX (40 mg/kg per day) significantly reduced bioluminescence signal (n = 3 mice, p < 0.02, four parameter non-linear regression analysis) in preclinical models. After 30 days of treatment, bioluminescent signal increased suggesting onset of resistance. BLI signal for control, vehicle-treated mice increased and then plateaued. Bioluminescent imaging revealed diffuse growth of GBM2 xenografts. With AshwaMAX, GBM neurospheres collapsed at nanomolar concentrations. Oral treatment studies on murine models confirmed that AshwaMAX is effective against orthotopic GBM. AshwaMAX is thus a promising candidate for future clinical translation in patients with GBM.

  13. Molecularly Targeted Dose-Enhancement Radiotherapy Using Gold and Luminescent Nanoparticles in an Orthotopic Human Prostate Cancer Rat Model

    DTIC Science & Technology

    2013-10-01

    cell lines, such as cervix cancer cell line (HeLa) and breast cancer cell line (MDA-MB-231), were also employed. The experiments with other cell lines...breast cancer cell line (MDA-MB- 231), and cervix cancer cell line (HeLa). Different from our hypothesis, prostate cancer cell lines did not present...Radiotherapy Using Gold and Luminescent Nanoparticles in an Orthotopic Human Prostate Cancer Rat Model PRINCIPAL INVESTIGATOR: Kwang Song

  14. MR-CBCT image-guided system for radiotherapy of orthotopic rat prostate tumors.

    PubMed

    Chiu, Tsuicheng D; Arai, Tatsuya J; Campbell Iii, James; Jiang, Steve B; Mason, Ralph P; Stojadinovic, Strahinja

    2018-01-01

    Multi-modality image-guided radiotherapy is the standard of care in contemporary cancer management; however, it is not common in preclinical settings due to both hardware and software limitations. Soft tissue lesions, such as orthotopic prostate tumors, are difficult to identify using cone beam computed tomography (CBCT) imaging alone. In this study, we characterized a research magnetic resonance (MR) scanner for preclinical studies and created a protocol for combined MR-CBCT image-guided small animal radiotherapy. Two in-house dual-modality, MR and CBCT compatible, phantoms were designed and manufactured using 3D printing technology. The phantoms were used for quality assurance tests and to facilitate end-to-end testing for combined preclinical MR and CBCT based treatment planning. MR and CBCT images of the phantoms were acquired utilizing a Varian 4.7 T scanner and XRad-225Cx irradiator, respectively. The geometry distortion was assessed by comparing MR images to phantom blueprints and CBCT. The corrected MR scans were co-registered with CBCT and subsequently used for treatment planning. The fidelity of 3D printed phantoms compared to the blueprint design yielded favorable agreement as verified with the CBCT measurements. The geometric distortion, which varied between -5% and 11% throughout the scanning volume, was substantially reduced to within 0.4% after correction. The distortion free MR images were co-registered with the corresponding CBCT images and imported into a commercial treatment planning software SmART Plan. The planning target volume (PTV) was on average 19% smaller when contoured on the corrected MR-CBCT images relative to raw images without distortion correction. An MR-CBCT based preclinical workflow was successfully designed and implemented for small animal radiotherapy. Combined MR-CBCT image-guided radiotherapy for preclinical research potentially delivers enhanced relevance to human radiotherapy for various disease sites. This novel protocol

  15. Isolation and (111)In-Oxine Labeling of Murine NK Cells for Assessment of Cell Trafficking in Orthotopic Lung Tumor Model.

    PubMed

    Malviya, Gaurav; Nayak, Tapan; Gerdes, Christian; Dierckx, Rudi A J O; Signore, Alberto; de Vries, Erik F J

    2016-04-04

    A noninvasive in vivo imaging method for NK cell trafficking is essential to gain further understanding of the pathogenesis of NK cell mediated immune response to the novel cancer treatment strategies, and to discover the homing sites and physiological distribution of NK cells. Although human NK cells can be labeled for in vivo imaging, little is known about the murine NK cell labeling and its application in animal models. This study describes the isolation and ex vivo radiolabeling of murine NK cells for the evaluation of cell trafficking in an orthotopic model of human lung cancer in mice. Scid-Tg(FCGR3A)Blt transgenic SCID mice were used to isolate NK cells from mouse splenocytes using the CD49b (DX5) MicroBeads positive selection method. The purity and viability of the isolated NK cells were confirmed by FACS analysis. Different labeling buffers and incubation times were evaluated to optimize (111)In-oxine labeling conditions. Functionality of the radiolabeled NK cell was assessed by (51)Cr-release assay. We evaluated physiological distribution of (111)In-oxine labeled murine NK cells in normal SCID mice and biodistribution in irradiated and nonirradiated SCID mice with orthotopic A549 human lung tumor lesions. Imaging findings were confirmed by histology. Results showed that incubation with 0.011 MBq of (111)In-oxine per million murine NK cells in PBS (pH 7.4) for 20 min is the best condition that provides optimum labeling efficiency without affecting cell viability and functionality. Physiological distribution in normal SCID mice demonstrated NK cells homing mainly in the spleen, while (111)In released from NK cells was excreted via kidneys into urine. Biodistribution studies demonstrated a higher lung uptake in orthotopic lung tumor-bearing mice than control mice. In irradiated mice, lung tumor uptake of radiolabeled murine NK cells decreased between 24 h and 72 h postinjection (p.i.), which was accompanied by tumor regression, while in nonirradiated mice

  16. Pleiotrophin and N-syndecan promote perineural invasion and tumor progression in an orthotopic mouse model of pancreatic cancer

    PubMed Central

    Yao, Jun; Zhang, Lu-Lin; Huang, Xu-Mei; Li, Wen-Yao; Gao, She-Gan

    2017-01-01

    AIM To detect the expression of pleiotrophin (PTN) and N-syndecan in pancreatic cancer and analyze their association with tumor progression and perineural invasion (PNI). METHODS An orthotopic mouse model of pancreatic cancer was created by injecting tumor cells subcapsularly in a root region of the pancreas beneath the spleen. Pancreatic cancer tissues were taken from 36 mice that survived for more than 90 d. PTN and N-syndecan proteins were detected by immunohistochemistry and analyzed for their correlation with pathological features, PNI, and prognosis. RESULTS The expression rates of PTN and N-syndecan proteins were 66.7% and 61.1%, respectively, in cancer tissue. PTN and N-syndecan expression was associated with PNI (P = 0.019 and P = 0.032, respectively). High PTN expression was closely associated with large bloody ascites (P = 0.009), liver metastasis (P = 0.035), and decreased survival time (P = 0.022). N-syndecan expression was significantly associated with tumor size (P = 0.025), but not with survival time (P = 0.539). CONCLUSION High PTN and N-syndecan expression was closely associated with metastasis and poor prognosis, suggesting that they may promote tumor progression and PNI in the orthotopic mouse model of pancreatic cancer. PMID:28638231

  17. Therapeutic Cell-Cycle-Decoy Efficacy of a Telomerase-Dependent Adenovirus in an Orthotopic Model of Chemotherapy-Resistant Human Stomach Carcinomatosis Peritonitis Visualized With FUCCI Imaging.

    PubMed

    Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M

    2017-11-01

    We have established an orthotopic nude-mouse model of gastric cancer carcinomatosis peritonitis, a recalcitrant disease in human patients. Human MKN45 poorly-differentiated human gastric cancer cells developed carcinomatosis peritonitis upon orthotopic transplantation in nude mice. The MKN45 cells expressed the fluorescent ubiquitination-based cell cycle indicator (FUCCI) that color codes the phases of the cell cycle. The intra-peritoneal tumors and ascites contained mostly quiescent G 1 /G o cancer cells visualized as red by FUCCI imaging. Cisplatinum (CDDP) treatment did not reduce bloody ascites, and larger tumors formed in the peritoneal cavity after CDDP treatment in an early-stage carcinomatosis peritonitis orthotopic mouse model. Paclitaxel-treated mice had reduced ascites, but also had large tumor masses in the peritonium after treatment with cancer cells mostly in G 0 /G 1 , visualized by FUCCI red. In contrast, OBP-301 telomerase-dependent adenovirus-treated mice had no ascites and only small tumor nodules consisting of cancer cells mostly in S/G 2 phases in the early-stage carcinomatosis peritonitis model, visualized by FUCCI green. Furthermore, OBP-301 significantly reduced the size of tumors (P < 0.01) and ascites even in a late-stage carcinomatosis peritonitis model. These results suggest that quiescent peritoneally-disseminated gastric cancer cells are resistant to conventional chemotherapy, but OBP-301 significantly reduced the weight of the tumors and increased survival, suggesting clinical potential. J. Cell. Biochem. 118: 3635-3642, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Asymptomatic bacteriuria: when the treatment is worse than the disease.

    PubMed

    Trautner, Barbara W

    2011-12-06

    Asymptomatic bacteriuria (ABU) is a condition in which bacteria are present in a noncontaminated urine sample collected from a patient without signs or symptoms related to the urinary tract. ABU must be distinguished from symptomatic UTI by the absence of signs and symptoms compatible with UTI or by clinical determination that a nonurinary etiology accounts for the patient's symptoms. Interactions between the organism, the host, and the bladder environment determine whether bacteriuria leads to ABU or to UTI. ABU is a very common condition that is often treated unnecessarily with antibiotics-it should be detected and treated in pregnant women and patients undergoing urologic surgery, but in most other patient groups, treatment does not confer benefit and can be harmful. A change in prescribing behavior for ABU has been achieved through several fairly high-intensity interventions, such as interactive educational sessions for physicians, but whether these improvements persist beyond the study period is not known. Further research is needed to determine whether screening for and treatment of ABU is beneficial in patients with renal transplants, patients with orthotopic neobladders, patients undergoing prosthetic joint implantation, and patients with neutropenia. © 2012 Macmillan Publishers Limited. All rights reserved

  19. Heterogeneous Binding and Central Nervous System Distribution of the Multitargeted Kinase Inhibitor Ponatinib Restrict Orthotopic Efficacy in a Patient-Derived Xenograft Model of Glioblastoma.

    PubMed

    Laramy, Janice K; Kim, Minjee; Gupta, Shiv K; Parrish, Karen E; Zhang, Shuangling; Bakken, Katrina K; Carlson, Brett L; Mladek, Ann C; Ma, Daniel J; Sarkaria, Jann N; Elmquist, William F

    2017-11-01

    This study investigated how differences in drug distribution and free fraction at different tumor and tissue sites influence the efficacy of the multikinase inhibitor ponatinib in a patient-derived xenograft model of glioblastoma (GBM). Efficacy studies in GBM6 flank (heterotopic) and intracranial (orthotopic) models showed that ponatinib is effective in the flank but not in the intracranial model, despite a relatively high brain-to-plasma ratio. In vitro binding studies indicated that flank tumor had a higher free (unbound) drug fraction than normal brain. The total and free drug concentrations, along with the tissue-to-plasma ratio (Kp) and its unbound derivative (Kp,uu), were consistently higher in the flank tumor than the normal brain at 1 and 6 hours after a single dose in GBM6 flank xenografts. In the orthotopic xenografts, the intracranial tumor core displayed higher Kp and Kp,uu values compared with the brain-around-tumor (BAT). The free fractions and the total drug concentrations, hence free drug concentrations, were consistently higher in the core than in the BAT at 1 and 6 hours postdose. The delivery disadvantages in the brain and BAT were further evidenced by the low total drug concentrations in these areas that did not consistently exceed the in vitro cytotoxic concentration (IC 50 ). Taken together, the regional differences in free drug exposure across the intracranial tumor may be responsible for compromising efficacy of ponatinib in orthotopic GBM6. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  20. [Orthotopic renal transplant: our experience].

    PubMed

    De Gracia, R; Jiménez, C; Gil, F; Escuin, F; Tabernero, A; Sanz, A; Hidalgo, L

    2007-01-01

    Orthotopic renal transplant (ORT) is useful in cases of severe atherosclerosis, heterotopic bilateral transplant, unsuitable pelvic vessels and in aortic thrombosis, but it is not available in all the institutions and it is only realized of exceptional form. To review the indication, surgical technique and outcome of the ORT at our hospital. The studied included five cases between January 1990 and December 2005. We analyzed several variables: demographic characteristics, characteristics of the donor, ischemia times, evolution of renal function and morbi-mortality associated. Left ORT was performed in three men and two women. Mean patient age was 52+/-5 years, all the patients received kidneys from cadaveric donors. Mean creatinine and urea one month postoperative were 2.2+/-0.72 mg/dl and 103+/-17.2 mg/dl and at 6 months postoperative were 1.8+/-0.59 mg/dl and 78+/-14 mg/dl respectively. Immediately all patients received prophylaxis with low molecular weight heparin but it was indicated antiaggregation to two patients when they left the hospital, anticoagulation to two patients and to one of them was decided to anticoagulation nor antiagregation for history of bled digestive. A patient died for bleeding episode at level of the renal graft six months after the transplant, she was in treatment with dicumarinics, they were indicated by venous deep thrombosis in right leg. The survival a year is 80 % of the graft and the patient. Only two patients returned to hospital later, one of them for presenting an episode of diverticulitis and the other one for renal obstructive failure that needed laying of catheter pig-tail. Four patients presented stenosis of renal native vassels detected in control magnetic nuclear resonance, not symptomatic. There are two patients who take more than three years transplanted with renal stable function (creatinina 1.3 mg/dl and 1.4 mg/dl respectively). ORT is an excellent option in patients with co-morbidity increased for atherosclerosis and

  1. SYMPATHETIC INNERVATION, NOREPINEPHRINE CONTENT, AND NOREPINEPHRINE TURNOVER IN ORTHOTOPIC AND SPONTANEOUS MODELS OF BREAST CANCER

    PubMed Central

    Dawes, Ryan P.; Madden, Kelley S.

    2016-01-01

    Activation of the sympathetic nervous system (SNS) drives breast cancer progression in preclinical breast cancer models, but it has yet to be established if neoplastic and stromal cells residing in the tumor are directly targeted by locally released norepinephrine (NE). In murine orthotopic and spontaneous mammary tumors, tyrosine hydroxylase (TH)+ sympathetic nerves were limited to the periphery of the tumor. No TH+ staining was detected deeper within these tumors, even in regions with a high density of blood vessels. NE concentration was much lower in tumors compared to the more densely innervated spleen, reflecting the relative paucity of tumor TH+ innervation. Tumor and spleen NE concentration decreased with increased tissue mass. In mice treated with the neurotoxin 6-hydroxydopamine (6-OHDA) to selectively destroy sympathetic nerves, tumor NE concentration was reduced approximately 50%, suggesting that the majority of tumor NE is derived from local sympathetic nerves. To evaluate NE utilization, NE turnover in orthotopic 4T1 mammary tumors was compared to spleen under baseline and stress conditions. In non-stressed mice, NE turnover was equivalent between tumor and spleen. In mice exposed to a stressor, tumor NE turnover was increased compared to spleen NE turnover, and compared to non-stressed tumor NE turnover. Together, these results demonstrate that NE in mammary tumors is derived from local sympathetic nerves that synthesize and metabolize NE. However, differences between spleen and tumor NE turnover with stressor exposure suggest that sympathetic NE release is regulated differently within the tumor microenvironment compared to the spleen. Local mammary tumor sympathetic innervation, despite its limited distribution, is responsive to stressor exposure and therefore can contribute to stress-induced tumor progression. PMID:26718447

  2. Targeted delivery of transferrin-conjugated liposomes to an orthotopic model of lung cancer in nude rats.

    PubMed

    Gaspar, Maria Manuela; Radomska, Anna; Gobbo, Oliviero L; Bakowsky, Udo; Radomski, Marek W; Ehrhardt, Carsten

    2012-12-01

    Lung cancer is the leading cause of cancer death worldwide. Pulmonary anticancer therapy might offer several advantages over systemic delivery, leading to an increased exposure of the lung tumor to the drug, while minimizing side effects, due to regional containment. Here, we studied if a combination of inhalation therapy and drug targeting holds potential as an even more efficient lung cancer therapy. Transferrin (Tf )-conjugated PEG liposomes loaded with doxorubicin (DOX) were administered using an intracorporeal nebulizing catheter to an orthotopic lung cancer model established in athymic Rowett nude rats. Different DOX formulations and doses (0.2 and 0.4 mg/kg) were tested and the influence on tumor progression and life span of rats was evaluated in comparison with the i.v. administration of Tf-PEG-liposomes loaded with DOX at a therapeutic dose of 2 mg/kg. Rats in the untreated control group showed significant weight loss 2 weeks after tumor induction and died between days 19 and 29. Lungs of these animals showed multiple foci of neoplastic deposits, ranging up to 20 mm replacing the entire lobe. Empty Tf-liposomes showed a significant effect on survival time. This might be caused by the secondary cytotoxicity via stimulation of pulmonary macrophages. All animal treated intravenously also perished before the end of the study. No significant (p<0.05) improvement in survival was observed between the groups treated with aerosols of free drug, DOX encapsulated in plain and in Tf-modified liposomes. However, more animals survived in the Tf-liposome groups than in the other treatment regimes, and their lung tissue generally had fewer and smaller tumors. Nevertheless, the size of the groups, and the duration of the trial render it impossible to come to a definite conclusion. Drug targeting demonstrated potential for improving the aerosol treatment of lung cancer.

  3. The customization of APACHE II for patients receiving orthotopic liver transplants

    PubMed Central

    Moreno, Rui

    2002-01-01

    General outcome prediction models developed for use with large, multicenter databases of critically ill patients may not correctly estimate mortality if applied to a particular group of patients that was under-represented in the original database. The development of new diagnostic weights has been proposed as a method of adapting the general model – the Acute Physiology and Chronic Health Evaluation (APACHE) II in this case – to a new group of patients. Such customization must be empirically tested, because the original model cannot contain an appropriate set of predictive variables for the particular group. In this issue of Critical Care, Arabi and co-workers present the results of the validation of a modified model of the APACHE II system for patients receiving orthotopic liver transplants. The use of a highly heterogeneous database for which not all important variables were taken into account and of a sample too small to use the Hosmer–Lemeshow goodness-of-fit test appropriately makes their conclusions uncertain. PMID:12133174

  4. Targeting Hypoxia-Inducible Factor 1α in a New Orthotopic Model of Glioblastoma Recapitulating the Hypoxic Tumor Microenvironment.

    PubMed

    Nigim, Fares; Cavanaugh, Jill; Patel, Anoop P; Curry, William T; Esaki, Shin-ichi; Kasper, Ekkehard M; Chi, Andrew S; Louis, David N; Martuza, Robert L; Rabkin, Samuel D; Wakimoto, Hiroaki

    2015-07-01

    Tissue hypoxia and necrosis represent pathophysiologic and histologic hallmarks of glioblastoma (GBM). Although hypoxia inducible factor 1α (HIF-1α) plays crucial roles in the malignant phenotypes of GBM, developing HIF-1α-targeted agents has been hampered by the lack of a suitable preclinical model that recapitulates the complex biology of clinical GBM. We present a new GBM model, MGG123, which was established from a recurrent human GBM. Orthotopic xenografting of stem-like MGG123 cells reproducibly generated lethal tumors that were characterized by foci of palisading necrosis, hypervascularity, and robust stem cell marker expression. Perinecrotic neoplastic cells distinctively express HIF-1α and are proliferative in both xenografts and the patient tissue. The xenografts contain scattered hypoxic foci that were consistently greater than 50 μm distant from blood vessels, indicating intratumoral heterogeneity of oxygenation. Hypoxia enhanced HIF-1α expression in cultured MGG123 cells, which was abrogated by the HIF-1α inhibitors digoxin or ouabain. In vivo, treatment of orthotopic MGG123 xenografts with digoxin decreased HIF-1α expression, vascular endothelial growth factor mRNA levels, and CD34-positive vasculature within the tumors, and extended survival of mice bearing the aggressive MGG123 GBM. This preclinical tumor model faithfully recapitulates the GBM-relevant hypoxic microenvironment and stemness and is a suitable platform for studying disease biology and developing hypoxia-targeted agents.

  5. Nanoparticle-enabled, image-guided treatment planning of target specific RNAi therapeutics in an orthotopic prostate cancer model.

    PubMed

    Lin, Qiaoya; Jin, Cheng S; Huang, Huang; Ding, Lili; Zhang, Zhihong; Chen, Juan; Zheng, Gang

    2014-08-13

    The abilities to deliver siRNA to its intended action site and assess the delivery efficiency are challenges for current RNAi therapy, where effective siRNA delivery will join force with patient genetic profiling to achieve optimal treatment outcome. Imaging could become a critical enabler to maximize RNAi efficacy in the context of tracking siRNA delivery, rational dosimetry and treatment planning. Several imaging modalities have been used to visualize nanoparticle-based siRNA delivery but rarely did they guide treatment planning. We report a multimodal theranostic lipid-nanoparticle, HPPS(NIR)-chol-siRNA, which has a near-infrared (NIR) fluorescent core, enveloped by phospholipid monolayer, intercalated with siRNA payloads, and constrained by apoA-I mimetic peptides to give ultra-small particle size (<30 nm). Using fluorescence imaging, we demonstrated its cytosolic delivery capability for both NIR-core and dye-labeled siRNAs and its structural integrity in mice through intravenous administration, validating the usefulness of NIR-core as imaging surrogate for non-labeled therapeutic siRNAs. Next, we validated the targeting specificity of HPPS(NIR)-chol-siRNA to orthotopic tumor using sequential four-steps (in vivo, in situ, ex vivo and frozen-tissue) fluorescence imaging. The image co-registration of computed tomography and fluorescence molecular tomography enabled non-invasive assessment and treatment planning of siRNA delivery into the orthotopic tumor, achieving efficacious RNAi therapy. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Marked elevation of hepatic transaminases in recipients of an orthotopic liver transplant from a brain-dead donor receiving extracorporeal membrane oxygenation.

    PubMed

    Teng-Wei, Chen; Chung-Bao, Hsieh; Chan, De-Chuan; Yu, Jyh-Cherng; Kuo, Shih-Ming; Tsai, Chien-Sung; Fan, Hsiu-Lung

    2014-12-29

    Hemodynamic instability can lead to failure of donor organ procurement in brain-dead donors. Extracorporeal membrane oxygenation (ECMO) has been used in non-heart-beating donors to increase the donor pool, but the use of ECMO to salvage donor organs has been rarely used. We aimed to analyze postoperative liver function test results in patients receiving orthotopic liver transplants from ECMO-supported brain-dead donors. We retrospectively reviewed the records of 43 recipients of orthotopic liver transplantation from May 2009 to June 2012. Six recipients received liver grafts from ECMO-maintained donors designated as the ECMO group (n=6). The remaining patients were assigned to the non-ECMO group (n=37). Complication and mortality rates and liver function test results on postoperative days 1, 3, 5, 7, and 14 were compared between the 2 groups. Serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase levels were significantly elevated on postoperative Day 1 in the ECMO group. There were no significant differences in the complication and overall survival rates between the 2 groups (P=0.411). Although serum transaminases markedly elevated on postoperative Day 1, ECMO successfully preserved potential liver grafts in hemodynamically unstable brain-dead donors.

  7. Development of a Preclinical Orthotopic Xenograft Model of Ewing Sarcoma and Other Human Malignant Bone Disease Using Advanced In Vivo Imaging

    PubMed Central

    Batey, Michael A.; Almeida, Gilberto S.; Wilson, Ian; Dildey, Petra; Sharma, Abhishek; Blair, Helen; Hide, I. Geoff; Heidenreich, Olaf; Vormoor, Josef; Maxwell, Ross J.; Bacon, Chris M.

    2014-01-01

    Ewing sarcoma and osteosarcoma represent the two most common primary bone tumours in childhood and adolescence, with bone metastases being the most adverse prognostic factor. In prostate cancer, osseous metastasis poses a major clinical challenge. We developed a preclinical orthotopic model of Ewing sarcoma, reflecting the biology of the tumour-bone interactions in human disease and allowing in vivo monitoring of disease progression, and compared this with models of osteosarcoma and prostate carcinoma. Human tumour cell lines were transplanted into non-obese diabetic/severe combined immunodeficient (NSG) and Rag2−/−/γc−/− mice by intrafemoral injection. For Ewing sarcoma, minimal cell numbers (1000–5000) injected in small volumes were able to induce orthotopic tumour growth. Tumour progression was studied using positron emission tomography, computed tomography, magnetic resonance imaging and bioluminescent imaging. Tumours and their interactions with bones were examined by histology. Each tumour induced bone destruction and outgrowth of extramedullary tumour masses, together with characteristic changes in bone that were well visualised by computed tomography, which correlated with post-mortem histology. Ewing sarcoma and, to a lesser extent, osteosarcoma cells induced prominent reactive new bone formation. Osteosarcoma cells produced osteoid and mineralised “malignant” bone within the tumour mass itself. Injection of prostate carcinoma cells led to osteoclast-driven osteolytic lesions. Bioluminescent imaging of Ewing sarcoma xenografts allowed easy and rapid monitoring of tumour growth and detection of tumour dissemination to lungs, liver and bone. Magnetic resonance imaging proved useful for monitoring soft tissue tumour growth and volume. Positron emission tomography proved to be of limited use in this model. Overall, we have developed an orthotopic in vivo model for Ewing sarcoma and other primary and secondary human bone malignancies, which

  8. Color-Coded Imaging of Syngeneic Orthotopic Malignant Lymphoma Interacting with Host Stromal Cells During Metastasis.

    PubMed

    Matsumoto, Takuro; Suetsugu, Atsushi; Hasegawa, Kosuke; Nakamura, Miki; Aoki, Hitomi; Kunisada, Takahiro; Tsurumi, Hisashi; Shimizu, Masahito; Hoffman, Robert M

    2016-04-01

    The EL4 cell line was previously derived from a lymphoma induced in a C57/BL6 mouse by 9,10-dimethyl-1,2-benzanthracene. In a previous study, EL4 lymphoma cells expressing red fluorescent protein (EL4-RFP) were established and injected into the tail vein of C57/BL6 green fluorescent protein (GFP) transgenic mice. Metastasis was observed at multiple sites which were also enriched with host GFP-expressing stromal cells. In the present study, our aim was to establish an orthotopic model of EL4-RFP. In the present study, EL4-RFP lymphoma cells were injected in the spleen of C57/BL6 GFP transgenic mice as an orthotopic model of lymphoma. Resultant primary tumor and metastases were imaged with the Olympus FV1000 scanning laser confocal microscope. EL4-RFP metastasis was observed 21 days later. EL4-RFP tumors in the spleen (primary injection site), liver, supra-mediastinum lymph nodes, abdominal lymph nodes, bone marrow, and lung were visualized by color-coded imaging. EL4-RFP metastases in the liver, lymph nodes, and bone marrow in C57/BL6 GFP mice were rich in GFP stromal cells such as macrophages, fibroblasts, dendritic cells, and normal lymphocytes derived from the host animal. Small tumors were observed in the spleen, which were rich in host stromal cells. In the lung, no mass formation of lymphoma cells occurred, but lymphoma cells circulated in lung peripheral blood vessels. Phagocytosis of EL4-RFP lymphoma cells by macrophages, as well as dendritic cells and fibroblasts, were observed in culture. Color-coded imaging of the lymphoma microenvironment suggests an important role of stromal cells in lymphoma progression and metastasis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. Ultrasound-Accelerated, Catheter-Directed Thrombolysis for Inferior Vena Cava Thrombosis After an Orthotopic Liver Transplant

    PubMed Central

    Latchana, Nicholas; Dowell, Joshua D.; Taani, Jamal Al; Michaels, Anthony; Elkhammas, Elmadhi; Black, Sylvester M.

    2015-01-01

    Inferior vena cava thrombosis is a rare occurrence after an orthotopic liver transplant that is associated with a high rate of retransplant and mortality. There is no consensus regarding the optimal therapeutic strategy. Surgical management, including thrombectomy with revision of the cavocaval anastomosis, has been described. With the use of endovascular therapies, several minimally invasive approaches are available that are effective and avoid the high morbidity associated with reoperative surgery. We describe our successful experience using an approach after a liver transplant in which the inferior vena cava thrombosis in a patient presenting with acute renal failure, anorexia, weight loss, and fatigue using an ultrasound-accelerated, catheter-directed thrombolysis platform in conjunction with systemic anticoagulation. PMID:24918871

  10. Emodin inhibits growth and induces apoptosis in an orthotopic hepatocellular carcinoma model by blocking activation of STAT3

    PubMed Central

    Subramaniam, Aruljothi; Shanmugam, Muthu K; Ong, Tina H; Li, Feng; Perumal, Ekambaram; Chen, Luxi; Vali, Shireen; Abbasi, Taher; Kapoor, Shweta; Ahn, Kwang Seok; Kumar, Alan Prem; Hui, Kam M; Sethi, Gautam

    2013-01-01

    BACKGROUND AND PURPOSE Aberrant activation of STAT3 is frequently encountered and promotes proliferation, survival, metastasis and angiogenesis in hepatocellular carcinoma (HCC). Here, we have investigated whether emodin mediates its effect through interference with the STAT3 activation pathway in HCC. EXPERIMENTAL APPROACH The effect of emodin on STAT3 activation, associated protein kinases and apoptosis was investigated using various HCC cell lines. Additionally, we also used a predictive tumour technology to analyse the effects of emodin. The in vivo effects of emodin were assessed in an orthotopic mouse model of HCC. KEY RESULTS Emodin suppressed STAT3 activation in a dose- and time-dependent manner in HCC cells, mediated by the modulation of activation of upstream kinases c-Src, JAK1 and JAK2. Vanadate treatment reversed emodin-induced down-regulation of STAT3, suggesting the involvement of a tyrosine phosphatase and emodin induced the expression of the tyrosine phosphatase SHP-1 that correlated with the down-regulation of constitutive STAT3 activation. Interestingly, silencing of the SHP-1 gene by siRNA abolished the ability of emodin to inhibit STAT3 activation. Finally, when administered i.p., emodin inhibited the growth of human HCC orthotopic tumours in male athymic nu/nu mice and STAT3 activation in tumour tissues. CONCLUSIONS AND IMPLICATIONS Emodin mediated its effects predominantly through inhibition of the STAT3 signalling cascade and thus has a particular potential for the treatment of cancers expressing constitutively activated STAT3. PMID:23848338

  11. Orthotopic transplantation of LH receptor knockout and wild-type ovaries.

    PubMed

    Chudgar, Daksha; Lei, Zhenmin; Rao, Ch V

    2005-10-07

    Luteinizing hormone (LH) receptor knockout animals have an ovarian failure due to an arrest in folliculogenesis at the antral stage. As a result, the animals have an infertility phenotype. The present study was undertaken to determine whether this phenotype could be reversed by orthotopic transplantation of wild-type ovaries. The results revealed that transplanting wild-type ovaries into null animals did not result in resumption of estrus cycles. Although the number of different types of follicles increased, none progressed to ovulation. The serum hormone profiles improved, reflecting the ovarian changes. The wild-type animals with null ovaries also failed to cycle and their ovaries and serum hormone levels were more like null animals with their own ovaries. Although the lack of rescue of null ovaries placed into wild-type animals was predicted, the failure of wild-type ovaries placed in null animals was not, which could be due to chronic exposure of transplanted tissue to high circulating LH levels and also possibly due to altered internal milieu in null animals. These findings may have implications for potential future considerations of grafting normal donor ovaries into women who have an ovarian failure resulting from inactivating LH receptor mutations.

  12. Newly Designed Y-configured Single-Catheter Stenting for the Treatment of Hilar-Type Nonanastomotic Biliary Strictures After Orthotopic Liver Transplantation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang Changming; Li Xuan, E-mail: lixuanbysy@163.com; Song Shibing

    2012-02-15

    Purpose: This study was designed to introduce our novel technique of percutaneous single catheter placement into the hilar bile ducts strictures while fulfilling the purpose of bilateral biliary drainage and stenting. We investigated the efficacy and safety of the technique for the treatment of hilar nonanastomotic biliary strictures. Methods: Ten patients who were post-orthotopic liver transplantation between July 2000 and July 2010 were enrolled in this study. Percutaneous Y-configured single-catheter stenting for bilateral bile ducts combined with balloon dilation was designed as the main treatment approach. Technical success rate, clinical indicators, complications, and recurrent rate were analyzed. Results: Technical successmore » rate was 100%. Nine of the ten patients had biochemical normalization, cholangiographic improvement, and clinical symptoms relief. None of them experienced recurrence in a median follow-up of 26 months after completion of therapy and removal of all catheters. Complications were minor and limited to two patients. The one treatment failure underwent a second liver transplantation but died of multiple system organ failure. Conclusions: Percutaneous transhepatic Y-configured single-catheter stenting into the hilar bile ducts is technically feasible. The preliminary trial of this technique combined with traditional PTCD or choledochoscopy for the treatment of hilar biliary strictures after orthotopic liver transplantation appeared to be effective and safe. Yet, further investigation is needed.« less

  13. A point-based prediction model for cardiovascular risk in orthotopic liver transplantation: The CAR-OLT score.

    PubMed

    VanWagner, Lisa B; Ning, Hongyan; Whitsett, Maureen; Levitsky, Josh; Uttal, Sarah; Wilkins, John T; Abecassis, Michael M; Ladner, Daniela P; Skaro, Anton I; Lloyd-Jones, Donald M

    2017-12-01

    Cardiovascular disease (CVD) complications are important causes of morbidity and mortality after orthotopic liver transplantation (OLT). There is currently no preoperative risk-assessment tool that allows physicians to estimate the risk for CVD events following OLT. We sought to develop a point-based prediction model (risk score) for CVD complications after OLT, the Cardiovascular Risk in Orthotopic Liver Transplantation risk score, among a cohort of 1,024 consecutive patients aged 18-75 years who underwent first OLT in a tertiary-care teaching hospital (2002-2011). The main outcome measures were major 1-year CVD complications, defined as death from a CVD cause or hospitalization for a major CVD event (myocardial infarction, revascularization, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism, and/or stroke). The bootstrap method yielded bias-corrected 95% confidence intervals for the regression coefficients of the final model. Among 1,024 first OLT recipients, major CVD complications occurred in 329 (32.1%). Variables selected for inclusion in the model (using model optimization strategies) included preoperative recipient age, sex, race, employment status, education status, history of hepatocellular carcinoma, diabetes, heart failure, atrial fibrillation, pulmonary or systemic hypertension, and respiratory failure. The discriminative performance of the point-based score (C statistic = 0.78, bias-corrected C statistic = 0.77) was superior to other published risk models for postoperative CVD morbidity and mortality, and it had appropriate calibration (Hosmer-Lemeshow P = 0.33). The point-based risk score can identify patients at risk for CVD complications after OLT surgery (available at www.carolt.us); this score may be useful for identification of candidates for further risk stratification or other management strategies to improve CVD outcomes after OLT. (Hepatology 2017;66:1968-1979). © 2017 by the American Association for the Study of Liver

  14. A preclinical orthotopic model for glioblastoma recapitulates key features of human tumors and demonstrates sensitivity to a combination of MEK and PI3K pathway inhibitors.

    PubMed

    El Meskini, Rajaa; Iacovelli, Anthony J; Kulaga, Alan; Gumprecht, Michelle; Martin, Philip L; Baran, Maureen; Householder, Deborah B; Van Dyke, Terry; Weaver Ohler, Zoë

    2015-01-01

    Current therapies for glioblastoma multiforme (GBM), the highest grade malignant brain tumor, are mostly ineffective, and better preclinical model systems are needed to increase the successful translation of drug discovery efforts into the clinic. Previous work describes a genetically engineered mouse (GEM) model that contains perturbations in the most frequently dysregulated networks in GBM (driven by RB, KRAS and/or PI3K signaling and PTEN) that induce development of Grade IV astrocytoma with properties of the human disease. Here, we developed and characterized an orthotopic mouse model derived from the GEM that retains the features of the GEM model in an immunocompetent background; however, this model is also tractable and efficient for preclinical evaluation of candidate therapeutic regimens. Orthotopic brain tumors are highly proliferative, invasive and vascular, and express histology markers characteristic of human GBM. Primary tumor cells were examined for sensitivity to chemotherapeutics and targeted drugs. PI3K and MAPK pathway inhibitors, when used as single agents, inhibited cell proliferation but did not result in significant apoptosis. However, in combination, these inhibitors resulted in a substantial increase in cell death. Moreover, these findings translated into the in vivo orthotopic model: PI3K or MAPK inhibitor treatment regimens resulted in incomplete pathway suppression and feedback loops, whereas dual treatment delayed tumor growth through increased apoptosis and decreased tumor cell proliferation. Analysis of downstream pathway components revealed a cooperative effect on target downregulation. These concordant results, together with the morphologic similarities to the human GBM disease characteristics of the model, validate it as a new platform for the evaluation of GBM treatment. © 2015. Published by The Company of Biologists Ltd.

  15. A preclinical orthotopic model for glioblastoma recapitulates key features of human tumors and demonstrates sensitivity to a combination of MEK and PI3K pathway inhibitors

    PubMed Central

    El Meskini, Rajaa; Iacovelli, Anthony J.; Kulaga, Alan; Gumprecht, Michelle; Martin, Philip L.; Baran, Maureen; Householder, Deborah B.; Van Dyke, Terry; Weaver Ohler, Zoë

    2015-01-01

    Current therapies for glioblastoma multiforme (GBM), the highest grade malignant brain tumor, are mostly ineffective, and better preclinical model systems are needed to increase the successful translation of drug discovery efforts into the clinic. Previous work describes a genetically engineered mouse (GEM) model that contains perturbations in the most frequently dysregulated networks in GBM (driven by RB, KRAS and/or PI3K signaling and PTEN) that induce development of Grade IV astrocytoma with properties of the human disease. Here, we developed and characterized an orthotopic mouse model derived from the GEM that retains the features of the GEM model in an immunocompetent background; however, this model is also tractable and efficient for preclinical evaluation of candidate therapeutic regimens. Orthotopic brain tumors are highly proliferative, invasive and vascular, and express histology markers characteristic of human GBM. Primary tumor cells were examined for sensitivity to chemotherapeutics and targeted drugs. PI3K and MAPK pathway inhibitors, when used as single agents, inhibited cell proliferation but did not result in significant apoptosis. However, in combination, these inhibitors resulted in a substantial increase in cell death. Moreover, these findings translated into the in vivo orthotopic model: PI3K or MAPK inhibitor treatment regimens resulted in incomplete pathway suppression and feedback loops, whereas dual treatment delayed tumor growth through increased apoptosis and decreased tumor cell proliferation. Analysis of downstream pathway components revealed a cooperative effect on target downregulation. These concordant results, together with the morphologic similarities to the human GBM disease characteristics of the model, validate it as a new platform for the evaluation of GBM treatment. PMID:25431423

  16. Influence of in vivo growth on human glioma cell line gene expression: Convergent profiles under orthotopic conditions

    PubMed Central

    Camphausen, Kevin; Purow, Benjamin; Sproull, Mary; Scott, Tamalee; Ozawa, Tomoko; Deen, Dennis F.; Tofilon, Philip J.

    2005-01-01

    Defining the molecules that regulate tumor cell survival is an essential prerequisite for the development of targeted approaches to cancer treatment. Whereas many studies aimed at identifying such targets use human tumor cells grown in vitro or as s.c. xenografts, it is unclear whether such experimental models replicate the phenotype of the in situ tumor cell. To begin addressing this issue, we have used microarray analysis to define the gene expression profile of two human glioma cell lines (U251 and U87) when grown in vitro and in vivo as s.c. or as intracerebral (i.c.) xenografts. For each cell line, the gene expression profile generated from tissue culture was significantly different from that generated from the s.c. tumor, which was significantly different from those grown i.c. The disparity between the i.c gene expression profiles and those generated from s.c. xenografts suggests that whereas an in vivo growth environment modulates gene expression, orthotopic growth conditions induce a different set of modifications. In this study the U251 and U87 gene expression profiles generated under the three growth conditions were also compared. As expected, the profiles of the two glioma cell lines were significantly different when grown as monolayer cultures. However, the glioma cell lines had similar gene expression profiles when grown i.c. These results suggest that tumor cell gene expression, and thus phenotype, as defined in vitro is affected not only by in vivo growth but also by orthotopic growth, which may have implications regarding the identification of relevant targets for cancer therapy. PMID:15928080

  17. Antimetastatic Efficacy of the Combination of Caffeine and Valproic Acid on an Orthotopic Human Osteosarcoma Cell Line Model in Nude Mice.

    PubMed

    Igarashi, Kentaro; Kawaguchi, Kei; Kiyuna, Tasuku; Murakami, Takashi; Yamamoto, Norio; Hayashi, Katsuhiro; Kimura, Hiroaki; Miwa, Shinji; Tsuchiya, Hiroyuki; Hoffman, Robert M

    2017-03-01

    We have previously reported that caffeine can enhance chemotherapy efficacy of bone and soft tissue sarcoma via cell-cycle perturbation. Valproic acid has histone deacetylase (HDAC) inhibitory activity. We have also reported the anti-tumor efficacy of combination treatment with caffeine and valproic acid against osteosarcoma primary tumors in a cell-line orthotopic mouse model. In this study, we performed combination treatment of caffeine and valproic acid on osteosarcoma cell lines in vitro and in spontaneous and experimental lung metastasis mouse models of osteosarcoma. Survival of 143B-RFP human osteosarcoma cells after exposure to caffeine and valproic acid for 72 hours was determined using the WST-8 assay. IC 50 values and combination indices were calculated. Mouse models of primary osteosarcoma and spontaneous lung metastasis were obtained by orthotopic intra-tibial injection of 143B-RFP cells. Valproic acid, caffeine, and combination of both drugs were administered from day 7, five times a week, for four weeks. Six weeks after orthotopic injection, lung samples were excised and observed with a fluorescence imaging system. A mouse model of experimental lung metastasis was obtained by tail vein injection of 143B-RFP cells. The mice were treated with these agents from day 0, five times a week for four weeks. Both caffeine and valproic acid caused concentration-dependent cell kill in vitro. Synergistic efficacy of the combination treatment was observed. In the spontaneous lung-metastasis model, the number of lung metastasis was 9.0±2.6 in the untreated group (G1); 10.8±2.9 in the caffeine group (G2); 10.0±3.1 in the valproic-acid group (G3); and 3.0±1.1 in the combination group (G4); (p=6.78E-5 control vs. combination; p=0.006 valproic acid vs. combination; p=0.003 caffeine vs. combination). In the experimental lung-metastasis model, the combination group significantly reduced lung metastases and improved overall survival (p=0.0005). Efficacy of the

  18. Hip joint replacement

    MedlinePlus

    ... Total hip replacement; Hip hemiarthroplasty; Arthritis - hip replacement; Osteoarthritis - hip replacement ... total hip replacement surgery in patients with hip osteoarthritis: a long-term follow-up of a randomised ...

  19. Recombinant methioninase combined with doxorubicin (DOX) regresses a DOX-resistant synovial sarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model

    PubMed Central

    Igarashi, Kentaro; Kawaguchi, Kei; Li, Shukuan; Han, Qinghong; Tan, Yuying; Gainor, Emily; Kiyuna, Tasuku; Miyake, Kentaro; Miyake, Masuyo; Higuchi, Takashi; Oshiro, Hiromichi; Singh, Arun S.; Eckardt, Mark A.; Nelson, Scott D.; Russell, Tara A.; Dry, Sarah M.; Li, Yunfeng; Yamamoto, Norio; Hayashi, Katsuhiro; Kimura, Hiroaki; Miwa, Shinji; Tsuchiya, Hiroyuki; Eilber, Fritz C.; Hoffman, Robert M.

    2018-01-01

    Synovial sarcoma (SS) is a recalcitrant subgroup of soft tissue sarcoma (STS). A tumor from a patient with high grade SS from a lower extremity was grown orthotopically in the right biceps femoris muscle of nude mice to establish a patient-derived orthotopic xenograft (PDOX) mouse model. The PDOX mice were randomized into the following groups when tumor volume reached approximately 100 mm3: G1, control without treatment; G2, doxorubicin (DOX) (3 mg/kg, intraperitoneal [i.p.] injection, weekly, for 2 weeks; G3, rMETase (100 unit/mouse, i.p., daily, for 2 weeks); G4 DOX (3mg/kg), i.p. weekly, for 2 weeks) combined with rMETase (100 unit/mouse, i.p., daily, for 2 weeks). On day 14 after treatment initiation, all therapies significantly inhibited tumor growth compared to untreated control, except DOX: (DOX: p = 0.48; rMETase: p < 0.005; DOX combined with rMETase < 0.0001). DOX combined with rMETase was significantly more effective than both DOX alone (p < 0.001) and rMETase alone (p < 0.05). The relative body weight on day 14 compared with day 0 did not significantly differ between any treatment group or untreated control. The results indicate that r-METase can overcome DOX-resistance in this recalcitrant disease. PMID:29721200

  20. Selective efficacy of zoledronic acid on metastasis in a patient-derived orthotopic xenograph (PDOX) nude-mouse model of human pancreatic cancer.

    PubMed

    Hiroshima, Yukihiko; Maawy, Ali A; Katz, Matthew H G; Fleming, Jason B; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

    2015-03-01

    Patient-derived orthotopic xenograft (PDOX) nude-mouse models replicate the behavior of clinical cancer, including metastasis. The objective of the study was to determine the efficacy of zoledronic acid (ZA) on metastasis of a patient-derived orthotopic xenograft (PDOX) nude-mouse model of pancreatic cancer. In the present study, we examined the efficacy of ZA on pancreatic cancer growth and metastasis in a PDOX nude-mouse model. ZA monotherapy did not significantly suppress primary tumor growth. However, the primary tumor weight of gemcitabine (GEM) and combination GEM + ZA-treated mice was significantly decreased compared to the control group (GEM: P = 0.003; GEM + ZA: P = 0.002). The primary tumor weight of GEM + ZA-treated mice was significantly decreased compared to GEM-treated mice (P = 0.016). The metastasis weight decreased in ZA- or GEM-treated mice compared to the control group (ZA: P = 0.009; GEM: P = 0.007. No metastasis was detected in combination GEM + ZA-treated mice compared to the control group (GEM + ZA; P = 0.005). The results of the present study indicate that ZA can selectively target metastasis in a pancreatic cancer PDOX model and that the combination of ZA and GEM should be evaluated clinically in the near future for this highly treatment-resistant disease. © 2014 Wiley Periodicals, Inc.

  1. Piggyback technique in adult orthotopic liver transplantation: an analysis of 1067 liver transplants at a single center

    PubMed Central

    Nakamura, Noboru; Vaidya, Anil; Levi, David M.; Kato, Tomoaki; Nery, Jose R.; Madariaga, Juan R.; Molina, Enrique; Ruiz, Phillip; Gyamfi, Anthony; Tzakis, Andreas G.

    2006-01-01

    Background. Orthotopic liver transplantation (OLT) in adult patients has traditionally been performed using conventional caval reconstruction technique (CV) with veno-venous bypass. Recently, the piggyback technique (PB) without veno-venous bypass has begun to be widely used. The aim of this study was to assess the effect of routine use of PB on OLTs in adult patients. Patients and methods. A retrospective analysis was undertaken of 1067 orthotopic cadaveric whole liver transplantations in adult patients treated between June 1994 and July 2001. PB was used as the routine procedure. Patient demographics, factors including cold ischemia time (CIT), warm ischemia time (WIT), operative time, transfusions, blood loss, and postoperative results were assessed. The effects of clinical factors on graft survival were assessed by univariate and multivariate analyses.In all, 918 transplantations (86%) were performed with PB. Blood transfusion, WIT, and usage of veno-venous bypass were less with PB. Seventy-five (8.3%) cases with PB had refractory ascites following OLT (p=NS). Five venous outflow stenosis cases (0.54%) with PB were noted (p=NS). The liver and renal function during the postoperative periods was similar. Overall 1-, 3-, and 5-year patient survival rates were 85%, 78%, and 72% with PB. Univariate analysis showed that cava reconstruction method, CIT, WIT, amount of transfusion, length of hospital stay, donor age, and tumor presence were significant factors influencing graft survival. Multivariate analysis further reinforced the fact that CIT, donor age, amount of transfusion, and hospital stay were prognostic factors for graft survival. Conclusions. PB can be performed safely in the majority of adult OLTs. Results of OLT with PB are as same as for CV. Liver function, renal function, morbidity, mortality, and patient and graft survival are similar to CV. However, amount of transfusion, WIT, and use of veno-venous bypass are less with PB. PMID:18333273

  2. Use of Panitumumab-IRDye800 to Image Microscopic Head and Neck Cancer in an Orthotopic Surgical Model

    PubMed Central

    Heath, C. Hope; Deep, Nicholas L.; Sweeny, Larissa; Zinn, Kurt R; Rosenthal, Eben L.

    2013-01-01

    Background Fluorescence imaging hardware (SPY) has recently been developed for intraoperative assessment of blood flow via detection of probes emitting in the near-infrared (NIR) spectrum. This study sought to determine if this imaging system was capable of detecting micrometastatic head and neck squamous cell carcinoma (HNSCC) in preclinical models. Methods A NIR fluorescent probe (IRDye800CW) was covalently linked to a monoclonal antibody targeting EGFR (panitumumab) or non-specific IgG. HNSCC flank (SCC-1) and orthotopic (FADU and OSC19) xenografts were imaged 48-96hrs following systemic injection of labeled panitumumab or IgG. The primary tumor and regional lymph nodes were dissected using fluorescence guidance with the SPY system and grossly assessed with a charge-coupled NIR system (Pearl). Histologic slides were also imaged with a NIR charged-coupled device (Odyssey) and fluorescence intensity was correlated with pathologic confirmation of disease. Results Orthotopic tongue tumors were clearly delineated from normal tissue with tumor-to-background ratios of 2.9(Pearl) and 2.3(SPY). Disease detection was significantly improved with panitumumab-IRDye compared to IgG-IRDye800 (P<0.05). Tissue biopsies (average size=3.7mm) positive for fluorescence were confirmed for pathologic disease by histology and immunohistochemistry (n=25/25). Biopsies of non-fluorescent tissue were proven to be negative for malignancy (n=28/28). The SPY was able to detect regional lymph node metastasis (<1.0mm) and microscopic areas of disease. Standard histological assessment in both frozen and paraffin-embedded histologic specimens was augmented using the Odyssey. Conclusions Panitumumab-IRDye800 may have clinical utility in detection and removal of microscopic HNSCC using existing intraoperative optical imaging hardware and may augment analysis of frozen and permanent pathology. PMID:22669455

  3. Orthotopic Transplantation of Achilles Tendon Allograft in Rats: With or without Incorporation of Autologous Mesenchymal Stem Cells.

    PubMed

    Aynardi, Michael; Zahoor, Talal; Mitchell, Reed; Loube, Jeffrey; Feltham, Tyler; Manandhar, Lumanti; Paudel, Sharada; Schon, Lew; Zhang, Zijun

    2018-02-01

    The biology and function of orthotopic transplantation of Achilles tendon allograft are unknown. Particularly, the revitalization of Achilles allograft is a clinical concern. Achilles allografts were harvested from donor rats and stored at -80 °C. Subcutaneous adipose tissue was harvested from the would-be allograft recipient rats for isolation of mesenchymal stem cells (MSCs). MSCs were cultured with growth differentiation factor-5 (GDF-5) and applied onto Achilles allografts on the day of transplantation. After the native Achilles tendon was resected from the left hind limb of the rats, Achilles allograft, with or without autologous MSCs, was implanted and sutured with calf muscles proximally and calcaneus distally. Animal gait was recorded presurgery and postsurgery weekly. The animals were sacrificed at week 4, and the transplanted Achilles allografts were collected for biomechanical testing and histology. The operated limbs had altered gait. By week 4, the paw print intensity, stance time, and duty cycle (percentage of the stance phase in a step cycle) of the reconstructed limbs were mostly recovered to the baselines recorded before surgery. Maximum load of failure was not different between Achilles allografts, with or without MSCs, and the native tendons. The Achilles allograft supplemented with MSCs had higher cellularity than the Achilles allograft without MSCs. Deposition of fine collagen (type III) fibers was active in Achilles allograft, with or without MSCs, but it was more evenly distributed in the allografts that were incubated with MSCs. In conclusion, orthotopically transplanted Achilles allograft healed with host tissues, regained strength, and largely restored Achilles function in 4 wk in rats. It is therefore a viable option for the reconstruction of a large Achilles tendon defect. Supplementation of MSCs improved repopulation of Achilles allograft, but large animal models, with long-term follow up and cell tracking, may be required to fully

  4. Targeting experimental orthotopic glioblastoma with chitosan-based superparamagnetic iron oxide nanoparticles (CS-DX-SPIONs).

    PubMed

    Shevtsov, Maxim; Nikolaev, Boris; Marchenko, Yaroslav; Yakovleva, Ludmila; Skvortsov, Nikita; Mazur, Anton; Tolstoy, Peter; Ryzhov, Vyacheslav; Multhoff, Gabriele

    2018-01-01

    Glioblastoma is the most devastating primary brain tumor of the central nervous system in adults. Magnetic nanocarriers may help not only for a targeted delivery of chemotherapeutic agents into the tumor site but also provide contrast enhancing properties for diagnostics using magnetic resonance imaging (MRI). Synthesized hybrid chitosan-dextran superparamagnetic nanoparticles (CS-DX-SPIONs) were characterized using transmission electron microscopy (TEM) and relaxometry studies. Nonlinear magnetic response measurements were employed for confirming the superparamagnetic state of particles. Following in vitro analysis of nanoparticles cellular uptake tumor targeting was assessed in the model of the orthotopic glioma in rodents. CS-DX-SPIONs nanoparticles showed a uniform diameter of 55 nm under TEM and superparamagentic characteristics as determined by T 1 (spin-lattice relaxation time) and T 2 (spin-spin relaxation time) proton relaxation times. Application of the chitosan increased the charge from +8.9 to +19.3 mV of the dextran-based SPIONs. The nonlinear magnetic response at second harmonic of CS-DX-SPIONs following the slow change of stationary magnetic fields with very low hysteresis evidenced superparamagnetic state of particles at ambient temperatures. Confocal microscopy and flow cytometry studies showed an enhanced internalization of the chitosan-based nanoparticles in U87, C6 glioma and HeLa cells as compared to dextran-coated particles. Cytotoxicity assay demonstrated acceptable toxicity profile of the synthesized nanoparticles up to a concentration of 10 μg/ml. Intravenously administered CS-DX-SPIONs in orthotopic C6 gliomas in rats accumulated in the tumor site as shown by high-resolution MRI (11.0 T). Retention of nanoparticles resulted in a significant contrast enhancement of the tumor image that was accompanied with a dramatic drop in T 2 values ( P <0.001). Subsequent histological studies proved the accumulation of the nanoparticles inside

  5. Intracranial AAV-sTRAIL combined with lanatoside C prolongs survival in an orthotopic xenograft mouse model of invasive glioblastoma.

    PubMed

    Crommentuijn, Matheus H W; Maguire, Casey A; Niers, Johanna M; Vandertop, W Peter; Badr, Christian E; Würdinger, Thomas; Tannous, Bakhos A

    2016-04-01

    Glioblastoma (GBM) is the most common malignant brain tumor in adults. We designed an adeno-associated virus (AAV) vector for intracranial delivery of secreted, soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) to GBM tumors in mice and combined it with the TRAIL-sensitizing cardiac glycoside, lanatoside C (lan C). We applied this combined therapy to two different GBM models using human U87 glioma cells and primary patient-derived GBM neural spheres in culture and in orthotopic GBM xenograft models in mice. In U87 cells, conditioned medium from AAV2-sTRAIL expressing cells combined with lan C induced 80% cell death. Similarly, lan C sensitized primary GBM spheres to sTRAIL causing over 90% cell death. In mice bearing intracranial U87 tumors treated with AAVrh.8-sTRAIL, administration of lan C caused a decrease in tumor-associated Fluc signal, while tumor size increased within days of stopping the treatment. Another round of lan C treatment re-sensitized GBM tumor to sTRAIL-induced cell death. AAVrh.8-sTRAIL treatment alone and combined with lanatoside C resulted in a significant decrease in tumor growth and longer survival of mice bearing orthotopic invasive GBM brain tumors. In summary, AAV-sTRAIL combined with lanatoside C induced cell death in U87 glioma cells and patient-derived GBM neural spheres in culture and in vivo leading to an increased in overall mice survival. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  6. The Antineoplastic Activity of Photothermal Ablative Therapy with Targeted Gold Nanorods in an Orthotopic Urinary Bladder Cancer Model.

    PubMed

    Yang, Xiaoping; Su, Lih-Jen; La Rosa, Francisco G; Smith, Elizabeth Erin; Schlaepfer, Isabel R; Cho, Suehyun K; Kavanagh, Brian; Park, Wounjhang; Flaig, Thomas W

    2017-07-27

    Gold nanoparticles treated with near infrared (NIR) light can be heated preferentially, allowing for thermal ablation of targeted cells. The use of novel intravesical nanoparticle-directed therapy in conjunction with laser irradiation via a fiber optic cystoscope, represents a potential ablative treatment approach in patients with superficial bladder cancer. To examine the thermal ablative effect of epidermal growth factor receptor (EGFR)-directed gold nanorods irradiated with NIR light in an orthotopic urinary bladder cancer model. Gold nanorods linked to an anti-EGFR antibody (Conjugated gold NanoRods - CNR) were instilled into the bladder cavity of an orthotopic murine xenograft model with T24 bladder cancer cells expressing luciferase. NIR light was externally administered via an 808 nm diode laser. This treatment was repeated weekly for 4 weeks. The anti-cancer effect was monitored by an in vivo imaging system in a non-invasive manner, which was the primary outcome of our study. The optimal approach for an individual treatment was 2.1 W/cm 2 laser power for 30 seconds. Using this in vivo model, NIR light combined with CNR demonstrated a statistically significant reduction in tumor-associated bioluminescent activity ( n  = 16) compared to mice treated with laser alone ( n  = 14) at the end of the study ( p  = 0.035). Furthermore, the CNR+NIR light treatment significantly abrogated bioluminescence signals over a 6-week observation period, compared to pre-treatment levels ( p  = 0.045). Photothermal tumor ablation with EGFR-directed gold nanorods and NIR light proved effective and well tolerated in a murine in vivo model of urinary bladder cancer.

  7. Diagnostic Value of Anti-Hepatitis C Virus (HCV) Core Immunoglobulin M in Recurrence of HCV Infection after Orthotopic Liver Transplantation†

    PubMed Central

    Casino, Carmela; Lilli, Daniela; Rivanera, Daniela; Comanducci, Antonella; Rossi, Massimo; Casciaro, Giovanni; Pecorella, Irene; Alfani, Dario; Mancini, Carlo

    1999-01-01

    The significance of anti-hepatitis C virus (HCV) core immunoglobulin M (IgM) and its relationship with genotypes, alanine aminotransferase abnormality, and histological data were studied for 18 patients who had undergone orthotopic liver transplantation due to HCV-related end-stage disease. During follow-up, IgM response seemed to be associated with the recurrence of HCV infection but did not correlate with abnormal alanine aminotransferase levels and histological data. In addition, the results of this study indicated that the detection of HCV RNA is critical for diagnosis of reinfection in liver transplantation. PMID:10405433

  8. Inorganic Nanovehicle Targets Tumor in an Orthotopic Breast Cancer Model

    NASA Astrophysics Data System (ADS)

    Choi, Goeun; Kwon, Oh-Joon; Oh, Yeonji; Yun, Chae-Ok; Choy, Jin-Ho

    2014-03-01

    The clinical efficacy of conventional chemotherapeutic agent, methotrexate (MTX), can be limited by its very short plasma half-life, the drug resistance, and the high dosage required for cancer cell suppression. In this study, a new drug delivery system is proposed to overcome such limitations. To realize such a system, MTX was intercalated into layered double hydroxides (LDHs), inorganic drug delivery vehicle, through a co-precipitation route to produce a MTX-LDH nanohybrid with an average particle size of approximately 130 nm. Biodistribution studies in mice bearing orthotopic human breast tumors revealed that the tumor-to-liver ratio of MTX in the MTX-LDH-treated-group was 6-fold higher than that of MTX-treated-one after drug treatment for 2 hr. Moreover, MTX-LDH exhibited superior targeting effect resulting in high antitumor efficacy inducing a 74.3% reduction in tumor volume compared to MTX alone, and as a consequence, significant survival benefits. Annexin-V and propidium iodine dual staining and TUNEL analysis showed that MTX-LDH induced a greater degree of apoptosis than free MTX. Taken together, our data demonstrate that a new MTX-LDH nanohybrid exhibits a superior efficacy profile and improved distribution compared to MTX alone and has the potential to enhance therapeutic efficacy via inhibition of tumor proliferation and induction of apoptosis.

  9. Inorganic nanovehicle targets tumor in an orthotopic breast cancer model.

    PubMed

    Choi, Goeun; Kwon, Oh-Joon; Oh, Yeonji; Yun, Chae-Ok; Choy, Jin-Ho

    2014-03-21

    The clinical efficacy of conventional chemotherapeutic agent, methotrexate (MTX), can be limited by its very short plasma half-life, the drug resistance, and the high dosage required for cancer cell suppression. In this study, a new drug delivery system is proposed to overcome such limitations. To realize such a system, MTX was intercalated into layered double hydroxides (LDHs), inorganic drug delivery vehicle, through a co-precipitation route to produce a MTX-LDH nanohybrid with an average particle size of approximately 130 nm. Biodistribution studies in mice bearing orthotopic human breast tumors revealed that the tumor-to-liver ratio of MTX in the MTX-LDH-treated-group was 6-fold higher than that of MTX-treated-one after drug treatment for 2 hr. Moreover, MTX-LDH exhibited superior targeting effect resulting in high antitumor efficacy inducing a 74.3% reduction in tumor volume compared to MTX alone, and as a consequence, significant survival benefits. Annexin-V and propidium iodine dual staining and TUNEL analysis showed that MTX-LDH induced a greater degree of apoptosis than free MTX. Taken together, our data demonstrate that a new MTX-LDH nanohybrid exhibits a superior efficacy profile and improved distribution compared to MTX alone and has the potential to enhance therapeutic efficacy via inhibition of tumor proliferation and induction of apoptosis.

  10. Shoulder replacement - discharge

    MedlinePlus

    Total shoulder arthroplasty - discharge; Endoprosthetic shoulder replacement - discharge; Partial shoulder replacement - discharge; Partial shoulder arthroplasty - discharge; Replacement - shoulder - discharge; Arthroplasty - shoulder - ...

  11. Ethanolic Extract of Traditional Chinese Medicine (TCM) Gamboge Inhibits Colon Cancer via the Wnt/Beta-Catenin Signaling Pathway in an Orthotopic Mouse Model.

    PubMed

    Wang, Wei; Li, Youran; Chen, Yiqi; Chen, Hongjin; Zhu, Ping; Xu, Minmin; Wang, Hao; Wu, Minna; Yang, Zhijian; Hoffman, Robert M; Gu, Yunfei

    2018-04-01

    The aim of the present study was to investigate the efficacy of an ethanolic extract of gamboge (EEG), a traditional Chinese medicine (TCM), both in vitro on colon cancer cells and in vivo in an orthotopic mouse model of human colon cancer. The in vitro cytotoxicity of EEG on colon cancer cells was determined with the CCK8 proliferation assay and the Annexin V-PE/7-AAD apoptosis assay. Efficacy of EEG in vivo was evaluated in an orthotopic mouse model of human colon cancer implated with the green fluorescent protein-expressing human colon cancer cell line SW480-GFP. The tumor-bearing mice were treated with vehicle (0.2 ml/dose normal saline, po, daily), irinotecan (50 mg/kg/dose, ip, twice a week), 5-FU (15 mg/kg/dose, ip, every other day) as positive controls or EEG at doses of 12.5, 25 and 50 mg/kg/dose, po, daily. Real-time fluorescence imaging was performed to determine tumor inhibition in each treated group compared to the untreated controls. The protein expression of β-catenin, MMP-7, cyclin D1 and E-cadherin in the tumors was analyzed by immunohistochemistry. EEG significantly induced proliferation inhibition and apoptosis of SW480 colon cancer cells in vitro in a dose-dependent manner. Tumor growth in the colon-cancer orthotopic model was significantly inhibited by irinotecan, 5-FU and all three doses of EEG. The efficacy of EEG was comparable to irinotecan and 5-FU. Irinotecan, 5-FU and 50 mg/kg EEG significantly decreased the protein expression of β-catenin and MMP-7. Cyclin D1 expression was decreased and E-cadherin expression was increased by irinotecan, 5-FU and all three doses of EEG. The present study demonstrates anti-tumor efficacy of EEG on colon cancer both in vitro and in vivo through inducing proliferation inhibition and apoptosis of SW480 colon cancer cells and inhibiting tumor growth, respectively. EEG exerts anti-tumor activity at least partly via down-regulation of the Wnt/β-catenin signaling pathway. Copyright© 2018, International

  12. Intravesical Toll-like receptor 7 agonist R-837: Optimization of its formulation in an orthotopic mouse model of bladder cancer

    PubMed Central

    Hayashi, Tomoko; Crain, Brian; Corr, Maripat; Chan, Michael; Cottam, Howard B; Maj, Roberto; Barberis, Alcide; Leoni, Lorenzo; Carson, Dennis A

    2013-01-01

    Objective To study the immune response caused by the intravesical administration of the immunomodulator R-837 in various formulations and to estimate its therapeutic potential for bladder cancer. Methods Female C57BL/6 mice were intravesically treated with different formulations of R-837, a Toll-like receptor 7 agonist used for treating genital warts and skin malignancy. The tested formulation mixtures contained different ratios of lactic acid, a thermosensitive poloxamer polymer (Lutrol F127) and 2-(hydroxypropyl)-β-cyclodextrin (HPβCD). Induction of tumor necrosis factor α (TNFα) and keratinocyte-derived chemokine (KC) was analyzed by Luminex microbeads assay. The therapeutic potential of intravesical administration of R-837 was assessed in an orthotopic, syngeneic mouse model of bladder cancer using MB49 cells. Results Intravesical administration of R-837 in lactic acid alone induced systemic and bladder TNFα and KC in a dose-dependent manner. Formulations including poloxamer decreased systemic absorption of R-837 and significantly reduced systemic and local induction of KC. Addition of HPβCD in the poloxamer formulation particularly reversed levels of systemic and local levels of TNFα and KC. Histological examination showed that poloxamer-HPβCD formulation allowed infiltration of mononuclear cells into urothelium and lamina propria. In studies using orthotopic mouse bladder cancer, the tumor loads in R-837-treated mice were significantly lower than those in vehicle-treated or non-treated mice. Conclusion The optimized poloxamer-HPβCD formulation of R-837 shows therapeutic potential for bladder cancer while avoiding adverse side-effects. PMID:20337728

  13. Zyflamend Suppresses Growth and Sensitizes Human Pancreatic Tumors to Gemcitabine in an Orthotopic Mouse Model Through Modulation of Multiple Targets

    PubMed Central

    Kunnumakkara, Ajaikumar B.; Sung, Bokyung; Ravindran, Jayaraj; Diagaradjane, Parmeswaran; Deorukhkar, Amit; Dey, Sanjit; Koca, Cemile; Tong, Zhimin; Gelovani, Juri G.; Guha, Sushovan; Krishnan, Sunil; Aggarwal, Bharat B.

    2011-01-01

    Agents that can potentiate the efficacy of standard chemotherapy against pancreatic cancer are of great interest. Because of their low cost and safety, patients commonly use a variety of dietary supplements, although evidence of their efficacy is often lacking. One such commonly used food supplement, Zyflamend, is a polyherbal preparation with potent anti-inflammatory activities, and preclinical efficacy against prostate and oral cancer. Whether Zyflamend has any efficacy against human pancreatic cancer alone or in combination with gemcitibine, a commonly used agent, was examined in cell cultures and in an orthotopic mouse model. In vitro, Zyflamend inhibited the proliferation of pancreatic cancer cell lines regardless of p53 status and also enhanced gemcitabine-induced apoptosis. This finding correlated with inhibition of NF-κB activation by Zyflamend and suppression of cyclin D1, c-myc, COX-2, Bcl-2, IAP, survivin, VEGF, ICAM-1, and CXCR4. In nude mice, oral administration of Zyflamend alone significantly inhibited the growth of orthotopically transplanted human pancreatic tumors, and when combined with gemcitabine, further enhanced the antitumor effects. Immunohistochemical and Western blot analyses of tumor tissue showed that the suppression of pancreatic cancer growth correlated with inhibition of proliferation index marker (Ki-67), COX-2, MMP-9, NF-κB, and VEGF. Overall, these results suggest that the concentrated multiherb product Zyflamend alone can inhibit the growth of human pancreatic tumors and, in addition, can sensitize pancreatic cancers to gemcitabine through the suppression of multiple targets linked to tumorigenesis. PMID:21935918

  14. Phenformin has anti-tumorigenic effects in human ovarian cancer cells and in an orthotopic mouse model of serous ovarian cancer.

    PubMed

    Jackson, Amanda L; Sun, Wenchuan; Kilgore, Joshua; Guo, Hui; Fang, Ziwei; Yin, Yajie; Jones, Hannah M; Gilliam, Timothy P; Zhou, Chunxiao; Bae-Jump, Victoria L

    2017-11-21

    Obesity and diabetes have been associated with increased risk and worse outcomes in ovarian cancer (OC). The biguanide metformin is used in the treatment of type 2 diabetes and is also believed to have anti-tumorigenic benefits. Metformin is highly hydrophilic and requires organic cation transporters (OCTs) for entry into human cells. Phenformin, another biguanide, was taken off the market due to an increased risk of lactic acidosis over metformin. However, phenformin is not reliant on transporters for cell entry; and thus, may have increased potency as both an anti-diabetic and anti-tumorigenic agent than metformin. Thus, our goal was to evaluate the effect of phenformin on established OC cell lines, primary cultures of human OC cells and in an orthotopic mouse model of high grade serous OC. In three OC cell lines, phenformin significantly inhibited cellular proliferation, induced cell cycle G1 arrest and apoptosis, caused cellular stress, inhibited adhesion and invasion, and activation of AMPK and inhibition of the mTOR pathway. Phenformin also exerted anti-proliferative effects in seven primary cell cultures of human OC. Lastly, phenformin inhibited tumor growth in an orthotopic mouse model of serous OC, coincident with decreased Ki-67 staining and phosphorylated-S6 expression and increased expression of caspase 3 and phosphorylated-AMPK. Our findings demonstrate that phenformin has anti-tumorigenic effects in OC as previously demonstrated by metformin but it is yet to be determined if it is superior to metformin for the potential treatment of this disease.

  15. Phenformin has anti-tumorigenic effects in human ovarian cancer cells and in an orthotopic mouse model of serous ovarian cancer

    PubMed Central

    Jackson, Amanda L.; Sun, Wenchuan; Kilgore, Joshua; Guo, Hui; Fang, Ziwei; Yin, Yajie; Jones, Hannah M.; Gilliam, Timothy P.; Zhou, Chunxiao; Bae-Jump, Victoria L.

    2017-01-01

    Obesity and diabetes have been associated with increased risk and worse outcomes in ovarian cancer (OC). The biguanide metformin is used in the treatment of type 2 diabetes and is also believed to have anti-tumorigenic benefits. Metformin is highly hydrophilic and requires organic cation transporters (OCTs) for entry into human cells. Phenformin, another biguanide, was taken off the market due to an increased risk of lactic acidosis over metformin. However, phenformin is not reliant on transporters for cell entry; and thus, may have increased potency as both an anti-diabetic and anti-tumorigenic agent than metformin. Thus, our goal was to evaluate the effect of phenformin on established OC cell lines, primary cultures of human OC cells and in an orthotopic mouse model of high grade serous OC. In three OC cell lines, phenformin significantly inhibited cellular proliferation, induced cell cycle G1 arrest and apoptosis, caused cellular stress, inhibited adhesion and invasion, and activation of AMPK and inhibition of the mTOR pathway. Phenformin also exerted anti-proliferative effects in seven primary cell cultures of human OC. Lastly, phenformin inhibited tumor growth in an orthotopic mouse model of serous OC, coincident with decreased Ki-67 staining and phosphorylated-S6 expression and increased expression of caspase 3 and phosphorylated-AMPK. Our findings demonstrate that phenformin has anti-tumorigenic effects in OC as previously demonstrated by metformin but it is yet to be determined if it is superior to metformin for the potential treatment of this disease. PMID:29245964

  16. Usefulness for Predicting Cardiac Events After Orthotopic Liver Transplantation of Myocardial Perfusion Imaging and Dobutamine Stress Echocardiography Preoperatively.

    PubMed

    Snipelisky, David; Ray, Jordan; Vallabhajosyula, Saraschandra; Matcha, Gautam; Squier, Samuel; Lewis, Jacob; Holliday, Rex; Aggarwal, Niti; Askew, J Wells; Shapiro, Brian; Anavekar, Nandan

    2017-04-01

    Patients undergoing orthotopic liver transplantation have high rates of cardiac morbidity and mortality. Although guidelines recommend noninvasive stress testing as part of the preoperative evaluation, little data have evaluated clinical outcomes following orthotopic liver transplantation. A retrospective study at 2 high-volume liver transplantation centers was performed. All patients undergoing noninvasive stress testing (myocardial perfusion imaging [MPI] or dobutamine stress echocardiography [DSE]) over a 5-year period were included. Descriptive analyses, including clinical outcomes and perioperative and postoperative ischemic events, were performed. Comparisons were made between subsets of patients within each stress modality based on abnormal versus normal results. A total of 506 patients were included, of which 343 underwent DSE and 163 MPI. Few patients had abnormal results, with 19 (5.5%) in the DSE group and 13 (8%) in the MPI group. Perioperative and postoperative cardiac complications were low (n = 20, 5.8% and n = 3, 0.9% in DSE group and n = 15, 9.2% and n = 3, 1.8% in MPI group). Comparisons between abnormal versus normal findings showed a trend toward periprocedural cardiac complications in the abnormal DSE group (n = 3, 15.8% vs n = 17, 5.25%; p = 0.09) with no difference in 6-month postprocedural complications (n = 0 vs n = 3, 0.9%; p = 1.0). In the MPI group, a trend toward periprocedural ischemic complications (n = 3, 23.1% vs n = 12, 8%; p = 0.1) was noted with no difference in 6-month postprocedural complications (n = 0 vs n = 3, 2%; p = 1.0). In conclusion, our study found a significantly lower than reported cardiac event rate. In addition, it demonstrated that ischemic cardiac events are uncommon in patients with normal stress testing. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. MicroPET/CT Imaging of an Orthotopic Model of Human Glioblastoma Multiforme and Evaluation of Pulsed Low-Dose Irradiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Park, Sean S.; Chunta, John L.; Robertson, John M.

    2011-07-01

    Purpose: Glioblastoma multiforme (GBM) is an aggressive tumor that typically causes death due to local progression. To assess a novel low-dose radiotherapy regimen for treating GBM, we developed an orthotopic murine model of human GBM and evaluated in vivo treatment efficacy using micro-positron-emission tomography/computed tomography (microPET/CT) tumor imaging. Methods: Orthotopic GBM xenografts were established in nude mice and treated with standard 2-Gy fractionation or 10 0.2-Gy pulses with 3-min interpulse intervals, for 7 consecutive days, for a total dose of 14 Gy. Tumor growth was quantified weekly using the Flex Triumph (GE Healthcare/Gamma Medica-Ideas, Waukesha, WI) combined PET-single-photon emission CTmore » (SPECT)-CT imaging system and necropsy histopathology. Normal tissue damage was assessed by counting dead neural cells in tissue sections from irradiated fields. Results: Tumor engraftment efficiency for U87MG cells was 86%. Implanting 0.5 x 10{sup 6} cells produced a 50- to 70-mm{sup 3} tumor in 10 to 14 days. A significant correlation was seen between CT-derived tumor volume and histopathology-measured volume (p = 0.018). The low-dose 0.2-Gy pulsed regimen produced a significantly longer tumor growth delay than standard 2-Gy fractionation (p = 0.045). Less normal neuronal cell death was observed after the pulsed delivery method (p = 0.004). Conclusion: This study successfully demonstrated the feasibility of in vivo brain tumor imaging and longitudinal assessment of tumor growth and treatment response with microPET/CT. Pulsed radiation treatment was more efficacious than the standard fractionated treatment and was associated with less normal tissue damage.« less

  18. MicroPET/CT imaging of an orthotopic model of human glioblastoma multiforme and evaluation of pulsed low-dose irradiation.

    PubMed

    Park, Sean S; Chunta, John L; Robertson, John M; Martinez, Alvaro A; Oliver Wong, Ching-Yee; Amin, Mitual; Wilson, George D; Marples, Brian

    2011-07-01

    Glioblastoma multiforme (GBM) is an aggressive tumor that typically causes death due to local progression. To assess a novel low-dose radiotherapy regimen for treating GBM, we developed an orthotopic murine model of human GBM and evaluated in vivo treatment efficacy using micro-positron-emission tomography/computed tomography (microPET/CT) tumor imaging. Orthotopic GBM xenografts were established in nude mice and treated with standard 2-Gy fractionation or 10 0.2-Gy pulses with 3-min interpulse intervals, for 7 consecutive days, for a total dose of 14 Gy. Tumor growth was quantified weekly using the Flex Triumph (GE Healthcare/Gamma Medica-Ideas, Waukesha, WI) combined PET-single-photon emission CT (SPECT)-CT imaging system and necropsy histopathology. Normal tissue damage was assessed by counting dead neural cells in tissue sections from irradiated fields. Tumor engraftment efficiency for U87MG cells was 86%. Implanting 0.5 × 10(6) cells produced a 50- to 70-mm(3) tumor in 10 to 14 days. A significant correlation was seen between CT-derived tumor volume and histopathology-measured volume (p = 0.018). The low-dose 0.2-Gy pulsed regimen produced a significantly longer tumor growth delay than standard 2-Gy fractionation (p = 0.045). Less normal neuronal cell death was observed after the pulsed delivery method (p = 0.004). This study successfully demonstrated the feasibility of in vivo brain tumor imaging and longitudinal assessment of tumor growth and treatment response with microPET/CT. Pulsed radiation treatment was more efficacious than the standard fractionated treatment and was associated with less normal tissue damage. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Indocyanine green plasma disappearance rate during the anhepatic phase of orthotopic liver transplantation.

    PubMed

    Bruegger, Lukas; Studer, Peter; Schmid, Stefan W; Pestel, Gunther; Reichen, Juerg; Seiler, Christian; Candinas, Daniel; Inderbitzin, Daniel

    2008-01-01

    Non-invasive pulse spectrophotometry to measure indocyanine green (ICG) elimination correlates well with the conventional invasive ICG clearance test. Nevertheless, the precision of this method remains unclear for any application, including small-for-size liver remnants. We therefore measured ICG plasma disappearance rate (PDR) during the anhepatic phase of orthotopic liver transplantation using pulse spectrophotometry. Measurements were done in 24 patients. The median PDR after exclusion of two outliers and two patients with inconstant signal was 1.55%/min (95% confidence interval [CI]=0.8-2.2). No correlation with patient age, gender, body mass, blood loss, administration of fresh frozen plasma, norepinephrine dose, postoperative albumin (serum), or difference in pre and post transplant body weight was detected. In conclusion, we found an ICG-PDR different from zero in the anhepatic phase, an overestimation that may arise in particular from a redistribution into the interstitial space. If ICG pulse spectrophotometry is used to measure functional hepatic reserve, the verified average difference from zero (1.55%/min) determined in our study needs to be taken into account.

  20. Inhibition of GLO1 in Glioblastoma Multiforme Increases DNA-AGEs, Stimulates RAGE Expression, and Inhibits Brain Tumor Growth in Orthotopic Mouse Models.

    PubMed

    Jandial, Rahul; Neman, Josh; Lim, Punnajit P; Tamae, Daniel; Kowolik, Claudia M; Wuenschell, Gerald E; Shuck, Sarah C; Ciminera, Alexandra K; De Jesus, Luis R; Ouyang, Ching; Chen, Mike Y; Termini, John

    2018-01-30

    Cancers that exhibit the Warburg effect may elevate expression of glyoxylase 1 (GLO1) to detoxify the toxic glycolytic byproduct methylglyoxal (MG) and inhibit the formation of pro-apoptotic advanced glycation endproducts (AGEs). Inhibition of GLO1 in cancers that up-regulate glycolysis has been proposed as a therapeutic targeting strategy, but this approach has not been evaluated for glioblastoma multiforme (GBM), the most aggressive and difficult to treat malignancy of the brain. Elevated GLO1 expression in GBM was established in patient tumors and cell lines using bioinformatics tools and biochemical approaches. GLO1 inhibition in GBM cell lines and in an orthotopic xenograft GBM mouse model was examined using both small molecule and short hairpin RNA (shRNA) approaches. Inhibition of GLO1 with S -( p -bromobenzyl) glutathione dicyclopentyl ester ( p- BrBzGSH(Cp)₂) increased levels of the DNA-AGE N ²-1-(carboxyethyl)-2'-deoxyguanosine (CEdG), a surrogate biomarker for nuclear MG exposure; substantially elevated expression of the immunoglobulin-like receptor for AGEs (RAGE); and induced apoptosis in GBM cell lines. Targeting GLO1 with shRNA similarly increased CEdG levels and RAGE expression, and was cytotoxic to glioma cells. Mice bearing orthotopic GBM xenografts treated systemically with p -BrBzGSH(Cp)₂ exhibited tumor regression without significant off-target effects suggesting that GLO1 inhibition may have value in the therapeutic management of these drug-resistant tumors.

  1. Inhibition of GLO1 in Glioblastoma Multiforme Increases DNA-AGEs, Stimulates RAGE Expression, and Inhibits Brain Tumor Growth in Orthotopic Mouse Models

    PubMed Central

    Jandial, Rahul; Neman, Josh; Tamae, Daniel; Kowolik, Claudia M.; Wuenschell, Gerald E.; Ciminera, Alexandra K.; De Jesus, Luis R.; Ouyang, Ching; Chen, Mike Y.

    2018-01-01

    Cancers that exhibit the Warburg effect may elevate expression of glyoxylase 1 (GLO1) to detoxify the toxic glycolytic byproduct methylglyoxal (MG) and inhibit the formation of pro-apoptotic advanced glycation endproducts (AGEs). Inhibition of GLO1 in cancers that up-regulate glycolysis has been proposed as a therapeutic targeting strategy, but this approach has not been evaluated for glioblastoma multiforme (GBM), the most aggressive and difficult to treat malignancy of the brain. Elevated GLO1 expression in GBM was established in patient tumors and cell lines using bioinformatics tools and biochemical approaches. GLO1 inhibition in GBM cell lines and in an orthotopic xenograft GBM mouse model was examined using both small molecule and short hairpin RNA (shRNA) approaches. Inhibition of GLO1 with S-(p-bromobenzyl) glutathione dicyclopentyl ester (p-BrBzGSH(Cp)2) increased levels of the DNA-AGE N2-1-(carboxyethyl)-2′-deoxyguanosine (CEdG), a surrogate biomarker for nuclear MG exposure; substantially elevated expression of the immunoglobulin-like receptor for AGEs (RAGE); and induced apoptosis in GBM cell lines. Targeting GLO1 with shRNA similarly increased CEdG levels and RAGE expression, and was cytotoxic to glioma cells. Mice bearing orthotopic GBM xenografts treated systemically with p-BrBzGSH(Cp)2 exhibited tumor regression without significant off-target effects suggesting that GLO1 inhibition may have value in the therapeutic management of these drug-resistant tumors. PMID:29385725

  2. In Vitro and In Vivo Comparison of Gemcitabine and the Gemcitabine Analog 1-(2'-deoxy-2'-fluoroarabinofuranosyl) Cytosine (FAC) in Human Orthotopic and Genetically Modified Mouse Pancreatic Cancer Models.

    PubMed

    Russell, James; Pillarsetty, Nagavarakishore; Kramer, Robin M; Romesser, Paul B; Desai, Pooja; Haimovitz-Friedman, Adriana; Lowery, Maeve A; Humm, John L

    2017-12-01

    Although gemcitabine is a mainstay of pancreatic cancer therapy, it is only moderately effective, and it would be desirable to measure drug uptake in patients. 1-(2'-deoxy-2'-fluoroarabinofuranosyl) cytosine (FAC), is an analog of gemcitabine, and when labeled with F-18, it may be a potential surrogate PET tracer for the drug. [ 18 F]FAC was synthesized to a radiochemical purity of >96 %. The human tumor lines AsPC1, BxPC3, Capan-1, Panc1, and MiaPaca2 were grown orthotopically in nude mice. KPC mice that conditionally express oncogenic K-ras and p53 mutations in pancreatic tissue were also used. The intra-tumoral distributions of [ 14 C]gemcitabine and [ 18 F]FAC were mapped with autoradiography. The inter-tumor correlation between [ 14 C]gemcitabine and [ 18 F]FAC was established in the orthotopic tumors. Expression of the equilibrative and concentrative nucleoside transporters (ENT, CNT) in vitro was detected by western blotting. Drug uptake was characterized in vitro using [ 3 H]gemcitabine and the effect of transporter inhibition on gemcitabine and FAC uptake was investigated. The relative affinity of cells for gemcitabine and FAC was tested in competition assays. The cell lines differed in sensitivity to transport inhibitors and in competition studies. There was a good in vivo correlation between the total uptake of [ 18 F]FAC and [ 14 C]gemcitabine, measured across all orthotopic tumors. Using the KPC and BxPC3 models, we found that [ 14 C]gemcitabine and [ 18 F]FAC were largely co-localized. In the lines examined here, [ 18 F]FAC uptake correlates well with gemcitabine in vivo, supporting the notion that [ 18 F]FAC can serve as a PET radiotracer surrogate to determine the uptake and distribution of gemcitabine within pancreatic tumors.

  3. Orthotopic Transplantation of Cryopreserved Mouse Ovaries and Gonadotrophin Releasing Hormone Analogues in the Restoration of Function following Chemotherapy-Induced Ovarian Damage

    PubMed Central

    Li, Qing; Szatmary, Peter; Liu, Yanyang; Ding, Zhenyu; Zhou, Jin; Sun, Yi; Luo, Feng

    2015-01-01

    Therapy advances are constantly improving survival rates of cancer patients, however the toxic effects of chemotherapy drugs can seriously affect patients’ quality of life. In women, fertility and premature ovarian endocrine dysfunction are of particular concern. It is urgently we find methods to preserve or reconstruct ovarian function for these women. This study compares GnRHa treatment with ovarian tissue cryopreservation and orthotopic transplantation in a chemotherapy-induced ovarian damage murine model. 56 inbred Lewis rats were divided into 4 treatment groups: Saline control (group I); cyclophosphamide only (group II); cyclophosphamide plus GnRHa (group III); cyclophosphamide and grafting of thawed cryopreserved ovaries (group IV). Body weight, estrous cycle recovery time, ovarian weight, morphology and follicle count, as well as breeding and fertility were compared among groups. Only group IV was able to restore to normal body weight by the end of the observation period and resumed normal estrous cycles in a shorter time compared to other treatment groups. There was a decrease in primordial follicles in all treatment groups, but group III had the greatest reduction. Although, there was no difference in pregnancy, only one animal littered normal pups in group II, none littered in group III and four littered in group IV. Thus, cryopreservation and orthotopic transplantation of ovarian tissue can restore the fertility of rats subjected to chemotherapy in a manner that is superior to GnRHa treatment. We also observed increased rates of hepatic, splenic and pulmonary haemorrhage in group III, suggesting there may be synergistic toxicity of GnRHa and cyclophosphamide. PMID:25811681

  4. Characteristics and Outcomes of Neutropenia after Orthotopic Liver Transplantation

    PubMed Central

    Alraddadi, B; Nierenberg, NE; Price, LL; Chow, JKL; Poutsiaka, DD; Rohrer, RJ; Cooper, JT; Freeman, RB; Snydman, DR

    2015-01-01

    Neutropenia after orthotopic liver transplantation (LT) is relatively common but the factors associated with its development remain elusive. We assessed possible predictors of neutropenia (absolute neutrophil count [ANC] less than or equal to 1000/mm3) within the first year of LT in a cohort of 304 patients at a tertiary medical center between 1999 and 2009 using time-dependent survival analysis to identify risk factors for neutropenia. In addition, we analyzed neutropenia as a predictor of the clinical outcomes of death, blood stream infection (BSI), invasive fungal infection (IFI), Cytomegalovirus (CMV) disease and graft rejection within the first year of LT. Of the 304 LT recipients, 73 (24%) developed neutropenia, 5 (7%) of whom had grade 4 neutropenia (ANC less than 500/mm3). The following were independent predictors for neutropenia: Child-Turcotte-Pugh score (HR 1.15; 95% CI 1.02, 1.28; p=0.02), BSI (HR 2.89; 95% CI 1.64, 5.11; p=<0.001), CMV disease (HR 4.28; 95% CI 1.55, 11.8; p=0.005), baseline tacrolimus trough level (HR 1.02; 95% CI 1.01, 1.03; p=0.007) and later era LT (2004–2009 versus 1999–2003) (HR 2.28; 95% CI 1.43, 3.65; p=<0.001). Moreover, neutropenia was found to be an independent predictor for mortality within the first year of LT (HR 3.76; 95% CI 1.84, 7.68; p= <0.001). Conclusion Our data suggest that neutropenia within a year after LT is not unusual and is an important predictor of mortality. PMID:26336061

  5. Improved therapeutic outcomes of thermal ablation on rat orthotopic liver allograft sarcoma models by radioiodinated hypericin induced necrosis targeted radiotherapy

    PubMed Central

    Gao, Long; Zhang, Jian; Ma, Tengchuang; Yao, Nan; Gao, Meng; Shan, Xin; Ni, Yicheng; Shao, Haibo; Xu, Ke

    2016-01-01

    Residual tumor resulting in tumor recurrence after various anticancer therapies is an unmet challenge in current clinical oncology. This study aimed to investigate the hypothesis that radioiodinated hypericin (131I-Hyp) may inhibit residual tumor recurrence after microwave ablation (MWA) on rat orthotopic liver allograft sarcoma models. Thirty Sprague-Dawley (SD) rats with hepatic tumors were divided into three groups: Group A received laparotomy MWA and sequential intravenous injection (i.v.) of 131I labelled hypericin (131I-Hyp) in a time interval of 24 h; Group B received only laparotomy MWA; Group C was a blank control. Tumor inhibitory effects were monitored with in vivo magnetic resonance imaging (MRI) and these findings were compared to histopathology data before (baseline, day 0) and 1, 4, and 8 days after MWA. In addition, biodistribution of 131I-Hyp was assessed with in vivo single-photon emission computed tomography-computed tomography (SPECT-CT) imaging, in vitro autoradiography, fluorescent microscopy, and gamma counting. A fast clearance of 131I-Hyp and increasing deposit in necrotic tumors appeared over time, with a significantly higher radioactivity than other organs (0.9169 ± 1.1138 % ID/g, P < 0.01) on day 9. Tumor growth was significantly slowed down in group A compared to group B and C according to MRI images and corresponding tumor doubling time (12.13 ± 1.99, 4.09 ± 0.97, 3.36 ± 0.72 days respectively). The crescent tagerability of 131I-Hyp to necrosis was visualized consistently by autoradiography and fluorescence microscopy. In conclusion, 131I-Hyp induced necrosis targeted radiotherapy improved therapeutic outcomes of MWA on rat orthotopic liver allograft sarcoma models. PMID:27285983

  6. Ultrasound-guided direct delivery of 3-bromopyruvate blocks tumor progression in an orthotopic mouse model of human pancreatic cancer.

    PubMed

    Ota, Shinichi; Geschwind, Jean-Francois H; Buijs, Manon; Wijlemans, Joost W; Kwak, Byung Kook; Ganapathy-Kanniappan, Shanmugasundaram

    2013-06-01

    Studies in animal models of cancer have demonstrated that targeting tumor metabolism can be an effective anticancer strategy. Previously, we showed that inhibition of glucose metabolism by the pyruvate analog, 3-bromopyruvate (3-BrPA), induces anticancer effects both in vitro and in vivo. We have also documented that intratumoral delivery of 3-BrPA affects tumor growth in a subcutaneous tumor model of human liver cancer. However, the efficacy of such an approach in a clinically relevant orthotopic tumor model has not been reported. Here, we investigated the feasibility of ultrasound (US) image-guided delivery of 3-BrPA in an orthotopic mouse model of human pancreatic cancer and evaluated its therapeutic efficacy. In vitro, treatment of Panc-1 cells with 3-BrPA resulted in a dose-dependent decrease in cell viability. The loss of viability correlated with a dose-dependent decrease in the intracellular ATP level and lactate production confirming that disruption of energy metabolism underlies these 3-BrPA-mediated effects. In vivo, US-guided delivery of 3-BrPA was feasible and effective as demonstrated by a marked decrease in tumor size on imaging. Further, the antitumor effect was confirmed by (1) a decrease in the proliferative potential by Ki-67 immunohistochemical staining and (2) the induction of apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphospate nick end labeling staining. We therefore demonstrate the technical feasibility of US-guided intratumoral injection of 3-BrPA in a mouse model of human pancreatic cancer as well as its therapeutic efficacy. Our data suggest that this new therapeutic approach consisting of a direct intratumoral injection of antiglycolytic agents may represent an exciting opportunity to treat patients with pancreas cancer.

  7. Using PEGylated iron oxide nanoparticles with ultrahigh relaxivity for MR imaging of an orthotopic model of human hepatocellular carcinoma

    NASA Astrophysics Data System (ADS)

    Wang, Ruizhi; Hu, Yong; Yang, Yuchan; Xu, Wei; Yao, Mingrong; Gao, Dongmei; Zhao, Yan; Zhan, Songhua; Shi, Xiangyang; Wang, Xiaolin

    2017-02-01

    Hepatocellular carcinoma (HCC) is the most common type of liver malignant tumor, which is often diagnosed in advanced stages, resulting in low survival rate. The sensitive diagnosis of early HCC presents a great interest. Herein, a novel superparamagnetic contrast agent composed of iron oxide nanoparticles is reported. Firstly, polyethyleneimine-coated iron oxide (Fe3O4@PEI) nanoparticles (NPs) were synthesized via a mild reduction route, followed by their modification of polyethylene glycol monomethyl ether ( mPEG-COOH) via 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide hydrochloride coupling chemistry. After acetylation of the remaining PEI amines, the PEGylated Fe3O4 (Fe3O4@PEI.Ac- mPEG-COOH) NPs were successively characterized via different techniques. The Fe3O4@PEI.Ac- mPEG-COOH probes with an Fe3O4 NP size of 9 nm are water dispersible and cytocompatible within the given concentration range. The percentages of PEI and m-PEG-COOH on the particles surface are calculated to be 15.5 and 7.2%, respectively. Prior to the administration of Fe3O4@PEI.Ac- mPEG-COOH NPs of ultrahigh r 2 relaxivity (461.29 mM-1 s-1) via tail intravenous injection for MR imaging of HCC, the orthotopic model of HCC was established in the nude mice by surgical transplantation with HCCLM3 cells. The analysis of MR signal intensity (SI) in the orthotopic tumor model demonstrated that the developed Fe3O4@PEI.Ac- mPEG-COOH NPs were able to infiltrate into the tumor area through the enhanced permeability and retention (EPR) effect reaching the bottom at 2 h postinjection. The developed Fe3O4@PEI.Ac- mPEG-COOH NPs may be further applied for theranostics of different diseases through combing various therapeutic agents.

  8. Fluorescently labeled chimeric anti-CEA antibody improves detection and resection of human colon cancer in a patient-derived orthotopic xenograft (PDOX) nude mouse model.

    PubMed

    Metildi, Cristina A; Kaushal, Sharmeela; Luiken, George A; Talamini, Mark A; Hoffman, Robert M; Bouvet, Michael

    2014-04-01

    The aim of this study was to evaluate a new fluorescently labeled chimeric anti-CEA antibody for improved detection and resection of colon cancer. Frozen tumor and normal human tissue samples were stained with chimeric and mouse antibody-fluorophore conjugates for comparison. Mice with patient-derived orthotopic xenografts (PDOX) of colon cancer underwent fluorescence-guided surgery (FGS) or bright-light surgery (BLS) 24 hr after tail vein injection of fluorophore-conjugated chimeric anti-CEA antibody. Resection completeness was assessed using postoperative images. Mice were followed for 6 months for recurrence. The fluorophore conjugation efficiency (dye/mole ratio) improved from 3-4 to >5.5 with the chimeric CEA antibody compared to mouse anti-CEA antibody. CEA-expressing tumors labeled with chimeric CEA antibody provided a brighter fluorescence signal on frozen human tumor tissues (P = 0.046) and demonstrated consistently lower fluorescence signals in normal human tissues compared to mouse antibody. Chimeric CEA antibody accurately labeled PDOX colon cancer in nude mice, enabling improved detection of tumor margins for more effective FGS. The R0 resection rate increased from 86% to 96% with FGS compared to BLS. Improved conjugating efficiency and labeling with chimeric fluorophore-conjugated antibody resulted in better detection and resection of human colon cancer in an orthotopic mouse model. © 2013 Wiley Periodicals, Inc.

  9. N-acetylcysteine induces shedding of selectins from liver and intestine during orthotopic liver transplantation

    PubMed Central

    Taut, F J H; Schmidt, H; Zapletal, C M; Thies, J C; Grube, C; Motsch, J; Klar, E; Martin, E

    2001-01-01

    In orthotopic liver transplantation (OLT), N-acetylcysteine (NAC) reduces ischaemia/reperfusion (I/R) injury, improves liver synthesis function and prevents primary nonfunction of the graft. To further elucidate the mechanisms of these beneficial effects of NAC, we investigated influence of high-dose NAC therapy on the pattern of adhesion molecule release from liver and intestine during OLT. Nine patients receiving allograft OLT were treated with 150 mg NAC/kg during the first hour after reperfusion; 10 patients received the carrier only. One hour after reperfusion, samples of arterial, portal venous and hepatic venous plasma were taken and blood flow in the hepatic artery and the portal vein was measured. Absolute concentrations of sICAM-1, sVCAM-1, sP-selectin and sE-selectin were not markedly different. However, balance calculations showed release of selectins from NAC-treated livers as opposed to net uptake in controls (P ≤ 0·02 for sP-selectin). This shedding of selectins might be a contributing factor to the decrease in leucocyte adherence and improved haemodynamics found experimentally with NAC-treatment. PMID:11422213

  10. Investigation into metastatic processes and the therapeutic effects of gemcitabine on human pancreatic cancer using an orthotopic SUIT-2 pancreatic cancer mouse model

    PubMed Central

    Higuchi, Tamami; Yokobori, Takehiko; Naito, Tomoharu; Kakinuma, Chihaya; Hagiwara, Shinji; Nishiyama, Masahiko; Asao, Takayuki

    2018-01-01

    Prognosis of pancreatic cancer is poor, thus the development of novel therapeutic drugs is necessary. During preclinical studies, appropriate models are essential for evaluating drug efficacy. The present study sought to determine the ideal pancreatic cancer mouse model for reliable preclinical testing. Such a model could accurately reflect human pancreatic cancer phenotypes and predict future clinical trial results. Systemic pathology analysis was performed in an orthotopic transplantation model to prepare model mice for use in preclinical studies, mimicking the progress of human pancreatic cancer. The location and the timing of inoculated cancer cell metastases, pathogenesis and cause of fatality were analyzed. Furthermore, the efficacy of gemcitabine, a key pancreatic cancer drug, was evaluated in this model where liver metastasis and peritoneal dissemination occur. Results indicated that the SUIT-2 orthotopic pancreatic cancer model was similar to the phenotypic sequential progression of human pancreatic cancer, with extra-pancreatic invasion, intra-peritoneal dissemination and other hematogenous organ metastases. Notably, survival was prolonged by administering gemcitabine to mice with metastasized pancreatic cancer. Furthermore, the detailed effects of gemcitabine on the primary tumor and metastatic tumor lesions were pathologically evaluated in mice. The present study indicated the model accurately depicted pancreatic cancer development and metastasis. Furthermore, the detailed effects of pancreatic cancer drugs on the primary tumor and on metastatic tumor lesions. We present this model as a potential new standard for new drug development in pancreatic cancer. PMID:29435042

  11. Esophageal replacement.

    PubMed

    Kunisaki, Shaun M; Coran, Arnold G

    2017-04-01

    This article focuses on esophageal replacement as a surgical option for pediatric patients with end-stage esophageal disease. While it is obvious that the patient׳s own esophagus is the best esophagus, persisting with attempts to retain a native esophagus with no function and at all costs are futile and usually detrimental to the overall well-being of the child. In such cases, the esophagus should be abandoned, and the appropriate esophageal replacement is chosen for definitive reconstruction. We review the various types of conduits used for esophageal replacement and discuss the unique advantages and disadvantages that are relevant for clinical decision-making. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. [Inhibitory effect of Xiaotan Sanjie Recipe on the microsatellite instability of orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice].

    PubMed

    Ye, Min; Sun, Da-Zhi; Wei, Pin-kang

    2014-05-01

    To study the inhibitory effect of Xiaotan Sanjie Recipe (XSR) on the microsatellite instability of orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice. The 3rd passage subcutaneous transplantation tumor was taken as the origin of the model by using MKN-45 human gastric cancer cell lines. MKN-45 human gastric cancer nude mouse model was established using OB glue adhesive method. Then 30 nude mice were divided into the model group, the XSR group, and the chemotherapy group. Mice in the XSR group were intragastrically given XSR at the daily dose of 0.4 mL. Mice in the chemotherapy group were intragastrically given Fluorouracil at the daily dose of 0.4 mL. No intervention was given to mice in the model group. After 6 weeks of medication, the tumor weight was measured, and the tumor inhibition rate calculated. The size, the peak height, and the peak area of 5 microsatellite instability sites were detected. The tumor inhibition rate was 40. 84% in the XSR group. The tumor weight was significantly lower in the XSR group than in the model group (P < 0.01), showing no statistical difference when compared with the chemotherapy group (P >0.05). The incidence of high microsatellite instability (MSI-H) in the model group was 70%, and the incidence of low microsatellite instability (MSI-L) was 30%. Microsatellite stable site tended be stable after 6 weeks of XSR treatment. XSR showed inhibition on microsatellite instable orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice.

  13. A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model.

    PubMed

    Fu, Yilong; Ong, Lai-Chun; Ranganath, Sudhir H; Zheng, Lin; Kee, Irene; Zhan, Wenbo; Yu, Sidney; Chow, Pierce K H; Wang, Chi-Hwa

    2016-01-01

    Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials.

  14. A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model

    PubMed Central

    Ranganath, Sudhir H.; Zheng, Lin; Kee, Irene; Zhan, Wenbo; Yu, Sidney; Chow, Pierce K. H.; Wang, Chi-Hwa

    2016-01-01

    Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/ 18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials. PMID:26844770

  15. An Orthotopic Mouse Model of Spontaneous Breast Cancer Metastasis.

    PubMed

    Paschall, Amy V; Liu, Kebin

    2016-08-14

    Metastasis is the primary cause of mortality of breast cancer patients. The mechanism underlying cancer cell metastasis, including breast cancer metastasis, is largely unknown and is a focus in cancer research. Various breast cancer spontaneous metastasis mouse models have been established. Here, we report a simplified procedure to establish orthotopic transplanted breast cancer primary tumor and resultant spontaneous metastasis that mimic human breast cancer metastasis. Combined with the bioluminescence live tumor imaging, this mouse model allows tumor growth and progression kinetics to be monitored and quantified. In this model, a low dose (1 x 10(4) cells) of 4T1-Luc breast cancer cells was injected into BALB/c mouse mammary fat pad using a tuberculin syringe. Mice were injected with luciferin and imaged at various time points using a bioluminescent imaging system. When the primary tumors grew to the size limit as in the IACUC-approved protocol (approximately 30 days), mice were anesthetized under constant flow of 2% isoflurane and oxygen. The tumor area was sterilized with 70% ethanol. The mouse skin around the tumor was excised to expose the tumor which was removed with a pair of sterile scissors. Removal of the primary tumor extends the survival of the 4T-1 tumor-bearing mice for one month. The mice were then repeatedly imaged for metastatic tumor spreading to distant organs. Therapeutic agents can be administered to suppress tumor metastasis at this point. This model is simple and yet sensitive in quantifying breast cancer cell growth in the primary site and progression kinetics to distant organs, and thus is an excellent model for studying breast cancer growth and progression, and for testing anti-metastasis therapeutic and immunotherapeutic agents in vivo.

  16. In Vitro and In Vivo Comparison of Gemcitabine and the Gemcitabine Analog 1-(2′-deoxy-2′-fluoroarabinofuranosyl) Cytosine (FAC) in Human Orthotopic and Genetically Modified Mouse Pancreatic Cancer Models

    PubMed Central

    Russell, James; Pillarsetty, Nagavarakishore; Kramer, Robin M; Romesser, Paul B; Desai, Pooja; Haimovitz-Friedman, Adriana; Lowery, Maeve A; Humm, John L

    2017-01-01

    Purpose Although gemcitabine is a mainstay of pancreatic cancer therapy, it is only moderately effective, and it would be desirable to measure drug uptake in patients. 1-(2′-deoxy-2′-fluoroarabinofuranosyl) cytosine (FAC), is an analog of gemcitabine, and when labeled with F-18, it may be a potential surrogate PET tracer for the drug. Procedures [18F]FAC was synthesized to a radiochemical purity of >96 %. The human tumor lines AsPC1, BxPC3, Capan-1, Panc1, and MiaPaca2 were grown orthotopically in nude mice. KPC mice that conditionally express oncogenic K-ras and p53 mutations in pancreatic tissue were also used. The intra-tumoral distributions of [14C]gemcitabine and [18F]FAC were mapped with autoradiography. The inter-tumor correlation between [14C]gemcitabine and [18F]FAC was established in the orthotopic tumors. Expression of the equilibrative and concentrative nucleoside transporters (ENT, CNT) in vitro was detected by western blotting. Drug uptake was characterized in vitro using [3H]gemcitabine and the effect of transporter inhibition on gemcitabine and FAC uptake was investigated. The relative affinity of cells for gemcitabine and FAC was tested in competition assays. The cell lines differed in sensitivity to transport inhibitors and in competition studies. There was a good in vivo correlation between the total uptake of [18F]FAC and [14C]gemcitabine, measured across all orthotopic tumors. Using the KPC and BxPC3 models, we found that [14C]gemcitabine and [18F]FAC were largely co-localized. Conclusions In the lines examined here, [18F]FAC uptake correlates well with gemcitabine in vivo, supporting the notion that [18F]FAC can serve as a PET radiotracer surrogate to determine the uptake and distribution of gemcitabine within pancreatic tumors. PMID:28349292

  17. Micro-positron emission tomography/contrast-enhanced computed tomography imaging of orthotopic pancreatic tumor-bearing mice using the αvβ₃ integrin tracer ⁶⁴Cu-labeled cyclam-RAFT-c(-RGDfK-)₄.

    PubMed

    Aung, Winn; Jin, Zhao-Hui; Furukawa, Takako; Claron, Michael; Boturyn, Didier; Sogawa, Chizuru; Tsuji, Atsushi B; Wakizaka, Hidekatsu; Fukumura, Toshimitsu; Fujibayashi, Yasuhisa; Dumy, Pascal; Saga, Tsuneo

    2013-09-01

    The purpose of this study was to develop a clinically relevant orthotopic xenotransplantation model of pancreatic cancer and to perform a preclinical evaluation of a new positron emission tomography (PET) imaging probe, ⁶⁴Cu-labeled cyclam-RAFT-c(-RGDfK-)₄ peptide (⁶⁴Cu-RAFT-RGD), using this model. Varying degrees of αvβ₃ integrin expression in several human pancreatic cancer cell lines were examined by flow cytometry and Western blotting. The cell line BxPC-3, which is stably transfected with a red fluorescence protein (RFP), was used for surgical orthotopic implantation. Orthotopic xenograft was established in the pancreas of recipient nude mice. An in vivo probe biodistribution and receptor blocking study, preclinical PET imaging coregistered with contrast-enhanced computed tomography (CECT) comparing ⁶⁴Cu-RAFT-RGD and ¹⁸F-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) accumulation in tumor, postimaging autoradiography, and histologic and immunohistochemical examinations were done. Biodistribution evaluation with a blocking study confirmed that efficient binding of probe to tumor is highly αvβ₃ integrin specific. ⁶⁴Cu-RAFT-RGD PET combined with CECT provided for precise and easy detection of cancer lesions. Autoradiography, histologic, and immunohistochemical examinations confirmed the accumulation of ⁶⁴Cu-RAFT-RGD in tumor versus nontumor tissues. In comparative PET studies, ⁶⁴Cu-RAFT-RGD accumulation provided better tumor contrast to background than ¹⁸F-FDG. Our results suggest that ⁶⁴Cu-RAFT-RGD PET imaging is potentially applicable for the diagnosis of αvβ₃ integrin-expressing pancreatic tumors.

  18. [Effects of Rhizoma kaempferiae volatile oil on tumor growth and cell cycle of MKN-45 human gastric cancer cells orthotopically transplanted in nude mice].

    PubMed

    Xiao, Yan; Wei, Pin-Kang; Li, Jun; Shi, Jun; Yu, Zhi-Hong; Lin, Hui-Ming

    2006-07-01

    To evaluate the effects of Rhizoma kaempferiae volatile oil on tumor growth and cell cycle of MKN-45 human gastric cancer cells orthotopically transplanted in nude mice. One hundred and five nude mice orthotopically transplanted with MKN-45 human gastric cancer cells were randomly divided into seven groups: untreated group, normal saline-treated group, dissolvant-treated group, cyclophosphamide (CTX)-treated group and high-, medium-, and low-dose Rhizoma kaempferiae volatile oil-treated groups. Corresponding interventions were implemented in each group except the untreated group. The antitumor effects in vivo were evaluated. Cell cycle distribution and apoptosis of MKN-45 human gastric cancer cells were determined by using flow cytometry (FCM). The ultrastructure of MKN-45 gastric cancer cells was observed by a transmission electron microscope. In the high-, medium-, and low-dose Rhizoma kaempferiae volatile oil-treated groups, the growth inhibition rates of gastric cancer were 57.2%, 28.0% and 5.0% respectively, and the gastric cancer cells were arrested at G(0)/G(1) phase. This antitumor effect was dose-dependent. The apoptotic cells occurred more frequently in the high-dose Rhizoma kaempferiae volatile oil-treated group and the CTX-treated group than those in the medium- and low-dose Rhizoma kaempferiae volatile oil-treated groups. The Rhizoma kaempferiae volatile oil is an effective composition for growth inhibition of gastric cancer, and its mechanism may be related to regulating the cell cycle and inducing apoptosis.

  19. Repurposing Mebendazole as a Replacement for Vincristine for the Treatment of Brain Tumors

    PubMed Central

    De Witt, Michelle; Gamble, Alexander; Hanson, Derek; Markowitz, Daniel; Powell, Caitlin; Al Dimassi, Saleh; Atlas, Mark; Boockvar, John; Ruggieri, Rosamaria; Symons, Marc

    2017-01-01

    The microtubule inhibitor vincristine is currently used to treat a variety of brain tumors, including low-grade glioma and anaplastic oligodendroglioma. Vincristine, however, does not penetrate well into brain tumor tissue, and moreover, it displays dose-limiting toxicities, including peripheral neuropathy. Mebendazole, a Food and Drug Administration–approved anthelmintic drug with a favorable safety profile, has recently been shown to display strong therapeutic efficacy in animal models of both glioma and medulloblastoma. Importantly, appropriate formulations of mebendazole yield therapeutically effective concentrations in the brain. Mebendazole has been shown to inhibit microtubule formation, but it is not known whether its potency against tumor cells is mediated by this inhibitory effect. To investigate this, we examined the effects of mebendazole on GL261 glioblastoma cell viability, microtubule polymerization and metaphase arrest, and found that the effective concentrations to inhibit these functions are very similar. In addition, using mebendazole as a seed for the National Cancer Institute (NCI) COMPARE program revealed that the top-scoring drugs were highly enriched in microtubule-targeting drugs. Taken together, these results indicate that the cell toxicity of mebendazole is indeed caused by inhibiting microtubule formation. We also compared the therapeutic efficacy of mebendazole and vincristine against GL261 orthotopic tumors. We found that mebendazole showed a significant increase in animal survival time, whereas vincristine, even at a dose close to its maximum tolerated dose, failed to show any efficacy. In conclusion, our results strongly support the clinical use of mebendazole as a replacement for vincristine for the treatment of brain tumors. PMID:28386621

  20. Isoflurane: An Ideal Anesthetic for Rodent Orthotopic Liver Transplantation Surgery?

    PubMed

    Cao, D; Liu, Y; Li, J; Gong, J

    2016-10-01

    Because the choice of anesthetic affects the rodent orthotopic liver transplantation (OLT) model, we compared the effects of isoflurane, ketamine, chloral hydrate, and pentobarbital on the OLT model. OLT was performed using the two-cuff technique. Two hundred male rats were randomly divided into five groups: control, isoflurane, ketamine, chloral hydrate, and pentobarbital groups. Rectal temperatures, respiratory rates, arterial blood values (pH, PaCO 2 , PaO 2 , and SatO 2 ), liver function tests and histopathology, recovery times, and anhepatic stage mortality rates were assessed. Compared with controls, respiratory rates decreased by 20% in the isoflurane group, and decreased by 40%-50% in the ketamine, chloral hydrate, and pentobarbital groups. The PaO 2 , SatO 2 , and pH levels in the ketamine, chloral hydrate, and pentobarbital groups were significantly lower than those in the isoflurane and control groups (P < .05). Only the pentobarbital group displayed significant liver histopathologic changes along with significantly higher levels of serum alanine aminotransferase and total bilirubin, but a significantly lower level of serum albumin, compared with the control group (P < .05). The isoflurane group had a 0% anhepatic stage mortality rate compared with rates of 30%-40% in the other anesthetic groups. Isoflurane should be the preferred anesthetic for rodent OLT surgery due to its minimal respiratory and hepatic physiological effects as well as its low anhepatic phase mortality rate. Secondary to isoflurane, ketamine and chloral hydrate may be administered as donor anesthetics. Pentobarbital use should be avoided entirely in rodent OLT surgery due to its significant hepatotoxic effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Hip Replacement Surgery

    MedlinePlus

    ... Download Download EPUB Download PDF What is it? Points To Remember About Hip Replacement Surgery Hip replacement ... This leaves your hands and arms free for balance or to use crutches. Use a long-handled " ...

  2. Novel model of orthotopic U-87 MG glioblastoma resection in athymic nude mice.

    PubMed

    Bianco, John; Bastiancich, Chiara; Joudiou, Nicolas; Gallez, Bernard; des Rieux, Anne; Danhier, Fabienne

    2017-06-01

    In vitro and in vivo models of experimental glioma are useful tools to gain a better understanding of glioblastoma (GBM) and to investigate novel treatment strategies. However, the majority of preclinical models focus on treating solid intracranial tumours, despite surgical resection being the mainstay in the standard care of patients with GBM today. The lack of resection and recurrence models therefore has undermined efforts in finding a treatment for this disease. Here we present a novel orthotopic tumour resection and recurrence model that has potential for the investigation of local delivery strategies in the treatment of GBM. The model presented is simple to achieve through the use of a biopsy punch, is reproducible, does not require specific or expensive equipment, and results in a resection cavity suitable for local drug delivery systems, such as the implantation or injection of hydrogels. We show that tumour resection is well tolerated, does not induce deleterious neurological deficits, and significantly prolongs survival of mice bearing U-87 MG GBM tumours. In addition, the resulting cavity could accommodate adequate amounts of hydrogels for local delivery of chemotherapeutic agents to eliminate residual tumour cells that can induce tumour recurrence. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Chemotherapy and Radiofrequency-Induced Mild Hyperthermia Combined Treatment of Orthotopic Pancreatic Ductal Adenocarcinoma Xenografts.

    PubMed

    Krzykawska-Serda, Martyna; Agha, Mahdi S; Ho, Jason Chak-Shing; Ware, Matthew J; Law, Justin J; Newton, Jared M; Nguyen, Lam; Curley, Steven A; Corr, Stuart J

    2018-04-02

    Patients with pancreatic ductal adenocarcinomas (PDAC) have one of the poorest survival rates of all cancers. The main reason for this is related to the unique tumor stroma and poor vascularization of PDAC. As a consequence, chemotherapeutic drugs, such as nab-paclitaxel and gemcitabine, cannot efficiently penetrate into the tumor tissue. Non-invasive radiofrequency (RF) mild hyperthermia treatment was proposed as a synergistic therapy to enhance drug uptake into the tumor by increasing tumor vascular inflow and perfusion, thus, increasing the effect of chemotherapy. RF-induced hyperthermia is a safer and non-invasive technique of tumor heating compared to conventional contact heating procedures. In this study, we investigated the short- and long-term effects (~20 days and 65 days, respectively) of combination chemotherapy and RF hyperthermia in an orthotopic PDAC model in mice. The benefit of nab-paclitaxel and gemcitabine treatment was confirmed in mice; however, the effect of treatment was statistically insignificant in comparison to saline treated mice during long-term observation. The benefit of RF was minimal in the short-term and completely insignificant during long-term observation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model.

    PubMed

    Huang, Feng-Yun J; Lee, Te-Wei; Chang, Chih-Hsien; Chen, Liang-Cheng; Hsu, Wei-Hsin; Chang, Chien-Wen; Lo, Jem-Mau

    2015-01-01

    In this study, the (188)Re-labeled PEGylated nanoliposome ((188)Re-liposome) was prepared and evaluated as a therapeutic agent for glioma. The reporter cell line, F98(luc) was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of (188)Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered (188)Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the (188)Re-liposome-treated rats. By using bioluminescent imaging, the well-established reporter cell line (F98(luc)) showed a high relationship between cell number and its bioluminescent intensity (R(2)=0.99) in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of (188)Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the (188)Re-liposome-treated group than the control group (P<0.05). As a result, the lifespan of glioma-bearing rats treated with (188)Re-liposome was prolonged 10.67% compared to the control group. The radiotherapeutic evaluation by dosimetry and survival studies have demonstrated that passive targeting (188)Re-liposome via systemic administration can significantly prolong the lifespan of orthotopic glioma

  5. Establishment and characterization of in vivo orthotopic bioluminescent xenograft models from human osteosarcoma cell lines in Swiss nude and NSG mice.

    PubMed

    Marques da Costa, Maria Eugenia; Daudigeos-Dubus, Estelle; Gomez-Brouchet, Anne; Bawa, Olivia; Rouffiac, Valerie; Serra, Massimo; Scotlandi, Katia; Santos, Conceição; Geoerger, Birgit; Gaspar, Nathalie

    2018-03-01

    Osteosarcoma is one of the most common primary bone tumors in childhood and adolescence. Metastases occurrence at diagnosis or during disease evolution is the main therapeutic challenge. New drug evaluation to improve patient survival requires the development of various preclinical models mimicking at best the complexity of the disease and its metastatic potential. We describe here the development and characteristics of two orthotopic bioluminescent (Luc/mKate2) cell-derived xenograft (CDX) models, Saos-2-B-Luc/mKate2-CDX and HOS-Luc/mKate2-CDX, in different immune (nude and NSG mouse strains) and bone (intratibial and paratibial with periosteum activation) contexts. IVIS SpectrumCT system allowed both longitudinal computed tomography (CT) and bioluminescence real-time follow-up of primary tumor growth and metastatic spread, which was confirmed by histology. The murine immune context influenced tumor engraftment, primary tumor growth, and metastatic spread to lungs, bone, and spleen (an unusual localization in humans). Engraftment in NSG mice was found superior to that found in nude mice and intratibial bone environment more favorable to engraftment compared to paratibial injection. The genetic background of the two CDX models also led to distinct primary tumor behavior observed on CT scan. Saos-2-B-Luc/mKate2-CDX showed osteocondensed, HOS-Luc/mKate2-CDX osteolytic morphology. Bioluminescence defined a faster growth of the primary tumor and metastases in Saos-2-B-Luc/mKate2-CDX than in HOS-Luc/mKate2-CDX. The early detection of primary tumor growth and metastatic spread by bioluminescence allows an improved exploration of osteosarcoma disease at tumor progression, and metastatic spread, as well as the evaluations of anticancer treatments. Our orthotopic models with metastatic spread bring complementary information to other types of existing osteosarcoma models. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  6. 3-Bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth

    PubMed Central

    WANG, TING-AN; ZHANG, XIAO-DONG; GUO, XING-YU; XIAN, SHU-LIN; LU, YUN-FEI

    2016-01-01

    Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor model in nude mice to explore the specific mechanisms of 3-BrPA and SCT. We found that both 3-BrPA and SCT effectively suppressed cancer cell proliferation, arrested the cell cycle, induced apoptosis, and decreased the production of lactate and ATP. 3-BrPA significantly reduced the glycolytic enzyme hexokinase activity, while SCT selectively inhibited phosphofructokinase-1 activity. Furthermore, 3-BrPA and SCT upregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3) and downregulated the expression of anti-apoptotic proteins (Bcl-2 and survivin). Finally, our animal model of gastric cancer indicated that intraperitoneal injection of 3-BrPA and SCT suppressed orthotopic transplantation tumor growth and induced tumor apoptosis. Taken together, these results suggest that 3-BrPA and SCT selectively suppress glycolytic enzymes, decrease ATP production, induce mitochondrial-mediated apoptosis, downregulate survivin, and inhibit tumor growth. Moreover, an intraperitoneal injection is an effective form of administration of 3-BrPA and SCT. PMID:26708213

  7. 3-bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth.

    PubMed

    Wang, Ting-An; Zhang, Xiao-Dong; Guo, Xing-Yu; Xian, Shu-Lin; Lu, Yun-Fei

    2016-03-01

    Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor model in nude mice to explore the specific mechanisms of 3-BrPA and SCT. We found that both 3-BrPA and SCT effectively suppressed cancer cell proliferation, arrested the cell cycle, induced apoptosis, and decreased the production of lactate and ATP. 3-BrPA significantly reduced the glycolytic enzyme hexokinase activity, while SCT selectively inhibited phosphofructokinase-1 activity. Furthermore, 3-BrPA and SCT upregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3) and downregulated the expression of anti-apoptotic proteins (Bcl-2 and survivin). Finally, our animal model of gastric cancer indicated that intraperitoneal injection of 3-BrPA and SCT suppressed orthotopic transplantation tumor growth and induced tumor apoptosis. Taken together, these results suggest that 3-BrPA and SCT selectively suppress glycolytic enzymes, decrease ATP production, induce mitochondrial-mediated apoptosis, downregulate survivin, and inhibit tumor growth. Moreover, an intraperitoneal injection is an effective form of administration of 3-BrPA and SCT.

  8. Curative potential of GM-CSF-secreting tumor cell vaccines on established orthotopic liver tumors: mechanisms for the superior antitumor activity of live tumor cell vaccines.

    PubMed

    Tai, Kuo-Feng; Chen, Ding-Shinn; Hwang, Lih-Hwa

    2004-01-01

    In preclinical studies, tumor cells genetically engineered to secrete cytokines, hereafter referred to as tumor cell vaccines, can often generate systemic antitumor immunity. This study investigated the therapeutic effects of live or irradiated tumor cell vaccines that secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) on established orthotopic liver tumors. Experimental results indicated that two doses (3 x 10(7) cells per dose) of irradiated tumor cell vaccines were therapeutically ineffective, whereas one dose (3 x 10(6) cells) of live tumor cell vaccines caused complete tumor regression. In vivo depletion of CD8+ T cells, but not natural killer cells, restored tumor formation in the live vaccine-treated animals. Additionally, the treatment of cells with live vaccine induced markedly higher levels of cytotoxic T lymphocyte activity than the irradiated vaccines in the draining lymph nodes. The higher levels of cytokine and antigen loads could partly explain the superior antitumor activity of live tumor cell vaccines, but other unidentified mechanisms could also play a role in the early T cell activation in the lymph nodes. A protocol using multiple and higher dosages of irradiated tumor cell vaccines also caused significant regression of liver tumors. These results suggest that the GM-CSF-secreting tumor cell vaccines are highly promising for orthotopic liver tumors if higher levels of immune responses are elicited during early tumor development. Copyright 2004 National Science Council, ROC and S. Karger AG, Basel

  9. Symptomatic osteonecrosis of the femoral head after adult orthotopic liver transplantation.

    PubMed

    Li, Hua; Zhang, Jian; He, Ji-Wen; Wang, Kun; Wang, Gen-Shu; Jiang, Nan; Fu, Bin-Sheng; Wang, Guo-Ying; Yang, Yang; Chen, Gui-Hua

    2012-07-01

    With the increase of survival in liver transplantation recipients, more patients are at a high risk of developing osteonecrosis, especially in the femoral head, due to immunosuppressive treatment. The purpose of this study was to report the incidence, possible risk factors, and outcome of symptomatic osteonecrosis of the femoral head (ONFH) in adult patients with current immunosuppressive agents and individual protocol after liver transplantation in China. A retrospective analysis was performed on 226 adult patients who underwent orthotopic liver transplantation (OLT) at a single liver transplantation institution between January 2004 and December 2008. The posttransplant survival time (or pre-retransplantation survival time) of all the patients were more than 24 months. The possible pre- and post-transplantation risk factors of symptomatic ONFH were investigated and the curative effects of the treatment were also reported. The incidence of ONFH was 1.33% in patients after OLT. ONFH occurred at a mean of (14 ± 6) months (range, 10 - 21 months) after transplantation. Male patients more often presented with osteonecrosis as a complication than female patients. The patients with lower pre-transplantation total bilirubin and direct bilirubin levels (P < 0.05). There was no difference in the cumulative dose of corticosteroids or tacrolimus between the patients with or without symptomatic ONFH. Patients were treated either pharmacologically or surgically. All patients showed a nice curative effect without major complications during the 18 - 63 months post-treatment follow up. The symptomatic ONFH does not occur commonly after adult OLT in the current individual immunosuppressive protocol in China.

  10. Liver Transplantation for Budd-Chiari Syndrome

    PubMed Central

    Putnam, Charles W.; Porter, Kendrick A.; Well, Richard; Reid, H. A. S.; Starzl, Thomas E.

    2011-01-01

    Orthotopic liver transplantation was accomplished in a 22-year-old woman dying of the Budd-Chiarl syndrome. She Is well and has normal liver function 16 months postoperatively. In view of the good early result, it will be appropriate to consider liver replacement for this disease in further well-selected cases. PMID:781334

  11. Implementing Replacement Cost Accounting

    DTIC Science & Technology

    1976-12-01

    cost accounting Clickener, John Ross Monterey, California. Naval Postgraduate School http://hdl.handle.net/10945/17810 Downloaded from NPS Archive...Calhoun IMPLEMENTING REPLACEMENT COST ACCOUNTING John Ross CHckener NAVAL POSTGRADUATE SCHOOL Monterey, California THESIS IMPLEMENTING REPLACEMENT COST ...Implementing Replacement Cost Accounting 7. AUTHORS John Ross Clickener READ INSTRUCTIONS BEFORE COMPLETING FORM 3. RECIPIENT’S CATALOG NUMBER 9. TYRE OF

  12. Tumor-Targeting Salmonella typhimurium A1-R Promotes Tumoricidal CD8+ T Cell Tumor Infiltration and Arrests Growth and Metastasis in a Syngeneic Pancreatic-Cancer Orthotopic Mouse Model.

    PubMed

    Murakami, Takashi; Hiroshima, Yukihiko; Zhang, Yong; Zhao, Ming; Kiyuna, Tasuku; Hwang, Ho Kyoung; Miyake, Kentaro; Homma, Yuki; Mori, Ryutaro; Matsuyama, Ryusei; Chishima, Takashi; Ichikawa, Yasushi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

    2018-01-01

    The present study determined the effect of the tumor-targeting strain Salmonella typhimurium A1-R (S. typhimurium A1-R) on CD8 + tumor-infiltrating lymphocytes (TILs) in a syngeneic pancreatic-cancer orthotopic mouse model. The effect of tumor-targeting S. typhimurium A1-R on CD8 + TILs was determined on the Pan02 murine pancreatic-adenocarcinoma implanted orthotopically in the pancreatic tail of C57BL/6 immunocompromised mice. Three weeks after orthotopic implantation, mice were randomized as follows G1: untreated control group (n = 8); and G2: S. typhimurium A1-R-treatment group (n = 8, 1 × 10 7 colony forming units [CFU]/body, iv, weekly, 3 weeks). On the 22nd day from initial treatment, all mice were sacrificed and tumors were harvested. The tumor-volume ratio was defined as ratio of tumor volume on the 22nd day relative to the 1st day. The tumor volume ratio was significantly lower in the S. typhimurium A1-R-treated group (G2) (3.0 ± 2.8) than the untreated control (G1) (39.9 ± 30.7, P < 0.01). Hematoxylin and easin (H&E) staining on tumor sections was performed to evaluate tumor destruction which was classified according to the Evans grading system and found to be much greater in the S. typhimurium A1-R-treated mice (G2). Six mice in G1 had peritoneal dissemination, whereas no mice showed peritoneal dissemination in G2 (P < 0.01). Immunohistochemical staining with anti-mouse CD8 + antibody was performed in order to detect TILs determined by calculating the average number of CD8 + cells in three high power fields (200×) in the treated and untreated tumors. The TIL score was significantly higher in G2 (133.5 ± 32.2) than G1 (45.1 ± 19.4, P < 0.001). The present study demonstrates that S. typhimurium A1-R promotes CD8 + T cell infiltration and inhibition of tumor growth and metastasis. J. Cell. Biochem. 119: 634-639, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Alendronate decreases orthotopic PC-3 prostate tumor growth and metastasis to prostate-draining lymph nodes in nude mice

    PubMed Central

    Tuomela, Johanna M; Valta, Maija P; Väänänen, Kalervo; Härkönen, Pirkko L

    2008-01-01

    Background Metastatic prostate cancer is associated with a high morbidity and mortality but the spreading mechanisms are still poorly understood. The aminobisphosphonate alendronate, used to reduce bone loss, has also been shown to inhibit the invasion and migration of prostate cancer cells in vitro. We used a modified orthotopic PC-3 nude mouse tumor model of human prostate cancer to study whether alendronate affects prostate tumor growth and metastasis. Methods PC-3 cells (5 × 105) were implanted in the prostates of nude mice and the mice were treated with alendronate (0.5 mg/kg/day in PBS, s.c.) or vehicle for 4 weeks. After sacrifice, the sizes of tumor-bearing prostates were measured and the tumors and prostate-draining regional iliac and sacral lymph nodes were excised for studies on markers of proliferation, apoptosis, angiogenesis and lymphangiogenesis, using histomorphometry and immunohistochemistry. Results Tumor occurrence in the prostate was 73% in the alendronate-treated group and 81% in the control group. Mean tumor size (218 mm3, range: 96–485 mm3, n = 11) in the alendronate-treated mice was 41% of that in the control mice (513 mm3, range: 209–1350 mm3, n = 13) (p < 0.05). In the iliac and sacral lymph nodes of alendronate-treated mice, the proportion of metastatic area was only about 10% of that in control mice (p < 0.001). Immunohistochemical staining of tumor sections showed that alendronate treatment caused a marked decrease in the number of CD34-positive endothelial cells in tumors (p < 0.001) and an increase in that of ISEL positive apoptotic cells in tumors as well as in lymph node metastases (p < 0.05) compared with those in the vehicle-treated mice. The density of m-LYVE-1-stained lymphatic capillaries was not changed. Conclusion Our results demonstrate that alendronate treatment opposes growth of orthotopic PC-3 tumors and decreases tumor metastasis to prostate-draining lymph nodes. This effect could be at least partly explained by

  14. Optimization of Glioblastoma Mouse Orthotopic Xenograft Models for Translational Research.

    PubMed

    Irtenkauf, Susan M; Sobiechowski, Susan; Hasselbach, Laura A; Nelson, Kevin K; Transou, Andrea D; Carlton, Enoch T; Mikkelsen, Tom; deCarvalho, Ana C

    2017-08-01

    Glioblastoma is an aggressive primary brain tumor predominantly localized to the cerebral cortex. We developed a panel of patient-derived mouse orthotopic xenografts (PDOX) for preclinical drug studies by implanting cancer stem cells (CSC) cultured from fresh surgical specimens intracranially into 8-wk-old female athymic nude mice. Here we optimize the glioblastoma PDOX model by assessing the effect of implantation location on tumor growth, survival, and histologic characteristics. To trace the distribution of intracranial injections, toluidine blue dye was injected at 4 locations with defined mediolateral, anterioposterior, and dorsoventral coordinates within the cerebral cortex. Glioblastoma CSC from 4 patients and a glioblastoma nonstem-cell line were then implanted by using the same coordinates for evaluation of tumor location, growth rate, and morphologic and histologic features. Dye injections into one of the defined locations resulted in dye dissemination throughout the ventricles, whereas tumor cell implantation at the same location resulted in a much higher percentage of small multifocal ventricular tumors than did the other 3 locations tested. Ventricular tumors were associated with a lower tumor growth rate, as measured by in vivo bioluminescence imaging, and decreased survival in 4 of 5 cell lines. In addition, tissue oxygenation, vasculature, and the expression of astrocytic markers were altered in ventricular tumors compared with nonventricular tumors. Based on this information, we identified an optimal implantation location that avoided the ventricles and favored cortical tumor growth. To assess the effects of stress from oral drug administration, mice that underwent daily gavage were compared with stress-positive and -negative control groups. Oral gavage procedures did not significantly affect the survival of the implanted mice or physiologic measurements of stress. Our findings document the importance of optimization of the implantation site for

  15. Optimization of Glioblastoma Mouse Orthotopic Xenograft Models for Translational Research

    PubMed Central

    Irtenkauf, Susan M; Sobiechowski, Susan; Hasselbach, Laura A; Nelson, Kevin K; Transou, Andrea D; Carlton, Enoch T; Mikkelsen, Tom; deCarvalho, Ana C

    2017-01-01

    Glioblastoma is an aggressive primary brain tumor predominantly localized to the cerebral cortex. We developed a panel of patient-derived mouse orthotopic xenografts (PDOX) for preclinical drug studies by implanting cancer stem cells (CSC) cultured from fresh surgical specimens intracranially into 8-wk-old female athymic nude mice. Here we optimize the glioblastoma PDOX model by assessing the effect of implantation location on tumor growth, survival, and histologic characteristics. To trace the distribution of intracranial injections, toluidine blue dye was injected at 4 locations with defined mediolateral, anterioposterior, and dorsoventral coordinates within the cerebral cortex. Glioblastoma CSC from 4 patients and a glioblastoma nonstem-cell line were then implanted by using the same coordinates for evaluation of tumor location, growth rate, and morphologic and histologic features. Dye injections into one of the defined locations resulted in dye dissemination throughout the ventricles, whereas tumor cell implantation at the same location resulted in a much higher percentage of small multifocal ventricular tumors than did the other 3 locations tested. Ventricular tumors were associated with a lower tumor growth rate, as measured by in vivo bioluminescence imaging, and decreased survival in 4 of 5 cell lines. In addition, tissue oxygenation, vasculature, and the expression of astrocytic markers were altered in ventricular tumors compared with nonventricular tumors. Based on this information, we identified an optimal implantation location that avoided the ventricles and favored cortical tumor growth. To assess the effects of stress from oral drug administration, mice that underwent daily gavage were compared with stress-positive and ‑negative control groups. Oral gavage procedures did not significantly affect the survival of the implanted mice or physiologic measurements of stress. Our findings document the importance of optimization of the implantation site for

  16. Perioperative management in orthotopic liver transplantation: results of an Italian national survey.

    PubMed

    Biancofiore, G; Della Rocca, G

    2012-06-01

    No data are available on the perioperative approach during orthotopic liver transplantation (OLT) in Italy, apart from sporadically single center studies. The Department of Anesthesia cooperating with each Italian licensed OLT center received a questionnaire regarding preoperative evaluation, intraoperative anesthesia management, anesthetic drugs, blood components therapy, perioperative monitoring, supportive therapies, postoperative care, staff and organization. Twenty-two centers were surveyed and 17 returned the questionnaire. Center specific protocols for OLT anesthesia exist in 12 centers. Balanced anesthesia (volatile anesthetic agents and continuous infusion of opioids) is the standard anesthetic method. In 14 cases a thromboelastogram is available; one center reported not to have a rapid infusion device available. Pulmonary artery catheterization with a continuous cardiac output device is the most used hemodynamic monitoring system; in case of hemodynamic instability, the combination of dopamine/noradrenaline resulted the first choice before vascular clamping whereas noradrenaline alone after graft's reperfusion. No difference about which intraoperative phase is mostly characterized by the use of blood components was reported. Postoperative care is provided on anesthesiological-guided Intensive Care Units (ICU) in all the surveyed centers and in three centers the ICU is dedicated only to transplant patients. The results of this survey show that in Italy the perioperative management of patients undergoing OLT is not homogeneous. This database allows to debate on the best practices and pathways for perioperative management of these patients, and to stimulate future clinical trials aimed to assess the different component and steps forwards of the whole process.

  17. Maintenance of airway epithelium in acutely rejected orthotopic vascularized mouse lung transplants.

    PubMed

    Okazaki, Mikio; Gelman, Andrew E; Tietjens, Jeremy R; Ibricevic, Aida; Kornfeld, Christopher G; Huang, Howard J; Richardson, Steven B; Lai, Jiaming; Garbow, Joel R; Patterson, G Alexander; Krupnick, Alexander S; Brody, Steven L; Kreisel, Daniel

    2007-12-01

    Lung transplantation remains the only therapeutic option for many patients suffering from end-stage pulmonary disease. Long-term success after lung transplantation is severely limited by the development of bronchiolitis obliterans. The murine heterotopic tracheal transplantation model has been widely used for studies investigating pathogenesis of obliterative airway disease and immunosuppressive strategies to prevent its development. Despite its utility, this model employs proximal airway that lacks airflow and is not vascularized. We have developed a novel model of orthotopic vascularized lung transplantation in the mouse, which leads to severe vascular rejection in allogeneic strain combinations. Here we characterize differences in the fate of airway epithelial cells in nonimmunosuppressed heterotopic tracheal and vascularized lung allograft models over 28 days. Up-regulation of growth factors that are thought to be critical for the development of airway fibrosis and interstitial collagen deposition were similar in both models. However, while loss of airway epithelial cells occurred in the tracheal model, airway epithelium remained intact and fully differentiated in lung allografts, despite profound vascular rejection. Moreover, we demonstrate expression of the anti-apoptotic protein Bcl-2 in airway epithelial cells of acutely rejected lung allografts. These findings suggest that in addition to alloimmune responses, other stimuli may be required for the destruction of airway epithelial cells. Thus, the model of vascularized mouse lung transplantation may provide a new and more physiologic experimental tool to study the interaction between immune and nonimmune mechanisms affecting airway pathology in lung allografts.

  18. Early Therapy Evaluation of Combined Anti-DR5 Antibody and Gemcitabine in Orthotopic Pancreatic Tumor Xenografts by Diffusion Weighted Magnetic Resonance Imaging

    PubMed Central

    Kim, Hyunki; Morgan, Desiree E.; Buchsbaum, Donald J.; Zeng, Huadong; Grizzle, William E.; Warram, Jason M.; Stockard, Cecil R.; McNally, Lacey R.; Long, Joshua W.; Sellers, Jeffrey C.; Forero, Andres; Zinn, Kurt R.

    2008-01-01

    Early therapeutic efficacy of anti-DR5 antibody (TRA-8) combined with gemcitabine was measured using diffusion-weighted magnetic resonance imaging (DWI) in an orthotopic pancreatic tumor model. Groups 1–4 of SCID mice (n=5–7/group) bearing orthotopically implanted, luciferase-positive human pancreatic tumors (MIA PaCa-2) were subsequently (4–5 weeks thereafter) injected with saline (control), gemcitabine (120mg/kg), TRA-8 (200μg), or TRA-8 combined with gemcitabine, respectively, on day 0. DWI, anatomical MRI, and bioluminescence imaging were performed on days 0, 1, 2, and 3 after treatment. Three tumors from each group were collected randomly on day 3 after imaging, and TUNEL staining was performed to quantify apoptotic cellularity. At just 1 day after starting therapy, the changes of apparent diffusion coefficient (ADC) in tumor regions for groups 3 (TRA-8) and 4 (TRA-8/Gem) were 21±9% (mean±SE) and 27±3%, respectively, significantly higher (p <0.05) than those of groups 1 (−1±5%) and 2 (−2±4%). There was no statistical difference in tumor volumes for the groups at this time. The mean ADC values of groups 2–4 gradually increased over 3 days, which were concurrent with tumor-volume regressions and bioluminescence-signal decreases. Apoptotic-cell densities of tumors in groups 1–4 were 0.7±0.4%, 0.6±0.2%, 3.1±0.9%, and 4.7±1.0%, respectively, linearly proportional to the ADC changes on day 1. Further, the ADC changes were highly correlated with the previously reported mean survival times of animals treated with the same agents and doses. This study supports the clinical use of DWI for pancreatic tumor patients for early assessment of drug efficacy. PMID:18922909

  19. Influence of Total Knee Arthroplasty on Gait Mechanics of the Replaced and Non-Replaced Limb During Stair Negotiation.

    PubMed

    Standifird, Tyler W; Saxton, Arnold M; Coe, Dawn P; Cates, Harold E; Reinbolt, Jeffrey A; Zhang, Songning

    2016-01-01

    This study compared biomechanics during stair ascent in replaced and non-replaced limbs of total knee arthroplasty (TKA) patients with control limbs of healthy participants. Thirteen TKA patients and fifteen controls performed stair ascent. Replaced and non-replaced knees of TKA patients were less flexed at contact compared to controls. The loading response peak knee extension moment was greater in control and non-replaced knees compared with replaced. The push-off peak knee abduction moment was elevated in replaced limbs compared to controls. Loading and push-off peak hip abduction moments were greater in replaced limbs compared to controls. The push-off peak hip abduction moment was greater in non-replaced limbs compared to controls. Future rehabilitation protocols should consider the replaced knee and also the non-replaced knee and surrounding joints. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Telomerase inhibition improves tumor response to radiotherapy in a murine orthotopic model of human glioblastoma.

    PubMed

    Ferrandon, Sylvain; Malleval, Céline; El Hamdani, Badia; Battiston-Montagne, Priscillia; Bolbos, Radu; Langlois, Jean-Baptiste; Manas, Patrick; Gryaznov, Sergei M; Alphonse, Gersende; Honnorat, Jérôme; Rodriguez-Lafrasse, Claire; Poncet, Delphine

    2015-07-17

    Glioblastoma (GBM) is the most frequent and aggressive type of adult brain tumor. Most GBMs express telomerase; a high level of intra-tumoral telomerase activity (TA) is predictive of poor prognosis. Thus, telomerase inhibitors are promising options to treat GBM. These inhibitors increase the response to radiotherapy (RT), in vitro as well as in vivo. Since typical treatments for GBM include RT, our objective was to evaluate the efficiency of Imetelstat (TA inhibitor) combined with RT. We used a murine orthotopic model of human GBM (N = 8 to11 mice per group) and μMRI imaging to evaluate the efficacy of Imetelstat (delivered by intra-peritoneal injection) alone and combined with RT. Using a clinically established protocol, we demonstrated that Imetelstat significantly: (i) inhibited the TA in the very center of the tumor, (ii) reduced tumor volume as a proportion of TA inhibition, and (iii) increased the response to RT, in terms of tumor volume regression and survival increase. Imetelstat is currently evaluated in refractory brain tumors in young patients (without RT). Our results support its clinical evaluation combined with RT to treat GBM.

  1. Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer.

    PubMed

    Fonseca-Filho, V C N; Katayama, M L H; Lyra, E C; Maria, D A; Basso, R A; Nonogaki, S; Guerra, J M; Maistro, S; Góes, J C G S; Folgueira, M A A K

    2017-11-01

    Calcitriol antiproliferative effects were observed in xenografts of breast cancer cell lines, however they were not yet investigated in tumorgrafts, consisting of freshly collected breast cancer samples xenografted into animals. To establish a tumorgraft model, from freshly collected breast cancer samples, which were directly implanted in nude mice, to study calcitriol effects. Breast cancer samples collected from 12 patients were orthotopically implanted into nude mice. Animals were treated with weekly intratumoral injections of calcitriol 3 μg/Kg, which was previously shown to induce peak serum calcitriol levels in the predicted therapeutic range. Success engraftment rate was 25%. Tumorgrafts were established from aggressive (HER2 positive or histological grade 3) highly proliferative samples and original tumor characteristics were preserved. Calcitriol highly induced its target gene, CYP24A1, indicating that the genomic vitamin D pathway is active in tumorgrafts. However, no differences in the expression of proliferation and apoptosis markers (BrdU incorporation, Ki67, CDKN1A, CDKN1B, BCL2 expression) were observed in these highly proliferative tumor samples. Tumorgrafts seem a promising model to explore other calcitriol doses and regimens, considering the heterogeneity of the disease and microenvironment interactions.

  2. Meiotic activity in orthotopic xenografts derived from human postpubertal testicular tissue.

    PubMed

    Van Saen, D; Goossens, E; Bourgain, C; Ferster, A; Tournaye, H

    2011-02-01

    Grafting of frozen-thawed testicular tissue has been suggested as a novel fertility preservation method for patients undergoing gonadotoxic treatments. However, this technique still needs further optimization before any clinical application. So far, grafting of human testicular tissue has only been performed to the back skin of nude mice and has shown spermatogonial stem-cell survival and occasionally differentiation up to primary spermatocytes. In this study, orthotopic grafting to mouse testes was evaluated as an alternative, and the effect of freezing and the donor's age was studied. Human testicular tissue was obtained from two prepubertal (aged 3 and 5) and two postpubertal (aged 12 and 13) boys. Both fresh and frozen-thawed testicular tissue was grafted to the testis of immuno-deficient nude mice. Four and nine months after transplantation, testes were analyzed by histology and immunohistochemistry. Four and nine months after transplantation, spermatogonial stem cells were observed in all tissue grafts. Germ cell survival was found to be higher in xenografts from the older boys when compared with that from younger donors. Furthermore, no differentiation was observed in the xenografts from younger patients, but the grafts of two older donors showed differentiation up to the primary spermatocyte level, with the presence of secondary spermatocytes in the oldest donor 9 months after transplantation. This xenografting study shows that intratesticular grafting results in high germ cell survival. In grafts derived from the older boys, meiotic activity was maintained in the xenografts for at least 9 months. Although difficult to conduct due to the scarcity of the tissue, more comparative research is needed to elucidate an optimal grafting strategy.

  3. Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model

    PubMed Central

    Huang, Feng-Yun J; Lee, Te-Wei; Chang, Chih-Hsien; Chen, Liang-Cheng; Hsu, Wei-Hsin; Chang, Chien-Wen; Lo, Jem-Mau

    2015-01-01

    Purpose In this study, the 188Re-labeled PEGylated nanoliposome (188Re-liposome) was prepared and evaluated as a therapeutic agent for glioma. Materials and methods The reporter cell line, F98luc was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of 188Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered 188Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the 188Re-liposome-treated rats. Results By using bioluminescent imaging, the well-established reporter cell line (F98luc) showed a high relationship between cell number and its bioluminescent intensity (R2=0.99) in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of 188Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the 188Re-liposome-treated group than the control group (P<0.05). As a result, the lifespan of glioma-bearing rats treated with 188Re-liposome was prolonged 10.67% compared to the control group. Conclusion The radiotherapeutic evaluation by dosimetry and survival studies have demonstrated that passive targeting 188Re-liposome via systemic administration can significantly prolong the

  4. Partial knee replacement - slideshow

    MedlinePlus

    ... page: //medlineplus.gov/ency/presentations/100225.htm Partial knee replacement - series—Normal anatomy To use the sharing ... A.M. Editorial team. Related MedlinePlus Health Topics Knee Replacement A.D.A.M., Inc. is accredited ...

  5. Hepatic gas gangrene following orthotopic liver transplantation: three cases treated with re-transplantation and a review of the literature.

    PubMed

    Doblecki-Lewis, S; Palaios, E; Bejarano, P A; Tzakis, A G; Selvaggi, G; Morris, M I

    2008-07-01

    Gas gangrene is a rare and devastating infectious process that can occur after liver transplantation, most often following hepatic artery thrombosis. We here report 3 cases of gas gangrene following orthotopic liver transplantation. Blood cultures were positive for Clostridium clostridiiforme in one case. In 2 other cases liver tissue from explanted specimens was positive for Enterobacter cloacae. Ultrasound demonstrated hepatic artery thrombosis and computed tomography imaging revealed diffuse liver necrosis with gas formation in each case. All 3 patients were successfully treated with a combination of antibiotics and emergent re-transplantation. We review previously published cases of gas gangrene after liver transplant and emphasize the importance of hepatic artery thrombosis in the development of this syndrome as well as the frequent involvement of non-clostridial organisms. Early diagnosis and aggressive combined medical and surgical treatment including re-transplantation are essential for successful treatment of these rare and catastrophic infections.

  6. Donor age does not influence 12-month outcome after orthotopic liver transplantation.

    PubMed

    Faber, W; Seehofer, D; Puhl, G; Guckelberger, O; Bertram, C; Neuhaus, P; Bahra, M

    2011-12-01

    Orthotopic liver transplantation (OLT) is the most effective treatment for patients with end-stage liver disease to date. The discrepancy between the numbers of donor livers and recipients has become a significant problem, resulting in a high patient mortality on the waiting list. Due to this, an expansion of the donor pool is necessary, for example, by accepting donor grafts from elderly donors. The aim of this study was to investigate the outcome after OLT depending on donor age. We retrospectively evaluated the outcome of 272 full-size cadaveric initial single OLTs within 12 months after OLT. The outcome was analyzed by dividing the collective into four donor age categories: donor age under 50, between 50 and 59, between 60 and 69, and 70 years or above. The outcome after OLT in these patients was retrospectively reviewed by using a prospective database. Patients positive for hepatitis C were excluded from the analysis. No increase of initial nonfunction was observed. Furthermore, no significant differences with regard to surgical complications and serum liver parameter were observed between the groups. Neither patient mortality rates nor rejection rates were different between the groups. However, ischemic-type biliary lesion rates increased significantly with donor age over 70 years (P<.05). The acceptance of liver grafts from older donors is a possible alternative to narrow the gap between donated and required organs. Safe use under optimal protocols is necessary to avoid a deterioration of post-OLT results. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. [Ursolic acid inhibits corneal graft rejection following orthotopic allograft transplantation in rats].

    PubMed

    Wang, Bo; Wu, Jing; Ma, Ming; Li, Ping-Ping; Yu, Jian

    2015-04-01

    To investigate the effects of ursolic acid on corneal graft rejection in a rat model of othotopic corneal allograft transplantation. Forty-eight recipient Wistar rats were divided into normal control group with saline treatment (group A), autograft group with saline treatment (group B), SD rat allograft group with saline treatment (group C), and SD rat allograft group with intraperitoneal ursolic acid (UA) treatment group (group D). The rats received saline or UC (20 mg·kg(-1)·d(-1)) treatment for 12 days following othotopic graft transplantation. The grafts were evaluated using the Larkin corneal rejection rating system, and the graft survival was assessed with Kaplan-Meier analysis. On day 14, the grafts were harvested for histological examination, Western blotting, and assessment of expressions of interlukin-2 (IL-2), interferon-γ (IFN-γ), nuclear transcription factor-κB (NF-κB) p65, vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1). The allograft survival was significantly longer in group D than in group C (29.12±9.58 vs 9.67±2.16 days, P<0.05). UC treatment obviously reduced the expression levels of IL-2, IFN-γ, NF-κBp65, ICAM-1 and VEGF and increased inhibitory kappa B alpha (IκB-α) expression in the grafts, where no obvious inflammatory cell infiltration or corneal neovascularization was found. As a NF-κB inhibitor, ursolic acid can prevent corneal neovascularization and corneal allograft rejection to promote graft survival in rats following orthotopic corneal allograft transplantation.

  8. Androgen replacement for women.

    PubMed Central

    Basson, R.

    1999-01-01

    OBJECTIVES: To determine whether a postmenopausal syndrome comprising specific changes in sexual desire and response associated with low free testosterone exists. To determine whether this syndrome is ameliorated by testosterone replacement. QUALITY OF EVIDENCE: Literature documenting that replacement of physiological levels of testosterone is beneficial and safe is scant. Only one randomized prospective blinded study examines sexual outcome in detail. MAIN MESSAGE: Testosterone is an important metabolic and sex hormone produced by the ovary throughout life. The variable reduction in ovarian testosterone production coincident with menopause is sometimes associated with a syndrome of specific changes in sexual desire and sexual response. Estrogen deficiency also impairs sexual response, but its replacement will not improve and might exacerbate sexual symptoms from androgen loss. Diagnosis of androgen deficiency is clinical, based on accurate assessment of a woman's sexual status before and after menopause and only confirmed (rather than diagnosed) by a low level of free testosterone. Partial androgen replacement restores much of the sexual response and facilitates sexual desire that is triggered by external cues. Avoiding supraphysiological levels of testosterone lessens risk of masculinization. Avoiding alkylated testosterone lessens hepatic or lipid impairment. CONCLUSION: Further prospective randomized studies of replacement of physiological levels of testosterone in women with androgen deficiency syndrome are needed, using formulations of testosterone available in Canada. The consistency of sexual changes, the associated personal and relationship distress, together with our clinical experience of the gratifying response to physiological replacement, make further studies urgently needed. PMID:10509222

  9. Carbohydrates as Fat Replacers.

    PubMed

    Peng, Xingyun; Yao, Yuan

    2017-02-28

    The overconsumption of dietary fat contributes to various chronic diseases, which encourages attempts to develop and consume low-fat foods. Simple fat reduction causes quality losses that impede the acceptance of foods. Fat replacers are utilized to minimize the quality deterioration after fat reduction or removal to achieve low-calorie, low-fat claims. In this review, the forms of fats and their functions in contributing to food textural and sensory qualities are discussed in various food systems. The connections between fat reduction and quality loss are described in order to clarify the rationales of fat replacement. Carbohydrate fat replacers usually have low calorie density and provide gelling, thickening, stabilizing, and other texture-modifying properties. In this review, carbohydrates, including starches, maltodextrins, polydextrose, gums, and fibers, are discussed with regard to their interactions with other components in foods as well as their performances as fat replacers in various systems.

  10. In vivo testing of Renilla luciferase substrate analogs in an orthotopic murine model of human glioblastoma.

    PubMed

    Otto-Duessel, Maya; Khankaldyyan, Vazgen; Gonzalez-Gomez, Ignacio; Jensen, Michael C; Laug, Walter E; Rosol, Michael

    2006-01-01

    In vivo bioluminescent imaging using cells expressing Renilla luciferase is becoming increasingly common. Hindrances to the more widespread use of Renilla luciferase are the high autoluminescence of its natural substrate, coelenterazine, in plasma, the relatively high absorbance by tissue of the light emitted by the enzyme-substrate reaction; rapid clearance of the substrate; and significant cost. These factors, save for the cost, which has its own limiting effect on use, can combine to reduce the sensitivity of in vivo assays utilizing this reporter system, and methods of increasing light output or decreasing autoluminescence could be of great benefit. A number of analogs of coelenterazine are being investigated may accomplish one or both of these goals. In this study that we report on the testing of two new substrate analogs, EnduRen and ViViren, manufactured by Promega Corporation, in an orthotopic murine model of human glioblastoma expressing Renilla luciferase. We have tested these analogs in this cell line both in vitro and in vivo, and find that the substrate viviren results in significantly greater light output than the natural substrate or the other analog EnduRen. This new substrate could be valuable for studies where greater sensitivity is important.

  11. Evolving experience with prevention and treatment of splenic artery syndrome after orthotopic liver transplantation.

    PubMed

    Mogl, Martina T; Nüssler, Natascha C; Presser, Sabine J; Podrabsky, Petr; Denecke, Timm; Grieser, Christian; Neuhaus, Peter; Guckelberger, Olaf

    2010-08-01

    Impaired hepatic arterial perfusion after orthotopic liver transplantation (OLT) may lead to ischemic biliary tract lesions and graft-loss. Hampered hepatic arterial blood flow is observed in patients with hypersplenism, often described as arterial steal syndrome (ASS). However, arterial and portal perfusions are directly linked via the hepatic arterial buffer response (HABR). Recently, the term 'splenic artery syndrome' (SAS) was coined to describe the effect of portal hyperperfusion leading to diminished hepatic arterial blood flow. We retrospectively analyzed 650 transplantations in 585 patients. According to preoperative imaging, 78 patients underwent prophylactic intraoperative ligation of the splenic artery. In case of postoperative SAS, coil-embolization of the splenic artery was performed. After exclusion of 14 2nd and 3rd retransplantations and 83 procedures with arterial interposition grafts, SAS was diagnosed in 28 of 553 transplantations (5.1%). Twenty-six patients were treated with coil-embolization, leading to improved liver function, but requiring postinterventional splenectomy in two patients. Additionally, two patients with SAS underwent splenectomy or retransplantation without preceding embolization. Prophylactic ligation could not prevent SAS entirely (n = 2), but resulted in a significantly lower rate of complications than postoperative coil-embolization. We recommend prophylactic ligation of the splenic artery for patients at risk of developing SAS. Post-transplant coil-embolization of the splenic artery corrected hemodynamic changes of SAS, but was associated with a significant morbidity.

  12. The use of TMZ embedded hydrogels for the treatment of orthotopic human glioma xenografts.

    PubMed

    Adhikari, Bandita; Li, Jie; Brandel, Michael G; Futalan, Diahnn; Akers, Johnny; Deming, Timothy; Chen, Clark C; Carter, Bob S

    2017-11-01

    The current treatment of glioblastoma multiforme (GBM) is limited by the restricted arsenal of agents which effectively cross the blood brain barrier (BBB). For example, only a fraction of temozolomide (TMZ) administered systemically is available for therapeutic effect because of the BBB and the instability of TMZ under physiologic conditions. A novel approach to overcome this obstacle is to bypass the BBB and locally deliver chemotherapeutic agents directly to the tumor mass. We have explored the loading of TMZ into a novel hydrogel matrix, which can be delivered in liquid form and then solidifies in situ and releases chemotherapy as the matrix dissolves. Here, we tested the effect of amphiphilic diblock copolypeptide hydrogels (DCHs) of 180-poly-lysine and 20-poly-leucine (K 180 L 20 ) on TMZ using Glioblastoma models. In both the in vitro model, which involved treatment of a human glioblastoma GSC line suspended as neurospheres, and in vivo using an orthotopic glioma xenograft mouse model, we found that K 180 L 20 could safely enhance the efficacy of TMZ. This technique may offer the opportunity to 'coat' the inner lining of the cavity following glioma resection with a slow-release TMZ and potentially decrease recurrence. Future studies in larger animals are needed to delineate this effect. Copyright © 2017. Published by Elsevier Ltd.

  13. Estrogen and Progestin (Hormone Replacement Therapy)

    MedlinePlus

    ... progestin are two female sex hormones. Hormone replacement therapy works by replacing estrogen hormone that is no ... Progestin is added to estrogen in hormone replacement therapy to reduce the risk of uterine cancer in ...

  14. Elbow replacement

    MedlinePlus

    ... arthroplasty Patient Instructions Elbow replacement - discharge Surgical wound care - open Images Elbow prosthesis References Cohen MS, Chen NC. Total elbow arthroplasty. In: Wolfe SW, Hotchkiss RN, Pederson ...

  15. ESTABLISHMENT AND EVALUATION OF ORTHOTOPIC HEPATOCELLULAR CARCINOMA AND DRUG-INDUCED HEPATOCELLULAR CARCINOMA IN MICE WITH SPLEEN-DEFICIENCY SYNDROME IN TRADITIONAL CHINESE MEDICINE.

    PubMed

    Luo, Haoxuan; Chen, Yan; Sun, Baoguo; Xiang, Ting; Zhang, Shijun

    2017-01-01

    Spleen-deficiency syndrome (SDS) in Traditional Chinese Medicine (TCM) played pivotal roles on the development of hepatocellular carcinoma (HCC). This study was performed to establish and evaluate HCC model in mice with SDS in TCM. A total of 90 C57BL/6 mice were randomized in six groups (n=15 for each group): A, Control group; B, SDS group; C, orthotopic HCC (OHCC) group; D, OHCC based on SDS (SDS-OHCC) group; E, Drug-induced HCC (DHCC) group; F, DHCC based on SDS (SDS-DHCC) group. The SDS model were established by subcutaneous injection of reserpine, followed by the OHCC or DHCC model establishment. The SDS scores, tumor formation rate and survival time were recorded and calculated, as well as the histochemical stain was performed. The SDS scores of mice in Group B, D, F were 17.57±4.86 (P<0.05 vs. Group A), 18.13±4.53 (P<0.05 vs. Group A and C) and 23.32±4.94 (P<0.05 vs. Group A and E) respectively. The tumor formation rate of mice in Group C, D, E and F were 73.33%, 100%, 60% and 80% respectively. The survival time of mice in Group C, D, E and F were 26.42±5.27, 17.33±4.76 (P<0.05 vs. Group C), 35.77±6.12 and 22.61±5.05 (P<0.05 vs. Group E) respectively. The SDS-oriented HCC mice models were simple and easily-operated models for further studies on SDS oriented tumor. Meanwhile, SDS was a pivotal factor for low outcome of hepatic tumor. Abbreviations: HCC, Hepatocellular carcinoma; OHCC, Orthotopic hepatocellular carcinoma; DHCC, Drug-induced hepatocellular carcinoma; SDS, Spleen-deficiency syndrome; TCM, Traditional Chinese Medicine; SPF, Specific pathogen-free; DEN, Diethylnitrosamine; CCl4, Carbon tetrachloride; HE, Hematoxylin-eosin; IACUC, Institutional Animal Care and Use Committee.

  16. Processing the Army’s Wartime Replacements: The Preferred CONUS Replacement Center Concept.

    DTIC Science & Technology

    1987-12-01

    Replacement System. The first model, the macro model, was a network flow model which was used to analyze the flow of replacements from their source through...individual CRCs. Through the analysis of the macro model, recommendations were made on how the CRC system should be configured in terms of size, location

  17. Knee Replacement - Multiple Languages

    MedlinePlus

    ... in a new window. Arabic (العربية) Expand Section Total Knee Replacement - العربية (Arabic) Bilingual PDF Health Information Translations Chinese, Simplified (Mandarin dialect) (简体中文) Expand Section Total Knee Replacement - 简体中文 (Chinese, Simplified (Mandarin dialect)) Bilingual PDF Health ...

  18. Hormone replacement therapy in the developing countries.

    PubMed

    Oei, P L; Ratnam, S S

    1998-05-01

    The sales data of oestrogen replacement products for 8 developing countries from 1993 to 1995 were analyzed. The data from Malaysia, Pakistan, Taiwan, Thailand, Indonesia, Philippines and South Korea showed the increasing use of oestrogen replacement products. The total usage however varied widely, from only US$11,153 (Philippines in 1993) to as much as US$6,306,717 (Taiwan in 1995). In Singapore, where oestrogen replacement is an accepted and established form of therapy for the postmenopausal woman, there has been an increase in the usage of the nonoestrogen replacement products. There are multiple reasons for the increasing sales of hormone replacement products in the developing countries and these are explored in this article. In some of the developing countries, for example China and India, hormone replacement therapy has just been introduced. However, in those developing countries in which hormone replacement therapy is already available, sales figures show increasing usage. The future augurs well for hormone replacement therapy.

  19. Fluorescence imaging of angiogenesis in green fluorescent protein-expressing tumors

    NASA Astrophysics Data System (ADS)

    Yang, Meng; Baranov, Eugene; Jiang, Ping; Li, Xiao-Ming; Wang, Jin W.; Li, Lingna; Yagi, Shigeo; Moossa, A. R.; Hoffman, Robert M.

    2002-05-01

    The development of therapeutics for the control of tumor angiogenesis requires a simple, reliable in vivo assay for tumor-induced vascularization. For this purpose, we have adapted the orthotopic implantation model of angiogenesis by using human and rodent tumors genetically tagged with Aequorea victoria green fluorescent protein (GFP) for grafting into nude mice. Genetically-fluorescent tumors can be readily imaged in vivo. The non-luminous induced capillaries are clearly visible against the bright tumor fluorescence examined either intravitally or by whole-body luminance in real time. Fluorescence shadowing replaces the laborious histological techniques for determining blood vessel density. High-level GFP-expressing tumor cell lines made it possible to acquire the high-resolution real-time fluorescent optical images of angiogenesis in both primary tumors and their metastatic lesions in various human and rodent tumor models by means of a light-based imaging system. Intravital images of angiogenesis onset and development were acquired and quantified from a GFP- expressing orthotopically-growing human prostate tumor over a 19-day period. Whole-body optical imaging visualized vessel density increasing linearly over a 20-week period in orthotopically-growing, GFP-expressing human breast tumor MDA-MB-435. Vessels in an orthotopically-growing GFP- expressing Lewis lung carcinoma tumor were visualized through the chest wall via a reversible skin flap. These clinically-relevant angiogenesis mouse models can be used for real-time in vivo evaluation of agents inhibiting or promoting tumor angiogenesis in physiological micro- environments.

  20. 22 CFR 51.10 - Replacement passports.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Replacement passports. 51.10 Section 51.10 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS General § 51.10 Replacement passports. A passport issuing office may issue a replacement passport without payment of applicable fees for...

  1. 22 CFR 51.10 - Replacement passports.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Replacement passports. 51.10 Section 51.10 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS General § 51.10 Replacement passports. A passport issuing office may issue a replacement passport without payment of applicable fees for...

  2. 22 CFR 51.10 - Replacement passports.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Replacement passports. 51.10 Section 51.10 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS General § 51.10 Replacement passports. A passport issuing office may issue a replacement passport without payment of applicable fees for...

  3. 22 CFR 51.10 - Replacement passports.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Replacement passports. 51.10 Section 51.10 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS General § 51.10 Replacement passports. A passport issuing office may issue a replacement passport without payment of applicable fees for...

  4. 22 CFR 51.10 - Replacement passports.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Replacement passports. 51.10 Section 51.10 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS General § 51.10 Replacement passports. A passport issuing office may issue a replacement passport without payment of applicable fees for...

  5. Mechanical valve replacement in congenital heart disease.

    PubMed

    Fiane, A E; Lindberg, H L; Saatvedt, K; Svennevig, J L

    1996-05-01

    Mechanical valves are the prosthesis of choice in valve replacement in children. However, the problem of somatic growth leading to patient-valve mismatch remains present, and the appropriate anticoagulation regimen remains controversial. We present our experience of valve replacement in a young population over 20 years. Between 1972 and 1992, 48 patients (34 males and 14 females), mean age 11.2 years (range 0.4-27.4 years), underwent mechanical valve replacement at our institution. Aortic valve replacement was performed in 28 patients (58.3%), mitral valve replacement in 13 (27.1%), tricuspid valve replacement in six (12.5%) and pulmonary valve replacement in one patient (2.1%). The prostheses used were: St. Jude Medical (n = 2), Björk-Shiley (n = 14), Medtronic Hall (n = 16), Duromedics (n = 2) and CarboMedics (n = 14). Early mortality was 14.3%, 10.7% for aortic valve replacement and 30.8% for mitral valve replacement. Mean follow up for all patients was 8.3 years (range 0-22 years), with a total of 398 patient-years. Seven patients died during the follow up (17.1%). Survival after 10 years, including operative mortality, was 81% for aortic valve replacement, 33% for mitral valve replacement, 83% for tricuspid valve replacement and 100% for pulmonary valve replacement. All patients were anticoagulated with warfarin. In eight patients (16.7%) an antiplatelet drug (aspirin or dipyridamole) was added. Major events included paravalvular leak in six patients (1.5%/pty), valve thrombosis in five (mitral position in two, tricuspid in three) (1.3%/pty) and endocarditis in one patient (0.3%/pty). Minor thromboembolic events occurred in three patients (0.8%/pty) and minor hemorrhagic events in three (0.8%/pty). No patients developed hemolytic anemia and there was no case of structural failure. In our experience, mechanical prostheses in congenital heart disease were associated with significant morbidity and mortality, however long term survival after aortic valve

  6. Long-life slab replacement concrete.

    DOT National Transportation Integrated Search

    2015-03-01

    This research was initiated following reports of high incidence of cracking on FDOT concrete pavement replacement : slab projects. Field slabs were instrumented for data acquisition from high-early-strength concrete pavement : replacement slabs place...

  7. Shoulder replacement

    MedlinePlus

    ... the opening at the end of the shoulder blade, called the socket. This type of joint allows ... head. The socket part (glenoid) of your shoulder blade will be replaced with a smooth plastic shell ( ...

  8. MDCA Needle 1 Replacement

    NASA Image and Video Library

    2013-04-22

    ISS035-E-025557(22 April 2013) ---Multi-user Droplet Combustion Apparatus (MDCA) Hardware Replacement: Cassidy accessed the Combustion Integration Rack (CIR) Combustion Chamber and removed the MDCA Chamber Insert Assembly (CIA). He then replaced the MDCA Needle 1 due to a fuel line that was damaged during previous activities when the MDCA CIA was being removed from the Combustion Chamber.

  9. Knee Replacement

    MedlinePlus

    ... a knee replacement is right for you, an orthopedic surgeon assesses your knee's range of motion, stability ... trademarks of Mayo Foundation for Medical Education and Research. © 1998-2018 Mayo Foundation for Medical Education and ...

  10. A novel orthotopic mouse model of head and neck cancer and lymph node metastasis

    PubMed Central

    Masood, R; Hochstim, C; Cervenka, B; Zu, S; Baniwal, S K; Patel, V; Kobielak, A; Sinha, U K

    2013-01-01

    Prognosis of head and neck squamous cell carcinoma (HNSCC) is largely determined by the extent of lymph node (LN) metastasis at diagnosis, and this appears to be controlled by cancer cell genetics. To examine the role of these genes in LN metastasis, we created a human-in-mouse orthotopic model of HNSCC and performed comparative microarray analysis of gene expression between populations of HNSCC cell lines derived before and after serial transplantation and in vivo metastasis in mice. Microarray analysis comparing the USC-HN3-GFP, USC-HN3-GFP-G1 and USC-HN3-GFP-G2 cell lines identified overexpression of genes implicated in epithelial-to- mesenchymal transition and the formation of cancer stem cells, including CAV-1, TLR-4 (Toll-like receptor 4), MMP-7 (matrix metalloproteinase 7), ALDH1A3, OCT-4 and TRIM-29. Ingenuity Pathway Analysis confirmed upregulation of respective gene signaling pathways in the USC-HN1-GFP-G2 cell line. Patient HNSCC samples from advanced stages overexpressed ALDH1A3, CAV-1 and MMP-7. Our results show that CAV-1, TLR-4, MMP-7, ALDH1A3, OCT-4 and TRIM-29 have increased expression in HNSCC cells selected for an enhanced metastatic phenotype and suggest that these genes may have an important role in the metastatic potential of HNSCC cells. Inhibition of these genes may therefore have prognostic and therapeutic utility in HNSCC. PMID:24018643

  11. Real-time Tumor Oxygenation Changes After Single High-dose Radiation Therapy in Orthotopic and Subcutaneous Lung Cancer in Mice: Clinical Implication for Stereotactic Ablative Radiation Therapy Schedule Optimization

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Song, Changhoon; Hong, Beom-Ju; Bok, Seoyeon

    Purpose: To investigate the serial changes of tumor hypoxia in response to single high-dose irradiation by various clinical and preclinical methods to propose an optimal fractionation schedule for stereotactic ablative radiation therapy. Methods and Materials: Syngeneic Lewis lung carcinomas were grown either orthotopically or subcutaneously in C57BL/6 mice and irradiated with a single dose of 15 Gy to mimic stereotactic ablative radiation therapy used in the clinic. Serial [{sup 18}F]-misonidazole (F-MISO) positron emission tomography (PET) imaging, pimonidazole fluorescence-activated cell sorting analyses, hypoxia-responsive element-driven bioluminescence, and Hoechst 33342 perfusion were performed before irradiation (day −1), at 6 hours (day 0), and 2 (daymore » 2) and 6 (day 6) days after irradiation for both subcutaneous and orthotopic lung tumors. For F-MISO, the tumor/brain ratio was analyzed. Results: Hypoxic signals were too low to quantitate for orthotopic tumors using F-MISO PET or hypoxia-responsive element-driven bioluminescence imaging. In subcutaneous tumors, the maximum tumor/brain ratio was 2.87 ± 0.483 at day −1, 1.67 ± 0.116 at day 0, 2.92 ± 0.334 at day 2, and 2.13 ± 0.385 at day 6, indicating that tumor hypoxia was decreased immediately after irradiation and had returned to the pretreatment levels at day 2, followed by a slight decrease by day 6 after radiation. Pimonidazole analysis also revealed similar patterns. Using Hoechst 33342 vascular perfusion dye, CD31, and cleaved caspase 3 co-immunostaining, we found a rapid and transient vascular collapse, which might have resulted in poor intratumor perfusion of F-MISO PET tracer or pimonidazole delivered at day 0, leading to decreased hypoxic signals at day 0 by PET or pimonidazole analyses. Conclusions: We found tumor hypoxia levels decreased immediately after delivery of a single dose of 15 Gy and had returned to the pretreatment levels 2 days after irradiation and had

  12. Anti-tumor angiogenesis effect of aminopeptidase inhibitor bestatin against B16-BL6 melanoma cells orthotopically implanted into syngeneic mice.

    PubMed

    Aozuka, Yasushi; Koizumi, Keiichi; Saitoh, Yurika; Ueda, Yasuji; Sakurai, Hiroaki; Saiki, Ikuo

    2004-12-08

    We investigated the effect of bestatin, an inhibitor of aminopeptidase N (APN)/CD13 and aminopeptidase B, on the angiogenesis induced by B16-BL6 melanoma cells. Oral administration of bestatin (100-200 mg/kg/day) was found to significantly inhibit the melanoma cell-induced angiogenesis in a mouse dorsal air sac assay. Additionally, anti-APN/CD13 mAb (WM15), which neutralizes the aminopeptidase activity in tumor cells, as well as bestatin inhibited the tube-like formation of human umbilical vein endothelial cells (HUVECs) in vitro. Furthermore, the intraperitoneal administration of bestatin (50-100 mg/kg/day) after the orthotopic implantation of B16-BL6 melanoma cells into mice reduced the number of vessels oriented towards the established primary tumor mass on the dorsal side of mice. These findings suggest that bestatin is an active anti-angiogenic agent that may inhibit tumor angiogenesis in vivo and tube-like formation of endothelial cells in vitro through its inhibition of APN/CD13 activity.

  13. Auxiliary partial orthotopic living donor liver transplantation with a small-for-size graft for congenital absence of the portal vein.

    PubMed

    Matsuura, Toshiharu; Soejima, Yuji; Taguchi, Tomoaki

    2010-12-01

    Congenital absence of the portal vein (CAPV) with an extrahepatic portosystemic shunt is a rare malformation; the completely absent type, Abernethy malformation type I, is especially rare. Liver transplantation for CAPV type I has been recently recognized as the only curative operation, but few reports have been published so far; meanwhile, auxiliary partial orthotopic liver transplantation (APOLT) has been proposed to be a very effective option, especially for pediatric patients. Here we present an 18-year-old adult patient with CAPV, asplenia, and an iliac shunt vessel who was managed successfully with APOLT using a small-for-size graft. To the best of our knowledge, this is the first adult patient who has experienced success with APOLT for CAPV. This is a feasible procedure: it not only fulfills the metabolic demands of the liver for adult patients but also potentially cures CAPV. Copyright © 2010 American Association for the Study of Liver Diseases.

  14. Imaging, autoradiography, and biodistribution of (188)Re-labeled PEGylated nanoliposome in orthotopic glioma bearing rat model.

    PubMed

    Huang, Feng-Yun J; Lee, Te-Wei; Kao, Chih-Hao K; Chang, Chih-Hsien; Zhang, Xiaoning; Lee, Wan-Yu; Chen, Wan-Jou; Wang, Shu-Chi; Lo, Jem-Mau

    2011-12-01

    The (188)Re-labeled pegylated nanoliposome (abbreviated as (188)Re-Liposome) was prepared and evaluated for its potential as a theragnostic agent for glioma. (188)Re-BMEDA complex was loaded into the pegylated liposome core with pH 5.5 ammonium sulfate gradient to produce (188)Re-Liposome. Orthotopic Fischer344/F98 glioma tumor-bearing rats were prepared and intravenously injected with (188)Re-Liposome. Biodistribution, pharmacokinetic study, autoradiography (ARG), histopathology, and nano-SPECT/CT imaging were conducted for the animal model. The result showed that (188)Re-Liposome accumulated in the brain tumor of the animal model from 0.28%±0.09% injected dose (ID)/g (n=3) at 1 hour to a maximum of 1.95%±0.35% ID/g (n=3) at 24 hours postinjection. The tumor-to-normal brain uptake ratio (T/N ratio) increased from 3.5 at 1 hour to 32.5 at 24 hours. Both ARG and histopathological images clearly showed corresponding tumor regions with high T/N ratios. Nano-SPECT/CT detected a very clear tumor image from 4 hours till 48 hours. This study reveals the potential of (188)Re-Liposome as a theragnostic agent for brain glioma.

  15. Orthotopic liver transplantation for portosystemic encephalopathy in an adult with congenital absence of the portal vein.

    PubMed

    Wojcicki, Maciej; Haagsma, Elizabeth B; Gouw, Annette S H; Slooff, Maarten J H; Porte, Robert J

    2004-09-01

    Congenital absence of the portal vein (CAPV) is a very rare venous malformation in which mesenteric venous blood drains directly into the systemic circulation. There is no portal perfusion of the liver and no portal hypertension. This abnormality is usually coincidentally discovered in children, the majority of whom have no signs of encephalopathy and only slightly abnormal liver function tests. Additional anomalies common in CAPV are cardiovascular abnormalities and hepatic tumors. To date, only 5 adult patients (>18 years) with CAPV have been described, none of whom underwent liver transplantation. We describe a 45-year-old man with CAPV and end-stage renal insufficiency due to focal segmental glomerulopathy, who developed therapy-resistant encephalopathy with intermittently high ammonia levels. The patient underwent a combined liver and kidney transplantation and is doing well at 2.5 years of follow-up. Histopathological examination of the native liver showed no portal vein branches in the portal tracts. In conclusion, our experience suggests that, although children with CAPV usually have no symptoms of encephalopathy, this may still develop at a later stage in adult life. When encephalopathy becomes refractory to medical therapy, orthotopic liver transplantation (OLT) can be successfully performed with restoration of normal cerebral function.

  16. Improvements of the surgical technique on the established mouse model of orthotopic single lung transplantation.

    PubMed

    Zheng, Zhikun; Wang, Jianjun; Huang, Xia; Jiang, Ke; Nie, Jun; Qiao, Xinwei; Li, Jinsong

    2013-01-01

    A wide range of knockout and transgenic murine models for the study of nonimmune and immune mechanisms in lung transplants are available nowadays, but the microsurgical techniques are difficult to learn. We describe methods to simplify techniques and facilitate learning. Traditional procedures were implemented to perform lung transplants in 30 cases (group 1). Improved techniques which included cuff without tail, broadening of the cuff diameter for bronchus, establishment of one tunnel between three structures, innovative technology of the vascular anastomosis and placement of the chest tube post-operation were used to perform lung transplants in 30 cases (group 2). The improved techniques considerably shorten operative times (96.75 ± 6.16 min and 85.32 ± 6.98 min in groups 1 and 2, respectively). The survival rates in the recipient animals were 86.7% and 96.7% in groups 1 and 2, respectively. Chest X-rays and macroscopic changes of transplanted recipients showed that grafts were well inflated on postoperative day 30. There was no significant difference of the arterial oxygen tension (PaO2) between two groups (115.9 ± 7.11 mm Hg and 116.3 ± 6.87 mm Hg in groups 1 and 2, respectively). Histologically, no lung injury was seen in grafts. We described the modified procedures of orthotopic left lung transplants in mice, which could shorten operative time and increase survival rate.

  17. ¹H MRS characterization of neurochemical profiles in orthotopic mouse models of human brain tumors.

    PubMed

    Hulsey, Keith M; Mashimo, Tomoyuki; Banerjee, Abhishek; Soesbe, Todd C; Spence, Jeffrey S; Vemireddy, Vamsidhara; Maher, Elizabeth A; Bachoo, Robert M; Choi, Changho

    2015-01-01

    Glioblastoma (GBM), the most common primary brain tumor, is resistant to currently available treatments. The development of mouse models of human GBM has provided a tool for studying mechanisms involved in tumor initiation and growth as well as a platform for preclinical investigation of new drugs. In this study we used (1) H MR spectroscopy to study the neurochemical profile of a human orthotopic tumor (HOT) mouse model of human GBM. The goal of this study was to evaluate differences in metabolite concentrations in the GBM HOT mice when compared with normal mouse brain in order to determine if MRS could reliably differentiate tumor from normal brain. A TE =19 ms PRESS sequence at 9.4 T was used for measuring metabolite levels in 12 GBM mice and 8 healthy mice. Levels for 12 metabolites and for lipids/macromolecules at 0.9 ppm and at 1.3 ppm were reliably detected in all mouse spectra. The tumors had significantly lower concentrations of total creatine, GABA, glutamate, total N-acetylaspartate, aspartate, lipids/macromolecules at 0.9 ppm, and lipids/macromolecules at 1.3 ppm than did the brains of normal mice. The concentrations of glycine and lactate, however, were significantly higher in tumors than in normal brain. Copyright © 2014 John Wiley & Sons, Ltd.

  18. Hypofractionated Radiotherapy Is Superior to Conventional Fractionation in an Orthotopic Model of Anaplastic Thyroid Cancer.

    PubMed

    Oweida, Ayman; Phan, Andy; Vancourt, Benjamin; Robin, Tyler; Hararah, Mohammad K; Bhatia, Shilpa; Milner, Dallin; Lennon, Shelby; Pike, Laura; Raben, David; Haugen, Bryan; Pozdeyev, Nikita; Schweppe, Rebecca; Karam, Sana D

    2018-06-01

    Anaplastic thyroid cancer (ATC) is an aggressive and highly lethal disease with poor outcomes and resistance to therapy. Despite multimodality treatment, including radiation therapy and chemotherapy, response rates remain <15%, with a median time to progression of less than three months. Recent advances in radiotherapy (RT) delivery and gene-expression profiling may help guide patient selection for personalized therapy. The purpose of this study was to characterize the response to radiation in a panel of ATC cell lines and to test alternative RT fractionation schedules for overcoming radioresistance. The cellular response to radiation was characterized based on clonogenic assays. Radiation response was correlated with microarray gene-expression data. Hypofractionated and conventional RT was tested in an orthotopic ATC tumor model, and tumor growth was assayed locally and distantly with in vivo and ex vivo bioluminescence imaging. A spectrum of radiosensitivities was observed in ATC cell lines. Radioresistant cell lines had higher levels of CXCR4 compared to radiosensitive cell lines. Compared to conventionally fractionated RT, hypofractionated RT resulted in significantly improved tumor growth delay, decreased regional and distant metastases, and improved overall survival. The findings demonstrate the heterogeneity of response to radiation in ATC tumors and the superiority of hypofractionated RT in improving local control, metastatic spread, and survival in preclinical models. These data support the design of clinical trials targeting radioresistant pathways in combination with hypofractionated RT.

  19. Repeated assessment of orthotopic glioma pO2 by multi-site EPR oximetry: A technique with the potential to guide therapeutic optimization by repeated measurements of oxygen

    PubMed Central

    Khan, Nadeem; Mupparaju, Sriram; Hou, Huagang; Williams, Benjamin B.; Swartz, Harold

    2011-01-01

    Tumor hypoxia plays a vital role in therapeutic resistance. Consequently, measurements of tumor pO2 could be used to optimize the outcome of oxygen-dependent therapies, such as, chemoradiation. However, the potential optimizations are restricted by the lack of methods to repeatedly and quantitatively assess tumor pO2 during therapies, particularly in gliomas. We describe the procedures for repeated measurements of orthotopic glioma pO2 by multi-site electron paramagnetic resonance (EPR) oximetry. This oximetry approach provides simultaneous measurements of pO2 at more than one site in the glioma and contralateral cerebral tissue. The pO2 of intracerebral 9L, C6, F98 and U251 tumors, as well as contralateral brain, were measured repeatedly for five consecutive days. The 9L glioma was well oxygenated with pO2 of 27 - 36 mm Hg, while C6, F98 and U251 glioma were hypoxic with pO2 of 7 - 12 mm Hg. The potential of multi-site EPR oximetry to assess temporal changes in tissue pO2 was investigated in rats breathing 100% O2. A significant increase in F98 tumor and contralateral brain pO2 was observed on day 1 and day 2, however, glioma oxygenation declined on subsequent days. In conclusion, EPR oximetry provides the capability to repeatedly assess temporal changes in orthotopic glioma pO2. This information could be used to test and optimize the methods being developed to modulate tumor hypoxia. Furthermore, EPR oximetry could be potentially used to enhance the outcome of chemoradiation by scheduling treatments at times of increase in glioma pO2. PMID:22079559

  20. Biological tooth replacement

    PubMed Central

    Sartaj, Rachel; Sharpe, Paul

    2006-01-01

    Teeth develop from a series of reciprocal interactions that take place between epithelium and mesenchyme during development of the mouth that begin early in mammalian embryogenesis. The molecular control of key processes in tooth development such as initiation, morphogenesis and cytodifferentiation are being increasingly better understood, to the point where this information can be used as the basis for approaches to produce biological replacement teeth (BioTeeth). This review outlines the current approaches, ideas and progress towards the production of BioTeeth that could form an alternative method for replacing lost or damaged teeth. PMID:17005022

  1. Impact of N-acetylcysteine on the hepatic microcirculation after orthotopic liver transplantation.

    PubMed

    Koeppel, T A; Lehmann, T G; Thies, J C; Gehrcke, R; Gebhard, M M; Herfarth, C; Otto, G; Post, S

    1996-05-15

    Recent observations showed an improvement of hepatic macro- and microhemodynamics as well as survival rates after warm ischemia of the liver following treatment with N-acetylcysteine (NAC). In this study we assessed the influence of NAC on the hepatic microcirculation after orthotopic liver transplantation (OLT) using intravital fluorescence microscopy. OLT with simultaneous arterialization was performed in 16 male Lewis rats following cold storage in University of Wisconsin solution for 24 hr. Within the experimental group (n = 8) donors received NAC (400 mg/kg) 25 min before hepatectomy. In addition, high-dose treatment of recipients with NAC (400 mg/kg) was started with reperfusion. Control animals (n = 8) received an equivalent amount of Ringer's solution. Intravital fluorescence microscopy was performed 30-90 min after reperfusion assessing acinar and sinusoidal perfusion, leukocyte-endothelium interaction, and phagocytic activity. Treatment with NAC reduced the number of nonperfused sinusoid from 52.4 +/- 0.8% to 15.7 +/- 0.5% (p = 0.0001) (mean +/- SEM). Furthermore, we achieved a significant reduction of leukocytes adhering to sinusoidal endothelium (per mm2 liver surface) from 351.9 +/- 13.0 in controls to 83.6 +/- 4.2 in the experimental group (P = 0.0001). In postsinusoidal venules, treatment with NAC decreased the number of sticking leukocytes (per mm2 endothelium) from 1098.5 +/- 59.6 to 425.9 +/- 37.7 (P = 0.0001). Moreover, bile flow was significantly increased after therapy with NAC (4.3 +/- 1.2 vs. 2.2 +/- 0.7 ml/90 min x 100g liver) (P < 0.05). Phagocytic activity was not influenced by application of NAC. We conclude that high-dose therapy with NAC in OLT attenuates manifestations of microvascular perfusion failure early after reperfusion and should be considered as a means to reduce reperfusion injury.

  2. Analysis of radical cystectomy and urinary diversion complications with the Clavien classification system in an Italian real life cohort.

    PubMed

    De Nunzio, C; Cindolo, L; Leonardo, C; Antonelli, A; Ceruti, C; Franco, G; Falsaperla, M; Gallucci, M; Alvarez-Maestro, M; Minervini, A; Pagliarulo, V; Parma, P; Perdonà, S; Porreca, A; Rocco, B; Schips, L; Serni, S; Serrago, M; Simeone, C; Simone, G; Spadavecchia, R; Celia, A; Bove, P; Zaramella, S; Crivellaro, S; Nucciotti, R; Salvaggio, A; Frea, B; Pizzuti, V; Salsano, L; Tubaro, A

    2013-07-01

    Standardized methods of reporting complications after radical cystectomy (RC) and urinary diversions (UD) are necessary to evaluate the morbidity associated with this operation to evaluate the modified Clavien classification system (CCS) in grading perioperative complications of RC and UD in a real life cohort of patients with bladder cancer. A consecutive series of patients treated with RC and UD from April 2011 to March 2012 at 19 centers in Italy was evaluated. Complications were recorded according to the modified CCS. Results were presented as complication rates per grade. Univariate and binary logistic regression analysis were used for statistical analysis. 467 patients were enrolled. Median age was 70 years (range 35-89). UD consisted in orthotopic neobladder in 112 patients, ileal conduit in 217 patients and cutaneous ureterostomy in 138 patients. 415 complications were observed in 302 patients and were classified as Clavien type I (109 patients) or II (220 patients); Clavien type IIIa (45 patients), IIIb (22 patients); IV (11 patients) and V (8 patients). Patients with cutaneous ureterostomy presented a lower rate (8%) of CCS type ≥IIIa (p = 0.03). A longer operative time was an independent risk factor of CCS ≥III (OR: 1.005; CI: 1.002-1.007 per minute; p = 0.0001). In our study, RC is associated with a significant morbidity (65%) and a reduced mortality (1.7%) when compared to previous experiences. The modified CCS represents an easily applicable tool to classify the complications of RC and UD in a more objective and detailed way. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Serious gaming for orthotopic liver transplant anesthesiology: A randomized control trial.

    PubMed

    Katz, Daniel; Zerillo, Jeron; Kim, Sang; Hill, Bryan; Wang, Ryan; Goldberg, Andrew; DeMaria, Samuel

    2017-04-01

    Anesthetic management of orthotopic liver transplantation (OLT) is complex. Given the unequal distributions of liver transplant surgeries performed at different centers, anesthesiology providers receive relatively uneven OLT training and exposure. One well-suited modality for OLT training is the "serious game," an interactive application created for the purpose of imparting knowledge or skills, while leveraging the self-motivating elements of video games. We therefore developed a serious game designed to teach best practices for the anesthetic management of a standard OLT and determined if the game would improve resident performance in a simulated OLT. Forty-four residents on the liver transplant rotation were randomized to either the gaming group (GG) or the control group (CG) prior to their introductory simulation. Both groups were given access to the same educational materials and literature during their rotation, but the GG also had access to the OLT Trainer. Performance on the simulations were recorded on a standardized grading rubric. Both groups experienced an increase in score relative to baseline that was statistically significant at every stage. The improvements in scores were greater for the GG participants than the CG participants. Overall score improvement between the GG and CG (mean [standard deviation]) was statistically significant (GG, 7.95 [3.65]; CG, 4.8 [4.48]; P = 0.02), as were scores for preoperative assessment (GG, 2.67 [2.09]; CG, 1.17 [1.43]; P = 0.01) and anhepatic phase (GG, 1.62 [1.01]; CG, 0.75 [1.28]; P = 0.02). Of the residents with game access, 81% were "very satisfied" or "satisfied" with the game overall. In conclusion, adding a serious game to an existing educational curriculum for liver transplant anesthesia resulted in significant learning gains for rotating anesthesia residents. The intervention was straightforward to implement and cost-effective. Liver Transplantation 23 430-439 2017 AASLD. © 2017 by the American Association

  4. Prioritizing equipment for replacement.

    PubMed

    Capuano, Mike

    2010-01-01

    It is suggested that clinical engineers take the lead in formulating evaluation processes to recommend equipment replacement. Their skill, knowledge, and experience, combined with access to equipment databases, make them a logical choice. Based on ideas from Fennigkoh's scheme, elements such as age, vendor support, accumulated maintenance cost, and function/risk were used.6 Other more subjective criteria such as cost benefits and efficacy of newer technology were not used. The element of downtime was also omitted due to the data element not being available. The resulting Periop Master Equipment List and its rationale was presented to the Perioperative Services Program Council. They deemed the criteria to be robust and provided overwhelming acceptance of the list. It was quickly put to use to estimate required capital funding, justify items already thought to need replacement, and identify high-priority ranked items for replacement. Incorporating prioritization criteria into an existing equipment database would be ideal. Some commercially available systems do have the basic elements of this. Maintaining replacement data can be labor-intensive regardless of the method used. There is usually little time to perform the tasks necessary for prioritizing equipment. However, where appropriate, a clinical engineering department might be able to conduct such an exercise as shown in the following case study.

  5. Prioritization methodology for chemical replacement

    NASA Technical Reports Server (NTRS)

    Cruit, Wendy; Goldberg, Ben; Schutzenhofer, Scott

    1995-01-01

    Since United States of America federal legislation has required ozone depleting chemicals (class 1 & 2) to be banned from production, The National Aeronautics and Space Administration (NASA) and industry have been required to find other chemicals and methods to replace these target chemicals. This project was initiated as a development of a prioritization methodology suitable for assessing and ranking existing processes for replacement 'urgency.' The methodology was produced in the form of a workbook (NASA Technical Paper 3421). The final workbook contains two tools, one for evaluation and one for prioritization. The two tools are interconnected in that they were developed from one central theme - chemical replacement due to imposed laws and regulations. This workbook provides matrices, detailed explanations of how to use them, and a detailed methodology for prioritization of replacement technology. The main objective is to provide a GUIDELINE to help direct the research for replacement technology. The approach for prioritization called for a system which would result in a numerical rating for the chemicals and processes being assessed. A Quality Function Deployment (QFD) technique was used in order to determine numerical values which would correspond to the concerns raised and their respective importance to the process. This workbook defines the approach and the application of the QFD matrix. This technique: (1) provides a standard database for technology that can be easily reviewed, and (2) provides a standard format for information when requesting resources for further research for chemical replacement technology. Originally, this workbook was to be used for Class 1 and Class 2 chemicals, but it was specifically designed to be flexible enough to be used for any chemical used in a process (if the chemical and/or process needs to be replaced). The methodology consists of comparison matrices (and the smaller comparison components) which allow replacement technology

  6. Permanent Quadriplegia Following Replacement of Voice Prosthesis.

    PubMed

    Ozturk, Kayhan; Erdur, Omer; Kibar, Ertugrul

    2016-11-01

    The authors presented a patient with quadriplegia caused by cervical spine abscess following voice prosthesis replacement. The authors present the first reported permanent quadriplegia patient caused by voice prosthesis replacement. The authors wanted to emphasize that life-threatening complications may be faced during the replacement of voice prosthesis. Care should be taken during the replacement of voice prosthesis and if some problems have been faced during the procedure patients must be followed closely.

  7. 25 CFR 700.189 - Expenditure of replacement home benefits.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false Expenditure of replacement home benefits. 700.189 Section... PROCEDURES Replacement Housing Payments § 700.189 Expenditure of replacement home benefits. Replacement home... maximum replacement home benefit. (b) All replacement home benefits shall be expended not later than one...

  8. 25 CFR 700.189 - Expenditure of replacement home benefits.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 2 2014-04-01 2014-04-01 false Expenditure of replacement home benefits. 700.189 Section... PROCEDURES Replacement Housing Payments § 700.189 Expenditure of replacement home benefits. Replacement home... maximum replacement home benefit. (b) All replacement home benefits shall be expended not later than one...

  9. 25 CFR 700.189 - Expenditure of replacement home benefits.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Expenditure of replacement home benefits. 700.189 Section... PROCEDURES Replacement Housing Payments § 700.189 Expenditure of replacement home benefits. Replacement home... maximum replacement home benefit. (b) All replacement home benefits shall be expended not later than one...

  10. 25 CFR 700.189 - Expenditure of replacement home benefits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Expenditure of replacement home benefits. 700.189 Section... PROCEDURES Replacement Housing Payments § 700.189 Expenditure of replacement home benefits. Replacement home... maximum replacement home benefit. (b) All replacement home benefits shall be expended not later than one...

  11. 25 CFR 700.189 - Expenditure of replacement home benefits.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 2 2013-04-01 2013-04-01 false Expenditure of replacement home benefits. 700.189 Section... PROCEDURES Replacement Housing Payments § 700.189 Expenditure of replacement home benefits. Replacement home... maximum replacement home benefit. (b) All replacement home benefits shall be expended not later than one...

  12. The management of failed ankle replacement.

    PubMed

    Kotnis, R; Pasapula, C; Anwar, F; Cooke, P H; Sharp, R J

    2006-08-01

    Advances in the design of the components for total ankle replacement have led to a resurgence of interest in this procedure. Between January 1999 and December 2004, 16 patients with a failed total ankle replacement were referred to our unit. In the presence of infection, a two-stage salvage procedure was planned. The first involved the removal of the components and the insertion of a cement spacer. Definitive treatment options included hindfoot fusion with a circular frame or amputation. When there was no infection, a one-stage salvage procedure was planned. Options included hindfoot fusion with an intramedullary nail or revision total ankle replacement. When there was suspicion of infection, a percutaneous biopsy was performed. The patients were followed up for a minimum of 12 months. Of the 16 patients, 14 had aseptic loosening, five of whom underwent a revision total ankle replacement and nine a hindfoot fusion. Of the two with infection, one underwent fusion and the other a below-knee amputation. There were no cases of wound breakdown, nonunion or malunion. Management of the failed total ankle replacement should be performed by experienced surgeons and ideally in units where multidisciplinary support is available. Currently, a hindfoot fusion appears to be preferable to a revision total ankle replacement.

  13. Twenty-Year Outcome After Right Ventricular Outflow Tract Repair Using Heterotopic Pulmonary Conduits in Infants and Children.

    PubMed

    Hoxha, Stiljan; Torre, Salvatore; Rungatscher, Alessio; Sandrini, Camilla; Rossetti, Lucia; Barozzi, Luca; Faggian, Giuseppe; Luciani, Giovanni Battista

    2016-01-01

    Durability of pulmonary conduits (PCs) used for reconstruction of the right ventricular outflow tract (RVOT) may be affected by a variety of factors. Among these, the technique used for PC implantation, whether in orthotopic or heterotopic position, strictly dependent upon the underlying anatomy, has been suggested to influence long-term outcome after RVOT repair. To determine the outcome of heterotopic implantation in infants and children treated at our institution, late results of heterotopic PC in non-Ross patients were analyzed and compared with data of orthotopic PC in age-matched pediatric Ross patients operated during the same time period. Between November 1991 and January 2015, 58 infants and children, 32 male and 26 female, with a median age of 9.4 years (range 1 day-18 years) underwent implantation of heterotopic PC (31 homografts [HG] and 27 xenografts [XG]) for reconstruction of RVOT. Median age in the XG group was significantly lower than in the HG group (0.9 vs. 13.4 years, P = 0.01), while male/female ratio was similar. Fifty (86%) patients had undergone one or more prior cardiac operations, while 32 (55%) required associated procedures during PC implantation. Comparison with data in 305 children and with a median age of 9.4 years, receiving orthotopic PC between 1990 and 2012 (Italian Pediatric Ross Registry), was undertaken. Descriptive, univariate, and Kaplan-Meier analysis defined outcome. There were three (5.2%) early and five (9.0%) late deaths, during a median follow-up of 7.6 years (range 2 months-23 years). Patients having XG had trend toward higher hospital mortality (2/27 vs. 1/31, P = 0.2), but similar late mortality (2/24 vs. 3/30, P = 0.3). Overall survival was 88 and 62%, while freedom from PC replacement was 49 and 21%, at 10 and 20 years, respectively. The latter proved significantly worse than freedom from orthotopic PC replacement, which was 94 ± 2 and 70 ± 9% at 10 and 20 years (P = 0.02). When stratified

  14. Repeated assessment of orthotopic glioma pO(2) by multi-site EPR oximetry: a technique with the potential to guide therapeutic optimization by repeated measurements of oxygen.

    PubMed

    Khan, Nadeem; Mupparaju, Sriram; Hou, Huagang; Williams, Benjamin B; Swartz, Harold

    2012-02-15

    Tumor hypoxia plays a vital role in therapeutic resistance. Consequently, measurements of tumor pO(2) could be used to optimize the outcome of oxygen-dependent therapies, such as, chemoradiation. However, the potential optimizations are restricted by the lack of methods to repeatedly and quantitatively assess tumor pO(2) during therapies, particularly in gliomas. We describe the procedures for repeated measurements of orthotopic glioma pO(2) by multi-site electron paramagnetic resonance (EPR) oximetry. This oximetry approach provides simultaneous measurements of pO(2) at more than one site in the glioma and contralateral cerebral tissue. The pO(2) of intracerebral 9L, C6, F98 and U251 tumors, as well as contralateral brain, were measured repeatedly for five consecutive days. The 9L glioma was well oxygenated with pO(2) of 27-36 mm Hg, while C6, F98 and U251 glioma were hypoxic with pO(2) of 7-12mm Hg. The potential of multi-site EPR oximetry to assess temporal changes in tissue pO(2) was investigated in rats breathing 100% O(2). A significant increase in F98 tumor and contralateral brain pO(2) was observed on day 1 and day 2, however, glioma oxygenation declined on subsequent days. In conclusion, EPR oximetry provides the capability to repeatedly assess temporal changes in orthotopic glioma pO(2). This information could be used to test and optimize the methods being developed to modulate tumor hypoxia. Furthermore, EPR oximetry could be potentially used to enhance the outcome of chemoradiation by scheduling treatments at times of increase in glioma pO(2). Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Management of the failed biaxial wrist replacement.

    PubMed

    Talwalkar, S C; Hayton, M J; Trail, I A; Stanley, J K

    2005-06-01

    Nine cases of failed biaxial wrist replacement underwent revision surgery and subsequent clinical and radiographic assessment at a mean follow-up of 28 months. Clinical assessment included the hospital for special surgery (HSS) and activities of daily living scoring systems. Five patients had a revision biaxial wrist replacement, three had wrist fusions and two underwent an excision arthroplasty. The mean HSS score was 73 for the revision biaxial replacements, 63 for the wrist fusions and 92 for the excision arthroplasties. The mean activities for daily living score was 16 for the revision biaxial replacements, 14 for the wrist fusion and 20 for the excision arthroplasties. Despite the experience of implant failure, six patients would still choose a primary wrist replacement again. All patients in this small series appear to have had good clinical outcomes. Revision to another wrist replacement appears no worse than a wrist fusion in the short term and patients value the preservation of movement that an implant offers.

  16. 25 CFR 700.53 - Dwelling, replacement.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Policies and Instructions Definitions § 700.53 Dwelling, replacement. The term replacement dwelling means a... unreasonable adverse environmental conditions from either natural or man-made sources and in an area not...

  17. Molecular replacement: tricks and treats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abergel, Chantal, E-mail: chantal.abergel@igs.cnrs-mrs.fr

    2013-11-01

    To be successful, molecular replacement relies on the quality of the model and of the crystallographic data. Some tricks that could be applied to the models or to the crystal to increase the success rate of MR are discussed here. Molecular replacement is the method of choice for X-ray crystallographic structure determination provided that suitable structural homologues are available in the PDB. Presently, there are ∼80 000 structures in the PDB (8074 were deposited in the year 2012 alone), of which ∼70% have been solved by molecular replacement. For successful molecular replacement the model must cover at least 50% ofmore » the total structure and the C{sub α} r.m.s.d. between the core model and the structure to be solved must be less than 2 Å. Here, an approach originally implemented in the CaspR server (http://www.igs.cnrs-mrs.fr/Caspr2/index.cgi) based on homology modelling to search for a molecular-replacement solution is discussed. How the use of as much information as possible from different sources can improve the model(s) is briefly described. The combination of structural information with distantly related sequences is crucial to optimize the multiple alignment that will define the boundaries of the core domains. PDB clusters (sequences with ≥30% identical residues) can also provide information on the eventual changes in conformation and will help to explore the relative orientations assumed by protein subdomains. Normal-mode analysis can also help in generating series of conformational models in the search for a molecular-replacement solution. Of course, finding a correct solution is only the first step and the accuracy of the identified solution is as important as the data quality to proceed through refinement. Here, some possible reasons for failure are discussed and solutions are proposed using a set of successful examples.« less

  18. 21 CFR 870.3925 - Replacement heart valve.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Replacement heart valve. 870.3925 Section 870.3925...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3925 Replacement heart valve. (a) Identification. A replacement heart valve is a device intended to perform the function of any...

  19. 40 CFR 1042.615 - Replacement engine exemption.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Replacement engine exemption. 1042.615... CONTROLS CONTROL OF EMISSIONS FROM NEW AND IN-USE MARINE COMPRESSION-IGNITION ENGINES AND VESSELS Special Compliance Provisions § 1042.615 Replacement engine exemption. For Category 1 and Category 2 replacement...

  20. 40 CFR 1042.615 - Replacement engine exemption.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Replacement engine exemption. 1042.615... CONTROLS CONTROL OF EMISSIONS FROM NEW AND IN-USE MARINE COMPRESSION-IGNITION ENGINES AND VESSELS Special Compliance Provisions § 1042.615 Replacement engine exemption. For Category 1 and Category 2 replacement...

  1. 21 CFR 870.3925 - Replacement heart valve.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Replacement heart valve. 870.3925 Section 870.3925...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3925 Replacement heart valve. (a) Identification. A replacement heart valve is a device intended to perform the function of any...

  2. 21 CFR 870.3925 - Replacement heart valve.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Replacement heart valve. 870.3925 Section 870.3925...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3925 Replacement heart valve. (a) Identification. A replacement heart valve is a device intended to perform the function of any...

  3. 21 CFR 870.3925 - Replacement heart valve.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Replacement heart valve. 870.3925 Section 870.3925...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3925 Replacement heart valve. (a) Identification. A replacement heart valve is a device intended to perform the function of any...

  4. 21 CFR 870.3925 - Replacement heart valve.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Replacement heart valve. 870.3925 Section 870.3925...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3925 Replacement heart valve. (a) Identification. A replacement heart valve is a device intended to perform the function of any...

  5. Evaluation of neovascularization patterns in an orthotopic rat glioma model with dynamic contrast-enhanced MRI.

    PubMed

    Xuesong, Du; Wei, Xue; Heng, Liu; Xiao, Chen; Shunan, Wang; Yu, Guo; Weiguo, Zhang

    2017-09-01

    Background Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been proved useful in evaluating glioma angiogenesis, but the utility in evaluating neovascularization patterns has not been reported. Purpose To evaluate in vivo real-time glioma neovascularization patterns by measuring glioma perfusion quantitatively using DCE-MRI. Material and Methods Thirty Sprague-Dawley rats were used to establish C6 orthotopic glioma model and underwent MRI and pathology detections. As MRI and pathology were performed at six time points (i.e. 4, 8, 12, 16, 20, and 24 days) post transplantation, neovascularization patterns were evaluated via DCE-MRI. Results Four neovascularization patterns were observed in glioma tissues. Sprout angiogenesis and intussusceptive microvascular growth located inside tumor, while vascular co-option and vascular mimicry were found in the tumor margin and necrotic area, respectively. Sprout angiogenesis and intussusceptive microvascular growth increased with K trans , K ep , and V p inside tumor tissue. In addition, K ep and V p were positively correlated with sprout angiogenesis and intussusceptive microvascular growth. Vascular co-option was decreased at 12 and 16 days post transplantation and correlated negatively with K trans and K ep detected in the glioma margin, respectively. Changes of vascular mimicry showed no significant statistical difference at the six time points. Conclusion Our results indicate that DCE-MRI can evaluate neovascularization patterns in a glioma model. Furthermore, DCE-MRI could be an imaging biomarker for guidance of antiangiogenic treatments in humans in the future.

  6. EGFR-targeted gelatin nanoparticles for systemic administration of gemcitabine in an orthotopic pancreatic cancer model.

    PubMed

    Singh, Amit; Xu, Jing; Mattheolabakis, George; Amiji, Mansoor

    2016-04-01

    In this study, we have formulated redox-responsive epidermal growth factor receptor (EGFR)-targeted type B gelatin nanoparticles as a targeted vector for systemic delivery of gemcitabine therapy in pancreatic cancer. The gelatin nanoparticles were formed by ethanol-induced desolvation process to encapsulate the bound drug. The surface of the nanoparticles was decorated either with poly(ethylene glycol) (PEG) chains to impart enhanced circulation time or with EGFR targeting peptide to confer target specificity. Our in vitro studies in Panc-1 human pancreatic ductal adenocarcinoma cells confirm that gemcitabine encapsulated in EGFR-targeted gelatin nanoparticles, released through disulfide bond cleavage, had a significantly improved cytotoxic profile. Further, the in vivo anticancer activity was evaluated in an orthotopic pancreatic adenocarcinoma tumor bearing SCID beige mice, which confirmed that EGFR-targeted gelatin nanoparticles could efficiently deliver gemcitabine to the tumor leading to higher therapeutic benefit as compared to the drug in solution. The treatment of pancreatic cancer remains unsatisfactory, with an average 5-year survival of less than 5%. New treatment modalities are thus urgently needed. In this study, the authors presented their formulation of redox-responsive epidermal growth factor receptor (EGFR)-targeted type B gelatin nanoparticles as a carrier for gemcitabine. In-vitro and in-vivo experiments showed encouraging results. It is hoped that the findings would provide a novel and alternative drug delivery platform for the future. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model

    PubMed Central

    Parajuli, Keshab Raj; Zhang, Qiuyang; Liu, Sen; You, Zongbing

    2016-01-01

    Aminomethylphosphonic acid (AMPA) has been shown to inhibit prostate cancer cell growth in vitro. The purpose of the present study was to determine if AMPA could inhibit growth and metastasis of prostate cancer in vivo. Human prostate cancer PC-3-LacZ-luciferase cells were implanted into the ventral lateral lobes of the prostate in 39 athymic Nu/Nu nude male mice. Seven days later, mice were randomized into the control group (n = 14, treated intraperitoneally with phosphate buffered saline), low dose group (n = 10, treated intraperitoneally with AMPA at 400 mg/kg body weight/day), and high dose group (n = 15, treated intraperitoneally with AMPA at 800 mg/kg body weight/day). Tumor growth and metastasis were examined every 4-7 days by bioluminescence imaging of live mice. We found that AMPA treatment significantly inhibited growth and metastasis of orthotopic xenograft prostate tumors and prolonged the survival time of the mice. AMPA treatment decreased expression of BIRC2 and activated caspase 3, leading to increased apoptosis in the prostate tumors. AMPA treatment decreased expression of cyclin D1. AMPA treatment also reduced angiogenesis in the prostate tumors. Taken together, these results demonstrate that AMPA can inhibit prostate cancer growth and metastasis, suggesting that AMPA may be developed into a therapeutic agent for the treatment of prostate cancer. PMID:26840261

  8. GSK3β and VDAC Involvement in ER Stress and Apoptosis Modulation during Orthotopic Liver Transplantation

    PubMed Central

    Zaouali, Mohamed Amine; Panisello, Arnau; Lopez, Alexandre; Castro, Carlos; Folch, Emma; Carbonell, Teresa; Rolo, Anabela; Palmeira, Carlos Marques; Garcia-Gil, Agustin; Adam, René; Roselló-Catafau, Joan

    2017-01-01

    We investigated the involvement of glycogen synthase kinase-3β (GSK3β) and the voltage-dependent anion channel (VDAC) in livers subjected to cold ischemia–reperfusion injury (I/R) associated with orthotopic liver transplantation (OLT). Rat livers were preserved in University of Wisconsin (UW) and Institute Georges Lopez (IGL-1) solution, the latter enriched or not with trimetazidine, and then subjected to OLT. Transaminase (ALT) and HMGB1 protein levels, glutamate dehydrogenase (GLDH), and oxidative stress (MDA) were measured. The AKT protein kinase and its direct substrates, GSK3β and VDAC, as well as caspases 3, 9, and cytochrome C and reticulum endoplasmic stress-related proteins (GRP78, pPERK, ATF4, and CHOP), were determined by Western blot. IGL-1+TMZ significantly reduced liver injury. We also observed a significant phosphorylation of AKT, which in turn induced the phosphorylation and inhibition of GSK3β. In addition, TMZ protected the mitochondria since, in comparison with IGL-1 alone, we found reductions in VDAC phosphorylation, apoptosis, and GLDH release. All these results were correlated with decreased ER stress. Addition of TMZ to IGL-1 solution increased the tolerance of the liver graft to I/R injury through inhibition of GSK3β and VDAC, contributing to ER stress reduction and cell death prevention. PMID:28282906

  9. Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model.

    PubMed

    Parajuli, Keshab Raj; Zhang, Qiuyang; Liu, Sen; You, Zongbing

    2016-03-01

    Aminomethylphosphonic acid (AMPA) has been shown to inhibit prostate cancer cell growth in vitro. The purpose of the present study was to determine if AMPA could inhibit growth and metastasis of prostate cancer in vivo. Human prostate cancer PC-3-LacZ-luciferase cells were implanted into the ventral lateral lobes of the prostate in 39 athymic Nu/Nu nude male mice. Seven days later, mice were randomized into the control group (n = 14, treated intraperitoneally with phosphate buffered saline), low dose group (n = 10, treated intraperitoneally with AMPA at 400 mg/kg body weight/day), and high dose group (n = 15, treated intraperitoneally with AMPA at 800 mg/kg body weight/day). Tumor growth and metastasis were examined every 4-7 days by bioluminescence imaging of live mice. We found that AMPA treatment significantly inhibited growth and metastasis of orthotopic xenograft prostate tumors and prolonged the survival time of the mice. AMPA treatment decreased expression of BIRC2 and activated caspase 3, leading to increased apoptosis in the prostate tumors. AMPA treatment decreased expression of cyclin D1. AMPA treatment also reduced angiogenesis in the prostate tumors. Taken together, these results demonstrate that AMPA can inhibit prostate cancer growth and metastasis, suggesting that AMPA may be developed into a therapeutic agent for the treatment of prostate cancer.

  10. 40 CFR 85.1714 - Replacement-engine exemption.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Replacement-engine exemption. 85.1714... Vehicle Engines § 85.1714 Replacement-engine exemption. (a) Engine manufacturers may use the provisions of 40 CFR 1068.240 to exempt new replacement heavy-duty highway engines as specified in this section. (b...

  11. 40 CFR 85.1714 - Replacement-engine exemption.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 19 2012-07-01 2012-07-01 false Replacement-engine exemption. 85.1714... Vehicle Engines § 85.1714 Replacement-engine exemption. (a) Engine manufacturers may use the provisions of 40 CFR 1068.240 to exempt new replacement heavy-duty highway engines as specified in this section. (b...

  12. 40 CFR 85.1714 - Replacement-engine exemption.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 19 2013-07-01 2013-07-01 false Replacement-engine exemption. 85.1714... Vehicle Engines § 85.1714 Replacement-engine exemption. (a) Engine manufacturers may use the provisions of 40 CFR 1068.240 to exempt new replacement heavy-duty highway engines as specified in this section. (b...

  13. 40 CFR 85.1714 - Replacement-engine exemption.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 18 2011-07-01 2011-07-01 false Replacement-engine exemption. 85.1714... Vehicle Engines § 85.1714 Replacement-engine exemption. (a) Engine manufacturers may use the provisions of 40 CFR 1068.240 to exempt new replacement heavy-duty highway engines as specified in this section. (b...

  14. 40 CFR 85.1714 - Replacement-engine exemption.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 19 2014-07-01 2014-07-01 false Replacement-engine exemption. 85.1714... Vehicle Engines § 85.1714 Replacement-engine exemption. (a) Engine manufacturers may use the provisions of 40 CFR 1068.240 to exempt new replacement heavy-duty highway engines as specified in this section. (b...

  15. Homologous gene replacement in Physarum

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Burland, T.G.; Pallotta, D.

    1995-01-01

    The protist Physarum polycephalum is useful for analysis of several aspects of cellular and developmental biology. To expand the opportunities for experimental analysis of this organism, we have developed a method for gene replacement. We transformed Physarum amoebae with plasmid DNA carrying a mutant allele, ardD{Delta}1, of the ardD actin gene; ardD{Delta}1 mutates the critical carboxy-terminal region of the gene product. Because ardD is not expressed in the amoeba, replacement of ardD{sup +} with ardD{Delta}1 should not be lethal for this cell type. Transformants were obtained only when linear plasmid DNA was used. Most transformants carried one copy of ardD{Delta}1more » in addition to ardD{sup +}, but in two (5%), ardD{sup +} was replaced by a single copy of ardD{Delta}1. This is the first example of homologous gene replacement in Physarum. ardD{Delta}1 was stably maintained in the genome through growth, development and meiosis. We found no effect of ardD{Delta}l on viability, growth, or development of any of the various cell types of Physarum. Thus, the carboxy-terminal region of the ardD product appears not to perform a unique essential role in growth or development. Nevertheless, this method for homologous gene replacement can be applied to analyze the function of any cloned gene. 38 refs., 6 figs., 1 tab.« less

  16. 43 CFR 4750.4-4 - Replacement animals.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Replacement animals. 4750.4-4 Section 4750... FREE-ROAMING HORSES AND BURROS Private Maintenance § 4750.4-4 Replacement animals. The authorized officer shall replace an animal, upon request by the adopter, if (a) within 6 months of the execution of...

  17. 43 CFR 4750.4-4 - Replacement animals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Replacement animals. 4750.4-4 Section 4750... FREE-ROAMING HORSES AND BURROS Private Maintenance § 4750.4-4 Replacement animals. The authorized officer shall replace an animal, upon request by the adopter, if (a) within 6 months of the execution of...

  18. 43 CFR 4750.4-4 - Replacement animals.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Replacement animals. 4750.4-4 Section 4750... FREE-ROAMING HORSES AND BURROS Private Maintenance § 4750.4-4 Replacement animals. The authorized officer shall replace an animal, upon request by the adopter, if (a) within 6 months of the execution of...

  19. 43 CFR 4750.4-4 - Replacement animals.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Replacement animals. 4750.4-4 Section 4750... FREE-ROAMING HORSES AND BURROS Private Maintenance § 4750.4-4 Replacement animals. The authorized officer shall replace an animal, upon request by the adopter, if (a) within 6 months of the execution of...

  20. Long-life slab replacement concrete : [summary].

    DOT National Transportation Integrated Search

    2015-04-01

    Concrete slab replacement projects in Florida have demonstrated a high incidence of : replacement slab cracking. Causes of cracking have not been reliably determined. University of South Florida researchers : sought to identify the factors or : param...

  1. Hip or knee replacement - in the hospital after

    MedlinePlus

    Hip replacement surgery - after - self-care; Knee replacement surgery - after - self-care ... taking walks in the hallways with help. After knee replacement, some surgeons recommend using a continuous passive ...

  2. Cobra Probes Containing Replaceable Thermocouples

    NASA Technical Reports Server (NTRS)

    Jones, John; Redding, Adam

    2007-01-01

    A modification of the basic design of cobra probes provides for relatively easy replacement of broken thermocouples. Cobra probes are standard tube-type pressure probes that may also contain thermocouples and that are routinely used in wind tunnels and aeronautical hardware. They are so named because in side views, they resemble a cobra poised to attack. Heretofore, there has been no easy way to replace a broken thermocouple in a cobra probe: instead, it has been necessary to break the probe apart and then rebuild it, typically at a cost between $2,000 and $4,000 (2004 prices). The modified design makes it possible to replace the thermocouple, in minimal time and at relatively low cost, by inserting new thermocouple wire in a tube.

  3. Ross procedure for ascending aortic replacement.

    PubMed

    Elkins, R C; Lane, M M; McCue, C

    1999-06-01

    Patients with aortic valve disease and aneurysm or dilatation of the ascending aorta require both aortic valve replacement and treatment of their ascending aortic disease. In children and young adults, the Ross operation is preferred when the aortic valve requires replacement, but the efficacy of extending this operation to include replacement of the ascending aorta or reduction of the dilated aorta has not been tested. We reviewed the medical records of 18 (5.9%) patients with aortic valve disease and an ascending aortic aneurysm and 26 (8.5%) patients with dilation of the ascending aorta, subgroups of 307 patients who had a Ross operation between August 1986 and February 1998. We examined operative and midterm results, including recent echocardiographic assessment of autograft valve function and ability of the autograft root and ascending aortic repair or replacement to maintain normal structural integrity. There was one operative death (2%) related to a perioperative stroke. Forty-two of 43 survivors have normal autograft valve function, with trace to mild autograft valve insufficiency, and one patient has moderate insufficiency at the most recent echocardiographic evaluation. None of the patients has dilatation of the autograft root or of the replaced or reduced ascending aorta. Early results with extension of the Ross operation to include replacement of an ascending aortic aneurysm or vertical aortoplasty for reduction of a dilated ascending aorta are excellent, with autograft valve function equal to that seen in similar patients without ascending aortic disease.

  4. Color-coding cancer and stromal cells with genetic reporters in a patient-derived orthotopic xenograft (PDOX) model of pancreatic cancer enhances fluorescence-guided surgery

    PubMed Central

    Yano, Shuya; Hiroshima, Yukihiko; Maawy, Ali; Kishimoto, Hiroyuki; Suetsugu, Atsushi; Miwa, Shinji; Toneri, Makoto; Yamamoto, Mako; Katz, Matthew H.G.; Fleming, Jason B.; Urata, Yasuo; Tazawa, Hiroshi; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M.

    2015-01-01

    Precise fluorescence-guided surgery (FGS) for pancreatic cancer has the potential to greatly improve the outcome in this recalcitrant disease. In order to achieve this goal, we have used genetic reporters to color code cancer and stroma cells in a patient-derived orthotopic xenograft (PDOX) model. The telomerase-dependent green fluorescent protein (GFP) containing adenovirus OBP401 was used to label the cancer cells of the pancreatic cancer PDOX. The PDOX was previously grown in a red fluorescent protein (RFP) transgenic mouse that stably labeled the PDOX stroma cells bright red. The color-coded PDOX model enabled FGS to completely resect the pancreatic tumors including stroma. Dual-colored FGS significantly prevented local recurrence, which bright-light surgery (BLS) or single color could not. FGS, with color-coded cancer and stroma cells has important potential for improving the outcome of recalcitrant cancer. PMID:26088297

  5. Evolution of high tooth replacement rates in sauropod dinosaurs.

    PubMed

    D'Emic, Michael D; Whitlock, John A; Smith, Kathlyn M; Fisher, Daniel C; Wilson, Jeffrey A

    2013-01-01

    Tooth replacement rate can be calculated in extinct animals by counting incremental lines of deposition in tooth dentin. Calculating this rate in several taxa allows for the study of the evolution of tooth replacement rate. Sauropod dinosaurs, the largest terrestrial animals that ever evolved, exhibited a diversity of tooth sizes and shapes, but little is known about their tooth replacement rates. We present tooth replacement rate, formation time, crown volume, total dentition volume, and enamel thickness for two coexisting but distantly related and morphologically disparate sauropod dinosaurs Camarasaurus and Diplodocus. Individual tooth formation time was determined by counting daily incremental lines in dentin. Tooth replacement rate is calculated as the difference between the number of days recorded in successive replacement teeth. Each tooth family in Camarasaurus has a maximum of three replacement teeth, whereas each Diplodocus tooth family has up to five. Tooth formation times are about 1.7 times longer in Camarasaurus than in Diplodocus (315 vs. 185 days). Average tooth replacement rate in Camarasaurus is about one tooth every 62 days versus about one tooth every 35 days in Diplodocus. Despite slower tooth replacement rates in Camarasaurus, the volumetric rate of Camarasaurus tooth replacement is 10 times faster than in Diplodocus because of its substantially greater tooth volumes. A novel method to estimate replacement rate was developed and applied to several other sauropodomorphs that we were not able to thin section. Differences in tooth replacement rate among sauropodomorphs likely reflect disparate feeding strategies and/or food choices, which would have facilitated the coexistence of these gigantic herbivores in one ecosystem. Early neosauropods are characterized by high tooth replacement rates (despite their large tooth size), and derived titanosaurs and diplodocoids independently evolved the highest known tooth replacement rates among archosaurs.

  6. Evolution of High Tooth Replacement Rates in Sauropod Dinosaurs

    PubMed Central

    Smith, Kathlyn M.; Fisher, Daniel C.; Wilson, Jeffrey A.

    2013-01-01

    Background Tooth replacement rate can be calculated in extinct animals by counting incremental lines of deposition in tooth dentin. Calculating this rate in several taxa allows for the study of the evolution of tooth replacement rate. Sauropod dinosaurs, the largest terrestrial animals that ever evolved, exhibited a diversity of tooth sizes and shapes, but little is known about their tooth replacement rates. Methodology/Principal Findings We present tooth replacement rate, formation time, crown volume, total dentition volume, and enamel thickness for two coexisting but distantly related and morphologically disparate sauropod dinosaurs Camarasaurus and Diplodocus. Individual tooth formation time was determined by counting daily incremental lines in dentin. Tooth replacement rate is calculated as the difference between the number of days recorded in successive replacement teeth. Each tooth family in Camarasaurus has a maximum of three replacement teeth, whereas each Diplodocus tooth family has up to five. Tooth formation times are about 1.7 times longer in Camarasaurus than in Diplodocus (315 vs. 185 days). Average tooth replacement rate in Camarasaurus is about one tooth every 62 days versus about one tooth every 35 days in Diplodocus. Despite slower tooth replacement rates in Camarasaurus, the volumetric rate of Camarasaurus tooth replacement is 10 times faster than in Diplodocus because of its substantially greater tooth volumes. A novel method to estimate replacement rate was developed and applied to several other sauropodomorphs that we were not able to thin section. Conclusions/Significance Differences in tooth replacement rate among sauropodomorphs likely reflect disparate feeding strategies and/or food choices, which would have facilitated the coexistence of these gigantic herbivores in one ecosystem. Early neosauropods are characterized by high tooth replacement rates (despite their large tooth size), and derived titanosaurs and diplodocoids independently

  7. Adrenergic Receptor Polymorphism and Maximal Exercise Capacity after Orthotopic Heart Transplantation.

    PubMed

    Métrich, Mélanie; Mehmeti, Fortesa; Feliciano, Helene; Martin, David; Regamey, Julien; Tozzi, Piergiorgio; Meyer, Philippe; Hullin, Roger

    Maximal exercise capacity after heart transplantion (HTx) is reduced to the 50-70% level of healthy controls when assessed by cardiopulmonary exercise testing (CPET) despite of normal left ventricular function of the donor heart. This study investigates the role of donor heart β1 and β2- adrenergic receptor (AR) polymorphisms for maximal exercise capacity after orthotopic HTx. CPET measured peak VO2 as outcome parameter for maximal exercise in HTx recipients ≥9 months and ≤4 years post-transplant (n = 41; mean peak VO2: 57±15% of predicted value). Donor hearts were genotyped for polymorphisms of the β1-AR (Ser49Gly, Arg389Gly) and the β2-AR (Arg16Gly, Gln27Glu). Circumferential shortening of the left ventricle was measured using magnetic resonance based CSPAMM tagging. Peak VO2 was higher in donor hearts expressing the β1-Ser49Ser alleles when compared with β1-Gly49 carriers (60±15% vs. 47±10% of the predicted value; p = 0.015), and by trend in cardiac allografts with the β1-AR Gly389Gly vs. β1-Arg389 (61±15% vs. 54±14%, p = 0.093). Peak VO2 was highest for the haplotype Ser49Ser-Gly389, and decreased progressively for Ser49Ser-Arg389Arg > 49Gly-389Gly > 49Gly-Arg389Arg (adjusted R2 = 0.56, p = 0.003). Peak VO2 was not different for the tested β2-AR polymorphisms. Independent predictors of peak VO2 (adjusted R2 = 0.55) were β1-AR Ser49Gly SNP (p = 0.005), heart rate increase (p = 0.016), and peak systolic blood pressure (p = 0.031). Left ventricular (LV) motion kinetics as measured by cardiac MRI CSPAMM tagging at rest was not different between carriers and non-carriers of the β1-AR Gly49allele. Similar LV cardiac motion kinetics at rest in donor hearts carrying either β1-AR Gly49 or β1-Ser49Ser variant suggests exercise-induced desensitization and down-regulation of the β1-AR Gly49 variant as relevant pathomechanism for reduced peak VO2 in β1-AR Gly49 carriers.

  8. Obscured hemorrhagic pancreatitis after orthotopic heart transplantation complicated with acute right heart failure and hepatic dysfunction: a case report.

    PubMed

    Lin, Ting-Wei; Tsai, Meng-Ta; Roan, Jun-Neng; Liu, Yi-Sheng; Tsai, Hong-Ming; Luo, Chwan-Yau

    2016-12-01

    Pancreatitis is a serious complication after cardiac surgery and can lead to significant morbidities and mortality. The incidence of pancreatitis is even higher in patients undergoing heart transplantation than in those undergoing other cardiac surgeries. Nevertheless, the clinical presentations of pancreatitis are frequently atypical in these patients. We report a heart recipient who was complicated with acute right heart failure initially after orthotopic heart transplantation and developed devastating unanticipated hemorrhagic pancreatitis 1 month after the transplantation. This crypto-symptomatic pancreatitis was not diagnosed until massive internal bleeding and hemorrhagic shock occurred, because the typical presentations of acute pancreatitis were masked by the intra-abdominal manifestations caused by right heart failure and congestive liver dysfunction. The patient underwent a successful transarterial embolization. The causes of pancreatitis after heart transplantation include low cardiac output, immunosuppressant use and cytomegalovirus infection. The typical symptoms of pancreatitis might be not apparent in patients after heart transplantation because of their immunosuppressive status. Furthermore, in patients complicated with right heart failure after transplantation, the manifestation of pancreatitis could be even more obscure. The prompt diagnosis is highly depended on the clinician's astuteness.

  9. 47 CFR 13.17 - Replacement license.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Replacement license. 13.17 Section 13.17 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMERCIAL RADIO OPERATORS General § 13.17 Replacement license. (a) Each licensee or permittee whose original document is lost, mutilated, or destroyed must...

  10. Hepatic Arterial Infusion of Low-Density Lipoprotein Docosahexaenoic Acid Nanoparticles Selectively Disrupts Redox Balance in Hepatoma cells and Reduces Growth of Orthotopic Liver Tumors in Rats

    PubMed Central

    Wen, Xiaodong; Reynolds, Lacy; Mulik, Rohit S.; Kim, Soo Young; Van Treuren, Tim; Nguyen, Liem H.; Zhu, Hao; Corbin, Ian R.

    2015-01-01

    Background & Aims Dietary intake of the natural omega-3 fatty acid docosahexaenoic acid (DHA) has been implicated in protecting patients with viral hepatitis B or C from developing hepatocellular carcinoma (HCC). Little is known about the effects of DHA on established solid tumors. Herein, we describe a low-density lipoprotein (LDL)-based nanoparticle that acts as a transporter for unesterified DHA (LDL–DHA) and demonstrates selective cytotoxicity towards HCC cells. We investigated the ability of LDL–DHA to reduce growth of orthotopic hepatomas in rats. Methods ACI rats were given intrahepatic injections of rat hepatoma cells (H4IIE); 24 tumor-bearing rats (mean tumor diameter, ~1 cm) were subject to a single hepatic artery injection of LDL nanoparticles (2 mg/kg) loaded with DHA (LDL–DHA), triolein (LDL–TO) or sham surgery controls. Tumor growth was measured by magnetic resonance imaging and other methods; tumor, liver and serum samples were collected and assessed by histochemical, immunofluorescence, biochemical and immunoblot analyses. Results Three days after administration of LDL–TO or sham surgery, the control rats had large, highly vascularized tumors that contained proliferating cells. However, rats given LDL–DHA had smaller, pale tumors that were devoid of vascular supply and greater than 80% of the tumor tissue was necrotic. Four to 6 days after injection of LDL–DHA, the tumors were 3-fold smaller than those of control rats. The liver tissue that surrounded the tumors showed no histologic or biochemical evidence of injury. Injection of LDL–DHA into the hepatic artery of rats selectively deregulated redox reactions in tumor tissues by: increasing levels of reactive oxygen species and lipid peroxidation, depleting and oxidizing glutathione and nicotinamide adenine dinucleotide phosphate, and significantly downregulating the antioxidant enzyme glutathione peroxidase-4. Remarkably, the redox balance in the surrounding liver was not disrupted

  11. Hepatic Arterial Infusion of Low-Density Lipoprotein Docosahexaenoic Acid Nanoparticles Selectively Disrupts Redox Balance in Hepatoma Cells and Reduces Growth of Orthotopic Liver Tumors in Rats.

    PubMed

    Wen, Xiaodong; Reynolds, Lacy; Mulik, Rohit S; Kim, Soo Young; Van Treuren, Tim; Nguyen, Liem H; Zhu, Hao; Corbin, Ian R

    2016-02-01

    Dietary intake of the natural omega-3 fatty acid docosahexaenoic acid (DHA) has been implicated in protecting patients with viral hepatitis B or C from developing hepatocellular carcinoma (HCC). Little is known about the effects of DHA on established solid tumors. Here we describe a low-density lipoprotein-based nanoparticle that acts as a transporter for unesterified DHA (LDL-DHA) and demonstrates selective cytotoxicity toward HCC cells. We investigated the ability of LDL-DHA to reduce growth of orthotopic hepatomas in rats. AxC-Irish (ACI) rats were given intrahepatic injections of rat hepatoma cells (H4IIE); 24 tumor-bearing rats (mean tumor diameter, ∼1 cm) were subject to a single hepatic artery injection of LDL nanoparticles (2 mg/kg) loaded with DHA (LDL-DHA), triolein (LDL-TO), or sham surgery controls. Tumor growth was measured by magnetic resonance imaging and other methods; tumor, liver, and serum samples were collected and assessed by histochemical, immunofluorescence, biochemical, and immunoblot analyses. Three days after administration of LDL-TO or sham surgery, the control rats had large, highly vascularized tumors that contained proliferating cells. However, rats given LDL-DHA had smaller, pale tumors that were devoid of vascular supply and >80% of the tumor tissue was necrotic. Four to 6 days after injection of LDL-DHA, the tumors were 3-fold smaller than those of control rats. The liver tissue that surrounded the tumors showed no histologic or biochemical evidence of injury. Injection of LDL-DHA into the hepatic artery of rats selectively deregulated redox reactions in tumor tissues by increasing levels of reactive oxygen species and lipid peroxidation, depleting and oxidizing glutathione and nicotinamide adenine dinucleotide phosphate, and significantly down-regulating the antioxidant enzyme glutathione peroxidase-4. Remarkably, the redox balance in the surrounding liver was not disrupted. LDL-DHA nanoparticle selectively kills hepatoma cells

  12. Porphysome nanoparticles for enhanced photothermal therapy in a patient-derived orthotopic pancreas xenograft cancer model: a pilot study

    NASA Astrophysics Data System (ADS)

    MacLaughlin, Christina M.; Ding, Lili; Jin, Cheng; Cao, Pingjiang; Siddiqui, Iram; Hwang, David M.; Chen, Juan; Wilson, Brian C.; Zheng, Gang; Hedley, David W.

    2016-08-01

    Local disease control is a major challenge in pancreatic cancer treatment, because surgical resection of the primary tumor is only possible in a minority of patients and radiotherapy cannot be delivered in curative doses. Despite the promise of photothermal therapy (PTT) for focal ablation of pancreatic tumors, this approach remains underinvestigated. Using photothermal sensitizers in combination with laser light irradiation for PTT can result in more efficient conversion of light energy to heat and improved spatial confinement of thermal destruction to the tumor. Porphysomes are self-assembled nanoparticles composed mainly of pyropheophorbide-conjugated phospholipids, enabling the packing of ˜80,000 porphyrin photosensitizers per particle. The high-density porphyrin loading imparts enhanced photonic properties and enables high-payload tumor delivery. A patient-derived orthotopic pancreas xenograft model was used to evaluate the feasibility of porphysome-enhanced PTT for pancreatic cancer. Biodistribution and tumor accumulation were evaluated using fluorescence intensity measurements from homogenized tissues and imaging of excised organs. Tumor surface temperature was recorded using IR optical imaging during light irradiation to monitor treatment progress. Histological analyses were conducted to determine the extent of PTT thermal damage. These studies may provide insight into the influence of heat-sink effect on thermal therapy dosimetry for well-perfused pancreatic tumors.

  13. [Longterm results of mitral valve replacement (author's transl)].

    PubMed

    Erhard, W; Reichmann, M; Delius, W; Sebening, H; Herrmann, G

    1977-04-22

    210 patients were followed up by the actuary method for over 5 years after isolated mitral valve replacement or a double valve replacement. After isolated valve replacement the one month survival including the operative mortality was 92+/-2%. The survival after one year was 83+/-3% and after 5 years 66+/-7%. The five year survival of patients in preoperative class III (according to the NYHA) was 73+/-8% and of class IV 57+/-8% (P less than or equal to 0.1). A comparison of valve replacements for pure mitral stenosis or mitral insufficiency showed no statistically significant differences. In the 37 patients who had a double valve replacement the survival risk was not increased in comparison with those patients who had had a single valve replacement. Age above 45 years and a preoperative markedly raised pulmonary arteriolar resistance reduced the chances of survival.

  14. Urban chaos and replacement dynamics in nature and society

    NASA Astrophysics Data System (ADS)

    Chen, Yanguang

    2014-11-01

    Replacements resulting from competition are ubiquitous phenomena in both nature and society. The evolution of a self-organized system is always a physical process substituting one type of components for another type of components. A logistic model of replacement dynamics has been proposed in terms of technical innovation and urbanization, but it fails to arouse widespread attention in the academia. This paper is devoted to laying the foundations of general replacement principle by using analogy and induction. The empirical base of this study is urban replacement, including urbanization and urban growth. The sigmoid functions can be employed to model various processes of replacement. Many mathematical methods such as allometric scaling and head/tail breaks can be applied to analyzing the processes and patterns of replacement. Among varied sigmoid functions, the logistic function is the basic and the simplest model of replacement dynamics. A new finding is that replacement can be associated with chaos in a nonlinear system, e.g., urban chaos is just a part of replacement dynamics. The aim of developing replacement theory is at understanding complex interaction and conversion. This theory provides a new way of looking at urbanization, technological innovation and diffusion, Volterra-Lotka’s predator-prey interaction, man-land relation, and dynastic changes resulting from peasant uprising, and all that. Especially, the periodic oscillations and chaos of replacement dynamics can be used to explain and predict the catastrophic occurrences in the physical and human systems.

  15. 25 CFR 700.187 - Utilization of replacement home benefits.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Utilization of replacement home benefits. 700.187 Section... PROCEDURES Replacement Housing Payments § 700.187 Utilization of replacement home benefits. The Commission... to the head of household as provided in these regulations for the acquisition of a replacement home...

  16. 25 CFR 700.187 - Utilization of replacement home benefits.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 2 2013-04-01 2013-04-01 false Utilization of replacement home benefits. 700.187 Section... PROCEDURES Replacement Housing Payments § 700.187 Utilization of replacement home benefits. The Commission... to the head of household as provided in these regulations for the acquisition of a replacement home...

  17. 25 CFR 700.187 - Utilization of replacement home benefits.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false Utilization of replacement home benefits. 700.187 Section... PROCEDURES Replacement Housing Payments § 700.187 Utilization of replacement home benefits. The Commission... to the head of household as provided in these regulations for the acquisition of a replacement home...

  18. 25 CFR 700.187 - Utilization of replacement home benefits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Utilization of replacement home benefits. 700.187 Section... PROCEDURES Replacement Housing Payments § 700.187 Utilization of replacement home benefits. The Commission... to the head of household as provided in these regulations for the acquisition of a replacement home...

  19. 25 CFR 700.187 - Utilization of replacement home benefits.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 2 2014-04-01 2014-04-01 false Utilization of replacement home benefits. 700.187 Section... PROCEDURES Replacement Housing Payments § 700.187 Utilization of replacement home benefits. The Commission... to the head of household as provided in these regulations for the acquisition of a replacement home...

  20. ReplacementMatrix: a web server for maximum-likelihood estimation of amino acid replacement rate matrices.

    PubMed

    Dang, Cuong Cao; Lefort, Vincent; Le, Vinh Sy; Le, Quang Si; Gascuel, Olivier

    2011-10-01

    Amino acid replacement rate matrices are an essential basis of protein studies (e.g. in phylogenetics and alignment). A number of general purpose matrices have been proposed (e.g. JTT, WAG, LG) since the seminal work of Margaret Dayhoff and co-workers. However, it has been shown that matrices specific to certain protein groups (e.g. mitochondrial) or life domains (e.g. viruses) differ significantly from general average matrices, and thus perform better when applied to the data to which they are dedicated. This Web server implements the maximum-likelihood estimation procedure that was used to estimate LG, and provides a number of tools and facilities. Users upload a set of multiple protein alignments from their domain of interest and receive the resulting matrix by email, along with statistics and comparisons with other matrices. A non-parametric bootstrap is performed optionally to assess the variability of replacement rate estimates. Maximum-likelihood trees, inferred using the estimated rate matrix, are also computed optionally for each input alignment. Finely tuned procedures and up-to-date ML software (PhyML 3.0, XRATE) are combined to perform all these heavy calculations on our clusters. http://www.atgc-montpellier.fr/ReplacementMatrix/ olivier.gascuel@lirmm.fr Supplementary data are available at http://www.atgc-montpellier.fr/ReplacementMatrix/

  1. The value of genetic information in selecting dairy replacements.

    PubMed

    Radke, Brian R; Lloyd, James W; Black, J Roy; Harsh, Stephen

    2005-09-30

    The objective of this study was to empirically determine the economic value of genetic information in the selection of dairy replacements, and assess whether this value was sufficient to prompt producers to select replacements on this basis. The data set consisted of 1982 Michigan Holstein replacements in 115 herds. Each herd had a minimum of 10 replacements that were born in the last 6 months of 1992 and calved within the last 6 months of 1994. The data for each replacement included the estimated breeding value (EBV) for milk at the beginning and end of the rearing period, and the estimated lifetime profit corrected for the opportunity cost of postponed replacement (ELPCOC). The replacement selection decision for a profit-maximizing dairy producer selecting 70 or 80% of the replacements was modeled. We modeled three methods of selection: genetic, random and ex poste. Genetic selection was evaluated using the EBV milk available at the beginning or end of the rearing period. For each herd, the profit associated with each of the three methods of selection was simulated. The value of the genetic information and perfect information were the differences in herd profits of genetic selection and ex poste selection relative to random selection, respectively. The difference in value of the genetic information between the end of the rearing period and the beginning of the rearing period was the increase in value of the genetic information due to updating. The value of information was calculated as the average herd profit per replacement. The value of the genetic information ranged from 22 dollars/replacement to 30 dollars/replacement and was statistically greater than zero at a 95% confidence level. It is unclear whether this value is sufficient to prompt producers to select replacements on the basis of EBV milk as has been recommended. The negative value of EBV milk (from the end of the rearing period when selecting 80% of the replacements) for 32 herds was consistent with

  2. Knee joint replacement

    MedlinePlus

    ... Knee joint replacement - series References American Academy of Orthopedic Surgeons (AAOS) website. Treatment of osteoarthritis of the knee: evidence-based guideline 2nd edition (summary) . www.aaos.org/research/guidelines/TreatmentofOsteoarthritisoftheKneeGuideline.pdf . Updated May 18, 2013. Accessed ...

  3. 30 CFR 823.14 - Soil replacement.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Soil replacement. 823.14 Section 823.14 Mineral... Soil replacement. (a) Soil reconstruction specifications established by the U.S. Soil Conservation Service shall be based upon the standards of the National Cooperative Soil Survey and shall include, as a...

  4. 30 CFR 823.14 - Soil replacement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Soil replacement. 823.14 Section 823.14 Mineral... Soil replacement. (a) Soil reconstruction specifications established by the U.S. Soil Conservation Service shall be based upon the standards of the National Cooperative Soil Survey and shall include, as a...

  5. 30 CFR 823.14 - Soil replacement.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Soil replacement. 823.14 Section 823.14 Mineral... Soil replacement. (a) Soil reconstruction specifications established by the U.S. Soil Conservation Service shall be based upon the standards of the National Cooperative Soil Survey and shall include, as a...

  6. 30 CFR 823.14 - Soil replacement.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Soil replacement. 823.14 Section 823.14 Mineral... Soil replacement. (a) Soil reconstruction specifications established by the U.S. Soil Conservation Service shall be based upon the standards of the National Cooperative Soil Survey and shall include, as a...

  7. 30 CFR 823.14 - Soil replacement.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Soil replacement. 823.14 Section 823.14 Mineral... Soil replacement. (a) Soil reconstruction specifications established by the U.S. Soil Conservation Service shall be based upon the standards of the National Cooperative Soil Survey and shall include, as a...

  8. Mercury Thermometer Replacements in Chemistry Laboratories

    ERIC Educational Resources Information Center

    Foster, Barbara L.

    2005-01-01

    The consequences of broken mercury-in-glass thermometers in academic laboratories results in various health and environmental hazards, which needs to be replaced, by long-stem digital thermometers and non-mercury glass thermometers. The factors that should be considered during the mercury replacement process are types of applications in the…

  9. 24 CFR 891.855 - Replacement reserves.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Partnerships and Mixed-Finance Development for Supportive Housing for the Elderly or Persons with Disabilities § 891.855 Replacement reserves. (a) The mixed-finance owner shall establish and maintain a replacement... requirements of 24 CFR 891.405. (b) The mixed-finance owner may obtain a disbursement from the reserve only if...

  10. [Vitrectomy: in search of the ideal vitreous replacement].

    PubMed

    Steijns, Daan; Stilma, Jan S

    2009-01-01

    Pars plana vitrectomy is a form of surgery to remove the vitreous body. It is performed with various eye diseases. Replacement of the vitreous body is necessitated by its removal. After more than 50 years the search for the ideal vitreous replacement has not yet ended. Different materials are used to replace the vitreous body. The advantages, disadvantages and applications of those materials are discussed. The lack of a material to successfully replace the vitreous body is a significant restriction in the treatment vitreoretinal pathologies.

  11. Cost-analysis comparison of robot-assisted laparoscopic radical cystectomy (RC) vs open RC.

    PubMed

    Lee, Richard; Chughtai, Bilal; Herman, Michael; Shariat, Shahrokh F; Scherr, Douglas S

    2011-09-01

    • To systematically review and compare the economic burden of open radical cystectomy (ORC) vs robot-assisted laparoscopic radical cystectomy (RALRC) with pelvic lymph node dissection and urinary diversion. • A Medline search was conducted to identify English language articles regarding RC with urinary diversion. The resulting articles were then further restricted by the terms 'laparoscopic', 'robotic', or 'robotic-assisted'.In all, three articles were identified. • Data from each of these articles were then collected on cost performance in addition to relevant clinical variables, such as length of stay (LOS), operative duration, and complication rates. • When possible, data were subdivided by ileal conduit (IC), continent cutaneous diversion (CCD), and orthotopic neobladder (ON) subgroups. • Direct costs resulting from ORC or RALRC with accompanying hospitalization were identified. The indirect costs of complications were considered. • Despite an increased materials cost, RALRC was less expensive than ORC when the cost of complications was considered. • RALRC was less expensive than ORC for IC and CCD, but the cost advantage deteriorated for ON. • The largest cost drivers cited in the published data were LOS, operative durations, and daily hospitalizations costs. • RALRC demonstrated shorter LOS compared with ORC, although this effect was insufficient to offset the increased cost of robotic surgery. • Complications materially affected cost performance. • Despite an increased materials cost, RALRC can be more cost efficient than ORC as a treatment for bladder cancer when the impact of complications are considered. • This effect is most pronounced for patients undergoing IC. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

  12. [Clinical study on patellar replacement in total knee arthroplasty].

    PubMed

    Bao, Liang; Gao, Zhihui; Shi, Xiaoqiang; Fang, Xiaomin; Jin, Qunhua

    2013-01-01

    To evaluate the influence of patellar replacement on total knee arthroplasty by comparing with non patellar replacement. Between September 2010 and November 2010, 63 patients (63 knees) with osteoarthritis who met the selection criteria and underwent total knee arthroplasty, were randomly divided into 2 groups: patellar replacement in 32 cases (replacement group), non patellar replacement in 31 cases (non patellar replacement group). There was no significant difference in gender, age, disease duration, osteoarthritis grading, the clinical and functional scores of American Knee Society Score (KSS), the patellar tilt angle, tibiofemoral angle, and patellar ligament ratio between 2 groups (P > 0.05), they were comparable. After 6 weeks, 3, 6, and 12 months of operation, clinical and imaging evaluation methods were used to assessment the effectiveness. Primary healing of incision was obtained in all patients of 2 groups. Deep venous thrombosis occurred in 6 cases of replacement group and in 8 cases of non patellar replacement group. All patients were followed up 12 months. The postoperative incidence of anterior knee pain in replacement group was significantly lower than that in non patellar replacement group (P < 0.05) at 3, 6, and 12 months after operation. No significant difference was found in the postoperative KSS clinical score between 2 groups at each time point (P > 0.05). The joint function score of the replacement group was significantly higher than that of the non patellar replacement group at the other time point (P < 0.05) except the score at 6 weeks and 3 months. Significant difference was found in the patella score between 2 groups at 12 months (P < 0.05), but no significant difference at the other time points (P > 0.05). X-ray film showed no patellar fracture and dislocation, or loosening and breakage of internal fixation. At 12 months after operation, the tibiofemoral angle, the patellar ligament ratio, and the patellar tilt angle showed no significant

  13. 14 CFR 21.9 - Replacement and modification articles.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Replacement and modification articles. 21.9... CERTIFICATION PROCEDURES FOR PRODUCTS AND PARTS General § 21.9 Replacement and modification articles. (a) If a person knows, or should know, that a replacement or modification article is reasonably likely to be...

  14. 14 CFR 21.9 - Replacement and modification articles.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Replacement and modification articles. 21.9... CERTIFICATION PROCEDURES FOR PRODUCTS AND PARTS General § 21.9 Replacement and modification articles. (a) If a person knows, or should know, that a replacement or modification article is reasonably likely to be...

  15. 14 CFR 21.9 - Replacement and modification articles.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Replacement and modification articles. 21.9... CERTIFICATION PROCEDURES FOR PRODUCTS AND PARTS General § 21.9 Replacement and modification articles. (a) If a person knows, or should know, that a replacement or modification article is reasonably likely to be...

  16. 14 CFR 21.9 - Replacement and modification articles.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Replacement and modification articles. 21.9... CERTIFICATION PROCEDURES FOR PRODUCTS AND PARTS General § 21.9 Replacement and modification articles. (a) If a person knows, or should know, that a replacement or modification article is reasonably likely to be...

  17. 14 CFR 21.9 - Replacement and modification articles.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Replacement and modification articles. 21.9... CERTIFICATION PROCEDURES FOR PRODUCTS AND PARTS General § 21.9 Replacement and modification articles. (a) If a person knows, or should know, that a replacement or modification article is reasonably likely to be...

  18. Managing the replacement cycle of laser inventory.

    PubMed

    Davis, C E

    1992-01-01

    Medical lasers are quickly moving into the replacement phase of technology management. Barnes Hospital (St. Louis, MO) is using its laser team to define a process of planned laser replacement using the experience gained from traditional medical equipment replacement cycles, quality improvement principles and tools, and other formalized interdisciplinary teams. The process described in this paper has six basic steps: (1) A decision is made to request a replacement laser. (2) An appropriation request form is completed and submitted with the clinical and/or technical justifications. (3) Those requests initiated outside of the Clinical Engineering Department are reviewed by the Clinical Engineer/Medical Laser Safety Officer (CE/MLSO). (4) The CE/MLSO presents the requests to the hospital Laser Committee, and (5) then to the Laser Users' Group. (6) Finally, an Expenditure Authorization Committee reviews all capital expense requests, including those for replacement lasers, and allocates funds for the next fiscal year. This paper illustrates and evaluates the process, using an example from the review process for 1993 equipment purchases at Barnes Hospital.

  19. Prioritization Methodology for Chemical Replacement

    NASA Technical Reports Server (NTRS)

    Cruit, W.; Schutzenhofer, S.; Goldberg, B.; Everhart, K.

    1993-01-01

    This project serves to define an appropriate methodology for effective prioritization of efforts required to develop replacement technologies mandated by imposed and forecast legislation. The methodology used is a semiquantitative approach derived from quality function deployment techniques (QFD Matrix). This methodology aims to weigh the full environmental, cost, safety, reliability, and programmatic implications of replacement technology development to allow appropriate identification of viable candidates and programmatic alternatives. The results are being implemented as a guideline for consideration for current NASA propulsion systems.

  20. 9 CFR 82.15 - Replacement birds and poultry.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Replacement birds and poultry. 82.15...- EASE (END) AND CHLAMYDIOSIS Exotic Newcastle Disease (END) § 82.15 Replacement birds and poultry. Birds and poultry that have been destroyed because of a quarantine for END may not be replaced by birds or...

  1. 9 CFR 82.15 - Replacement birds and poultry.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Replacement birds and poultry. 82.15...- EASE (END) AND CHLAMYDIOSIS Exotic Newcastle Disease (END) § 82.15 Replacement birds and poultry. Birds and poultry that have been destroyed because of a quarantine for END may not be replaced by birds or...

  2. Tissue responses to hexyl 5-aminolevulinate-induced photodynamic treatment in syngeneic orthotopic rat bladder cancer model: possible pathways of action

    NASA Astrophysics Data System (ADS)

    Arum, Carl-Jørgen; Gederaas, Odrun A.; Larsen, Eivind L. P.; Randeberg, Lise L.; Hjelde, Astrid; Krokan, Hans E.; Svaasand, Lars O.; Chen, Duan; Zhao, Chun-Mei

    2011-02-01

    Orthotopic bladder cancer model in rats mimics human bladder cancer with respect to urothelial tumorigenesis and progression. Utilizing this model at pT1 (superficial stage), we analyze the tissue responses to hexyl 5-aminolevulinate-induced photodynamic therapy (HAL-PDT). In comparison to untreated rats, HAL-PDT causes little change in tumor-free rat bladder but induces inflammatory changes with increased lymphocytes and mononuclear cell infiltration in rat bladders with tumor. Immunohistochemistry reveals that HAL-PDT is without effect on proliferating cell nuclear antigen expression within the tumor and increases caspase-3 expression in both normal urothelium and the tumor. Transmission electron microscopy reveals severe mitochondrial damage, formations of apoptotic bodies, vacuoles, and lipofuscin bodies, but no microvillus-formed niches in HAL-PDT-treated bladder cancer rats. Bioinformatics analysis of the gene expression profile indicates an activation of T-cell receptor signaling pathway in bladder cancer rats without PDT. HAL-PDT increases the expression of CD3 and CD45RA in the tumor (determined by immunohistochemistry). We suggest that pathways of action of HAL-PDT may include, at least, activations of mitochondrial apoptosis and autophagy, breakdown of cancer stem cell niches, and importantly, enhancement of T-cell activation.

  3. Suppressive effects of a proton beam on tumor growth and lung metastasis through the inhibition of metastatic gene expression in 4T1 orthotopic breast cancer model.

    PubMed

    Kwon, Yun-Suk; Lee, Kyu-Shik; Chun, So-Young; Jang, Tae Jung; Nam, Kyung-Soo

    2016-07-01

    A proton beam is a next generation tool to treat intractable cancer. Although the therapeutic effects of a proton beam are well known, the effect on tumor metastasis is not fully described. Here, we investigated the effects of a proton beam on metastasis in highly invasive 4T1 murine breast cancer cells and their orthotopic breast cancer model. Cells were irradiated with 2, 4, 8 or 16 Gy proton beam, and changes in cell proliferation, survival, and migration were observed by MTT, colony forming and wound healing assays. 4T1 breast cancer cell-implanted BALB/c mice were established and the animals were randomly divided into 4 groups when tumor size reached 200 mm3. Breast tumors were selectively irradiated with 10, 20 or 30 Gy proton beam. Breast tumor sizes were measured twice a week, and breast tumor and lung tissues were pathologically observed. Metastasis-regulating gene expression was assessed with quantitative RT-PCR. A proton beam dose-dependently decreased cell proliferation, survival and migration in 4T1 murine breast cancer cells. Also, growth of breast tumors in the 4T1 orthotopic breast cancer model was significantly suppressed by proton beam irradiation without significant change of body weight. Furthermore, fewer tumor nodules metastasized from breast tumor into lung in mice irradiated with 30 Gy proton beam, but not with 10 and 20 Gy, than in control. We observed correspondingly lower expression levels of urokinase plasminogen activator (uPA), uPA receptor, cyclooxygenase (COX)-2, and vascular endothelial growth factor (VEGF), which are important factors in cancer metastasis, in breast tumor irradiated with 30 Gy proton beam. Proton beam irradiation did not affect expressions of matrix metalloproteinase (MMP)-9 and MMP-2. Taken together, the data suggest that, although proton beam therapy is an effective tool for breast cancer treatment, a suitable dose is necessary to prevent metastasis-linked relapse and poor prognosis.

  4. Fleet replacement modeling : final report, July 2009.

    DOT National Transportation Integrated Search

    2009-07-01

    This project focused on two interrelated areas in equipment replacement modeling for fleets. The first area was research-oriented and addressed a fundamental assumption in engineering economic replacement modeling that all assets providing a similar ...

  5. 42 CFR 433.117 - Initial approval of replacement systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... and Information Retrieval Systems § 433.117 Initial approval of replacement systems. (a) A replacement... information retrieval system. (b) The agency must submit a APD that includes— (1) The date the replacement...

  6. 42 CFR 433.117 - Initial approval of replacement systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... and Information Retrieval Systems § 433.117 Initial approval of replacement systems. (a) A replacement... information retrieval system. (b) The agency must submit a APD that includes— (1) The date the replacement...

  7. 42 CFR 433.117 - Initial approval of replacement systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... and Information Retrieval Systems § 433.117 Initial approval of replacement systems. (a) A replacement... information retrieval system. (b) The agency must submit a APD that includes— (1) The date the replacement...

  8. 42 CFR 433.117 - Initial approval of replacement systems.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... and Information Retrieval Systems § 433.117 Initial approval of replacement systems. (a) A replacement... information retrieval system. (b) The agency must submit a APD that includes— (1) The date the replacement...

  9. Alterations in NO- and PGI2- dependent function in aorta in the orthotopic murine model of metastatic 4T1 breast cancer: relationship with pulmonary endothelial dysfunction and systemic inflammation.

    PubMed

    Buczek, E; Denslow, A; Mateuszuk, L; Proniewski, B; Wojcik, T; Sitek, B; Fedorowicz, A; Jasztal, A; Kus, E; Chmura-Skirlinska, A; Gurbiel, R; Wietrzyk, J; Chlopicki, S

    2018-05-22

    Patients with cancer develop endothelial dysfunction and subsequently display a higher risk of cardiovascular events. The aim of the present work was to examine changes in nitric oxide (NO)- and prostacyclin (PGI 2 )-dependent endothelial function in the systemic conduit artery (aorta), in relation to the formation of lung metastases and to local and systemic inflammation in a murine orthotopic model of metastatic breast cancer. BALB/c female mice were orthotopically inoculated with 4T1 breast cancer cells. Development of lung metastases, lung inflammation, changes in blood count, systemic inflammatory response (e.g. SAA, SAP and IL-6), as well as changes in NO- and PGI 2 -dependent endothelial function in the aorta, were examined 2, 4, 5 and 6 weeks following cancer cell transplantation. As early as 2 weeks following transplantation of breast cancer cells, in the early metastatic stage, lungs displayed histopathological signs of inflammation, NO production was impaired and nitrosylhemoglobin concentration in plasma was decreased. After 4 to 6 weeks, along with metastatic development, progressive leukocytosis and systemic inflammation (as seen through increased SAA, SAP, haptoglobin and IL-6 plasma concentrations) were observed. Six weeks following cancer cell inoculation, but not earlier, endothelial dysfunction in aorta was detected; this involved a decrease in basal NO production and a decrease in NO-dependent vasodilatation, that was associated with a compensatory increase in cyclooxygenase-2 (COX-2)- derived PGI 2 production. In 4 T1 metastatic breast cancer in mice early pulmonary metastasis was correlated with lung inflammation, with an early decrease in pulmonary as well as systemic NO availability. Late metastasis was associated with robust, cancer-related, systemic inflammation and impairment of NO-dependent endothelial function in the aorta that was associated with compensatory upregulation of the COX-2-derived PGI 2 pathway.

  10. Mitochondrial replacement techniques: egg donation, genealogy and eugenics.

    PubMed

    Palacios-González, César

    2016-03-01

    Several objections against the morality of researching or employing mitochondrial replacement techniques have been advanced recently. In this paper, I examine three of these objections and show that they are found wanting. First I examine whether mitochondrial replacement techniques, research and clinical practice, should not be carried out because of possible harms to egg donors. Next I assess whether mitochondrial replacement techniques should be banned because they could affect the study of genealogical ancestry. Finally, I examine the claim that mitochondrial replacement techniques are not transferring mitochondrial DNA but nuclear DNA, and that this should be prohibited on ethical grounds.

  11. Prioritization methodology for chemical replacement

    NASA Technical Reports Server (NTRS)

    Goldberg, Ben; Cruit, Wendy; Schutzenhofer, Scott

    1995-01-01

    This methodology serves to define a system for effective prioritization of efforts required to develop replacement technologies mandated by imposed and forecast legislation. The methodology used is a semi quantitative approach derived from quality function deployment techniques (QFD Matrix). QFD is a conceptual map that provides a method of transforming customer wants and needs into quantitative engineering terms. This methodology aims to weight the full environmental, cost, safety, reliability, and programmatic implications of replacement technology development to allow appropriate identification of viable candidates and programmatic alternatives.

  12. Cadmium plating replacements

    NASA Technical Reports Server (NTRS)

    Nelson, Mary J.; Groshart, Earl C.

    1995-01-01

    The Boeing Company has been searching for replacements to cadmium plate. Two alloy plating systems seem close to meeting the needs of a cadmium replacement. The two alloys, zinc-nickel and tin-zinc are from alloy plating baths; both baths are neutral pH. The alloys meet the requirements for salt fog corrosion resistance, and both alloys excel as a paint base. Currently, tests are being performed on standard fasteners to compare zinc-nickel and tin-zinc on threaded hardware where cadmium is heavily used. The Hydrogen embrittlement propensity of the zinc-nickel bath has been tested, and just beginning for the tin-zinc bath. Another area of interest is the electrical properties on aluminum for tin-zinc and will be discussed. The zinc-nickel alloy plating bath is in production in Boeing Commercial Airplane Group for non-critical low strength steels. The outlook is promising that these two coatings will help The Boeing Company significantly reduce its dependence on cadmium plating.

  13. Hormone replacement therapy and risk of malignancy.

    PubMed

    Diamanti-Kandarakis, Evanthia

    2004-02-01

    The fact that today our concern is oriented towards the risks rather than the benefits of hormone replacement therapy could be the clearest message about our current position. The safety of hormone replacement therapy, an estrogen-progestin combination which has been sympathetic to and supportive of disturbing menopausal symptoms of women, is seriously challenged. Four randomized trials have now reported on the results of hormone replacement therapy in major potentially fatal conditions, in more than 20,000 women studied for about 5 years. The main concern regarding the increased risk of malignancy in healthy postmenopausal women in western countries has been breast cancer. It is estimated to cause an extra case in about six per 1000 users aged 50-59 and 12 per 1000 aged 60-69. Over the same period the estimated risk of endometrial cancer rates are not increased, with a relative risk of 0.76 per 1000 users aged 50-59. Overall, however, the increased incidence of malignancies is greater than any reduction, one per 230 users aged 50-59 and one per 150 aged 60-69. Randomized trials examining other important but rarer malignancies, like ovarian, gall bladder and urinary bladder cancer, are either nonexistent or too small to reliably describe any effects of hormone replacement therapy. Conclusively epidemiological evidence suggests that hormone replacement therapy is associated with a small but substantial increase in breast cancer risk and combined estrogen-progesterone regimens further increase this hazard. Additionally, the evidence from the recent double blind placebo controlled randomized trial on the slight increase in the incidence of adverse cardiovascular events, has turned our orientation away from hormone replacement therapy as a long term therapy in postmenopausal women. In this review, the effort is to approach comprehensively and globally the information on the risks of hormone replacement therapy on several cancer sites.

  14. Frequency and impact of informant replacement in Alzheimer disease research.

    PubMed

    Grill, Joshua D; Zhou, Yan; Karlawish, Jason; Elashoff, David

    2015-01-01

    Informants serve an essential role in Alzheimer disease research. Were an informant to be replaced during a longitudinal study, this could have negative implications. We used data from the National Alzheimer's Coordinating Center Uniform Data Set to examine the frequency of informant replacement among Alzheimer disease dementia participants, whether patient and informant characteristics were associated with replacement, and how replacement affected research outcome measures. Informant replacement was common (15.5%) and typically occurred after the first or the second research visit. Adult child (24%) and other (38%) informants were more frequently replaced than spouse informants (10%). Older spouse informant age and younger adult child informant age were associated with replacement. The between-visit change in Functional Assessment Questionnaire scores was greater in patients who replaced informants than in those with stable informants. Clinical Dementia Rating-Sum of Boxes, Functional Assessment Questionnaire, and Neuropsychiatric Inventory scores showed greater variability in between-visit change in patients who replaced informants compared with those with stable informants. These findings suggest that informant replacement is relatively common, may have implications to study analyses, and warrant further examination in the setting of clinical trials.

  15. Fabrication method, structure, mechanical, and biological properties of decellularized extracellular matrix for replacement of wide bone tissue defects.

    PubMed

    Anisimova, N Y; Kiselevsky, M V; Sukhorukova, I V; Shvindina, N V; Shtansky, D V

    2015-09-01

    The present paper was focused on the development of a new method of decellularized extracellular matrix (DECM) fabrication via a chemical treatment of a native bone tissue. Particular attention was paid to the influence of chemical treatment on the mechanical properties of native bones, sterility, and biological performance in vivo using the syngeneic heterotopic and orthotopic implantation models. The obtained data indicated that after a chemical decellularization treatment in 4% aqueous sodium chlorite, no noticeable signs of the erosion of compact cortical bone surface or destruction of trabeculae of spongy bone in spinal channel were observed. The histological studies showed that the chemical treatment resulted in the decellularization of both bone and cartilage tissues. The DECM samples demonstrated no signs of chemical and biological degradation in vivo. Thorough structural characterization revealed that after decellularization, the mineral frame retained its integrity with the organic phase; however clotting and destruction of organic molecules and fibers were observed. FTIR studies revealed several structural changes associated with the destruction of organic molecules, although all organic components typical of intact bone were preserved. The decellularization-induced structural changes in the collagen constituent resulted changed the deformation under compression mechanism: from the major fracture by crack propagation throughout the sample to the predominantly brittle fracture. Although the mechanical properties of radius bones subjected to decellularization were observed to degrade, the mechanical properties of ulna bones in compression and humerus bones in bending remained unchanged. The compressive strength of both the intact and decellularized ulna bones was 125-130 MPa and the flexural strength of humerus bones was 156 and 145 MPa for the intact and decellularized samples, respectively. These results open new avenues for the use of DECM samples as

  16. Knee joint transplantation combined with surgical angiogenesis in rabbits – a new experimental model

    PubMed Central

    Kremer, Thomas; Giusti, Guilherme; Friedrich, Patricia F.; Willems, Wouter; Bishop, Allen T.; Giessler, Goetz A.

    2012-01-01

    Summary Purpose We have previously described a means to maintain bone allotransplant viability, without long-term immune modulation, replacing allogenic bone vasculature with autogenous vessels. A rabbit model for whole knee joint transplantation was developed and tested using the same methodology, initially as an autotransplant. Materials/Methods Eight New Zealand White rabbit knee joints were elevated on a popliteal vessel pedicle to evaluate limb viability in a non-survival study. Ten additional joints were elevated and replaced orthotopically in a fashion identical to allotransplantation, obviating only microsurgical repairs and immunosuppression. A superficial inferior epigastric facial (SIEF) flap and a saphenous arteriovenous (AV) bundle were introduced into the femur and tibia respectively, generating a neoangiogenic bone circulation. In allogenic transplantation, this step maintains viability after cessation of immunosuppression. Sixteen weeks later, x-rays, microangiography, histology, histomorphometry and biomechanical analysis were performed. Results Limb viability was preserved in the initial 8 animals. Both soft tissue and bone healing occurred in 10 orthotopic transplants. Surgical angiogenesis from the SIEF flap and AV bundle was always present. Bone and joint viability was maintained, with demonstrable new bone formation. Bone strength was less than the opposite side. Arthrosis and joint contractures were frequent. Conclusion We have developed a rabbit knee joint model and evaluation methods suitable for subsequent studies of whole joint allotransplantation. PMID:22113889

  17. Replacement solvents for use in chemical synthesis

    DOEpatents

    Molnar, Linda K.; Hatton, T. Alan; Buchwald, Stephen L.

    2001-05-15

    Replacement solvents for use in chemical synthesis include polymer-immobilized solvents having a flexible polymer backbone and a plurality of pendant groups attached onto the polymer backbone, the pendant groups comprising a flexible linking unit bound to the polymer backbone and to a terminal solvating moiety. The polymer-immobilized solvent may be dissolved in a benign medium. Replacement solvents for chemical reactions for which tetrahydrofuran or diethyl may be a solvent include substituted tetrahydrofurfuryl ethers and substituted tetrahydro-3-furan ethers. The replacement solvents may be readily recovered from the reaction train using conventional methods.

  18. Intraductal delivery of adenoviruses targets pancreatic tumors in transgenic Ela-myc mice and orthotopic xenografts.

    PubMed

    José, Anabel; Sobrevals, Luciano; Miguel Camacho-Sánchez, Juan; Huch, Meritxell; Andreu, Núria; Ayuso, Eduard; Navarro, Pilar; Alemany, Ramon; Fillat, Cristina

    2013-01-01

    Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p less than 0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors.

  19. Characterization of the murine orthotopic adamantinomatous craniopharyngioma PDX model by MRI in correlation with histology.

    PubMed

    Hölsken, Annett; Schwarz, Marc; Gillmann, Clarissa; Pfister, Christina; Uder, Michael; Doerfler, Arnd; Buchfelder, Michael; Schlaffer, Sven; Fahlbusch, Rudolf; Buslei, Rolf; Bäuerle, Tobias

    2018-01-01

    Adamantinomatous craniopharyngiomas (ACP) as benign sellar brain tumors are challenging to treat. In order to develop robust in vivo drug testing methodology, the murine orthotopic craniopharyngioma model (PDX) was characterized by magnetic resonance imaging (MRI) and histology in xenografts from three patients (ACP1-3). In ACP PDX, multiparametric MRI was conducted to assess morphologic characteristics such as contrast-enhancing tumor volume (CETV) as well as functional parameters from dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) including area-under-the-curve (AUC), peak enhancement (PE), time-to-peak (TTP) and apparent diffusion coefficient (ADC). These MRI parameters evaluated in 27 ACP PDX were correlated to histological features and percentage of vital tumor cell content. Qualitative analysis of MRI and histology from PDX revealed a similar phenotype as seen in patients, although the MRI appearance in mice resulted in a more solid tumor growth than in humans. CETV were significantly higher in ACP2 xenografts relative to ACP1 and ACP3 which correspond to respective average vitality of 41%, <10% and 26% determined histologically. Importantly, CETV prove tumor growth of ACP2 PDX as it significantly increases in longitudinal follow-up of 110 days. Furthermore, xenografts from ACP2 revealed a significantly higher AUC, PE and TTP in comparison to ACP3, and significantly increased ADC relative to ACP1 and ACP3 respectively. Overall, DCE-MRI and DWI can be used to distinguish vital from non-vital grafts, when using a cut off value of 15% for vital tumor cell content. MRI enables the assessment of craniopharyngioma PDX vitality in vivo as validated histologically.

  20. Bottom ash as aggregate replacement in concrete.

    DOT National Transportation Integrated Search

    2013-06-01

    The objective of the proposed study is to evaluate bottom ash as a partial or total replacement of the fine and coarse aggregate in : concrete. This program will characterize and evaluate available bottom ash sources as potential replacement of both ...

  1. Total ankle replacement systems available in the United States.

    PubMed

    Coetzee, J Chris; Deorio, James K

    2010-01-01

    Ankle replacement continues to be a viable option for treating patients with ankle arthritis. Over the past 10 years, there has been a significant increase in the number of ankle replacement systems available for use. Current controversy centers on whether fixed- or mobile-bearing devices are most advantageous. Most total ankle systems used outside the United States are mobile-bearing devices, whereas ankle replacement systems used in the United States are all essentially fixed-bearing devices. Not all ankles with degenerative changes are amenable to replacement surgery, and several exclusion criteria are well documented. Ankle replacement is especially complicated because of the ankle's proximity to the foot and the important role that the balance and alignment of the foot play in the success of the ankle replacement. Foot deformities should be treated before or at the time of ankle replacement surgery. Ignoring foot deformities can lead to failure of the ankle replacement. It is also of paramount importance to consider the stability of the ankle ligaments. An unstable ankle with a varus or valgus deformity of more than 20 degrees is probably not amenable to ankle replacement. There are currently no reliable options to predictably reconstruct the lateral or medial ligaments in these severe deformities. It is important to be aware of the ankle replacement systems currently available in the United States and understand the key features of each design. Devices approved by the US Food and Drug Administration, a device that is awaiting approval, and a device that is being evaluated by the Food and Drug Administration in a prospective randomized clinical trial are discussed, along with an objective comparison of fixed- and mobile-bearing devices.

  2. Detection of Phosphatidylcholine-Coated Gold Nanoparticles in Orthotopic Pancreatic Adenocarcinoma using Hyperspectral Imaging

    PubMed Central

    England, Christopher G.; Huang, Justin S.; James, Kurtis T.; Zhang, Guandong; Gobin, André M.; Frieboes, Hermann B.

    2015-01-01

    Nanoparticle uptake and distribution to solid tumors are limited by reticuloendothelial system systemic filtering and transport limitations induced by irregular intra-tumoral vascularization. Although vascular enhanced permeability and retention can aid targeting, high interstitial fluid pressure and dense extracellular matrix may hinder local penetration. Extravascular diffusivity depends upon nanoparticle size, surface modifications, and tissue vascularization. Gold nanoparticles functionalized with biologically-compatible layers may achieve improved uptake and distribution while enabling cytotoxicity through synergistic combination of chemotherapy and thermal ablation. Evaluation of nanoparticle uptake in vivo remains difficult, as detection methods are limited. We employ hyperspectral imaging of histology sections to analyze uptake and distribution of phosphatidylcholine-coated citrate gold nanoparticles (CGN) and silica-gold nanoshells (SGN) after tail-vein injection in mice bearing orthotopic pancreatic adenocarcinoma. For CGN, the liver and tumor showed 26.5±8.2 and 23.3±4.1 particles/100μm2 within 10μm from the nearest source and few nanoparticles beyond 50μm, respectively. The spleen had 35.5±9.3 particles/100μm2 within 10μm with penetration also limited to 50μm. For SGN, the liver showed 31.1±4.1 particles/100μm2 within 10μm of the nearest source with penetration hindered beyond 30μm. The spleen and tumor showed uptake of 22.1±6.2 and 15.8±6.1 particles/100μm2 within 10μm, respectively, with penetration similarly hindered. CGH average concentration (nanoparticles/μm2) was 1.09±0.14 in the liver, 0.74±0.12 in the spleen, and 0.43±0.07 in the tumor. SGN average concentration (nanoparticles/μm2) was 0.43±0.07 in the liver, 0.30±0.06 in the spleen, and 0.20±0.04 in the tumor. Hyperspectral imaging of histology sections enables analysis of phosphatidylcholine-coated gold-based nanoparticles in pancreatic tumors with the goal to improve

  3. HST Replacement Battery Initial Performance

    NASA Technical Reports Server (NTRS)

    Krol, Stan; Waldo, Greg; Hollandsworth, Roger

    2009-01-01

    The Hubble Space Telescope (HST) original Nickel-Hydrogen (NiH2) batteries were replaced during the Servicing Mission 4 (SM4) after 19 years and one month on orbit.The purpose of this presentation is to highlight the findings from the assessment of the initial sm4 replacement battery performance. The batteries are described, the 0 C capacity is reviewed, descriptions, charts and tables reviewing the State Of Charge (SOC) Performance, the Battery Voltage Performance, the battery impedance, the minimum voltage performance, the thermal performance, the battery current, and the battery system recharge ratio,

  4. In vitro culture and characterization of human lung cancer circulating tumor cells isolated by size exclusion from an orthotopic nude-mouse model expressing fluorescent protein.

    PubMed

    Kolostova, Katarina; Zhang, Yong; Hoffman, Robert M; Bobek, Vladimir

    2014-09-01

    In the present study, we demonstrate an animal model and recently introduced size-based exclusion method for circulating tumor cells (CTCs) isolation. The methodology enables subsequent in vitro CTC-culture and characterization. Human lung cancer cell line H460, expressing red fluorescent protein (H460-RFP), was orthotopically implanted in nude mice. CTCs were isolated by a size-based filtration method and successfully cultured in vitro on the separating membrane (MetaCell®), analyzed by means of time-lapse imaging. The cultured CTCs were heterogeneous in size and morphology even though they originated from a single tumor. The outer CTC-membranes were blebbing in general. Abnormal mitosis resulting in three daughter cells was frequently observed. The expression of RFP ensured that the CTCs originated from lung tumor. These readily isolatable, identifiable and cultivable CTCs can be used to characterize individual patient cancers and for screening of more effective treatment.

  5. Precast concrete replacement slabs for bridge decks.

    DOT National Transportation Integrated Search

    1982-01-01

    The report illustrates and evaluates the first use in Virginia of precast concrete replacement slabs for bridge decks. It shows that a bridge deck can be replaced with the precast slabs while traffic is maintained in the adjacent traffic lane. The qu...

  6. Orthotopic ileal bladder substitution in women: factors influencing urinary incontinence and hypercontinence.

    PubMed

    Gross, Tobias; Meierhans Ruf, Susan D; Meissner, Claudia; Ochsner, Katharina; Studer, Urs E

    2015-10-01

    Urinary incontinence or the inability to void spontaneously after ileal orthotopic bladder substitution is a frequent finding in female patients. To evaluate how hysterectomy and nerve sparing affect functional outcomes and whether these relate to pre- and postoperative urethral pressure profile (UPP) results. Prospectively performed pre- and postoperative UPPs of 73 female patients who had undergone cystectomy and bladder substitution were correlated with postoperative voiding and continence status. Outcome analyses were performed with the Kruskal-Wallis test, Wilcoxon-Mann-Whitney, or two-group post hoc testing with the Bonferroni correction. Chi-square or Fisher exact tests were applied for the categorical data. Of postoperatively continent or hypercontinent patients, 22 of 43 (51.2%) had the uterus preserved; of incontinent patients, only 4 of 30 (13.3%, p<0.01) had the uterus preserved. Of postoperatively continent or hypercontinent patients, 27 of 43 patients (62.8%) had bilateral and 15 of 43 (34.9%) had unilateral attempted nerve sparing. In incontinent patients, 11 of 30 (36.7%) had bilateral and 16 of 30 (53.3%) had unilateral attempted nerve sparing (p=0.02). When compared with postoperatively incontinent patients, postoperatively continent patients had a longer functional urethral length (median: 32mm vs 24mm; p<0.001), a higher postoperative urethral closing pressure at rest (56cm H2O vs 35cm H2O; p<0.001) as well as a higher preoperative urethral closing pressure at rest (74cm H2O vs 47.5cm H2O; p=0.01). The main limitation was the limited number of patients. In female patients undergoing radical cystectomy and bladder substitution, preservation of the uterus and attempted nerve sparing results in better functional outcomes. The preoperative UPPs correlate with postoperative voiding and continence status and may predict which patients are at a higher risk of functional failure after bladder substitution. If preservation of the urethra's innervation is

  7. MicroRNA-Regulated Non-Viral Vectors with Improved Tumor Specificity in an Orthotopic Rat Model of Hepatocellular Carcinoma

    PubMed Central

    Ronald, John A.; Katzenberg, Regina; Nielsen, Carsten H.; Jae, Hwan Jun; Hofmann, Lawrence V.; Gambhir, Sanjiv S.

    2013-01-01

    In hepatocellular carcinoma, tumor specificity of gene therapy is of utmost importance to preserve liver function. MicroRNAs are powerful negative regulators of gene expression and many are down-regulated in human HCC. We identified seven miRNAs that are also down-regulated in tumors in a rat hepatoma model (p<0.05) and attempted to improve tumor specificity by constructing a panel of luciferase-expressing vectors containing binding sites for these microRNAs. Attenuation of luciferase expression by the corresponding microRNAs was confirmed across various cell lines and in mouse liver. We then tested our vectors in tumor-bearing rats and identified two microRNAs, miR-26a and miR-122, that significantly decreased expression in liver compared to control vector (6.40% and 0.26%, respectively; p<0.05). In tumor, miR-122 had a non-significant trend towards decreased (~50%) expression , while miR-26 had no significant effect on tumor expression. To our knowledge this is the first work using differentially expressed microRNAs to de-target transgene expression in an orthotopic hepatoma model and identification of miR-26a in addition to miR-122 for de-targeting liver. Considering the heterogeneity of microRNA expression in human HCC, this information will be important in guiding development of more personalized vectors for the treatment of this devastating disease. PMID:23719066

  8. Implementation of a timed, electronic, assessment-driven potassium-replacement protocol.

    PubMed

    Zielenski, Christopher; Crabtree, Adam; Le, Tien; Marlatt, Alyse; Ng, Dana; Tran, Alan

    2017-06-15

    The adherence to and effectiveness and safety of a timed, electronic, assessment-driven potassium-replacement protocol (TARP) were compared with an electronic nurse-driven replacement protocol (NRP) are reported. A retrospective observational study was conducted in a community hospital evaluating protocol adherence, effectiveness, and safety for 2 potassium-replacement protocols. All adults on medical units with an order for potassium replacement per protocol during the 3-month trial periods were reviewed. All patients requiring potassium replacement per protocol were included in the analysis. Adherence to the protocol was assessed by evaluating the dose of potassium administered and performance of reassessments. Effectiveness of the protocol was assessed by evaluating the time to achieve target potassium levels. Safety was assessed by evaluating the route of administration and occurrence of hyperkalemia. A total of 300 patients treated using potassium-replacement protocols required potassium replacement during the study period, with 148 patients in the NRP group requiring 491 instances of potassium replacement. In the TARP group a total of 564 instances requiring potassium replacement corresponded to 152 patients. Of the 491 instances requiring replacement in the NRP group, the correct dose was administered and reassessment performed 117 times (23.8%). Overall adherence ( p < 0.05), correct dose given ( p < 0.05), average time from blood draw to potassium replacement ( p < 0.0001), use of oral replacement ( p < 0.05), and time to achieve target potassium level within 12 hours ( p < 0.05) were significantly improved in the TARP group. The TARP improved the effectiveness and safety of potassium-replacement therapy over the traditional NRP without negatively affecting timeliness of care. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  9. Differences in the stress distribution in the distal femur between patellofemoral joint replacement and total knee replacement: a finite element study

    PubMed Central

    2012-01-01

    Background Patellofemoral joint replacement is a successful treatment option for isolated patellofemoral osteoarthritis. However, results of later conversion to total knee replacement may be compromised by periprosthetic bone loss. Previous clinical studies have demonstrated a decrease in distal femoral bone mineral density after patellofemoral joint replacement. It is unclear whether this is due to periprosthetic stress shielding. The main objective of the current study was to evaluate the stress shielding effect of prosthetic replacement with 2 different patellofemoral prosthetic designs and with a total knee prosthesis. Methods We developed a finite element model of an intact patellofemoral joint, and finite element models of patellofemoral joint replacement with a Journey PFJ prosthesis, a Richards II prosthesis, and a Genesis II total knee prosthesis. For each of these 4 finite element models, the average Von Mises stress in 2 clinically relevant regions of interest were evaluated during a simulated squatting movement until 120 degrees of flexion. Results During deep knee flexion, in the anterior region of interest, the average Von Mises stress with the Journey PFJ design was comparable to the physiological knee, while reduced by almost 25% for both the Richards II design and the Genesis II total knee joint replacement design. The average Von Mises stress in the supracondylar region of interest was similar for both patellofemoral prosthetic designs and the physiological model, with slightly lower stress for the Genesis II design. Conclusions Patellofemoral joint replacement results in periprosthetic stress-shielding, although to a smaller degree than in total knee replacement. Specific patellofemoral prosthetic design properties may result in differences in femoral stress shielding. PMID:22704638

  10. Recombinant methioninase effectively targets a Ewing's sarcoma in a patient-derived orthotopic xenograft (PDOX) nude-mouse model

    PubMed Central

    Murakami, Takashi; Li, Shukuan; Han, Qinghong; Tan, Yuying; Kiyuna, Tasuku; Igarashi, Kentaro; Kawaguchi, Kei; Hwang, Ho Kyoung; Miyake, Kentaro; Singh, Arun S.; Nelson, Scott D.; Dry, Sarah M.; Li, Yunfeng; Hiroshima, Yukihiko; Lwin, Thinzar M.; DeLong, Jonathan C.; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Eilber, Fritz C.; Hoffman, Robert M.

    2017-01-01

    Methionine dependence is due to the overuse of methionine for aberrant transmethylation reactions in cancer. Methionine dependence may be the only general metabolic defect in cancer. In order to exploit methionine dependence for therapy, our laboratory previously cloned L-methionine α-deamino-γ-mercaptomethane lyase [EC 4.4.1.11]). The cloned methioninase, termed recombinant methioninase, or rMETase, has been tested in mouse models of human cancer cell lines. Ewing's sarcoma is recalcitrant disease even though development of multimodal therapy has improved patients'outcome. Here we report efficacy of rMETase against Ewing's sarcoma in a patient-derived orthotopic xenograft (PDOX) model. The Ewing's sarcoma was implanted in the right chest wall of nude mice to establish a PDOX model. Eight Ewing's sarcoma PDOX mice were randomized into untreated control group (n = 4) and rMETase treatment group (n = 4). rMETase (100 units) was injected intraperitoneally (i.p.) every 24 hours for 14 consecutive days. All mice were sacrificed on day-15, 24 hours after the last rMETase administration. rMETase effectively reduced tumor growth compared to untreated control. The methionine level both of plasma and supernatants derived from sonicated tumors was lower in the rMETase group. Body weight did not significantly differ at any time points between the 2 groups. The present study is the first demonstrating rMETase efficacy in a PDOX model, suggesting potential clinical development, especially in recalcitrant cancers such as Ewing's sarcoma. PMID:28404944

  11. Recombinant methioninase effectively targets a Ewing's sarcoma in a patient-derived orthotopic xenograft (PDOX) nude-mouse model.

    PubMed

    Murakami, Takashi; Li, Shukuan; Han, Qinghong; Tan, Yuying; Kiyuna, Tasuku; Igarashi, Kentaro; Kawaguchi, Kei; Hwang, Ho Kyoung; Miyake, Kentaro; Singh, Arun S; Nelson, Scott D; Dry, Sarah M; Li, Yunfeng; Hiroshima, Yukihiko; Lwin, Thinzar M; DeLong, Jonathan C; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Eilber, Fritz C; Hoffman, Robert M

    2017-05-30

    Methionine dependence is due to the overuse of methionine for aberrant transmethylation reactions in cancer. Methionine dependence may be the only general metabolic defect in cancer. In order to exploit methionine dependence for therapy, our laboratory previously cloned L-methionine α-deamino-γ-mercaptomethane lyase [EC 4.4.1.11]). The cloned methioninase, termed recombinant methioninase, or rMETase, has been tested in mouse models of human cancer cell lines. Ewing's sarcoma is recalcitrant disease even though development of multimodal therapy has improved patients'outcome. Here we report efficacy of rMETase against Ewing's sarcoma in a patient-derived orthotopic xenograft (PDOX) model. The Ewing's sarcoma was implanted in the right chest wall of nude mice to establish a PDOX model. Eight Ewing's sarcoma PDOX mice were randomized into untreated control group (n = 4) and rMETase treatment group (n = 4). rMETase (100 units) was injected intraperitoneally (i.p.) every 24 hours for 14 consecutive days. All mice were sacrificed on day-15, 24 hours after the last rMETase administration. rMETase effectively reduced tumor growth compared to untreated control. The methionine level both of plasma and supernatants derived from sonicated tumors was lower in the rMETase group. Body weight did not significantly differ at any time points between the 2 groups. The present study is the first demonstrating rMETase efficacy in a PDOX model, suggesting potential clinical development, especially in recalcitrant cancers such as Ewing's sarcoma.

  12. Involvement of endothelin and ET(A) endothelin receptor in mechanical allodynia in mice given orthotopic melanoma inoculation.

    PubMed

    Fujita, Masahide; Andoh, Tsugunobu; Saiki, Ikuo; Kuraishi, Yasushi

    2008-02-01

    We investigated whether endothelin (ET) would be involved in skin cancer pain in mice. Orthotopic inoculation of B16-BL6 melanoma cells into the plantar region of the hind paw produced marked mechanical allodynia in C57BL/6 mice. Intraplantar injections of the ET(A)-receptor antagonist BQ-123 (0.3 - 3 nmol/site), but not the ET(B)-receptor antagonist BQ-788 (1 and 3 nmol/site), inhibited mechanical allodynia in mice with grown melanoma. In naive mice, an intraplantar injection of tumor extract (1 and 3 mg/site), which was prepared from the grown melanoma in the paw, produced mechanical allodynia, which was inhibited by BQ-123 and BQ-788 at doses of 3 and 10 nmol/site. An intraplantar injection of ET-1 (1 and 10 pmol/site) elicited licking behavior, which was increased in the melanoma-bearing hind paw. BQ-123 (3 and 10 nmol/site) inhibited licking induced by ET-1 (10 pmol/site). The level of mRNA of ET(A), but not ET(B), receptor, was significantly increased in the dorsal root ganglia on the inoculated side. Cultured B16-BL6 cells contained ET, and the melanoma mass increased the concentration of ET as it grew bigger. These results suggest that ET-1 and ET(A) receptor are at least partly involved in the induction of pain induced by melanoma cell inoculation.

  13. Epsilon-aminocaproic acid improves postrecirculation hemodynamics by reducing intraliver activated protein C consumption in orthotopic liver transplantation.

    PubMed

    Kong, H Y; Wen, X H; Huang, S Q; Zhu, S M

    2014-01-01

    Activated protein C (APC) is related to regulating the inflammatory response and hemodynamic stability upon reperfusion in cardiac operations and orthotopic liver transplantation (OLT). Epsilon-aminocaproic acid (EACA) is frequently used to treat fibrinolysis during OLT. It also has inhibitory effects related to the inflammatory response. However, it remains to be determined whether EACA can attenuate intraliver APC consumption and improve hemodynamic stability after reperfusion during OLT. Fifty-nine recipients were randomized to receive either EACA (150 mg kg(-1) given intravenously prior to incision, followed by 15 mg kg(-1) h(-1) infusion until 2 h after the graft reperfusion) or the same volume of saline. Blood samples to assess plasma APC and protein C were obtained immediately before and after reperfusion from the inferior caval effluent or the portal veins for calculation of transliver differences (Δ). Hemodynamics and vasoactive medication use during the reperfusion period were observed in both groups. No transhepatic changes in protein C were found in either group. Immediately after reperfusion, a marked intraliver consumption of APC was noted in all recipients (P < 0.001), and intraliver consumption of APC in the control group was greater than that in the EACA-treated group (P < 0.05). Fewer requirements for vasoactive medication use after reperfusion and better initial graft function were noted in the EACA-treated group (P < 0.05). EACA can attenuate intraliver APC consumption and improve hemodynamic stability after reperfusion and initial graft function during OLT.

  14. Management of end stage liver disease (ESLD): what is the current role of orthotopic liver transplantation (OLT)?

    PubMed

    Miró, José M; Laguno, Montserrat; Moreno, Asuncion; Rimola, Antonio

    2006-01-01

    Liver disease due to chronic hepatitis B and C is now a leading cause of morbidity and mortality among HIV-infected patients in the developed world, where classical opportunistic complications of severe immunodeficiency have declined dramatically. Orthotopic liver transplantation (OLT) is the only therapeutic option for patients with end-stage liver disease (ESLD). Accumulated experience in North America and Europe in the last 5 years indicates that 3-year survival in selected HIV-infected recipients of liver transplants was similar to that of HIV-negative recipients. So, HIV infection by itself is not therefore a contraindication for liver transplantation. As survival of HIV-infected patients with ESLD is shorter than non-HIV-infected population, the evaluation for OLT should be made after the first liver decompensation. The current selection criteria for HIV-positive transplant candidates include: no history of opportunistic infections or HIV-related neoplasms, CD4 cell count > 100 cells/mm(3), and plasma HIV viral load suppressible with antiretroviral treatment. For drug abusers, a 2-year abstinence from heroin and cocaine is required, although patients can be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretrovirals and immunosuppressive drugs, and the management of relapse of HCV infection. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. Currently, HCV re-infection is the main cause for concern.

  15. Toxoplasmosis in the non-orthotopic heart transplant recipient population, how common is it? Any indication for prophylaxis?

    PubMed

    Dhakal, Reshika; Gajurel, Kiran; Montoya, Jose G

    2018-06-06

    Unlike in orthotopic heart transplant (OHT) setting where toxoplasma prophylaxis is a standard practice in pretransplant toxoplasma seronegative recipients who have received donor hearts from seropositive donors (D+/R-), there is no consensus regarding prophylaxis in non-OHT recipients. The incidence of toxoplasma disease in non-OHT recipients is less than 1% but its true burden is underestimated. Among 31 cases of toxoplasma disease reported from 2004 through 2017, renal and liver transplant recipients comprised of 90% of cases. A total of 94% of 18 recipients with known pretransplant serology were seronegative recipients (mostly D+/R-). Out of 16 recipients with adequate information, 10 (63%) and five (31%) were deemed to be donor derived and nondonor-derived primary toxoplasmosis respectively. Tissue invasive reactivation was uncommon. Almost all cases were described in patients not on prophylaxis at the time of presentation. Universal screening of donor/recipient toxoplasma serology for risk stratification is beneficial as illustrated by reports of fatal cases of toxoplasmosis due to unavailability of positive donor serology results. Toxoplasma disease in non-OHT predominantly occurs in pretransplant seronegative recipients- mostly in D+/R- group and is rare in seropositive recipients. Posttransplant prophylaxis should be targeted against the high-risk D+/R- group and should be considered in seropositive recipients in whom unusually high immunosuppression is implemented. Toxoplasma serologies and PCR should be used in combination for the diagnosis of toxoplasmosis in non-OHT patients.

  16. Applying stand replacement prescribed fires in Alaska

    Treesearch

    Larry A. Vanderlinden

    1996-01-01

    Stand replacement prescribed burning has been applied in Alaska on several occasions. Based on that experience, perspectives can be provided, issues can be discussed, and keys to success can be identified that are applicable to stand replacement prescribed burning activities in areas outside Alaska.

  17. Adjacent level effects of bi level disc replacement, bi level fusion and disc replacement plus fusion in cervical spine--a finite element based study.

    PubMed

    Faizan, Ahmad; Goel, Vijay K; Biyani, Ashok; Garfin, Steven R; Bono, Christopher M

    2012-03-01

    Studies delineating the adjacent level effect of single level disc replacement systems have been reported in literature. The aim of this study was to compare the adjacent level biomechanics of bi-level disc replacement, bi-level fusion and a construct having adjoining level disc replacement and fusion system. In total, biomechanics of four models- intact, bi level disc replacement, bi level fusion and fusion plus disc replacement at adjoining levels- was studied to gain insight into the effects of various instrumentation systems on cranial and caudal adjacent levels using finite element analysis (73.6N+varying moment). The bi-level fusion models are more than twice as stiff as compared to the intact model during flexion-extension, lateral bending and axial rotation. Bi-level disc replacement model required moments lower than intact model (1.5Nm). Fusion plus disc replacement model required moment 10-25% more than intact model, except in extension. Adjacent level motions, facet loads and endplate stresses increased substantially in the bi-level fusion model. On the other hand, adjacent level motions, facet loads and endplate stresses were similar to intact for the bi-level disc replacement model. For the fusion plus disc replacement model, adjacent level motions, facet loads and endplate stresses were closer to intact model rather than the bi-level fusion model, except in extension. Based on our finite element analysis, fusion plus disc replacement procedure has less severe biomechanical effects on adjacent levels when compared to bi-level fusion procedure. Bi-level disc replacement procedure did not have any adverse mechanical effects on adjacent levels. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Kinetic studies of halon replacements.

    NASA Astrophysics Data System (ADS)

    Orkin, Vladimir L.

    2013-04-01

    Despite their excellence as fire suppressants, the production of halons (bromofluorocarbons) is being phased out because of the danger they pose to the Earth's stratospheric ozone layer. A number of bromine free substances have been proposed and tested, but the effort to find replacements continues to return to bromine-containing compounds because of the properties of bromine as a chemically active flame suppressant. The primary approach to this problem has been to test candidate replacement compounds that have short atmospheric lifetimes or/and lack bromine, the halogen atoms that catalyze ozone destruction. Various chemical classes (alkanes, ethers, alkenes) have been studied both earlier and recently. The reaction with atmospheric hydroxyl radicals dictates the residence time and accumulation in the atmosphere of all potential halon replacements. Therefore, we improved a flash photolysis - resonance fluorescence apparatus to provide the most accurate OH reaction rate constants measured over the atmospheric temperatures. Supplementary UV absorption spectra were measured to allow the estimation of ODPs. Although a thorough 3-D modeling is required to assess ODPs, the simplified estimations can be made based on the compounds lifetimes.

  19. [Local infiltration analgesia in total joint replacement].

    PubMed

    de Jonge, Tamás; Görgényi, Szabolcs; Szabó, Gabriella; Torkos, Miklós Bulcsú

    2017-03-01

    Total hip and knee replacment surgeries are characterized by severe postoperative pain. Local infiltration analgesia is proved to be very effective. However this method has not been widely used in Hungary. To evaluate the efficacy of the local infiltration analgesia with modified components in patients underwent total hip or knee replacement surgery. Data of 99 consecutive patients underwent primary total hip or knee replacement surgery were evaluated prospectively. In all the 99 surgeries modified local infiltration analgesia was applied. Postoperative pain reported on a visual analog scale was recorded as well as the need for further analgetics during the first 18 hours after surgery. The cost of the analgetic drugs was calculated. The control group comprised 97 consecutive patients underwent total hip or knee replacement, where local infiltration analgesia was not applied. Statistical analysis was done. Patients received local infiltration analgesia reported significantly less pain (p<0.001). The need for postoperatively given analgetics was almost 50% less, and the cost of all postoperative analgetics was 47% less than in the control group. In total hip and knee replacement surgeries the modified local infiltration analgesia decreases postoperative pain effectively and contribute to the early mobilization of the patients. Orv. Hetil., 2017, 158(9), 352-357.

  20. 21 CFR 870.3710 - Pacemaker repair or replacement material.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Pacemaker repair or replacement material. 870.3710... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3710 Pacemaker repair or replacement material. (a) Identification. A pacemaker repair or replacement material is an...

  1. 21 CFR 870.3710 - Pacemaker repair or replacement material.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Pacemaker repair or replacement material. 870.3710... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3710 Pacemaker repair or replacement material. (a) Identification. A pacemaker repair or replacement material is an...

  2. 21 CFR 870.3710 - Pacemaker repair or replacement material.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Pacemaker repair or replacement material. 870.3710... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3710 Pacemaker repair or replacement material. (a) Identification. A pacemaker repair or replacement material is an...

  3. 21 CFR 870.3710 - Pacemaker repair or replacement material.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Pacemaker repair or replacement material. 870.3710... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3710 Pacemaker repair or replacement material. (a) Identification. A pacemaker repair or replacement material is an...

  4. 38 CFR 21.220 - Replacement of supplies.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Vocational Rehabilitation and Employment Under 38 U.S.C... will replace articles which are necessary to further pursuit of the veteran's program and which are... advancement from the Vocational Rehabilitation Revolving Fund to a veteran to replace articles for which VA...

  5. 30 CFR 872.29 - What are prior balance replacement funds?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false What are prior balance replacement funds? 872... § 872.29 What are prior balance replacement funds? “Prior balance replacement funds” are moneys we must... SMCRA, we distribute prior balance replacement funds to you, the State or Indian tribe, for seven years...

  6. 30 CFR 872.29 - What are prior balance replacement funds?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false What are prior balance replacement funds? 872... § 872.29 What are prior balance replacement funds? “Prior balance replacement funds” are moneys we must... SMCRA, we distribute prior balance replacement funds to you, the State or Indian tribe, for seven years...

  7. Hip joint replacement - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100006.htm Hip joint replacement - series—Normal anatomy To use the ... to slide 5 out of 5 Overview The hip joint is made up of two major parts: ...

  8. Valve Repair or Replacement

    MedlinePlus

    ... called anticoagulants) for the rest of their lives. Biological valves are made from animal tissue (called a ... for valve replacement (called an autograft). Patients with biological valves usually do not need to take blood- ...

  9. ARRANGEMENT FOR REPLACING FILTERS

    DOEpatents

    Blomgren, R.A.; Bohlin, N.J.C.

    1957-08-27

    An improved filtered air exhaust system which may be continually operated during the replacement of the filters without the escape of unfiltered air is described. This is accomplished by hermetically sealing the box like filter containers in a rectangular tunnel with neoprene covered sponge rubber sealing rings coated with a silicone impregnated pneumatic grease. The tunnel through which the filters are pushed is normal to the exhaust air duct. A number of unused filters are in line behind the filters in use, and are moved by a hydraulic ram so that a fresh filter is positioned in the air duct. The used filter is pushed into a waiting receptacle and is suitably disposed. This device permits a rapid and safe replacement of a radiation contaminated filter without interruption to the normal flow of exhaust air.

  10. Solid-State Thyratron Replacement. Final Report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Roth, Ian

    2017-12-12

    Under this SBIR, DTI developed a solid-state switch as an alternative to legacy thyratron equipment. Our Phase II objective was to make a solid-state thyratron replacement that would provide equivalent or better performance, much higher reliability (at least a 20 year lifetime, compared to a thyratron’s two-year lifetime) and would sell for ~3x the cost of a thyratron, or less than $40k. We were successful in building a solid-state switch which could reliably function as a thyratron replacement. The unit was designed to directly replace the thyratrons currently being used at SLAC’s Linac Coherent Light Source (LCLS), and was builtmore » in a tank that was small enough to fit into the existing thyratron cabinet, providing a true form-fit-function replacement path. We tested the switch at the full operating specifications: 48 kV, 6.3 kA, and 1 µs risetime. We also demonstrated a peak-to-peak pulse jitter of 1.5 ns, which is five times shorter than is typical for thyratrons. This lower jitter would improve the performance of the LCLS beam. The predicted reliability is more than 80 years, which is 40 times greater than a thyratron.« less

  11. 42 CFR 433.117 - Initial approval of replacement systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... and Information Retrieval Systems § 433.117 Initial approval of replacement systems. (a) A replacement system must meet all conditions of initial approval of a mechanized claims processing and information retrieval system. (b) The agency must submit a APD that includes— (1) The date the replacement system will...

  12. 48 CFR 908.7101-4 - Replacement of motor vehicles.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... vehicles. 908.7101-4 Section 908.7101-4 Federal Acquisition Regulations System DEPARTMENT OF ENERGY....7101-4 Replacement of motor vehicles. (a) The replacement of motor vehicles shall be in accordance with... Activities may arrange to sell, as exchange sales, used motor vehicles being replaced and to apply the...

  13. 48 CFR 908.7101-4 - Replacement of motor vehicles.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Replacement of motor....7101-4 Replacement of motor vehicles. (a) The replacement of motor vehicles shall be in accordance with... Heads of Contracting Activities may arrange to sell, as exchange sales, used motor vehicles being...

  14. Slab replacement maturity guidelines.

    DOT National Transportation Integrated Search

    2014-04-01

    This study investigated the use of maturity method to determine early age strength of concrete in slab : replacement application. Specific objectives were (1) to evaluate effects of various factors on the compressive : maturity-strength relationship ...

  15. Hereditary hemochromatosis as a risk factor for joint replacement surgery.

    PubMed

    Sahinbegovic, Enijad; Dallos, Tomás; Aigner, Elmar; Axmann, Roland; Engelbrecht, Matthias; Schöniger-Hekele, Maximilian; Karonitsch, Thomas; Farkas, Martin; Karger, Thomas; Willeit, Johann; Stölzel, Ulrich; Keysser, Gernot; Datz, Christian; Kiechl, Stefan; Schett, Georg; Zwerina, Jochen

    2010-07-01

    Hemochromatosis is an inherited disease with iron overload and joint involvement resembling osteoarthritis. To determine the rate of joint replacement surgery in patients with hemochromatosis, we performed a cross-sectional cohort study. A total of 199 individuals with hereditary hemochromatosis were included. The prevalence of joint replacement surgery in hip, knee, and ankle joints because of secondary osteoarthritis was assessed. Data were compared with 917 healthy subjects from the population-based Bruneck study. A total of 32 of 199 individuals with hemochromatosis received joint replacement surgery with a total number of 52 joints replaced. Compared with expected rates in healthy individuals, patients with hemochromatosis had a significantly higher risk for joint replacement surgery (odds ratio 9.0; confidence interval, 4.6-17.4). Joint replacement occurred significantly earlier in life in patients with hemochromatosis; 21.9% of the patients with hemochromatosis and 1.7% of healthy individuals required joint replacement before the age of 50 years (P=.0027). Moreover, patients with hemochromatosis were more likely to require multiple joint replacements (8.5%) than the control group (expected rate 0.3%; P=.0001). Hemochromatosis is a risk factor for joint replacement surgery because of severe secondary osteoarthritis. Copyright 2010 Elsevier Inc. All rights reserved.

  16. 46 CFR 59.01-5 - Repairs, replacements, or alterations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Repairs, replacements, or alterations. 59.01-5 Section 59.01-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING REPAIRS TO BOILERS, PRESSURE VESSELS AND APPURTENANCES General Requirements § 59.01-5 Repairs, replacements, or alterations. (a) No repairs, replacements, or...

  17. 46 CFR 59.01-5 - Repairs, replacements, or alterations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Repairs, replacements, or alterations. 59.01-5 Section 59.01-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING REPAIRS TO BOILERS, PRESSURE VESSELS AND APPURTENANCES General Requirements § 59.01-5 Repairs, replacements, or alterations. (a) No repairs, replacements, or...

  18. 46 CFR 59.01-5 - Repairs, replacements, or alterations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Repairs, replacements, or alterations. 59.01-5 Section 59.01-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING REPAIRS TO BOILERS, PRESSURE VESSELS AND APPURTENANCES General Requirements § 59.01-5 Repairs, replacements, or alterations. (a) No repairs, replacements, or...

  19. 46 CFR 59.01-5 - Repairs, replacements, or alterations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Repairs, replacements, or alterations. 59.01-5 Section 59.01-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING REPAIRS TO BOILERS, PRESSURE VESSELS AND APPURTENANCES General Requirements § 59.01-5 Repairs, replacements, or alterations. (a) No repairs, replacements, or...

  20. 46 CFR 59.01-5 - Repairs, replacements, or alterations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Repairs, replacements, or alterations. 59.01-5 Section 59.01-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING REPAIRS TO BOILERS, PRESSURE VESSELS AND APPURTENANCES General Requirements § 59.01-5 Repairs, replacements, or alterations. (a) No repairs, replacements, or...

  1. Hip or knee replacement - after - what to ask your doctor

    MedlinePlus

    ... chap 7. Read More Hip joint replacement Hip pain Knee joint replacement Knee pain Osteoarthritis Patient Instructions Getting your home ready - knee or hip surgery Hip or knee replacement - before - ...

  2. Hip or knee replacement - before - what to ask your doctor

    MedlinePlus

    ... chap 7. Read More Hip joint replacement Hip pain Knee joint replacement Knee pain Osteoarthritis Patient Instructions Getting your home ready - knee or hip surgery Hip or knee replacement - after - ...

  3. Scaffolds for whole organ tissue engineering: Construction and in vitro evaluation of a seamless, spherical and hollow collagen bladder construct with appendices.

    PubMed

    Hoogenkamp, Henk R; Pot, Michiel W; Hafmans, Theo G; Tiemessen, Dorien M; Sun, Yi; Oosterwijk, Egbert; Feitz, Wout F; Daamen, Willeke F; van Kuppevelt, Toin H

    2016-10-01

    The field of regenerative medicine has developed promising techniques to improve current neobladder strategies used for radical cystectomies or congenital anomalies. Scaffolds made from molecularly defined biomaterials are instrumental in the regeneration of tissues, but are generally confined to small flat patches and do not comprise the whole organ. We have developed a simple, one-step casting method to produce a seamless large hollow collagen-based scaffold, mimicking the shape of the whole bladder, and with integrated anastomotic sites for ureters and urethra. The hollow bladder scaffold is highly standardized, with uniform wall thickness and a unidirectional pore structure to facilitate cell infiltration in vivo. Human and porcine bladder urothelial and smooth muscle cells were able to attach to the scaffold and maintained their phenotype in vitro. The closed luminal side and the porous outside of the scaffold facilitated the formation of an urothelial lining and infiltration of smooth muscle cells, respectively. The cells aligned according to the provided scaffold template. The technology used is highly adjustable (shape, size, materials) and may be used as a starting point for research to an off-the-shelf medical device suitable for neobladders. In this study, we describe the development of a simple, one-step casting method to produce a seamless large hollow collagen-based scaffold mimicking the shape of the whole bladder with integrated anastomotic sites for ureters and urethra. The hollow bladder scaffold is highly standardized with uniform wall thickness and a unidirectional pore structure to facilitate cell infiltration in vivo. The closed luminal surface and the porous exterior of the scaffold facilitated the formation of a urothelial lining and infiltration of smooth muscle cells, respectively. The applied technology is highly adjustable (shape, size, materials) and can be the starting point for research to an off-the-shelf medical device suitable for

  4. Insurance and education predict long-term survival after orthotopic heart transplantation in the United States.

    PubMed

    Allen, Jeremiah G; Weiss, Eric S; Arnaoutakis, George J; Russell, Stuart D; Baumgartner, William A; Shah, Ashish S; Conte, John V

    2012-01-01

    Insurance status and education are known to affect health outcomes. However, their importance in orthotopic heart transplantation (OHT) is unknown. The United Network for Organ Sharing (UNOS) database provides a large cohort of OHT recipients in which to evaluate the effect of insurance and education on survival. UNOS data were retrospectively reviewed to identify adult primary OHT recipients (1997 to 2008). Patients were stratified by insurance at the time of transplantation (private/self-pay, Medicare, Medicaid, and other) and college education. All-cause mortality was examined using multivariable Cox proportional hazard regression incorporating 15 variables. Survival was modeled using the Kaplan-Meier method. Insurance for 20,676 patients was distributed as follows: private insurance/self-pay, 12,298 (59.5%); Medicare, 5,227 (25.3%); Medicaid, 2,320 (11.2%); and "other" insurance, 831 (4.0%). Educational levels were recorded for 15,735 patients (76.1% of cohort): 7,738 (49.2%) had a college degree. During 53 ± 41 months of follow-up, 6,125 patients (29.6%) died (6.7 deaths/100 patient-years). Survival differed by insurance and education. Medicare and Medicaid patients had 8.6% and 10.0% lower 10-year survival, respectively, than private/self-pay patients. College-educated patients had 7.0% higher 10-year survival. On multivariable analysis, college education decreased mortality risk by 11%. Medicare and Medicaid increased mortality risk by 18% and 33%, respectively (p ≤ 0.001). Our study examining insurance and education in a large cohort of OHT patients found that long-term mortality after OHT is higher in Medicare/Medicaid patients and in those without a college education. This study points to potential differences in the care of OHT patients based on education and insurance status. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  5. Recurrent protein-losing enteropathy and tricuspid valve insufficiency in a transplanted heart: a causal relationship?

    PubMed

    Aggarwal, Sanjeev; Delius, Ralph E; Walters, Henry L; L'Ecuyer, Thomas J

    2012-01-01

    This case report describes a toddler who developed a protein-losing enteropathy (PLE) 4 years after orthotopic heart transplantation (OHT). He was born with a hypoplastic left heart syndrome for which he underwent a successful Norwood procedure, a Hemi-Fontan palliation, and a Fontan palliation at 18 months of age. Fifteen months following the Fontan operation, he developed a PLE and Fontan failure requiring OHT. Four years after OHT, he developed a severe tricuspid regurgitation and a PLE. His PLE improved after tricuspid valve replacement. It is now 2 years since his tricuspid valve replacement and he remains clinically free of ascites and peripheral edema with a normal serum albumin level. His prosthetic tricuspid valve is functioning normally. © 2011 Wiley Periodicals, Inc.

  6. Is physiological glucocorticoid replacement important in children?

    PubMed Central

    Porter, John; Blair, Joanne; Ross, Richard J

    2017-01-01

    Cortisol has a distinct circadian rhythm with low concentrations at night, rising in the early hours of the morning, peaking on waking and declining over the day to low concentrations in the evening. Loss of this circadian rhythm, as seen in jetlag and shift work, is associated with fatigue in the short term and diabetes and obesity in the medium to long term. Patients with adrenal insufficiency on current glucocorticoid replacement with hydrocortisone have unphysiological cortisol concentrations being low on waking and high after each dose of hydrocortisone. Patients with adrenal insufficiency complain of fatigue, a poor quality of life and there is evidence of poor health outcomes including obesity potentially related to glucocorticoid replacement. New technologies are being developed that deliver more physiological glucocorticoid replacement including hydrocortisone by subcutaneous pump, Plenadren, a once-daily modified-release hydrocortisone and Chronocort, a delayed and sustained absorption hydrocortisone formulation that replicates the overnight profile of cortisol. In this review, we summarise the evidence regarding physiological glucocorticoid replacement with a focus on relevance to paediatrics. PMID:27582458

  7. Effects of primary and recurrent sacral chordoma on the motor and nociceptive function of hindlimbs in rats: an orthotopic spine model.

    PubMed

    Sarabia-Estrada, Rachel; Ruiz-Valls, Alejandro; Shah, Sagar R; Ahmed, A Karim; Ordonez, Alvaro A; Rodriguez, Fausto J; Guerrero-Cazares, Hugo; Jimenez-Estrada, Ismael; Velarde, Esteban; Tyler, Betty; Li, Yuxin; Phillips, Neil A; Goodwin, C Rory; Petteys, Rory J; Jain, Sanjay K; Gallia, Gary L; Gokaslan, Ziya L; Quinones-Hinojosa, Alfredo; Sciubba, Daniel M

    2017-08-01

    OBJECTIVE Chordoma is a slow-growing, locally aggressive cancer that is minimally responsive to conventional chemotherapy and radiotherapy and has high local recurrence rates after resection. Currently, there are no rodent models of spinal chordoma. In the present study, the authors sought to develop and characterize an orthotopic model of human chordoma in an immunocompromised rat. METHODS Thirty-four immunocompromised rats were randomly allocated to 4 study groups; 22 of the 34 rats were engrafted in the lumbar spine with human chordoma. The groups were as follows: UCH1 tumor-engrafted (n = 11), JHC7 tumor-engrafted (n = 11), sham surgery (n = 6), and intact control (n = 6) rats. Neurological impairment of rats due to tumor growth was evaluated using open field and locomotion gait analysis; pain response was evaluated using mechanical or thermal paw stimulation. Cone beam CT (CBCT), MRI, and nanoScan PET/CT were performed to evaluate bony changes due to tumor growth. On Day 550, rats were killed and spines were processed for H & E-based histological examination and immunohistochemistry for brachyury, S100β, and cytokeratin. RESULTS The spine tumors displayed typical chordoma morphology, that is, physaliferous cells filled with vacuolated cytoplasm of mucoid matrix. Brachyury immunoreactivity was confirmed by immunostaining, in which samples from tumor-engrafted rats showed a strong nuclear signal. Sclerotic lesions in the vertebral body of rats in the UCH1 and JHC7 groups were observed on CBCT. Tumor growth was confirmed using contrast-enhanced MRI. In UCH1 rats, large tumors were observed growing from the vertebral body. JHC7 chordoma-engrafted rats showed smaller tumors confined to the bone periphery compared with UCH1 chordoma-engrafted rats. Locomotion analysis showed a disruption in the normal gait pattern, with an increase in the step length and duration of the gait in tumor-engrafted rats. The distance traveled and the speed of rats in the open field test

  8. Survival benefits of interferon-based therapy in patients with recurrent hepatitis C after orthotopic liver transplantation

    PubMed Central

    Zanaga, L.P.; Vigani, A.G.; Angerami, R.N.; Giorgetti, A.; Escanhoela, C.A.F.; Ataíde, E.C.; Boin, I.F.S.F.; Stucchi, R.S.B.

    2017-01-01

    Recurrent hepatitis C after orthotopic liver transplantation (OLT) is universal and can lead to graft failure and, consequently, reduced survival. Hepatitis C treatment can be used to prevent these detrimental outcomes. The aim of this study was to describe rates of hepatitis C recurrence and sustained virological response (SVR) to interferon-based treatment after OLT and its relationship to survival and progression of liver disease through retrospective analysis of medical records of 127 patients who underwent OLT due to cirrhosis or hepatocellular carcinoma secondary to chronic hepatitis C between January 2002 and December 2013. Fifty-six patients were diagnosed with recurrent disease, 42 started interferon-based therapy and 37 completed treatment. Demographic, treatment- and outcome-related variables were compared between SVR and non-responders (non-SVR). There was an overall 54.1% SVR rate with interferon-based therapies. SVR was associated with longer follow-up after treatment (median 66.5 vs 37 months for non-SVR, P=0.03) and after OLT (median 105 vs 72 months, P=0.074), and lower rates of disease progression (15 vs 64.7%, P=0.0028) and death (5 vs 35.3%, P=0.033). Regardless of the result of therapy (SVR or non-SVR), there was a significant difference between treated and untreated patients regarding the occurrence of death (P<0.001) and months of survival (P<0.001). Even with suboptimal interferon-based therapies (compared to the new direct-acting antivirals) there is a 54.1% SVR rate to treatment. SVR is associated with improved survival and reduced risks of clinical decompensation, loss of the liver graft and death. PMID:28076451

  9. Preclinical evaluation of transcriptional targeting strategy for human hepatocellular carcinoma in an orthotopic xenograft mouse model.

    PubMed

    Sia, Kian Chuan; Huynh, Hung; Chung, Alexander Yaw Fui; Ooi, London Lucien Peng Jin; Lim, Kiat Hon; Hui, Kam Man; Lam, Paula Yeng Po

    2013-08-01

    Gene regulation of many key cell-cycle players in S-, G(2) phase, and mitosis results from transcriptional repression in their respective promoter regions during the G(0) and G(1) phases of cell cycle. Within these promoter regions are phylogenetically conserved sequences known as the cell-cycle-dependent element (CDE) and cell-cycle genes homology regions (CHR) sites. Thus, we hypothesize that transcriptional regulation of cell-cycle regulation via the CDE/CHR region together with liver-specific apolipoprotein E (apoE)-hAAT promoter could bring about a selective transgene expression in proliferating human hepatocellular carcinoma. We show that the newly generated vector AH-6CC-L2C could mediate hepatocyte-targeted luciferase gene expression in tumor cells and freshly isolated short-term hepatocellular carcinoma cultures from patient biopsy. In contrast, normal murine and human hepatocytes infected with AH-6CC-L2C expressed minimal or low luciferase activities. In the presence of prodrug 5-fluorocytosine (5-FC), AH-6CC-L2C effectively suppressed the growth of orthotopic hepatocellular carcinoma patient-derived xenograft mouse model via the expression of yeast cytosine deaminase (yCD) that converts 5-FC to anticancer metabolite 5-fluoruracil. More importantly, we show that combination treatment of AH-6CC-L2C with an EZH2 inhibitor, DZNep, that targets EpCAM-positive hepatocellular carcinoma, can bring about a greater therapeutic efficacy compared with a single treatment of virus or inhibitor. Our study showed that targeting proliferating human hepatocellular carcinoma cells through the transcriptional control of therapeutic gene could represent a feasible approach against hepatocellular carcinoma.

  10. Mastracchio during EMU FPS Remove and Replace OPS

    NASA Image and Video Library

    2014-04-14

    Expedition 39 flight engineer Rick Mastracchio poses for a photo with the replacement Fan Pump Separator (FPS) and Extravehicular Mobility Unit (EMU) 3005. Image was taken in the Quest Airlock (A/L) during FPS remove and replace operations.

  11. Losartan activates sirtuin 1 in rat reduced-size orthotopic liver transplantation

    PubMed Central

    Pantazi, Eirini; Bejaoui, Mohamed; Zaouali, Mohamed Amine; Folch-Puy, Emma; Pinto Rolo, Anabela; Panisello, Arnau; Palmeira, Carlos Marques; Roselló-Catafau, Joan

    2015-01-01

    AIM: To investigate a possible association between losartan and sirtuin 1 (SIRT1) in reduced-size orthotopic liver transplantation (ROLT) in rats. METHODS: Livers of male Sprague-Dawley rats (200-250 g) were preserved in University of Wisconsin preservation solution for 1 h at 4 °C prior to ROLT. In an additional group, an antagonist of angiotensin II type 1 receptor (AT1R), losartan, was orally administered (5 mg/kg) 24 h and 1 h before the surgical procedure to both the donors and the recipients. Transaminase (as an indicator of liver injury), SIRT1 activity, and nicotinamide adenine dinucleotide (NAD+, a co-factor necessary for SIRT1 activity) levels were determined by biochemical methods. Protein expression of SIRT1, acetylated FoxO1 (ac-FoxO1), NAMPT (the precursor of NAD+), heat shock proteins (HSP70, HO-1) expression, endoplasmic reticulum stress (GRP78, IRE1α, p-eIF2) and apoptosis (caspase 12 and caspase 3) parameters were determined by Western blot. Possible alterations in protein expression of mitogen activated protein kinases (MAPK), such as p-p38 and p-ERK, were also evaluated. Furthermore, the SIRT3 protein expression and mRNA levels were examined. RESULTS: The present study demonstrated that losartan administration led to diminished liver injury when compared to ROLT group, as evidenced by the significant decreases in alanine aminotransferase (358.3 ± 133.44 vs 206 ± 33.61, P < 0.05) and aspartate aminotransferase levels (893.57 ± 397.69 vs 500.85 ± 118.07, P < 0.05). The lessened hepatic injury in case of losartan was associated with enhanced SIRT1 protein expression and activity (5.27 ± 0.32 vs 6.08 ± 0.30, P < 0.05). This was concomitant with increased levels of NAD+ (0.87 ± 0.22 vs 1.195 ± 0.144, P < 0.05) the co-factor necessary for SIRT1 activity, as well as with decreases in ac-FoxO1 expression. Losartan treatment also provoked significant attenuation of endoplasmic reticulum stress parameters (GRP78, IRE1α, p-eIF2) which was

  12. Losartan activates sirtuin 1 in rat reduced-size orthotopic liver transplantation.

    PubMed

    Pantazi, Eirini; Bejaoui, Mohamed; Zaouali, Mohamed Amine; Folch-Puy, Emma; Pinto Rolo, Anabela; Panisello, Arnau; Palmeira, Carlos Marques; Roselló-Catafau, Joan

    2015-07-14

    To investigate a possible association between losartan and sirtuin 1 (SIRT1) in reduced-size orthotopic liver transplantation (ROLT) in rats. Livers of male Sprague-Dawley rats (200-250 g) were preserved in University of Wisconsin preservation solution for 1 h at 4 °C prior to ROLT. In an additional group, an antagonist of angiotensin II type 1 receptor (AT1R), losartan, was orally administered (5 mg/kg) 24 h and 1 h before the surgical procedure to both the donors and the recipients. Transaminase (as an indicator of liver injury), SIRT1 activity, and nicotinamide adenine dinucleotide (NAD(+), a co-factor necessary for SIRT1 activity) levels were determined by biochemical methods. Protein expression of SIRT1, acetylated FoxO1 (ac-FoxO1), NAMPT (the precursor of NAD+), heat shock proteins (HSP70, HO-1) expression, endoplasmic reticulum stress (GRP78, IRE1α, p-eIF2) and apoptosis (caspase 12 and caspase 3) parameters were determined by Western blot. Possible alterations in protein expression of mitogen activated protein kinases (MAPK), such as p-p38 and p-ERK, were also evaluated. Furthermore, the SIRT3 protein expression and mRNA levels were examined. The present study demonstrated that losartan administration led to diminished liver injury when compared to ROLT group, as evidenced by the significant decreases in alanine aminotransferase (358.3 ± 133.44 vs 206 ± 33.61, P < 0.05) and aspartate aminotransferase levels (893.57 ± 397.69 vs 500.85 ± 118.07, P < 0.05). The lessened hepatic injury in case of losartan was associated with enhanced SIRT1 protein expression and activity (5.27 ± 0.32 vs 6.08 ± 0.30, P < 0.05). This was concomitant with increased levels of NAD(+) (0.87 ± 0.22 vs 1.195 ± 0.144, P < 0.05) the co-factor necessary for SIRT1 activity, as well as with decreases in ac-FoxO1 expression. Losartan treatment also provoked significant attenuation of endoplasmic reticulum stress parameters (GRP78, IRE1α, p-eIF2) which was consistent with reduced

  13. Protective effects against hepatic ischemia-reperfusion injury after rat orthotopic liver transplantation because of BCL-2 overexpression.

    PubMed

    Wu, Kun; Ma, Long; Xu, Ting; Qin, Zhensheng; Xia, Tianfang; Wang, Yi; Yu, Xiangyou; Pang, Liqun

    2015-01-01

    This study aims to investigate the protective effects and mechanism of recombinant adenovirus Ad.VSG-hBCL-2 towards ischemia/reperfusion injury in rat liver graft. Recombinant adenovirus Ad.VSG-hBCL-2 was injected into the donor rat liver of the experiment group through the portal vein, the laparotomy was performed for liver 36 h later, and the liver was save in lactated Ringer's solution at 4°C for 4 h, "two-cuff method" was used to perform the orthotopic liver transplantation. The bile secretion situations of two groups were observed 6 h after the portal vein reflow; the recipient rats were killed to detect the plasma levels of AST, ALT and LDH. And the expressions of Bcl-2 and TNF-α in liver tissue, and TUNEL assay was used to detect the apoptosis of liver tissue cells, electron microscopy was used to observe the changes of subcellular structures of liver tissue. 6 h after the surgery, the immunohistochemistry and Western Blot test showed that the Bcl-2 expression in the liver of the experiment group significantly increased than the control group, the bile secretion increased, the levels of AST, ALT and LDH were significantly lower, and the TNF-α expression increased significantly. The changes of cellular morphology of the experiment group were milder, and the apoptotic index was significantly lower than the control group. The portal vein-transfected recombinant adenovirus Ad.VSG-hBCL-2 could be effectively expressed in rat liver, and the high expressed Bcl-2 could reduce the ischemia/reperfusion injury in the transplanted liver.

  14. The growth of glioblastoma orthotopic xenografts in nude mice is directly correlated with impaired object recognition memory.

    PubMed

    Wasilewska-Sampaio, Ana Paula; Santos, Tiago G; Lopes, Marilene Hohmuth; Cammarota, Martin; Martins, Vilma Regina

    2014-01-17

    Cognitive dysfunction is found in patients with brain tumors and there is a need to determine whether it can be replicated in an experimental model. In the present study, the object recognition (OR) paradigm was used to investigate cognitive performance in nude mice, which represent one of the most important animal models available to study human tumors in vivo. Mice with orthotopic xenografts of the human U87MG glioblastoma cell line were trained at 9, 14, and 18days (D9, D14, and D18, respectively) after implantation of 5×10(5) cells. At D9, the mice showed normal behavior when tested 90min or 24h after training and compared to control nude mice. Animals at D14 were still able to discriminate between familiar and novel objects, but exhibited a lower performance than animals at D9. Total impairment in the OR memory was observed when animals were evaluated on D18. These alterations were detected earlier than any other clinical symptoms, which were observed only 22-24days after tumor implantation. There was a significant correlation between the discrimination index (d2) and time after tumor implantation as well as between d2 and tumor volume. These data indicate that the OR task is a robust test to identify early behavior alterations caused by glioblastoma in nude mice. In addition, these results suggest that OR task can be a reliable tool to test the efficacy of new therapies against these tumors. © 2013 Elsevier Inc. All rights reserved.

  15. Laparoscopic Sleeve Gastrectomy for Morbid Obesity in Patients After Orthotopic Liver Transplant: a Matched Case-Control Study.

    PubMed

    Tsamalaidze, Levan; Stauffer, John A; Arasi, Lisa C; Villacreses, Diego E; Franco, Jose Salvador Serrano; Bowers, Steven; Elli, Enrique F

    2018-02-01

    Obesity is frequently encountered in patients with orthotopic liver transplant (OLT). The role of bariatric surgery is still unclear for this specific population. The aim of this study was to review our experience with laparoscopic sleeve gastrectomy (LSG) after OLT. We performed a retrospective case-control study of patients undergoing LSG after OLT from 2010 to 2016. OLT-LSG patients were matched by age, sex, body mass index (BMI), and year to non-OLT patients undergoing LSG. Demographics, operative variables, postoperative events, and long-term weight loss with comorbidity resolution were collected and compared between cases and controls. Of 303 patients undergoing LSG, 12 (4%) had previous OLT. They were matched to 36 non-OLT patients. No difference was found between groups in the American Society of Anesthesiologists class, mean operative time, or postoperative morbidity. The non-OLT group, however, had a significantly shorter mean hospital stay than the OLT group (1.7 vs 3.1 days; P < .001). There were no conversions to open procedures. For patients with long-term follow-up, change in BMI after LSG was similar between the groups, but the non-OLT patients had significantly more excess body weight loss at 2 years (53.7 vs 45.2%; P < .001). Similar resolution of comorbid conditions was noted in both groups. LSG caused no changes in dosage of immunosuppressive medications, and no liver complications occurred. LSG after OLT in appropriately selected patients appears to have similar outcomes to LSG in non-OLT patients.

  16. Cardiovascular risk after orthotopic liver transplantation, a review of the literature and preliminary results of a prospective study.

    PubMed

    Pisano, Giuseppina; Fracanzani, Anna L; Caccamo, Lucio; Donato, Maria F; Fargion, Silvia

    2016-10-28

    Improved surgical techniques and greater efficacy of new anti-rejection drugs have significantly improved the survival of patients undergoing orthotopic liver transplantation (OLT). This has led to an increased incidence of metabolic disorders as well as cardiovascular and cerebrovascular diseases as causes of morbidity and mortality in OLT patients. In the last decade, several studies have examined which predisposing factors lead to increased cardiovascular risk ( i.e ., age, ethnicity, diabetes, NASH, atrial fibrillation, and some echocardiographic parameters) as well as which factors after OLT ( i.e ., weight gain, metabolic syndrome, immunosuppressive therapy, and renal failure) are linked to increased cardiovascular mortality. However, currently, there are no available data that evaluate the development of atherosclerotic damage after OLT. The awareness of high cardiovascular risk after OLT has not only lead to the definition of new but generally not accepted screening of high risk patients before transplantation, but also to the need for careful patient follow up and treatment to control metabolic and cardiovascular pathologies after transplant. Prospective studies are needed to better define the predisposing factors for recurrence and de novo occurrence of metabolic alterations responsible for cardiovascular damage after OLT. Moreover, such studies will help to identify the timing of disease progression and damage, which in turn may help to prevent morbidity and mortality for cardiovascular diseases. Our preliminary results show early occurrence of atherosclerotic damage, which is already present a few weeks following OLT, suggesting that specific, patient-tailored therapies should be started immediately post OLT.

  17. Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles for the neovascular imaging of orthotopic glioblastomas

    NASA Astrophysics Data System (ADS)

    Kawamura, Wataru; Miura, Yutaka; Kokuryo, Daisuke; Toh, Kazuko; Yamada, Naoki; Nomoto, Takahiro; Matsumoto, Yu; Sueyoshi, Daiki; Liu, Xueying; Aoki, Ichio; Kano, Mitsunobu R.; Nishiyama, Nobuhiro; Saga, Tsuneo; Kishimura, Akihiro; Kataoka, Kazunori

    2015-06-01

    Introduction of ligands into 100 nm scaled hollow capsules has great potential for diagnostic and therapeutic applications in drug delivery systems. Polyethylene glycol-conjugated (PEGylated) polyion complex vesicles (PICsomes) are promising hollow nano-capsules that can survive for long periods in the blood circulation and can be used to deliver water-soluble macromolecules to target tissues. In this study, cyclic RGD (cRGD) peptide, which is specifically recognized by αVβ3 and αvβ5 integrins that are expressed at high levels in the neovascular system, was conjugated onto the distal end of PEG strands on PICsomes for active neovascular targeting. Density-tunable cRGD-conjugation was achieved using PICsomes with definite fraction of end-functionalized PEG, to substitute 20, 40, and 100% of PEG distal end of the PICsomes to cRGD moieties. Compared with control-PICsomes without cRGD, cRGD-PICsomes exhibited increased uptake into human umbilical vein endothelial cells. Intravital confocal laser scanning microscopy revealed that the 40%-cRGD-PICsomes accumulated mainly in the tumor neovasculature and remained in the perivascular region even after 24 h. Furthermore, we prepared superparamagnetic iron oxide (SPIO)-loaded cRGD-PICsomes for magnetic resonance imaging (MRI) and successfully visualized the neovasculature in an orthotopic glioblastoma model, which suggests that SPIO-loaded cRGD-PICsomes might be useful as a MRI contrast reagent for imaging of the tumor microenvironment, including neovascular regions that overexpress αVβ3 integrins.

  18. Roguing with replacement in perennial crops: conditions for successful disease management.

    PubMed

    Sisterson, Mark S; Stenger, Drake C

    2013-02-01

    Replacement of diseased plants with healthy plants is commonly used to manage spread of plant pathogens in perennial cropping systems. This strategy has two potential benefits. First, removing infected plants may slow pathogen spread by eliminating inoculum sources. Second, replacing infected plants with uninfected plants may offset yield losses due to disease. The extent to which these benefits are realized depends on multiple factors. In this study, sensitivity analyses of two spatially explicit simulation models were used to evaluate how assumptions concerning implementation of a plant replacement program and pathogen spread interact to affect disease suppression. In conjunction, effects of assumptions concerning yield loss associated with disease and rates of plant maturity on yields were simultaneously evaluated. The first model was used to evaluate effects of plant replacement on pathogen spread and yield on a single farm, consisting of a perennial crop monoculture. The second model evaluated effects of plant replacement on pathogen spread and yield in a 100 farm crop growing region, with all farms maintaining a monoculture of the same perennial crop. Results indicated that efficient replacement of infected plants combined with a high degree of compliance among farms effectively slowed pathogen spread, resulting in replacement of few plants and high yields. In contrast, inefficient replacement of infected plants or limited compliance among farms failed to slow pathogen spread, resulting in replacement of large numbers of plants (on farms practicing replacement) with little yield benefit. Replacement of infected plants always increased yields relative to simulations without plant replacement provided that infected plants produced no useable yield. However, if infected plants produced useable yields, inefficient removal of infected plants resulted in lower yields relative to simulations without plant replacement for perennial crops with long maturation periods

  19. Total Knee Replacement

    PubMed Central

    2005-01-01

    Executive Summary Objective The aim of this review was to assess the effectiveness, in terms of pain reduction and functional improvement, and costing of total knee replacement (TKR) for people with osteoarthritis for whom less invasive treatments (such as physiotherapy, analgesics, anti-inflammatory drugs, intra-articular steroids, hyaluronic acids, and arthroscopic surgery) have failed. Clinical Need Osteoarthritis affects an estimated 10% to 12% of Canadian adults. The therapeutic goals of osteoarthritis treatment are to improve joint mobility and reduce pain. Stepwise treatment options include exercise, weight loss, physiotherapy, analgesics, anti-inflammatory drugs, intra-articular steroids and hyaluronic acids, arthroscopic surgery, and, in severe cases, total joint replacement with follow-up rehabilitation. These treatments are delivered by a range of health care professionals, including physiotherapists, occupational therapists, family physicians, internists, rheumatologists, and orthopedic surgeons. TKR is an end-of-line treatment for patients with severe pain and functional limitations. More women than men undergo knee replacement, and most patients are between 55 and 84 years old. The Technology TKR is a surgical procedure in which an artificial joint or prosthesis replaces a damaged knee joint. The primary indication for TKR is pain, followed by functional limitation. Usually, a person’s daily activities must be substantially affected by pain and functional limitations for him or her to be considered a candidate for TKR. There are 3 different types of knee replacement prostheses. Non-constrained prostheses use the patient’s ligaments and muscles to provide the stability for the prosthesis. Semi-constrained prostheses provide some stability for the knee and do not rely entirely on the patient’s ligaments and muscles to provide the stability. Constrained prostheses are for patients whose ligaments and muscles are not able to provide stability for

  20. Radiofrequency catheter ablation in patients with symptomatic atrial flutter/tachycardia after orthotopic heart transplantation.

    PubMed

    Li, Yi-gang; Grönefeld, Gerian; Israel, Carsten; Lu, Shang-biao; Wang, Qun-shan; Hohnloser, Stefan H

    2006-12-20

    Atrial tachycardia or flutter is common in patients after orthotopic heart transplantation. Radiofrequency catheter ablation to treat this arrhythmia has not been well defined in this setting. This study was conducted to assess the incidence of various symptomatic atrial arrhythmias and the efficacy and safety of radiofrequency catheter ablation in these patients. Electrophysiological study and catheter ablation were performed in patients with symptomatic tachyarrhythmia. One Halo catheter with 20 poles was positioned around the tricuspid annulus of the donor right atrium, or positioned around the surgical anastomosis when it is necessary. Three quadripolar electrode catheters were inserted via the right or left femoral vein and positioned in the recipient atrium, the bundle of His position, the coronary sinus. Programmed atrial stimulation and burst pacing were performed to prove electrical conduction between the recipient and the donor atria and to induce atrial arrhythmias. Out of 55 consecutive heart transplantation patients, 6 males [(58 +/- 12) years] developed symptomatic tachycardias at a mean of (5 +/- 4) years after heart transplantation. Electrical propagation through the suture line between the recipient and the donor atrium was demonstrated during atrial flutter or during recipient atrium and donor atrium pacing in 2 patients. By mapping around the suture line, the earliest fragmented electrogram of donor atrium was assessed. This electrical connection was successfully ablated in the anterior lateral atrium in both patients. There was no electrical propagation through the suture line in the other 4 patients. Two had typical atrial flutter in the donor atrium which was successfully ablated by completing a linear ablation between the tricuspid annulus and the inferior vena cava. Two patients had atrial tachycardia which was ablated in the anterior septal and lateral donor atrium. There were no procedure-related complications. Patients were free of

  1. Replacement of Mushroom Cage Gastrostomy Tube Using a Modified Technique to Allow Percutaneous Replacement with an Endoscopic Tube in Patients with Amyotrophic Lateral Sclerosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ammar, Thoraya; Rio, Alan; Ampong, Mary Ann

    2010-06-15

    Radiologic inserted gastrostomy (RIG) is the preferred method in our institution for enteral feeding in amyotrophic lateral sclerosis (ALS). Skin-level primary-placed mushroom cage gastrostomy tubes become tight with weight gain. We describe a minimally invasive radiologic technique for replacing mushroom gastrostomy tubes with endoscopic mushroom cage tubes in ALS. All patients with ALS who underwent replacement of a RIG tube were included. Patients were selected for a modified replacement when the tube length of the primary placed RIG tube was insufficient to allow like-for-like replacement. Replacement was performed under local anesthetic and fluoroscopic guidance according to a preset technique, withmore » modification of an endoscopic mushroom cage gastrostomy tube to allow percutaneous placement. Assessment of the success, safety, and durability of the modified technique was undertaken. Over a 60-month period, 104 primary placement mushroom cage tubes in ALS were performed. A total of 20 (19.2%) of 104 patients had a replacement tube positioned, 10 (9.6%) of 104 with the modified technique (male n = 4, female n = 6, mean age 65.5 years, range 48-85 years). All tubes were successfully replaced using this modified technique, with two minor complications (superficial wound infection and minor hemorrhage). The mean length of time of tube durability was 158.5 days (range 6-471 days), with all but one patient dying with a functional tube in place. We have devised a modification to allow percutaneous replacement of mushroom cage gastrostomy feeding tubes with minimal compromise to ALS patients. This technique allows tube replacement under local anesthetic, without the need for sedation, an important consideration in ALS.« less

  2. Final Environmental Assessment, Horse Creek Bridge Replacement

    DTIC Science & Technology

    2010-10-01

    Final Environmental Assessment Horse Creek Bridge Replacement 78th Civil Engineer Group...Final Environmental Assessment Horse Creek Bridge Replacement 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 FINDING OF NO SIGNIFICANT IMPACT (FONSI)/ FINDING OF NO PRACTICABLE ALTERNATIVE (FONP A) HORSE

  3. Dead pixel replacement in LWIR microgrid polarimeters.

    PubMed

    Ratliff, Bradley M; Tyo, J Scott; Boger, James K; Black, Wiley T; Bowers, David L; Fetrow, Matthew P

    2007-06-11

    LWIR imaging arrays are often affected by nonresponsive pixels, or "dead pixels." These dead pixels can severely degrade the quality of imagery and often have to be replaced before subsequent image processing and display of the imagery data. For LWIR arrays that are integrated with arrays of micropolarizers, the problem of dead pixels is amplified. Conventional dead pixel replacement (DPR) strategies cannot be employed since neighboring pixels are of different polarizations. In this paper we present two DPR schemes. The first is a modified nearest-neighbor replacement method. The second is a method based on redundancy in the polarization measurements.We find that the redundancy-based DPR scheme provides an order-of-magnitude better performance for typical LWIR polarimetric data.

  4. Importance of milk replacer intake and composition in rearing orphan foals

    PubMed Central

    Cymbaluk, Nadia F.; Smart, Marion E.; Bristol, Frank M.; Pouteaux, Victor A.

    1993-01-01

    Effects of milk replacer composition and intake on the growth of orphan foals were evaluated. Twenty foals were assigned to four treatments: 1) mare-nursed, 2) commercial foal milk replacer at recommended intakes (standard), 3) commercial foal milk replacer at high intakes (high), and 4) acidified replacer at recommended intakes (acidified). Foals fed milk replacer diets were weaned at 12-24 hours postpartum and fed milk replacer for 50 days. Mare-nursed foals were weaned between 52 and 56 days of age. Foals fed replacer diets gained 12% to 28% less weight than mare-nursed foals up to two weeks of age. However, by four months of age, weights of replacer-fed foals were similar to those of mare-nursed foals and 32 other mare-nursed foals at the farm weaned between three and four months postparium. Foals drank 10 to 12 L/100 kg body weight (BW) in fluid replacer daily over the trial period. During the first week, high intake foals consumed 26% more replacer (p<0.05) than foals fed acidified or standard diets. This higher intake resulted in diarrhea earlier (6-11 days vs 11-22 days) and for a longer time (6.3 days vs 2.5-3.6 days) than in foals fed recommended amounts. Mare-nursed foals developed “foal heat scours” in the second week postpartum. After the first week, foals fed high replacer diet voluntarily consumed the same volume of fluid replacer as foals fed the standard intake. Foals ate less than 1 kg grain mix/100 kg BW daily to one month of age, then increased intake to 1.5-2 kg/ 100 kg BW to weaning. Water intake was 20-40% of daily fluid intake and was correlated (r = 0.85) to dry matter intake. Foals in the high intake group ate less (p<0.05) solid feed and drank less water than foals fed the standard and acidified diets. The foal's stomach capacity appears to limit meal size and thus replacer intake. If recommended feeding intervals are used, replacer intakes by foals are less than 15% BW daily. High volume intakes appeared to prolong diarrhea. Normal

  5. 23 CFR 650.407 - Application for bridge replacement or rehabilitation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 23 Highways 1 2011-04-01 2011-04-01 false Application for bridge replacement or rehabilitation... ENGINEERING AND TRAFFIC OPERATIONS BRIDGES, STRUCTURES, AND HYDRAULICS Highway Bridge Replacement and Rehabilitation Program § 650.407 Application for bridge replacement or rehabilitation. (a) Agencies participate...

  6. 23 CFR 650.407 - Application for bridge replacement or rehabilitation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Application for bridge replacement or rehabilitation... ENGINEERING AND TRAFFIC OPERATIONS BRIDGES, STRUCTURES, AND HYDRAULICS Highway Bridge Replacement and Rehabilitation Program § 650.407 Application for bridge replacement or rehabilitation. (a) Agencies participate...

  7. Two-level total lumbar disc replacement.

    PubMed

    Di Silvestre, Mario; Bakaloudis, Georgios; Lolli, Francesco; Vommaro, Francesco; Parisini, Patrizio

    2009-06-01

    Total lumbar disc replacement (TDR) has been widely used as a treatment option for 2-level symptomatic degenerative disc disease. However, recent studies have presented conflicting results and some authors concluded that outcome deteriorated when disc replacement was performed bisegmentally, with an increase of complications for bisegmental replacements in comparison with monosegmental disc arthroplasty. The goal of the present retrospective study is to investigate results in a group of patients who have received bisegmental TDR with SB Charitè III artificial disc for degenerative disc disease with a minimum follow-up of 3 years, and to compare the results of 2-level disc replacement versus 1-level patients treated with the same prosthesis. A total of 32 patients had at least 3-years follow-up and were reviewed. The average age of the patients was 38.5 years. There were 11 males and 21 females. About 16 patients received 2-level TDR (SB Charitè III) and 16 received 1-level TDR (SB Charitè III). Both radiographic and functional outcome analysis, including patient's satisfaction, was performed. There were no signs of degenerative changes of the adjacent segments in any case of the 2- or 1-level TDR. There was no statistically significant difference between 2- and 1-level TDR both at 12 months and at 3-years follow-up on functional outcome scores. There was a statistically insignificant difference concerning the patients satisfaction between 1- and 2-level surgeries at the last follow-up (P = 0.46). In the 2-level TDR patients, there were 5 minor complications (31.25%), whereas major complications occurred in 4 more patients (25%) and required a new surgery in 2 cases (12.5%). In the 1-level cases there were 2 minor complications (12.5%) and 2 major complications (12.5%) and a new revision surgery was required in 1 patient (6.25%). In conclusion, the use of 2-level disc replacement at last follow-up presented a higher incidence of complications than in cases with 1

  8. Heart valve replacement with the Sorin tilting-disc prosthesis. A 10-year experience.

    PubMed

    Milano, A; Bortolotti, U; Mazzucco, A; Mossuto, E; Testolin, L; Thiene, G; Gallucci, V

    1992-02-01

    From 1978 to 1988, 697 patients with a mean age of 48 +/- 11 years (range 5 to 75 years) received a Sorin tilting-disc prosthesis; 358 had had aortic valve replacement, 247 mitral valve replacement, and 92 mitral and aortic valve replacement. Operative mortality rates were 7.8%, 11.3%, and 10.8%, respectively, in the three groups. Cumulative duration of follow-up is 1650 patient-years for aortic valve replacement (maximum follow-up 11.4 years), 963 patient-years for mitral valve replacement (maximum follow-up 9.9 years) and 328 patient-years for mitral and aortic valve replacement (maximum follow-up 9.4 years). Actuarial survival at 9 years is 72% +/- 4% after mitral valve replacement, 70% +/- 3% after aortic valve replacement, and 50% +/- 12% after mitral and aortic valve replacement, and actuarial freedom from valve-related deaths is 97% +/- 2% after mitral valve replacement, 92% +/- 2% after aortic valve replacement, and 62% +/- 15% after mitral and aortic valve replacement. Thromboembolic events occurred in 21 patients with aortic valve replacement (1.3% +/- 0.2%/pt-yr), in 12 with mitral valve replacement (1.2% +/- 0.3% pt-yr), and in seven with mitral and aortic valve replacement (2.1% +/- 0.8%), with one case of prosthetic thrombosis in each group; actuarial freedom from thromboembolism at 9 years is 92% +/- 3% after mitral valve replacement, 91% +/- 3% after aortic valve replacement, and 74% +/- 16% after mitral and aortic valve replacement. Anticoagulant-related hemorrhage was observed in 15 patients after aortic valve replacement (0.9% +/- 0.2%/pt-yr), in 9 after mitral valve replacement (0.9% +/- 0.3%/pt-yr), and in 6 with mitral and aortic valve replacement (0.9% +/- 0.5%/pt-yr); actuarial freedom from this complication at 9 years is 94% +/- 2% after aortic valve replacement, 91% +/- 4% after mitral valve replacement, and 68% +/- 16% after mitral and aortic valve replacement. Actuarial freedom from reoperation at 9 years is 97% +/- 2% after mitral and

  9. Recent Advances in Hydrocortisone Replacement Treatment.

    PubMed

    Mallappa, Ashwini; Debono, Miguel

    2016-01-01

    Since the first use of cortisone in patients around 65 years ago, the use of synthetic glucocorticoids has made a crucial impact on the treatment of several diseases in medicine. Although significant reductions in morbidity and mortality have occurred in patients suffering from cortisol deficiency, conventional hydrocortisone replacement treatment is still inadequate. A major limitation is that it fails to replace cortisol in a physiological manner. Cortisol has a distinct circadian rhythm and acts as a secondary messenger synchronizing the central to peripheral clocks, hence playing a key role in biological processes and the circadian timing system. Circadian misalignment has been associated with ill-health and so nonphysiological glucocorticoid treatment could explain the increased mortality rate, poor quality of life and metabolic complications in patients suffering from adrenal insufficiency. Attempts at replacing cortisol in a physiological manner have shown significant progress in the past decade with the development of modified-release formulations of hydrocortisone (Chronocort® and Plenadren®) and continuous subcutaneous hydrocortisone infusions. Initial studies investigating the use of these replacement regimens are promising, demonstrating both clinical and biochemical improvement. Larger studies are needed to determine whether this novel approach enhances long-term outcomes in both children and adults with cortisol deficiency. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. Published by S. Karger AG, Basel.

  10. The economics of robotic cystectomy: cost comparison of open versus robotic cystectomy.

    PubMed

    Lee, Richard; Ng, Casey K; Shariat, Shahrokh F; Borkina, Anna; Guimento, Robert; Brumit, Kevin F; Scherr, Douglas S

    2011-12-01

    • To assess and compare the economic burden of open radical cystectomy (OC) vs robotic-assisted laparoscopic radical cystectomy (RC) with pelvic lymph node dissection and urinary diversion. • A series of 103 and 83 consecutive patients undergoing OC and RC, respectively, were prospectively studied at a tertiary care institution from April 2002 to February 2009. • Data were collected on patient demographics, perioperative parameters and length of stay (LOS) in hospital. Cohorts were subdivided into ileal conduit (IC), continent cutaneous diversion (CCD) and orthotopic neobladder (ON) subgroups. • A linear cost model was created to simulate treatment with OC vs RC. Procedural costs were derived from the Medicare Resource Based Relative Value Scale. Materials costs were obtained from the respective suppliers. The indirect costs of complications were considered. • Sensitivity analyses were performed. • Despite a higher cost of materials, RC was less expensive than OC for IC and CCD, although the cost advantage deteriorated for ON. • The per-case costs of RC with IC, CCD and ON were $20,659, $22,102 and $22,685, respectively, compared to $25,505, $22,697 and $20,719 for their OC counterparts. • The largest cost driver in the study was LOS in hospital. • RC showed a shorter LOS compared to OC, although this effect was insufficient to offset the higher cost of robotic surgery. • Complications materially affected cost performance. • Despite a higher cost of materials, RC can be more cost efficient than OC as a treatment for bladder cancer at a high-volume, tertiary care referral centre, particularly with IC. • Complications significantly impact cost performance. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

  11. COMPUTER AIDED DESIGN OF REPLACEMENT SOLVENTS UNDER VARYING ENVIRONMENTAL CONSTRAINTS

    EPA Science Inventory

    There is a great need to replace many solvents that are commonly used by industry and the public, but whose continued use entails a number of human health and environmental risks. One problem hampering solvent replacement is the thought that replacement, particularly for environm...

  12. Menopausal Symptom Relief and Side Effects Experienced by Women Using Bioidentical Hormone Replacement Therapy and Synthetic Conjugated Equine Estrogen and/or Progestin Hormone Replacement Therapy, Part 1.

    PubMed

    Deleruyelle, Laura J

    2016-01-01

    The use of compounded bioidentical hormone replacement therapy by menopausal women has become a popular alternative to traditional synthetic conjugated equine estrogen and progestin hormone replacement therapy due to safety concerns raised by recent studies. However, due to the lack of randomized, large-scale trials to evaluate the efficacy and side-effect profile of compounded bioidentical hormone replacement therapy many healthcare providers are reluctant to prescribe such therapy. The purpose of this study was to compare women's menopausal symptom relief and side effects experienced when using compounded bioidentical hormone replacement therapy and traditional hormone replacement therapy. A descriptive comparative design was used. Inferential and descriptive statistical procedures including a paired difference t -test, two-sample t -test, and f tests (percentage, mean, standard deviation, frequency) were run on the Statistical Package for the Social Sciences. The framework used to guide this study was Lenz and Pugh's Theory of Unpleasant Symptoms. Surveys were distributed once to a convenient sample of women aged 35 and older when they dropped off or picked up their prescriptions at a pharmacy. Of the 216 surveys distributed, 70 were returned from those women taking compounded bioidentical hormone replacement therapy and 53 from traditional hormone replacement therapy. The survey contained 15 questions pertaining to age, duration of hormone replacement therapy, type and formulation of hormone replacement therapy, reasons for initiating hormone replacement therapy, symptoms before and one month after hormone replacement therapy, and side effects related to hormone replacement therapy. The results of this study will be summarized in forthcoming articles in this series. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

  13. Sugar replacers: from technological challenges to consequences on health.

    PubMed

    Lê, Kim-Anne; Robin, Frédéric; Roger, Olivier

    2016-07-01

    Dietary sugars play a role in noncommunicable diseases and represent a clear target for reduction. In this context, product reformulation can have a positive impact on health. Several technological solutions are available to replace sugar, all with benefits and limitations. The goal of this review is to describe the main sugar replacement alternatives and discuss their impact on health and product physicochemical properties. Although high intensity sweeteners and polyols have been used for a long time to replace sucrose and despite no clear evidence of harm, the trend is today to look for alternatives such as sweet enhancers or alternative sugars such as allulose or tagatose, which are both low caloric. To replace the physical properties of sugars, new trends are to substitute widely used maltodextrins by dietary fibres to confer added health benefits. A wide range of solutions is currently available to replace dietary sugars and compensate for the impact on bulking properties and sweetness profile of food products.

  14. Evaluation of Heterogeneous Metabolic Profile in an Orthotopic Human Glioblastoma Xenograft Model Using Compressed Sensing Hyperpolarized 3D 13C Magnetic Resonance Spectroscopic Imaging

    PubMed Central

    Park, Ilwoo; Hu, Simon; Bok, Robert; Ozawa, Tomoko; Ito, Motokazu; Mukherjee, Joydeep; Phillips, Joanna J.; James, C. David; Pieper, Russell O.; Ronen, Sabrina M.; Vigneron, Daniel B.; Nelson, Sarah J.

    2013-01-01

    High resolution compressed sensing hyperpolarized 13C magnetic resonance spectroscopic imaging was applied in orthotopic human glioblastoma xenografts for quantitative assessment of spatial variations in 13C metabolic profiles and comparison with histopathology. A new compressed sensing sampling design with a factor of 3.72 acceleration was implemented to enable a factor of 4 increase in spatial resolution. Compressed sensing 3D 13C magnetic resonance spectroscopic imaging data were acquired from a phantom and 10 tumor-bearing rats following injection of hyperpolarized [1-13C]-pyruvate using a 3T scanner. The 13C metabolic profiles were compared with hematoxylin and eosin staining and carbonic anhydrase 9 staining. The high-resolution compressed sensing 13C magnetic resonance spectroscopic imaging data enabled the differentiation of distinct 13C metabolite patterns within abnormal tissues with high specificity in similar scan times compared to the fully sampled method. The results from pathology confirmed the different characteristics of 13C metabolic profiles between viable, non-necrotic, nonhypoxic tumor, and necrotic, hypoxic tissue. PMID:22851374

  15. Evaluation of heterogeneous metabolic profile in an orthotopic human glioblastoma xenograft model using compressed sensing hyperpolarized 3D 13C magnetic resonance spectroscopic imaging.

    PubMed

    Park, Ilwoo; Hu, Simon; Bok, Robert; Ozawa, Tomoko; Ito, Motokazu; Mukherjee, Joydeep; Phillips, Joanna J; James, C David; Pieper, Russell O; Ronen, Sabrina M; Vigneron, Daniel B; Nelson, Sarah J

    2013-07-01

    High resolution compressed sensing hyperpolarized (13)C magnetic resonance spectroscopic imaging was applied in orthotopic human glioblastoma xenografts for quantitative assessment of spatial variations in (13)C metabolic profiles and comparison with histopathology. A new compressed sensing sampling design with a factor of 3.72 acceleration was implemented to enable a factor of 4 increase in spatial resolution. Compressed sensing 3D (13)C magnetic resonance spectroscopic imaging data were acquired from a phantom and 10 tumor-bearing rats following injection of hyperpolarized [1-(13)C]-pyruvate using a 3T scanner. The (13)C metabolic profiles were compared with hematoxylin and eosin staining and carbonic anhydrase 9 staining. The high-resolution compressed sensing (13)C magnetic resonance spectroscopic imaging data enabled the differentiation of distinct (13)C metabolite patterns within abnormal tissues with high specificity in similar scan times compared to the fully sampled method. The results from pathology confirmed the different characteristics of (13)C metabolic profiles between viable, non-necrotic, nonhypoxic tumor, and necrotic, hypoxic tissue. Copyright © 2012 Wiley Periodicals, Inc.

  16. Effects of a non thermal plasma treatment alone or in combination with gemcitabine in a MIA PaCa2-luc orthotopic pancreatic carcinoma model.

    PubMed

    Brullé, Laura; Vandamme, Marc; Riès, Delphine; Martel, Eric; Robert, Eric; Lerondel, Stéphanie; Trichet, Valérie; Richard, Serge; Pouvesle, Jean-Michel; Le Pape, Alain

    2012-01-01

    Pancreatic tumors are the gastrointestinal cancer with the worst prognosis in humans and with a survival rate of 5% at 5 years. Nowadays, no chemotherapy has demonstrated efficacy in terms of survival for this cancer. Previous study focused on the development of a new therapy by non thermal plasma showed significant effects on tumor growth for colorectal carcinoma and glioblastoma. To allow targeted treatment, a fibered plasma (Plasma Gun) was developed and its evaluation was performed on an orthotopic mouse model of human pancreatic carcinoma using a MIA PaCa2-luc bioluminescent cell line. The aim of this study was to characterize this pancreatic carcinoma model and to determine the effects of Plasma Gun alone or in combination with gemcitabine. During a 36 days period, quantitative BLI could be used to follow the tumor progression and we demonstrated that plasma gun induced an inhibition of MIA PaCa2-luc cells proliferation in vitro and in vivo and that this effect could be improved by association with gemcitabine possibly thanks to its radiosensitizing properties.

  17. Effects of a Non Thermal Plasma Treatment Alone or in Combination with Gemcitabine in a MIA PaCa2-luc Orthotopic Pancreatic Carcinoma Model

    PubMed Central

    Brullé, Laura; Vandamme, Marc; Riès, Delphine; Martel, Eric; Robert, Eric; Lerondel, Stéphanie; Trichet, Valérie; Richard, Serge; Pouvesle, Jean-Michel; Le Pape, Alain

    2012-01-01

    Pancreatic tumors are the gastrointestinal cancer with the worst prognosis in humans and with a survival rate of 5% at 5 years. Nowadays, no chemotherapy has demonstrated efficacy in terms of survival for this cancer. Previous study focused on the development of a new therapy by non thermal plasma showed significant effects on tumor growth for colorectal carcinoma and glioblastoma. To allow targeted treatment, a fibered plasma (Plasma Gun) was developed and its evaluation was performed on an orthotopic mouse model of human pancreatic carcinoma using a MIA PaCa2-luc bioluminescent cell line. The aim of this study was to characterize this pancreatic carcinoma model and to determine the effects of Plasma Gun alone or in combination with gemcitabine. During a 36 days period, quantitative BLI could be used to follow the tumor progression and we demonstrated that plasma gun induced an inhibition of MIA PaCa2-luc cells proliferation in vitro and in vivo and that this effect could be improved by association with gemcitabine possibly thanks to its radiosensitizing properties. PMID:23300736

  18. Tomography of epidermal growth factor receptor binding to fluorescent Affibody in vivo studied with magnetic resonance guided fluorescence recovery in varying orthotopic glioma sizes

    NASA Astrophysics Data System (ADS)

    Holt, Robert W.; Demers, Jennifer-Lynn H.; Sexton, Kristian J.; Gunn, Jason R.; Davis, Scott C.; Samkoe, Kimberley S.; Pogue, Brian W.

    2015-02-01

    The ability to image targeted tracer binding to epidermal growth factor receptor (EGFR) was studied in vivo in orthotopically grown glioma tumors of different sizes. The binding potential was quantified using a dual-tracer approach, which employs a fluorescently labeled peptide targeted to EGFR and a reference tracer with similar pharmacokinetic properties but no specific binding, to estimate the relative bound fraction from kinetic compartment modeling. The recovered values of binding potential did not vary significantly as a function of tumor size (1 to 33 mm3), suggesting that binding potential may be consistent in the U251 tumors regardless of size or stage after implantation. However, the fluorescence yield of the targeted fluorescent tracers in the tumor was affected significantly by tumor size, suggesting that dual-tracer imaging helps account for variations in absolute uptake, which plague single-tracer imaging techniques. Ex vivo analysis showed relatively high spatial heterogeneity in each tumor that cannot be resolved by tomographic techniques. Nonetheless, the dual-tracer tomographic technique is a powerful tool for longitudinal bulk estimation of receptor binding.

  19. Anionic clay as the drug delivery vehicle: tumor targeting function of layered double hydroxide-methotrexate nanohybrid in C33A orthotopic cervical cancer model.

    PubMed

    Choi, Goeun; Piao, Huiyan; Alothman, Zeid A; Vinu, Ajayan; Yun, Chae-Ok; Choy, Jin-Ho

    2016-01-01

    Methotrexate (MTX), an anticancer agent, was successfully intercalated into the anionic clay, layered double hydroxides to form a new nanohybrid drug. The coprecipitation and subsequent hydrothermal method were used to prepare chemically, structurally, and morphologically well-defined two-dimensional drug-clay nanohybrid. The resulting two-dimensional drug-clay nanohybrid showed excellent colloidal stability not only in deionized water but also in an electrolyte solution of Dulbecco's Modified Eagle's Medium with 10% fetal bovine serum, in which the average particle size in colloid and the polydispersity index were determined to be around 100 and 0.250 nm, respectively. The targeting property of the nanohybrid drug was confirmed by evaluating the tumor-to-blood and tumor-to-liver ratios of the MTX with anionic clay carrier, and these ratios were compared to those of free MTX in the C33A orthotopic cervical cancer model. The biodistribution studies indicated that the mice treated with the former showed 3.5-fold higher tumor-to-liver ratio and fivefold higher tumor-to-blood ratio of MTX than those treated with the latter at 30 minutes postinjection.

  20. Hip Replacement - Multiple Languages

    MedlinePlus

    ... Hip Replacement - العربية (Arabic) Bilingual PDF Health Information Translations Chinese, Simplified (Mandarin dialect) (简体中文) Expand Section Total ... Chinese, Simplified (Mandarin dialect)) Bilingual PDF Health Information Translations Chinese, Traditional (Cantonese dialect) (繁體中文) Expand Section Total ...

  1. VH Replacement Footprint Analyzer-I, a Java-Based Computer Program for Analyses of Immunoglobulin Heavy Chain Genes and Potential VH Replacement Products in Human and Mouse

    PubMed Central

    Huang, Lin; Lange, Miles D.; Zhang, Zhixin

    2014-01-01

    VH replacement occurs through RAG-mediated secondary recombination between a rearranged VH gene and an upstream unrearranged VH gene. Due to the location of the cryptic recombination signal sequence (cRSS, TACTGTG) at the 3′ end of VH gene coding region, a short stretch of nucleotides from the previous rearranged VH gene can be retained in the newly formed VH–DH junction as a “footprint” of VH replacement. Such footprints can be used as markers to identify Ig heavy chain (IgH) genes potentially generated through VH replacement. To explore the contribution of VH replacement products to the antibody repertoire, we developed a Java-based computer program, VH replacement footprint analyzer-I (VHRFA-I), to analyze published or newly obtained IgH genes from human or mouse. The VHRFA-1 program has multiple functional modules: it first uses service provided by the IMGT/V-QUEST program to assign potential VH, DH, and JH germline genes; then, it searches for VH replacement footprint motifs within the VH–DH junction (N1) regions of IgH gene sequences to identify potential VH replacement products; it can also analyze the frequencies of VH replacement products in correlation with publications, keywords, or VH, DH, and JH gene usages, and mutation status; it can further analyze the amino acid usages encoded by the identified VH replacement footprints. In summary, this program provides a useful computation tool for exploring the biological significance of VH replacement products in human and mouse. PMID:24575092

  2. Semantic Factors Predict the Rate of Lexical Replacement of Content Words

    PubMed Central

    Vejdemo, Susanne; Hörberg, Thomas

    2016-01-01

    The rate of lexical replacement estimates the diachronic stability of word forms on the basis of how frequently a proto-language word is replaced or retained in its daughter languages. Lexical replacement rate has been shown to be highly related to word class and word frequency. In this paper, we argue that content words and function words behave differently with respect to lexical replacement rate, and we show that semantic factors predict the lexical replacement rate of content words. For the 167 content items in the Swadesh list, data was gathered on the features of lexical replacement rate, word class, frequency, age of acquisition, synonyms, arousal, imageability and average mutual information, either from published databases or gathered from corpora and lexica. A linear regression model shows that, in addition to frequency, synonyms, senses and imageability are significantly related to the lexical replacement rate of content words–in particular the number of synonyms that a word has. The model shows no differences in lexical replacement rate between word classes, and outperforms a model with word class and word frequency predictors only. PMID:26820737

  3. Esophageal replacement in children: Challenges and long-term outcomes.

    PubMed

    Soccorso, Giampiero; Parikh, Dakshesh H

    2016-01-01

    Replacement of a nonexistent or damaged esophagus continues to pose a significant challenge to pediatric surgeons. Various esophageal replacement grafts and techniques have not produced consistently good outcomes to emulate normal esophagus. Therefore, many techniques are still being practiced and recommended with no clear consensus. We present a concise literature review of the currently used techniques and with discussions on the advantages and anticipated morbidity. There are no randomized controlled pediatric studies to compare different types of esophageal replacements. Management and graft choice are based on geographical and personal predilections rather than on any discernible objective data. The biggest series with long-term outcome are reported for gastric transposition and colonic replacement. Comparison of different studies shows no significant difference in early (graft necrosis and anastomotic leaks) or late complications (strictures, poor feeding, gastro-esophageal reflux, tortuosity of the graft, and Barrett's esophagus). The biggest series seem to have lower complications than small series reflecting the decennials experience in their respective centers. Long-term follow-up is recommended following esophageal replacement for the development of late strictures, excessive tortuosity, and Barrett's changes within the graft. Once child overcomes initial morbidity and establishes oral feeding, long-term consequences and complications of pediatric esophageal replacement should be monitored and managed in adult life.

  4. Esophageal replacement in children: Challenges and long-term outcomes

    PubMed Central

    Soccorso, Giampiero; Parikh, Dakshesh H.

    2016-01-01

    Replacement of a nonexistent or damaged esophagus continues to pose a significant challenge to pediatric surgeons. Various esophageal replacement grafts and techniques have not produced consistently good outcomes to emulate normal esophagus. Therefore, many techniques are still being practiced and recommended with no clear consensus. We present a concise literature review of the currently used techniques and with discussions on the advantages and anticipated morbidity. There are no randomized controlled pediatric studies to compare different types of esophageal replacements. Management and graft choice are based on geographical and personal predilections rather than on any discernible objective data. The biggest series with long-term outcome are reported for gastric transposition and colonic replacement. Comparison of different studies shows no significant difference in early (graft necrosis and anastomotic leaks) or late complications (strictures, poor feeding, gastro-esophageal reflux, tortuosity of the graft, and Barrett's esophagus). The biggest series seem to have lower complications than small series reflecting the decennials experience in their respective centers. Long-term follow-up is recommended following esophageal replacement for the development of late strictures, excessive tortuosity, and Barrett's changes within the graft. Once child overcomes initial morbidity and establishes oral feeding, long-term consequences and complications of pediatric esophageal replacement should be monitored and managed in adult life. PMID:27365900

  5. 7 CFR 274.6 - Replacement issuances and cards to households.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 4 2014-01-01 2014-01-01 false Replacement issuances and cards to households. 274.6 Section 274.6 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION... Excessive Replacement Card Notice if they have chosen to exercise the option to withhold the replacement...

  6. 49 CFR 172.338 - Replacement of identification numbers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Replacement of identification numbers. 172.338..., TRAINING REQUIREMENTS, AND SECURITY PLANS Marking § 172.338 Replacement of identification numbers. If more than one of the identification number markings on placards, orange panels, or white square-on-point...

  7. 49 CFR 172.338 - Replacement of identification numbers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Replacement of identification numbers. 172.338..., TRAINING REQUIREMENTS, AND SECURITY PLANS Marking § 172.338 Replacement of identification numbers. If more than one of the identification number markings on placards, orange panels, or white square-on-point...

  8. 49 CFR 172.338 - Replacement of identification numbers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Replacement of identification numbers. 172.338..., TRAINING REQUIREMENTS, AND SECURITY PLANS Marking § 172.338 Replacement of identification numbers. If more than one of the identification number markings on placards, orange panels, or white square-on-point...

  9. 14 CFR 45.15 - Replacement and modification parts.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Replacement and modification parts. 45.15 Section 45.15 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Identification of Aircraft and Related Products § 45.15 Replacement and...

  10. 14 CFR 45.15 - Replacement and modification parts.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Replacement and modification parts. 45.15 Section 45.15 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Marking of Products and Articles § 45.15 Replacement and modification...

  11. Role of near-infrared fluorescence imaging in the resection of metastatic lymph nodes in an optimized orthotopic animal model of HNSCC.

    PubMed

    Atallah, I; Milet, C; Quatre, R; Henry, M; Reyt, E; Coll, J-L; Hurbin, A; Righini, C A

    2015-12-01

    To study the role of near-infrared fluorescence imaging in the detection and resection of metastatic cervical lymph nodes in head and neck cancer. CAL33 head and neck cancer cells of human origin were implanted in the oral cavity of nude mice. The mice were followed up after tumor resection to detect the development of lymph node metastases. A specific fluorescent tracer for αvβ3 integrin expressed by CAL33 cells was injected intravenously in the surviving mice between the second and the fourth month following tumor resection. A near-infrared fluorescence-imaging camera was used to detect tracer uptake in metastatic cervical lymph nodes, to guide of lymph-node resection for histological analysis. Lymph node metastases were observed in 42.8% of surviving mice between the second and the fourth month following orthotopic tumor resection. Near-infrared fluorescence imaging provided real-time intraoperative detection of clinical and subclinical lymph node metastases. These results were confirmed histologically. Near infrared fluorescence imaging provides real-time contrast between normal and malignant tissue, allowing intraoperative detection of metastatic lymph nodes. This preclinical stage is essential before testing the technique in humans. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  12. Replacement Condition Detection of Railway Point Machines Using an Electric Current Sensor.

    PubMed

    Sa, Jaewon; Choi, Younchang; Chung, Yongwha; Kim, Hee-Young; Park, Daihee; Yoon, Sukhan

    2017-01-29

    Detecting replacement conditions of railway point machines is important to simultaneously satisfy the budget-limit and train-safety requirements. In this study, we consider classification of the subtle differences in the aging effect-using electric current shape analysis-for the purpose of replacement condition detection of railway point machines. After analyzing the shapes of after-replacement data and then labeling the shapes of each before-replacement data, we can derive the criteria that can handle the subtle differences between "does-not-need-to-be-replaced" and "needs-to-be-replaced" shapes. On the basis of the experimental results with in-field replacement data, we confirmed that the proposed method could detect the replacement conditions with acceptable accuracy, as well as provide visual interpretability of the criteria used for the time-series classification.

  13. Enzyme replacement therapy of Fabry disease.

    PubMed

    Clarke, Joe T R; Iwanochko, R Mark

    2005-08-01

    Fabry disease is an X-linked lysosomal storage disease caused by deficiency of the enzyme alpha-galactosidase A and results in pain, progressive renal impairment, cardiomyopathy, and cerebrovascular disease. The results of two major randomized, double-blind, placebo-controlled clinical trials and open-label extensions have shown that replacement of the deficient enzyme with either of two preparations of recombinant human alpha-galactosidase A, agalsidase-alfa, and agalsidase-beta is safe. Biweekly i.v. infusions of 0.2 mg/kg of agalsidase-alfa were associated with a significant decrease in pain and stabilization of renal function. Biweekly infusions of 1 mg/kg of agalsidase-beta were associated with virtually complete clearing of accumulated glycolipid substrate from renal and cutaneous capillary endothelial cells. Several smaller, open-label studies, along with observations made in the course of monitoring large numbers of patients on enzyme replacement therapy, indicated that treatment stabilizes renal function and produces significant improvements in myocardial mass and function. Treatment of Fabry disease by enzyme replacement has a significant impact on at least some serious complications of the disease.

  14. 10 CFR 490.8 - Replacement fuel production goal.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Replacement fuel production goal. 490.8 Section 490.8 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ALTERNATIVE FUEL TRANSPORTATION PROGRAM General... sufficient to replace, on an energy equivalent basis, at least 30 percent of motor fuel consumption in the...

  15. 10 CFR 490.8 - Replacement fuel production goal.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Replacement fuel production goal. 490.8 Section 490.8 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ALTERNATIVE FUEL TRANSPORTATION PROGRAM General... sufficient to replace, on an energy equivalent basis, at least 30 percent of motor fuel consumption in the...

  16. 10 CFR 490.8 - Replacement fuel production goal.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Replacement fuel production goal. 490.8 Section 490.8 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ALTERNATIVE FUEL TRANSPORTATION PROGRAM General... sufficient to replace, on an energy equivalent basis, at least 30 percent of motor fuel consumption in the...

  17. 10 CFR 490.8 - Replacement fuel production goal.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Replacement fuel production goal. 490.8 Section 490.8 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ALTERNATIVE FUEL TRANSPORTATION PROGRAM General... sufficient to replace, on an energy equivalent basis, at least 30 percent of motor fuel consumption in the...

  18. 10 CFR 490.8 - Replacement fuel production goal.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Replacement fuel production goal. 490.8 Section 490.8 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ALTERNATIVE FUEL TRANSPORTATION PROGRAM General... sufficient to replace, on an energy equivalent basis, at least 30 percent of motor fuel consumption in the...

  19. Replacement predictions for drinking water networks through historical data.

    PubMed

    Malm, Annika; Ljunggren, Olle; Bergstedt, Olof; Pettersson, Thomas J R; Morrison, Gregory M

    2012-05-01

    Lifetime distribution functions and current network age data can be combined to provide an assessment of the future replacement needs for drinking water distribution networks. Reliable lifetime predictions are limited by a lack of understanding of deterioration processes for different pipe materials under varied conditions. An alternative approach is the use of real historical data for replacement over an extended time series. In this paper, future replacement needs are predicted through historical data representing more than one hundred years of drinking water pipe replacement in Gothenburg, Sweden. The verified data fits well with commonly used lifetime distribution curves. Predictions for the future are discussed in the context of path dependence theory. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Replacing America's Job Bank

    ERIC Educational Resources Information Center

    Vollman, Jim

    2009-01-01

    The Job Central National Labor Exchange (www.jobcentral.com) has become the effective replacement for America's Job Bank with state workforce agencies and, increasingly, with community colleges throughout the country. The American Association of Community Colleges (AACC) has formed a partnership with Job Central to promote its use throughout the…

  1. Histologic differences between orthotopic xenograft pancreas models affect Verteporfin uptake measured by fluorescence microscopy and spectroscopy

    NASA Astrophysics Data System (ADS)

    O'Hara, Julia A.; Samkoe, Kimberley S.; Chen, Alina; Isabelle, Martin; Hoopes, P. J.; Hasan, Tayyaba; Pogue, Brian W.

    2012-02-01

    Photodynamic therapy (PDT) that uses the second generation photosensitizer, verteporfin (VP), is a developing therapy for pancreatic cancer. The optimal timing of light delivery related to VP uptake and distribution in pancreatic tumors will be important information to obtain to improve treatment for this intractable disease. In this work we examined uptake and distribution of VP in two orthotopic pancreatic tumors with different histological structure. ASPC-1 (fast-growing) and Panc-1 (slower growing) tumors were implanted in SCID mice and studied when tumors were approximately 100mm3. In a pilot study, these tumors had been shown to differ in uptake of VP using lightinduced fluorescence spectroscopy (LIFS) in vivo and fluorescence imaging ex vivo and that work is extended here. In vivo fluorescence mean readings of tumor and liver increased rapidly up to 15 minutes after photosensitizer injection for both tumor types, and then continued to increase up to 60 minutes post injection to a higher level in ASPC-1 than in Panc-1. There was variability among animals with the same tumor type, in both liver and tumor uptake and no selectivity of tumor over liver. In this work we further examined VP uptake at multiple time points in relation to microvascular density and perfusion, using DiOC7 (to mark blood vessels) and VP fluorescence in the same tissue slices. Analysis of DiOC7 fluorescence indicates that AsPC-1 and Panc-1 have different vascular densities but AsPC-1 vasculature is more perfusive. Analysis of colocalized DiOC7 and VP fluorescence showed ASPC-1 with higher accumulation of VP 3 hrs after injection and more VP at a distance from blood vessels compared to Panc-1. This work shows the need for techniques to analyze photosensitizer distribution in order to optimize photodynamic therapy as an effective treatment for pancreatic tumors.

  2. Valve assembly having remotely replaceable bearings

    DOEpatents

    Johnson, Evan R.; Tanner, David E.

    1980-01-01

    A valve assembly having remotely replaceable bearings is disclosed wherein a valve disc is supported within a flow duct for rotation about a pair of axially aligned bearings, one of which is carried by a spindle received within a diametral bore in the valve disc, and the other of which is carried by a bearing support block releasably mounted on the duct circumferentially of an annular collar on the valve disc coaxial with its diametrical bore. The spindle and bearing support block are adapted for remote removal to facilitate servicing or replacement of the valve disc support bearings.

  3. 3D tumor tissue analogs and their orthotopic implants for understanding tumor-targeting of microenvironment-responsive nanosized chemotherapy and radiation.

    PubMed

    Sethi, Pallavi; Jyoti, Amar; Swindell, Elden P; Chan, Ryan; Langner, Ulrich W; Feddock, Jonathan M; Nagarajan, Radhakrishnan; O'Halloran, Thomas V; Upreti, Meenakshi

    2015-11-01

    An appropriate representation of the tumor microenvironment in tumor models can have a pronounced impact on directing combinatorial treatment strategies and cancer nanotherapeutics. The present study develops a novel 3D co-culture spheroid model (3D TNBC) incorporating tumor cells, endothelial cells and fibroblasts as color-coded murine tumor tissue analogs (TTA) to better represent the tumor milieu of triple negative breast cancer in vitro. Implantation of TTA orthotopically in nude mice, resulted in enhanced growth and aggressive metastasis to ectopic sites. Subsequently, the utility of the model is demonstrated for preferential targeting of irradiated tumor endothelial cells via radiation-induced stromal enrichment of galectin-1 using anginex conjugated nanoparticles (nanobins) carrying arsenic trioxide and cisplatin. Demonstration of a multimodal nanotherapeutic system and inclusion of the biological response to radiation using an in vitro/in vivo tumor model incorporating characteristics of tumor microenvironment presents an advance in preclinical evaluation of existing and novel cancer nanotherapies. Existing in-vivo tumor models are established by implanting tumor cells into nude mice. Here, the authors described their approach 3D spheres containing tumor cells, enodothelial cells and fibroblasts. This would mimic tumor micro-environment more realistically. This interesting 3D model should reflect more accurately tumor response to various drugs and would enable the design of new treatment modalities. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Meal Replacement Mass Reduction Integration and Acceptability Study

    NASA Technical Reports Server (NTRS)

    Sirmons, T.; Douglas, G.; Schneiderman, J.; Slack, K.; Whitmire, A.; Williams, T.; Young, M.

    2018-01-01

    The Orion Multi-Purpose Crew Vehicle (MPCV) and future exploration missions are mass constrained; therefore we are challenged to reduce the mass of the food system by 10% while maintaining safety, nutrition, and acceptability to support crew health and performance for exploration missions. Meal replacement with nutritionally balanced, 700-900 calorie bars was identified as a method to reduce mass. However, commercially available products do not meet the requirements for a meal replacement in the spaceflight food system. The purpose of this task was to develop a variety of nutritionally balanced, high quality, breakfast replacement bars, which enable a 10% food mass savings. To date, six nutrient-dense meal replacement bars have been developed, all of which meet spaceflight nutritional, microbiological, sensory, and shelf-life requirements. The four highest scoring bars were evaluated based on final product sensory acceptability, nutritional stability, qualitative stability of analytical measurements (i.e. color and texture), and microbiological compliance over a period of two years to predict long-term acceptability. All bars maintained overall acceptability throughout the first year of storage, despite minor changes in color and texture. However, added vitamins C, B1, and B9 degraded rapidly in fortified samples of Banana Nut bars, indicating the need for additional development. In addition to shelf-life testing, four bar varieties were evaluated in the Human Exploration Research Analog (HERA), campaign 3, to assess the frequency with which actual meal replacement options may be implemented, based on impact to satiety and psychosocial measurements. Crewmembers (n=16) were asked to consume meal replacement bars every day for the first fifteen days of the mission and every three days for the second half of the mission. Daily surveys assessed the crew's responses to bar acceptability, mood, food fatigue and perceived stress. Preliminary results indicate that the

  5. Replacing missing data between airborne SAR coherent image pairs

    DOE PAGES

    Musgrove, Cameron H.; West, James C.

    2017-07-31

    For synthetic aperture radar systems, missing data samples can cause severe image distortion. When multiple, coherent data collections exist and the missing data samples do not overlap between collections, there exists the possibility of replacing data samples between collections. For airborne radar, the known and unknown motion of the aircraft prevents direct data sample replacement to repair image features. Finally, this paper presents a method to calculate the necessary phase corrections to enable data sample replacement using only the collected radar data.

  6. Replacing missing data between airborne SAR coherent image pairs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Musgrove, Cameron H.; West, James C.

    For synthetic aperture radar systems, missing data samples can cause severe image distortion. When multiple, coherent data collections exist and the missing data samples do not overlap between collections, there exists the possibility of replacing data samples between collections. For airborne radar, the known and unknown motion of the aircraft prevents direct data sample replacement to repair image features. Finally, this paper presents a method to calculate the necessary phase corrections to enable data sample replacement using only the collected radar data.

  7. Medicare Program; Comprehensive Care for Joint Replacement Payment Model for Acute Care Hospitals Furnishing Lower Extremity Joint Replacement Services. Final rule.

    PubMed

    2015-11-24

    This final rule implements a new Medicare Part A and B payment model under section 1115A of the Social Security Act, called the Comprehensive Care for Joint Replacement (CJR) model, in which acute care hospitals in certain selected geographic areas will receive retrospective bundled payments for episodes of care for lower extremity joint replacement (LEJR) or reattachment of a lower extremity. All related care within 90 days of hospital discharge from the joint replacement procedure will be included in the episode of care. We believe this model will further our goals in improving the efficiency and quality of care for Medicare beneficiaries with these common medical procedures.

  8. Pulsed Versus Conventional Radiation Therapy in Combination With Temozolomide in a Murine Orthotopic Model of Glioblastoma Multiforme

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, David Y.; Chunta, John L.; Park, Sean S.

    Purpose: To evaluate the efficacy of pulsed low-dose radiation therapy (PLRT) combined with temozolomide (TMZ) as a novel treatment approach for radioresistant glioblastoma multiforme (GBM) in a murine model. Methods and Materials: Orthotopic U87MG hGBM tumors were established in Nu-Foxn1{sup nu} mice and imaged weekly using a small-animal micropositron emission tomography (PET)/computed tomography (CT) system. Tumor volume was determined from contrast-enhanced microCT images and tumor metabolic activity (SUVmax) from the F18-FDG microPET scan. Tumors were irradiated 7 to 10 days after implantation with a total dose of 14 Gy in 7 consecutive days. The daily treatment was given as amore » single continuous 2-Gy dose (RT) or 10 pulses of 0.2 Gy using an interpulse interval of 3 minutes (PLRT). TMZ (10 mg/kg) was given daily by oral gavage 1 hour before RT. Tumor vascularity and normal brain damage were assessed by immunohistochemistry. Results: Radiation therapy with TMZ resulted in a significant 3- to 4-week tumor growth delay compared with controls, with PLRT+TMZ the most effective. PLRT+TMZ resulted in a larger decline in SUVmax than RT+TMZ. Significant differences in survival were evident. Treatment after PLRT+TMZ was associated with increased vascularization compared with RT+TMZ. Significantly fewer degenerating neurons were seen in normal brain after PLRT+TMZ compared with RT+TMZ. Conclusions: PLRT+TMZ produced superior tumor growth delay and less normal brain damage when compared with RT+TMZ. The differential effect of PLRT on vascularization may confirm new treatment avenues for GBM.« less

  9. Vγ9Vδ2 T cells and zoledronate mediate antitumor activity in an orthotopic mouse model of human chondrosarcoma.

    PubMed

    Sun, L; Li, Y; Jiang, Z; Zhang, J; Li, H; Li, B; Ye, Z

    2016-06-01

    Chondrosarcoma (CS) is a cartilaginous malignant neoplasm characterized by resistance to conventional adjuvant therapy. The prognosis of unresectable or metastatic CS is poor. Therefore, it is imperative to explore novel therapeutic approaches to improve the treatment efficacy for those CS patients. Emerging data has implicated the synergistic antitumor activity of zoledronate (ZOL) and Vγ9Vδ2 T cells. However, whether ZOL-stimulated Vγ9Vδ2 T cells could infiltrate bone sarcoma and inhibit tumor growth has not been thoroughly answered yet. In this study, Vγ9Vδ2 T cells from healthy donors and CS patients were expanded in the presence of ZOL (1 μM) and IL-2 (400 IU/ml). The antitumor activity of Vγ9Vδ2 T cells to ZOL-pretreated human CS was examined both in vitro and in vivo. ZOL pretreatment substantially enhanced the cytotoxicity of Vγ9Vδ2 T cells to SW1353 and primary CS cells. ZOL potentiated the migration and cytotoxicity of Vγ9Vδ2 T cells to SW1353 in dose- and time-dependent manner. Moreover, weekly intravenous ZOL followed by Vγ9Vδ2 T cells inhibited subcutaneous xenograft growth. Thus, Vγ9Vδ2 T cells were able to infiltrate bone tumor and significantly suppressed the development of orthotopic SW1353 xenografts. Altogether, the study raises the possibility of combining ZOL with Vγ9Vδ2 T cells for CS treatment.

  10. Patient-derived orthotopic xenograft models for cancer of unknown primary precisely distinguish chemotherapy, and tumor-targeting S. typhimurium A1-R is superior to first-line chemotherapy.

    PubMed

    Miyake, Kentaro; Kiyuna, Tasuku; Miyake, Masuyo; Kawaguchi, Kei; Yoon, Sang Nam; Zhang, Zhiying; Igarashi, Kentaro; Razmjooei, Sahar; Wangsiricharoen, Sintawat; Murakami, Takashi; Li, Yunfeng; Nelson, Scott D; Russell, Tara A; Singh, Arun S; Hiroshima, Yukihiko; Momiyama, Masashi; Matsuyama, Ryusei; Chishima, Takashi; Singh, Shree Ram; Endo, Itaru; Eilber, Fritz C; Hoffman, Robert M

    2018-01-01

    Cancer of unknown primary (CUP) is a recalcitrant disease with poor prognosis because it lacks standard first-line therapy. CUP consists of diverse malignancy groups, making personalized precision therapy essential. The present study aimed to identify an effective therapy for a CUP patient using a patient-derived orthotopic xenograft (PDOX) model. This paper reports the usefulness of the PDOX model to precisely identify effective and ineffective chemotherapy and to compare the efficacy of S. typhimurium A1-R with first-line chemotherapy using the CUP PDOX model. The present study is the first to use a CUP PDOX model, which was able to precisely distinguish the chemotherapeutic course. We found that a carboplatinum (CAR)-based regimen was effective for this CUP patient. We also demonstrated that S. typhimurium A1-R was more effective against the CUP tumor than first-line chemotherapy. Our results indicate that S. typhimurium A1-R has clinical potential for CUP, a resistant disease that requires effective therapy.

  11. Prevalence of Total Hip and Knee Replacement in the United States.

    PubMed

    Maradit Kremers, Hilal; Larson, Dirk R; Crowson, Cynthia S; Kremers, Walter K; Washington, Raynard E; Steiner, Claudia A; Jiranek, William A; Berry, Daniel J

    2015-09-02

    Descriptive epidemiology of total joint replacement procedures is limited to annual procedure volumes (incidence). The prevalence of the growing number of individuals living with a total hip or total knee replacement is currently unknown. Our objective was to estimate the prevalence of total hip and total knee replacement in the United States. Prevalence was estimated using the counting method by combining historical incidence data from the National Hospital Discharge Survey and the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases from 1969 to 2010 with general population census and mortality counts. We accounted for relative differences in mortality rates between those who have had total hip or knee replacement and the general population. The 2010 prevalence of total hip and total knee replacement in the total U.S. population was 0.83% and 1.52%, respectively. Prevalence was higher among women than among men and increased with age, reaching 5.26% for total hip replacement and 10.38% for total knee replacement at eighty years. These estimates corresponded to 2.5 million individuals (1.4 million women and 1.1 million men) with total hip replacement and 4.7 million individuals (3.0 million women and 1.7 million men) with total knee replacement in 2010. Secular trends indicated a substantial rise in prevalence over time and a shift to younger ages. Around 7 million Americans are living with a hip or knee replacement, and consequently, in most cases, are mobile, despite advanced arthritis. These numbers underscore the substantial public health impact of total hip and knee arthroplasties. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

  12. Replacing and Additive Horizontal Gene Transfer in Streptococcus

    PubMed Central

    Choi, Sang Chul; Rasmussen, Matthew D.; Hubisz, Melissa J.; Gronau, Ilan; Stanhope, Michael J.; Siepel, Adam

    2012-01-01

    The prominent role of Horizontal Gene Transfer (HGT) in the evolution of bacteria is now well documented, but few studies have differentiated between evolutionary events that predominantly cause genes in one lineage to be replaced by homologs from another lineage (“replacing HGT”) and events that result in the addition of substantial new genomic material (“additive HGT”). Here in, we make use of the distinct phylogenetic signatures of replacing and additive HGTs in a genome-wide study of the important human pathogen Streptococcus pyogenes (SPY) and its close relatives S. dysgalactiae subspecies equisimilis (SDE) and S. dysgalactiae subspecies dysgalactiae (SDD). Using recently developed statistical models and computational methods, we find evidence for abundant gene flow of both kinds within each of the SPY and SDE clades and of reduced levels of exchange between SPY and SDD. In addition, our analysis strongly supports a pronounced asymmetry in SPY–SDE gene flow, favoring the SPY-to-SDE direction. This finding is of particular interest in light of the recent increase in virulence of pathogenic SDE. We find much stronger evidence for SPY–SDE gene flow among replacing than among additive transfers, suggesting a primary influence from homologous recombination between co-occurring SPY and SDE cells in human hosts. Putative virulence genes are correlated with transfer events, but this correlation is found to be driven by additive, not replacing, HGTs. The genes affected by additive HGTs are enriched for functions having to do with transposition, recombination, and DNA integration, consistent with previous findings, whereas replacing HGTs seen to influence a more diverse set of genes. Additive transfers are also found to be associated with evidence of positive selection. These findings shed new light on the manner in which HGT has shaped pathogenic bacterial genomes. PMID:22617954

  13. MELD score measured day 10 after orthotopic liver transplantation predicts death and re-transplantation within the first year.

    PubMed

    Rostved, Andreas A; Lundgren, Jens D; Hillingsø, Jens; Peters, Lars; Mocroft, Amanda; Rasmussen, Allan

    2016-11-01

    The impact of early allograft dysfunction on the outcome after liver transplantation is yet to be established. We explored the independent predictive value of the Model for End-Stage Liver Disease (MELD) score measured in the post-transplant period on the risk of mortality or re-transplantation. Retrospective cohort study on adults undergoing orthotopic deceased donor liver transplantation from 2004 to 2014. The MELD score was determined prior to transplantation and daily until 21 days after. The risk of mortality or re-transplantation within the first year was assessed according to quartiles of MELD using unadjusted and adjusted stepwise Cox regression analysis. We included 374 consecutive liver transplant recipients of whom 60 patients died or were re-transplanted. The pre-transplant MELD score was comparable between patients with good and poor outcome, but from day 1 the MELD score significantly diversified and was higher in the poor outcome group (MELD score quartile 4 versus quartile 1-3 at day 10: HR 5.1, 95% CI: 2.8-9.0). This association remained after adjustment for non-identical blood type, autoimmune liver disease and hepatocellular carcinoma (adjusted HR 5.3, 95% CI: 2.9-9.5 for MELD scores at day 10). The post-transplant MELD score was not associated with pre-transplant MELD score or the Eurotransplant donor risk index. Early determination of the MELD score as an indicator of early allograft dysfunction after liver transplantation was a strong independent predictor of mortality or re-transplantation and was not influenced by the quality of the donor, or preoperative recipient risk factors.

  14. The application of surgical navigation system using optical molecular imaging technology in orthotopic breast cancer and metastasis studies

    NASA Astrophysics Data System (ADS)

    Chi, Chongwei; Zhang, Qian; Kou, Deqiang; Ye, Jinzuo; Mao, Yamin; Qiu, Jingdan; Wang, Jiandong; Yang, Xin; Du, Yang; Tian, Jie

    2014-02-01

    Currently, it has been an international focus on intraoperative precise positioning and accurate resection of tumor and metastases. The methods such as X-rays, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role in preoperative accurate diagnosis. However, most of them are inapplicable for intraoperative surgery. We have proposed a surgical navigation system based on optical molecular imaging technology for intraoperative detection of tumors and metastasis. This system collects images from two CCD cameras for real-time fluorescent and color imaging. For image processing, the template matching algorithm is used for multispectral image fusion. For the application of tumor detection, the mouse breast cancer cell line 4T1-luc, which shows highly metastasis, was used for tumor model establishment and a model of matrix metalloproteinase (MMP) expressing breast cancer. The tumor-bearing nude mice were given tail vein injection of MMP 750FAST (PerkinElmer, Inc. USA) probe and imaged with both bioluminescence and fluorescence to assess in vivo binding of the probe to the tumor and metastases sites. Hematoxylin and eosin (H&E) staining was performed to confirm the presence of tumor and metastasis. As a result, one tumor can be observed visually in vivo. However liver metastasis has been detected under surgical navigation system and all were confirmed by histology. This approach helps surgeons to find orthotopic tumors and metastasis during intraoperative resection and visualize tumor borders for precise positioning. Further investigation is needed for future application in clinics.

  15. Menopausal Symptom Relief and Side Effects Experienced by Women Using Compounded Bioidentical Hormone Replacement Therapy and Synthetic Conjugated Equine Estrogen and/or Progestin Hormone Replacement Therapy, Part 2.

    PubMed

    Deleruyelle, Laura J

    2016-01-01

    The use of compounded bioidentical hormone replacement therapy by menopausal women has become a popular alternative to traditional synthetic conjugated equine estrogen and progestin hormone replacement therapy due to safety concerns raised by recent studies. However, due to the lack of randomized, large-scale trials to evaluate the efficacy and side-effect profile of compounded bioidentical hormone replacement therapy many healthcare providers are reluctant to prescribe such therapy. The purpose of this study was to compare women's menopausal symptom relief and side effects experienced when using compounded bioidentical hormone replacement therapy and traditional hormone replacement therapy. A descriptive comparative design was used. Inferential and descriptive statistical procedures including a paired difference t-test, two-sample t-test, and f-tests (percentage, mean, standard deviation, frequency) were run on the Statistical Package for the Social Sciences. The framework used to guide this study was Lenz and Pugh's Theory of Unpleasant Symptoms. Surveys were distributed once to a convenient sample of women aged 35 and older when they dropped off or picked up their prescriptions at a pharmacy. Of the 216 surveys distributed, 70 were returned from those women taking compounded bioidentical hormone replacement therapy and 53 from traditional hormone replacement therapy. The survey contained 15 questions pertaining to age, duration of hormone replacement therapy, type and formulation of hormone replacement therapy, reasons for initiating hormone replacement therapy, symptoms before and one month after hormone replacement therapy, and side effects related to hormone replacement therapy. Included in part 1 of this series of articles was the introduction to the study conducted and the results of the literature review that was conducted for the purpose of examining the current data related to the topic of hormone replacement therapy. Part 2 provides a brief discussion

  16. Menopausal Symptom Relief and Side Effects Experienced by Women Using Compounded Bioidentical Hormone Replacement Therapy and Synthetic Conjugated Equine Estrogen and/or Progestin Hormone Replacement Therapy, Part 3.

    PubMed

    Deleruyelle, Laura J

    2017-01-01

    The use of compounded bioidentical hormone replacement therapy by menopausal women has become a popular alternative to traditional synthetic conjugated equine estrogen and progestin hormone replacement therapy due to safety concerns raised by recent studies. However, due to the lack of randomized, large-scale trials to evaluate the efficacy and side-effect profile of compounded bioidentical hormone replacement therapy many healthcare providers are reluctant to prescribe such therapy. The purpose of this study was to compare women's menopausal symptom relief and side effects experienced when using compounded bioidentical hormone replacement therapy and traditional hormone replacement therapy. A descriptive comparative design was used. Inferential and descriptive statistical procedures including a paired difference t-test, two-sample t-test, and f-tests (percentage, mean, standard deviation, frequency) were run on the Statistical Package for the Social Sciences. The framework used to guide this study was Lenz and Pugh's Theory of Unpleasant Symptoms. Surveys were distributed once to a convenient sample of women aged 35 and older when they dropped off or picked up their prescriptions at a pharmacy. Of the 216 surveys distributed, 70 were returned from those women taking compounded bioidentical hormone replacement therapy and 53 from traditional hormone replacement therapy. The survey contained 15 questions pertaining to age, duration of hormone replacement therapy, type and formulation of hormone replacement therapy, reasons for initiating hormone replacement therapy, symptoms before and one month after hormone replacement therapy, and side effects related to hormone replacement therapy. Included in part 1 of this series of articles was the introduction to the study conducted and the results of the literature review that was conducted for the purpose of examining the current data related to the topic of hormone replacement therapy. Part 2 provided a brief discussion

  17. Astronaut tool development: An orbital replaceable unit-portable handhold

    NASA Technical Reports Server (NTRS)

    Redmon, John W., Jr.

    1989-01-01

    A tool to be used during astronaut Extra-Vehicular Activity (EVA) replacement of spent or defective electrical/electronic component boxes is described. The generation of requirements and design philosophies are detailed, as well as specifics relating to mechanical development, interface verifications, testing, and astronaut feedback. Findings are presented in the form of: (1) a design which is universally applicable to spacecraft component replacement, and (2) guidelines that the designer of orbital replacement units might incorporate to enhance spacecraft on-orbit maintainability and EVA mission safety.

  18. Options for Heart Valve Replacement

    MedlinePlus

    ... which may include human or animal donor tissue) Ross Procedure — “Borrowing” your healthy valve and moving it ... Considerations for Surgery Medications Valve Repair Valve Replacement - Ross Procedure - Newer Surgery Options - What is TAVR? - Types ...

  19. Gastric Transposition for Esophageal Replacement in Children

    PubMed Central

    Hirschl, Ronald B.; Yardeni, Dani; Oldham, Keith; Sherman, Neil; Siplovich, Leo; Gross, Eitan; Udassin, Raphael; Cohen, Zehavi; Nagar, Hagith; Geiger, James D.; Coran, Arnold G.

    2002-01-01

    Objective To evaluate the authors’ experience with gastric transposition as a method of esophageal replacement in children with congenital or acquired abnormalities of the esophagus. Summary Background Data Esophageal replacement in children is almost always done for benign disease and thus requires a conduit that will last more than 70 years. The organ most commonly used in the past has been colon; however, most series have been fraught with major complications and conduit loss. For these reasons, in 1985 the authors switched from using colon interpositions to gastric transpositions for esophageal replacement in infants and children. Methods The authors retrospectively reviewed the records of 41 patients with the diagnoses of esophageal atresia (n = 26), corrosive injury (n = 8), leiomyomatosis (n = 5), and refractory gastroesophageal reflux (n = 2) who underwent gastric transposition for esophageal replacement. Results Mean ± SE age at the time of gastric transposition was 3.3 ± 0.6 years. All but two transpositions were performed through the posterior mediastinum without mortality or loss of the gastric conduit despite previous surgery on the gastric fundus in 8 (20%), previous esophageal operations in 15 (37%), and previous esophageal perforations in 6 (15%) patients. Complications included esophagogastric anastomotic leak (n = 15, 36%), which uniformly resolved without intervention; stricture formation (n = 20, 49%), all of which no longer require dilation; and feeding intolerance necessitating jejunal feeding (n = 8, 20%) due to delayed gastric emptying (n = 3), feeding aversion related to the underlying anomaly (n = 1), or severe neurological impairment (n = 4). No redo anastomoses were required. Conclusions Gastric transposition reestablishes effective gastrointestinal continuity with few complications. Oral feeding and appropriate weight gain are achieved in most children. Therefore, gastric transposition is an appropriate alternative for esophageal

  20. Power Plant Replacement Study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Reed, Gary

    2010-09-30

    This report represents the final report for the Eastern Illinois University power plant replacement study. It contains all related documentation from consideration of possible solutions to the final recommended option. Included are the economic justifications associated with the chosen solution along with application for environmental permitting for the selected project for construction. This final report will summarize the results of execution of an EPC (energy performance contract) investment grade audit (IGA) which lead to an energy services agreement (ESA). The project includes scope of work to design and install energy conservation measures which are guaranteed by the contractor to bemore » self-funding over its twenty year contract duration. The cost recovery is derived from systems performance improvements leading to energy savings. The prime focus of this EPC effort is to provide a replacement solution for Eastern Illinois University’s aging and failing circa 1925 central steam production plant. Twenty-three ECMs were considered viable whose net impact will provide sufficient savings to successfully support the overall project objectives.« less